outlook for equities in context of emerging technologies

Outlook for Equities in context of Emerging Technologies

Chetan J. Parikh

Jeetay Investments Private Limited

Global economy: accelerating creative destruction

Source: Economist

Nanotechnology

Nanotechnology involves the use of man-made materials so small, they are measured on the scale of a nanometer. The word ‘Nano’ is derived from the Greek word for ‘dwarf’, which means ‘a billionth’. A nanometer is a billionth of a metre, that is, about 1/80,000 of the diameter of a hydrogen atom. This new science concerns the properties and behavior of aggregates of atoms and molecules, at a scale not yet large enough to be considered macroscopic but far beyond what can be called microscopic. It is the science of the mesoscale and it encompasses many fields.

Nanotechnology is the craft of constructing things that span a few scores of atoms strung together. Move automated assembly down to such scales and the implications for manufacturing are pretty clear: Whole sectors of production become redundant. It will start with semiconductors in the 2010s, then spread to other small products.

Nanotechnology

“At the atomic level, we have new kinds of forces and new kinds of possibilities, new kinds of effects. The problems of manufacture and reproduction of materials will be quite different.”

- Richard Feynman

Nanotechnology

A Few 10-9 Milestones

3.5 billion years ago the first living cells emerge. Cells house nanoscale biomachines that perform such tasks as manipulating genetic material and supplying energy. 400 B.C. Democritus coins the word "atom," which means "not cleavable" in ancient Greek. 1905 Albert Einstein publishes a paper that estimates the diameter of a sugar molecule as about one nanometer.


1931 Max Knoll and Ernst Ruska develop the electron microscope, which enables subnanometer imaging. 1959 Richard Feynman gives his famed talk "There's Plenty of Room at the Bottom," on the prospects for miniaturization. 1968 Alfred Y. Cho and John Arthur of Bell Laboratories and their colleagues invent molecular-beam epitaxy, a technique that can deposit single atomic layers on a surface.


1974 Norio Taniguchi conceives the word "nanotechnology" to signify machining with tolerances of less than a micron. 1981 Gerd Binnig and Heinrich Rohrer create the scanning tunneling microscope, which can image individual atoms. 1985 Robert F. Curl, Jr., Harold W. Kroto and Richard E. Smalley discover buckminsterfullerenes, also known as buckyballs, which measure about a nanometer in diameter.


1986 K. Eric Drexler publishes Engines of Creation, a futuristic book that popularizes nanotechnology. 1989 Donald M. Eigler of IBM writes the letters of his company's name using individual xenon atoms. 1991 Sumio Iijima of NEC in Tsukuba, Japan, discovers carbon nanotubes.


1993 Warren Robinett of the University of North Carolina and R. Stanley Williams of the University of California at Los Angeles devise a virtual-reality system connected to a scanning tunneling microscope that lets the user see and touch atoms. 1998 Cees Dekker's group at the Delft University of Technology in the Netherlands creates a transistor from a carbon nanotube. 1999 James M. Tour, now at Rice University, and MarkA. Reed of Yale University demonstrate that single molecules can act as molecular switches.


2000 The Clinton administration announces the National Nanotechnology Initiative, which provides a big boost in funding and gives the field greater visibility. 2000 Eigler and other researchers devise a quantum mirage. Placing a magnetic atom at one focus of an elliptical ring of atoms creates a mirage of the same atom at another focus, a possible means of transmitting information without wires.

Nano for Sale

Not all nanotechnology lies 20 years hence, as the following sampling of already commercialized applications indicates.

Nano for Sale

APPLICATION: CATALYSTSCOMPANY: EXXONMOBILDESCRIPTION: Zeolites, minerals with pore sizes of less than one nanometer, serve as more efficient catalysts to break down, or crack, large hydrocarbon molecules to form gasoline. APPLICATION: DATA STORAGECOMPANY: IBMDESCRIPTION: In the past few years, disk drives have added nanoscale layering-which exploits the giant magneto-resistive effect-to attain highly dense data storage. APPLICATION: DRUG DELIVERYCOMPANY: GILEAD SCIENCESDESCRIPTION: Lipid spheres, called liposomes, which measure about 100 nanometers in diameter, encase an anti cancer drug to treat the AIDS-related Kaposi's sarcoma.

