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Essays Future of Chemistry Assumptions: Taking Chemistry in New Directions** George M. Whitesides* Keywords: ftioorganic chemistry • genomics • medicinal chemistry philosophy of chemistry it When a distinguishedbut elderly scien- polish a new facet of reality and that mixture of a lot of the relatively pre- tist states that something is possible, he change the way some part of the world dictable "ordinary", and a little of the is almost certainly right. When he states works—is both satisfying intellectually quite unpredictable "extraordinary". that something is impossible, he is very and rewarding professionally. The pan of science that is ordinary and probably wrong." The second reason is to feed our business-as-usual—useful, important. Arthur C. Clarke curiosity. We wonder about the world of familiar science—can often be extrapo• the future. What neat widgets will make lated into the future with fair accuracy. that world run? Which of our fantasies It is the extraordinary science—the sur- The Temptations and Hazards of will grow into our grandchildren's real- prises—that we cannot predict. and it is Predicting the Future ities? this science that gives speculation about The third is philosophical. Science the future its well-deserved bad reputa- Speculating about the future of sci- and technology are major elements of tion. It is also the surprises that make ence seems to be genetically encoded in the culture of our times. They, probably science so intensely interesting, and that scientists. We all do it. We also take it as more than other elements (materialism, have the power, for better or worse, to an article of faith that serious predic- religious fundamentalism, capitalism, turn the lives of our grandchildren up- tions are almost always wrong. Is think- ...), will change the nature of individuals side down. ing about the future an important thing and of society. We wonder: What will One of the many charms of science is to do. or just a diversion—like day- the big changes be? How will science be that it provides an endless string of dreaming, or gardening, or playing the involved? surprises. Some surprises grow slowly lottery? Why do we spend our time The fourth is that society expects us and incrementally, while some come. guessing about matters we believe we to speculate. We are pan of its early apparently, out of the blue. Each of us cannot predict? warning system for change. can make two lists of surprises: one of There arc at least five reasons. The The fifth is to answer an uncomfort- personal favorites, and one of surprises first is utilitarian: to plan our work. able question: "Is there research that we that have remade the world. These two Thinking about the future is a part of should not do?" We scientists generally lists are usually rather different. We choosing research problems. We who cohabit quite comfortably with an amor- have a particular affection for what we make our living in science tell ourselves al curiosity. We should know, and find small that we work for the satisfaction of ask if there is research quirks in familiar sci- solving problems and for the thrill of we can do now—re- The objective of ence endearing. Appre- discovery; sociologists. less charitably, search that is technical- science is to make a ciation for big discover- suggest that we do so to make a living ly feasible and scientifi- difference. ies in unfamiliar fields and to get ahead professionally. The cally interesting—that requires more effort. truth is probably a mixture of the two. we should forgo be- Since I am a chemist. Finding good problems—problems that cause it is ethically I was immediately de- problematic. Are there questions we lighted—in fact, ecstatic—to learn that Prof. G. M. Whitesides don't want to ask, because there are no XeF., is a stable compound: because I Department of Chemistry and circumstances in which we might want knew less about biology, it took me Chemical Biology to know the answers? years to assimilate the discovery of Harvard University apoptosis. and to begin to appreciate 12 Oxford Street how the cell chooses between life and Cambridge, MA 02138-2902 (USA) Science is a Mixture of the death. Not all surprises are equal: xenon Pal: (+1)617.495.98S7 E-mail: gwhitesidesegmwgroup.harvard. Ordinary and the Extraordinary tetralluoride clarified the chemical bond edu for chemists; apoptosis changed the (al I thank Michael Mayer, Mila Boncheva. Surprises: Is the future of science understanding of "life" for all of science. and Barbara Whitesides for their sugges- really so unpredictable? The answer is One unstated objective of science is tions and editorial help with this paper. both "no" and "yes". Science is a to make a difference: to learn something, 3632 O 2004 WileyNCH Vedas GmbH & Co. Ma. Weinheim DOI: io.loo2/aniciaoimoin6 MOW Chem. tat. Ed. 2004. 43. 