Chemistry's Golden Age While continuing to nurture the core of their discipline, chemists in the next 25 years will unlock many secrets of biology, create materials with almost magical properties Rudy M. Baum

C&EN Washington

W hat will chemistry look like in 2023, the 100th anniversary ofChemical & Engineering News? What research will dominate the pages of the Journal of the American Chemical Society? Will there be paper pages of JACS, or will the contents of JACSand other journals be disseminated exclusively by electronic means? Where will the best chemistry research be carried out-in traditional chemistry departments of universities or in departments of structural biology and materials science? Who will support the research? Will most universities still have chemistry departments? In an effort to answer these and other questions, C&EN assembled a panel of distinguished chemists to discuss the evolution of chemistry over the next 25 years. Columbia University chemistry professor Ronald Breslow moderated the discussion. Also participating were John D. Baldeschwieler, chemistry professor, California Institute of Technology; Allen J. Bard, chemistry professor, University of Texas, Austin; Jacqueline K. Barton, chemistry professor, Caltech; Theodore L. Brown, chemistry professor (emeritus), University of Illinois, Urbana-Champaign; Barbara Imperiali, chemistry professor, Caltech; Robert S. Langer, chemical engineering professor, Massachusetts Institute of Technology; Koji Nakanishi, chemistry professor, Columbia University; Daniel G. Nocera, chemistry professor, MIT; Douglas Raber, director, Board on Chemical Sciences & Technology, National Research Council, Washington, D.C.; Stuart A. Rice, chemistry professor, University of Chicago; and Richard E. Smalley, chemistry and physics professor, Rice University, Houston. In interviews with C&EN Managing Editor Rudy M. Baum, Richard N. Zare, chairman of the National Science Board and chemistry professor, Stanford University, and Stephen J. Lippard, chairman of the MIT chemistry department, also contributed their thoughts about the future of chemistry.



Ronald Breslow Seventy-five years ago, a new age was dawning in chemistry, an age when new techniques and new instrumentation would open a window on molecular structure and quantum mechanics would provide a truer view of the behavior of atoms. That window never closed, and molecular structure and quantum mechanics became the organizing principles of chemistry. The focus on structure was, in many ways, what set chemistry apart from other sciences-chemists insisted on an intimacy with the objects of their science unmatched by other disciplines.

Chemistry has fulfilled its extraordinary potential. It is, in fact, the "central, useful, and creative" science that Ronald Breslow called it in the title of his 1996 book on chemistry for nonscientists. So successful has chemistry been that its approach, its focus on structure and reactivity, now productively dominates other scientific disciplines. Is not molecular biology, in reality, chemical biology? Is not materials science, in fact, materials chemistry? But this very success has given rise to doubts about the future health of the science of chemistry. Are the hottest areas of chemical research being appropriated by disciplines not identified as chemistry? The group assembled by C&EN to discuss the future of chemistry seemed relatively sanguine about the future of the discipline. "We speak of chemistry as if we all know what it is," observed Breslow. "But there are fields of materials science (now departments of materials science) or fields of environmental science (now departments of environmental sciences), departments of biochemistry and molecular biology-all areas in which a large component is chemistry. Are chemistry departments going to encompass all this?" Jacqueline Barton provided one answer to Breslow's question. "I predict there will be fewer chemistry departments, but not fewer chemists," she said." Some universities won't have a chemistry department, but there will be chemists in departments of life processes, new materials, neurological investigations. I think we should embrace this, because if you believe chemistry is a central science, which I do, then in fact we're all doing chemistry in these different areas." Some panel members took issue with Barton's prediction of fewer chemistry departments, arguing that the discipline is simply too fundamental for a university to abandon the department altogether. Stuart Rice, for example, said, "Somewhere the intellectual core of chemistry has to be taught, advanced, maintained." And Robert Langer, the sole chemical engineer on the panel, noted, "Some universities have gotten rid of departments, sure. But chemistry? If they're going to get to the point where they're going to get rid of chemistry, that just seems to me like a very long way to go." Douglas Raber, whose board at NRC spans both chemistry and chemical engineering, pointed out that there already has been a strong effort in many parts of the community-including funding agencies-to exploit the interdisciplinary nature of the chemical sciences, and that the real strength of the field lies at its interfaces with other disciplines.



Douglas Raber While all panel members agreed that chemistry's push into related disciplines is irreversible, they also expressed a sense that chemists, even those working somewhere other than in a place explicitly called a chemical laboratory, retained a unique identity. Daniel Nocera, for example, observed, "Whenever I come up against this question, I always ask: How do you define a chemist? What makes a chemist unique? And then the question is: Will that ever go away? Chemists make new things and we study reactions. That's the core of this profession. And that can never go away. People will always rely on us for that."