Nano for Sale

APPLICATION: MANUFACTURE OF RAW MATERIALSCOMPANY: CARBON NANOTECHNOLOGIESDESCRIPTION: Co-founded by buckyball discoverer Richard E. Smalley, the company has made carbon nanotubes more affordable by exploiting a new manufacturing process. APPLICATION: MATERIALS ENHANCEMENTCOMPANY: NANOPHASE TECHNOLOGIESDESCRIPTION: Nanocrystalline particles are incorporated into other materials to produce tougher ceramics, transparent sunblocks to block infrared and ultraviolet radiation, and catalysts for environmental uses, among other applications.

Nanophysics

Smaller than macroscopic objects but larger than molecules, nanotechnological devices exist in a unique realm-the mesoscale-where the properties of matter are governed by a complex and rich combination of classical physics and quantum mechanics. Engineers will not be able to make reliable or optimal nanodevices until they comprehend the physical principles that prevail at the mesoscale.

Nanophysics

Scientists are discovering mesoscale laws by fashioning unusual, complex systems of atoms and measuring their intriguing behavior.

Once we understand the science underlying nanotechnology, we can fully realize the prescient vision of Richard Feynman: that nature has left plenty of room in the nanoworld to create practical devices that can help humankind.

Nanofabrication

The development of nanotechnology will depend on the ability of researchers to efficiently manufacture structures smaller than 100 nanometers (100 billionths of a meter) across.

Photolithography, the technology now used to fabricate circuits on microchips, can be modified to produce nanometer-scale structures, but the modifications would be technically difficult and hugely expensive.

Nanofabrication

Nanofabrication methods can be divided into two categories: top-down methods, which carve out or add aggregates of molecules to a surface, and bottom-up methods, which assemble atoms or molecules into nanostructures.

Two examples of promising top-down methods are soft lithography and dip-pen lithography. Researchers are using bottom-up methods to produce quantum dots that can serve as biological dyes.

Microelectronics will change to

nanoelectronics

The electronics industry is deeply interested in developing new methods for nanofabrication so that it can continue its long term trend of building ever smaller, faster and less expensive devices. It would be a natural evolution of microelectronics to become nanoelectronics. But because conventional photolithography becomes more difficult as the dimensions of the structures become smaller, manufacturers are exploring alternative technologies for making future nanochips.

Nanofabrication: Comparing the Methods

Researchers are developing an array of techniques for building structures smaller than 100 nanometers. Here is a summary of the advantages and disadvantages of four methods.

Photolithography

Advantages: The electronics industry is already familiar with this technology because it is currently used to fabricate microchips. Manufacturers can modify the technique to produce nanometer-scale structures by employing electron beams, x-rays or extreme ultraviolet light. Disadvantages: The necessary modifications will be expensive and technically difficult. Using electron beams to fashion structures is costly and slow. X-rays and extreme ultraviolet light can damage the equipment used in the process.

Scanning Probe Methods

Advantages: The scanning tunneling microscope and the atomic force microscope can be used to move individual nanoparticles and arrange them in patterns. The instruments can build rings and wires that are only one atom wide. Disadvantages: The methods are too slow for mass production. Applications of the microscopes will probably be limited to the fabrication of specialized devices.

Soft Lithography

Advantages: This method allows researchers to inexpensively reproduce patterns created by electron-beam lithography or other related techniques. Soft lithography requires no special equipment and can be carried out by hand in an ordinary laboratory. Disadvantages: The technique is not ideal for manufacturing the multilayered structures of electronic devices. Researchers are trying to overcome this drawback, but it remains to be seen whether these efforts will be successful.

Bottom-Up Methods

Advantages: By setting up carefully controlled chemical reactions, researchers can cheaply and easily assemble atoms and molecules into the smallest nanostructures, with dimensions between two and 10 nanometers. Disadvantages: Because these methods cannot produce designed, interconnected patterns, they are not well suited for building electronic devices such as microchips.