3632-3641 EFTA_R1_01521460 EFTA02444545  Angetvandte Chemie or make something, that changes the ability that it will eventually fracture— good and bad. At one time, knowledge way people think or behave. Many of the for better or worse—under the blows of could be passed on only through speech: biggest discoveries—the most important science is very high. Let me give an the written word and moveable type scientifically, and the most consequential example. We assume, as an ankle of gave our society a long-term memory. socially—are surprises, and their conse- faith—a deeply held assumption—that At one time it was impossible to talk to quences are unimaginable at the time we arc the most intelligent entities on or to see others over long distances; the they are made. Who would have pre- the planet. We would certainly be dis- telephone. radio. TV, and the web are dicted the changes in society that have concerted to discover that science and now among the threads that hold society come from classification of the elements technology had generated an entity together. Controlling human fertility into the periodic table, or from quantum more intelligent than we: a peer com- fundamentally changed the relation of mechanics, or the world wide web? Who petitor (or perhaps a peer partner, women to society. Society changes when could have guessed that the first NMR although, as a species, we have never it discards a major assumption. spectrum of ethanol would grow into the been good at "sharing"). How probable, Thinking about assumptions and ability to watch the brain think? technically, is it that working backward is The unpredictability of these big science will do so? The not necessarily less falli- surprises makes us timid in our spec- answer to this question Society changes when ble than thinking about ulations: it is embarrassing to be pub- depends on whether it discards a major science and working for- licly wrong, and big surprises make you believe that intelli- assumption. wards, but it tends to dunces of us all. But, avoiding specula- gence is an oddity char- focus more on big soci- tion makes science dreary, and neglects acteristic of highly etal problems and less our responsibility to society to warn of evolved living organisms (humans, por- on small technological evolutions. Con- change. even as we cause it. poises, whales, chimpanzees), or wheth- centrating on assumptions might. there- er it is inevitable in (or perhaps can be fore, provide better advance warning engineered into) any information-proc- about issues that the scientific commun- Picking Assumptions, Not Making essing system of sufficient complexity. ity (and society) should consider care- Predictions So, will information science produce fully than extrapolating from existing intelligent machines? (... and what is science. It would also accomplish four In speculating about the future, "intelligence" in a machine, anyway?) I other ends It would: 1) show that the we—scientists and nonscientists—are don't know, but I (and others more dreary intellectual senescence suggested really interested in knowing what the knowledgeable than I) also don't know by John Horgan's stimulating book "The science and technology will be that will that it is impossible. Hence it is an area End of Science" is wrong-headed: make a big difference, and in knowing that we, and society, should watch care- 2) identify directions where science whether that difference will be good, or fully. would unquestionably have large im- bad, or both, or a matter of context, or Where, in the past. has science dis- pact; 3) indicate especially interesting circumstance, or personal opinion. solved important assumptions with pro- problems on which scientists might The process of starting with current found consequences for society? Failed work; and 4) suggest new ways of doing science, extrapolating it into the future. assumptions are easy to identify in business: big problems do not have and then guessing how society will use hindsight: they are the facts of daily life disciplinary boundaries—academic or abuse this future science is so un- that we now accept as routine, but that departments do. certain it will probably fail. I suggest would, at some earlier time, have pro- In what follows, I list nine assump- that a different and perhaps more direct voked a reaction of "impossible!" If one tions that. I believe, are fundamental to approach to identifying where science had asked Frederick the Great or Sun western society, and that, I believe, are might reshape society is to start by Tsu if it would ever be possible utterly to vulnerable to disproof by science. This identifying areas where change would destroy a city on the other side of the list is entirely personal: others would matter, and then ask if imaginable sci- globe in a single stroke, their answer make other lists. These assumptions are ence might cause this change. would have