Notes

You should also draw on the Abelkop / Fitzmier lab’s Deep Sea Exploration files. Many of those cards don’t apply to this aff, but some do.

1AC

Plan

The United States Federal Government should increase its biomedical exploration of ocean microbes.

Pandemics

Contention 1: Pandemics—

We are entering an era of global diseases that will kill humans and destroy biodiversityKock 13 – R. A. Kock of the Department of Pathology and Pathobiology, Royal Veterinary College, Hawkshead Lane Hatfield, UK (23 October 2013, "Will the damage be done before we feel the heat? Infectious disease emergence,” Cambridge University Press 2013 Animal Health Research Reviews 14(2); 127–132, ISSN 1466-2523, doi:10.1017/S1466252313000108, ADL)This initial progress in resolving age-old infectious disease problems might well turn out to be a false dawn. If we take a broader view on

disease at the ecosystem level, rather than human infection alone, the situation is not looking so promising. There are a growing number of diseases at the interface between humans, animals and the environment (including

plants), which are having a significant impact on human well-being, mostly through food systems. For

example, the USA has suffered a series of highly significant and costly disease epidemics in the last decade West Nile Virus (WNV) in New York City, which subsequently spread to all 48 States of the continental USA, caused mortalities and sickness in a wide

range of domestic animals, wild birds and people (Kilpatrick, 2011). Although the costs are still being calculated, WNV showed how rapidly such disease events can occur and there was nothing that could be done to stop the epidemic. This was followed shortly after by another epidemic disease coined ‘white nose syndrome’ affecting bats (Blehert et al., 2009). This is caused by a fungus Geomyces destructans, most probably introduced by travelers and cavers (Warnecke et al., 2012), which, to date, has killed an estimated 6.5 million bats. The consequences are a conservation crisis and a multi-billion dollar cost to the agricultural industry from lost predation on agricultural pests, a significant ecosystem service provided by bats (Boyles et al., 2011).

Similarly, a global insidious spread of a fungal disease of amphibians is resulting in an unexpected and ‘premature’ extinction crisis, long before the planet heats up (Berger et al., 1998; Rosenblum et al., 2010). Over a third of amphibian species are expected to disappear in the coming years but these extinctions are not only a result of this disease (Heard

et al., 2011). These taxa have provided significant unappreciated benefits to humanity through the control of mosquitos and other vectors of serious infectious diseases. Moreover, if this is not enough, there are numerous tree diseases that are spreading globally, some fungal and others insect-based, which are devastating

woodlands and individual tree species populations in North America and Europe with wide spread economic consequences. It seems the rapid increase in transportation networks and frequency of human and animal movements by air and sea, a consequence of free market capitalism and globalization, has created a ‘perfect storm’ for infectious disease emergence across ecosystems (Brown, 2004). It is rather like humans picking up Pandora’s box, giving it a thorough shake, and then sending its contents to every corner of the earth. A massive experiment in human-assisted pathogen evolution and spread, gives every advantage to the microorganisms to gain access to immunologically naive hosts and for them to gain dominance over larger organisms, the latter

too sluggish in their ability to respond immunologically and adapt. This physical reassortment and distribution of current pathogens alone could drive an era of plague and pestilence affecting most biological taxa. Unfortunately the story does not stop here, human engineering of landscapes and biological systems are associated with pathogen evolution and disease emergence at the interface, but almost without exception the drivers are poorly researched (Jones et al., 2013). These events are not

all new but we are only just beginning to appreciate the extent of our influence on their occurrence. Wolfe et al., 2007 elegantly described how several major human diseases, including smallpox, malaria, campylobacteriosis, rotavirus, measles, diphtheria, mumps, HIV-AIDS and influenza virus, are derived from our domestication of animals and/or harvesting of wild animals over the millennia. These diseases became firmly established in humans, no longer driven or dependent on zoonotic cycles. This is on top of approximately 900 zoonotic infections recorded; of which about 292 are significant pathogens, most associated with domestic animals but many originating from wildlife, sometimes directly (e.g. Ebola virus) (Cleaveland et al., 2001). It

seems that this process is accelerating, with the majority (75%) of emerging human pathogens being zoonotic (Taylor et al., 2001). The trend in zoonotic disease emergence correlates with the expansion of domestic animal populations in parallel to that of human growth. This has fundamentally altered the epidemiological environment. Paradoxically, increasing animal production for human use, through industrialization of crop

and animal agriculture, has resulted in an increasing opportunity for pathogen evolution (Arzt et al.,

2010; Jones et al., 2013). These larger epidemiological units of plants and animals, with considerable homogeneity,

when densely packed (ironically for reasons of biosecurity and production efficiency) are perfect pathogen factories. The

recent ‘bird flu’ panzootic is an example of this. The emergence of the atypical, highly pathogenic influenza virus H5N1 was coincident with a massive expansion of the duck and poultry industry in South East Asia. Water birds are natural hosts of avian influenza viruses and are highly tolerant of infection (Alexander, 2007). However, the growth in domestic duck farms including exploitation of semidomestic ducks in close proximity to both wild bird populations and densely packed chicken farms, created an opportunity for the rapid evolution of this highly virulent strain of avian influenza, its amplification and spread. H5N1 was first isolated in 1997 (Xu et al., 1999) with epidemics recorded in Hong Kong in 1998 and with a significant wild bird epidemic between 2005 and 2007 (Chen et al., 2006). The infection spread rapidly across Eurasia between poultry systems and as far as Egypt (Abdelwhab and Hafez, 2011) and Nigeria (Newman et al., 2008). Wild bird cases reported appear to be mostly during epidemics or spillover cases from poultry epidemics (Feare and Yasue´, 2006; Lebarbenchon et al., 2010; Soliman et al., 2012), and wild bird epidemics appear to have been largely independent of domestic bird disease. The infections burned out in wildlife with no evidence of a long-term reservoir and only rare cases based on circumstantial evidence of spillover from wild birds to poultry (Hars et al., 2008), predators (Desvaux et al., 2009; Globig et al., 2009) and humans (bird hunters) (Newman et al., 2008).

The great fear has been that should this virus, which rarely infects humans, evolve into a form that is highly transmissible among humans, it will then cause a severe pandemic. Whilst the immediate threat has subsided, with apparent resilience in the wild bird populations to H5N1 increasing (Siembieda et al., 2010) and with mass vaccination and slaughter of poultry providing temporary relief, endemic foci in domestic birds still persist. This strain of virus has been recently joined by a new, more sinister low pathogenic strain (in poultry) of H7N9, which is lethal in humans and can be transmitted more readily between humans than was the case with H5N1. The main reason for failure to stop the emergence of these diseases is the continued expansion of agroecological systems and industry, which cause the problem in the first place. It is not always necessary to have a farm for these spillover events, other concentrations of mixed animal species in e.g. food markets has led to emergence, exemplified by the SARS epidemic. Here a bat virus was involved, most probably spilling into a market and replicating in (probably) a number of species, adapting and amplifying until it was established in humans and an epidemic ensued. Globally, the virus infected approximately 8000 people and caused several hundred deaths. The remarkable fact is that this pathogen jump probably only took a period of 2–3 years (Wang et al., 2005; Zhao, 2007; Tang et al., 2009). Another important driver of disease at the interface has been changing landscapes, with increasing incursion into and modification of diverse habitats for settlement and exploitation of resources. An example is the creation of new vector niche habitats, mostly through urban development (Globig et al., 2009) enabling persistence and emergence of significant problems e.g. dengue fever virus; once only found in primates (Mackenzie et al., 2004). HIV is the most famous example, where frequent spillover of SIV to humans through their exploitation of chimpanzee and gorilla for food, resulted in the establishment of human infection and adaptation of the virus (Gao et al., 1999). However, it was not until road networks were put into the Congo basin that the epidemic really took hold. There were probably a series of stuttering epidemics until the virus entered the urban environment and then the world. It is sobering to note that the African mortality statistics (WHO, 2012) indicate that, far from following the pattern in the Western world, the life expectancy from birth in two of the richest nations, South Africa and Botswana, has significantly decreased between 1990 and 2010; and this was from the impact

of only one emerging disease, HIV–AIDS. What if we have ten novel diseases occurring simultaneously?

Biodiversity loss causes human extinctionCoyne, professor of ecology and evolution – University of Chicago, and Hoekstra, associate professor of biology – Harvard, 9/24/‘7(Jerry and John L., “The Greatest Dying,” http://www.truthout.org/article/jerry-coyne-and-hopi-e-hoekstra-the-greatest-dying)   But it isn't just the destruction of the rainforests that should trouble us. Healthy ecosystems the world over provide hidden services like waste disposal, nutrient cycling, soil formation, water purification, and oxygen production. Such services are best rendered by ecosystems that are diverse. Yet, through both intention and accident, humans have introduced exotic species that turn biodiversity into monoculture. Fast-growing zebra mussels, for example, have outcompeted more than 15 species of native mussels in North America's Great Lakes and have damaged harbors and water-treatment plants. Native prairies are becoming dominated by single species (often genetically homogenous) of corn or wheat. Thanks to these developments, soils will erode and become unproductive - which, along with temperature change, will diminish agricultural yields. Meanwhile, with increased pollution and runoff, as well as reduced forest cover, ecosystems will no longer be able to purify water; and a shortage of clean water spells disaster. In many ways, oceans are the most vulnerable areas of all. As overfishing eliminates major predators, while polluted and warming waters kill off phytoplankton, the intricate aquatic food web could collapse from both sides. Fish, on which so many humans depend, will be a fond memory. As phytoplankton vanish, so does the ability of the oceans to absorb carbon dioxide and produce oxygen. (Half of the oxygen we breathe is made by phytoplankton, with the rest coming from land plants.) Species extinction is also imperiling coral reefs - a major problem since these reefs have far more than recreational value: They provide tremendous amounts of food for human populations and buffer coastlines against erosion. In fact, the global value of "hidden" services provided by ecosystems - those services, like waste disposal, that aren't bought and sold in the marketplace - has been estimated to be as much as $50 trillion per year, roughly equal to the gross domestic product of all countries combined. And that doesn't include tangible goods like fish and timber. Life as we know it would be impossible if ecosystems collapsed. Yet that is where we're heading if species extinction continues at its current pace. Extinction also has a huge

impact on medicine. Who really cares if, say, a worm in the remote swamps of French Guiana goes extinct? Well, those who suffer from cardiovascular disease. The recent discovery of a rare South American leech has led to the isolation of a powerful enzyme that, unlike other anticoagulants, not only prevents blood from clotting but also dissolves existing clots. And it's not just this one species of worm: Its wriggly relatives have evolved other biomedically valuable proteins, including antistatin (a potential anticancer agent), decorsin and ornatin (platelet aggregation inhibitors), and hirudin (another anticoagulant). Plants, too, are pharmaceutical gold mines. The bark of trees, for example, has given us quinine (the first cure for malaria), taxol (a drug highly effective against ovarian and breast cancer), and aspirin. More than a quarter of the medicines on our pharmacy shelves were originally derived from plants. The sap of the Madagascar periwinkle contains more than 70 useful alkaloids, including vincristine, a powerful anticancer drug that saved the life of one of our friends. Of the roughly 250,000 plant species on Earth, fewer than 5 percent have been screened for pharmaceutical properties. Who knows what life-saving drugs remain to be discovered? Given current extinction rates, it's estimated that we're losing one valuable drug every two years. Our arguments so far have tacitly assumed that species are worth saving only in proportion to their economic value and their effects on our quality of life, an attitude that is strongly ingrained, especially in Americans. That is why conservationists always base their case on an economic calculus. But we biologists know in our hearts that there are deeper and equally compelling reasons to worry about the loss of biodiversity: namely, simple morality and intellectual values that transcend pecuniary interests. What, for example, gives us the right to destroy other creatures? And what could be more thrilling than looking around us, seeing that we are surrounded by our evolutionary cousins, and realizing that we all got here by the same simple process of natural selection? To biologists, and potentially everyone else, apprehending the genetic kinship and common origin of all species is a spiritual experience - not necessarily religious, but spiritual nonetheless, for it stirs the soul. But, whether or not one is moved by such concerns, it is certain that our future is bleak if we do nothing to stem this sixth extinction. We are creating a world in which exotic diseases flourish but natural medicinal cures are lost ; a world in which carbon waste accumulates while food sources dwindle ; a world of sweltering heat, failing crops, and impure water. In the end, we must accept the possibility that we ourselves are not immune to extinction. Or, if we survive, perhaps only a few of us will remain, scratching out a grubby existence on a devastated planet. Global warming will seem like a secondary problem when humanity finally faces the consequences of what we have done to nature: not just another Great Dying, but perhaps the greatest dying of them all.

New zoonotic diseases are inevitable – they will go globalKaresh et al 12 - Dr William B Karesh, Prof Andy Dobson DPhil, Prof James O Lloyd-Smith PhD, Juan Lubroth DVM h, Matthew A Dixon MSc i, Prof Malcolm Bennett PhD j, Stephen Aldrich BA k, Todd Harrington MBA k, Pierre Formenty DVM l, Elizabeth H Loh MS a, Catherine C Machalaba MPH a, Mathew Jason Thomas MPH m, Prof David L Heymann MD i n (1/12/2012, "Ecology of zoonoses: natural and unnatural histories," www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61678-X/fulltext, ADL)More than 60% of human infectious diseases are caused by pathogens shared with wild or

domestic animals. Zoonotic disease organisms include those that are endemic in human populations or enzootic in animal populations

with frequent cross-species transmission to people. Some of these diseases have only emerged recently.

Together, these organisms are responsible for a substantial burden of disease, with endemic and

enzootic zoonoses causing about a billion cases of illness in people and millions of deaths every year.

Emerging zoonoses are a growing threat to global health and have caused hundreds of billions of US dollars of economic damage in the past 20 years. We aimed to review how zoonotic diseases result from natural pathogen ecology, and how other circumstances, such as animal production, extraction of natural resources,

and antimicrobial application change the dynamics of disease exposure to human beings. In view of present anthropogenic trends, a more effective approach to zoonotic disease prevention and control will require a broad view of medicine that emphasises evidence-based decision making and integrates ecological and

evolutionary principles of animal, human, and environmental factors. This broad view is essential for the successful development of policies and practices that reduce probability of future zoonotic emergence, targeted surveillance and strategic prevention, and engagement of partners outside the medical community to help improve health outcomes and reduce disease threats. This is the first in a Series of three papers about zoonoses Introduction Pathogens shared with wild or domestic animals cause more than 60% of infectious diseases in man.1 Such pathogens and diseases include leptospirosis, cysticercosis and echinococcosis, toxoplasmosis, anthrax, brucellosis, rabies, Q fever, Chagas disease, type A influenzas, Rift Valley fever, severe acute respiratory syndrome (SARS), Ebola haemorrhagic fever, and the original emergence of HIV.2—6 Zoonotic diseases are often categorised according to their route of transmission (eg, vector-borne or foodborne), pathogen type (eg, microparasites, macroparasites, viruses, bacteria, protozoa, worms, ticks, or fleas), or degree of person-to-person transmissibility.7 The greatest burden on human health and livelihoods, amounting to about 1 billion cases of illness and millions of deaths every year, is caused by endemic zoonoses that are persistent regional health problems around the world.2 Many of these infections are enzootic (ie, stably established) in animal populations, and transmit from animals to people with little or no subsequent person-to-person transmission—for example, rabies or trypanosomiasis. Other zoonotic pathogens can spread efficiently between people once introduced from an animal reservoir, leading to

localised outbreaks (eg, Ebola virus) or global spread (eg, pandemic influenza). Zoonoses made up most of the emerging infectious diseases identified in people in the past 70 years which, although relatively

rare compared with endemic zoonoses, are a substantial threat to global health and have caused economic damage exceeding hundreds of billions of US dollars in the past 20 years.8, 9 Apart from the appearance of a pathogen for the first time in human beings, the distinction between endemic and emerging zoonoses can be viewed as temporal or geographical. An endemic disease in one location would be regarded as an emerging disease if it crossed from its natural reservoir and entered the human or animal populations in a new geographical area, or if an endemic pathogen evolved new traits that created an epidemic (eg, drug resistance). Key messages Nearly two-thirds of human infectious diseases arise from pathogens shared with wild or domestic animals Endemic and enzootic zoonoses cause about a billion cases of illness in people and millions of deaths every year, and emerging zoonoses are a rising threat to global health,

having caused hundreds of billions of US dollars of economic damage in the past 20 years Ecological and evolutionary perspectives can provide valuable insights into pathogen ecology and can inform zoonotic disease-control programmes Anthropogenic practices, such as changes in land use and extractive industry

actions, animal production systems, and widespread antimicrobial applications affect zoonotic disease transmission Risks are not limited to low-income countries; as global trade and travel expands, zoonoses are increasingly posing health concerns for the global medical community Ecological, evolutionary, social, economic, and epidemiological mechanisms affecting zoonoses' persistence and emergence are not well understood; such information could inform evidence-based policies, practices, and targeted zoonotic disease surveillance, and prevention and control efforts Multisectoral collaboration, including clinicians, public health scientists, ecologists and disease ecologists, veterinarians, economists, and others is necessary for effective management of the causes and prevention of zoonotic diseases Transmission of pathogens into human populations from other species is a natural product of our relation with animals and the environment. The emergence of zoonoses, both recent and historical, can be considered as a logical consequence of pathogen ecology and evolution, as microbes exploit new niches and adapt to new hosts. The underlying causes that create or provide access to these new niches seem to be mediated by human action in most cases, and include changes in land use, extraction of natural resources, animal production systems, modern transportation, antimicrobial drug use, and global trade. Although underlying ecological principles that shape how these pathogens survive and change have remained similar, people have changed the environment in which these principles operate. Domestication of animals, clearing of land for farming and grazing, and hunting of wildlife in new habitats, have resulted in zoonotic human infection with microorganisms that cause diseases such as rabies, echinococcosis, and the progenitors of measles and smallpox that had historically affected only animal populations through changes in contact and increased transmission opportunities from animals to people.10—12 As human societies have developed, each era of livestock revolution presented new health challenges and new

opportunities for emergence of zoonotic pathogens.13 In the past few decades, accelerating global changes linked to an expanding global population have led to the emergence of a striking number of newly described zoonoses, including hantavirus pulmonary syndrome, monkeypox, SARS, and simian immunodeficiency virus (the animal precursor to HIV). Some of these zoonoses, such as HIV, have become established as substantial new human pathogens that circulate persistently without repeat animal-to-person transmission. SARS could have established, but was contained by rapid global response to its emergence;14 other zoonoses, such as Ebola virus and Nipah virus, have not become established because of local control efforts or their intrinsic inability to transmit efficiently between people. However, others such as hantavirus pulmonary syndrome, which is enzootic in rodents in many locations, cause sporadic and infrequent clusters of infections in human beings.15 In all cases, these emerging zoonoses are defined by their relatively recent appearance (or detection) in a population or, in some cases, an amplification of transmission that increases the incidence, prevalence, or geographical distribution of previously rare pathogens.15 Emergence of a zoonosis depends on several factors that often act simultaneously to change pathogen dynamics. The capacity of a pathogen to transmit or spread in a population is commonly quantified by the basic reproduction number, or R0 (panel 1). In addition to inherent properties of the pathogen, factors affecting emergence or spread include environmental factors or changes in land use, human population growth, changes to human behaviour or social structure, international travel or trade,

microbial adaptation to drug or vaccine use or to new host species, and breakdown in public health infrastructure.17 With more than a billion international travellers every year, infected individuals could potentially spread zoonotic diseases anywhere in the world . Thus, with the emergence of new infectious diseases and the chronic presence of known zoonotic diseases in many low-income and middle-income countries that might or might not be adequately diagnosed or reported, zoonoses are increasingly relevant to the global medical community.

Zoonoses cause human extinction – different from other diseasesQuammen, award-winning science writer, long-time columnist for Outside magazine, writer for National Geographic, Harper's, Rolling Stone, the New York Times Book Review and others, 9/29/2012(David, “Could the next big animal-to-human disease wipe us out?,” The Guardian, pg. 29, Lexis) Infectious disease is all around us . It's one of the basic processes that ecologists study, along with predation and competition. Predators are big beasts that eat their prey from outside. Pathogens (disease-causing agents, such as viruses) are small beasts that eat their prey from within. Although infectious disease can seem grisly and dreadful, under ordinary conditions, it's every bit as natural as what lions do to wildebeests and zebras. But conditions aren't always ordinary.Just as predators have their accustomed prey, so do pathogens. And just as a lion might occasionally depart from its normal behaviour - to kill a cow instead of a wildebeest, or a human instead of a zebra - so a pathogen can shift to a new target. Aberrations occur. When a pathogen leaps from an animal into a person, and succeeds in establishing itself as an infectious presence, sometimes causing illness or death, the result is a zoonosis.It's a mildly technical term, zoonosis, unfamiliar to most people, but it helps clarify the biological complexities behind the ominous headlines about swine flu, bird flu, Sars, emerging diseases in general, and the threat of a global pandemic. It's a word of the future, destined for heavy use in the 21st century.Ebola and Marburg are zoonoses. So is bubonic plague. So was the so-called Spanish influenza of 1918-1919, which had its source in a wild aquatic bird and emerged to kill as many as 50 million people. All of the human influenzas are zoonoses. As are monkeypox, bovine tuberculosis, Lyme disease, West Nile fever, rabies and a strange new affliction called Nipah encephalitis, which has killed pigs and pig farmers in Malaysia. Each of these zoonoses reflects the action of a pathogen that can "spillover", crossing into people from other animals .Aids is a disease of zoonotic origin caused by a virus that, having reached humans through a few accidental events in western and central Africa, now passes human-to-human. This form of interspecies leap is not rare; about 60% of all human infectious diseases currently known either cross routinely or have recently crossed between other animals and us. Some of those - notably rabies - are familiar, widespread and still horrendously lethal, killing humans by the thousands despite centuries of efforts at coping with their effects. Others are new and inexplicably sporadic, claiming a few victims or a few hundred, and then disappearing for years.Zoonotic pathogens can hide. The least conspicuous strategy is to lurk within what's called a reservoir host: a living organism that carries the pathogen while suffering little or no illness. When a disease seems to disappear between outbreaks, it's often still lingering nearby, within some reservoir host. A rodent? A bird? A butterfly? A bat? To reside undetected is probably easiest wherever biological diversity is high and the ecosystem is relatively undisturbed. The converse is also true: ecological disturbance causes diseases to emerge. Shake a tree and things fall out.Michelle Barnes is an energetic, late 40s-ish woman, an avid rock climber and cyclist. Her auburn hair, she told me cheerily, came from a bottle. It approximates the original colour, but the original is gone. In 2008, her hair started falling out; the rest went grey "pretty much overnight". This was among the lesser effects of a mystery illness that had nearly killed her during January that year, just after she'd returned from Uganda.Her story paralleled the one Jaap Taal had told me about Astrid, with several key differences - the main one being that Michelle Barnes was still alive. Michelle and her husband, Rick Taylor, had wanted to see mountain gorillas, too. Their guide had taken them through Maramagambo Forest and into Python Cave. They, too, had to clamber across those slippery boulders. As a rock climber, Barnes said, she tends to be very conscious of where she places her hands. No, she didn't touch any guano. No, she was not bumped by a bat. By late afternoon they were back, watching the sunset. It was Christmas evening 2007.They arrived home on New Year's Day. On 4 January, Barnes woke up feeling as if someone had driven a needle into her skull. She was achy all over, feverish. "And then, as the day went on, I started developing a rash across my stomach." The rash spread. "Over the next 48 hours, I just went down really fast."By the time Barnes turned up at a hospital in suburban Denver, she was dehydrated; her white blood count was imperceptible; her kidneys and liver had begun shutting down. An infectious disease specialist, Dr Norman K Fujita, arranged for her to be tested for a range of infections that might be contracted in Africa. All came back negative, including the test for Marburg.Gradually her body regained strength and her organs began to recover. After 12 days, she left hospital, still weak and anaemic, still undiagnosed. In March she saw Fujita on a follow-up visit and he had her serum tested again for Marburg. Again, negative. Three more months passed, and Barnes, now grey-haired, lacking her old energy, suffering abdominal pain, unable to focus, got an email from a journalist she and Taylor had met on the Uganda trip, who had just seen a news article. In the Netherlands, a woman had died of Marburg after a Ugandan holiday during which she had visited a cave full of bats.Barnes spent the next 24 hours Googling every article on the case she could find. Early the following Monday morning, she was back at Dr Fujita's door. He agreed to test her a third time for Marburg. This time a lab technician crosschecked the third sample, and then the first sample.The new results went to Fujita, who called Barnes: "You're now an honorary infectious disease doctor. You've self-diagnosed, and the Marburg test came back positive."The Marburg virus had reappeared in Uganda in 2007. It was a small outbreak, affecting four miners, one of whom died, working at a site called Kitaka Cave. But Joosten's death, and Barnes's diagnosis, implied a change in the potential scope of the situation. That local Ugandans were dying of Marburg was a severe concern - sufficient to bring a response team of scientists in haste. But if tourists, too, were involved, tripping in and out of some python-infested Marburg repository, unprotected, and then boarding their return flights to other continents, the place was not just a peril for Ugandan miners and their families. It was also an international threat.The first team of scientists had collected about 800 bats from Kitaka Cave for dissecting and sampling, and marked and released more than 1,000, using beaded collars coded with a number. That team, including scientist Brian Amman, had found live Marburg virus in five bats.

Entering Python Cave after Joosten's death, another team of scientists, again including Amman, came across one of the beaded collars they had placed on captured bats three months earlier and 30 miles away."It confirmed my suspicions that these bats are moving," Amman said - and moving not only through the forest but from one roosting site to another. Travel of individual bats between far-flung roosts implied circumstances whereby Marburg virus might ultimately be transmitted all across Africa, from one bat encampment to another. It voided the comforting assumption that this virus is strictly localised. And it highlighted the complementary question: why don't outbreaks of Marburg virus disease happen more often? Marburg is only one instance to which that question applies. Why not more Ebola? Why not more Sars?

In the case of Sars, the scenario could have been very much worse . Apart from the 2003 outbreak and the aftershock cases in early 2004, it hasn't recurred. . . so far. Eight thousand cases are relatively few for such an explosive infection; 774 people died, not 7 million. Several factors contributed to limiting the scope and impact of the outbreak, of which humanity's good luck was only one. Another was the speed and excellence of the laboratory diagnostics - finding the virus and identifying it. Still another was the brisk efficiency with which cases were isolated, contacts were traced and quarantine measures were instituted, first in southern China, then in Hong Kong, Singapore, Hanoi and Toronto. If the virus had arrived in a different sort of big city - more loosely governed, full of poor people, lacking first-rate medical institutions - it might have burned through a much larger segment of humanity .One further factor, possibly the most crucial, was inherent in the way Sars affects the human body: symptoms tend to appear in a person before, rather than after, that person becomes highly infectious. That allowed many Sars cases to be recognised, hospitalised and placed in isolation before they hit their peak of infectivity. With influenza and many other diseases, the order is reversed. That probably helped account for the scale of worldwide misery and death during the 1918-1919 influenza. And that infamous global pandemic occurred in the era before globalisation. Everything nowadays moves around the planet faster, including viruses. When the Next Big One comes, it will likely conform to the same perverse pattern as the 1918 influenza: high infectivity preceding notable symptoms. That will help it move through cities and airports like an angel of death.The Next Big One is a subject that disease scientists around the world often address. The most recent big one is Aids, of which the eventual total bigness cannot even be predicted - about 30 million deaths, 34 million living people infected, and with no end in sight. Fortunately, not every virus goes airborne from one host to another. If HIV-1 could, you and I might already be dead. If the rabies virus could, it would be the most horrific pathogen on the planet . The influenzas are well adapted for airborne transmission, which is why a new strain can circle the world within days. The Sars virus travels this route, too, or anyway by the respiratory droplets of sneezes and coughs - hanging in the air of a hotel corridor, moving through the cabin of an aeroplane - and that capacity, combined with its case fatality rate of almost 10%, is what made it so scary in 2003 to the people who understood it best.Human-to- human transmission is the crux . That capacity is what separates a bizarre, awful, localised, intermittent and mysterious disease (such as Ebola) from a global pandemic. Have you noticed the persistent, low-level buzz about avian influenza, the strain known as H5N1, among disease experts over the past 15 years? That's because avian flu worries them deeply, though it hasn't caused many human fatalities. Swine flu comes and goes periodically in the human population (as it came and went during 2009), sometimes causing a bad pandemic and sometimes (as in 2009) not so bad as expected; but avian flu resides in a different category of menacing possibility. It worries the flu scientists because they know that H5N1 influenza is extremely virulent in people, with a high lethality. As yet, there have been a relatively low number of cases, and it is poorly transmissible, so far, from human to human. It'll kill you if you catch it, very likely, but you're unlikely to catch it except by butchering an infected chicken. But if H5N1 mutates or reassembles itself in just the right way, if it adapts for human-to-human transmission, it could become the biggest and fastest killer disease since 1918.It got to Egypt in 2006 and has been especially problematic for that country. As of August 2011, there were 151 confirmed cases, of which 52 were fatal. That represents more than a quarter of all the world's known human cases of bird flu since H5N1 emerged in 1997. But here's a critical fact: those unfortunate Egyptian patients all seem to have acquired the virus directly from birds. This indicates that the virus hasn't yet found an efficient way to pass from one person to another.Two aspects of the situation are dangerous, according to biologist Robert Webster. The first is that Egypt, given its recent political upheavals, may be unable to staunch an outbreak of transmissible avian flu, if one occurs. His second concern is shared by influenza researchers and public health officials around the globe: with all that mutating, with all that contact between people and their infected birds, the virus could hit upon a genetic configuration making it highly transmissible among people.