Some prominent bottom-up methods

Two of the most prominent bottom-up methods are those used to make nanotubes and quantum dots. Scientists have made long, cylindrical tubes of carbon by a catalytic growth process that employs a nanometer-scale drop of molten metal (usually iron) as a catalyst. The most active area of research in quantum dots originated in the laboratory of Louis E. Brus (then at Bell Laboratories) and has been developed by A. Paul Alivisatos of the University of California at Berkeley, Moungi G. Bawendi of the Massachusetts Institute of Technology, and others. Quantum dots are crystals containing only a few hundred atoms. Because the electrons in a quantum dot are confined to widely separated energy levels, the dot emits only one wavelength of light when it is excited. This property makes the quantum dot useful as a biological marker.

Nanomedicine

The potential medical advances that will be made possible by successful nanostructures span a wide range of practical applications. Drugs could be delivered with pinpoint accuracy. Tagged molecules could bind with and reveal diseased organs or blooming cancers before they become runaway problems. Biological samples could be quickly screened with nano-sized mechanical devices that bind to certain genetic sequences. The development and refining of these and other devices promise to change the very nature of medical intervention.

Nano-bio-technology

Nanometer-scale objects made of inorganic materials can serve in biomedical research, disease diagnosis and even therapy.

Biological tests measuring the presence or activity of selected substances become quicker, more sensitive and more flexible when certain nanoscale particles are put to work as tags, or labels.

Nano-bio-technology

Nanoparticles could be used to deliver drugs just where they are needed, avoiding the harmful side effects that so often result from potent medicines.

Artificial nanoscale building blocks may one day be used to help repair such tissues as skin, cartilage and bone-and they may even help patients to ,regenerate organs.

Global Market Size of nano-bio-

technology

The, overall market impact of nano-bio-technology applications is projected to reach $300 billion within the next 12 years.

Some promising application in nano-bio-technology

One of the most promising early applications of nanotechnology to the practice of medicine is targeted drug delivery using nanocapsules. In cancer therapy, targeting and localized delivery are the key challenges. The ability to selectively attack the cancer cells and save normal tissue from drug toxicity is crucial. However, because many anti-cancer drugs are designed to simply kill cancer cells, often in a semi-specific fashion, they result in severe side effects.


Drug-filled nanocapsules can be covered with antibodies or cell-surface receptors that bind to cancer or other cells and release the drug upon contact with these cells. Nanocapsules also provide one of the few ways to get drugs across the blood-brain barrier for treatment of diseases affecting the eyes, brain, and other portions of the central nervous system.


One of the other modes of cancer treatment has been using nanoscale iron oxide. It is observed that blood circulation is irregular in the cancer cells. Since it is blood that circulates both oxygen and heat that’s generated inside the cell, on insertion of nanoscale iron oxide within the body, it reaches all parts of the body including the cancer cells. The heat that is generated due to the magnetic field carries with it the potential to kill the carcinogenic cells. Thus detrimental radiation therapy can be avoided.

Nano-bio-technology in India

Dendrimer therapy

The California Cancer Institute has developed a new technique that can cure cancer at the early stages using dendrimers. These are a new class of three-dimensional, man-made molecules produced by an unusual synthetic route, which incorporate repetitive branching sequences to create a unique novel architecture.

Dr N Jayaraman of the Indian Institute of Science has recently synthesized a new class of three-dimensional dendrimer molecules. It incorporates various guest molecules within its repetitive branching sequences to create a unique host system.

Nano-bio-technology in India

Dendrimer therapy

These are treelike macro-molecules, with branching tendrils reaching out from a central core. The first dendrimer-based pharmaceuticals are poised to enter the market as early as 2008.

Nano-bio-technology in India (Cont.)

The Indian Institute of Science is attempting to develop various nanoscopic systems. The goal is to investigate both synthetic and natural materials, engineered at the nanoscale, for new properties that can be exploited in nanobiotechnological applications. A major thrust of the program is the design and synthesis of novel biocompatible and biodegradable materials. These materials are then employed for achieving complex nanoparticles with selected genetic materials. These nanoparticles are then used to facilitate a systematic study of factors that control nucleic acid delivery across cellular barriers. These will provide materials for diverse applications such as gene or protein delivery, probing biological systems, altering biological functions, gene slicing and incorporating bioactive materials into cellular devices.