been "Nor They. and their different in nature: some are conceptu- How are we to identify areas where societies, assumed this limitation to the al, some are practical, and some are society is vulnerable to change? Or art of war. We now accept as unremark- sociological. where the push of a new idea or a new able a world in which science and technology might topple established in- technology—born as quantum mechan- stitutions? I propose that we begin by ics and grown to be nuclear-tipped Where Does Chemistry Fit In? identifying the assumptions that our intercontinental ballistic missiles society makes, and then ask about the (ICBMs; or perhaps just a rental truck Chemistry has had a wonderful peri- vulnerability of these assumptions in the containing an amateur's fully functional od of two centuries in which it revolu- face of plausible science. fission bomb)—make this single stroke tionized the understanding and manip- An assumption is an idea that is distressingly possible. The failure of this ulation of the physical world: it revealed taken for granted: it tacitly separates the assumption has changed society. the atomic and molecular structure of imaginable from the unimaginable. If an We have discarded many other as- matter, and provided physical things— assumption is vulnerable, then the prob- sumptions, with consequences both drugs, clothing, fuels, weapons. materi- blew. Cheat tat. Ed. 2004, 43. 3632-360 www.angewandte.org O 2004 WileyNCH Verlag GmbH & Co. KGA. Weinheim 3633 EFTA_R1_01521481 EFTA02444546 Essays als—that changed society. There is still sizing primers and probes, and for Assumptions much to be learned about molecules, separating restriction endonucleases in- bonds. and reactivity, but these subjects to pure activities. There would be no I. We Are Mortal seem of a different character than aging. nuclear ICBMs without methods of machine intelligence, and privacy— refining plutonium and uranium, and We assume we are mortal: we will more evolutionary than revolutionary. making explosive lenses. There would die. We know that from experience, Are the revolutionary discoveries now be no drugs without synthesis and mass albeit the experience of others. But die elsewhere, or are there still chemical spectrometry. There would be no inter- of what? One hundred years ago, infec- discoveries as profound as the laws of planetary probes without fuels, and tious disease was a major cause of death; thermodynamics. the nature of the carbon/carbon rocket throat nozzles, now, it is a relatively minor problem. chemical bond, and the molecular basis and silicon single crystals. Most of us now alive will die of cardio- of inheritance waiting to be made? Those arc the past. What about the vascular disease, cancer, Alzheimer's dis- Any answers to this question hinge future? Chemistry is, still. everywhere: ease. diabetes degenerative disease. Re- on personal opinion, and on the defini- It nuts: be! It is the science of the real gardless of the details, we die of old age. tion of "chemistry". Is it profound to world. But, to remain a star in the play We know, however, that some cells understand the origin of life, or the rather than a stagehand. it must open its age differently than others. Transformed nature of sentience? It is, to me. Are eyes to new problems. It is impossible cells are in some sense immortal (al- these subjects "chemistry"? They are, to that the human life span will increase though they are not an organism); me. Is it profound to understand com- dramatically without manipulation of single-celled organisms that replicate plexity (whatever "complexity" means), the molecules of the human organism. by division have a kind of immortality. or to develop nonliving intelligence? but understanding this problem will There are strategies that strongly pro- Yes, and both have important chemical require more than manipulating mole- long life: caloric deprivation does so in components. Is it profound to hybridize cules. Communication between the liv- mice and fruit flies, and probably also living and nonliving systems? Of course, ing and nonliving will also require does so in man. Inheritance certainly and chemistry offers much to the effort. engineering a molecular interface be- makes a difference. This Essay is about the assumptions tween them, but designing this interface Molecular biology has begun to that our society accepts and the poten- will require understanding the nature of illuminate each of our infirmities and tial of science to sweep aside these "information" in organisms and in com- to suggest remedies. Cardiovascular assumptions. It is not specifically about puters, and how to translate between (CV) disease is already following the chemistry. However. I am a chemist, and them. A society that uses information path of infectious disease: the combina- I believe that chemistry can be every- technology to interweave all its parts