Synthesizing the FuturePaul McEuen†,* and Cees Dekker‡

†Laboratory of Atomic and Solid State Physics, Cornell University, Ithaca, New York 14853 and ‡Kavli Institute of Nanoscience, DelftUniversity, The Netherlands

T he latter half of the 20th century hasseen explosive progress in the fields ofmicroelectronics and biotechnology.

The roots of these advances lie in the 19thcentury, when the doors were opening on themolecular world. James Clerk Maxwell dem-onstrated once and for all that atoms existand then wrote down the electromagnetic

laws that governtheir interactions.He immediately be-gan to wonderabout whether hecould control atomsand speculated

where that might lead. Two years earlier, Gre-gor Mendel, an Austrian monk studying peasin his garden, discerned that inherited traitsin his peas were binary. Tall or short. Smoothor wrinkled. Mendel had discovered genes.Moreover, he’d found the patterns by whichgenes were handed down. By selecting for adesired trait, he could affect the geneticmakeup of a population.

These two discoveries, Maxwell’s andMendel’s, followed separate developmen-tal paths after their joint birth in the late1860s. The biggest steps for both happenedin the 1950s. With the invention of transis-tors and integrated circuits, Maxwell’sdream of control over the small was finallyrealized, giving birth to the modern com-puter industry. It was not atoms that gotsorted but electrons, pushed and pulledthrough the hierarchical semiconductor so-cieties by transistors opening and closingtiny doorways. After decade upon decade ofMoore’s Law, electronic societies have

reached the nanoscale, possessing thecomplexity of large cities in a space thesize of a postage stamp. Furthermore, thesecities run on a sped-up clock so fast thatthey have a lifetime of thoughts everysecond.

The biotech revolution got underwayabout the same time, when Watson andCrick unlocked the structure of the doublehelix of DNA in 1953. The microscopic ori-gins of Mendel’s genes were finally re-solved, and biology’s evolution from ataxonomy-based discipline to an infor-mation-based one was fully underway. Thisgenetic revolution has transformed the waywe think about ourselves and the way wepractice medical science. A few decadeslater, we have usurped nature’s tools, cut-ting and pasting genes between organismswith ever-increasing skill.

These two paths, Maxwell’s and Men-del’s, represent two completely separatevisions for controlling matter at the nano-scale. They play with different materials andwork by different rules, the former corre-sponding to the rigid control of computer cir-cuits and the latter the flexible variability ofbiological systems. Now, these two ap-proaches are crashing together. Biologistsdream of controlling the machinery of lifelike engineers control device layouts on acomputer chip, and engineers dream ofevolving adaptive architectures that can,among other things, build themselves. Whatwill happen as these two worlds collide?What is the future of bio meets nano?

In June 2007, we held a symposium toaddress this question, sponsored by the

*Corresponding author,mceuen@ccmr.cornell.edu.

Published online January 18, 2008

10.1021/cb700263r CCC: $40.75

© 2008 American Chemical Society

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Kavli Foundation. Seventeen scientists froma broad spectrum of disciplines assembledat an isolated location where the sun neversets (Ilulissat, Greenland) to ponder this fu-ture. We held three focused days of discus-sion on one theme: what is the biggest thingthat will happen when bio meets nano?Amazingly enough, we reached a consen-sus answer.

That answer? Synthetic biology. (Thecomplete text of the Ilulissat Statementcan be found at www.kavlifoundation.org/uploads/1187777771_ilulissat_statement.pdf.)

Synthetic biology is the code name for en-gineering using the machinery of the cell,

from tinkering with existing organisms allthe way to the design of life from scratch.The idea is pretty radical: in the past 50years we engineered in silicon; now we willengineer in life. The signs that this is hap-pening are already clear. Biotech is on itsown Moore’s Law that is even steeper thanthat of semiconductors: DNA sequencingcosts halve every year. We can now synthe-size strands of DNA the size of small ge-nomes. Soon, we will be able to expressthese genomes in cells, giving us controlover biological development and evolution.Humans will soon fully insert themselves inthe reproductive process of simple organ-isms, taking full control of genome changes

between successive generations. Then, wecan design by whatever algorithm wechoose, Maxwells’ hypercontrol or Men-del’s shuffle-and-see.

The first steps of the synthbio revolutionhave already been made. A toolbox of “stan-dardized genetic parts” is being built, asDrew Endy from the Massachusetts Insti-tute of Technology explained at the meet-ing. These will allow human design of bio-logical networks down to the molecularscale, assembling complex, interactive, andfunctional systems to meet a particular goal.In other words, to engineer in the domainpreviously monopolized by life.

Does this mean that bio wins, and nanois unimportant? Au contraire: nano makesthe revolution possible. It will be the hard-ware that makes synthetic biology happen,as was emphasized by Freeman Dyson fromPrinceton. Still, we face enormous hurdlesin the creation of the input/output tools toconnect up the electronic world to the nano:laboratory-on-a-chip systems to synthesizeand sequence DNA and load it into cells, forexample. If we could learn to sequenceDNA at the clock speed of a cheap com-puter, we could sequence the human ge-nome in a few seconds. Furthermore, wemay be able to expand the palette of life.Imagine cells with artificial organelles for en-ergy generation made from inorganic mate-rials, for example.