"The fantastic thing about chemists," said Barbara Imperiali, "is that we all speak the same language. We share the same fundamental science. And therefore we can talk to each other about what we are doing. We have to ensure that the next generations can keep on doing that, that they don't slide away from us and become specialists in a field where they can't talk with a physical chemist, for example." On a very practical level, Allen Bard noted: "I think as long as chemists keep getting jobs, there will be chemistry departments, especially at the graduate level. There are places that have eliminated, for example, physics departments. But as long as we can turn out students who can find employment, we'll be okay." The comprehensive sequencing of the human genome and the genomes of various pathogens is going to have a profound effect on the future. The impact for intervention, for therapy, for dealing with resistant microorganisms-the potential is enormous. And that will transform the way we look at the practice of medicine.John Baldeschwieler



John D. Baldeschwieler So chemists will still be practicing chemistry in 25 years. They will be doing it in traditional chemistry departments, but they will be doing it in a lot of other places, too. But what research will they be carrying out? And what will they have accomplished between now and then? A lot of the activity, according to our panel, will be at those interfaces with biology and with materials science. Although some members of the panel believed that government and foundation funding patterns had distorted research priorities toward biological questions, the majority believed that chemistry applied to biology is one of the most intellectually stimulating of today's research frontiers.

"One of the greatest challenges of the next century will be for chemists to make life," Richard Zare said in an interview after the panel met. "A system that is self-replicating, self-organizing, and even has the possibility of evolving into other things-I think this is possible." Creating life is, perhaps, the ultimate expression of chemistry turning toward biology, but it is not the only daring prediction Zare was willing to make. "We're going to move more toward bionic man," he predicted, "toward the possibility of putting man and machine together, at least for medical purposes, and being able to understand how to make implants of materials which will aid our health or which will monitor our health and tell us ahead of time, like on a car, when you should take it in to the service station rather than waiting for it to blow up on the freeway. I think there's going to be much more done with sensors and the connections of people with them." Panel members, while no less excited about the prospects of chemistry applied to biological questions, were somewhat more circumspect than Zare in their predictions. But Zare wasn't entirely alone in his sense that chemists are on the verge of creating life, as this exchange between Nocera and Breslow indicates:



Danial G. Nocera Nocera: And I imagine that in the next 25 years, chemists will literally build membranes. And I'll bet you they will be able to pump protons across a membrane. Breslow: We'll get functioning membranes. Will we turn them into cells? Nocera: It will be the next step. Breslow: Will they be alive? Will they take in nutrients and do some functions one can take seriously? Nocera: Yes.

Raber noted that chemists already are making remarkable progress toward the improvement of life, if not actually creating it. For example, Koji Nakanishi pointed to alternative medicine as a source of new compounds for organic and medicinal chemists. But not just biologically active single compounds. Herbs and other plants used in alternative medicine contain complex mixtures of compounds, Nakanishi observed, and drugs based on traditional remedies will increasingly incorporate many of the compounds present in such sources. "It's not going to be easy to find out what is going on," Nakanishi said. "There are lots of synergies. We have to understand the biology, isolate the individual compounds, put them together as they were isolated from nature." That is, apply the powerful techniques of traditional chemistry to understand the total effect of an alternative medicine. Imperiali echoed Nakanishi: "To bring this back to technology, we're in a position to screen synergistic mixtures like Koji described. The diagnostic tools are all becoming available. They were not available five to 10 years ago. That will bring alternative medicine into the realm of real-world medicine."



Koji Nakanishi "Let's expand this beyond alternative medicine," Barton argued. "We've been thinking about gene therapy or protein therapies. I think, as you look to the future, it's going to go back more to small molecules, whether discovered through alternative medicine or rationally from the standpoint of using small molecules as regulators. In terms of signal transduction regulators, in terms of antiviral agents, it's not necessarily that we're going to go to bigger and bigger. As we figure out how these molecules interact with large molecules, we can use small molecules as the basis of a whole set of general tools-general solutions that we can use to fight different diseases."

Another area where chemistry will have a significant impact in the coming 25 years is in neuroscience. John Baldeschwieler, for example, predicted that "in 25 years, we will understand neurochemistry well enough that we really will have some comprehension of brain function, the nature of memory-how, where, and what sort of systems format the memories that are stored. And we'll be able to intervene constructively in such matters as drug addiction, psychoses, appetite, rage, fear, stress, human intelligence, learning."