tion of medications that control blood where, if chemists so choose, or that it requires new systems for generating, pressure, and others (HMGA-CoA re- can contract into an invisible part of the distributing, and storing power, but duettist inhibitors; aspirin) that control infrastructure of technology, if they batteries will be only one part of these cholesterol concentrations and the clot- don't. Chemistry, by its culture, has been systems. ting of blood is decreasing mortality as a almost blindly reductionist. I am repeat- Chemistry has always been the in- result of CV disease; these benefits will edly reminded that "Chemists work on visible hand that builds and operates the increase when treatment begins earlier molecules", as if to do anything else tools, and sustains the infrastructure. It in life, before the damage is done. were suspect. Chemists do and should can be more. We think of ourselves as Understanding the role of free radicals work on molecules, but also on the uses experts in quarrying blocks from gran- in damage to tissues can help to limit of molecules, and on problems of which ite; we have not thought it our job to injury after blockage to a blood supply. molecules may be only a pan of the build cathedrals from them. Whether we Infectious disease may also play an solution. If chemists move beyond mol- choose to focus on the molecules, mate- important role in the damage to the ecules to learn the entire problem—from rials, and tools that are at the beginnings intima of the blood vessels, and help to design of surfactants, to synthesis of of discovery, or bring our particular, initiate plaque formation. Changes in colloids. to MRI contrast agents. to the unique understanding of the world to lifestyle—eating less fat and red meat. trajectories of cells in the embryo, to the bear on unraveling the problems at the smoking fewer cigarettes—contribute to applications of regenerative medicine— end, is for us to decide. limiting injury. Many of the causes of then the flow of ideas problems. and I believe that everything from meth- CV disease seem understandable, and. solutions between chemistry and society ane to sentience is chemistry, and that in principle, controllable. Minimize will animate both. we should reexamine our own assump- these causes, and when these medical As a technology, chemistry has built tions concerning the boundaries of our strategies finally fail, replace the dys- the foundation from which many of the field. Examining the broader assump- functional organ with one from a pig discoveries of "biology", or "microelec- tions that follow may provide some engineered immunologically to resem- tronics", or "brain science" (or "plane- stimulus to do so. ble a human, or regenerate the organ tary exploration", for that matter) have entirely. There seems a realistic possi- grown. There would be no genomics bility that CV disease—now the largest without chemical methods for separat- single cause of death—may cease to be a ing fragments of DNA, and for synthe- significant contributor to mortality. 3634 0 2004 WileyNCH Wdag GmbH & Co. KG.), Weinhom www.angewandte.org MOW Chem. lot. Ed. ao04. 43. 3632-364' EFTA_R1_01521462 EFTA02444547  Angewandte Chemie If CV disease were marginalized, ever, an enormously expanded molec- ular chemistry, molecular biology, and other diseases would take center stage. ular understanding of the disease, and medicine are fundamentally the same Cancer is next in line, and is a much. ideas for therapies. subject—the understanding of mole- much more difficult problem. The enor- After cancer come the diseases of cules important to life, and the applica- mous advances in cancer biology have aging. The details of these diseases are tion of that understanding to the im- taught, if nothing else, how complicated even less-well understood than are those provement of human health. cancer is. Cancer is fundamentally a of cancer. For most, we have only hints cumulative derangement of the genome of the importance of genetic suscepti- within a population of cells. By the time bility. infection, environmental expo- z Only Living Creatures Think; We Think the disease is detectable, there is usually sure. and genomic programming. A Best already extensive damage to genes and flood of genetic information will, how- chromosomes. The growing, molecular- ever. emerge from studies of multiple We arc, at least in our own opinion. level understanding of the etiology of human and non-human genomes; we the crown of creation: the most intelli- cancer explains why success in cancer can control many infectious diseases and gent and versatile of species, and re- therapy has been so halting. environmental exposures; we will be nowned for our ability to subjugate While genomics has so far primarily able to reset biological clocks and repair other species. We assume that there is been useful in understanding, rather genetic