What areas of chemistry could AI impact the most? An opinion poll

The other day I asked the following as a survey question regarding potential areas of chemistry where AI could have the biggest impact.

There were 163 responses which wasn't a bad representative sample. The responses are in fact in line with my own thinking: synthesis planning and automation emerge as the leading candidates. 

I think synthesis planning AI will have the biggest impact on everyday lab operations during the next decade. Synthesis planning, while still challenging, is still a relatively deterministic protocol based on a few good reactions and a large but digestible number of data points. Reliable reactions like olefin metathesis and metal-mediated coupling have now become fairly robust and heavily used to generate thousands of machine-readable data points and demonstrate reliability and relative predictability; there are now fewer surprises, and whatever surprises exist are well-documented. As recent papers make it clear, synthesis planning had been waiting in the wings for several years for the curation of millions of examples pertaining to successful and unsuccessful reactions and chemotypes as well as for better neural networks and computing power. Without the first development the second wouldn't have made a big difference, and it seems like we are finally getting there with good curation.

I was a bit more surprised that materials science did not rank higher. Quantum chemical calculations for estimating optical, magnetic, electronic and other properties have been successful in materials science and have started enabling high-throughout studies in areas like MOF and battery technology, so I expect this field to expand quite a bit during the next few years. Similar to how computation has worked in drug discovery, AI approaches don't need to accurately predict every material property to three decimal places; they will have a measurable impact even if they can qualitatively rank different options and narrow down the pool so that chemists have to spend fewer resources making them.

Drug design, while already a beneficiary of compute, will see mixed results in my opinion over the next decade. For one thing, "drug design" is a catchall phrase that can include everything from basic protein-ligand structure prediction to toxicity prediction, with the latter being at the challenging end of the spectrum. Structure-based design will likely benefit from deep learning that learns basic intermolecular interactions which are transferable across target classes, so that they are limited by the paucity of training data.

Areas like synthesis planning do contribute to drug design, but the real crux of successful drug design will be multiparameter optimization and SAR prediction, where an algorithm is able to successfully calculate multiple properties of interest like affinity, PK/PD and toxicity. PK/PD and toxicity are systemic effects that are complex and emergent, and I think the field will still not be able to make a significant dent in predicting idiosyncratic toxicity except for obvious cases. One area in which I see AI having a bigger impact is any field of drug discovery involving image recognition; for instance phenotypic screening, and perhaps the processing of images in cryo-EM and standard x-ray crystallography.

Finally, automation is one area where I do think AI will make substantial progress. This is partly due to better seamless integration of hardware and software and partly because of better data generation and recording that will enable machine learning and related models to improve. This development, combined with reaction planning that allows scientists to test multiple hypotheses will contribute, in my opinion, in automation making heavy inroads in the day-to-day work of chemists fairly soon.

Another area which I did not mention in the survey but which will impact all of the above areas is text mining. There the problem is one of discovering relationships between different entities (drugs and potential targets, for instance) that are not novel per se but that are just hidden in a thicket of patents, papers and other text sources which are too complicated for humans to parse. Ideally, one would be able to combine text mining with intelligent natural language processing algorithms to enable new discovery through voice commands.

Memo to chemists: Move away from the molecule

Derek's latest post on the 'end of synthesis' reminded me of this perspicacious essay by George Whitesides which I had blogged about on Scientific American last year. I am reposting the piece here.

Harvard chemist George Whitesides probably does not consider himself a philosopher of chemistry, but he is rapidly turning into one with his thought-provoking pronouncements on the future of the field and its practitioners. In 2013 he wrote a rumination in the Annual Reviews of Analytical Chemistry provocatively titled “Is the Focus on Molecules Obsolete?” where he uses analytical chemistry as an excuse to really pontificate on the state and progress of chemical science. Along the way he also has some valuable words of advice for aspiring chemists.