Jacqueline K. Barton In an interview conducted after C&EN's panel met, Stephen Lippard said he plans to focus on neurochemistry during the sabbatical he is taking this year at the University of California, San Diego. "There are going to be very exciting, important discoveries in the neurosciences in the next 25 years, and chemistry will make major contributions to them," Lippard said. "We need to understand a great deal more about the molecular events that take place at the synapse. We know a lot about the conduction of current down nerves and the firing of muscles-much of it has to do with ion transport through channels and pumps-but many of the structural and molecular mechanistic details of these processes remain to be uncovered."

Zare also focused on neurochemistry." We are going to learn much more about the connection of chemistry and the mind," he predicted. One example Zare pointed to concerned sleep. "We don't understand sleep. We may discover that sleep actually is a vestige of a previous time that we don't need any more. Some sleep is needed, but not nearly as much as most people get. I am not so sanguine about extending the lifetime of people because of limitations on cell division, for example. But we may actually greatly change the nature of life if by taking the right combination of chemicals we only have to sleep an hour a night. There is so much to be learned about this, and ultimately it will involve chemistry. Ultimately the solutions will be chemical." Artificial intelligence will be used to design syntheses, and, in fact, run them. We carry out synthesis in a 19th-century style-we have better glass, better analytical tools. But there hasn't been a real advance in the automation and computerization of synthesis. That's going to change.Allen Bard



Richard N. Zare Panel members predicted significant advances in all areas of synthesis. Breslow, for example, pointed to work on synthesizing complex carbohydrates. "Focusing on carbohydrates is way overdue," he said." Every cell surface is identified, essentially, with cell-surface antigens, which are all carbohydrates. And there's pretty good evidence that bacteria recognize cells and invade them, in part, by binding to complex carbohydrates. There's a lot of synthetic work going on to develop the methodology to make these materials. It's clear that this is going to lead to very important pharmaceutical applications."

And chemists will increasingly harness cells to carry out syntheses for them, Imperiali argued." We're going to get a far better appreciation of how to use biological systems to create compounds on demand. We're really at the brink of that already with advances in genetic engineering." Over the next quarter century, the fundamental understanding of chemical reactivity also will advance significantly, panelists predicted. "Within 25 years, most reaction mechanism studies of the kind that we do now on simple reactions will be replaced by computational studies," Breslow predicted. "Right now, a computer can generate a complete reaction profile and create a movie showing everything that happens during a reaction. The problem is, we don't know whether it is accurate. We will get to the point where computations will be good enough that every time we check the thing, it will turn out to be consistent with experiment, and we will finally conclude that we don't have to do the experiments any more." Such a capability, Breslow added, will make it possible "to predict, for example, what kind of catalyst you would need to add to make a reaction go, and how that catalyst would operate. You should also be able to predict what reaction would occur between two materials that have not yet been put together-predict products and reaction rates that haven't occurred yet." Advances in catalysis-moving toward rational design of catalysts-caught the attention of Theodore Brown. "In spite of all we know about catalysis, a lot remains Edisonian," he pointed out. "Catalysis research is pretty much a trial-and-error business. When we discover a new catalyst, we're delighted and we exploit it as much as we can. But we don't know where the next one is going to come from. The combination of combinatorial chemistry and computational methods may lead us to the point where we actually have a library of catalysts designed to do specific things. That has tremendous implications because it allows you to produce compounds more or less on demand." Barton seconded Brown on the ability to "design a catalyst to tailor-make a material that we want." She also predicted that "manufacturing will be cleaner. We will be doing oxidation chemistry with oxygen rather than with chlorine. And we will focus manufacturing on preserving the materials used and minimizing the energy required to carry out the necessary reactions."



Stuart A. Rice Another area that several panel members focused on was increasing sophistication in analytical techniques. "I think there will be continued development of techniques to measure smaller and smaller quantities-single-molecule quantities-to the point where there will be a vast array of probes of all kinds for biomedical and industrial applications so that one can continuously monitor or test events of chemical importance," Rice said. Added Richard Smalley: "One of my favorite dreams is developing true spectroscopies for individual molecules, spectroscopies that are really worthy of the name. Not just touching the top of the molecule or pulling a macroscopic electric current through it, but actually doing, for example, NMR on a single molecule."

Well before 25 years from now, carbon fibers and boron nitride fibers of molecular perfection, both in small random lengths and in continuous lengths in cables, will be produced in millions of tons per year.Richard Smalley



Richard E. Smalley Another area where chemistry will have a major impact in the next 25 years is materials science. "I think we are already seeing advances in materials science in the broad sense, ranging from metals to polymers," observed Rice. "And I think that manufacturing processes are going to take advantage of this, in the sense that we will be using more 'designer material' instead of bulk material. For instance, if you want a bridge to withstand certain stresses for a certain period of time, then you will be able to order up the materials you want to make the bridge out of. And the economies of manufacture will be sufficient to make that possible, and we will understand enough about designing materials to make that possible."