"As long as H5N1 is out there in the world," Webster told me, "there is the possibility of disaster. . . There is the theoretical possibility that it can acquire the ability to transmit human-to-human." He paused. "And then God help us."We're unique in the history of mammals. No other primate has ever weighed up on the planet to anything like the degree we do . In ecological terms, we are almost paradoxical: large-bodied and long-lived but grotesquely abundant. We are an outbreak.And here's the thing about outbreaks : they end . In some cases they end after many years, in others they end rather soon. In some cases they end gradually, in others they end with a crash. In certain cases, they end and recur and end again. Populations of tent caterpillars, for example,

seem to rise steeply and fall sharply on a cycle of anywhere from five to 11 years. The crash endings are dramatic, and for a long while they seemed mysterious. What could account for such sudden and recurrent collapses? One possible factor is infectious disease, and viruses in particular.

Disease has played a role in every state collapse in history – pandemics go nuclearMorris, professor of history at Stanford University, 3/22/2013(Ian, “The Measure of Civilization: How Social Development Decides the Fate of Nations,” Carnegie Council, Lexis)There are several periods when we get discontinuities, when we get collapses in social development scores. You can see several very clear examples on this graph.When we look back at the history of what happens when we get these great collapses in social development, every time we see the same five forces involved:Mass migrations that the societies of the day cannot cope with. This is always in the mix. The mass migrations often lead to huge epidemic diseases, as previously separate disease pools get merged. Epidemic diseases regularly killing half the population, it would seem, tend to lead to state failure. Governments cannot cope with catastrophe on this scale. The collapse of the governments tends to lead to breakdown in long-distance trade. Famines ensue, many, many more people die. And then, always there in the mix in some way, although it varies in every case, is climate change. It always plays into this. Now, I'm sure you don't need me to tell you these are forces that plenty of people are talking about as threats we are facing in the early 21st century.It seems to me perfectly possible that the 21st century is going to see another collapse of the kind we have seen so many times in the past. So in some ways it's possible the 21st century might be a rerun of what has happened many times before—but with one big difference: We now have nuclear weapons, which ancient people didn't have. The Romans would have loved nuclear weapons. Luckily, they didn't have them. I think if we do stumble into a collapse on the scale that I'm talking about here, we should seriously expect there is a possibility of these being used. It's quite possible that the 21st century will see a disaster that dwarfs anything we have seen earlier.

Antibiotic Resistance

Contention 2: Antibiotic Resistance—

Superbugs are a ticking time bomb without new antibioticsThe Week 4/1 The Week is a weekly news magazine, “Antibiotic-resistant bacteria 'pose risk of pandemic'”, 4/1/14, http://www.theweek.co.uk/health-science/58362/antibiotic-resistant-bacteria-pose-risk-pandemic//OFTHE World Health Organisation [WHO] has warned that antibiotic-resistant bacteria have now spread to every part of the world, giving rise to the potential for a series of untreatable epidemics. Its

report says that global misuse of antibiotics has increased the number of drug-resistant superbugs, which can render curable diseases lethal again. "The world is headed for a post-antibiotic era where common infections and minor injuries will kill once again," said Keiji Fukuda, assistant director-general for health security at the WHO. The study, which is the first of its kind, correlated data from 114 different countries to measure resistance to antibiotics. It focused on bacteria that cause common but serious diseases. In some countries, treatment is ineffective in more than half the cases of E. coli, The Guardian reports, as the bacteria is now resistant to the fluoroquinolone antibiotics used to treat it. In the UK, the report found

high rates of resistance in gonorrhoea. Carmen Pessoa Da Silva, the doctor who leads the WHO's programme, says: "If no action is taken to reduce the spread of resistance and find new solutions, we will reach a point where some infections will no-longer be treatable." When antibiotics entered widespread use in the

1950s they have were regarded as a miracle cure, but no new antibiotic drug has been discovered in more than 30 years. According to New Scientist, pharmaceutical companies are unwilling to invest large sums in developing new drugs that are used only for brief courses of treatment. In 2013 Britain's Chief Medical Officer, Dr Sally Davies, described antibiotic resistance as "a ticking time bomb" that posed a similar threat to terrorism, CBS reports.

Scenario 1 is CRE:

It’s everywhereReuters 2013 Reuters is a news organization that focuses on international news, “Doctors warned to be vigilant for warn new deadly virus sweeping the globe from Middle East”, 3/8/13, http://www.dailymail.co.uk/news/article-2290033/Doctors-warned-vigilant-warn-new-deadly-virus-sweeping-globe-Middle-East.html//OFWarnings of the deadly virus come as the CDC announced concerns over an increasing number of infections from a 'nightmare bacteria' found in U.S. hospitals. Public health officials have warned that in a growing number of cases existing antibiotics do not work against the superbug, Carbapenem-

Resistant Enterobacteriaceae (CRE). Patients became infected with the bacteria in nearly four per cent of US hospitals and in almost 18 per cent of specialist medical facilities in the first half of 2012, according to the Centers for Disease Control and Prevention (CDC). Dr Tom Frieden, director of the

CDC, said in a statement that the strongest antibiotics 'don't work and patients are left with potentially untreatable infections. ' He said scientists were 'raising the alarm' over the problem following increasing concern. Increasing numbers of patients in US hospitals have become infected with CRE, which kills up to half of patients who get bloodstream infections from them, according to a new CDC report. Some of the more than 70 types of Enterobacteriaceae bacteria - including E-coli - have become gradually resistant over a long period of time, even to so-called, 'last resort drugs' called

carbapenem. During the last 10 years, the percentage of Enterobacteriaceae that are resistant to these last-ditch antibiotics rose by 400 percent. One type of CRE has increased by a factor of seven over the last decade, Fox News reports. CRE infections usually affect patients being treated for serious conditions in hospitals, long-term acute-care facilities and nursing homes. Many of these people will use catheters or ventilators as part of their treatment - which are thought to be used by bacteria to enter deep into the patient's body.

And it decimates the global populationAdams 7/17 Mark Adams (Citing Doctors and the CDC) is a reporter for Naturalnews.com, an online news source specializing in medicine and natural sciences, “Drug-resistant superbug infections explode across U.S. hospitals: 500% increase foreshadows 'new plague' caused by modern medicine”, 7/17/14, Natural News, http://www.naturalnews.com/046041_CRE_superbugs_drug-resistant_infections_modern_plague.html#//OF(NaturalNews) Drug-resistant superbug infections have reached near-epidemic levels across U.S. hospitals, with an alarming 500% increase now documented in a study just published in the August issue of Infection Control and Hospital Epidemiology (the journal of the Society for Healthcare Epidemiology of

America). (1) Lead author of the study, Dr. Joshua Thaden, warned "This dangerous bacteria is finding its way into healthcare facilities nationwide... A CRE epidemic is fast approaching... Even this marked increase likely underestimates the true scope of the problem given variations in hospital surveillance practices." The study also found that an astonishing 94 percent of CRE infections were caused by healthcare

activities or hospital procedures. CRE superbugs explained CRE (carbapenem-resistant Enterobacteriaceae) is an incredibly dangerous superbug causing nearly a fifty percent fatality rate once a patient is infected. The World Health Organization calls it "one of the three greatest threats to human health," and all known antibiotics are useless in treating it. CRE arose out of the systematic abuse of antibiotics by doctors, who inadvertently created the perfect breeding ground for deadly bacteria by using narrowly-targeted chemical medications that lack the kind of full-spectrum action found in nature (in herbs like garlic, for example). Because of their highly-targeted chemical approach, antibiotics encouraged bacteria to develop molecular defenses that resulted in widespread resistance to Big Pharma's drugs. The situation is so bad today that the entire pharmaceutical industry has no drug, no chemicals and no experimental medicines which can kill CRE superbugs. Even worse, there are virtually no new antibiotics drugs in the research pipelines, either. Drug companies have discovered that it's far more profitable to sell "lifestyle management" drugs like statin drugs and blood pressure drugs than to sell antibiotics which treat acute infections. Antibiotics simply aren't very profitable because relatively few people acquire such infections. Meanwhile, everyone can be convinced they might have high cholesterol and therefore need to take a statin drug for life. Drug companies, in other words, have all but abandoned the industry of treating infections. Instead, they now primarily engage in the promotion of disease symptoms while selling drugs that attempt to alter measurable markers of those symptoms such as cholesterol numbers. Even though drug companies caused the superbug pandemic that's now upon us, in other words, they have deliberately abandoned humanity in defending against those superbugs because it's simply not profitable to do so. The end of antibiotics has arrived: Humanity faces a new plague caused by modern medicine The CDC has admitted that we are now living in a "post-antibiotics era." As

Infection Control Today states, "Antibiotic resistance is no longer a prediction for the future. It is happening right now in every region of the world and has the potential to affect anyone." (2) Dr. Arjun Srinivasan, associate director at the Centers for Disease Control and Prevention, went even further in a PBS interview, stating: (3) We've reached the end of antibiotics, period... We're here. We're in the post-antibiotic era. There are patients for whom we have no therapy, and we are literally in a position of having a patient in a bed who has an infection, something that five years ago even we could have treated, but now we can't. Keep in mind that doctors refuse to use natural substances to treat infections, which is why they believe no defenses against superbugs exist. Their indoctrination into the world of pharmaceuticals is so deeply embedded in their minds, in other words, that they cannot even conceive of the idea that an herb, a food or something from Mother Nature might provide the answer to superbugs. See this Natural News article on natural antibiotics that kill superbugs. The list includes honey. Hospitals are the perfect breeding grounds for superbugs By their very design, hospitals are prefect breeding grounds for superbugs for six very important reasons: 1) They put all the infected people under one roof, creating a high density infectious environment. 2) They allow doctors and medical staff to quickly and easily carry and transmit infectious diseases to new patients. Previous studies have documented how superbugs easily ride on doctors' ties, for example, or their mobile phones. 3) Medical staff still don't wash their hands as frequently as they should. The intense time demands placed on them discourage careful hand washing, causing many to skip this crucial step between patient visits. 4) Hospitals almost universally refuse to use broad-spectrum antibacterial remedies which are not drugs. Natural substances like honey and garlic show extraordinary multi-faceted antibacterial properties, as do certain metals such as silver and copper. Yet because these substances are not developed by pharmaceutical companies which dominate the field of medical practice, they are simply ignored even though they could save many lives. (And a doctor who prescribes "honey" doesn't sound as amazing and all-knowing as a doctor who prescribes "the latest, greatest laboratory breakthrough patented chemical medication.") 5) Hospital practices suppress human immune function to the point of systemic failure. Rather than boosting immune function, conventional medical treatments such as antibiotics and chemotherapy cause immune system failure. Hospitals lack sunlight and hospital food lacks key immune-boosting minerals such as zinc and selenium. On top of that, most of the drugs prescribed to patients by hospitals deplete key nutrients required for healthy immune function, leaving patients even more susceptible to superbug infections. 6) Hospital staff spread infectious diseases to their private homes. After acquiring an infection at work (at the hospital), staffers easily spread those infections to their own family members at home. The antibiotics plague is upon us We are right now living through the early stages of a global plague caused by modern

medicine. The industry that created this plague is utterly defenseless against it, leaving humanity to fight for survival in a world that's now far more dangerous than the one that existed before the invention of antibiotics. Antibiotics have indeed saved millions of lives, and they forever have an important place in any medical practice. Yet their careless use -- combined with medicine's willful and foolish abandonment of natural antibiotics that work far better -- has led humanity down the path of its own destruction. Today, a simple scrape of your arm or leg might now be fatal. Infections that occur during routine medical procedures which would have once been considered minor issues

are now deadly. And the worst part is that the bacteria continue to evolve more elaborate defenses against drugs while increasing their transmissibility. Human hospitals (and entire cities) are, by design, ideal pandemic hubs that rapidly spread disease. Like it or not, humanity has created the perfect storm for a pandemic decimation of the global population.

Scenario 2 is Tuberculosis:

Resistant TB causes extinctionPBS, funded by viewers like you, cites scientists, summarizes a documentary about science – generally reflects science, 2001(http://www.pbs.org/wgbh/evolution/about.html)"Survival of the fittest." — Raw competition? Or, a level of cooperation indispensable to life? Evolution tells us that both are important. We explore our own spiraling arms race with microorganisms, the only entities that can pose a threat to our existence . We follow the struggles of medical detectives uncovering the roots of epidemics and trace the alarming spread of resistance among pathogens that cause disease, like the new virulent t u b erculosis — nicknamed "Ebola with wings." Interactions between species are among the most powerful evolutionary forces on earth, and understanding them may be key to our own survival .

And it collapses RussiaTucker 2001 JONATHAN B. TUCKER is Director of the Chemical and Biological Weapons Nonproliferation Program at the Monterey Institute, “Contagious Fears; Infectious Disease and National Security.”, 6/22/2001, Harvard International Review, http://www.freepatentsonline.com/article/Harvard-International-Review/75213388.html//OFIn the short term, the NIE predicts that, in the hardest-hit countries of the developing and former communist worlds, the persistent burden of infectious disease is likely to aggravate and even provoke economic decay, social fragmentation, and political polarization. Already, the collapse of public health systems in Russia and the former Soviet republics has led to

a dramatic rise in HIV infection and drug-resistant tuberculosis in those countries. By 2010, AIDS and malaria combined will reduce the gross domestic products of several sub-Saharan African countries by 20 percent or more, bringing these nations to the brink of economic collapse as they lose the most productive segment of their populations. If current trends continue, a decade from now some 41.6 million children in 27 countries will have lost one or both parents to AIDS, creating a "lost generation" of orphans with little hope of education or employment. These young people may become marginalized or easily exploited for political ends, as in the increasingly pervasive phenomenon of the child-soldier, putting AIDS-stricken countries at risk of further economic decay, increased crime, and political instability. The NIE suggests that by the year 2020, AIDS and tuberculosis will account for the overwhelming majority of infectious disease deaths in the developing world. Nevertheless, a somewhat more hopeful picture has emerged in recent months as growing political pressure has led multinational pharmaceutical companies to lower the price of AIDS drugs sold to poor countries. The NIE on the global infectious disease threat provides unsettling but enlightening reading. It strongly suggests that unless the United States helps to contain the spread of infectious diseases such as AIDS, malaria, and tuberculosis in the developing

and former communist worlds, the resulting socioeconomic collapse could require massive infusions of emergency aid and perhaps even the deployment of US troops to restore order. The Bush administration, which unlike its predecessor has shown little interest in nontraditional threats, would do well to heed this warning.

That causes nuclear lashoutBlank December ‘13

Stephen, served as the Strategic Studies Institute’s expert on the Soviet bloc and the post-Soviet world from 1989 to 2013. Prior to that, he was Associate Professor of Soviet Studies at the Center for Aerospace Doctrine, Research, and Education, Maxwell Air Force Base, AL; he taught at the University of Texas, San Antonio; and he taught at the University of California, Riverside, “POLITICS AND ECONOMICS IN PUTIN’S RUSSIA: WHAT DO THEY MEAN FOR THE U.S. ARMY?,” In SSI’s “POLITICS AND ECONOMICS IN PUTIN’S RUSSIA,” ed. BlankThe defense and security implications of this dysfunctional and archaic system are equally negative.

Currently, there is a huge defense buildup that aims to spend $716 billion between now and 2020 to make the Russian armed forces a competitive high-tech armed force, with 70 percent of its weapons

being modern (whatever that category means to Moscow). Yet this system already has shown repeatedly that it cannot deliver the goods and that the attempt to remilitarize at this relatively breakneck speed

(relative to other comparable powers) is failing to produce the weapons Moscow wants . Consequently, it is clear not only that nuclear weapons will remain the mainstay of Russian military might through 2020,

but it is also equally likely, from the current vantage point, that this nuclear preeminence will remain well into the decade 2020-30 as well. This means that, for a whole range of contingencies, Moscow will have to rely more than any other comparable power on nuclear threats and deterrence, and deterrence presupposes a hostile relationship with the targets of that strategy. Apart from issues of democracy promotion and regional security in Eurasia, this conclusion has sobering implications for U.S. defense policy as a whole because it will place limits on what can be achieved through arms control treaties, obstruct the Barack Obama administration’s declared ambition to move on to a zero nuclear weapons trajectory, and inhibit a genuine military and

political partnership with Russia. Furthermore, given the postulate presented here of a deteriorating domestic situation due to an increasingly sclerotic economic-political formation, we could well encounter a situation where a revolutionary situation inside Russia due to the blockage of progress intersects with a

massive security crisis that could , as in 1991, involve a coup and the danger of seizure of nuclear weapons and potential wars across Eurasia. Or, we could see a diversionary war as the Russo-Japanese

war was launched in part in order to busy “giddy minds with foreign wars.” Arguably, we are witnessing the first signs in today’s Russia of the advent of a long-term crisis culminating in such a domestic and then

international crisis. This crisis would combine mounting disaffection, if not protest, and continuing subpar economic performance is a situation that approximates Vladimir Lenin’s 1915 definition of a revolutionary situation. According to Lenin’s oft-quoted definition: What, generally speaking, are the symptoms of a revolutionary situation? We shall certainly not be mistaken if we indicate the following three major symptoms: (1) when it is impossible for the ruling classes to maintain their rule without any change; when there is a crisis, in one form or another, among the “upper classes,” a crisis in the policy of the ruling class, leading to a fissure through which the discontent and indignation of the oppressed classes burst forth. For a revolution to take place, it is usually insufficient for “the lower classes not to want” to live in the old way; it is also necessary that “the upper classes should be unable” to live in the old way; (2) when the suffering and want of the oppressed classes have grown more acute than usual; (3) when, as a consequence of the above causes, there is a considerable increase in the activity of the masses, who uncomplainingly allow themselves to be

robbed in “peace time,” but, in turbulent times, are drawn both by all the circumstances of the crisis and by the “upper classes” themselves into independent historical action.13 (italics in original) To be sure, none of this suggests the imminence of a revolution . Rather, it suggests the imminence of a structural crisis leading to the situation defined here by Lenin and which evermore characterized Tsarist Russia after the great reforms of the 1860s and the Soviet state after Leonid Brezhnev. Neither we, nor any other reputable observer, expect an imminent collapse of the Putin system. But Russia already appears to be visibly bearing the seeds of its own entropy and ultimate collapse. Distinguished Russian scholars like Lilia Shevtsova and Olga Kryshtanovskaya openly state that Russia has slipped into a revolutionary situation.14 That process took some 50 years in Tsarist Russia and a generation in Soviet Russia, suggesting the acceleration of large-scale socio-political change and its growing department, even if we are talking about a long-gestating process. But if this assessment has merit, then we are only at its inception, not its conclusion, and many more negative phenomena and Russian behaviors can be expected before the advent of a crisis that could occur, if this acceleration of protest trends and institutional entropy occur by 2030. Potential contingencies could even possibly entail the use of force either at home (and not just in a counterinsurgency mode against jihadi rebels as in the North Caucasus) or beyond Russia’s borders as in the Russo-Georgian war of 2008. Indeed, as the regime moves further along its current trajectory, such belligerent behavior increasingly appears to be the norm. As Andrei Illarionov, a former economic advisor to Putin, has observed: Since its outset, the Siloviki regime has been aggressive. At first it focused on actively destroying centers of independent political, civil, and economic life within Russia. Upon achieving those goals, the regime’s aggressive behavior turned outward beyond Russia’s borders. At least since the assassination of the former Chechen President Zelimkhan Yandarbiyev in Doha, Qatar, on 14 February 2004, aggressive behavior by SI (Siloviki-men of the structures of force-author) in the international arena has become the rule rather than the exception . Over the last five years the regime has waged ten different “wars” (most of them involving propaganda, intelligence operations, and

economic coercion rather than open military force) against neighbors and other foreign nations. The most recent targets have included Ukraine (subjected to a “second gas war” in early 2009), the United States (subjected to a years-long campaign to rouse anti-American sentiment), and, most notoriously, Georgia (actually bombed and invaded in 2008). In addition to their internal psychological need to wage aggressive wars, a rational motive is also driving the Siloviki to resort to conflict. War furnishes the best opportunities to distract domestic public opinion and

destroy the remnants of the political and intellectual opposition within Russia itself. An undemocratic regime worried about the prospect of domestic economic social and political crises—such as those that now haunt Russia amid recession and falling oil prices – is likely to be pondering further acts of aggression. The note I end on, therefore, is a gloomy one: To me the probability that Siloviki Incorporated well be launching new wars seems alarmingly high.15 Accordingly, even though no observer expects a comparable revolution anytime

soon, the signs of crisis are also quite visible for anyone who cares to look for them. At the same time, the advent of social and information technologies, as well as Russia’s partial integration into the global economy, suggests that any repeat performance will take even less time than this, so it is not inconceivable that within 10-20 years, we could see a Russia openly enmeshed in a structural crisis from which there is no way out other than large-scale transformation, if not revolution. Given Russia’s strategic weight and military capability, this prognosis poses immense questions, if not problems, for the U.S. Government as a whole as it seeks to grapple with the realities of Russian policy. Were this a monograph on the subject of U.S.-Russian relations, it would take a long report to work through all those issues. But here, we must content ourselves with recommendations for the U.S. Army in its activities. To do that, we must view the Army in its current strategic context.

Scenario 3 is agriculture:

Resistant disease collapses farming and results in global famineClark, professor of microbiology at Southern Illinois University, 2010(David, Germs, Genes, and Civilization, p. 250-251)One way to combat resistance is to replace old antibiotics with newly invented ones. Soon after they were first discovered, there was a big rush to discover new antibiotics or modify old ones chemically, yielding new variants. When most known bacterial diseases had cures, complacency set in. Recently, drug resistance has hit the headlines and research has picked up again. Although some new antibiotics are now in the pipeline, it takes several years to get a new drug from laboratory to hospital. As new antibiotics are deployed, resistance will inevitably appear. We can look forward to a permanent cold war between bacteria and pharmaceutical companies.Where do the resistance genes on plasmids come from? They are gifts from Mother Nature, like most antibiotics. Long before humans isolated penicillin from the mold Penicillium, or streptomycin from the bacterium Streptomyces, these antibiotics were deployed to wage biological warfare in the soil. Bacteria and molds have been slugging it out for eons before humans joined in the fray. Not only did microorganisms develop antibiotics to kill each other, but they developed resistance mechanisms to counter each other’s attacks. Some bacterial cultures stored before penicillin was discovered already had resistance genes. Thus, resistance to most antibiotics probably predates their use by humans. Increased use has led to the spread of these resistance genes.Disease and the food supplyWe have focused on human disease, but remember that livestock and crop plants suffer from infections, too. Modern farmers tend to rely heavily on a few main crops, with little crop rotation. Large areas of a single crop provide the same opportunities for plant diseases that overcrowded cities provide for human infections. The warmer, wetter weather that is becoming more prevalent favors fungal infections that attack plants. For example, wheat scab outbreaks in the United States and Canada caused massive losses in the 1990s.Decreased surpluses in the major grain exporters undermine the safety net for overpopulated third world nations. If major drought in tropical areas such as Africa or India coincides with major crop losses in the grain exporters, the result could be widespread famine. In 2006-2007, world grain reserves fell to 57 days of consumption, the lowest since 1972.Perhaps the most serious current threat to our food supply is the wheat rust fungus (Puccinia graminis). A new and highly virulent strain emerged from Uganda in 1999 and was, therefore, named Ug99. It is presently in Africa and parts of Asia. Because the spores are airborne, this fungus will inevitably spread worldwide. Breeding resistant wheat varieties is in progress but takes several years.Overpopulation and microbial evolution

Overpopulation does not merely threaten starvation; it sets the scene for the evolution of new infectious diseases. The more people there are—and the more crowded, unhygienic, and malnourished they are—the greater the opportunity for some new and virulent plague to emerge. So far, we have kept ahead.

That causes World War 3Calvin, theoretical neurophysiologist at the University of Washington, 1998(William H., The Atlantic Monthly, v281 i1 pcover,47-50,52+, infotrac)The population-crash scenario is surely the most appalling. Plummeting crop yields would cause some powerful countries to try to take over their neighbors or distant lands--if only because their armies, unpaid and lacking food, would go marauding, both at home and across the borders. The better-organized countries would attempt to use their armies, before they fell apart entirely, to take over countries with significant remaining resources, driving out or starving their inhabitants if not using modern weapons to accomplish the same end: eliminating competitors for the remaining food. This would be a worldwide problem--and could lead to a Third World War--but Europe's vulnerability is particularly easy to analyze. The last abrupt cooling, the Younger Dryas, drastically altered Europe's climate as far east as Ukraine. Present-day Europe has more than 650 million people. It has excellent soils, and largely grows its own food. It could no longer do so if it lost the extra warming from the North Atlantic.

Solvency

Contention 3: Solvency –

Terrestrial research is failing – only marine microbes solve for new emerging diseasesXiong et al 2013 - from the Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutesfor Biological Sciences, Chinese Academy of Sciences, Shanghai (Zhi-Qiang, Jian-Feng Wang, Yu-You Hao, Yong Wang, "Recent Advances in the Discovery and Development of MarineMicrobial Natural Products," Mar. Drugs 2013, 11, 700-717, doi:10.3390/md11030700, ISSN 1660-3397, ADL)There is a perpetual need for new chemo-therapeutants, especially novel antibiotics, to combat new diseases and drug-resistant pathogens that are becoming a significant threat to public health [1]. The discovery and development of new drugs from natural products

(NPs) has played a significant role over the last few decades. Over 28% of the new chemical entities and 42% of the anticancer drugs introduced into the market can be traced back to NPs [2]. In addition to plants and animals, microorganisms are a major resource for the discovery of new drugs. More than 50,000 microbial natural products (MNPs) have been obtained and have played an important role in drug discovery. The majority of these have been isolated from terrestrial-borne microbes [3]. However, after 50 years of intensive screening from terrestrial-borne microbes, the pace of MNPs’ discovery and development with a unique scaffold has dramatically declined over the last two decades. Meanwhile, the emergence of severe resistance to antibiotics in microbial pathogens, such as Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-

resistant S. aureus (VRSA), and the current increase in the number of new diseases/pathogens,

e.g., Gram-negative New Delhi metallo-beta-lactmase(NMD-1) bacteria have caused a resurgence of interest in the discovery of MNPs with unique scaffolds to meet the urgent demand for new drugs. Recent trends in drug discovery emphasize that marine microorganisms are a

potentially productive source of novel secondary metabolites and have great potential to increase the number of marine NPs in clinical trials [4]. In contrast to the terrestrial environment, the oceans are a rich and relatively untapped reservoir of novel NPs . Over 15,000 structurally diverse NPs with an astounding assortment of bioactivities have been identified from marine environments since the 1970s [5]. This diversity has attracted researchers to screen MMNPs in drug discovery. Over 30 compounds derived from marine microbes such as didemnin B (Aplidine™)and thiocoraline are in clinical or preclinical studies for the treatment of different types of cancers [6].However, the search for MMNPs has only just begun [6,7]. In this paper, we review the recent advances in MMNP discovery and development, especially addressing two important topics: (i) isolation and cultivation approaches of marine microorganisms, and (ii) strategies for the discovery and development of MMNPs

Ocean compounds are six times more likely to produce medicine – key to address resistance and zoonotic diseaseInstitute of Medicine Board on Population Health and Public Health Practice June 2014(Roundtable on Environmental Health Sciences, Research, and Medicine, “Understanding the Connections Between Coastal Waters and Ocean Ecosystem Services and Human Health: Workshop Summary,” National Academies Press, http://www.ncbi.nlm.nih.gov/books/NBK209255/)There are many other types of diseases that are poorly treated, such as microbial infections. Staphylococcus aureus, for example, has gone from being a highly sensitive strain to an increasingly drug-resistant strain (methicillin-resistant S. aureus that is now encountered in the community as well as in hospitals). It is a danger to population health, and current pharmaceuticals do not work effectively against the infection (Chambers and DeLeo, 2009).

New pharmaceuticals are needed to treat these types of resistant organisms, Gerwick said. New methods for their application are needed as well because the same problem will recur if antibiotics continue to be used in the way they have in the past. Also newly emergent diseases, particularly viral diseases, are being transmitted from wild animal populations to human populations and giving rise to various diseases such as AIDS and many others. As humans continue to erode the natural habitat, there will be more contact with wild animals and an increased risk of viral diseases in the wild animal population transmitted to human populations.Pharmaceuticals are derived from diverse sources, Gerwick explained. Of 1,355 new approved drugs spanning the period 1981 to 2010, about 26 percent were derived from natural products. A growing number of pharmaceuticals, about 21 percent, come from biologics or vaccines. Just over half of pharmaceuticals are synthetic drugs, but it can be seen that in many cases the synthetic chemist has looked to nature for an aspect of a molecule and then embedded this special feature into another molecule of synthetic origin, which now has the needed pharmaceutical properties. In this way, a majority of pharmaceuticals are in some sense natural product derivatives or inspired by natural products (Newman and Cragg, 2012).The Oceans Are a Productive Source of New MedicinesThe marine environment and its unique life forms, with their myriad colors and shapes and sizes and adaptations to underwater life, have been a tremendous resource of novel chemistries, many of which have successfully been translated into new medicines. Gerwick mentioned nine marine natural products, derivatives, or inspired agents approved by the U.S. Food and Drug Administration (FDA) or European Medicines Agency (EMEA) (see Figure 5-1). For example, there is a series of pure nucleosides deriving from sponges which has given rise to three very useful anticancer agents and one antiviral agent. Then, there is a peptide used by the cone snail to prey on fish, which has been used in medications for treatment of chronic pain that is no longer responsive to opioids. These and many other new drugs look to nature for inspiration. Gerwick pointed out that the success record of marine natural products in this field, namely one drug per 2,450 compounds, is six times more productive than the industry standard (Gerwick and Moore, 2012).