Whitesides’s main message to young chemists is to stop focusing on molecules. Given the nature of chemistry this advice may seem strange, even blasphemous. After all it’s the molecule that has always been the heart and soul of chemical science. And for chemists, the focus on molecules has manifested itself through two important activities – structure determination and synthesis. The history of chemistry is essentially the history of finding out the structure of molecules and of developing new and efficient methods of making them. Putting these molecules to new uses is what underpins our modern world, but it was really a secondary goal for most of chemistry’s history. Whitesides tells us that the focus of the world’s foremost scientific problems is moving away from composition to use, from molecules to properties. Thus the new breed of chemists should really focus on creating properties rather on creating molecules. The vehicle for Whitesides’s message is the science and art of analytical chemistry which has traditionally dealt with developing new instrumentation and methods for analyzing the structure and properties of molecules.

Of course, since properties depend on structures, Whitesides is not telling us to abandon our search for better, cleaner and more efficient techniques of synthesis. Rather, I see what he is saying as a kind of “platform independence”. Let’s take a minute to talk about platform independence. As the physicist Leo Kadanoff has demonstrated, you can build a computer by moving around 1s and 0s or by moving around buckets of water, with full buckets essentially representing 1s and empty ones representing 0s. Both models can give rise to computing. Just like 1s and 0s simply turn out to be convenient abstract moving parts for building computers, similarly a certain kind of molecule should be seen as no more than a convenient vehicle for creating a particular property. That property can be anything from “better stability in whole blood” to “efficient capture of solar energy” to “tensile strength”. The synthesis of whatever molecular material gives rise to particular properties is important, but it should be secondary; a convenient means to an end that can be easily replaced with another means. As an example from his own childhood, Whitesides describes a project carried out in his father’s company in which his job was to determine the viscosities of different coal-tar blacks. The exact kind of coal-tar black was important, but what really counted was the property – viscosity – and not the molecular composition.

A focus on properties is accompanied by one on molecular systems, since often it’s a collection of different, diverse molecules rather than of a single type that gives rise to a desired property. What kind of problems will benefit from a molecular systems approach? Whitesides identifies four critical ones; health care, environmental management, national security and megacity management. We have already been living with the first three challenges, and the fourth one looms large on the horizon.

Firstly, health care. Right now most of the expenditure on health care, especially in the United States, is on end-of-life care. Preventative medicine and diagnostics are still relegated to the sidelines. One of the most important measures to drive down the cost of healthcare will be to focus on prevention, thus avoiding the expensive, all-out war that is often waged – and lost – on diseases like cancer during their end stages. Prevention and diagnostics are areas where chemistry can play key roles. We still lack methods that can quickly and comprehensively analyze disease markers in whole blood, and this is an area where analytical and other kinds of chemists can have a huge impact. And no method of diagnostics is going to be useful if it’s not cheap, so it’s obvious that chemistry will also have to struggle to minimize material cost, another goal which it has traditionally been good at addressing, especially in industry.

Secondly, the environment. We live in an age when the potentially devastating effects of climate change and biodiversity loss demand quick and comprehensive action. Included in this response will be the ability to monitor the environment, and to relate local monitoring parameters to global ones. Just like we still lack methods to analyze the composition of complex whole blood, we also lack methods to quickly analyze and compare the composition of the atmosphere, soil and seawater in different areas of the world. Analyzing heterogeneous systems with different phases like the atmosphere is a tricky and quintessentially chemical problem, and chemists have their work cut out in front of them to make such routine analysis a reality.

Thirdly, national security. Here chemists will face even greater challenges, since the solutions are as much political and social as they are scientific. Nonetheless, science will play an important role in the resolution of scores of challenges that have to be met to make the world more secure; these include quickly analyzing the composition of a suspicious liquid, solid or gas, unintrusively finding out whether a particular individual has spent time in certain volatile parts of the world or has been handling certain materials, and using techniques to track the movements of suspicious individuals in diverse locations. Chemistry will undoubtedly have to interface with other disciplines in addressing these problems and questions of privacy will be paramount, but there is little doubt that chemists have traditionally not participated much in such endeavors and need to step up to the plate in order to address what are obviously important security issues.

Fourthly, megacities. As we pick up speed and move into the second decade of the twenty-first century, one of the greatest social challenges confronting us is how to have very large, heterogeneous populations ranging across diverse levels of income and standards of living co-existing in peace over vast stretches of land. This is the vision of the megacity whose first stirrings we are already witnessing around the world. Among the problems that megacities will encounter will be monitoring air, water and food quality (vida supra). A task like analyzing the multiple complex components of waste effluent, preferably with a readout that quantifies each component and assesses basic qualities like carcinogenicity would be invaluable. There is no doubt that chemists could play an indispensable role in meeting such challenges.