Research on the electronic properties of organic compounds will result in new electronic devices such as displays, memories, and field-effect transistors, according to Bard. "I think there will be an organic electronics industry growing out of this." "I agree," Smalley responded." In fact, I'll up you two or three orders of magnitude. I now am beginning to believe that molecular electronics really is possible and will happen." Smalley, who shared the 1996 Nobel Prize in Chemistry for the discovery of the fullerenes, based his prediction on work in his laboratory and others directed at synthesizing and characterizing carbon nanotubes. Certain nanotubes are truly metallic, Smalley said, which means" we have a way in organic chemistry to make metallic wires. And by hooking these things together with chemical perfection, we ought to be able to make the equivalent of essentially every circuit element that we can make in the macroscopic world out of molecules. If that's true, it may well end up that, well before 25 years from now, there is a very robust side of organic chemistry where the practitioners, instead of making pharmaceuticals or polymers, will be making electronic devices." Smalley also foresees numerous other applications of carbon nanotubes and their boron-nitrogen analogs. He calls one of them "paint by numbers." "I imagine that a single buckytube is the stick of a paintbrush," Smalley said." The bristles are catalyst molecules bound to the tip of this nanotube stick." The" paint" in Smalley's metaphor is composed of reactant molecules drifting by in solution. The canvas is some surface "on which we want to build structures of molecular precision. Paint adheres to the canvas whenever the surface, the catalyst, and the reactant molecules come together at the same time. Depending on the 'number' for the region to be painted, the reactant molecule and the catalyst on the end of the nanotube stick are changed.



Robert S. Langer "This gives you at least one way, in principle, to build something as complex as a Pentium chip with molecular precision," Smalley suggested. "The more we think about these things, the less ridiculous they seem." Langer pointed to an intersection between advances in materials and biomedical research. "Biomaterials will advance due to basic research that is now being done on dendrimers, electrically conducting polymers, polymers that can undergo phase transitions, and many others," he said. "These will be applied to new drug-delivery systems, and to creation of new tissues such as skin, cartilage, or even nerves."

It will become increasingly clear that it is a crime against the future to take petroleum and burn it. Not just because of global warming, but because we are burning away materials that are tremendously valuable for other uses.Ronald Breslow

Chemistry is a practical science, and C&EN's panel predicted that the next 25 years would see contributions from chemistry toward addressing a variety of societal problems. "It seems to me that the problems in 25 years for mankind are going to involve energy and food," Bard said. "I think world population is bound to keep increasing, and both food and energy will be issues. We need portable fuels. If we stop burning oil-and even if we don't, we're going to run out of it-we need to harness chemistry to make different liquid fuels. A hydrogen economy sounds good, but unless we develop good ways of storing hydrogen very densely and safely, there will still be a lot of liquid fuel needed." As to food, "chemistry is starting to make food," Bard said. "We make artificial fats that are not fats. I have a feeling that trend will continue, that we will make food of different types." "Twenty-five years from now the internal combustion engine will be found in museums, battery technology will finally have solved the problem of how we transport electrical power, and fuel cells will be practical devices, not just interesting things to talk about in freshman chemistry courses-cheap enough and powerful enough to be used routinely," Smalley predicted. "We may have solved the problem of cheap solar energy, cheap enough so that you would be a fool to build a power plant any other way." "One of the biggest failures of chemistry in the 20th century has been the inability to develop good fuel-cell catalysts," Lippard said. "I think the electric car is the invention which chemistry can make a reality. Electric cars would dramatically restore the beautiful cities of the world to their previous pristine glory. Imagine what Mexico City, Florence, Rome, and Paris would be like without automobile pollution. That's really important, fundamental research-new batteries, new fuel-cell catalysts that would push that technology forward."