Marine microbes make the pharmaceutical pipeline sustainable – there is no alternativeWaters, Hamann, Department of Pharmacognosy @ University of Mississippi, Hill, and Place, Institute of Marine and Environmental Technology @ University of Maryland, 2010(Amanda, Mark, Russell and Allen, “The expanding role of marine microbes in pharmaceutical development,” Current Opinion in Biotechnology, December)Marine natural products provide an excellent opportunity to study diverse and unique compounds not readily accessible from any other source leading to expansion of the pharmaceutical pipeline. Marine microbes can produce unique compounds covering new chemical space and the utility of marine natural products is expanding beyond its original role in identification of new prototype drug leads into fields of study involving sustainable supplies of unique molecule using biosynthesis in conjunction with synthesis. Perhaps the greatest impact marine natural products has played is in revealing that unexplored and previously inaccessible chemical space can contribute to growth in the pharmaceutical pipeline. Improved methodologies in fermentation technologies, biosynthesis and synthesis provide opportunities to both create and supply drug leads which would not be available by any single method independently. As a result pharmaceutical biotechnology in the future is certain to provide increasingly sophisticated molecular architecture assembled using biosynthesis and synthesis in concert.

U.S. Key

Contention 4: U.S. key—

U.S. action is needed – NOAA can develop the necessary technology and partner with pharmaceutical companies – and a fee-based system will pay for itselfValette-Silver, oceanographer @ NOAA, and Bohan, science program coordinator @ NOAA, report of the NOAA Marine Microbes Workshop, November 2011(Natholie and Margot, http://explore.noaa.gov/sites/OER/Documents/Marine-Microbes-Workshop-Report.pdf)There is a great need to develop new technologies and tools to study marine microbes. In particular, it is essential to work towards a new technology, such as a microchip, that would allow for the in-situ sequencing of microbe genomes, similar to the coral reef microarray. It is indispensable to develop and maintain a well-established and robust observing system for marine microbes. In particular, NOAA should use the National Estuarine Research Reserve System, Integrated Ocean Observing System and other regularly sampled stations (e.g., National Status and Trends, etc.) to add biogeochemical and microbes observations as well as microbial sampling to activities already in progress. The data obtained would directly be used for the development of a regional Earth model with location perspective. Great advances could be achieved in NOAA by creating a Marine Microbe Program and a core facility for natural products derived from marine microbes,. This last item could be fee-based and would provide a standardized set of tests especially centered on enzymes of interest to NOAA. Finally, in collaboration with DOE, NOAA should investigate the potential role of the National Oceanographic Data Center (NODC) in storing data and metadata regarding microbes and sequences for viruses and prokaryotes. Partners For all these proposed activities, NOAA should work collaboratively with academic institutions, especially cooperative institutes, and with other agencies (such as NSF, National Institute of Science & Technology (NIST), Department of Energy (DOE), Department of Interior (DOI), Department of Defense (DOD) and the Smithsonian Institution) to create a National Marine Microbe Program. In NOAA, partners include scientists and managers from OAR, NOS, NMFS and NESDIS. NWS is not yet involved but in light of their recent association with the Ecological Forecasting Working Group, an effort should be made to bring them into the fold of the NOAA Marine Microbes Working Group. Private sectors partners should be sought after to enlarge the circle of interested parties, especially entities dealing with biotechnology and pharmaceuticals.

The private sector watches federal microbe policy – key to new antibioticsDr. Avery, president and director of the Woods Hole Oceanographic Institution, 6/11/2013(Susan k., testimony before the Senate Committee on Commerce, Science, and Transportation: Subcommittee on Oceans, Atmosphere, Fisheries and Coast Guard, CQ Congressional Testimony, Lexis)There is the microbial frontier, where 90 percent of the ocean biomass resides and which is invisible to the human eye. There are about 300,000 times more microbes in the ocean than there are observable stars in the universe.5 Ocean scientists have just begun to explore this universe of marine microbes, which holds the key to healthy biological

functioning of the ocean ecosystem, much as the microbiome in the human body is critical to our health. They are also searching for unknown biochemical pathways and compounds, for new antibiotics, and for novel treatments for diseases such as Alzheimer's and cystic fibrosis.Then there is the frontier of temporal and spatial scales that must be overcome to monitor and forecast changes to the deep and open ocean. The ocean exhibits large, basin-wide patterns of variability that change over periods ranging from days and weeks to years, decades, and longer. Understanding and observing these patterns, including El Nino- Southern Oscillation (ENSO), offer potential for improved prediction of climate variability in the future. For most of my career, I have been an atmospheric scientist. The atmosphere and ocean are both fluids (one that is compressible, the other incompressible). These two systems are interwoven and inseparable.But while we have long-established, extensive networks of meteorological instruments continually monitoring our atmosphere, we have just begun to establish a relative toehold of long-term observatories to understand, and monitor how the ocean operates.To truly comprehend Earth's dynamic behavior and to monitor how it affects us back on land, scientists must establish a long-term presence in the ocean, including platforms and suites of physical, chemical, and biological sensors from which to view how the ocean and seafloor change in fine resolution over seasons, years, and decades. This same observing capability will provide the basis for improved forecasts from models that incorporate data and observations from the ocean, atmosphere, and land and that provide the basis for decision making by national, state, and local agencies.Variability such as weather events associated with ENSO has significant societal and economic impacts in the U.S., and a combination of a dedicated ocean-observing system in the tropical Pacific plus models that forecast ENSO impacts is now in place to help society adapt in times of increased variability. The promise of additional benefits from observing, understanding, and predicting the ocean and its impacts is real. Modeled reconstructions by Hoerling and Kumar of the 1930's drought in the Central U.S. recently linked that event to patterns of anomalies in sea-surface temperature far from the U.S.The global scale of the circulation of the ocean and basin-scale patterns of ocean variability on decadal and longer time scales may present sources of improved predictive skill in future weather and climate models.Moving forward, we need to be even more adaptive and agile, applying new technologies in ways that both make crucial observations more effectively and make coincident observations of the biology, chemistry, and physics of the ocean. At the same time we need at our modeling and prediction centers to establish the resources and mindset that will support testing and adoption of research results that lead to improved predictions.We are on the edge of exploration of many ocean frontiers that will be using new eyes in the ocean. Public-funded/private-funded investment in those eyes is required, but will not be successful without adequate and continuing federal commitment to ocean science. Support such as Jim's and the Schmidt Ocean Institute, which was founded by Eric Schmidt and operates the research vessel Falkor, help fill gaps in support for research and development or for access to the ocean.However, the fact remains that federal funding is by far the leading driver of exploration, observation, and technical research and development that has a direct impact on the lives of people around the world and on U.S. economic growth and leadership. It also remains the bellwether by which philanthropic entrepreneurs judge the long-term viability of the impact their investment will have on the success that U.S. ocean science research will have around the globe.

Only U.S. research gets drugs to the marketplace – it has a dominant advantage over any other countryDeVol, chief research officer at the Milken Institute, Bedroussian, research economist at the Millken Institute, and Yeo, senior research analyst at the Millken Institute, Sept 2011

(Ross, Armen, and Benjamin, “The Global Biomedical Industry: Preserving U.S. Leadership,” http://www.milkeninstitute.org/pdf/CASMIFullReport.pdf)Biomedical innovation is an intricate process that begins in the lab and spans years of effort to transform scientific discoveries into vaccines, diagnostics, devices, and therapies that improve patients’ lives. Over the past few decades, the United States has created and refined a remarkably productive framework for developing new biomedical innovations and bringing them to the marketplace—in fact, it’s one of the most dramatic success stories written by any American industry in the past century. Whether measured by international or domestic market share, revenue, jobs, number of regulatory approvals, patents, R&D expenditures, or publications in the biomedical field, the U.S. holds a commanding position. Prior to 1980, European firms defined the industry, both in terms of market presence and in their ability to create and produce innovative new products. Historical advantages and an enviable concentration of resources fueled the success of firms in Germany, France, the U.K., and Switzerland. Japan had a presence in the industry as well.But beginning in the 1980s, the United States surged to the forefront of biomedical innovation. This sudden and remarkable shift was no accident: It was the result of strong policy positions taken by the federal government. The absence of price controls, the clarity of regulatory approvals, a thoughtful intellectual property system, and the ability to attract foreign scientific talent to outstanding research universities put the U.S. on top. The resulting ecosystem—defined by university-business collaborations, industry clusters, private equity finance, and entrepreneurship—far surpassed the prevailing model in Europe. The innovative leaps made in biopharmaceutical research, medical devices, and diagnostics gave the U.S. a major advantage that it continues to hold today.

U.S. research gives us the best chance of more drugs fast – a pandemic could emerge any day – it’s a race to new cures – and federal funding is keyDeVol, chief research officer at the Milken Institute, Bedroussian, research economist at the Millken Institute, and Yeo, senior research analyst at the Millken Institute, Sept 2011(Ross, Armen, and Benjamin, “The Global Biomedical Industry: Preserving U.S. Leadership,” http://www.milkeninstitute.org/pdf/CASMIFullReport.pdf)U.S. Competitive AdvantagesA nation's biomedical industry cannot be viewed solely through the prism of the results achieved by individual firms. It is shaped in crucial ways by a broader set of institutions, market conditions, infrastructures, and government policies that influence those companies' strategies. The US. industry has been fostered by favorable intellectual property policies; government funding for basic research through the NIH, which has helped to build a strong STEM workforce; a competitive free market for innovative products; and the ability to access robust capital markets. Another major factor was the foresight of the federal government in adopting policies that support the connection between research and entrepreneurship, helping universities commercialize their discoveries in the marketplace. We will examine some of these advantages in the section that follows.Size of the Consumer MarketThe United States enjoys substantial benefits due to the sheer size of its consumer market. As of 2008, the U.S. biomedical product market was almost four times larger than Japan's, which ranked second in terms of total expenditures. Although the rise of the European Union allowed for greater economies of scale, the linguistic and cultural demands of its member nations keep the market more fractured than that in the U.S.38In 2008, Americans spent $234 billion on pharmaceuticals and related products. This translates to $769 per capita, the highest per-capita expenditure among the OECD countries and 25 percent higher than that of the secondhighest-ranking country, Canada. On the other hand, Japan, Germany, and France spent $60 billion ($471 per capita), $41 billion ($501 per capita) and $31 billion ($488 per capita), respectively. The growth trend of these expenditures

has dramatically progressed since 1995.39 Market sales of pharmaceuticals equaled 2.1 percent of U5. GDP (France was second-highest in this measure at 1.54 percent).4°ln 2010, the US. medical device market was the world's largest at an estimated $94.9 billion.“Strength in Human CapitalInnovation is the key to the survival and continued growth of the biomedical industries—and well-educated and highly trained human capital is the driving force behind innovation. In 2006, the United States awarded the largest number of science and engineering doctoral degrees of any country, followed by China, Russia, Germany, and the United Kingdom.42The United States has built excellent biomedical science research competencies at its universities and research institutions, which are able to obtain funding from both federal and industry sources. When university R&D can be leveraged for commercialization in the private sector, the partnerships can be beneficial to both parties. Funding from commercialization enables an institution to further its research agenda and help recruit talent, while the biomedical industry can expand the scope and depth of its research with the help of outside experts, often at much lower cost.The depth of a region’s talent pool determines its ability to attract large corporations and small firms alike. Physical proximity to top universities and research institutions allows corporations to tap into the specialized human capital they need to build their workforces. Together they form an ecosystem that provides fertile ground for biomedical innovation.According to the OS World University Rankings 2010, the United States has seven of the top 10 schools in the world for life science and biomedicine programs.46 Harvard ranks No. 1, with MIT at No. 8; together these institutions form the cornerstone of a major life sciences cluster in the Boston metro area. Stanford and UC Berkeley rank 4th and 5th, respectively, fostering another cluster of innovation in the San Francisco Bay Area.

Pandemics – Ext.

Civil Wars Impact Add-on

Pandemics cause global civil wars – regression analysis provesLetendre, Fincher, Department of Biology at the University of New Mexico, and Thornhill, Department of Computer Science at the University of New Mexico, 2010 (Kenneth, Corey, and Randy, “Does infectious disease cause global variation in the frequency of intrastate armed conflict and civil war?,” Biological Reviews, p. 669)Geographic and cross-national variation in the frequency of intrastate armed conflict and civil war is a subject of great interest. Previous theory on this variation has focused on the influence on human behaviour of climate, resource competition, national wealth, and cultural characteristics. We present the parasite-stress model of intrastate conflict, which unites previous work on the correlates of intrastate conflict by linking frequency of the outbreak of such conflict, including civil war, to the intensity of infectious disease across countries of the world. High intensity of infectious disease leads to the emergence of xenophobic and ethnocentric cultural norms. These cultures suffer greater poverty and deprivation due to the morbidity and mortality caused by disease, and as a result of decreased investment in public health and welfare. Resource competition among xenophobic and ethnocentric groups within a nation leads to increased frequency of civil war. We present support for the parasite-stress model with regression analyses. We find support for a direct effect of infectious disease on intrastate armed conflict, and support for an indirect effect of infectious disease on the incidence of civil war via its negative effect on national wealth. We consider the entanglements of feedback of conflict into further reduced wealth and increased incidence of disease, and discuss implications for international warfare and global patterns of wealth and imperialism.

Those go nuclearShehadi, Research Associate at the International Institute for Strategic Studies, 1993(Kamal, Ethnic Self Determination And the Break Up of States, Dec 1993, p. 81)This paper has argued that self-determination conflicts have direct adverse consequences on international security. As they begin to tear nuclear states apart, the likelihood of nuclear weapons falling into the hands of individuals or groups willing to use them, or to trade them to others, will reach frightening levels. This likelihood increases if a conflict over self-determination escalates into a war between two nuclear states. The Russian Federation and Ukraine may fight over the Crimea and the Donbass area; and India and Pakistan may fight over Kashmir. Ethnic conflicts may also spread both within a state and from one state to the next. This can happen in countries where more than one ethnic self-determination conflict is brewing: Russia, India and Ethiopia, for example. The conflict may also spread by contagion from one country to another if the state is weak politically and militarily and cannot contain the conflict on its doorstep. Lastly, there is a real danger that regional conflicts will erupt over national minorities and borders.

Biodiversity

No defense – Zoonotic diseases will mutate and cause species extinctionVandegrift, Wale, and Epstein 11 - Kurt J, Nina, Jonathan H. respectively of the Center for Infectious Disease Dynamics and EcoHealth Alliance (15 April 2011, "An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses," http://www.mdpi.com/1999-4915/3/4/379, ADL)Our planet is currently experiencing the sixth mass extinction event in history [1]. Although there

are problems with estimating the total number of extant animal species [2], recent extinction rates are thought to be 100- to

1000-times greater than past rates determined from the fossil record. It is estimated that as many as 140,000 species are perishing each year [3]. Although habitat loss and fragmentation are the main drivers of this

high extinction rate, infectious disease also contributes to animal population declines either independently, by reducing population size, or through interactions with other processes

[4,5]. Indeed, these anthropogenic changes to habitat are also contributing to a second biological crisis: an increase in the rate of emerging and re-emerging infectious diseases (EIDs) [6,7]. Of

these EIDs, 75% are zoonotic (see Table 1 for a definition) [8] and 37% are RNA viruses [9]. The high mutation rate of

RNA viruses coupled with their ability to recombine and reassort allows for a rapid rate of evolution. In turn, this makes them highly adaptable and thus able to both exploit the new hosts and habitats afforded by a changing environment, as well as to develop resistance to treatments [10].

Examples of zoonotic RNA viruses which have emerged relatively recently include SARS coronavirus (SARS CoV), West Nile virus (WNV), Chikungunya virus, the 2009 influenza A (H1N1)

and human immunodeficiency virus type 1 (HIV-1) and 2 (HIV-2). Cumulatively, these ailments have claimed hundreds of millions of human lives and cost the global economy hundreds of billions of US dollars. Among all viruses, HIV-1 causes the greatest amount of human mortality [11] and its immunosuppressive nature is facilitating the

resurgence of ―old‖ pathogens (i.e., tuberculosis) in human populations [12]. It is possible that the emergence of HIV is also encouraging cross-species transmission and that these disease threats may have a severe, negative impact on wild animal populations [13]. A multi-disciplinary approach will be necessary to combat

the crises of extinction and disease emergence because human, ecosystem and animal health are inextricably linked. In recent years, great advances have been made in virology and disease ecology, particularly towards elucidating the mechanisms behind the emergence and evolution of zoonotic viruses. Thus, it is important to review and consider how advances in virology and disease ecology complement each other. The roots of ecology date back to Theophrastus in the 4th century B.C. [14]. The concept of food chains originated in the 17th century and Darwin and Wallace put forth the theory of evolution in the 18th century [15], but ecology did not become a prominent field until 1927 when two key advances transformed the study into a proper discipline. In this year, Charles Elton published his Animal Ecology [16] and Kirmack and McKendrick (1927) [17] formulated a model to describe the progress of an epidemic in a homogenous population [16,17]. In the 1960s, Rachael Carson‘s Silent Spring Viruses 2011, 3 381 generated concern for the environment and thrust ecologists into a new political field where preserving the integrity of our global ecosystems was the priority [18]. Even so, the Society for Conservation Biology was not established until 1985 [19]. As a part of this transition, ecology shifted from a descriptive science to one of prediction, reflecting the hope that ecologists might mitigate changes which can have negative impacts upon the ecosystem. Ecologists have branched out into the study of parasites and disease as it has become increasingly apparent that parasites are inextricably linked to the ecology of their hosts and environments, to the point where they have been a driving force in the evolution of sexual reproduction and in the shaping of biodiversity [20,21]. Over the past 30 years, disease ecologists have developed the study of parasites and pathogens in the wild. This knowledge has been synthesized into mathematical models which describe the dynamic properties of ecosystems and predict how parasites and pathogens flow through them. [22,23]. These models are becoming more commonly integrated into epidemiological studies that seek to predict outbreaks or periods of time when cross-species spillover risk is highest. Parallel to this progress, the field of virology, particularly the subfields of molecular virology and viral evolution, have also been burgeoning, largely due to advances in technology that have made molecular assays and genetic sequencing more accessible to a greater number of scientists. The development of high-throughput sequencing has greatly increased our ability to efficiently detect known viruses as well as to discover new types of viruses, thereby improving our understanding of viral diversity, pathology and evolution. This increased capacity has spawned the development of new fields of study. For example, phylodynamics allows researchers to determine the origin of circulating viruses in space and time. Mutations among viral strains can be used to investigate interactions among host species as well as long-range host movement via corridors and flyways. Phylodynamic analyses can also inform livestock management practices, as was the

case with Foot and Mouth disease in the United Kingdom [24]. Conducting viral surveillance in animal reservoirs and invertebrate

vectors can help explain circulation within host species; observed patterns of zoonotic transmission; and even allow for the prediction of periods of increased risk of zoonotic transmission (e.g., Rift valley fever and rainfall [25]; West Nile virus (WNV) and American robin (Turdus turdus) migration [26]; as

well as hantavirus in mice [27,28]). Understanding viral ecology in wildlife reservoirs and identifying high-risk human-wildlife

interfaces is especially critical in the context of ever increasing globalization, whereby transportation networks facilitate rapid spread of pathogens well beyond bounds where traditional epidemiological methods can be effective [29–31]. The 2009 influenza A (H1N1) pandemic spread

from the presumptive point of emergence in La Gloria Mexico to New Zealand in just under a month [32] while SARS radiated from

Guangdong, China to 26 different countries within several months [29]. The negative impacts of emerging infectious diseases are not limited to humans. Indeed, wildlife conservationists have documented several mass mortality events in other animal species. Western lowland gorillas (Gorilla gorilla gorilla) have been decimated by Ebola virus [33] and an especially virulent calicivirus, rabbit hemorrhagic disease virus, spread through both domestic and wild rabbit populations, resulting in tens of millions of deaths [34]. In some instances the viruses have attenuated, while

in others the animal populations have been brought to the brink of extinction. Importantly, the risk from disease to humans and animals should not be separated. The global Viruses 2011, 3

382 transportation network facilitated the introduction of infected vectors (e.g., mosquitoes) into

New York and WNV caused both avian and human mortality, and this virus has subsequently spread across the United States [26].

Zoonoses – On the Way

New drug resistant zoonoses are coming nowJones et al 2008 - Kate E Jones, Nikkita G Patel, Marc A Levy, Adam Storeygard, Deborah Balk, John L Gittleman, & Peter Daszak (21 Feb 2008, "Global trends in emerging infectious diseases," www.ecohealthalliance.org/writable/publications/nature06536.pdf, ADL)Emerging infectious diseases (EIDs) are a significant burden on global economies and public health1–3. Their emergence is thought to be driven largely by socio-economic, environmental and ecological factors1–9, but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs. Here we analyse a database of 335 EID ‘events’ (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias,

with their peak incidence (in the 1980s) concomitant with the HIV pandemic. EID events are dominated by zoonoses

(60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. We find that 54.3% of EID events are caused by bacteria or rickettsia,

reflecting a large number of drug-resistant microbes in our database. Our results confirm that EID origins are significantly correlated with socio-economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease ‘hotspots’). They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs

originating at lower latitudes where reporting effort is low. We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries

from where the next important EID is least likely to originate. In the global human population, we report the emergence of 335 infectious diseases between 1940 and 2004. Here we define the first temporal

origination of an EID (that is, the original case or cluster of cases representing an infectious disease emerging in human populations for the first time—see Methods and Supplementary Table 1) as an EID ‘event’. Our database includes EID events caused by newly evolved strains of pathogens (for example, multi-drug-resistant tuberculosis and chloroquine-resistant malaria), pathogens that have recently entered human populations for the first time (for example, HIV-1, severe acute respiratory syndrome (SARS) coronavirus), and pathogens that have probably been present in humans historically, but which have recently increased in

incidence (for example, Lyme disease). The emergence of these pathogens and their subsequent spread have caused an extremely significant impact on global health and economies1–3. Previous efforts to understand patterns of EID emergence have highlighted viral pathogens (especially

RNA viruses) as a major threat, owing to their often high rates of nucleotide substitution, poor mutation error-correction ability and therefore higher capacity to adapt to new hosts, including humans5,8,10,11. However, we find that the majority of pathogens involved in EID events are bacterial or

rickettsial (54.3%). This group is typically represented by the emergence of drug-resistant bacterial strains (for example, vancomycin-resistant Staphylococcus aureus). Viral or prion pathogens constitute only 25.4% of EID events, in contrast to previous analyses which suggest that 37–44% of emerging pathogens are viruses or prions and 10–30% bacteria or

rickettsia5,8,11. This follows our classification of each individual drug-resistant microbial strain as a separate pathogen in our database,

and reflects more accurately the true significance of antimicrobial drug resistance for global health, in which different pathogen strains can cause separate significant outbreaks12. In broad concurrence with previous studies on the characteristics of emerging human pathogens5,8,11, we find the percentages of EID events caused by other pathogen types to be 10.7% for protozoa, 6.3% for fungi and 3.3% for helminths (see Supplementary Data and Supplementary Table 2 for a detailed comparison to previous studies). The incidence of EID events has increased since 1940, reaching a maximum in the 1980s (Fig. 1). We tested whether the increase through time was largely attributable to increasing infectious disease reporting effort (that is, through more efficient diagnostic methods and more thorough surveillance2,3,13) by calculating the annual number of articles published in the Journal of Infectious Diseases (JID) since 1945 (see Methods). Controlling for reporting effort, the number of EID events still shows a highly significant relationship with time (generalized linear model with Poisson errors, offset by log(JID articles)

(GLMP,JID), F596.4, P,0.001, d.f.557). This provides the first analytical support for previous suggestions that the threat of EIDs to global health is increasing1,2,14. To further investigate the peak in EID events in the 1980s, we examined the most frequently cited driver of EID emergence during this period (see Supplementary Table 1). Increased susceptibility to infection caused the highest proportion of events during 1980–90 (25.5%), and we therefore suggest that the spike in EID events in the 1980s is due largely to the emergence of new diseases associated with the HIV/AIDS pandemic2,13. The majority (60.3%) of EID events are caused by zoonotic pathogens (defined here as those which have a non-human animal source), which is consistent with previous analyses of human EIDs5,8. Furthermore, 71.8% of these zoonotic EID events were caused by pathogens with a wildlife origin—for example, the emergence of Nipah virus in Perak, Malaysia and SARS in Guangdong Province, China. The number of EID events caused by pathogens originating in wildlife has increased significantly with time, controlling for reporting effort (GLMP,JID F560.7, P,0.001, d.f.557), and they constituted 52.0% of EID events in the most recent decade (1990–2000) (Fig. 1). This supports the suggestion that zoonotic EIDs represent an increasing and very significant threat to global health1,2,7,13,14. It also highlights the importance of understanding the factors that increase contact between wildlife and humans in developing predictive approaches to disease emergence4,6,9,15. Vector-borne diseases are responsible for 22.8% of EID events in our database, and 28.8% in the last decade (Fig. 1). Our analysis 1Institute of Zoology, Zoological Society of London, Regents Park, LondonNW14RY, UK. 2Consortium for Conservation Medicine, Wildlife Trust, 460 West 34th Street, 17th Floor,New York, New York 10001, USA. 3Center for International Earth Science InformationNetwork, Earth Institute, Columbia University, 61 Route 9W, Palisades, New York 10964, USA. 4Odum School of Ecology, University of Georgia, Athens, Georgia 30602, USA. {Present addresses: Department of Economics, Brown University, Providence, Rhode Island 02912, USA (A.S.); School of Public Affairs, Baruch College, City

University of New York, 1 Bernard Baruch Way, Box D-0901, New York, New York 10010, USA (D.B.). Vol 451| 21 February 2008| doi:10.1038/nature06536 990 © 2008 Nature PublishingGroup reveals a significant rise in the number of EID events they have caused over time, controlling for reporting effort (GLMP,JID F549.8, P,0.001, d.f.557). This rise corresponds to climate anomalies occurring during the 1990s16, adding support to hypotheses that climate change may drive the emergence of diseases that have vectors sensitive to changes in environmental conditions such as rainfall, temperature and severe weather events17. However, this controversial issue requires further

analyses to test causal relationships between EID events and climate change18. We also report that EID events caused by drug-resistant microbes (which represent 20.9% of the EID events in our database) have significantly increased with time, controlling for reporting effort (GLMP,JID F55.19, P,0.05, d.f.557). This is probably related to a corresponding rise in antimicrobial drug use, particularly in high-latitude developed countries2,7,12. A recent analysis showed a latitudinal spatial gradient in human pathogen species richness increasing towards the Equator19, in common with the distributional pattern of species richness found in many other taxonomic groups20. Environmental parameters that promote pathogen transmission at lower latitudes (for example, higher temperatures and precipitation) are hypothesized to drive this pattern19. Our analyses suggest that there is no such pattern in EID events, which are concentrated in higher latitudes (Supplementary Fig. 1). The highest concentration of EID events per million square kilometres of land was found between 30 and 60 degrees north and between 30 and 40 degrees south, with the main hotspots in the northeastern United States, western Europe, Japan and southeastern Australia (Fig. 2). We hypothesize that (1) socioeconomic drivers (such as human population density, antibiotic drug use and agricultural practices) are major determinants of the spatial distribution of EID events, in addition to the ecological or environmental conditions that may affect overall (emerging and non-emerging) human pathogen distribution19, and (2) that the importance of these

drivers depends on the category of EID event. In particular, we hypothesize that EID events caused by zoonotic pathogens from wildlife are significantly correlated with wildlife biodiversity, and those caused

by drug-resistant pathogens are more correlated with socio-economic conditions than those caused by zoonotic pathogens. We tested these hypotheses by examining the relationship between the spatial pattern of the different categories of EID events (zoonotic pathogens originating in wildlife and non-wildlife, drug-resistant and vector-borne pathogens, Supplementary Fig. 2), and socioeconomic variables (human population density and human population growth), environmental variables (latitude, rainfall) and an ecological variable (wildlife host species richness) (see Methods). We found that human population density was a common significant independent predictor of EID events in all categories, controlling for spatial reporting bias by country (see Methods, Table 1 and Supplementary Table 3). This

supports previous hypotheses that disease emergence is largely a product of anthropogenic and demographic changes, and is a hidden ‘cost’ of human economic development 2,4,7,9,13.

Wildlife host species richness is a significant predictor for the emergence of zoonotic EIDs with a wildlife origin, with no role for human population growth, latitude or rainfall (Table 1). The emergence of zoonotic EIDs from non-wildlife hosts is predicted by human population density, human population growth, and latitude, and not by wildlife host species richness. EID events caused by drug-resistant microbes are affected by human population density and growth, latitude and rainfall. The pattern of EID events caused by vector-borne diseases was not correlated with any of the environmental or ecological variables we examined, although we note that the climate variable used in this analysis (rainfall) does not represent climate change phenomena.

Unpredictable zoonotic diseases are coming – only the Aff solvesHayman 11 - David Hayman of the Department of Biology of Colorado State University (David T. S., "Wildlife Zoonoses," omicsonline.org/wildlife-zoonoses-2161-1165.S2-001.pdf, ADL).In the late 1960s and 1970s, many people working in public health in industrialized societies such as the

USA believed that infectious diseases would cease to be a major health threat [1]. Vaccines existed for some of the most devastating diseases, including poliomyelitis, measles, and smallpox, and malaria had been eradicated from large regions, including Europe [2,3]. In 1977 the last case of smallpox was reported and it became the first infectious disease to be eradicated globally. Rabies vaccines, which had existed since Pasteur in 1885, had successfully been trialled in an oral bait delivery system, and signs were

that one of the most feared animal infections could be controlled [4]. However, it is now well into the 21st Century and infectious diseases are still to be found among the top causes of human deaths globally [5] (Figure 1). The majority of human pathogens are now recognized to be zoonotic [6-8]. Zoonotic infections are those of

non-human origin that infect humans, and most zoonotic infections are of wildlife origin [6-8]. Here I review the history and impacts of emerging infectious diseases in today’s society, and processes of infection emergence from wildlife. The importance of factors relating to host ecology, receptor usage and host range, and pathogen adaptation in spillover and emergence into human populations will be discussed. Finally, recent advances in technology and the challenges emerging zoonoses pose for epidemiologists will be highlighted.