dysfunction. We see the begin- no threat to this position (barring the than in treating, the disease, it offers nings of broad strategies to combat the appearance of aliens, or some other many suggestions for the future. There diseases of aging. although we have no incalculable improbability). are many genomic defects that are idea of effective tactics. Will we continue to be unique? Is common among cancers: damage to These changes in the understanding there another species that could become the signaling pathways responsible for of disease and aging, and of medical as intelligent as we are? It seems control of the cell cycle; breakdown in treatment, do not promise immortality. unlikely that other living creatures could the processes that check for genetic But, they are constructing, for the first emerge as superior intelligences: bio- damage. and guide the damaged cell to time, a true molecular science of disease logical evolution is relatively slow, and its own death through apoptosis; break- and of medicine. The change from we would probably not be kind or down in the pathways that prevent cells empiricism to understanding, and from hospitable to a potential competitor. from leaving their origin and colonizing reaction to anticipation. forms the basis An alternative to the improbable emer- other organs. Understanding the role of for a revolution in health care. As this gence of another intelligent animal (or telomers—the chromosomal structures revolution unfolds, it has the potential to insect, or plant) species is that the next that count the age of cells by progressive transform society. sentience on the planet might be silicon- shortening during each cell division— Immortality is not necessary to rather than carbon-based. and resetting this internal clock may change the world: much less will do. Individual computers probably do have important consequences. New ap- How would our social institutions per- not currently have the complexity nec- proaches to cancer—especially blocking form if the average life span were 200+ essary to be intelligent (or at least self- factors that are essential for metastasis: years? What would happen if the period conscious) in the way that we are. As the preventing vascularization of tumors: of female fertility were 100 years? How global information network—the world developing viruses that are specific to would we behave if life expectancy wide web; high bandwidth communica- tumor cells—all suggest new strategies could be extended by a factor of five. tions systems; universal connectivity—is for control. Other strategies will cer- but only the very, very rich could afford assembled (or. increasingly, as it self- tainly appear; some will certainly be the extension? How would the world assembles, to use the phrase from or- useful. The nascent field of systems change if the difference in life span ganic chemistry), there will be an oppor- biology will help to coordinate these between first and third world countries tunity (or perhaps even a certainty) for a strategies. were a factor of ten? complexity that rivals or exceeds that of For cancer (and perhaps for most Chemistry is at the core of changes each of us as individuals. A global, diseases) prevention (or presymptomat- in biomedicine. Chemistry makes drugs interconnected entity that operates at ic detection) may be more important and vaccines. Chemistry makes the an- frequencies of petaflops will do things than cure. Avoiding influences that alytical systems that will enable detailed that we cannot begin to imagine. Why cause genetic damage—most obviously. genomic analysis of individuals. Chemis- not think? Why not think about itself? specific compounds in the environment try provides the understanding of the Perhaps even think about us? or in foods (and especially in tobacco changes in molecules that accompany The probability of a new intelligence smoke) that rcact with DNA—and disease and aging. Chemistry identifies emerging by biological evolution is avoiding exposure to ultraviolet light (and sometimes generates) the environ- limited by the decades-long generation- or ionizing radiation may be the most mental factors that lead to biological al times of complex organisms, by the cost-effective method of reducing this damage. What chemistry does not do low rate at which new variants arise by risk. now is to integrate molecular-level char- mutation, and by the complexity and We certainly do not see an end to acteristics with cellular and organismic functional form of the central nervous cancer. nor even. yet. a real beginning to behavior—to see the picture in the system. Evolution and selection have its prevention and cure. We have, how- pointillist splatter of dots. Still, molec- taken millennia to jostle us into our Met am bit Et 2004, 43. 