There are hurdles beyond the technicalones, however. Synthetic biology faces aconceptual challenge: What is the best wayto design life? How do you design to achievea specific goal but with robustness? Do youpainstakingly plan or simply evolve? Canyou even tell a designed system from anevolved one? Which is better? Under whatcircumstances? Here, we are in the dark. Ev-ery time we look more deeply at organisms,the more complexity and subtlety we find.The simple dogmas of molecular biology arefading, and we have only glimpses at whatlies beyond. What we do see, however, isthat the threads connecting the genome to

Figure 1. The roots of synthetic biology. Left: James Clerk Maxwell wanted to control the nanoworld. His dream found reality in the transistor and the information revolution. Photo from TheLife of James Clerk Maxwell by Lewis Campbell and William Garnett, digitized from an engravingby G. J. Stodart from a photograph by Fergus of Greenock. (http://commons.wikimedia.org/wiki/Image:James_Clerk_Maxwell_big.jpg). Microprocessor manufactured by photographicprocess. Picture by Angeloleithold 2004, Dec (http://commons.wikimedia.org/wiki/Image:InternalIntegratedCircuit2.JPG) Right: Gregor Mendel discovered the laws of heredity, the ran-dom shuffling of genetic traits that underlies the diversity of life. Synthetic biology seeks tomarry the two, using both design and evolution to create new forms of life. From The History ofBiology (Nordenskiold, E., Ed.) Knopf, New York, 1928. (http://commons.wikimedia.org/wiki/Image:Mendel_Gregor_1822-1884.jpg). Sunflowers in Fargo, North Dakota. Photo by Bruce Fritz,USDA/ARS (http://www.ars.usda.gov/is/graphics/photos/k5751-1.htm).

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the ecological environment are many andtangled. The map between the inner andouter worlds is subtle. We are preparing totravel in a landscape whose rules we onlydimly understand.

Still, we see the first stumbling strides toexplore this. First, one can approach lifefrom bottom up, for example, by contem-plating small liposome vesicles as proto-cells to which one adds protein and nucleicacid components one by one, as discussedby Petra Schwille from Dresden at the meet-ing. The challenges are huge, and successwill probably demand the integration of newcell components, such as an alternativeRNA synthesizer that is much simpler thanthe current, dauntingly complex, ribosome,something dreamed of by Julie Theriot fromStanford. Alternatively, one can come fromthe top down and strip an existing “simple”parasitic bacteria of all inessential genes tocreate a Mycoplasma laboratrium that mayact as a minimal but functional chassis—agoal pursued by John Glass from the J. CraigVenter Institute.

What are the potential risks and ben-efits? Some benefits are obvious: new medi-cal devices, treatments, and medicine, forexample. Jay Keasling from Berkeley dis-cussed his efforts to produce medicine formalaria at a fraction of the current cost by in-serting genes of various origins into bacte-ria and yeast. New ways to generate energyare another big potential benefit, as dis-cussed by Steven Chu from Berkeley. Thenumbers demonstrate the promise: all ofhumanity uses 12 TW of power, while theaverage solar flux is �174 PW, a factor of15,000 more. Can we use synthetic biologyto consume a larger piece of this solar pie,using bacteria to directly convert sunlight tofuel or creating fast-growing, low-lignin treesthat are easily converted to energy? Ofcourse, the most radical changes will bethings we can barely imagine now.

Are there risks? Yes, both obvious andsubtle. As we use agricultural crops in newways, manufacturing and energy needs will

compete with food; we are already seeingthis with the recent spikes in corn prices.Will some people starve so that others candrive Hummers? There is also the possibil-ity of malevolent organisms wreaking havoc,either by accident or by design. This is a ma-jor concern, and the true risk is very diffi-cult to accurately assess because we under-stand so little about the relation betweengenomics and ecology. Of course, the waythe natural world deals with this risk of inno-vation is to accept the occasional large die-off. This is a method we prefer not toemulate.

So, how do we maximize benefits andmitigate risks? By being proactive. Weshould make steps to establish best prac-tices, such as “signing” your work with DNAtags. Rules and regulations on this shouldevolve, first within relevant professional so-cieties, and later in law, as discussed at themeeting following a thoughtful presenta-tion by Endy. Also, we must properly regu-late the intellectual property (IP) and innova-tion environment. The semiconductor andbiotech worlds provide interesting con-trasts. The semiconductor industry haslearned to work together, setting communalgoals, cross-licensing widely�practicingwhat is really a massive collusion to keepto Moore’s Law, within which companiescompete. The new biotech, on the otherhand, tends to view IP as a goal in itself,leading to a mass of legal hurdles to creat-ing complex synthetic biological systems.Many believe this has been an enormousimpediment to future developments. Again,decisions now will have enormous impact.

The year 2050 will likely be as different astoday is from the 1950: synthetic biologicalorganisms will be as pervasive as electroniccomputing is now. The shape of that futurewill be determined by the policy decisionswe make in the coming years. The choicesare not easy. Do we try to highly regulatesynthetic biology, or do we let it evolve how-ever it likes? The answer is surely a little ofboth. But beyond the means, the key is to

concentrate on the ends. We can put our re-sources into building bugs that eat flesh orbugs that eat trash and make fuel. That is upto us. We must first decide the future wewant. Then, we can use synthetic biologyhelp us to synthesize that future.

12 VOL.3 NO.1 • 10–12 • 2008 www.acschemicalbiology.orgMCEUEN AND DEKKER