History of Emerging Infectious Diseases It is now generally recognized that even the most “human” of infectious diseases at some time had their origins in other animals, typically wild, but also domesticated [8]. For example, well-known Old World human pathogens that now only infect humans, such as measles and smallpox, have animal origins [8,9]. Measles is thought to have derived from spillover of rinderpest or canine distemper virus infection in Mesopotamia following urbanization

circa 8000BCE and human population sizes reached a threshold size that allowed persistence [10-12]. The increase in human population density and today’s increase in connectivity and encroachment into wild areas probably means that we are more susceptible to infection emergence, and subsequent disease, than ever [13,14]. Numbers and Costs of Emerging Zoonoses Relatively recent reviews have estimated that

approximately 175 of the 1400 human pathogen species recognized are emerging or reemerging, and

between 58-75% of all infections are zoonotic [7,15]. The cost to humans of these emerging infections can be substantial, both in terms of lives and economics (Figure 2). A pertinent example is the emergence of human immunodeficiency virus (HIV), which occurred due to bush meat hunting of simian immunodeficiency virus (SIV) infected primates in Africa in the early part of the 20th Century [16-18]. Indeed, many groups of HIV-2, a relative of an SIV that infects sooty mangabeys (Cercocebus atys atys), still largely circulate only in African human populations, and have yet to become pandemic infections [19,20]. In 2009 the WHO estimated 33.3 million people lived with HIV infection, 2.6 million new HIV infections occurred and 1.8 million people died due to acquired immune deficiency

syndrome (AIDS) related illnesses [21]. New HIV infections in the United States in 2002 alone were estimated to cost $36.4 billion per

annum, including $6.7 billion in direct medical costs and $29.7 billion in productivity losses [22]. Infection emergence is complex because many species share infections and jumps between host species are common and natural. Recent estimates suggest that there may be 8.7 million eukaryote species on earth [23]. It is likely that each of these has a suite of viral infections, many of which they may share with other species. Given the number of wildlife species humans have contact with around the globe; the exposure rate of

humans to infectious agents vastly exceeds the rate of spillover from wildlife to humans. The many orders of magnitude difference between exposure and spillover rates make predicting emergence difficult. There have, however, been several efforts aimed at predicting infection emergence, both relating to the likely infections or regions of the globe where new emergence events may occur. Jones et al analyzed data to predict likely hot-spots for infections to emerge from, whereas other efforts have aimed to determine from which animal species or orders infections emerge [7,13,15,24]. Further analyses have identified that viral traits can predict emergence [25,26].

Zoonotic diseases are diverse, unpredictable, and getting worseWaltzek et al 11 T.B. Waltzek, G. Cortés-Hinojosa, J. F. X. Wellehan Jr. and Gregory C. Gray teach at the Department of Health, the Emerging Pathogens institute, and the College of Veterinary Medicine at the University of Florida, “Marine Mammal Zoonoses: A Review of Disease Manifestations “, 12/16/11, http://academicdepartments.musc.edu/mbes/mbessa/documents/zoonoses%20and%20marine%20mammals.pdf//OFRecent studies have underscored the importance of domesticated and feral animal populations in both the emergence of novel and re-emergence of existing human pathogens (Woolhouse

and Gowtage-Sequeria, 2005). This is illustrated by the fact that 75% of known human pathogens are zoonotic, and the incidences of their associated diseases are increasing (Cunningham, 2005).

Most recent emerging diseases have been associated with host switches, including severe acute respiratory syndrome coronavirus, H5N1 avian influenza, Hendra virus, Nipah virus and acquired

immunodeficiency syndrome (AIDS) (Woolhouse and Gowtage-Sequeria, 2005). The rise in zoonotic diseases is driven by a complex interplay of environmental (global warming, ocean acidification,

pollution), ecological (habitat destruction or fragmentation) and epidemiologic (increasing human densities

encroach- ing on decreasing wildlife populations, global movements of plants and animals) factors (Van Bressem et al., 2009; Bossart, 2011). Humans are having a major impact on marine environments, with negative impacts on marine mammal populations (Bejder et al., 2006). As the closest oceanic relatives of humans, marine mammals are sentinel species for both human and ocean health and they are long-lived, top-tier consumers, inhabiting the same inshore ecosystems utilized by man (Jessup et al., 2004; Bossart, 2011). Our knowledge of the diversity of marine mammal pathogens is now expanding rapidly (Nollens et al., 2010; Palacios et al., 2011; Wellehan et al., 2011). Future progress in zoonotic and emerging disease research will require the coordination of multidisciplinary teams addressing the nexus of human, animal and environment that has been referred to as the ‘One Health’ paradigm. Marine mammals are beloved by the general public, and numerous recreational industries permit intimate contact with these charismatic megafauna, including whale-watching tours, ‘swim-with-the-dolphin/manatee’ programs, and oceanaria. Marine mammal researchers, rehabilitators, trainers, veterinarians and volunteers have an increased risk of being injured or acquiring zoonotic diseases through extended occupational exposure (Hunt et al., 2008). Subsistence hunters (e.g. whalers and sealers) are also at occupational risk of disease acquisition through their direct physical contact with infected marine mammals or through the ingestion of marine mammal food products (Boggild, 1969; Bender et al., 1972; Caw- thorn, 1997; Tryland, 2000;

McLaughlin et al., 2004). Finally, during marine mammal stranding events, human rescuers have acquired zoonotic infections following contact with infected carcasses (Webster et al., 1981). The most

common marine mammal zoonotic diseases are localized infections, although life-threatening systemic diseases have been reported. A recent study evaluating the risk of illness associated with occupational contact with marine mammals found that more than 10% of the par- ticipants reported having contracted localized infections colloquially referred to as ‘seal finger’ (Hunt et al., 2008). ‘Seal finger’ is caused by a variety of bacterial and viral species (Table 1). Here, we provide a comprehensive review of the bacterial, viral and fungal marine mammal zoonotic diseases. The review provides a synopsis of each disease, its clinical and pathologic manifestation in marine mammals, followed by a review of transmission of the disease to humans.

New drug resistant zoonoses are coming nowJones et al 8 - Kate E Jones, Nikkita G Patel, Marc A Levy, Adam Storeygard, Deborah Balk, John L Gittleman, & Peter Daszak (21 Feb 2008, "Global trends in emerging infectious diseases," www.ecohealthalliance.org/writable/publications/nature06536.pdf, ADL)

Emerging infectious diseases (EIDs) are a significant burden on global economies and public health1–3. Their emergence is thought to be driven largely by socio-economic, environmental and ecological factors1–9, but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs. Here we analyse a database of 335 EID ‘events’ (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias,

with their peak incidence (in the 1980s) concomitant with the HIV pandemic. EID events are dominated by zoonoses

(60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. We find that 54.3% of EID events are caused by bacteria or rickettsia,

reflecting a large number of drug-resistant microbes in our database. Our results confirm that EID origins are significantly correlated with socio-economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease ‘hotspots’). They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs

originating at lower latitudes where reporting effort is low. We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries

from where the next important EID is least likely to originate. In the global human population, we report the emergence of 335 infectious diseases between 1940 and 2004. Here we define the first temporal

origination of an EID (that is, the original case or cluster of cases representing an infectious disease emerging in human populations for the first time—see Methods and Supplementary Table 1) as an EID ‘event’. Our database includes EID events caused by newly evolved strains of pathogens (for example, multi-drug-resistant tuberculosis and chloroquine-resistant malaria), pathogens that have recently entered human populations for the first time (for example, HIV-1, severe acute respiratory syndrome (SARS) coronavirus), and pathogens that have probably been present in humans historically, but which have recently increased in

incidence (for example, Lyme disease). The emergence of these pathogens and their subsequent spread have caused an extremely significant impact on global health and economies1–3. Previous efforts to understand patterns of EID emergence have highlighted viral pathogens (especially

RNA viruses) as a major threat, owing to their often high rates of nucleotide substitution, poor mutation error-correction ability and therefore higher capacity to adapt to new hosts, including humans5,8,10,11. However, we find that the majority of pathogens involved in EID events are bacterial or

rickettsial (54.3%). This group is typically represented by the emergence of drug-resistant bacterial strains (for example, vancomycin-resistant Staphylococcus aureus). Viral or prion pathogens constitute only 25.4% of EID events, in contrast to previous analyses which suggest that 37–44% of emerging pathogens are viruses or prions and 10–30% bacteria or

rickettsia5,8,11. This follows our classification of each individual drug-resistant microbial strain as a separate pathogen in our database,

and reflects more accurately the true significance of antimicrobial drug resistance for global health, in which different pathogen strains can cause separate significant outbreaks12. In broad concurrence with previous studies on the characteristics of emerging human pathogens5,8,11, we find the percentages of EID events caused by other pathogen types to be 10.7% for protozoa, 6.3% for fungi and 3.3% for helminths (see Supplementary Data and Supplementary Table 2 for a detailed comparison to previous studies). The incidence of EID events has increased since 1940, reaching a maximum in the 1980s (Fig. 1). We tested whether the increase through time was largely attributable to increasing infectious disease reporting effort (that is, through more efficient diagnostic methods and more thorough surveillance2,3,13) by calculating the annual number of articles published in the Journal of Infectious Diseases (JID) since 1945 (see Methods). Controlling for reporting effort, the number of EID events still shows a highly significant relationship with time (generalized linear model with Poisson errors, offset by log(JID articles)

(GLMP,JID), F596.4, P,0.001, d.f.557). This provides the first analytical support for previous suggestions that the threat of EIDs to global health is increasing1,2,14. To further investigate the peak in EID events in the 1980s, we examined the most frequently cited driver of EID emergence during this period (see Supplementary Table 1). Increased susceptibility to infection caused the highest proportion of events during 1980–90 (25.5%), and we therefore suggest that the spike in EID events in the 1980s is due largely to the emergence of new diseases associated with the HIV/AIDS pandemic2,13. The majority (60.3%) of EID events are caused by zoonotic pathogens (defined here as those which have a non-human animal source), which is consistent with previous analyses of human EIDs5,8. Furthermore, 71.8% of these zoonotic EID events were caused by pathogens with a wildlife origin—for example, the emergence of Nipah virus in Perak, Malaysia and SARS in Guangdong Province, China. The number of EID events caused by pathogens originating in wildlife has increased significantly with time, controlling for reporting effort (GLMP,JID F560.7, P,0.001, d.f.557), and they constituted 52.0% of EID events in the most recent decade (1990–2000) (Fig. 1). This supports the suggestion that zoonotic EIDs represent an increasing and very significant threat to global health1,2,7,13,14. It also highlights the importance of understanding the factors that increase contact between wildlife and humans in developing predictive approaches to disease emergence4,6,9,15. Vector-borne diseases are responsible for 22.8% of EID events in our database, and 28.8% in the last decade (Fig. 1). Our analysis 1Institute of Zoology, Zoological Society of London, Regents Park, LondonNW14RY, UK. 2Consortium for Conservation Medicine, Wildlife Trust, 460 West 34th Street, 17th Floor,New York, New York 10001, USA. 3Center for International Earth Science InformationNetwork, Earth Institute, Columbia University, 61 Route 9W, Palisades, New York 10964, USA. 4Odum School of Ecology, University of Georgia, Athens, Georgia 30602, USA. {Present addresses: Department of Economics, Brown University, Providence, Rhode Island 02912, USA (A.S.); School of Public Affairs, Baruch College, City University of New York, 1 Bernard Baruch Way, Box D-0901, New York, New York 10010, USA (D.B.). Vol 451| 21 February 2008| doi:10.1038/nature06536 990 © 2008 Nature PublishingGroup reveals a significant rise in the number of EID events they have caused over time, controlling for reporting effort (GLMP,JID F549.8, P,0.001, d.f.557). This rise corresponds to climate anomalies occurring during the 1990s16, adding support to hypotheses that climate change may drive the emergence of diseases that have vectors sensitive to changes in environmental conditions such as rainfall, temperature and severe weather events17. However, this controversial issue requires further

analyses to test causal relationships between EID events and climate change18. We also report that EID events caused by drug-resistant microbes (which represent 20.9% of the EID events in our database) have significantly increased with time, controlling for reporting effort (GLMP,JID F55.19, P,0.05, d.f.557). This is probably related to a corresponding rise in antimicrobial drug use, particularly in high-latitude developed countries2,7,12. A recent analysis showed a latitudinal spatial gradient in human pathogen species richness increasing towards the Equator19, in common with the distributional pattern of species richness found in many other taxonomic groups20. Environmental

parameters that promote pathogen transmission at lower latitudes (for example, higher temperatures and precipitation) are hypothesized to drive this pattern19. Our analyses suggest that there is no such pattern in EID events, which are concentrated in higher latitudes (Supplementary Fig. 1). The highest concentration of EID events per million square kilometres of land was found between 30 and 60 degrees north and between 30 and 40 degrees south, with the main hotspots in the northeastern United States, western Europe, Japan and southeastern Australia (Fig. 2). We hypothesize that (1) socioeconomic drivers (such as human population density, antibiotic drug use and agricultural practices) are major determinants of the spatial distribution of EID events, in addition to the ecological or environmental conditions that may affect overall (emerging and non-emerging) human pathogen distribution19, and (2) that the importance of these

drivers depends on the category of EID event. In particular, we hypothesize that EID events caused by zoonotic pathogens from wildlife are significantly correlated with wildlife biodiversity, and those caused

by drug-resistant pathogens are more correlated with socio-economic conditions than those caused by zoonotic pathogens. We tested these hypotheses by examining the relationship between the spatial pattern of the different categories of EID events (zoonotic pathogens originating in wildlife and non-wildlife, drug-resistant and vector-borne pathogens, Supplementary Fig. 2), and socioeconomic variables (human population density and human population growth), environmental variables (latitude, rainfall) and an ecological variable (wildlife host species richness) (see Methods). We found that human population density was a common significant independent predictor of EID events in all categories, controlling for spatial reporting bias by country (see Methods, Table 1 and Supplementary Table 3). This

supports previous hypotheses that disease emergence is largely a product of anthropogenic and demographic changes, and is a hidden ‘cost’ of human economic development 2,4,7,9,13.

Wildlife host species richness is a significant predictor for the emergence of zoonotic EIDs with a wildlife origin, with no role for human population growth, latitude or rainfall (Table 1). The emergence of zoonotic EIDs from non-wildlife hosts is predicted by human population density, human population growth, and latitude, and not by wildlife host species richness. EID events caused by drug-resistant microbes are affected by human population density and growth, latitude and rainfall. The pattern of EID events caused by vector-borne diseases was not correlated with any of the environmental or ecological variables we examined, although we note that the climate variable used in this analysis (rainfall) does not represent climate change phenomena.

Zoonoses – Structural Violence

Zoonotic diseases exacerbate structural violenceBryner 12 Jeanna Bryner is the Managing Editor for LiveScience.com, an online science news website, “Zoonoses Study Finds Animal-To-Human Diseases Kill Millions Each Year”, 7/7/12, Huffington Post, http://www.huffingtonpost.com/2012/07/07/zoonoses-study-finds-anim_n_1654967.html//OFDiseases that can be transmitted between animals and humans, such as bird flu and tuberculosis,

can wreak havoc on the health of both organisms . Now researchers have found 13 so-called zoonoses are responsible for 2.2 million human deaths every year. The study, detailed this week in

the report "Mapping of Poverty and Likely Zoonoses Hotspots," shows the vast majority of these illnesses and deaths occur in low- and middle-income countries. For instance, Africa's Ethiopia, Nigeria and Tanzania, along with India, had the highest rates of associated illness and death .

"From cyst-causing tapeworms to avian flu, zoonoses present a major threat to human and animal health," lead study author Delia Grace, a veterinary epidemiologist and food safety expert with the

International Livestock Research Institute (ILRI) in Kenya, said in a statement. "Targeting the diseases in the hardest-hit countries is crucial to protecting global health as well as to reducing severe levels of poverty and illness among the world's 1 billion poor livestock keepers." The new

global zoonosis map, an update of one published in the journal Nature in 2008, also revealed the northeastern United States, Western Europe (particularly the United Kingdom), Brazil and parts of Southeast Asia may be hotspots of "emerging zoonoses." An emerging zoonosis is a disease that is newly infecting humans, has just become virulent, or has just become drug-resistant. [10 Deadly

Diseases That Hopped Across Species] Animal-human disease About 60 percent of all human diseases and 75 percent of all emerging infectious diseases are zoonotic , according to the researchers. Most human infections with zoonoses come from livestock, including pigs, chickens, cattle, goats, sheep and camels. Out of 56 zoonoses studied, the researchers found 13 that were most important in terms of their impact on human deaths, the livestock sector and the severity of disease in people, along with their amenability to agriculture-based control. These

were, in descending order: zoonotic gastrointestinal disease; leptospirosis; cysticercosis; zoonotic

tuberculosis (TB); rabies; leishmaniasis (caused by a bite from certain sandflies); brucellosis (a bacterial

disease that mainly infects livestock); echinococcosis; toxoplasmosis; Q fever; zoonotic trypanosomiasis

(sleeping sickness), hepatitis E; and anthrax. They found many livestock were infected with these zoonoses in poor countries, where: 27 percent of livestock showed signs of current or past infection with bacterial food-borne disease that causes food contamination (a type of zoonotic gastrointestinal disease) 12 percent of animals have recent or current infections with brucellosis 10 percent of livestock in Africa are infected with trypanosomiasis 7 percent of livestock are currently infected with TB 17 percent of smallholder pigs show signs of current infection with cysticercosis 26 percent of livestock show signs of current or past infection with leptospirosis 25 percent of

livestock show signs of current or past infection with Q fever Dependence on livestock Nearly three-quarters of rural poor people and about one-third of the urban poor depend on livestock for food, income, manure and other services, the researchers say. As such, the loss of one milking animal can devastate these households, though even worse, the researchers point out, is the loss of a loved one to a zoonotic disease. The new map of hotspots will give researchers and officials places on which to focus their efforts. The highest zoonosis burden, they found, occurs in just a few countries, particularly Ethiopia, Nigeria and India. These three countries

also have the highest number of poor livestock keepers and the highest number of malnourished people. "These findings allow us to focus on the hotspots of zoonoses and poverty, within which we should be able to make a difference," Grace said in a statement.

Zoonoses – True vs. K

Our methods are sound (specific to the Jones et al evidence)Jones et al 8 - Kate E Jones, Nikkita G Patel, Marc A Levy, Adam Storeygard, Deborah Balk, John L Gittleman, & Peter Daszak (21 Feb 2008, "Global trends in emerging infectious diseases," www.ecohealthalliance.org/writable/publications/nature06536.pdf, ADL)Methods Summary. Biological, temporal and spatial data on human EID ‘events’ were collected from the literature from 1940 (yellow fever virus, Nuba Mountains, Sudan) until 2004 (poliovirus type 2 in Uttar Pradesh, India) (n5335, see Supplementary Data for data and sources). Global allocation of scientific resources for disease surveillance has been focused on rich, developed countries (Supplementary Fig. 3). It is thus likely that EID discovery is biased both temporally (by increasing research effort into human pathogens over the period of the database) and spatially (by the uneven levels of surveillance across countries).We account for these biases by quantifying reporting effort in JID and including it in our temporal and spatial analyses. JID is the premier international journal (highest ISI impact factor 2006: http://portal.isiknowledge.com/) of human infectious disease research that publishes papers on both emerging and non-emerging infectious diseases

without a specific geographical bias. To investigate the drivers of the spatial pattern of EID events, we compared the location of EID events to five socio-economic, environmental and ecological variables matched onto a terrestrial one degree grid of the globe. We carried out the spatial

analyses using a multivariable logistic regression to control for co-variability between drivers, with the presence/ absence of EID events as the dependent variable and all drivers plus our measure of spatial reporting bias by country as independent variables (n518,307 terrestrial grid cells). Analyses were conducted on subsets of the EID events—those caused by zoonotic pathogens (defined in our analyses as pathogens that originated in non-human animals) originating in wildlife and non-wildlife species, and those caused by drug-resistant and vector-borne pathogens. METHODS EID event definition. In this paper, we are analysing the process of disease emergence, not just the pathogens that cause them. Therefore, we focus on EID ‘events’, which we define as the first temporal emergence of a pathogen in a human population which was related to the increase in distribution, increase in incidence or increase in virulence or other factor which led to that pathogen being classed as an emerging disease2,4,5,8,13,15. We chose the 1940 cut-off based on the Institute of Medicine’s2 examples of a currently or very recently emerging disease, all of which had their likely temporal origins within this time period. Single case reports of a new pathogen were not considered to represent the emergence of a disease, and emergence was normally represented by reports,

in more than one peer-reviewed paper, of a cluster of cases that were identified in humans for the first time, or (for previously known diseases) considered significantly above background. Only events that had sufficient corroborating evidence for their geographic and temporal origin were included in our analysis. We based our data collection on the list of EIDs in ref. 5 updated to 2004. Unlike this previous study5, we treated different drug-resistant strains of the same microbial species as separate pathogens and the cause of separate EID events (for example, the emergence of the chloroquine-resistant strain of the malaria pathogen (Plasmodium falciparum) in Trujillo, Venezuela in 1957 and the sulphadoxinepyrimethamine- resistant strain in Sa Kaeo, Thailand in 1981). Variable definitions. The biological, temporal and spatial variable definitions of an EID event used are as follows: italic font indicates classes of the variables. (1) ‘Pathogen’, name of pathogen associated with the EID event. (2) ‘Year’ (the earliest year in which the first cluster of cases representing each EID event was reported to have occurred was taken where a range of years was given). (3) ‘Pathogen type’ (PathType): (i) bacterial; (ii) rickettsial; (iii) viral; (iv) prion; (v) fungal; (vi) helminth; (vii) protozoan. (4) ‘Transmission type’ (TranType): (0) non-zoonotic (disease emerged without involvement of a non-human host); (1) zoonotic (disease emerged via non-human to human transmission, not including vectors). (5) ‘Zoonotic type’ (ZooType): (0) non-zoonotic (disease emerged via human to human transmission); (1) non-wildlife (zoonotic EID event caused by a pathogen with no known wildlife origin); (2) wildlife (zoonotic EID event caused by a pathogen with a wildlife origin); (3) unspecified (zoonotic EID event caused by a pathogen with an unknown origin). (6) ‘Drug resistance’ (DrugRes): (0) event not caused by a drug-resistant microbe; and (1) event caused by a drug-resistant microbe. (7) ‘Transmission mode’ (TranMode): (0) pathogen causing the EID event not normally transmitted by a vector; and (1) pathogen causing the event transmitted by a vector. (8) ‘Driver’.Weclassified the most commonly cited underlying primary causal factor (or ‘driver’) associated with the EID event according to the classes listed in refs 2, 13. We re-classified ‘Economic development and land use’ and ‘Technology and industry’ to form more descriptive categories: ‘Agricultural industry changes’, ‘Medical industry changes’, ‘Food industry changes’, ‘Land use changes’ and ‘Bushmeat’. (9) ‘Location’. Description of where the first cluster of cases representing each EID event was reported to have occurred. For these descriptions, accurate spatial coordinates (point location data) were found for 51.8% of EID events (n5220) using Global Gazetteer v.2.1 (http://www.fallingrain.com/world/) and these were assigned to corresponding one degree terrestrial spatial grids. Some EID event locations were lesser known and only described sub-regionally or regionally (for example, SARS in ‘‘Guangdong Province, China’’ or enterohaemorrhagic Escherichia coli in ‘‘Peru’’). These locations were assigned corresponding boundaries from ESRI sub-regional or regional data24 and we randomly selected only one grid cell from the possible grid cells to represent each particular event. This treated these lesser known events equivalently to those that were assigned a specific point location. Driver definitions. Definitions of the spatial drivers used are as follows: (1) ‘Human population density’ for 200025 (persons per km2); (2) ‘Human population growth’, calculated

between 1990 and 200025.We used a dummy variable to indicate grid cells that experienced rapid growth in human population. This variable was set to 1 for grid cells where the 1990–2000 human population growth exceeded 25% over the decade, and was set to 0 elsewhere; (3) ‘Latitude’ (absolute latitude of the central point of each grid cell, decimal degrees); (4) ‘Rainfall’26 (average rainfall per year, mm); (5) ‘Wildlife host species richness’. We calculated mammalian species richness as a proxy for wildlife host species richness. Richness grids were generated from geographic distribution maps for 4,219 terrestrial mammalian species27. Controlling for sampling bias. For our temporal analysis, we included the number of JID articles per year since 1945 (nTOTAL517,979 articles) as an offset in our generalized linear model using a Poisson error structure. To control for bias in our spatial analysis, we calculated the frequency of the country listed as the address for every author (lead author

and coauthors) in each JID article since 1973. This generated a measure of reporting effort for each

country which was matched to the one degree spatial grid for analysis and was included in the multiple logistic regression models. Regression analysis. Each logistic regression was repeated ten times using a separate random draw of the EID event grids for those events where the region reported covered more than one grid cell. The analyses are summarized in Table 1, and given in full in Supplementary Table 3. Different random draws can produce a different number of grid cells with events, even though the number of events does not change. For graphical purposes (that is, in Figs 2 and 3, and Supplementary Figs 1 and 2), we display the first random draw of the EID event grids. Human population density and number of JID articles were logtransformed before analysis. Statistical analyses were carried out using SPSS (v. 12.0)28 and R (v. 2.2.1)29. As the spatial autocorrelation (measured using Moran’s I) in the EID event occurrence spatial grids was low (0.1), the data were assumed to represent independent points in these analyses.

Antiobiotic Resistance – 2AC

Microbes Solve

Ocean organisms solve antibiotic resistanceNational Academies 2009 (The National Academies—the National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and the National Research Council—provide a public service by working outside the framework of government to ensure independent advice on matters of science, technology, and medicine. They enlist committees of the nation’s top scientists, engineers, and other experts— all of whom volunteer their time to study specific concerns. The results of these deliberations are authoritative, peer-reviewed reports that have inspired some of the nation’s most significant efforts to improve the health, education, and welfare of the population. August, 2009, “Oceans a n d Human HealtHhttp://dels.nas.edu/resources/static-assets/osb/miscellaneous/Oceans-Human-Health.pdf)

Historically, many medicines have come from nature —mostly from land-based natural organisms. Because

scientists have nearly exhausted the supply of terrestrial plants, animals, and microorganisms that have interesting medical properties, new sources of drugs are needed. Occupying more than 70 percent of the Earth’s surface, the ocean is a virtually unexplored treasure chest of new and unidentified species—one of the last frontiers for sources of new natural products. These

natural products are of special interest because of the dazzling diversity and uniqueness of the creatures that make the sea their home. One reason marine organisms are so interesting to scientists is because in adapting to the various ocean environments, they have evolved fascinating repertoires of unique chemicals to help them survive. For example,

anchored to the seafloor, a sponge that protects itself from an animal trying to take over its space by killing the invader has been compared with the human immune system trying to kill foreign cancer cells. That same sponge, bathed in seawater containing millions of bacteria, viruses, and fungi, some of which could be pathogens, has developed antibiotics to keep those pathogens under control. Those same antibiotics could be used to treat infections in humans. Sponges, in fact, are among the most prolific sources of diverse chemical compounds. An estimated 30 percent of all potential marine-derived medications currently in the pipeline—and about 75 percent of recently patented marine-derived anticancer compounds—come from marine sponges. Marine-based microorganisms are another particularly rich source of new medicines. More than 10 drugs available today derive from land-based microbes. Scientists see marine-based microbes as the most promising source of novel medicines from the sea. In all, more thanthat the exploration of unique habitats, such as deep-sea environments, and the isolation and culture of marine microor- ganisms offer two underexplored opportunities for discovery of novel chemicals with therapeutic potential. The successes to date, which are based upon a very limited investigation of both deep-sea organisms and marine microorganisms, suggest a high potential for continued discovery of new drugs. 0,000 biochemical compounds have been isolated from sea creatures since the 1980s. Because drug discovery in the marine frontier is a rela- tively young field, only a few marine-derived drugs are in use today. Many others are in the pipeline. One example is Prialt, a drug developed from the venom of a fish-killing cone snail. The cone snails produce neurotoxins to paralyze and kill prey; those neurotoxins are being developed as neuromuscular blocks for individuals with chronic pain, stroke, or epilepsy. Other marinederived drugs are being tested against herpes, asthma, and breast cancer.

Oceans solve emerging antibiotic resistanceAAAS 9 (American Association for the Advancement of Scientists, February 13, 2009, “Fighting the Rising Tide of Antibiotic Resistance: Causes and Cures in the Sea”)Virulent bacteria are winning the arms race against our current arsenal of antibiotic drugs, posing a significant and growing threat to global public and ocean health. In the United States,

diseases and secondary infections related to antibiotic resistance are on the rise, difficult to treat, cost in excess of 5 billion dollars annually and may account for more deaths than from HIV-AIDS, Parkinson's disease, emphysema or homicide. Research has turned to the ocean to provide insight about potential causes and cures in this evolutionary battle. Methicillin-resistant Staphylococcus aureus (MRSA) has been detected and isolated from coastal waters and beaches, and resistance patterns in bacteria that commonly cause seafood illness have been discovered. The presence of these bacteria in coastal environments may increase the exposure of humans to resistant infections , increase

the potential for new, stronger strains to emerge and prevent common treatment. At the same time, marine natural products researchers are discovering new ways to potentially render out-of-use antibiotics

effective again, find novel drugs and help fight the resistance war. In this symposium, an

interdisciplinary panel of government, academic and non-profit scientists will present the latest research on the spreading, strengthening, and evolution of antibiotic resistance in the ocean, and promising new solutions and treatments from undersea medicine cabinets.