The above discussion of major challenges makes Whitesides’s words about moving away from the molecule clear. The problems encompassing health care, national security and environmental and megacity management involve molecules, but what they really are are collages resulting from the interaction of molecules with other scientific entities, and with the interaction of chemists with many other kinds of professional scientists and policy makers. In one sense Whitesides is simply asking chemists to leave the familiar environment of their provincial roots and diversify. What chemists really need to think of is molecules embedded in a broad context involving other disciplines and human problems.

Part of the challenge of addressing the above issues will be the proper training of chemists. The intersection of chemistry with social issues and public policy demands interdisciplinary and general skills, and Whitesides urges chemists to be trained in general areas rather than specialized subfields. Courses in applied mathematics and statistics, public policy, urban planning, healthcare management and environmental engineering are traditionally missing from chemistry curricula, and chemists should branch out and take as many of these as is possible within a demanding academic environment. It is no longer sufficient for chemists to limit themselves to analysis and synthesis if they want to address society’s most pressing problems. And at the end of it they need not feel that a movement away from the molecule is tantamount to abandoning the molecule; rather it is an opportunity to press the molecule into interacting with the human world on a canvas bigger than ever before.

Memo to chemists: Move away from the molecule

Megacities of the future - with their heterogeneous population and large-scale problems - will challenges the imagination of chemists (Image: Bldg Blog)

Harvard chemist George Whitesides probably does not consider himself a philosopher of chemistry, but he is rapidly turning into one with his thought-provoking pronouncements on the future of the field and its practitioners. His latest rumination is a piece in the Annual Reviews of Analytical Chemistry provocatively titled "Is the Focus on Molecules Obsolete?" where he uses analytical chemistry as an excuse to really pontificate on the state and progress of chemical science. Along the way he also has some valuable words of advice for aspiring chemists.

Whitesides's main message to young chemists is to stop focusing on molecules. Given the nature of chemistry this advice may seem strange, even blasphemous. After all it's the molecule that has always been the heart and soul of chemical science. And for chemists, the focus on molecules has manifested itself through two important activities - structure determination and synthesis. The history of chemistry is essentially the history of finding out the structure of molecules and of developing new and efficient methods of making them. Putting these molecules to new uses is what underpins our modern world, but it was really a secondary goal for most of chemistry's history. Whitesides tells us that the focus of the world's foremost scientific problems is moving away from composition to use, from molecules to properties. Thus the new breed of chemists should really focus on creating properties rather on creating molecules. The vehicle for Whitesides's message is the science and art of analytical chemistry which has traditionally dealt with developing new instrumentation and methods for analyzing the structure and properties of molecules.

Of course, since properties depend on structures, Whitesides is not telling us to abandon our search for better, cleaner and more efficient techniques of synthesis. Rather, I see what he is saying as a kind of "platform independence". Let's take a minute to talk about platform independence. As the physicist Leo Kadanoff has demonstrated, you can build a computer by moving around 1s and 0s or by moving around buckets of water, with full buckets essentially representing 1s and empty ones representing 0s. Both models can give rise to computing. Just like 1s and 0s simply turn out to be convenient abstract moving parts for building computers, similarly a certain kind of molecule should be seen as no more than a convenient vehicle for creating a particular property. That property can be anything from "better stability in whole blood" to "efficient capture of solar energy" to "tensile strength". The synthesis of whatever molecular material gives rise to particular properties is important, but it should be secondary; a convenient means to an end that can be easily replaced with another means. As an example from his own childhood, Whitesides describes a project carried out in his father's company in which his job was to determine the viscosities of different coal-tar blacks. The exact kind of coal-tar black was important, but what really counted was the property - viscosity - and not the molecular composition.

A focus on properties is accompanied by one on molecular systems, since often it's a collection of different, diverse molecules rather than of a single type that gives rise to a desired property. What kind of problems will benefit from a molecular systems approach? Whitesides identifies four critical ones; health care, environmental management, national security and megacity management. We have already been living with the first three challenges, and the fourth one looms large on the horizon.