Stephen J. Lippard By contrast, Rice predicted that concerns about global warming will have led in 25 years to a revitalization of the nuclear power industry. "Without understanding the mechanism of global warming, one can get confidence that the consequence of apparently small changes in temperature can have dramatic changes on humankind," Rice said. "If that is accepted, then the consequences of ignoring it, I think, will become so apparent that people will be willing to say, 'We don't know whether fossil fuel burning is the primary or only source of global warming. But there are alternatives, and we ought to at least ensure that the alternatives are available to us and start using some of them.' "

These experiments in electronic publishing, many of them may be failures. But with the power of this methodology and the capacity to reach larger numbers of people more quickly than ever before, it's inevitable that people will find legitimate ways to use them to publish their scientific results. And they're going to usurp the traditional methods.Theodore Brown



Theodore L. Brown Communicating the results of research is the hallmark of all science. Members of C&EN's panel were unanimous in predicting that current trends in electronic publishing will profoundly change how chemists communicate. "When a new discovery is made, will it be possible for someone to post the discovery on the Internet, obviating the normal means of publishing through peer review?" Brown asked. "In the high-energy physics community, which is a small, self-contained community, there is already a new process. Los Alamos National Laboratory runs an electronic publishing operation that allows people to post their papers on the server. Others read them, comment on them, communicate about them. Eventually, they get printed, but they're old hat by then.

"Chemistry hasn't adopted that practice yet, although there are electronic conferences going on. I have a feeling that, as these technologies become more and more thoroughly embedded in our day-to-day practices, they are going to affect the ways in which we communicate with one another and the ways in which we disseminate our results." Bard, who is the editor of JACS, responded to Brown: "My feeling is that the high-energy physics community can get away with that because they are a tiny community, and there's very little practical import to what they do. I don't think it is going to be popular among chemists. My own feeling is that the signal-to-noise ratio in these electronic publications is really bad. It may be readily available, but you spend a lot of time gleaning out what's worth looking at from a lot of junk. So I guess I'm old-fashioned. But I have a feeling that traditional modes of publishing are going to be with us for a long time." To which Brown replied: "I'm not arguing that we already have a process that is a good substitute for what we've done traditionally. What I am arguing is that there are new forms of communication out there. And it just doesn't make sense for us to expect that in 25 years we are going to be still doing journal publishing the same way we do it today." Imperiali weighed in with a defense of traditional publishing and a plug for the Internet. "The volume of material on the Internet is getting out of control. And the quality control has to go down because of the volume. I have to echo Al. I feel very old-fashioned about this. I think we have to maintain a certain level of things that we know we can trust the quality."



Barbara Imperiali That said, Imperiali continued, "I think the Internet is an outstanding medium for collaborative work between colleagues. In addition to increasing access to information, it takes away the fact that we are in different cities and allows us to communicate and make things happen." Smalley's vision encompassed the immediacy of electronic journals with the quality control of peer review. "In 25 years, we will be getting our journals transmitted directly to a little thing that will feel like a book. If we want, it could smell like a book. But it will be every book that has ever been written. However, it will still be true that the best researchers will want their work to be published in the most exclusive environments.

"Almost like advertising, you pay for readership. You want people to read it. That's one of our responsibilities in science. It doesn't matter if you discovered it; you've got to affect the corporate knowledge. And so I know in my own group, and I assume in most groups, we try to wait so we can really put a blockbuster out there, rather than dribbling it out in journals that won't get read. But I can't imagine waiting for a piece of paper to arrive in Texas before I read it 25 years from now." At the beginning of the forum, the panel was instructed to take an optimistic view of research support over the next 25 years. But sources of support for basic research, the types of research that are being supported, and the relationship between industry and academe are subjects of interest and real concern for these academic chemists. One message that came through loud and clear was that it is imperative for the government to continue strong support for basic research. "I think there's a true concern for people who are entering academia right now, that they are stuck between a rock and a hard place, deciding whether to follow application-driven science or curiosity-driven science," Imperiali said. "The funding opportunities are becoming so limited. I think we should be very concerned about moving away from truly fundamental science just because of funding decisions." Barton suggested that industry is likely to support some basic research at universities out of self-interest." The relationships are changing between industry and universities, and they are going to continue to change," she said. "Industry isn't interested, by and large, in having universities do their research. They want universities to do the more fundamental research, and then let industry run with it." In terms of protecting basic research, perhaps Bard said it best: "I think my gravest concern is how to protect basic research. If I have to make a prediction about the future, I would predict that five of the most important things that will be developed in the next 25 years have not been discussed at this table. And they will be the result of fundamental research that some young scientists being supported by the federal government are going to come up with."



Allen J. Bard With adequate funding, the next 25 years look at least as bright as the past 75 for chemistry. Indeed, the chemists assembled by C&EN to project the future were almost irrepressible in their enthusiasm for what chemistry can accomplish. "What is most important about chemistry is that we make new things," said Lippard. "We don't just study the natural world, we make new molecules, new catalysts, new compounds of uncommon reactivity. Part of our subject allows us to be creatively artistic through the synthesis of beautiful and symmetric molecules. Our ability to rearrange atoms in new ways allows us a tremendous opportunity for creation that other sciences don't have."