Plan solves antibiotic resistanceNOAA 2009 (National Oceanic and Atmospheric Association, 2/19/2009, “Antibiotic Resistance: A Rising Concern In Marine Ecosystems”, http://www.noaanews.noaa.gov/stories2009/20090213_antibiotic.html)

A team of scientists, speaking today at the annual meeting of the American Association for the Advancement of Science, called for new awareness of the potential for antibiotic-resistant illnesses from the marine environment, and pointed to the marine realm as a source for possible cures of those threats. The group stated that newly completed studies of ocean beach users point to an increasing risk of staph infections, and that current treatments for seafood poisoning may be less effective due to higher than expected antibiotic resistance. The group also asserts that new research has identified sponge and coral-derived chemicals with the potential for breaking down antibiotic resistant compounds and that could lead to new personalized medical treatments. “While the marine environment can indeed be hostile to humans, it may also provide new resources to help reduce our risks from illnesses such as those caused by water borne staph or seafood poisoning,” stated Paul Sandifer, Ph.D., former member of the U.S. Commission on Ocean Policy, chief scientist of NOAA’s Oceans and Human Health Initiative, and co-organizer of the symposium. Carolyn Sotka, also with the NOAA Oceans and Human Health Initiative and lead organizer of the session, stated “It is critically important that we continue research on the complex interactions between the condition of our oceans and human health. Without doubt, this research will develop new understandings of ocean health risks and perhaps more importantly crucial discoveries that will lead to new solutions to looming public health problems.” Sponges and coral. Sponges and coral. High resolution (Credit: NOAA) Coral, Sponges Point To Personalized Medicine Potential “We’ve found significant new tools to fight the antibiotic resistance war,” says NOAA research scientist Peter Moeller, Ph.D., in describing the identification of new compounds derived from a sea sponge and corals. “The first hit originates with new compounds that remove the shield bacteria utilize to protect themselves from antibiotics. The second hit is the discovery of novel antibiotics derived from marine organisms such as corals, sponges and marine microbes that fight even some of the worst infectious bacterial strains. With the variety of chemicals we find in the sea and their highly specific

activities, medicines in the near future can be customized to individuals’ needs, rather than relying on broad spectrum antibiotics.” The research team, a collaboration between scientists at NOAA’s Hollings Marine Laboratory in Charleston, S.C., the Medical University of South Carolina and researchers at North Carolina State University in Raleigh, N.C., noticed a sponge that seemed to thrive despite being located in the midst of a dying coral reef. After extraction, testing showed that one of the isolated chemicals, algeliferin, breaks down a biofilm barrier that bacteria use to protect themselves from threats including antibiotics. The same chemical can also disrupt or inhibit formation of biofilm on a variety of bacteria previously resistant to antibiotics which could lead to both palliative and curative response treatment depending on the problem being addressed. “This could lead to a new class of helper drugs and result in a rebirth for antibiotics no longer thought effective,” notes Moeller. “Its potential application to prevent biofilm build-up in stents, intravenous lines and other medical uses is incredible.”

Marine Bacteriophages allow for Phage Therapy which is used to control Antibiotic resistant diseases Sekar and Kandasamy 13 (Anandhan, Kathiresan, International Journal of Current Microbiology and Applied Sciences, “Bacterial viruses in marine environment and their ecological role and bioprospecting potential: a review”, http://ijcmas.com/vol-2-7/Anandhan%20Sekar%20and%20Kathiresan%20 Kandasamy.pdf)Interest in bacterial viruses is increasing due to their applications in phage therapy (Housby and Mann. 2009), detection and diagnostics (Shen et al., 2009), bacterial infection treatment (Wall et aL9 2010) and recombinant protein production (Oh et ah, 2007). The bacterial viruses have been identified as important tools in many aspects of nano-medicine (Villaverde. 2010). However, most of these works are confined to bacterial viruses of terrestrial origin.

Marine bacteriophages have received only little attention. There is a possibility for exploring the potential of marine cyanophages to be used to prevent or reverse eutrophication. Kurtboke (2005)have developed an improved technique that involves the exploitation of marine actinophages as a tool to reduce the numbers of common marine bacteria, which impedes the growth of rare actinomycetes on isolation plates. Phage therapy is the recent development in the field of phage research due primarily to the increasing incidence of antibiotic- resistant bacteria and the lack of development of new types of antibiotics to control infections caused by these antibiotic-resistant organisms (Cerveny et ah, 2002). The therapeutic uses of phages in humans have been recently reviewed by Alisky et ah, (1998); the overall reported success rate for phage therapy is found to be in the range of 80-95%. Phage therapy has been applied to a variety of infections like bacterial dysentery, wound infections- gastrointestinal tract infections, infections of skin nasal mucosa and gastrointestinal tract infections (Mathur et ah, 2003).In nanomedicines, viral nanoparticles (VNPs) are particularly valuable because they are not only biocompatible but also biodegradable, and also they are non- infectious and non- hazardous to humans and other mammals (Kaiser et al., 2007). The basic VNP structure is without nucleic acid but with only protein coat and this can be 'programmed' in a number of ways so that the internal cavity can be filled with drug molecules, imaging reagents- quantum dots and other nanoparticles- whereas the external surface can be attached with targeting ligands to allow cell-specific delivery of drugs (Pokorski and Steinmetz- 2011). The potential of bacteriophages to control infectious diseases in fishes is known (Vinod et ah, 2006). Karunasagar et ah, (2007) have isolated lytic bacteriophages against V. harveyi and proved that the bacteriophage treatment at 2x106 pfu ml-1 level results in over 85% survival of Penaeus monodon larvae suggesting that bacteriophage therapy will be an effective alternative to antibiotics in shrimp hatcheries since there is a ban on use of most antibiotics in aquaculture. Phage display is a very powerful technique for obtaining libraries containing millions or even billions of different peptides or proteins. Phage display (Smith. 1985) has been used for affinity screening of combinatorial peptide libraries to identify lisands for peptide receptors, define epitopes for monoclonal antibodies, select enzyme substrates (Kay et ah, 1996). and screen cloned antibody repertoires (Griffiths and Duncan, 1998).

Resistance Now / Bad

Antibiotics are our primary weapon in the war against disease and we are losing on all fronts – antibiotic resistance is growing from every corner of the globeInnes 4/30 Emma Innes (citing WHO and independent medical studies), is a contributor to Agora Dialogue, “‘Antibiotic resistance is now a bigger crisis than the AIDS epidemic’: Impact of bacteria evading drugs means you could die from a mild scratch”, 4/30/14, http://agora-dialogue.com/antibiotic-resistance-is-now-a-bigger-crisis-than-the-aids-epidemic-impact-of-bacteria-evading-drugs-means-you-could-die-from-a-mild-scratch//OFAntibiotic resistance is now a bigger crisis than the AIDS epidemic of the 1980s, a landmark report

warned today. The spread of deadly superbugs that evade even the most powerful antibiotics is happening across the world, United Nations officials have confirmed. The effects will be devastating – meaning a simple scratch or urinary tract infection could kill. Antibiotic resistance has the potential to affect anyone, of any age, in any country, the U.N.’s World Health

Organisation (WHO) said in a report. It is now a major threat to public health, of which ‘the implications will be devastating’. ‘The world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill,’ said Keiji Fukuda, the WHO’s assistant director-general for health security. In its first global report on

antibiotic resistance, with data from 114 countries, the WHO said superbugs able to evade event the hardest-hitting antibiotics – a class of drugs called carbapenems – have now been found in all regions of the world. Drug resistance is driven by the misuse and overuse of antibiotics, which encourages

bacteria to develop new ways of overcoming them. Only a handful of new antibiotics have been developed and brought to market in the past few decades, and it is a race against time to find more as bacterial infections increasingly evolve into superbugs resistant to even the most powerful last-resort

medicines reserved for extreme cases. One of the best known superbugs, MRSA, is alone estimated to kill around 19,000 people every year in the U.S. – far more than HIV and AIDS – and a similar number in

Europe. The WHO said in some countries, because of resistance, carbapenems now do not work in more than half of people with common hospital-acquired infections caused by a bacteria called K. pneumoniae,

such as pneumonia, blood infections, and infections in newborn babies and intensive-care patients. Resistance to one of the most widely used antibiotics for treating urinary tract infections caused by E. coli -medicines

called fluoroquinolones – is also very widespread, it said. In the 1980s, when these drugs were first introduced,

resistance was virtually zero, according to the WHO report. The spread of deadly superbugs that evade even the most powerful antibiotics is happening across the world , United Nations officials have

confirmed. Image shows the superbug MRSA which already kills almost 20,000 people a year in Europe But now there are countries in many parts of the world where the drugs are ineffective in more than half of patients. ‘Unless we take significant actions to improve efforts to prevent infections and also change how we

produce, prescribe and use antibiotics, the world will lose more and more of these global public health goods and the implications will be devastating ,’ Dr Fukuda said. Laura Piddock, director of Antibiotic Action campaign group and a professor of microbiology at Birmingham University, said the world needed to

respond as it did to the AIDS crisis of the 1980s. ‘Defeating drug resistance will require political will, commitment from all stakeholders and considerable investment in research , surveillance and stewardship programmes,’ she said. Jennifer Cohn of the international medical charity Médecins Sans Frontières agreed

with the WHO’s assessment and confirmed the problem had spread to many corners of the world . ‘We see horrendous rates of antibiotic resistance wherever we look in our field operations , including children admitted to nutritional centres in Niger, and people in our surgical and trauma units in Syria,’ she said.

Top experts conclude that antibiotic resistance will be apocalyptic Sample 13 Ian Sample (Citing medical studies) is the science correspondent for the Guardian, a British newspaper, “Antibiotic-resistant diseases pose 'apocalyptic' threat, top expert says”, 1/23/13, The Guardian, http://www.theguardian.com/society/2013/jan/23/antibiotic-resistant-diseases-apocalyptic-threat//OFBritain's most senior medical adviser has warned MPs that the rise in drug-resistant diseases could trigger a national emergency comparable to a catastrophic terrorist attack , pandemic flu or

major coastal flooding. Dame Sally Davies, the chief medical officer, said the threat from infections that are resistant to frontline antibiotics was so serious that the issue should be added to the government's national risk register of civil emergencies. She described what she called an "apocalyptic scenario" where people going for simple operations in 20 years' time die of routine infections "because we have run out of antibiotics". The register was established in 2008 to advise the public and businesses on national emergencies that Britain could face in the next five years. The highest priority risks on the latest register include a deadly flu outbreak, catastrophic terrorist attacks, and major flooding on the scale of 1953, the last occasion on which a national emergency was declared in the UK. Speaking to MPs on the Commons science and technology committee, Davies said she would ask the Cabinet Office to add antibiotic resistance to the national risk register in the light of an annual report on infectious disease she will publish in March. Davies declined to elaborate on the report, but said its publication would coincide with a government strategy to promote more responsible use of antibiotics among doctors and the clinical professions. "We need to get our act together in this country," she told the committee. She

told the Guardian: ""There are few public health issues of potentially greater importance for society than antibiotic resistance. It means we are at increasing risk of developing infections that cannot be treated – but resistance can be managed. "That is why we will be publishing a new cross-government strategy and action plan to tackle this issue in early spring." The issue of drug resistance is as old as antibiotics themselves, and arises when drugs knock out susceptible infections, leaving hardier, resilient strains behind. The survivors then multiply, and over time can become unstoppable with frontline medicines. Some of the best known are

so-called hospital superbugs such as MRSA that are at the root of outbreaks among patients. " In the past, most people haven't worried because we've always had new antibiotics to turn to," said Alan

Johnson, consultant clinical scientist at the Health Protection Agency. "What has changed is that the development pipeline is running dry. We don't have new antibiotics that we can rely on in the immediate future or in the longer term." Changes in modern medicine have exacerbated the problem by making patients more susceptible to infections. For example, cancer treatments weaken the immune system, and the use of catheters

increases the chances of bugs entering the bloodstream. "We are becoming increasingly reliant on antibiotics in a whole range of areas of medicine. If we don't have new antibiotics to deal with the problems of resistance we see, we are going to be in serious trouble," Johnson added. The supply of new antibiotics has dried up for several reasons, but a major one is that drugs companies see greater profits in medicines that treat chronic conditions, such as heart disease, which patients must take for years or even decades. "There is a broken market model for making new antibiotics," Davies told the MPs. Davies has met senior officials at the World Health Organisation and her counterparts in other countries to develop a strategy to tackle antibiotic

resistance globally. Drug resistance is emerging in diseases across the board. Davies said 80% of gonorrhea was now resistant to the frontline antibiotic tetracycline, and infections were rising in young and middle-aged people. Multi-drug resistant TB was also a major threat, she said. Another worrying trend is the rise in infections that are resistant to powerful antibiotics called carbapenems, which doctors rely on to tackle the most serious infections.

Resistant bugs carry a gene variant that allows them to destroy the drug. What concerns some

scientists is that the gene variant can spread freely between different kinds of bacteria , said Johnson. Bacteria resistant to carbapenems were first detected in the UK in 2003, when three cases were reported. The numbers remained low until 2007, but have since leapt to 333 in 2010, with 217 cases in the first six months of 2011, according to the latest figures from the HPA.

Antibiotic resistance is increasing nowBMJ 8 The British Medical Journal is a renowned medical publication, “World Faces Global Pandemic Of Antibiotic Resistance, Experts Warn”, 9/18/2008, Science Daily, http://www.sciencedaily.com/releases/2008/09/080918192836.htm//OFA concerted global response is needed to address rising rates of bacterial resistance caused

by the use and abuse of antibiotics or "we will return to the pre-antibiotic era", write Professor Otto Cars and colleagues in an editorial. All antibiotic use "uses up" some of the effectiveness of that antibiotic, diminishing the ability to use it in the future, write the authors, and antibiotics can no longer be considered as a renewable source. They

point out that existing antibiotics are losing their effect at an alarming pace, while the development of new antibiotics is declining. More than a dozen new classes of antibiotics were developed between 1930 and 1970, but only two new classes have been developed since then. According to the European Centre for Disease Prevention and

Control, the most important disease threat in Europe is from micro-organisms that have become resistant to antibiotics. As far back as 2000, the World Health Organisation was calling for a massive effort to address the problem of antimicrobial resistance to prevent the "health catastrophe of tomorrow". So why has so little been done to address the problem of resistance, ask the authors? Antibiotics are over prescribed, still illegally sold

over the counter in some EU countries, and self medication with leftover medicines is commonplace. There are alarming reports about serious consequences of antibiotic resistance from all around the world. However, there is still a dearth of data on the magnitude and burden of antibiotic resistance, or its economic impact on individuals, health care, and society. This, they suggest, may explain why there has been little response to this

public health threat from politicians, public health workers, and consumers. In addition, there are significant scientific challenges but few incentives to developing new antibiotics , state the authors. The authors believe that priority must be given to the most urgently needed antibiotics and incentives given for developing antibacterials with new mechanisms of action. In addition, "the use of new antibiotics must be safeguarded by regulations and practices that ensure rational use, to avoid repeating the mistakes we have made by overusing the old ones", they say.

Resistance Now -- MRSA

A MRSA superbug just popped up in Brazil – Doctors conclude this is a worst-case scenarioHSNW 4/18 Homeland Security Newswire (Citing Doctors and NIH reports) is a news organization that deals with security issues, “New MRSA superbug discovered in Brazil”, 4/18/14, Homeland Security Newswire, http://www.homelandsecuritynewswire.com/dr20140418-new-mrsa-superbug-discovered-in-brazil//OFResearchers have identified a new superbug that caused a bloodstream infection in Brazil ian patients.

The new superbug is part of a class of highly-resistant bacteria known as methicillin-resistant

Staphylococcus aureus, or MRSA, which is a major cause of hospital and community-associated infections. The superbug has also acquired high levels of resistance to vancomycin, the most common and least expensive antibiotic used to treat severe MRSA infections worldwide . The most worrisome aspect of the discovery is that genomic analyses indicated that this novel vancomycin-resistant MRSA superbug belongs to a genetic lineage that is commonly found outside hospitals (designated community-associated MRSA). An international research team led by Cesar A. Arias, M.D., Ph.D., at the University of Texas Health Science Center at Houston (UTHealth) has identified a new superbug that caused a bloodstream infection in a Brazilian patient. The report appeared in the 17 April issue of the New England Journal of Medicine. The new superbug is part of a class of highly-resistant bacteria known as methicillin-resistant Staphylococcus aureus or MRSA, which is a major cause of hospital and community-associated infections. The superbug has also acquired high levels of resistance to vancomycin, the most common and least expensive antibiotic used to treat severe MRSA infections worldwide. A UTHealth release

quotes Arias to say that the most worrisome aspect of the discover is that genomic analyses indicated

that this novel vancomycin-resistant MRSA superbug belongs to a genetic lineage that is commonly found outside hospitals (designated community-associated MRSA). Arias is the report’s senior author and an associate professor of medicine, microbiology and molecular genetics at the UTHealth Medical School.

Previous research has suggested that community-associated MRSA can disseminate rapidly among people and is responsible for the majority of skin and soft tissue infections (sores) in patients of all ages. Some of these infections can become serious and even fatal. Since

community-associated MRSA is thought to be transmitted mainly by skin contact, the new superbug may affect not only sick people or those with a weakened immune system but also healthy individuals, according to Arias. Apart from causing localized skin infections, the MRSA superbug has the ability to invade the bloodstream and may become a serious threat. “This is the first-ever reported bloodstream infection caused by a highly vancomycin-resistant MRSA bacteria,” Arias said. “If we lose vancomycin, it would make it very difficult and expensive to treat these infections,” he said. Arias and his colleagues conducted microbiological and genetic analyses of an MRSA superbug recovered from the blood of a 35-year-old Brazilian man and identified a novel transferable genetic element (plasmid) that carries the genes necessary for vancomycin resistance (vanA gene cluster). “The presence and dissemination of community-associated MRSA containing vanA could become a serious public health concern,” report the authors in the paper. Since this is the only documented case of this type of infection, Arias said, it is too early to tell whether this specific superbug will lead to a bigger threat. Barbara E. Murray, M.D., report co-author and director of the

Division of Infectious Diseases at the UTHealth Medical School, said, “The worst resistance possible has now appeared in the community-associated MRSA clone.” What is the next step? “There will have to be increased surveillance in South America and worldwide in the future,” said Murray, who is the holder of the J. Ralph Meadows Professorship in Internal Medicine at the UTHealth Medical School and president of the Infectious Diseases Society of America. Arias leads the UTHealth Medical School Laboratory for Antimicrobial Research, which focuses on studying the clinical and molecular aspects of antibiotic resistance, attempting to understand the complex mechanisms by which superbugs become resistant to antibiotics and then designing new strategies to fight them. Arias is also the founder and scientific director of the Molecular Genetics and Antimicrobial Resistance Unit at Universidad El Bosque in Bogota, Colombia and co-directs the International Center for Microbial Genomics at the same university. These research units have become a major surveillance center for resistance pathogens in South America. The collaborative work derived from these laboratories has identified novel trends in antimicrobial resistance and has characterized the emergence of particular superbugs in the region. Arias and Murray are on the faculty of the University of Texas Graduate School of Biomedical Sciences at Houston. The report received support from the National Institute of Allergy and Infectious Diseases and the National Institutes of Health.

CRE – No Safeguards

No early intervention – CRE is in stealth modeMNT 6/4/14 Medical News Today is a periodical that reports medical news, “’Phantom' superbugs cloak themselves to avoid detection”, 6/4/2014, http://www.medicalnewstoday.com/articles/277663.php//OFResearch led by the University of Queensland in Australia has uncovered antibiotic-resistant bacteria in the Middle East that avoid detection by cloaking themselves with genetic material. The

"phantom" superbugs belong to a particularly deadly class of antibiotic-resistant bacteria

called carbapenem resistant Enterobacteriaceae (CRE), which kill up to half of infected patients . In

2013, the Centers for Disease Control and Prevention warned that CRE superbugs are on the rise in US hospitals. By cloaking themselves, the newly discovered phantom versions of CRE place the population at increased risk of deadly infections, say the researchers, who report their findings in the journal

Antimicrobial Agents and Chemotherapy. They warn the hard-to-detect superbugs may quickly spread globally, given that the Middle East is a popular medical tourism destination and its highly paid job market attracts workers from all over the world. Hosam Mamoon Zowawi, a researcher in the Centre for Clinical Research at the University of Queensland (UQ) says they found the phantom superbug during a region-wide collaborative study on antibiotic-resistant bacteria in the Gulf Cooperation Council (GCC) states of

Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and United Arab Emirates . bacteria in a petri dish By

cloaking themselves, the newly discovered phantom versions of CRE place the population at increased risk of deadly infections. He says the phantom superbug was present in samples from all the GCC states, and "not only were the bacteria widespread, but they were found to be carrying genetic material that empowers them to resist antibiotics and avoid detection in routine laboratory testing . This means patients are not being treated quickly with the right

antibiotics, allowing the bacteria time to spread." The team also found several clusters of the phantom superbug in different patients from the same hospitals, suggesting infection is spreading from patient to patient. They hope their findings will encourage labs to bring in more specific techniques to detect phantom superbugs. This will be essential to minimize spread, says Mr. Zowawi. The team is now working on new tools that can rapidly identify the phantom superbug and other drug-resistant bacteria. Mr. Zowawi says the intention is to advance surveillance of superbugs by reducing turnaround times for test results and to help clinicians "apply targeted treatment and implement infection control precautions sooner."

Phantom CRE is widespread in the middle East and its moving fastStallard 6/4 Brian Stallard is a reporter for Nature World News, a news organization that focuses on scientific topics, “Cloaked "Phantom" Bacteria Threaten the Middle East”, 6/4/14, Nature World News, http://www.natureworldnews.com/articles/7403/20140604/cloaked-phantom-bacteria-threaten-middle-east.htm//OFAlready highly dangerous bacteria called carbapenem resistant Enterobacteriaceae (CRE) have learned to "cloak" themselves with genetic material, effectively hiding from the body's natural defenses. Experts are calling these new types of CRE "phantom bacteria" and have already found a multitude of them in the Middle East . According to a study published in the journal

Antimicrobial Agents and Chemotherapy, these hard-to-detect superbugs may soon find their way into other parts of the world through international travel , just as other diseases such as Middle East respiratory system (MERS) already have. Researcher Hosam Mamoon Zowawi, from the University of Queensland, said

the "phantom" superbugs were found during a field survey of antibiotic-resistant microbes in the Gulf Cooperation Council (GCC) states of Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Oman and Bahrain. "Not only were the bacteria widespread, but they were found to be carrying genetic material which empowers them to resist antibiotics and avoid detection in routine laboratory testing ," Zoawawi said in a statement. And since these bugs are difficult to

detect, he added, they avoid being treated with the right antibiotics, allowing them to spread not only to new hosts, but from patient-to-patient. Close examination of these "phantom" CRE

has allowed the research team to develop an early interpretation as to how the bacteria cloaks itself, stealing away into a host and colonizing long before it is finally noticed. Zowawi and his colleagues are

now in the midst of developing new diagnostic techniques based off of their findings in hopes that they can help identify this elusive superbug fast enough to prevent it from becoming a global problem. "We hope this will help in advancing the surveillance of superbugs by reducing the turnaround time to identify the deadly bacteria," Zowawi said. "It will also assist clinicians to apply targeted treatment and implement infection control precautions sooner."

TB – Threat Is Real

It gets worse – there are growing strains of totally drug resistant TB and we know nothing about how to treat itVelayati et al 13 Ali Akbar Velayati and Parissa Farnia are doctors at the Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Disease, Mohammad Reza Masjedi is a doctor at the Chronic Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Disease, “The totally drug resistant tuberculosis (TDR-TB)”, 4/12/13, US National Library of Medicine, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631557//OFIn 2009, we proposed the term “Totally Drug–Resistant Tuberculosis (TDR-TB) “for TB strains that showed in-vitro resistance to all first and second line drugs tested (isoniazid, rifampicin, streptomycin, ethambutol, pyrazinamide, ethionamide, para-aminosalicylic acid, cycloserine, ofloxacin, amikacin,

ciprofloxacin, capreomycin, kanamycin) [1]. Our detected TDR-TB patients remained smear and culture positive after 18 months median treatment despite second line drugs. Even changing the treatment to coamoxiclav (625 mg per 8 h) or clarithromycin (1,000 mg/day-1) along with high dose of isoniazid (15 mg/kg-1) led to no

improvement [1]. Majority of cases were expired or remained positive in the next 4 years of follow-up. These dangerous forms of TB bacilli were also found in other countries i.e., Italy and India [2,3]. Just earlier this month “Centers for Diseases Control and Preventions” reported the first cases of TDR-

TB in South Africa and they stated the disease is “virtually untreatable” [4]. National Reference TB laboratory (NRL) of Iran was among the first laboratories who could identify TDR-TB bacilli. Based on availability of TDR-culture isolates, investigation was started at cellular and molecular level. The primary results using transmission and atomic force microscopes, confirmed morphological variation in TDR-TB isolates [5,6]. Considerable number of bacilli were round (35%), oval (15%) or even multiple branching forms. In addition, various type of cell division i.e., symmetrical, asymmetrical and budding were found in their exponential phase of growth (Figure 1) [5]. The cell wall was significantly thicker than MDR-TB isolates and recently, pilli like structure (10-15%) that protruded from the head, tail or side poles of the bacilli were also detected [7-9]. Whether they use them for genetically or nutrients exchanges are still under

investigations. These findings will rage a new debate on untreatable TB drug resistance phenomena, for example, whether variation in shape and size of bacilli could affect transmission rate? If so, then

what will be the time that droplet nuclei (round or oval cells) can remain suspended in air?

Secondly, how to protect the health care workers when TDR-TB reported in the hospital? Do we need to keep the TDR-TB patients in “isolated ward” and if yes for how long? If size of bacilli reaches to minimum of 0.3 μm [6] what will be the best protective cloth for laboratory personal? Third concern is about host–microbe’s interaction? What is the fate of round or oval shape TB bacilli inside the host cells? Because, it is known that the shapes of microorganisms and not size considered as the dominant factor for being recognized or phagocytized by immune cells [10]. Finally, do we have to consider the thicker cell wall [7] in TDR-TB bacilli while designing new drugs and if it is so,

whether the previously designed drugs could be effective? Last but not the least; as far as, there is no cure for TDR-TB patient, hence it is not exaggeration to say that world is on danger of untreatable drug resistant tuberculosis strain. Therefore, if authorized health organization do not consider immediate action plan for such bacilli, then we may face a new outbreaks of untreatable TB.

It’s a timebomb – global epidemicNew England Journal of Medicine, 2002(http://www.amazon.com/Timebomb-Epidemic-Multi-Drug-Resistant-Tuberculosis/dp/0071359249)Timebomb, written by Lee Reichman with Janice Hopkins Tanne, shows that this desperate situation has already occurred. Though clearly unintentionally, a combination of politics, economics, the emergence of a new infectious disease, and scientific belief has contributed to a major epidemic of tuberculosis in Russia. Multidrug resistance is a major component of this epidemic in prisons and parts of the civilian population. What makes the situation so worrisome is that the epidemic was well under way even without the added boost of HIV infection. Recent statistics from the World Health Organization and the Joint United Nations Programme on

HIV/AIDS confirm that the pandemic of HIV infection is growing faster in Russia than anywhere else in the world. This appalling combination of HIV infection and multidrug-resistant tuberculosis is -- as the authors quite rightly assert -- a deadly time bomb, with consequences that reach far beyond the borders of any one country.

Only getting worseSinha, writer for Voice of America, 1/23/2012(Vidushi, Untreatable New Forms of TB Raising Alarm, http://www.voanews.com/content/untreatable-new-forms-of-tb-raising-alarm-137987628/160344.html)In the world of tuberculosis (TB) control, it is the worst-case scenario. Doctors in Mumbai, India, reported last month they are seeing a group of patients infected with what they called "totally drug-resistant" tuberculosis. Indian health officials are still investigating those cases, but untreatable strains of the bacterial respiratory disease have turned up before: in 15 patients in Iran in 2009 and in two patients in Italy in 2007. Public health experts responding and there is new hope some for new weapons against a disease that is killing 5,000 people every day.The World Health Organization (WHO) lists 69 countries that have reported what is officially called "extensively drug-resistant" tuberculosis (XDR-TB). It's a form of the mycobacterium that, like the one reported in India, isn't killed by first- and second-line anti-TB injectable drugs. The WHO says at least 25,000 cases of XDR-TB are reported worldwide every year.Dr. Margaret Chan, WHO's director-general, views the emergence of drug-resistant tuberculosis with alarm."Call it what you may, a time bomb or a powder keg. Any way you look at it, this is a potentially explosive situation," she said.