Firstly, health care. Right now most of the expenditure on health care, especially in the United States, is on end-of-life care. Preventative medicine and diagnostics are still relegated to the sidelines. One of the most important measures to drive down the cost of healthcare will be to focus on prevention, thus avoiding the expensive, all-out war that is often waged - and lost - on diseases like cancer during their end stages. Prevention and diagnostics are areas where chemistry can play key roles. We still lack methods that can quickly and comprehensively analyze disease markers in whole blood, and this is an area where analytical and other kinds of chemists can have a huge impact. And no method of diagnostics is going to be useful if it's not cheap, so it's obvious that chemistry will also have to struggle to minimize material cost, another goal which it has traditionally been good at addressing, especially in industry.

Secondly, the environment. We live in an age when the potentially devastating effects of climate change and biodiversity loss demand quick and comprehensive action. Included in this response will be the ability to monitor the environment, and to relate local monitoring parameters to global ones. Just like we still lack methods to analyze the composition of complex whole blood, we also lack methods to quickly analyze and compare the composition of the atmosphere, soil and seawater in different areas of the world. Analyzing heterogeneous systems with different phases like the atmosphere is a tricky and quintessentially chemical problem, and chemists have their work cut out in front of them to make such routine analysis a reality.

Thirdly, national security. Here chemists will face even greater challenges, since the solutions are as much political and social as they are scientific. Nonetheless, science will play an important role in the resolution of scores of challenges that have to be met to make the world more secure; these include quickly analyzing the composition of a suspicious liquid, solid or gas, unintrusively finding out whether a particular individual has spent time in certain volatile parts of the world or has been handling certain materials, and using techniques to track the movements of suspicious individuals in diverse locations. Chemistry will undoubtedly have to interface with other disciplines in addressing these problems and questions of privacy will be paramount, but there is little doubt that chemists have traditionally not participated much in such endeavors and need to step up to the plate in order to address what are obviously important security issues.

Fourthly, megacities. As we pick up speed and move into the second decade of the twenty-first century, one of the greatest social challenges confronting us is how to have very large, heterogeneous populations ranging across diverse levels of income and standards of living co-existing in peace over vast stretches of land. This is the vision of the megacity whose first stirrings we are already witnessing around the world. Among the problems that megacities will encounter will be monitoring air, water and food quality (vida supra). A task like analyzing the multiple complex components of waste effluent, preferably with a readout that quantifies each component and assesses basic qualities like carcinogenicity would be invaluable. There is no doubt that chemists could play an indispensable role in meeting such challenges.

The above discussion of major challenges makes Whitesides's words about moving away from the molecule clear. The problems encompassing health care, national security and environmental and megacity management involve molecules, but what they really are are collages resulting from the interaction of molecules with other scientific entities, and with the interaction of chemists with many other kinds of professional scientists and policy makers. In one sense Whitesides is simply asking chemists to leave the familiar environment of their provincial roots and diversify. What chemists really need to think of is molecules embedded in a broad context involving other disciplines and human problems.

Part of the challenge of addressing the above issues will be the proper training of chemists. The intersection of chemistry with social issues and public policy demands interdisciplinary and general skills, and Whitesides urges chemists to be trained in general areas rather than specialized subfields. Courses in applied mathematics and statistics, public policy, urban planning, healthcare management and environmental engineering are traditionally missing from chemistry curricula, and chemists should branch out and take as many of these as is possible within a demanding academic environment. It is no longer sufficient for chemists to limit themselves to analysis and synthesis if they want to address society's most pressing problems. And at the end of it they need not feel that a movement away from the molecule is tantamount to abandoning the molecule; rather it is an opportunity to press the molecule into interacting with the human world on a canvas bigger than ever before.

First published on the Scientific American Blog Network.

On synthesis, design and chemistry's outstanding philosophical problems

Chemists need to move from designing structure - exemplified by this synthetic receptor - to designing function (Image: Max Planck Institute).

Yesterday I wrote a post about a perspective by multifaceted chemist George Whitesides in which he urged chemists to broaden the boundaries of their discipline and think of big picture problems. But the article spurred me to think a bit more about a question which I (and I am sure other chemists) have often thought about; what’s the next big challenge for chemistry?