3632-360 www.angewandte.org O 2004 Wley-VCH Vedas GmbH & Co. KG.A. Weinheim 3635 EFTA_R1_01521483 EFTA02444548 Essays present situation; I suspect it would sity of connections enough, or is there of the great intellectual challenges hu- require special circumstances for anoth- something about the human brain that mans face is to understand intelligence er to jostle us aside quickly. Our intelli- makes it uniquely capable of intelli- as a property that emerges from the gence, adaptability. and self-awareness gence? I personally doubt that there is interactions of molecules (which, what- (aided by the chance development dur- anything special about the wetware in- ever they are, are not intelligent). ing evolution of an opposed thumb and side my skull other than its complexity, Chemistry is familiar with complexity. an oddly positioned larynx) have ena- the three-dimensional density with but has not yet embraced the task of bled us to survive and out-reproduce which it is internally connected, and its understanding the forms of complex many more voracious but less-intelligent ability to modify itself through experi- behavior that can emerge from large and self-aware forms of life. ence: I doubt, but cannot disprove, that groups of molecules, or of systems (for Computers operate by different there are quantum subtleties to self- example, cells) formed from molecules. rules, and without the constraints of consciousness. A third question deals In studying intelligence in a complex biology. Computer cycles are much with the relationship between intelli- system. our own intelligence is probably faster than the diffusion of neurotrans- gence and self-awareness. Is there a the best example with which to begin. mitters across synapses in the brain; correlation, or is self-awareness some- This effort is the best preparation we can change through evolutionary selection is thing different in character than intelli- presently imagine for an encounter with much slower than change by adaptive gence? A fourth question touches on another intelligence. whether met on reprogramming. With the Internet. com- the delicate issue of the relation be- our own planet or encountered else- puter interconnectivity will become very tween life and intelligence. We speculate where. large, and communication among nodes endlessly about evolution in living sys- very rapid. tems, and whether biological evolution Perhaps most importantly. the leads inevitably to intelligence. What Redrawing the Line between growth of complexity in the web is about intelligence without life? An in- Living and Dead driven by us: a significant part of the telligent web would certainly not be creativity of the human race—perhaps alive in any sense a biologist would 3. Animals and Machines are Different hundreds of thousands of creative, en- recognize. ergetic, purposeful people—is now de- We have opinions about the poten- Humankind tends to categorize. voted to the mission of making more tial of computer networks to support Among the categories that have been competent components for the web, to sentience, but not knowledge. Self- separate in the past have been "living" enabling those components to commu- awareness is probably not unique to and "nonliving". and "animal" and nicate as efficiently as possible, and to humans, and not all that is Homo "machine". An animal is a biological encouraging the resulting systems to sapiens is self-aware. A porpoise or a entity made of tissue and bone. It is born perform their tasks with little or no chimpanzee is probably self-aware. A of other animals, lives, and dies, and has human supervision. As we develop soft- human fetus is certainly not self-aware: characteristics that are what they are by ware agents, applets, and autonomous a baby grows into self-awareness; an virtue of evolution and genetic inheri- systems, we seek local performance: Alzheimer's patient grows out of it. Can tance. In the past. we have not designed what global connectivity among these we guarantee that a computer system animals, although their performance local systems will bring remains for us to would not grow to be self-aware? I may in a few cases have been optimized experience. doubt it. empirically through domestication and We could ask at least four interesting Would we even know if some future selective breeding to meet certain of our questions about the potential for sen- version of the world wide web had needs. Since we and animals arc alive, tience in computer networks. The first developed self-awareness? I suspect we recognize various degrees of ethical question concerns the connections be- that we would not, at least for a long responsibility toward them. tween complexity, emergence, and in- time. Our ability to imagine existences A machine is qualitatively different: telligence. (The word "emergence" is not our own is profoundly limited. The an object of metal, ceramic, and plastic, taken to mean the appearance of prop- ability of a silicon-based intelligence— which we design and build de