TB – Russia

TB is back in Russia with a vengeanceCallaway 14 Ewen Callaway is a writer for Nature, a weekly science journal, “Russia's drug-resistant TB spreading more easily”, 1/26/14, Nature, http://www.nature.com/news/russia-s-drug-resistant-tb-spreading-more-easily-1.14589//OFBacterial 'superbugs' are getting ever more potent. Tuberculosis (TB) strains in Russia carry mutations that not only make them resistant to antibiotics but also help them to spread more effectively, according to an analysis of 1,000 genomes from different TB isolates — one of the largest whole-

genome study of a single bacterial species so far. TB, which is caused by the bacterium Mycobacterium tuberculosis, exploded in Russia and other former Soviet nations in the early 1990s , after the collapse of the Soviet Union and its health system. The incomplete antibiotic regimens some patients received, meanwhile, sparked rampant drug resistance. But the latest study of TB cases in Russia, published today in Nature Genetics1, indicates that such ‘programmatic’ failures may not be the only explanation for the rise of drug-resistant TB in the region — biological factors also play a big part. As part of a long-standing effort to study the rampant drug-resistant TB in Samara, a region of Russia about 1,000 kilometres southeast of Moscow, researchers collected TB isolates from 2,348 patients and sequenced the entire genomes of 1,000 of them. This enabled the team to identify previously unknown mutations linked to

antibiotic resistance, as well as 'compensatory mutations' that improve the ability of drug-resistant TB to spread. Nearly half of the TB isolates were multi-drug resistant, which means that they were impervious to the two common

first-line antibiotics that cure most TB infections, while 16% of these isolates also harboured mutations that made them impervious to ‘second-line’ drugs . These infections are more expensive to treat, and patients

who receive ineffective drugs are more likely to spread TB. “It certainly adds an extra layer of worry, because one had assumed if you could solve programmatic weaknesses, you would solve the problem of the drug-resistant TB,” says the study's lead author Francis Drobniewski, a microbiologist at Queen Mary

University of London. “But this does seem to be a biological problem as well.” “Although we know the general story of TB drug resistance in Russia, these new findings are still shocking,” says Christopher Dye, an

epidemiologist at the World Health Organization in Geneva, Switzerland. "Truly scary," he adds. Antibiotics block essential functions in bacteria, such as making proteins or building cell walls . Mutations in the genes involved in these duties can lead to antibiotic resistance, but they also tend to make bacteria divide more slowly.

But laboratory experiments have shown that bacteria can develop compensatory mutations that restore the pathogen's ability to divide quickly . Drobniewski’s team found such mutations in more than 400 isolates that were resistant to the first-line antibiotic rifampicin, and the authors suggest that the mutations might

overcome the growth-slowing effect of evolving resistance. “The worst scenario is that the organisms are developing resistance, compensating for it, and evolving into something that’s new and different, that’s much less treatable,” says Megan Murray, an epidemiologist at the Harvard School of Public Health in

Boston, Massachusetts. In a 2013 study2, her team found both widespread drug resistance and compensatory mutations in their analysis of 123 TB genomes from around the world.

TB – Russia Impact

Copulos 2k Milton Copulos is the president of the National Defense Council Foundation, a nonprofit think tank that specializes in security concerns, “POTENTIAL RUSSIAN DESTABILIZATION RESULTING FROM AN MDR-TB EPIDEMIC”, 10/15/2000, ndcf.org, http://ndcf.dyndns.org/ndcf/Publications/2000/Bertek/Bertek.htm//OFBy the late 1970s, it was widely believed that by the end of the century, tuberculosis might be totally eradicated. This appeared reasonable as TB rates steadily declined following World War II. In the middle

1980s, however, it became increasingly evident that there was little basis for such optimism. In the industrialized West, TB rates stabilized, and in the developing world they began to rise. Today, tuberculosis has reached epidemic proportions in some lesser-developed countries. The World Health Organization reports that tuberculosis kills between 2 million and 3 million people each year. Some 8 million become sick from the disease. To put these figures in

perspective, TB kills more people each year than AIDS, malaria and tropical diseases combined. Indeed, it is the leading cause of death in the developing world. Percent of Total TB Cases: Foreign Born Residents 1989-1999While significant progress has been made in eliminating TB in the United States, the job is far from complete. In 1998, the latest year for which data is available, 18 states reported at least 100 cases of TB, and every state reported at least one case. California, Florida, Illinois, New York and Texas had the highest number of reported cases, representing 54 percent of the total. The prevalence of TB cases in New York and California is attributed in part to their substantial foreign-born populations. The proportion of TB cases represented by the foreign-born has steadily increased in

recent years. More disturbing were reports of drug resistance among TB isolates (MDR-TB). Overall, 8.1 percent of all cases (1086) showed resistance to at least isoniazid. Roughly 150 cases (1.1 percent) of isolates resistant to both isoniazid and rifampin, i.e. Multi-Drug Resistant Tuberculosis, were reported. Almost half of these cases were reported by New York and California. Among foreign-born residents, the proportion of MDR-TB cases increases 31 percent. Indeed, it is the advent of MDR-TB that holds the seeds of worldwide disaster. THE ROOT OF THE PROBLEM

Like other drug-resistant strains of bacteria, the advent of Multi-Drug Resistant Tuberculosis is most likely a consequence of the misuse of antibiotics , particularly in the

developing world. Typically, tuberculosis is treated with a combination of drugs that have two essential properties: antibacterial activity and the ability to inhibit the development of resistance. The Centers for Disease Control and Prevention protocol for treatment of TB in adults calls for the use of a combination of isoniazid, rifampin, pyrazinamide and either ethambutol or

streptomycin. The treatment is generally continued for a period of roughly six months in routine cases. If the disease progression is severe, however, the treatment may take as long as one year. Where the conventional treatment is successful, improvement will be observed in the patient within a month. Patient compliance, however, has been a major problem in treating conventional tuberculosis. For many patients, especially in developing countries, the importance of taking all of their medication on a regular schedule is simply not well understood. Also, the cost of medications can prove problematical in poverty-stricken nations. Whatever the cause, poor patient compliance has

had a devastating consequence: the advent of Drug Resistant and Multi-Drug Resistant Tuberculosis. MDR-TB: THE SEEDS OF AN EPIDEMIC The World Health Organization (WHO)

estimates that more than 50 million people are currently infected with Drug Resistant TB. In a March 2000 report, the WHO documenting the prevalence of MDR-TB in some 38 "Hot Spots" around the

globe. In several, specifically Estonia, Latvia, China, Iran and Russia, the rates of infection have reached alarming proportions. In Estonia, for example, 18 percent of all TB cases were of the Multi-Drug Resistant strain - up from 14 percent in 1997. But, the phenomenon is not limited to regions outside the developed world. The Canadian Bureau of AIDS, STD and TB reports that all but two provinces in Canada have experienced cases of Drug Resistant TB. A 1998 study by the Bureau found that 11.8 percent of all TB cases in Canada evidenced some

drug resistance, and 1.2 percent were MDR-TB. Russian Prison for TB Patients One of the "Hot Spots" causing the greatest concern is the Russian prison system . According to a survey of Russian prisons

by Medecins Sans Frontiers (Doctors Without Borders) more than 10 percent of all inmates - roughly 110,000 individuals - are infected with TB. Of these, roughly 30 percent are infected with MDR-TB. With some 300,000 prisoners released annually, this means that around 10,000 individuals infected with MDR-TB will enter the civilian population each year. Since every individual infected with MDR-TB could infect from 10 to 14 people over the course of a year , by 2010, Russian could have as many as one million of its citizens infected with MDR-TB . A 1999 report by the Public

Health Research Institute echoes the concern over the situation in Russian prisons stating: "The tuberculosis epidemic in Russia, particularly Russian prisons has reached alarming proportions. The prison system acts as an epidemiological pump, releasing into society tens of thousands of active TB cases and hundreds of thousands of infected individuals each year . The high rate of multi-drug resistant tuberculosis among them is especially threatening." The report warned that "transnational cases"; infections contracted in one country and then transported to another will become increasingly common. This notion is supported by the fact that the proportion of reported TB cases accounted for by foreign-born residents in industrialized nations such as the United States and Canada have been rising for several years. The question, however, is what to do to prevent the problem from becoming a global pandemic. Fortunately, there is an answer.

TB – China

China has a growing MDR-TB and XDR-TBMcNeil 12 Donald McNeil is a reporter for the New York Times, “China: Survey Reveals a Growing Number of Drug-Resistant Tuberculosis Cases”, 6/11/12, The New York Times, http://www.nytimes.com/2012/06/12/health/drug-resistant-tuberculosis-on-the-rise-in-china.html//OFChina has a “serious epidemic of drug-resistant tuberculosis ,” according to the first national survey of the disease, which was carried out by the Chinese Center for Disease Control and published last week in The New

England Journal of Medicine. Of the roughly 4,000 tuberculosis patients tested, a third of those with new cases and half of those with previously treated cases had drug-resistant disease .

Moreover, a quarter of the previously treated patients had multi-drug-resistant, or MDR, strains.

Eight percent of those had “extensively drug resistant” TB, as defined by its resistance to four

antibiotics: isoniazid, rifampin, ofloxacin and kanamycin. Strains resistant to that many drugs are nearly incurable. Even treating MDR tuberculosis can require several years and cost $16,000 for drugs and far more for

hospitalization. China, which has about one-fifth of the world’s people , has about a quarter of its drug-resistant TB cases, the Chinese center estimated. The report made it clear that China’s current treatment strategies were a failure. More than 40 percent of those treated for MDR tuberculosis had not taken

their last dose. The problem was particularly acute among people seen in general hospitals. Despite the fact that many newly infected patients had drug-resistant strains of TB, clinics did not test them for this. Some patients had been started on drugs without even receiving a firm diagnosis.

MDR-TB will run China dry – their economy can’t take itJuan 13 Shan Juan is a reporter for China Daily, an online Chinese news source, “Nearly 120,000 new cases of MDR-TB in China every year”, 4/19/2013, ChinaDaily.com, http://africa.chinadaily.com.cn/china/2013-04/19/content_16423982.htm//OFHeavily burdened by rising multi-drug-resistant Tuberculosis, China now has nearly 120,000 new cases on the mainland each year, according to public health experts. That accounts for 25 percent of the world's total per year, according to statistics from the Chinese Center for Disease Control and Prevention. MDR-

TB is defined as TB, which is resistant to isoniazid and rifampicin, the most powerful first-line anti-TB drugs. "MDR-TB needs more complicated diagnosis methods, longer and much more expensive treatment compared with common TB, which causes huge economic and human resource loss ," said

Chen Mingting, deputy director of the National Center for Tuberculosis of China CDC. With no effective intervention, the number of MDR-TB patients in China is expected to reach 710,000 on the mainland by 2020, which would incur an economic loss of more than 99 billion yuan mostly in medical

treatment, he said, citing previous studies by CDC. "That might upset social stability and harm economic development of the nation," he said.

Studies prove – China has a high rate of MDR and XDR TBTang et al 11 Shenjie Tang, Qing Zhang, Jinming Yu, Yidian Liu, Wei Sha, Hua Sun, Lin Fan, Jin Gu, Xiaohui Hao, Lan Yao, and Heping Xiao, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China (S. Tang, Q. Zhang, J. Yu, Y. Liu, W. Sha, H. Sun, L. Fan, J. Gu, X. Hao, L. Yao, H. Xiao); Shanghai Key Laboratory of Tuberculosis, Shanghai (S. Tang, Q. Zhang, J. Yu, Y. Liu, W. Sha, H. Sun, L. Fan, J. Gu, X. Hao, L. Yao, H. Xiao); Fudan University School of Public Health, Shanghai (J. Yu), “Extensively Drug-Resistant Tuberculosis, China”, March 2011, US National Library of Medicine, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166004//OFThe prevalence of drug-resistant tuberculosis (TB) is a serious problem in the People’s Republic of China. China is 1 of 22 countries with the highest incidence of TB (1). It is also

1 of 27 countries with the highest incidence of multidrug-resistant TB (MDR TB) and extensively

drug-resistant TB (XDR TB). According to the national baseline survey on TB in 2007 and 2008, the frequency of MDR

TB among pulmonary TB patients in China was 8.3%. We estimate that there are 120,000 new cases of MDR TB in China per year, which accounts for 24.0% of new cases worldwide (510,000) per year. XDR TB has recently emerged as a global public health problem (2). It is defined as TB with resistance to at least isoniazid, rifampin, a fluoroquinolone, and 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). XDR TB is a type of MDR TB that shows resistance to isoniazid and rifampin. Recent reports on current prevalence of XDR TB (3,4) indicate

that China now has the second highest incidence of MDR TB worldwide . However, there is no information available on XDR TB in China. To obtain information on XDR TB in China, we conducted a study at Shanghai Pulmonary Hospital. It is the only specialized hospital for TB in Shanghai and plays a major role in treating TB patients and providing state-of- the-art treatment. Most patients referred to this hospital have been previously treated or have recurrent TB. Therefore, higher rates of MDR TB and XDR TB are expected in this setting, which is not comparable to community or multicenter-based studies. Patients with culture-proven MDR TB during January 2008–June 2009 were retrospectively evaluated. All patients were HIV negative. Drug susceptibility testing was conducted for culture-positive isolates by using the BACTEC 960 System (Becton Dickinson, Franklin Lakes, NJ, USA) at concentrations of 0.1 μg/mL for isoniazid, 1 μg/mL for rifampin, 5 μg/mL for ethambutol, 1 μg/mL for streptomycin, 2.5 μg/mL for capreomycin, 1μg/mL for amikacin, and 2 μg/mL for ofloxacin. Among 518 strains that were culture positive for Mycobacterium tuberculosis, 350 (67.6%) were drug resistant and 168 (32.4%) were drug sensitive. A total of 217 (41.9%) of 518 strains were classified as MDR and accounted for 62.0% of drug-resistant strains. Among 217 MDR strains, 45 (20.7%) were from patients who had a new diagnosis of TB, and 172 (79.3%) were from patients whose medical history included treatment for TB for >4 weeks. A total of 65 (12.6%) strains were XDR, of which 51 were from patients previously treated. These strains accounted for 18.6% of drug-resistant strains and 30.0% of MDR strains. Of 217 MDR isolates, 217 (100.0%), 217 (100.0%), 172 (79.3%), 175 (80.6%), 170 (78.3%), 68 (31.3%), and 69 (31.8%) were resistant to isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, capreomycin, and amikacin, respectively. Of 65 XDR isolates, 65 (100.0%), 65 (100.0%), 61 (93.9%), 60 (92.3%), 65 (100.0%), 60 (92.3%), and 60 (92.3%) were resistant to isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, capreomycin, and amikacin, respectively. Our results indicate that 30.0% of MDR

strains were XDR strains. Although our study was conducted in only 1 hospital, this prevalence of XDR strains indicates that XDR TB in China is a serious concern . A total of 78.3% of MDR isolates were resistant to ofloxacin, which is higher than rates reported for South Korea (42.8%) (5) and Taiwan (16.6%) (6). Population-based studies have reported lower frequencies of XDR strains among MDR strains; 9.9% for 14 qualified reference laboratories (7), 5.3% for South Korea (8), and 23.9% for South Africa among patients co-infected with HIV and TB (9). In our study, 2 factors may have contributed to high drug-resistance rates. First, fluoroquinolones have been widely used for treatment of respiratory tract bacterial infections because of their efficacy and mild adverse reactions. Second, we also prescribed fluoroquinolones for treatment of patients with drug-resistant TB and some patients with drug-sensitive TB who could not tolerate first-line anti-TB drugs. More than 90% of patients with XDR TB had strains resistant to streptomycin, ethambutol, capreomycin, and amikacin, which was higher than rates reported in other studies (5,9,10). Currently, anti-TB

medications in China for treatment of patients with XDR TB are scarce. This scarcity has resulted in poor treatment outcomes in patients with XDR TB. One limitation of our study is that we investigated patients at only 1 specialized TB hospital in Shanghai. Therefore, data are not representative for the general population. A community-based multicenter study is needed to determine the true prevalence of XDR TB in China. Nevertheless, our study confirms

that the prevalence of MDR TB and XDR TB is high in some areas. It also emphasizes the need to increase TB prevention and therapy, educate society about TB, implement modern TB control strategies, and strengthen basic and clinical research to curb the spread of MDR TB and XDR TB.

Agriculture / Instability

Antibiotic resistance undermines food production and causes global instabilityWahlberg, Swedish Civil Contingencies Agency, et al, 2012(Maria, “Five challenging future scenarios for societal security,” https://www.msb.se/RibData/Filer/pdf/26562.pdf)In particular, the inability of healthcare to use established methods of treatment is perceived as a problem, but antibiotic resistance is also causing major problems for food producers through diseases in animals and plants. Human behaviour and habits have also changed worldwide. People stay at home even for simple colds and increasingly refrain from travelling.To some extent, the new methods of treatment that biotechnology has created compensate for the treatments that require antibiotics no longer working, but common infections are difficult to treat. Surgical intervention is avoided wherever possible because of the risk of bacterial infection, and many people are waiting as long as possible to replace a worn-out hip or choose to treat the various forms of cancer with new, less proven treatments rather than surgery.The situation has created a lot of tension and unrest around the world. Some countries have been identified as being more lax in managing both the ban on antibiotics and in protecting against infections. A constant cause of concern is what would happen if a worldwide pandemic were to break out. In conjunction with an influenza outbreak, many people suffered bacterial complications, which are now very difficult to treat. Additionally, control of the pandemic itself was complicated by the fact that the virus developed resistance to antiviral drugs. Many people across the world harbour a deep distrust of the authorities' handling of the antibiotic resistance issue. Conspiracy theories and rumours spread quickly through various communication channels.

Solvency

Microorganisms Best

Microbes are key – compounds produced much more easily than in macroorganismsWaters, Hamann, Department of Pharmacognosy @ University of Mississippi, Hill, and Place, Institute of Marine and Environmental Technology @ University of Maryland, 2010(Amanda, Mark, Russell and Allen, “The expanding role of marine microbes in pharmaceutical development,” Current Opinion in Biotechnology, December)Marine natural products are a continued focus for drug discovery and have provided many important therapeutic agents [1]. Lead compounds with biomedical potential have been isolated from marine invertebrates, bacteria and fungi. Each year numerous compounds with an array of biological activities are reported [2], but to-date only 13 molecules have entered into the clinical pipeline. Four molecules have been approved for clinical use, one of which is approved only in the EU. The approved molecules include two nucleosides based on sponge-derived nucleosides, a cone snail peptide, and a metabolite isolated from a tunicate [3].Marine microbes have received growing attention as the sources for bioactive metabolites and have great potential to increase the number of marine natural products in clinical trials. The sustainable and economic supply of the active pharmaceutical ingredient (API) is often easier to achieve for compounds produced through microbial fermentation approaches vs the cultivation of slower growing macroorganism. Bacterial derived marine natural products have been the subject of two recent reviews, one dealing with symbiotic bacteria and one on marine microbes as drug leads in general [4,5]. In this volume, marine actinomycetes (Jensen), cyanobacteria (Gerwick), symbionts of ascidians (Schmidt and Donia) and bryozoans (Trindade-Silva et al.) are discussed separately.

Ocean Drugs Best / AT: Terrestrial CP

Oceans are key to new discoveriesNational Academies 9 (The National Academies—the National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and the National Research Council—provide a public service by working outside the framework of government to ensure independent advice on matters of science, technology, and medicine. They enlist committees of the nation’s top scientists, engineers, and other experts— all of whom volunteer their time to study specific concerns. The results of these deliberations are authoritative, peer-reviewed reports that have inspired some of the nation’s most significant efforts to improve the health, education, and welfare of the population. August, 2009, “ocean Exploration”, http://oceanleadership.org/wp-content/uploads/2009/08/Ocean_Exploration.pdf)

Ocean explOratiOn and Human HealtH At least 20,000 new biochemical substances from marine plants and animals have been identified during the past 30 years, many with unique properties useful in fighting disease. “Biodiscovery” researchers have had success in all types of ocean environments. A 1991 expedition by the Scripps Institution of Oceanography’s Paul Jensen and William Fenical resulted in the discovery of a new marine bacterium, Salinispora tropica, found in the shallow waters off the Bahamas. This bacterium produces compounds that are being developed as anticancer agents and antibiotics. It is related to the land-based Streptomyces genus, the source of more than half of our current suite of antibiotics.3 Deep-water marine habitats constitute a relatively untapped resource for the discovery of drugs. In early 2000, Shirley Pomponi and Amy Wright from Harbor Branch Oceanographic Institution explored deep waters a few miles off the shore of the Florida Keys. Using the robotic claws and high-powered vacuums of the Johnson Sea-Link submersibles, the team gathered a host of deep-water organisms. They met success with the discovery of a new genus of sponge, nicknamed the “Rasta” sponge, containing anticancer compounds.4 The promise and problems of developing novel marine chemicals into bioproducts, from pharmaceuticals to compounds used in agriculture, is examined in the National

Research Council report Marine Biotechnology in the Twenty-First Century. The report recommends revitalizing the search for new products by making it a priority to explore unexamined habitats for new marine organisms.

Plan solves – ocean drugs are better than those in the squoAAAS 9 (American Association for the Advancement of Scientists, February 13, 2009, “Fighting the Rising Tide of Antibiotic Resistance: Causes and Cures in the Sea”)Abstract: National Oceanic and Atmospheric Administration (NOAA)’s investigations into coral disease, red tides and other marine environmental issues have led to discoveries of novel chemicals as a source for new pharmaceuticals. A class of these chemicals function as antibiotics for microorganisms providing survival advantages and may be applied for use in human health care. Our research has found several compounds such as euglenophycin, recently

isolated and characterized from Euglena sanguinea (a freshwater and estuarine microbe) which exhibits very strong antibiotic, antifungal, and antiviral potential as well as some anti-cancer and angiogenesis

activities. Also, our research into coral disease has resulted in thousands of new bacterial isolates producing highly selective antimicrobial compounds such as in the Gorgonian coral Pseudopterogoria americana that yields highly selective small peptide antibiotics.

Many of these novel anti-biotics are advantageous, as they demonstrate no cytotoxic responses to human cells and may minimize negative side effects associated with those drugs in current usage. Observations from the sponge Agelas conifera’s ability to protect itself against fouling and

disease led to the discovery of ageliferin isolates that demonstrate very strong anti-biofilm activity. The compounds with this specific activity hold promise to increase the efficacy of current and out of use antibiotics with their ability to inhibit and/or disperse the protective layer that infectious agents often produce to protect themselves. Such compounds are also finding potential use in other areas of human health as well, including cystic fibrosis, chemo-therapy,

anti-fungal agents, and for use in medical stints and prosthetics. Marine natural products hold much promise in combating both the trend of antibiotic resistance but also to discover new antibiotics. The one-two punch of discovering new antibiotics as well as novel chemicals that make older generation drugs more effective represents cutting edge science addressing a critical need in human health care.

AT: Terrestrial CP

The CP is 300 to 400 times less effectiveBruckner, coral reef ecologist in the National Marine Fisheries Service’s Office of Protected Resources, Spring 2002(Andrew, “Life-Saving Products from Coral Reefs,” Issues in Science & Technology, posted online 11-27-2013, http://issues.org/18-3/p_bruckner/)

Coral reefs are storehouses of genetic resources with vast medicinal potential, but they must be properly managed.

During the past decade, marine biotechnology has been applied to the areas of public health and human disease, seafood safety, development of new materials and processes, and marine ecosystem restoration and remediation. Dozens of promising products from marine organisms are being advanced, including a cancer therapy made from algae and a painkiller taken from the venom in cone snails. The antiviral drugs Ara-A and AZT and the anticancer agent Ara-C, developed from extracts of sponges found on a Caribbean reef, were among the earliest modern medicines obtained from coral reefs. Other products, such as Dolostatin 10, isolated from a sea hare found in the Indian Ocean, are under clinical trials for use in the treatment of breast and liver cancers, tumors, and leukemia. Indeed, coral reefs represent an important and as yet largely untapped source of natural products with enormous potential as pharmaceuticals, nutritional supplements, enzymes, pesticides, cosmetics, and other novel commercial products. The potential importance of coral reefs as a source of life-saving and life-enhancing products, however, is still not well understood by the public or policymakers. But it is a powerful reason for bolstering efforts to protect reefs from degradation and overexploitation and for managing them in sustainable ways.

Between 40 and 50 percent of all drugs currently in use, including many of the anti-tumor and anti-infective agents introduced during the 1980s and 1990s, have their origins in natural products. Most of these were derived from terrestrial plants, animals, and microorganisms, but marine biotechnology is rapidly expanding. After all, 80 percent of all life forms on Earth are present only in the oceans. Unique medicinal properties of coral reef organisms were recognized by Eastern cultures as early as the 14th century, and some species continue to be in high demand for traditional medicines. In China, Japan, and Taiwan, tonics and medicines derived from seahorse extracts are used to treat a wide range of ailments, including sexual disorders, respiratory and circulatory problems, kidney and liver diseases, throat infections, skin ailments, and pain. In recent decades, scientists using new methods and techniques have intensified the search for valuable chemical compounds and genetic material found in wild marine organisms for the development of new commercial products. Until recently, however, the technology needed to reach remote and deepwater reefs and to commercially develop marine biotechnology products from organisms occurring in these environments was largely inadequate.

The prospect of finding a new drug in the sea, especially among coral reef species, may be 300 to 400 times more likely than isolating one from a terrestrial ecosystem. Although terrestrial organisms exhibit great species diversity, marine organisms have greater phylogenetic diversity, including several phyla and thousands of species found nowhere else. Coral reefs are home to sessile plants and fungi similar to those found on land, but coral reefs also contain a diverse assemblage of invertebrates such as corals, tunicates, molluscs, bryozoans, sponges, and echinoderms that are absent from terrestrial ecosystems. These animals spend most of their time firmly attached to the reef and cannot escape environmental perturbations, predators, or other stressors. Many engage in a form of chemical warfare, using bioactive compounds to deter predation, fight disease, and

prevent overgrowth by fouling and competing organisms. In some animals, toxins are also used to catch their prey. These compounds may be synthesized by the organism or by the endosymbiotic microorganisms that inhabit its tissues, or they are sequestered from food that they eat. Because of their unique structures or properties, these compounds may yield life-saving medicines or other important industrial and agricultural products.

Exploration Works

Deep-Sea exploration is viable and key to drug researchNeill 13 - Director of the World Ocean Observatory, a web-based place of exchange for information and educational services about the ocean (Peter, 7/12/13, "Ocean Bio-Prospecting," www.huffingtonpost.com/peter-neill/law-of-the-sea-ocean-bioprospecting_b_3575098.html, ADL)But it is the pharmaceutical exploration that should also be of great concern. Again, there are

structures in place -- the Convention on Biological Diversity foremost among them. But this exploration is less physical in a way, and much more complicated, with the knowledge and value available from ocean resources located everywhere -- in the length of the water column, coral reefs, deep ocean vents, and the sea floor. The issues are many: access, research costs, transaction costs, intellectual property and patent issues, regulatory structure, benefit-sharing, fairness and equity issues, and the right to traditional knowledge sustained by indigenous

peoples. All the major pharmaceutical companies and research institutions are already fully engaged in the drug development and profit implications of these resources, make no mistake

about it. At a conference on bioscience and the ocean, sponsored in 2012 by the New York Academy of Sciences, the extent of this research potential was apparent, with presentations on the

synthesis of DNA from ocean species such as sponges and mollusks, imitating certain biological functions that could be applied to disease in humans. A significant number of new drugs in preliminary

testing for cancer treatment are derived this way from the information decoded from marine plants and animals. A very recent U.S. Supreme Court decision clarified one of the larger questions for such research: by protecting knowledge derived from the discovery of such natural processes from the exclusivity of patent protection, while nonetheless permitting "ownership" of processes invented or synthesized from them for manufacture and application as vaccines or medicines beneficial to human health. It is a profound distinction, and a major step toward protection of such ocean resources over time. It is interesting to note, however, that this U.S. judicial decision notwithstanding, the United States Congress has not approved either the UN Convention on Biological Diversity or the UN Convention on the Law of the Sea, even though both are now international law, having been ratified by the requisite number of nations.

Fee-Based System

Easy to collect federal revenue from bioprospectingU.S. Commission on Ocean Policy 04 (2004, "An Ocean Blueprint for the 21st Century: Final Report," govinfo.library.unt.edu/oceancommission/documents/full_color_rpt/000_ocean_full_report.pdf, ADL)Various parts of this report discuss federal revenues that are, or may be, generated from offshore activities. Chapter 6 introduces the concept of resource rents, the economic value derived from the use or development of a natural resource. It recommends that the use of a publicly-owned resource by the private sector be contingent on providing a reasonable return of some portion of the revenues to taxpayers. For example, the proposal in Chapter 22 for a new marine aquaculture

management framework includes a recommendation for a revenue collection process that recognizes the public interest in the ocean areas and resources used for aquaculture operations in federal waters.

Chapter 23 recommends a similar process for bioprospecting

U.S. Key

Notes

Use the 1AC cards!

U.S. Key – Best Biomedicine

U.S. research productivity outpaces everyone elseDeVol, chief research officer at the Milken Institute, Bedroussian, research economist at the Millken Institute, and Yeo, senior research analyst at the Millken Institute, Sept 2011(Ross, Armen, and Benjamin, “The Global Biomedical Industry: Preserving U.S. Leadership,” http://www.milkeninstitute.org/pdf/CASMIFullReport.pdf)Because of the legal and regulatory framework discussed above and the subsequent formation of a superior ecosystem of biomedical innovation, US. firms were able to reinvest more of their profits back into R&D—and their European counterparts began to shift more of their R&D operations to the US. The research productivity of the United States tops all other nations as measured by the ratio of world-first patents filed for marketed new molecular entities relative to R&D spending by biopharmaceutical firms. Additionally, the US. captured 68.3 percent of total venture capital investment in the life sciences among OECD nations in 2007.