And when I ask this question I am not necessarily thinking of specific fields like energy or biotechnology or food production. Rather, I am thinking of the next outstanding philosophical question confronting chemistry. By philosophical question I don’t mean an abstract goal which only armchair thinkers worry about. The philosophical questions in a field are those which define the field’s big problems in the most general sense of the term. For physicists it might be understanding the origin of the universe, for biologists the origin of life. These problems can also be narrowly defined questions that nonetheless expand the understanding and scope of a field; for instance in the early twentieth century physicists were struggling to make sense of atomic spectra, which turned out to be important for the development of quantum theory. It’s also important to note that the philosophical problems of a field change over time, and this is one reason why chemists should be aware of them; you want to move with the times. If you were a “chemist” in the sixteenth century the big question was transmutation. In the nineteenth century when chemistry finally was cast in the language of elements and molecules the big question became theconstitution of molecules in the form of atomic arrangements.

Synthesis is no longer chemistry’s outstanding general problem

When I think about the next philosophical question confronting chemistry I also feel a sense of despondency. That’s because I increasingly feel that the great philosophical question that chemists are going to face in the near future is emphatically not one whose answer they will locate in the all-pervasive activity that always made chemistry unique: synthesis. What always set chemistry apart was its ability to make new molecules that never existed before. Through this activity chemistry has played a central role in improving our quality of life.

The point is, synthesis was the great philosophical question of the twentieth century, not the twenty-first. Now I am certainly not claiming that synthesizing a complex natural product with fifty rotatable bonds and twenty chiral centers is even today a trivial task. I am also not saying that synthesis will cease to be a fruitful source of solutions for humanity’s most pressing problems, such as disease or energy; as a tool the importance of synthesis will remain undiminished. What I am saying is that the general problem of synthesis has now been solved in an intellectual sense (as an aside, this would be consistent with the generally pessimistic outlook regarding total synthesis seen on many blogs.)

The general problem of synthesis was unsolved in the 30s. It was also unsolved in the 50s. Then Robert Burns Woodward came along. Woodward was a wizard who made molecules whose construction had defied belief. He had predecessors, of course, but it was Woodward who solved the general problem by proving that one could apply well-known principles of physical organic chemistry, conformational analysis and spectroscopy to essentially synthesize any molecule. He provided the definitive proof of principle. All that was needed after that was enough time, effort and manpower. If chemistry were computer science, then Woodward could be said to have created a version of the Turing Machine, a general formula that could allow you to synthesize the structure of any complex molecule, as long as you had enough NIH funding and cheap postdocs to fill in the specific gaps. Every synthetic chemist who came after Woodward has really developed his or her own special versions of Woodward’s recipe. They might have built new models of cars, but their Ferraris, Porches and Bentleys – as elegant and impressive as they are – are a logical extension of Woodward and his predecessor’s invention of the internal combustion engine and the assembly line.

A measure of how the general problem of synthesis has been solved is readily apparent to me in my own small biotech company which specializes in cyclic peptides, macrocycles and other complex bioactive molecules. The company has a vibrant internship program for undergraduates in the area. To me the most remarkable thing is to see how quickly the interns can bring themselves up to speed on the synthetic protocols. Within a month or so of starting at the bench they start churning out these compounds with the same expertise and efficiency as chemists with PhDs. The point is, synthesizing a 16-membered ring with five stereocenters has not only become a routine, high-throughput task but it’s something that can be picked up by a beginner in a month. This kind of synthesis might have easily fazed a graduate student twenty years ago and taken up a good part of his or her PhD project. The bottom line is that we chemists have to now face an uncomfortable fact: there are still a lot of unexpected gems to be found in synthesis, but the general problem is now solved and the incarnation of chemical synthesis as a tool for other disciplines is now essentially complete.

Functional design and energetics are now chemistry’s outstanding general problems

So if synthesis is no longer the general problem, what is? My own field of medicinal chemistry and molecular modeling provides a good example. It may be easy to synthesize a highly complex drug molecule using routine techniques, but it is impossible, even now, to calculate the free energy of binding of an arbitrary simple small molecule with an arbitrary protein. There is simply no general formula, no Turing Machine that can do this. There are of course specific cases where the problem can be solved, but the general solution seems light years away. And not only is the problem unsolved in practice but it is also unsolved in principle. Sure, we modelers have been saying for over twenty years that we have not been able to calculate entropy or not been able to account for tightly bound water molecules. But these are mostly convenient questions which when enunciated make us feel more emotionally satisfied. There have certainly been some impressive strides in addressing each of these and other problems, but the fact is that when it comes to calculating the free energy of binding, we are still today where we were in 1983. So yes, the calculation of free energies – for any system – is certainly a general problem that chemists should focus on.