novo. We erties in a complex system that we one inhabiting a distributed web of now feel no ethical responsibilities to- cannot predict from the properties of cunningly doped crystals and giant mag- ward machines. its individual components.) How com- netoresistive films, of optical fibers and This convenient distinction between plex must a system be to think? ... to satellite repeaters, and "thinking" animal and machine is beginning to fail become sentient? Can we—scientists, through the flow of photons and elec- at several levels. In the most biological and especially chemists. who generally trons—to imagine a world of water, salt sense, we are developing the ability to are committed reductionists—predict gradients, food, and sex seems equally design animals. We are rapidly develop- complex behaviors based on knowledge improbable. If aqueous and silicon in- ing biological tools that will enable us to of simple components? Understanding telligences did become aware of one specify the characteristics of animals in a complexity has not been a strength of another, it is not clear what the outcome way similar to that in which we specify reductionist science. A second question would be. the characteristics of machines. We al- concerns the basic requirements for What does this have to do with ready use genetic engineering with ani- "intelligence". Are complexity and den- chemistry? Probably everything. One mals for the same sorts of tasks as we use 3636 C 2OO.4 leyNCH Verlag GmbH & Co. KG.', Weinheim www.angewandte.org Anew. clam. Mt. Ed. 2004. 43. 3632-3641 EFTA_R1_01521464 EFTA02444549  Angesvandte Chemie mechanical engineering with machines. These efforts point toward an extra- others that are silicon—the issue of We have chimeras that build compo- ordinarily complex (and perhaps un- whether computer networks might nents of one species into another: we achievable) future goal: the ability to emerge as sentient entities capable of can add or delete genes: we can re- connect brain and computer directly— competing with humans could become engineer entire subsystems of one ani- that is, to allow information flowing in moot: one could imagine wetware and mal to resemble that of another. We are the nerves of an organism to shift silicon co-developing, and a blurring of learning how to modify the surface directly into information flowing as the concepts of "animal" and "machine" antigens of one species to make its electrons or photons in a computer. and "alive" and "dead" in a way that is organs compatible with transfer into The technological barriers to this kind unimaginable now. another species. We have taken the first of fusion of animate and inanimate are Many of the most important of these steps in learning how to regenerate immense, but do not violate any funda- problems ultimately have components organs from stem cells, and perhaps to mental physical laws, and do not seem that arc molecular. Although molecules de-differentiate differentiated tissue. ultimately insurmountable. Progress in may be only a part of the systems that and then regrow it into regenerated solving some of them—for example, in transmit and interpret information in parts. We arc developing a toolkit that developing interfaces that are biocom- organisms, building interfaces between is making possible the machinelike de- patible—has been rapid; progress to- the living and nonliving. and designing sign of animals using pans that can wards others—for example, learning translators to bridge the languages of range from nucleotide sequences to how to transfer information between ions and electrons, both depend inti- whole organs. neural and silicon-based systems—has mately upon chemistry. The tools for Most of this work has, of course, been slow. Given the unarguable fact genetic engineering of specialized neu- been focused on objectives in biology that biology and information technology ral tissues will require chemical manip- and biomedicine. As the capabilities of have been the scientific revolutions of ulation of genetic materials. Biocompat- biology extend, however, the idea of the last half of the 20th century, it is ibility is a molecular and materials animals (or insects) for other uses almost certain that the 21st century will problem. quickly follows. Animals as sensors— see their overlap and fusion. The 21st century will almost certain- that is, as "canaries"—is now plausible. What are the major technical prob- ly see us redraw the line between Plants and microorganisms are unques- lems? One must learn the code used in "living" and "dead," and many of the tionably already alternatives to chem- the brain and the nerves to convey, tools to do so must ultimately be mo- ical reactors for carrying out some prorn and interpret information; (we lecular. chemical transformations. We know that already know the code used in comput- selective breeding can produce unusual ers, since