U.S. Key – Federal Waters

Federal government key - environmental leadership, permits, and licensingU.S. Commission on Ocean Policy 04 (2004, "An Ocean Blueprint for the 21st Century: Final Report," govinfo.library.unt.edu/oceancommission/documents/full_color_rpt/000_ocean_full_report.pdf, ADL)Based on the potentially large health benefits to society, the federal government should encourage and support the search for new

bioproducts from marine organisms, known as bioprospecting. However, before wide-scale bioprospecting proceeds in federal waters, requirements need to be established to minimize environmental impacts. Planning and oversight will help ensure that public resources are not exploited solely for private gain and will help protect resources for future generations. Individual states regulate the collection of marine organisms quite differently, sometimes requiring an array of research permits to collect organisms and licenses to gain access to particular areas. Regulations that ban the removal of specific organisms, such as corals and other sensitive species, often exist in both state and federal protected areas. In protected federal waters, such as national marine sanctuaries, research permits are required for all collections. However, bioprospecting outside state waters and federal protected areas is unrestricted, except for certain species subject to regulation under existing legislation, such as the Endangered Species Act. Both U.S. and foreign researchers, academic and commercial, are free to collect a wide range of living marine organisms without purchasing a permit and without sharing any profits from resulting products. On

land, the National Park Service has successfully asserted the government’s right to enter into benefit

sharing agreements in connection with substances harvested for commercial purposes in Yellowstone

National Park. The National Park Service is in the process of conducting a full environmental impact statement on the use of such agreements for benefit sharing in other parks. This practice could serve as a model for the management of bioprospecting in U.S. waters. Similar to other offshore activities, bioprospecting in federal waters will require appropriate permitting and licensing regulations to protect public resources while encouraging future research. Furthermore, when allocating use of federal ocean areas for bioprospecting, it is important that consideration be given to other potential uses of those areas, including oil and gas exploration, renewable energy, and aquaculture. A proposal for better coordinated governance of offshore uses is discussed in detail in Chapter 6.

Federal government key for permitsU.S. Comission on Ocean Policy 04 (2004, "An Ocean Blueprint for the 21st Century: Final Report," govinfo.library.unt.edu/oceancommission/documents/full_color_rpt/000_ocean_full_report.pdf, ADL)The National Ocean Council should ensure that each current and emerging activity in federal waters is administered by a lead federal agency and make recommendations for Congressional action where needed. The lead agency should coordinate with other applicable authorities and should ensure full consideration of the public interest. Establishing a Coordinated Offshore Management Regime There are two main categories of ocean uses: those that are confined to a specific location, typically linked to an offshore structure such as an oil rig, a wind turbine, an aquaculture pen, or a sunken vessel, and those, such as fishing or recreation, that are more diffuse, taking place within broad, flexible areas. Some activities combine these characteristics and could be managed according to either scenario. As an example, bioprospecting could be treated as a site-specific use by granting exclusive rights to explore for organisms in a particular area, or as a moveable activity by granting permits to collect certain organisms regardless of their location. To move toward an ecosystem-based management approach, the federal government needs to develop a better understanding of offshore areas and resources, prioritize uses, and ensure that activities in a given area are compatible.

NIH Key – Expertise

NIH expertise is keyNational Research Council, the policy wing of the U.S. National Academies, scientific national academy of the United States, 1999(Commission on Geosciences, Environment and Resources, National Research Council, Division on Earth and Life Studies, Ocean Studies Board, From Monsoons to Microbes: Understanding the Ocean's Role in Human Health, pg. 81)The Discovery and Development of Marine Pharmaceuticals: Needs for the 21st Century- Marine organisms as a source of pharmaceuticalsThe successes to date in the discovery of novel chemicals from marine organisms that have demonstrated potential as new treatments for cancer, infectious diseases, and inflammation, suggest that there needs to be a greater focus on the development of drugs from marine sources. Exploration of unique habitats, such as deep sea environments, and the isolation and culture of marine microorganisms offer two underexplored opportunities for discovery of novel chemicals with therapeutic potential. The successes to date based on a very limited investigation of both deep sea organisms and marine microorganisms suggests a high potential for continued discovery of new drugs. Marine microorganisms are particularly attractive because they fit in with the traditional pharmaceutical “model” of a natural product drug source. Moreover, supply of bulk amounts of a microbially derived drug can be addressed by large-scale fermentation of bioactive marine microorganisms.- Expand marine drug discovery beyond cancer to include other diseasesPrograms such as the Natural Products National Cancer Drug Discovery Groups (NPNCDDGs) at the National Cancer Institute have been tremendously successful in interfacing non-tradilional drug sources, such as marine organisms, with the screening and development potential of major pharmaceutical companies. Similarly, the Small Business Innovative Research (SBIR) grants have fostered interactions on a smaller scale. Other institutes within the NIH should consider developing programs for marine-based drug discovery for diseases that desperately need new therapies, such as neurodegenerative, cardiovascular, and infectious diseases.In particular, there needs to be a more organized approach to the development of antibiotics from marine sources. The increasingly limited effectiveness of currently available drugs has dire consequences for public health, although the consequences have not yet been felt by the public or the medical community. The United States is faced with the serious threat of re-emerging infectious diseases, such as tuberculosis, indicating that a radical and aggressive approach needs to be taken to control these multiple-drug-resistant pathogens.

NIH Key – FDA Approval

NIH research has the highest impact and receives priority FDA reviewChatterjee and Rohrbaugh, Office of Technology Transfer, US National Institutes of Health, 1/9/2014(Sabarni and Mark, “NIH inventions translate into drugs and biologics with high public health impact,” Nature Biotechnology, issue 32, p. 52-58)The contribution of inventions from public-sector research institutions (PSRIs) to the development of drug and biologic products has long been recognized1, 2, 3. Until now, however, no study has carried out an in-depth comparison of the specific contributions of the US National Institutes of Health (NIH) Intramural Research Program (IRP) and other US PSRIs to the development of drugs and biologics approved by the US Food and Drug Administration (FDA). In the following article, we analyze the number of products resulting from inventions from these sources (Fig. 1), assess their public health impact, categorize the type of licenses made and the licensee organizations that made them and estimate the funding invested that resulted in drug and biologic products. We show that NIH-IRP inventions have had a disproportionately greater impact in three respects: first, the overall number of products, particularly vaccines, cancer therapeutics and in vivo diagnostics; second, the number of drugs granted orphan status; and third, the number of drugs developed under New Drug Applications (NDAs) granted priority review by the FDA because they offer major advances in treatment. Gross annual commercial sales of these products serve as a limited but direct measure of their economic impact, which for the drugs and biologics that utilize NIH-IRP inventions is double the government's total annual investment in the NIH-IRP.

FDA incentivizes cooperation between scientists which facilitates coordination and data sharing. NIH is key to solve Woodcock and Woosley 8 (Janet, Raymond, “The FDA Critical Path Initiative and its Influence on New Drug”, http://www.annualreviews.org.turing.library.northwestern.edu/doi/pdf/10.1146/ annurev.med.59.09 0506.155819)The novel aspects of these C-Path projects are the core neutral funding and the scientifically qualified team leaders of the consortia. C-Path brings together scientists from highly competitive companies and then maintains a productive environment through modern project management techniques.

Continued participation by the consortium members depends on the rewards they receive for the

investment of time and effort. These rewards are expected to be science-based regulatory standards enabled by the work of the consortium, which define a development process that has the greatest possible efficiency

and safety. The future of the Critical Path Initiative is increasingly secure because the many stake- holders in medical product development have come to recognize the value of and need for process improvement. They also recognize the importance of having a safe haven such at MIT’s Center for Biomedical Innovation or a neutral third party such as C-Path where members of the pharmaceutical industry and the FDA can work as scientists and not be inhibited by their usual roles as regulators and regulated.

Likewise, industry scientists are finding it very rewarding to share with their competitors their knowledge and experiences, especially their failures, in precompetitive areas of development. Therefore, it is likely that the work of the critical path will continue indefinitely. What is not yet clear is where it will take place and how it will be coordinated. The NIH is increasingly involved in critical path projects. The NCI collaborates with the FDA through the Oncology Biomarker Qualification Initiative (OBQI). The National Heart, Lung, and Blood Institute has been working with the FDA to coordinate studies of the genetic testing of warfaring. However, tremendous potential remains for the NIH to play an important role in providing FDA with the data and scientific information needed to improve medical product development. Examples include the NIH roadmap initiatives, the facilities of the

National Center for Research Resources, and the growing network of Clinical Translational Research Awards. These are almost all devoted to translational science and have the potential to interface directly with some of the 76 projects on the 2006 Critical Path Opportunities List.

FDA Approval Good

Pharmaceutical innovation has been stagnant the last 30 years FDA action is critical to reinvigorating R&DWoodcock and Woosley 8 (Janet, Raymond, “The FDA Critical Path Initiative and its Influence on New Drug”, http://www.annualreviews.org.turing.library.northwestern.edu/doi/pdf/10.1146/ annurev.med.59.09 0506.155819)

The failure of this surge to materialize has prompted extensive speculation on the cause of this “pipeline problem.” Many in the drug development community believe that genomics and other newer technologies are not yet sufficiently mature to reliably support drug development. Others blame industry business decisions or regulatory requirements. In 2004, the FDA published a White Paper entitled “Innovation or Stagnation: Challenges and Opportunities on the Critical Path to Medical Product Development” (7). While acknowledging that a combination of factors has likely led to the current drug development situation, this paper called attention to an important and Drug development can be conceptualized as a process leading from basic research through a series of developmental steps to a commercial product (Figure 2). The FDA White Paper identified the “Critical Path” as a process beginning with identification of a drug candidate and culminating in marketing approval. Along the path to marketing, the product is subjected to a series of evaluations to predict its safety and effectiveness and to enable its mass production. Despite extensive investment in

basic biomedical science over the past three decades, there has been very little change in the science of the development process. The sophisticated scientific tools used in drug discovery and lead optimization are generally not utilized in the preclinical and clinical development stages. Instead, traditional empirical evaluation is used in both animal and human testing. We are using the tools of the last century to evaluate this century’s advances. How did this situation come about? The FDA’s analysis, which has been generally accepted, is that “no one is charged” with improving developmental science. The National Institutes of Health (NIH) focus on innovative biomedical science, not the applied science of the development process; as a result, academia also concentrates on basic science. The pharmaceutical industry is concerned with developing innovative products. The FDA, as a regulator, is not charged with— nor is it funded for—improving the process, although it has been involved in such efforts. Additionally, the science needed is generally integrative “big science” that requires contributions from multiple disciplines and sectors and is not within the purview of a single investigator or firm.

FDA is the only way to facilitate effective biomarkers which are essential to drug development Woodcock and Woosley 8 (Janet, Raymond, “The FDA Crtical Path Initiative and its Influence on New Drug”, http://www.annualreviews.org.turing.library.northwestern.edu/doi/pdf/10.1146/ annurev.med.59.09 0506.155819)

Interindividual drug target heterogeneity due to genetic polymorphisms may be important in diseases other than cancer. Using biomarkers to classify patients by disease type or response probability can improve drug development by reducing variability and increasing the size of the treatment effect. If the biomarkers

are then incorporated into clinical practice, clinical variability can also be reduced. Decreasing

interindividual differences in drug exposure is another strategy to reduce response variability. Recently, FDA has approved a number of assays for genetic polymorphisms in drug-metabolizing enzymes. Many marketed drugs are subject to polymorphic metabolism, leading to a wide range of exposures in the treated population (13). The safety and effectiveness of these drugs, as well as investigational drugs with

variable metabolism, could be improved by using dose adjustments directed by genetic tests. The absence of practical processes to establish the clinical significance of a given biomarker has severely limited the use of existing biomarkers in drug development and the clinic. The return on investment for diagnostic test manufacturers is seldom sufficient to enable extensive clinical trials, and investigational drugs are rarely developed in concert with new diagnostic tests. To address these issues, FDA and other stakeholders have established the concept of biomarker qualification, which means determining the clinical significance of the biomarker in a specific context (14). For example, a genetic test might be qualified to

identify a subset of disease for the purpose of trial enrollment. The quantity of data needed for qualification depends on the intended use, and most uses require far less data than would be required to establish a surrogate endpoint for efficacy.

Biomarkers are super important for disease prevention Woodcock and Woosley 8 (Janet, Raymond, “The FDA Critical Path Initiative and its Influence on New Drug”, http://www.annualreviews.org.turing.library.northwestern.edu/doi/pdf/10.1146/ annurev.med.59.09 0506.155819)

Development of new biomarkers was identified as the highest priority for scientific effort. Genomic, proteomic, and metabolomic technologies, as well as advanced imaging techniques, hold tremendous promise for generating new biomarkers that can reflect the state of health or disease at the molecular level (11). Although much prior discussion about the use of biomarkers in drug development has focused on surrogate endpoints for effectiveness, most uses of new biomarkers are not expected to involve surrogacy. For example, prediction of adequate safety is an essential part of drug development. Currently, preclinical safety testing involves traditional animal toxicology studies, as well as in vitro assays such as the Ames test. Animal toxicology tests are very useful for assessing safety for initial human testing; however, they often fail to uncover the types of toxicities seen after widespread human exposure. New technologies, such as gene expression assays in whole cell or animal systems, proteomics, or metabolomics, may provide much greater insight into the whole spectrum of pharmacologic effects of a candidate drug. Such technologies may also be useful in comparing the candidate’s effects (particularly off-target effects) to those of other drugs in its class or other drugs intended for similar uses (12). Drug developers are just beginning to use such technologies in the preclinical safety workup, and the clinical implications of such findings have not been worked out. The current scheme for clinical safety testing has also failed to incorporate recent scientific advances. Human safety during drug development is primarily evaluated on an observational basis from subjects exposed in the various developmental trials. The markers used to assess potential human toxicity are also assays that have been available for decades, e.g., clinical chemistries and hemograms. Few explanatory studies are carried out to determine the mechanism of an observed side effect, and assays to predict rare side effects are not available. Despite premarket exposure of thousands of subjects, serious side effects are frequently uncovered after marketing. New types of biomarkers may provide opportunities for prevention or early detection of these adverse events. The current problems with predicting and evaluating

drug efficacy could also be ameliorated by using biomarkers. Many drug efficacy problems stem from the extreme variability of human disease response. New biomarkers can improve diagnosis, define

disease subsets that may differ in response, define individual variability in the drug’s molecular target, and provide an early readout of response to therapy (11). For example, both in vitro diagnostics and imaging techniques are expected to provide additional information about disease subsets. This is already beginning to happen in cancer, where gene expression assays are being used to supplement histologic and clinical assessments of tumors, e.g., evaluating the likelihood of recurrence and the need for adjuvant therapy. For disorders such as psychiatric conditions that are currently diagnosed by clinical symptoms, it is hoped that genetic or imaging markers may help to distinguish biologically based subsets. A related type of biomarker is one used to predict treatment responsiveness. Many new cancer therapies target a specific molecule or cellular pathway. Genetic, proteomic, or other molecular assays that assess target status within a tumor may be used to predict responsiveness to a targeted drug. This is the strategy used with the drugs trastuzumab (Herceptin®) and imatinib (Gleevec®).

FDA is key to data analysis that’s critical to develop disease models Woodcock and Woosley 8 (Janet, Raymond, “The FDA Critical Path Initiative and its Influence on New Drug”, http://www.annualreviews.org.turing.library.northwestern.edu/doi/pdf/10.1146/ annurev.med.59.09 0506.155819)

One of the greatest scientific flaws in the current process of medical product development is its failure to produce generalized knowledge despite a huge investment in data generation. For example, FDA holds the world’s largest collection of animal test data and correlated human trial data, but most of this information is unusable in its current form, except to document a specific development program. As a result, opportunities for major improvement are missed. Under the Critical Path Initiative, stakeholders are beginning to take advantage of these opportunities. For example, FDA and various partners have created a standard for a digital electrocardiogram (ECG) recording, and FDA requested that ECG data submitted to it be in this format. At the same time, a data warehouse to hold the ECG data was established. Since that time, > 500,000 digital ECGs have been added to the warehouse, and a collaboration with Duke University has been established for overall data analysis (17). This resource may help scientists efficiently evaluate candidate drugs for adverse cardiac repolarization effects, a concern that is currently addressed (somewhat less than satisfactorily) by extensive

clinical testing. As data standards for regulatory submissions are implemented, processes and protocols to utilize the data for research purposes without compromising proprietary interests need to be

developed. One important use of such data will be to construct quantitative models of disease processes, incorporating what is known about biomarkers, clinical outcomes, and the effects of various interventions.

These models can then be used for trial simulations, to better design appropriate trials and clinical outcome measures (18). Although the FDA has constructed several disease models, this work is in its early

stages and will require extensive partnerships. However, there is little doubt that such quantitative approaches constitute the future of product development and assessment.

FDA’s Critical Path Initiative key to new innovative safe medicine Woodcock and Woosley 8 (Janet, Raymond, “The FDA Crtical Path Initiative and its Influence on New Drug”, http://www.annualreviews.org.turing.library.northwestern.edu/doi/pdf/10.1146/ annurev.med.59.09 0506.155819)

In 2004, the US Food mid Drug Administration (FDA) launched the Critical Path Initiative, a project that is intended to improve the drug and medical device development processes, the quality of evidence generated during development, and the outcomes of clinical use of these products. Why would a regulatory agency be involved in such a modernization effort? FDA's mission is to protect and promote the health of the public. With respect to drugs, biological products, and medical devices, this translates into ensuring reasonable product safety while also facilitating the translation of scientific innovations into commercial products. The ongoing tension between process are the best way to resolve these conflicts to the satisfaction of most parties and to the benefit of the public. Although the initiative concerns all regulated medical products, this review discusses Critical Path in the context of drug development.

FDA Chief Innovation Officer key to effective solvency Dutton 11 (Gail, Genetic Engineering & Biotechnology News, Volume 31, No. 18, “Can the FDA be a Catalyst for Innovation?”, http://online.liebertpub.com.turing.library.northwestern.edu/doi /pdf/10.1089/gen.31.18.05)

BIO is working with the FDA to reduce the risks of timidity by triaging new technologies by their

potential contributions to science and healthcare (such as their ability to reduce false positives and false negatives), and providing the information necessary to help reviewers make informed decisions when they encounter these technologies. For the future, Greenwood suggested creating the position of “chief innovation officer”. This is different from the chief science officer already in place, Emmett said. “The chief science officer is tasked with enhancing the internal science infrastructure,” he explained. A chief innovation officer, in contrast, would work

with external consortia and public/private/academic partnerships to coordinate and integrate their advances into the FDA as pilot programs. “For example, as new clinical trial designs or new biomarkers or new ways to

develop or use electronic medical records are developed, the chief innovation officer would work with their developers to see that they are validated and tested in the FDA’s centers, to increase the FDA’s comfort level with these innovations.” Despite the significant challenges the FDA is facing, Dr. Rodell said there also are significant opportunities to design an efficient, 21st century agency. “Many of the recommended changes require legislation,” Emmett admitted, “but we want to elevate the FDA’s role to focus on innovation. “BIO advocates reinvigorating the Regan Udall Foundation as a place for public/ private partnerships.” That foundation was created by the Food and Drug Administration Amendments Act of 2007 to support the FDA’s regulatory science priorities, which aim to clarify issues at the intersection of science and regulation. BIO also supports a progressive approval pathway so that even before final trials are completed, promising therapeutics could be released and monitored. Dr. Rodell suggested that could be accomplished safely and effectively by designing electronic medical records systems to accommodate retrospective, anonymous analysis of drug safety in real time. Therefore, drug developers could track adverse events associated with the commercial release of particular therapies more accurately than under the current system, which depends upon harried physicians taking the time to voluntarily report adverse events. Dr. Rodell added that the FDA is exploring this already with its pilot Sentinel initiative. That approach can also be used to generate comparative effectiveness data. As

Hrusovsky elaborated, “Databases have 10 years of retrospective samples, in which you know the therapies, outcomes, expression levels, etc.” Leveraging that data could yield practice guidelines that address specific details rather than broad generalities, as well as reimbursement guidelines.

FDA is forming new programs that will create high level coordination and leadership over pharmaceuticalsDutton 11 (Gail, Genetic Engineering & Biotechnology News, Volume 31, No. 18, “Can the FDA be a Catalyst for Innovation?”, http://online.liebertpub.com.turing.library.northwestern.edu/doi /pdf/10.1089/gen.31.18.05)

Following the April release of its Strategic Priorities 2011–2015 document, the FDA has released several proposals to streamline drug testing, nanotechnology, and low-risk diagnostics, as well as draft companion diagnostics guidance, in an attempt to increase regulatory uncertainty and the speed and accuracy of reviews. But, as Dr. Hamburg recently wrote to colleagues, “The most obvious change is that the Agency’s programs will be divided into directorates that reflect the core functions and responsibilities of the Agency.” Her goal is to better support core functions and to link programs that share common regulatory and scientific foundations. The seven existing centers, she emphasized, will remain under their current leadership. To enhance consistency, the position of Deputy Commissioner for Medical Products and Tobacco is being established

to oversee the “Special Medical” programs and to provide “high-level coordination and leadership” across the seven centers. The FDA is also establishing the Directorate of Global Regulatory Operations and Policy, to move the FDA from “an organization regulating domestic products to one overseeing a worldwide enterprise.” The Office of the Chief Scientist will continue its efforts to “improve FDA’s science and address issues of cross-cutting scientific concern.” The National Center for Toxicological Research will report to this office. The FDA is also forming the Office of Foods to implement the Food Safety Modernization Act, and the Office of Operations to oversee administrative functions, including information technology and finance. This implementation shares some commonalities with the improvements proposed by BIO CEO Jim Greenwood in his keynote speech at this year’s BIO International convention in Washington, D.C. There, he advocated establishing the FDA as an independent agency, updating its mission statement to create a clear mandate to encourage the development of innovative products.

U.S. Patents can solve for developing countries- increasing investment and education structures Morel et al 5 (Carlos, Tara Acharya, Denis Broun, Ajit Dangi, Christopher Elias, N.K. Ganguly, American Association for the Advancement of Science, “Health innovation networks to help developing countries address neglected diseases”, http://go.galegroup.com.turing.library.northwestern.edu/p /i.do?&id=GALE|A134675149&v=2.1&u=northwestern&it=r&p=AONE&sw=w)

Improving the health of the poorest people in the developing world depends on the development and deployment of many varieties of health innovations, including new drugs, vaccines, devices, and diagnostics, as well as new techniques in process engineering and manufacturing, management approaches, software, and policies in health systems and services. In developed countries, philanthropic and government donors have created and invested more than $1 billion in global product development partnerships (PDPs) to develop and help to ensure access to new drugs, vaccines, and diagnostics for diseases of the poor (1). These PDPs have made major progress in a relatively short time period (2) but continue to face many challenges. All developing countries can undertake health innovation to varying degrees. Some developing countries, however, are more scientifically advanced than others and are starting to reap benefits from decades of investments in education, health research infrastructure, and manufacturing capacity. We refer to these as innovative developing countries (IDCs) (3, 4). It is a challenge to get complete data on health research spending. According to the most recent available data, public spending on health research by developing countries totaled at least $2 billion (5). This number does not include China, for which data were not available. That investment, which has already led to important innovations, is projected to continue to grow (3, 5-7). Furthermore, lower labor and other costs have the potential to magnify the impact of this investment. To put it in a different perspective, just 1/10th of these IDC public health research resources amounts to more than all that was spent in 2004 by the above-mentioned PDPs engaged in the development of drugs, vaccines, and diagnostics for diseases of the poor (8, 9). Patents and well-cited publications indicate the productivity of research investments, and in this light, IDCs have made major

progress. The number of U.S. patents per capita is a common proxy used to measure the relative innovation efficiency of countries, but we believe that this computation underestimates the innovative capacity of developing countries, because it fails to detect the productivity of highly capable centers of excellence within countries with large populations. Adjusting for both relative economic status and population (U.S. patents per gross domestic product per capita) (10), the top 25 most productive countries in the world include India, China, Brazil, South Africa, Thailand, Argentina, Malaysia, Mexico, and Indonesia (10). For Brazil, China, India, and South Africa, the

number of highly cited academic papers rose nearly twofold from 1993-1997 to 1997-2001 (11), whereas the number of U.S. patents has increased 10-fold (12).

U.S. Key – EEZ

The US has the largest and most unique EEZAOC no date - America's Ocean Challenge ("AMERICA'S EEZ - $ VALUE," www.americasoceanchallenge.com/pages/eez.html, ADL)America’s EEZ is an area of nearly 4.5 million square miles – 23% larger than the land area of the US - stretching from the Arctic ocean to the tropics composed of at least 11 different ecosystems. The ecosystems are relatively large regions on the order of 200,000 sq. km. or greater, characterized by distinct: (1) bathymetry, (2) hydrography, (3) productivity, and (4) trophically dependent populations. US EEZ encompass the eleven following Large Marine Ecosystems: 1. East Bering Sea – off eastern Alaska 2. Gulf of Alaska – off the south of Alaska 3. California Current – off the west coast 4. Gulf of Mexico – off the south cost 5. SE U.S. Continental Shelf – off the NE US 6.

Northeast U. S. Continental Shelf – Off the SE US 7. Insular Pacific Hawaiian – Around Hawaiian Islands 8.

Caribbean Sea - Caribbean 9. Chukchi Sea – North of the Bering Strait 10. Beaufort Sea – Off northern Alaska 11.

Unnamed Central Pacific Marine ecosystem – Including the Line Islands. An ecosystem is defined as a system formed by the interaction of a community of organisms with their environment. All life on Earth resides within ecosystems. Ecosystems are bounded by physical conditions that interact with the life that is adapted to them. If the spiraling degradation of coastal and marine ecosystems globally is to be reversed so that these ecosystems continue to provide both livelihood benefits to coastal communities and foreign exchange to governments, a more ecosystem-based management approach needs to be implemented. It is concluded that the fragmentation and competition characteristic of coastal ocean activities should be overcome and stakeholders enlisted as a force for reform in the economic sectors creating the stress on marine ecosystems. Currently, following the World Summit on Sustainable Development

(2002) a global effort is underway by the World Conservation Union (IUCN), the Intergovernmental Oceanographic

Commission of UNESCO (IOC), other United Nations agencies, and the US National Oceanic and Atmospheric Administration (NOAA)

to improve the long-term sustainability of resources and environments of the world's Large Marine Ecosystems (LMES) and linked watersheds. Large Marine Ecosystems are regions of ocean space encompassing coastal areas from river basins and estuaries to the seaward boundaries of continental shelves and the outer margins of the major current systems. They are relatively large regions on the order of 200,000 km2 or greater, characterized by distinct: (1) bathymetry, (2) hydrography, (3) productivity, and (4) trophically dependent populations. America’s Ocean Challenge seeks to educate the general public and provide the understanding and support for new policies and actions. It is our hope to eliminate the causes of transboundary environmental and resource-use practices that are leading to serious degradation of coastal environments, linked watersheds, and losses in biodiversity and food security from overexploiting of marine ecosystems. Implicit in the conclusions of the two recent ocean commission reports, the Pew’s Ocean Commission (POC), 2003, and the United States Commission on Ocean Policy (USCOP), 2004, is the requirement to manage the health of marine ecosystems. As the Pew’s Ocean Commission puts it “Marine scientists need to develop an understanding of what good health means for each major ecosystem in U.S. ocean waters, and then policymakers and those who use ocean resources need to practice preventative medicine.” The USCOP reflects the same conclusion with the statement, “The Commission recommends moving toward an ecosystem-based management approach by focusing on three cross-cutting themes: (1) a new, coordinated national ocean policy framework to improve decision making; (2) cutting edge ocean data and science translated into high-quality information for managers; and (3) lifelong ocean-related education to create well-informed citizens with a strong stewardship ethic. These themes are woven throughout the report, appearing again and again in chapters dealing with a wide variety of ocean challenges.” These are the goals of America's Ocean Challenge. It is clear that for these changes to occur the stakeholders have to be engaged in addressing these issues. The primary stakeholder of America’s EEZ in the US is the public at large. Research by agencies such as The Ocean Project, The American Association for the Advancement of Science (AAAS), Frameworks and others, have concluded that the understanding of these is issues by the general public is low. America’s Ocean Challenge is the program designed to address the chasm of understanding between the general public and the profound knowledge that science has provided in the recent past decades. AOC’s Core Program Content—EEZ Ecosystems: AOC’s

Scientific Advisory Group has endorsed the presentation of America’s Exclusive Economic Zone (EEZ) marine ecosystems as the umbrella strategy with which to educate the public about the value and vulnerability of our marine resources. The U.S. EEZ was proclaimed by President Reagan on March 10, 1983 using the legal precepts of the UN Convention of the Law of the Sea (which has yet to be ratified by the USA). AOC Program will use examples of marine organisms that exemplify the structure and function of marine ecosystems. The program will encompass all 11 large marine ecosystems over the course of its development but rarely all in a single component. For example, the large format film will exemplify just five contrasting marine ecosystems within the EEZ and illustrate how specific species interact and function as part of the whole. The public will learn that these ecosystems are not isolated ecological units but, rather, part of a single living and connected ocean whose health is tied inextricably to the health and survival of all of life on Earth, including humans. AOC components will convey scientific content about the faunas’ biological functions and ecological relationships; upon what they feed or prey; who preys upon them and how, where and when reproduction occurs; the fate of spawn, larvae and recruits; the trials and perils of the species’ lives and the interrelationships between species, as well as the environment and other organisms that make up the ecosystem. The AOC program includes an integrated suite of inspirational/immersion components such as large format films and associated educational materials. Treatments will feature scientists whose research is related to ecosystem stories and will articulate reasons why we should be engaged in conserving our ecosystems. The scientists’ work and on-camera interviews will show how the knowledgebase of science lays the foundation for rehabilitation of damaged marine ecosystems and their pathway to restoration of functionality. The AOC program intent is to inspire audiences and society to care not only about the fate of all marine life, but also the functionality and integrity of the ecosystems in which they live. Specific EEZ Regions Identified for AOC Coverage: The AOC Program has selected the following five EEZ Marine Ecosystems for the first large format film with which to educate the American public about the wonder and diversity of our marine heritage: Eastern

Bering Sea Ecosystem: The Eastern Bering Sea ecosystem is characterized by its Sub-Arctic climate and is bounded by the Bering strait on the north, by the Alaskan Peninsula and Aleutian island chain on the south, and by the

Alaskan coast on the east. It has a wide shelf and a seasonal ice cover that reaches its maximum extent of 80% coverage in March. Our program will examine the ecosystem function of a region near Unimak Pass just north of the Aleutian archipelago, where several

ecosystem pillar species gather in June and July. California Current Ecosystem: This ecosystem is characterized by a temperate climate that is a transition ecosystem between subtropical and sub arctic water masses with an upwelling coastal phenomenon. The California Current Ecosystem is separated from the Gulf of Alaska by the Sub arctic Current, which flows eastward from the western Rim of the Pacific Ocean. The AOC program will examine

the relationship of a suite of species within this ecosystem, featuring the sea otter, whose influence controls the dynamics of the

nearshore environment. Northeast U.S. Continental Shelf Ecosystem: The Northeast US Continental Shelf Large Marine Ecosystem is characterized by its temperate climate. It extends from the Gulf of Maine to Cape Hatteras along the Atlantic Ocean. Scientists are examining the changing ecosystem states and the relative health of four major sub areas: the Gulf of Maine, Georges Bank, Southern New England and the estuarine-dominated waters of the Mid-Atlantic Bight. Historically this ecosystem has been one of the most productive of the Northern Hemisphere. Today, for numerous anthropogenic reasons it is considerably less economically productive. The AOC program will present this ecosystem through the lens of one of its rarest inhabitants,

the North Atlantic Right Whale. This species and its viability is used metaphorically for the health and sustainability of the entire ecosystem. Southeast U.S. Continental Shelf Ecosystem: This southeast continental shelf ecosystem is characterized by its temperate climate. It borders the Atlantic Ocean,

extending from the Straits of Florida to Cape Hatteras, North Carolina. It contains many bays and sounds, and extensive coastal marshes that provide unique habitats for living marine resources. This ecosystem is presented in the large format film using the goliath grouper, one of the large charismatic megafauna of the region to illustrate ecosystem structure and function.