But here’s the even bigger challenge that I really want to talk about: We chemists have been phenomenal in being able to design structure, but we have done a pretty poor job in designing function. We have of course determined the function of thousands of industrial and biological compounds, but we are still groping in the dark when it comes to designing function. Here are a few examples: Through combinatorial techniques we can now synthesize antibodies that we want to bind to a specific virus or molecule, but the very fact that we have to adopt a combinatorial, brute force approach means that we still can’t start from scratch and design a single antibody with the required function (incidentally this problem subsumes the problem of calculating the free energy of antigen-antibody binding). Or consider solar cells. Solid-state and inorganic chemists have developed an impressive array of methods to synthesize and characterize various materials that could serve as more efficient solar materials. But it’s still very hard to lay out the design principles – in general terms – for a solar material with specified properties. In fact I would say that the ability to rapidly make molecules has even hampered the ability to think through general design principles. Who wants to go to the trouble of designing a specific case when you can simply try out all combinations by brute force?

I am not taking anything away from the ingenuity of chemists – nor am I refuting the belief that you do whatever it takes to solve the problem – but I do think that in their zeal to perfect the art of synthesis chemists have neglected the art of de novo design. Yet another example is self-assembly, a phenomenon which operates in everything from detergent action to the origin of life. Today we can study the self-assembly of diverse organic and inorganic materials under a variety of conditions, but we still haven’t figured out the rules – either computational or experimental – that would allow us to specific the forces between multiple interacting partners so that these partners assembly in the desired geometry when brought together in a test tube. Ideally what we want is the ability to come up with a list of parts and the precise relationships between them that would allow us to predict the end product in terms of function. This would be akin to what an architect does when he puts together a list of parts that allows him to not only predict the structure of a building but also the interplay of air and sunlight in it.

I don’t know what we can do to solve this general problem of design but there are certainly a few promising avenues. A better understanding of theory is certainly one of them. The fact is that when it comes to estimating intermolecular interactions, the theories of statistical thermodynamics and quantum mechanics do provide – in principle – a complete framework. Unfortunately these theories are usually too computationally expensive to apply to the vast majority of situations, but we can still make progress if we understand what approximations work for what kind of systems. Psychologically I do think that there has to be a general push away from synthesis and toward understanding function in a broad sense. Synthesis still rules chemical science and for good reason; it's what makes chemistry unique among the sciences. But that also often makes synthetic chemists immune to the (well deserved) charms of conformation, supramolecular interactions and biology. It’s only when synthetic chemists seamlessly integrate themselves into the end stages of their day job that they will learn better to appreciate synthesis as an opportunity to distill general design principles. Let the synthetic chemist interact with the physical biochemist, the structural engineer, the photonics expert; let him or her see synthesis through the requirement of function rather than structure. Whitesides was right when he said that chemists need to broaden out, but another way to interpret his statement would be to ask other scientists to channel their thoughts into synthesis in a feedback process. As chemists we have nailed structure, but nailing design will bring us untold dividends and will help make the world a better place.

First published on the Scientific American Blog Network.

George Whitesides on the responsibility of chemists and the future of chemistry

Catching up on a few articles I had missed, I came across a characteristically deep and wide-ranging essay called "Assumptions" by George Whitesides about science, its future and our responsibility as scientists. It's a very general and kaleidoscopic essay not restricted to chemistry, but the bits about chemistry, its role in understanding the major problems confronting humanity and chemists' responsibility in extending the scope of chemical science are quite thought-provoking:

Chemistry, by its culture, has been almost blindly reductionist. I am repeatedly reminded that “Chemists work on molecules”, as if to do anything else was suspect. Chemists do and should work on molecules, but also on the uses of molecules, and on problems of which molecules may be only a part of the solution. If chemists move beyond molecules to learn the entire problem—from design of surfactants, to synthesis of colloids, to MRI contrast agents, to the trajectories of cells in the embryo, to the applications of  regenerative medicine—then the flow of ideas, problems, and solutions between chemistry and society will animate both. 