Nanotechnology in orthopaedics

Grafts of natural bone can carry disease or trigger immune rejection by the host. Sterilising the bone to reduce the chances of disease can weaken the bone. Artificial bone cement without nanotechnology can work for small applications, but tends not to have sufficient strength for load bearing bone replacement. However, artificial bone paste made with nanoceramic particles shows considerable promise for bone repair and replacement, even in load-bearing applications.

Nanotechnology in neurology

Nanotechnology can also be used to partially repair neurological damage. For example, it can improve the accuracy of cochlear implants that turn sound into electrical impulses; and create light-activated implants in the retina to partially restore lost vision. In addition, biomemetic scaffolds can help damaged nerves to regrow and reconnect.

Indian companies looking at nano-bio-

technology

1. Marico – looking at nanotechnology applications in the nutraceuticals they manufacture

2. L’Oreal – Nanomaterials are used in surfactants, emulsifiers and sunscreen lotions of L’Oreal’s cosmetic products.

Indian companies looking at nano-bio-technology

However no successful nano-bio-technology product in the Indian market as of now.

Motors from molecules

To make a molecular motor, it isn't enough just to make a miniature version of an ordinary motor. Researchers have had to rethink the very premises on which a motor operates.

Motors from molecules

In ordinary motors, an energy input causes motion. In molecular motors, an energy input restrains motion. By selectively stopping the motions it doesn't want and let ting through the ones it does – the motor turns momentum from random environmental influences into organized motion.

Nanobot Construction Crews

Molecular manufacturing - the heady notion of assembling almost anything, from computers to caviar, from individual molecules - would change the world, if someone could just find a way to make it work. Imagine nanoassemblers: busy work gangs of "pick and place" robotic manipulator arms, each one tens of nanometers in size. Controlled from on high by a powerful computer, these simple devices would arrange blocks of molecules to make copies of themselves-and these machines would, in turn, build still other nanomachines, which, in turn, would create others, and so on in an exponential expansion. These nanobot construction crews could then be directed to accomplish astonishing tasks such as curing diseases from inside the body and fabricating intricately engineered materials from basic bulk feedstocks at extraordinarily low cost.

Nanobot Construction Crews

Comment: Not much funding currently available. The technology is 10-20 years away from commercial reality.

Nanoelectronics

Silicon chips, circuit boards, soldering irons: these are the icons of modern electronics. But the electronics of the future may look more like a chemistry set. Conventional techniques can shrink circuits only so far; engineers will soon need to shift to a whole new way of organizing and assembling electronics. One day your computer may be built in a beaker.

Researchers have created nanometer-scale electronic components-transistors, diodes, relays, logic gates from organic molecules, carbon nanotubes and semiconductor nanowires. Now the challenge is to wire these tiny components together.

Nanoelectronics

Unlike conventional circuit design, which proceeds from blueprint to photographic pattern to chip, nanocircuit design will probably begin with the chip-a haphazard jumble of as many as 1024 components and wires, not all of which will even work-and gradually sculpt it into a useful device.

DNA Computers

Why limit ourselves to electronics? Most efforts to shrink computers assume that these machines will continue to operate much as they do today, using electrons to carry information and transistors to process it. Yet a nanoscale computer could operate by completely different means. One of the most exciting possibilities is to exploit the carrier of genetic information in living organisms, DNA.

DNA Computers

The molecule of life can store vast quantities of data in its sequence of four bases (adenine, thymine, guanine and cytosine), and natural enzymes can manipulate this information in a highly parallel manner. The power of this approach was first brought to light by computer scientist Leonard M. Adleman in 1994. He showed that a DNA based computer could solve a type of problem that is particularly difficult for ordinary computers - the Hamiltonian path problem, which is related to the infamous traveling salesman problem.

DNA Computers

Adleman started by creating a chemical solution of DNA. The individual DNA molecules encoded every possible pathway between two points. By going through a series of separation and amplification steps, Adleman weeded out the wrong paths - those, for example, that contained points they were not supposed to contain - until he had isolated the right one. More recently, Lloyd M. Smith's group at the University of Wisconsin-Madison implemented a similar algorithm using gene chips, which may lend themselves better to practical computing.

DNA Computers

Despite the advantages of DNA computing for otherwise intractable problems, many challenges remain, including the high incidence of errors caused by base-pair mismatches and the huge number of DNA nanoelements needed for even a modest computation. DNA computing may ultimately merge with other types of nanoelectronics, taking advantage of the integration and sensing made possible by nanowires and nanotubes.