Bioprospecting in the EEZ of the US falls under federal jurisdictionLeroux and Mbengue no date - Dr. Nicolas Leroux of the Lalive Attorneys-at-law, Geneva and Dr. Makane Moise Mbengue of the University of Geneva Law School ("DEEP-SEA MARINE BIOPROSPECTING UNDER UNCLOS AND THE CBD," www.gmat.unsw.edu.au/ablos/ABLOS10Folder/S3P1-P.pdf, ADL)3.1 Marine bioprospecting in the EEZ Article 56(1) of UNCLOS provides that States have „sovereign rights [in their

EEZ] for the purpose of exploring and exploiting, conserving and managing the natural resources, whether living or non-living, of the waters superjacent to the seabed and of the seabed and its subsoil‟. Marine genetic material extracted from living organisms clearly fall under the category of „natural resources‟ as

defined by Article 56(1). Coastal States therefore have sovereign rights to undertake, authorize, and/or supervise the exploration and commercial exploitation of marine genetic resources in their EEZs.[19] This includes the crucial right to impose taxes and/or royalties on benefits accrued as a result of commercialization of marine biotech products.[20] The freedom of coastal States to explore marine genetic resources in their EEZ is not unfettered. Article 192 of UNCLOS imposes upon States a general „obligation to protect and preserve the environment‟, which covers marine genetic resources

falling under their territorial jurisdiction.[21] Therefore, when engaging or permitting private and public entities to conduct marine bioprospecting, States have a duty to ensure that those activities will not damage the environment. In practice, Article 192 arguably compels States to implement an effective environmental preservation framework

applicable to marine bioprospecting activities conducted within their EEZ. This general obligation to protect and preserve the environment is supplemented by a specific obligation to prevent, reduce, and control pollution arising out of marine bioprospecting cruises conducted in the EEZ.[22] Articles 194 to 196 of UNCLOS cover all sorts of pollution, including light and noise pollution which are of particular concern in the total darkness and nearly absolute silence of the abyss.[23] Pollution may also result the introduction of invasive alien species by the machines used for exploring and sampling deep-sea habitats.[24] Environmental duties under UNCLOS are complemented and indeed refined by various obligations arising out of the CBD.[25] Under Article 7 of the CBD, States must identify and monitor marine genetic resources in their areas of national jurisdiction, with a particular emphasis on any resource requiring conservation measures.[26] Although the CBD does not define „areas of national jurisdiction‟, it can be safely argued that such identification and monitoring obligations apply in the EEZ. In addition, Article 7(c) of the CBD forces States to; „Identify processes and categories of activities which have or are likely to have significant adverse impacts on the conservation and sustainable use of biological diversity, and monitor their effects through sampling and other techniques.‟ Marine bioprospecting plainly qualifies as an activity that may have „significant adverse impacts on the conservation and sustainable use‟ of marine genetic resources seen by the CBD as part of biological diversity.[27] Under the CBD, States are, therefore, under an obligation to monitor the environmental effects of marine bioprospecting cruises conducted under their control, including in their EEZ.[28] Finally, and perhaps most importantly, the CBD calls for the implementation of access and benefit-sharing („ABS’) mechanisms by State Parties.[29] ABS is beyond the scope of this paper, but it is worth noting that marine genetic resources will likely be covered by the Protocol to the CBD which State Parties may adopt in late October 2010 in Nagoya.[30] 3.2 Marine

bioprospecting on the continental shelf Article 77(1) of UNCLOS provides that coastal States exercise „sovereign rights for the purpose of exploring […] and exploiting [the] natural resources‟ of their continental shelf. Article 77(4) states that such natural resources include „living organisms belonging to sedentary species‟. The definition of „sedentary species‟ under Article 77(4) has been the subject of academic and diplomatic debate. It is clear, however, that marine bioprospecting associated with sedentary species, including certain fish and octopus species, falls under the purview of Article 77.

[31] In other words, coastal States have the right to undertake, or authorize and supervise, marine bioprospecting activities over the genetic resources of sedentary living organisms on their continental shelf.

Misc. Answers To

AT: Environment DA

Plan doesn’t disrupt ecosystems and biosynthesis means we only need to collect specimens once Imhoff 11 (Johannes, Antje Labes, Jutta Wiese, Biotechnology Advances, Volume 29, Issue 5, “Marine Biotechnology in Europe”, http://www.sciencedirect.com.turing.library.northwestern .edu/science/article/pii/S0734975011000346)

In contrast to the macroorganisms that are directly taken from the habitat (sometimes in large amounts), microorganisms are not even seen in the environmental sample but need enrichment and cultivation techniques to make them available for laboratory approaches. Therefore, only tiny amounts of the original sample (such as a piece of sponge, coral, sediment or other) are needed. Environmental damage by harvest from the habitat is avoided. Fig. 4 illustrates the path of isolation of microbes from the marine habitat in order to gain bioactive compounds for further drug development. Once bacteria and fungi have been brought into pure culture, straightforward procedures are available to cultivate them in larger volumes, to chemically analyze

the natural products and identify the compounds, as well as to optimize the production by strain selection

and elaboration of the optimal physico-chemical conditions for production. This includes design and development of the fermenta- tion process and selection of strains from a larger panel of similar strains that produce the desired compound as well as strain improvement by random or directed genetic manipulatioa Though these methods need to be adapted to each bacterium and each process separately, straightforward ways to do so are available. Additional improvement of the biosynthetic abilities of the producing strains is possible by combinatorial biosynthesis, which has emerged as an attractive tool in natural product discovery and development. Genetic engineering may be used to modify biosynthetic pathways of natural products in order to produce new and altered structures (Floss, 2006). This is of great advantage for the establishment of reproducible processes for the synthesis of desired natural products.

Removing specimens is minimally invasiveHunt and Vincent 6 - Royal Swedish Academy of Sciences (Bob Hunt and Amanda C.J. Vincent, “Scale and Sustainability of Marine Bioprospecting for Pharmaceuticals,” http://www.jstor.org/stable/4315687, ADL)Conservation concerns about the exploitation of marine organisms in bioprospecting include i) nonselective or de- structive collection methods (43), ii) possible introduction of pathogens or exotic species by collectors (43), and, most often, iii) possible overcollection of target organisms (23-25). With respect to the first concern, nonselective and de- structive collection methods, such as trawls, benthic sleds, and grabs, are usually only deployed in conditions where more careful methods, such as hand collecting on scuba, are not possible. With indiscriminate gear, sample sizes per species or parts taken cannot easily be controlled, nor can secondary collections easily exclude or avoid nontarget species. However, these methods can be regulated with the use of mandatory collection protocols (see below) and environmental impact assessments (EIA). With respect to the second concern about exotic species or pathogens, an inquiry into bioprospecting in Australia (43) found that the risk of introduction was minimal and the same as from the existing use of these habitats. Again, collection protocols could be established to minimize the introduction risk. The third concern, for overexploitation, appears to be unlikely with most contemporary primary collections on populations or species. Primary collection programs generally remove small amounts (0.5-1 kg) and operate haphazardly, maximizing the taxonomic diversity of the collection within a limited time frame (30, 39). Although advances in screening technology has allowed the collection of species previously ignored (because of their smaller size, lower abundance, or lower tissue mass), we would anticipate that most viable populations should tolerate a removal of <1 kg of specimens

Bioprospecting won’t hurt the environmentHunt and Vincent 6 - Royal Swedish Academy of Sciences (Bob Hunt and Amanda C.J. Vincent, “Scale and Sustainability of Marine Bioprospecting for Pharmaceuticals,” http://www.jstor.org/stable/4315687, ADL)INDUSTRY SELF-REGULATION Possible risks of ecological impact from bioprospecting may be minimized with a combination of self-regulation by industry and research-associated groups, and active management by the "owners" of biodiversity. Industry self-regulation for environmental best practice involves i) development of collection protocols or guidelines, ii) timely and precautionary assessments of economic and ecological viability, and iii) development of alternative supply strategies. As well, funding for research can carry environmental stipulations, and journals that publish associated research can demand authors adhere to an environmental code of conduct (55, 56)

COLLECTIONP ROTOCOLS Codes of conduct for the use of wild organisms can help ensure that collection is sustainable (25). The US National Science Foundation and the NCI, which fund

considerable biomedical research and collecting, require that research permits be obtained for all projects they fund in tropical countries (57). Similarly, the members of the American Society of Pharmacognosy made a resolution to "abide by all source country regulations governing the collection of materials" and to require brokers or other intermediariest o do the same (58, p. 655). The sustainability of this approach is, however, entirely dependent on source countries having adequate legislation combined with the managerial capacity and political will to enforce it. Collection agreements between prospectors and source countries currently focus on economic and

intellectual property aspects of access, but could also outline environmental responsibility (59). In general,

researchers and bioprospectors appear to be aware of environmental considerations associated with collecting (23, 24). As noted above, most investigators initially collect 0.5-1 kg of each species, a level that probably leads to diverse collections without damaging biological diversity (39). Some groups, such as AIMS, have developed their own collection guidelines and protocols (43). Nonetheless, only half of the collectors surveyed at Costa Rica's Instituto Nacional de Biodiversidad (INBio) knew about species that should not be collected, and none had specific training on ecologically sustainable collecting methods (60).

AT: Violates UNCLOS

Marine Bioprospecting isn’t bound by LOST countries have the right to “free sea”Leroux 10 (Nicolas, Makane Mbengue, “Deep- Sea Marine Bioprospecting Under UNCLOS and the CBD”, https://www.iho.int/mtg_docs/com_wg/ABLOS/ABLOS_Conf6/S3P1-P.pdf)

The freedom to conduct marine bioprospecting in the high seas more likely stems from the general principle set out at the first paragraph of Article 87(1). The list of freedoms at Article 87(l)(a-f) is not exhaustive, as apparent from the words 'inter

alia' in Article 87(1). Freedom of the high seas covers other uses of the seas unforeseen at the time of drafting, including marine bioprospecting.'-36-' That freedom extends to genetic resources both in the water column beyond the limits of EEZs. and on the seabed beyond the outer edge of the continental shelf, since living resources are not covered by the exploration and exploitation regime applicable to the Area's mineral resources codified at Part XI of the Convention.'-37-' Marine genetic resources in the high seas, therefore, remain subject to a free-access regime. This does not mean that any private operator is free to explore, collect, and exploit such

resources: nor does it mean that UNCLOS fails to provide a legal regime for marine bioprospecting. Simply put, the free-access regime means that each State, rather than the international community, may implement a legal regime for marine bioprospecting in the high seas. Those national regimes will then apply to their nationals, whether individuals or corporate entities, and to activities conducted by vessels flying their flags.

AT: Free Market

Private sector won’t do it – it’s a social goodFrisvold, professor of agricultural and resource economics at the University of Arizona, and Day-Rubenstein, economist at the USDA Economic Research Service, Summer 2009(George and Kelly, “Bioprospecting and Biodiversity Conservation: What Happens When Discoveries are Made?,” 50 Ariz. L. Rev. 545, Lexis)While natural products have been important sources of pharmaceutical materials and information, historically the pharmaceutical industry has hesitated to engage in much collecting and testing of genetic materials. This reluctance may stem from public-good aspects of information about the value of genetic materials. n11 A firm collecting and screening biological samples would have difficulty excluding others from the information that a sample showed promising medical activity. This would be particularly true as a compound's origins, mechanism of action, and efficacy were revealed through required disclosures during the drug-development application process and through clinical trials. Although the knowledge of a compound's medical activity may be valuable, firms [*548] have an incentive to free-ride off the search and discovery activities of others. Thus, expected private economic gains to bioprospecting by individual companies are considerably less than social gains.

AT: India CP

India lack of licensing kills tech transfer and global adoption of drugs Feinberg and Majumdar 1 (Susan E, Sunlit K, Journal of International Business Studies, “Technology Spillovers from Foreign Direct Investment in the Indian Pharmaceutical Industry”, http://web.a.ebscohost.com.turing.library.northwestern.edu/ehost/pdfviewer/pdfviewer?sid=facad10c-ab9f-406c-b604-3a6fe6ce9529%40sessionmgr4004&vid=2&hid=4204)

However, developing country technology polices have often favored the objective of national self-determination at the expense of foreign technology transfer. In particular, host country policies of weak intellectual property protection and forced licensing of technology, although intended to facilitate

technology spillovers, are more likely to discourage FDI and the transfer of leading-edge technologies by MNCs (Lee and Mans- field, 1996). Moreover, policies that encourage foreign technology transfer, such

as greater recognition of intellectual property rights, can also conflict with the objective of equitable distribution. In sectors such as biotech and pharmaceuticals, the allocation of intellectual property rights may have severe implications for the availability of low-cost drugs in poor countries.

Expanding Indian drug development sets a global model, undermining intellectual property and innovation – ensures no new drugsPipes, president of the Pacific Research Institute, 9/16/2013(Sally, “India's War On Intellectual Property Rights May Bring With It A Body Count,” http://www.forbes.com/sites/sallypipes/2013/09/16/indias-war-on-intellectual-property-rights-may-bring-with-it-a-body-count/)Earlier this year, the heads of more than a dozen of America’s industry associations — from the National Association of Manufacturing to the Semiconductor Industry Association to several leading pharmaceutical associations — wrote to President Obama pleading for action against India’s attacks on industries that rely heavily on intellectual property.Given that India’s economy now tops $4.7 trillion and that it trades close to $1 trillion in goods and services each year, this is hardly an idle concern for these U.S. industries, which employ about 40 million Americans and make up more than 60 percent of merchandise exports.And if nothing is done to discourage India from abusing intellectual property rights, other developing countries may follow suit, under the assumption that doing so will help them secure cheap copycat drugs for their citizens — and simultaneously develop their own domestic drug industries.If India’s way becomes the global norm, there may soon be no more innovative drugs with patents to infringe upon. And that’s bad news for patients the world over.

AT: IPR Bad / Generics Good

No link to patents – the plan produces public scientific knowledge not products – (perm solves)Neill 13 - Director of the World Ocean Observatory, a web-based place of exchange for information and educational services about the ocean (Peter, 7/12/13, "Ocean Bio-Prospecting," www.huffingtonpost.com/peter-neill/law-of-the-sea-ocean-bioprospecting_b_3575098.html, ADL)At a conference on bioscience and the ocean, sponsored in 2012 by the New York Academy of Sciences, the extent of this research potential was apparent, with presentations on the synthesis of DNA from ocean species such as sponges and mollusks, imitating certain biological functions that could be applied to disease in humans. A significant number of new drugs in preliminary testing for cancer treatment are derived this way from the information decoded from marine plants and animals. A very recent U.S. Supreme Court decision clarified one of the larger questions for such research: by protecting knowledge derived from the discovery of such natural processes from the exclusivity of patent protection, while nonetheless permitting "ownership" of processes invented or synthesized from them for manufacture and application as vaccines or medicines beneficial to human health. It is a profound distinction, and a major step toward protection of such ocean resources over time. It is interesting to note, however, that this U.S. judicial decision notwithstanding, the United States Congress has not approved either the UN Convention on Biological Diversity or the UN Convention on the Law of the Sea, even

though both are now international law, having been ratified by the requisite number of nations. A very recent U.S. Supreme Court decision clarified one of the larger questions for such research: by protecting knowledge derived from the discovery of such natural processes from the exclusivity of patent protection, while nonetheless permitting "ownership" of processes invented or synthesized from them for manufacture and application as vaccines or medicines beneficial to human health. It is a profound distinction, and a major step toward protection of such ocean resources over time. It is interesting to note, however, that this U.S. judicial decision notwithstanding, the United States Congress has not approved either the UN Convention on Biological Diversity or the UN Convention on the Law of the Sea, even though both are now international law, having been ratified by the requisite number of nations.

IPR Good: Allows for financial recovery for the inventor and creates disclosure for society to build on the invention Harrelson 1 (John, “TRIPS, Pharmaceutical Patents, and the HIV/AIDS Crisis: Finding the Proper Balance between Intellectual Property Rights and Compassion”, http://heinonline.org/HOL/LandingPage?handle=hein.journals/wlsj7&div=12&id=&page=)

To understand the controversy surrounding compulsory licensing of patents, one must first understand why patents are granted. Two rationales have been used to justify the grant of a patent The first rationale is based on a natural rights theory."3 This theory holds that a person is entided to some property rights from one's own

intellectual creations.1" This rationale allows inventors and investors to financially recover their development costs."5 A second rationale is based on the benefit to society."6 This theory holds that the

inventor will disclose the details of his invention to society and, in return, will be granted a limited monopoly

to exploit his invention."7 As a result of the disclosure, society can build on the invention and the overall knowledge will increase."1 In addition, by granting patents, people will be forced to invent around the patent and expand the state of art by necessity."9 The Western concept of intellectual property does not meet

the societal norms of many countries.'20 In some countries, intellectual property is viewed as Western individualism.12' Many countries view liberty and self-autonomy as less important.'22 The key unit is not the individual, or even the family, but rather the larger societal group.123 Therefore, ownership of an intangible right by an individual is foreign to their societal traditions.'24 Opponents of TRIPS in developing countries also put forth economic arguments against intellectual property protection. They argue that by allowing foreigners to control technology through patents, an economic hardship will result from foreigners controlling the terms, and even whether, a technology can be practiced in a particular country.126 The control of technology is particularly important in medicine, agriculture, and education.'27 While these arguments are sound from a short term perspective, failing to protect intellectual property with financial incentives will, in the long ran, decrease the number of new products that benefit society. * In arguing against tying intellectual property to trade, some commentators have argued that the developed nations are hypocritical.'28 In particular, critics point to the fact that many Western nations have only recently allowed patent protection for pharmaceuticals.'25 For example, Germany (1968), Japan (1976), Switzerland (1977), Italy (1978), and Spain (1992) only implemented protection after their own domestic producers increased in size.'*0 Another frequentiy mentioned example of Western hypocrisy is that the United States was slow to adopt the Berne Convention and harmonize its copyright laws with international standards.'3' The United States' main motivating factor in conforming was not a desire to protect foreign works in the United States but rather the United States

had become the leading exporter of copyrighted material.'32 Most developing countries, despite their reservations about TRIPS, decided that the benefits outweighed the risks.'33 International trade and participation in the WTO was key to this growth.'34

IPR promotes increased investment in new product development while alternatives lack motive and don’t solve anything Harrelson 1 (John, “TRIPS, Pharmaceutical Patents, and the HIV/AIDS Crisis: Finding the Proper Balance between Intellectual Property Rights and Compassion”, http://heinonline.org/HOL/LandingPage?handle=hein.journals/wlsj7&div=12&id=&page=)

Patent protection plays an important role in promoting economic growth by offering incentives for investment in the development of new products. One of the requirements of the Agreement on Trade-Related Aspects of Intellectual Property (TRIPS)1 is that all member nations grant patents for pharmaceutical drug inventions.2 Recently, the issue of affordability of HTV/ AIDS medications3 has caused debate on the proper strength of pharmaceutical patent protection. Much of the conflict between those who support strong patent rights and those who oppose them has focused on the use of compulsory licensing and parallel imports as means to of lowering HIV/AIDS pharmaceutical prices in poorer countries. Even liberal compulsory licensing and parallel imports, however,

may not sufficiently lower the cost of these pharmaceuticals to make them affordable in the poorest countries.4 Intellectual property and trade were formally linked on a global basis as a result of the TRIPS Agreement which was conducted under the umbrella of the General Agreement on Tariffs and Trade (GATQ.5 The World Trade Organization (WTO), which succeeded the GAIT, oversees the TRIPS and dispute settlement between member states.6 The linkage between intellectual property and trade has not been without controversy.7 Protection of intellectual property, including pharmaceutical patents, is not part of the culture of many countries.8 Despite this lack of tradition, on April 15,1994,117 nations signed the TRIPS Agreement9 that allows intellectual property rights to be enforced by trade sanctions. Many developing countries that had reservations about strengthening intellectual property rights signed the TRIPS because international trade was of major importance to their economic growth.10 Participation in the World Trade Organization was essential to realize that growth." Before TRIPS, the patent laws of many developing countries allowed the government to routinely require a patent holder to license his invention to a local producer.12 This compulsory licensing was used in some developing countries to provide pharmaceutical products to their population at lower prices." Other countries denied patent protection for pharmaceuticals.14 TRIPS requires countries to grant pharmaceutical patents but does allow compulsory licensing of patents under limited circumstances." The United States, home to many of the research-based pharmaceutical companies, has tried to influence countries to adopt patent laws that exceed the minimum provisions of TRIPS and totally exclude compulsory licensing.'6 The pharmaceutical treatment needs of HIV infected and AIDS diagnosed persons provides an emotional battleground for the issue of compulsory licensing. Eighty-nine percent of the world's HIV infected population lives in the poorest ten percent of countries.17 In some nations, local genetic manufacturing would decrease the price and make drugs more affordable to the population.'8 In other countries, a lack of sufficient manufacturing resources prevents compulsory licensing from being a viable solution to the high cost of pharmaceuticals.19 While new drugs have lowered the impact of HIV infection in the Western world, the $10,000 or more annual cost of these pharmaceuticals is not affordable for the average HIV-infected person in a developing country.2'1 Much recent attention has been on the development of an HIV vaccine to combat the spread of HTV in Africa as well as worldwide.21 Such a vaccine is years away.22 Even if a vaccine is developed, sixteen African countries already have an HTV infection rate of ten percent or more of their adult population.23 The pharmaceutical treatment of HIV-infected individuals will last well beyond the development of a successful vaccine. Section two of the article reviews the patent provisions of the TRIPS agreement and the current controversy over strong pharmaceutical patent rights. Section three analyzes the positions of those supporting and opposing compulsory licensing and the viability of alternatives. This article concludes with a recommendation that the United States should not pressure countries to adopt patent laws that prohibit

compulsory licensing. Rather, the United States should work to assure that countries provide adequate compensation to patent owners for compulsory licensing as required by TRIPS. This approach can decrease drug costs to HIV infected people in some countries while adequately compensating pharmaceutical companies. Under this policy, countries like Thailand, which has a large HIV crisis but also possesses the infrastructure to manufacture HIV drugs, should be allowed to produce the needed drugs while paying the reasonable licensing fee required by TRIPS. Compulsory licensing, however, will not adequately help the poorest developing countries, such as those in sub- Saharan Africa, afford needed HTV medications. A workable plan, promoted by the International Intellectual Property Institute (HPI), combines tiered pricing, national patent exhaustion, and pharmaceutical subsidies to provide a balance of the seemingly conflicting interests. The IIPI plan provides developing nations with the drugs they need to lessen human suffering while providing pharmaceutical companies with increased revenues and incentives to invest in new treatments.

Absent IPR companies has no incentive to innovate kills industry effectivenessScherer 2k (F.M., “Taking Stock: The Law and Economics of Intellectual Property Rights: The Pharmaceutical Industry and World Intellectual Property Standards”, http://www.lexisnexis.com.turing.library.northwestern.edu/hottopics/lnacademic/?verb=sr&csi=7362&sr=AUTHOR(Scherer)%2BAND%2BTITLE(TAKING+STOCK%3A+THE+LAW+AND+ECONOMICS+OF+INTELLECTUAL+PROPERTY+RIGHTS%3A+The+Pharmaceutical+Industry+and+World+Intellectual+Property+Standards)%2BAND%2BDATE%2BIS%2B2000)

The benefits of modern pharmaceutical therapy have accrued mainly to the citizens of the world's more prosperous nations. United Nations staff have estimated that average purchases per capita of modern pharmaceutical products (excluding traditional [*2246] medicines) in 1990 (calculated at prevailing exchange rates) in diverse parts of the world were as follows: n2 [SEE TABLE IN ORIGINAL] A rough extrapolation of these figures reveals that the 73 percent of the world's 1990 population located in south and east Asia, including China, Sub-Saharan Africa, and Latin America, consumes only 16.2 percent of modern pharmaceutical output by dollar volume. One consequence of the inadequate purchasing power that limits such nations' ability to consume pharmaceuticals is a

higher rate of morbidity and debility, which in turn impairs the growth of income so that pharmaceuticals can be afforded--a vicious cycle. Nearly all of the research-oriented pharmaceutical companies responsible for innovations in drug therapy have their home bases in the United States, the European Community nations, or Japan, where demand is most intense and highly able scientists interacting with first-rate universities are at hand. Excepting those of Japan, the research-oriented pharmaceutical companies are among the most multinationally oriented enterprises in the world. Discovering a new drug and carrying it through the tests required to obtain marketing approval from regulatory agencies in the United States and Europe costs upwards of $ 100 million per successful new chemical entity. Once such a large investment has been made, there are powerful incentives to obtain requisite regulatory approvals in other nations and sell the product as widely as possible. Foreign markets are served both by exporting, often from a tax haven such as Puerto Rico, Ireland, or Singapore, and through direct plant investment in consuming nations. According to United Nations estimates, pharmaceutical imports averaged 8.2 percent of domestic consumption during 1989 in developed nations and 19.8 [*2247] percent in less-developed nations. n3 In 1980, approximately 27 percent of the world's demand was satisfied through local production by foreign-owned companies. n4 Since then, the extent of multi-national operation has increased, in part due to numerous cross-border mergers. In 1995, members of the Pharmaceutical Research and Manufacturers of America trade association recorded prescription drug sales of $ 65 billion within the United States and $ 37 billion outside the United States. n5 Most of the R&D outlays incurred by pharmaceutical companies are made to discover therapeutically interesting molecules and prove their efficacy and safety through extensive human trials--i.e., to create knowledge that approximates what

economists call a pure public good. Absent legal barriers to copying, once a drug has been found to be safe and effective, another firm might come up with a generic equivalent by spending roughly a million

dollars on production process methods and formulation and begin to compete with the pioneering firm. If such generic imitation were widespread and rapid, surplus revenues that repay pioneers' initial R&D outlays and make them worthwhile would be severely eroded, undermining incentives to invest in research and product testing. Because of the huge disparity between drug finding and imitation costs, multi-

industry surveys show, pharmaceutical manufacturers attach unusually high importance to the patent system, which in effect grants them 20 years of exclusive rights to their invention from the time a patent application is filed, as a means of recouping their R&D expenditures. n6 The combination of multinationality and heavy stress on patent protection set the stage for a conflict between the pharmaceutical manufacturers and the world's developing nations. Under the Paris Convention to which most of the nations with patent systems adhered, nations were free to structure their patent laws however they desired, as long as they did not discriminate between local and foreign inventors. Many nations excluded drug products from patentability because they considered drugs (and for analogous reasons, food products) to be of such great importance to the national welfare. Even Switzerland, home to three of the world's leading pharmaceutical companies, abstained until 1977 from [*2248] granting drug product patents. Most less-developed countries ("LDCs") followed that pattern and tended more generally to provide weaker patent protection than the most industrialized nations--actions perfectly compatible with the Paris Convention.

Multiple Structural Barriers to Generics hinder their effectivenessKesselheim et al 6 (Aaron, Michael A. Fischer, Jerry Avorn, Health Affairs, “Extensions of Intellectual Property Rights and Delayed Adoption of Generic Drugs: Effects on Medicaid Spending”, http://content.healthaffairs.org/content/25/6/1637.full.pdf+html)

Delay and underuse of inexpensive generics. Despite some success in promoting the availability of generic medications, three important factors can hinder the optimization of savings from generic drug use. First, generic drugs are often delayed from reaching the U.S. marketplace after expiration of the patent or

other IP protection. To extend monopoly protection of the underlying active ingredients in their drug products, brand-name manufacturers sometimes engage in a process known as “evergreening” by patenting peripheral features of products, including aspects of their formulation, their metabolites, or methods of administration. A 2002 report from the Federal Trade Commission (FTC) detailed instances where brand-name manufacturers maintained market exclusivity by listing improper or invalid patents with the FDA.9 Also, the U.S. government has authorized further extensions in market exclusivity after the Hatch-Waxman Act. For example, in 1997 the FDA Modernization Act (FDAMA) provided six more months of market exclusivity if a drug company studies its brand-name product in

pediatric populations.10Second, generic prices can remain elevated because the Hatch-Waxman Act provides six months of exclusivity to the first generic product on the market. A market controlled by such a duopoly does not provide the same cost savings as an open market with multiple generic manufacturers.11 Finally, physicians can be slow to switch to generic versions of brandname pharmaceuticals, and payers’ formularies often do not require such substitution.