Whitesides is clearly making a plea for chemists to become even more interdisciplinary than what they already are, to pursue not just the development of the solution but its application and integration; his own group provides a remarkable example of chemists, physicists, biologists and engineers working together on highly multidisciplinary problems. It's quite clear that to achieve this interdisciplinary expertise we have to completely break down the traditional barriers between synthesis, structure determination, biology and materials (in this world the professor who rejected my biochemical literature seminar topic because it "did not include any synthesis" would be an anachronism). The next paragraph makes clear the role of the "central science"

As a technology, chemistry has built the foundation from which many of the discoveries of “biology” or “microelectronics” or “brain science” (or “planetary exploration”, for that matter) have grown. There would be no genomics without chemical methods for separating fragments of DNA, and for synthesizing primers and probes, and for separating restriction endonucleases into pure activities. There would be no nuclear ICBMs without methods of refining plutonium, and making explosive lenses. There would be no drugs without synthesis and mass spectroscopy. There would be no interplanetary probes without fuels, and carbon/carbon rocket throat nozzles, and silicon single crystals. 

And here's something about what the future of chemistry should be:

Those are the past. What about the future? Chemistry is, still, everywhere: It must be! It is the science of the real world. But to remain a star in the play rather than a stagehand, it must open its eyes to new problems. It is impossible that the human life span will increase dramatically without manipulation of the molecules of the human organism, but understanding this problem will require more than manipulating molecules. Communication between the living and non-living will require engineering a molecular interface between them, but designing this interface will require understanding the nature of “information” in organisms and in computers, and how to translate between them. A society that uses information technology to interweave all its parts requires new systems for generating, distributing, and storing power, but batteries will be only one part of these systems.  

Chemistry has always been the invisible hand that builds and operates the tools, and sustains the infrastructure. It can be more. We think of ourselves as experts in quarrying blocks from granite; we have not thought it our job to build cathedrals from them. Whether we choose to focus on the molecules, materials, and tools that are at the beginnings of discovery, or bring our particular, unique understanding of the world to bear on unraveling the problems at the end, is for us to decide.  I believe that everything from methane to sentience is chemistry, and that we should reexamine our own assumptions concerning the boundaries of our field. Examining the broader assumptions that follow may provide some stimulus to do so.  

Indeed, examining the "broader assumptions" of their field in the broadest sense of the term is what chemists should do. The first paragraph presents a fair sampling of the myriad problems in which chemistry can play a central role. They involve everything from engineering interfaces between computers or electronics and human brains to harnessing the power of chemistry in generating, storing, interconverting and deploying energy in all its forms. I strongly think that the future of chemistry lies in recasting itself as an informational science in the broadest sense. At the level of biology chemistry has already manipulated information in the form of sequencing and genomics; synthetic biology will take this capability to a whole new level. But there are other areas in which chemistry can serve to manipulate information, and part of what Whitesides is doing is challenging chemists to become informational scientists in hitherto unexplored areas like energy and transportation.

The essay ends with a systems-level view of chemistry that every chemist should keep in mind, even as she works in her narrow world of natural products, zeolites, ROMP or kinases.

Because chemistry contributes broadly to the foundations of technology, it is particularly difficult to guess its future impact: a new chemical reaction might be used to make a cancer therapeutic, or a chemical weapon. Some of the opportunities that seem within the reach of investigation, if not within the reach of solution—technologies that might substantially prolong life, or develop new forms of life, or lead to sentient systems that rival us in intelligence—will do both good and harm. At minimum, those of us whopursue these problems should accept an obligation to explain to our fellow citizens fully and clearly what we are doing, and why, and (to the limited extent we can) with what possible outcomes. Humankind will do what it will do, but at least everyone should understand—in so far as is possible—what the choices are, and what the consequences might be. Chemistry, if it takes more interest in (and responsibility for) the full scope of programs—from molecules, to applications, and to influence on society—may be able to use the very breadth of its connections to technology to help in this explanation.

Whitesides Image: Boston.com