Carbon Nanotubes

Nearly 13 years ago Sumio Iijima, sitting at an electron microscope at the NEC Fundamental Research Laboratory in Tsukuba, Japan, first noticed odd nanoscopic threads lying in a smear of soot. Made of pure carbon, as regular and symmetric as crystals, these exquisitely thin, impressively long macromolecules soon became known as nanotubes.

Carbon Nanotubes

Many of the extraordinary properties attributed to nanotubes-among them, superlative resilience, tensile strength and thermal stability-have fed fantastic predictions of microscopic robots, dent-resistant car bodies and earthquake-resistant buildings. The first products to use nanotubes, however, exploit none of these. Instead the earliest applications are electrical. Some General Motors cars already include plastic parts to which nanotubes were added; such plastic can be electrified during painting so that the paint will stick more readily. And two nanotube-based lighting and display products are well on their way to market.

Carbon Nanotubes

In the long term, perhaps the most valuable applications will take further advantage of nanotubes' unique electronic properties. Carbon nanotubes can in principle play the same role as silicon does in electronic circuits, but at a molecular scale where silicon and other standard semiconductors cease to work. Although the electronics industry is already pushing the critical dimensions of transistors in commercial chips below 200 nanometers (billionths of a meter)-about 400 atoms wide - engineers face large obstacles in continuing this miniaturization. Within this decade, the materials and processes on which the computer revolution has been built will begin to hit fundamental physical limits. Still, there are huge economic incentives to shrink devices further, because the speed, density and efficiency of microelectronic devices all rise rapidly as the minimum feature size decreases.

Other Uses for Nanotubes Beyond Electronics

The seven potential uses for nanotubes listed below are given "feasibility ratings." A rating of 4 means "ready for market"; a rating of 2 means "demonstrated"; and a rating of 0 means the concept is now just "science fiction."

Chemical and Genetic Probes

A nanotube-tipped atomic force microscope can trace a strand of DNA and identify chemical markers that reveal which of several possible variants of a gene is present in the strand.

Obstacles: This is the only method yet invented for imaging the chemistry of a surface, but it is not yet used widely. So far it has been used only on relatively short pieces of DNA.Feasibility: 3

Mechanical Memory

A screen of nanotubes laid on support blocks has been tested as a binary memory device, with voltage forcing some tubes to contact (the "on" state) and other to separate (the "off" state).

Obstacles: The switching speed of the device was not measured, but the speed limit for a mechanical memory is probably around one megahertz, which is much slower than conventional memory chips.Feasibility: 2

Nanotweezers

Two nanotubes, attached to electrodes on a glass rod, can be opened and closed by changing voltage. Such tweezers have been used to pick up and move objects that are 500 nanometers in size.

Obstacles: Although the tweezers can pick up objects that are large compared with their width, nanotubes are so sticky that most objects can't be released. And there are simpler ways to move such tiny objects.Feasibility: 2

Supersensitive Sensors

Semiconducting nanotubes change their electrical resistance dramatically when exposed to alkalls, halogens, and other gases at room temperature, raising hopes for better chemical sensors.

Obstacles: Nanotubes are exquisitely sensitive to so many things (including oxygen and water) that they may not be able to distinguish one chemical or gas from another. Feasibility: 3

Hydrogen and Ion Storage

Nanotubes might store hydrogen in their hollow centers and release it gradually in efficient and inexpensive fuel cells. They can also hold lithium ions, which could lead to longer-lived batteries. Obstacles: So far the best reports indicate a 6.5 percent hydrogen uptake, which is not quite dense enough to make fuel cells economical. The work with lithium ions is still preliminary.Feasibility: 1

Sharper Scanning Microscope

Attached to the tip of a scanning probe microscope, nanotubes can boost the instrument's lateral resolution by a factor of 10 or more, allowing clear views of proteins and other large molecules.