we designed it); one must learn plants and animals; applied biology can how to build a physical interface be- 4. Human life Is Invaluable only increase our skills at "species tween the two—perhaps between nerves engineering". We will ultimately consid- and microelectrodes. One must learn The idea of a long, healthy life fits er—perhaps will hove to consider— how to convert between the currencies neatly with the assumption of western species-engineering for ourselves. Were used by the neurons to transfer infor- civilizations that life is invaluable, and we to cmbark on mulligenerational mation—ion gradients across mem- that prolonging it, when possible. is a space flight, would we be better off with branes and pulses of neurotransmitters moral obligation. This obligation is in- artificial gravity and our current phys- in synapses—and the currencies used by creasingly in conflict with the need to ical form. or with a physical form better silicon-based systems—electrons and limit the costs of medical treatments. to adapted for low gravity, high radiation, photons. The goal of direct communica- balance the distribution of health bene- and whatever other aspects of the envi- tion between human brain and comput- fits, and to stabilize population levels. ronment the ship could best provide? er also faces a serious problem of We may be forced to confront the value More radical, but much earlier in dimensional translation: computers are of prolonging life on two fronts: development, is work intended to fuse now intrinsically 2D in their architec- First, as we move toward the objec- the world of man and machines. Current tures, and brains arc 3D. We have no tive of a long, healthy life, we already technology builds implantable sensors solution yet to the problem of making a see that there is an interval where life to control cardiac rhythm and glucose sufficient number of the correct kinds of can be prolonged, but only at great levels. Cochlear implants help the deaf neural-to-computer connections. Per- expense. and not necessarily with high to hear. The targets are becoming more haps growing specialized neural tissues quality. If, for example, we can extend ambitious: electrodes implanted in in- to act as connectors—that is, genetic life through combinations of artificial sects and rats that begin to control their modification of the human to fit better devices (artificial joints and organs). motion or relay information about their to the computer—will be the final xenotransplantation, immunosuppres- environment; retinal chips to provide approach. sion, and organ regeneration, the cost sight for the blind: systems that trans- With a capability to build hybrid to the patient may be a life of immuno- duce thought directly into mechanical systems—systems containing not just logical crisis and constant flirtation with motion. For the more distant future, the two kinds of biological molecule or infection. We may be able to buy a goal is direct, efficient. communication tissue, but systems containing some longer life, but only an expensive and between human brains and machines. components that are biological and uncomfortable one. As biomedical sci- Angew. Own. he. Et goal, 43. 3632-1641 www.angewandte.org O 2004 Wile/NCH Vedas GmbH & Co. KGaA. Weinheim 3637 EFTA_R1_01521485 EFTA02444550 Essays ence makes it possible to patch up (but teins, and that genomics will open a induced chemicals to disease or dys- not cure) many previously terminal window directly onto behavior and ca- function—will all depend centrally on conditions, a serious collision of inter- pability; it is more probable that these chemistry to build the tools to study ests seems inevitable. characteristics reflect the behavior of genomics, proteomics and metabo- Second, and more complicated, are complex biological systems, and will lism... the demographic consequences of require many decades to decipher. In ...and, eventually, to sort human reaching the technical goal of building any event. even with dramatic improve- beings according to their characteristics a medical capability that greatly pro- ments in the relevant technologies— and potentials. longs healthy life. Balancing prolonga- both for the collection of the needed tion of life span. birthrate, and popula- biological information and for its anal- tion control requires arithmetically that ysis—the task of correlating genetic 6. We Are Individuals, and Privacy is something give: there must be either constitution with the potential strengths Important limitations on birthrates or limitations and weaknesses of individuals will re- on life spans. We may find that we have quire decades (hut probably not centu- We are accustomed to thinking of a choice: "New life or old?" Placing ries) of work. ourselves as individuals and as such we termination of life—killing a person— This enterprise—the mapping of value the accoutrements of indivi