Obstacles: Although commercially available, each tip is still made individually. The nanotube tips don't improve vertical resolution, but they do allow imaging deep pits in nano-structures that were previously hidden.Feasibility: 4

Superstrong Materials

Embedded into a composite, nanotubes have enormous resilience and tensile strength and could be used to make cars that bounce in a wreck or buildings that sway rather than crack in an earth quake. Obstacles: Nanotubes can still cost 10 to 1,000 times more than the carbon fibers currently used in composites. And nanotubes are so smooth that they slip out of the matrix, allowing it to fracture easily. Feasibility: 0

Bio-generics

Bio-generics are generic versions of patent protected biologicals or protein drugs. Biological companies resort to genetic engineering technologies on bacteria and other cells to produce such drugs on a large scale.

Current biopharmaceutical market =

$18 billion

US 45%EU 30%JAPAN 20%ROW 5%

Table I

Brand Active Substances

Mareketer Approval date

1999 sales US$ million

Generies under development

Epogen Epoetin Alfa

Amgen Inc 1989 1,760.00 +

Procrit Epoetin Alfa

Ortho Biotech Inc

1990 1,505.00 +

Table I (Cont.)





Neupogen Fligastin Amgen Inc 1991 1,260.00 +

Humulin 50 percent human insulin isophane suspension and 50 percent human insulin (recombin-anant human origin)

Eli Lilly & Co

1992 1,088.00 +

Table I (Cont.)





Intron A

Interferon alpha-2b recombinant

Schering Oncology Biotech

1986 650 +

Avonex Interferon beta la

Biotech Inc

1996 621 +

Table I (Cont.)





Rebetron Ribavarin and interferon alpha-2b, recombin-ant

Schering Corporation

1998 530 +

Genotropin Somatotr-opin

Pharmacia Corp

1995 460.8 +

Table 1 (Cont.)





Enbrel Etanercapt Immunex Corp and Wyeth Ayerst

1998 366.9 +

Key Challenges

Assessment of bio-equivalence

Regulating framework for biogenerics

EU ahead of the US on regulatory matters.

Some hurdles

The key issue in biogenerics is the assessment of “bio-equivalence”. Biologics are far more complicated than synthetic products and unlike the latter, they are not produced by chemical synthesis, but by cells in culture or whole organisms. As majority of them are defined by the manufacturer’s procedure, like fermentation and purification, product characteristics are dependent on the procedure. A slight change in any of the parameters can potentially change the pharmacokinetics of the product. Though the regulatory framework for biogenerics has started to modify from essential similarity to product comparability, another hiccup is the lack of specific regulations for bio-generic products. Biogenerics are also surrounded by the most intricate web of patents, including process, product, formulation and indication.

Table II

Firm Products on Market (Indian)

Products in development

Shanta Biotech (Hyderabad)

Hepatitis B Vaccine; interferon (IFN)-a

Insulin; GM-CSF; Streptokinase, tPA, EPO, hGH

Bharat Biotech (Hyderabad)

Hepatitis B Vaccine; streptokinase; lysotaphin

VEGF

Dr Reddy’s Lab (Hyderabad)

G-CSF tPA, EPO, hGH, IFN-B, IFN-y, Recombinant proteins

Wockhardt EPO; Hepatitis B Vaccine; insulin

IFN-a-2b

Source: BioCentury

Leading service providers

Manufacturing & Formulations: Jubilant Organosys (speciality chemicals/bulk drugs), Shasun Chemicals (Custom Synthesis), Medreich, Elder, Divi’s Laboratories Clinical Research: Quintiles, Syngene, Chembiotek, Aurigene, Synchron, Reliance, Covance, Parexel Bio-informatics and other IT services: Strand Genomics, TCS, Satyam, Infosys, GVK Bio, Ocimum, Jubilant Biosys

Leading service providers

Drug Discovery/Medicinal Chemistry: Aurigene, Divi’s Laboratories, Syngene, Suven Lifesciences, G V K Bio Pre-clinicals: Vimta Labs, Lambda Therapeutic Research, Lotus Labs Central Lab Services: S R L Ranbaxy, Vimta Labs

The new paradigm

Positive SumZero Sum

Knowledge ManagementData Processing

Networks and WebsCommand and Control

Nonlinear DynamicsComparative Statics

Increasing Returns Diminishing Returns

Intangible AssetsTangible Assets

Knowledge CapitalPhysical Capital

Excess supplyScarcity

21st Century20th Century

Thank you

outlook for equities in context of emerging technologies

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