Perhaps, if it's done right. But the vision for the new center does not inspire me with much confidence. The center seems to mainly be a result of NIH director Francis Collins's conviction that gene-based drug discovery is the wave of the future. Collins is disappointed with the fact that Big Pharma has been unsuccessful with "translational genomics" in spite of spending millions of man hours and dollars. He thinks that if done right, this kind of translational approach will result in new drugs. As he makes it clear in his book "The Language of Life", Collins is a longstanding proponent of genomics-based medicine.
But isn't this what everyone has been saying ever since genome sequencing became possible? We all remember the hype about genomics enabling a new generation of 'rational' drugs based on intimate knowledge of genes and their protein products. The fact that this vision has not panned out could partly be ascribed to the lackluster efforts and the constant waves of lay-offs in industry, but maybe there's also a deeper reason why the optimism has hit a wall. Maybe, and experts have been saying this for a while now, it's simply because taking a genomics-based approach to drug discovery ignores all the other complexities of biological systems like signal-transduction and epigenetics. Discovering the gene and protein is one thing, understanding the intricate interactions of the protein as part of a multi-layered cellular communication network is quite another. We are still struggling to understand the very basics of how proteins and genes link up in cells to enable complex physiological and behavioral responses, let alone rationally design drugs to block specific parts of those responses. In the absence of such understanding, simply pinning your hopes on the promise of 'translational genomics' seems to me to be another big sink for money and personnel.
So what else can a government center for drug discovery do which could be more concrete and fruitful? Ironically, the article contains part of the answer when it highlights the complexity of biological systems stated above.
Consider this remarkable fact; in the last century, only two breakthrough treatments for mental illness have been developed, lithium for bipolar illness and chlorpromazine (Thorazine) for schizophrenia. Many other successful antipsychotic drugs were spinoffs of thorazine. Also consider that even today we have little clue about how these drugs work, let alone how to rationally design them. Thorazine likely affects multiple neurotransmitter pathways involving serotonin, norepinephrine, dopamine etc. While we have made great advances in the last fifty years, brain chemistry remains as complex as ever. At a molecular level, the main problem is in understanding the basic mechanisms and specificity through which a molecule as simple as dopamine binds to only certain subtypes of a neurotransmitter receptor, stimulates multiple second-messenger pathways to different extents and elicits a complex behavioral response. In this case we know most of the genes and we know most of the protein products, yet we are light years away from understanding how Thorazine works. Lithium is an even more mysterious substance whose workings are almost akin to black magic. Instead of chasing the genes, thoroughly understand the action of a few of these drugs on a biochemical level and we can make significant inroads into understanding brain chemistry.
So if there's one thing a new government center for drug discovery can do, it should be to focus on these specific problems in the most general way rather than pool together resources for "translational genomics". Doing translational genomics will simply mean advancing work which industry is already involved in; it will largely be more of the same and there's good reasons why it may not work.
The government has always been good at this kind of free-for-all interaction among talented scientists who are unencumbered by research funds and job insecurity. A new government center for drug discovery could be a great idea, but only if it provides the kind of freedom to operate that brings out the best in creative minds. Focusing on translational genomics to me seems to be another way to repeat what has been done and to waste more funds, time and personnel. Instead, do what the government does best; let them think, and let their minds soar.
Fekry, M., Tipton, P., & Gates, K. (2011). Kinetic Consequences of Replacing the Internucleotide Phosphorus Atoms in DNA with Arsenic ACS Chemical Biology DOI: 10.1021/cb2000023
Linus Pauling seems to be voted at the top by common consensus. But to me the lack of agreement on the other names seems to be both a tribute to the diverse nature of chemistry as well as an indicator of problems with its public image. Consider the numero uno himself. Rather than making one single, very deep contribution like Einstein's relativity or Heisenberg's uncertainty principle, Pauling became the greatest chemist ever through the sheer variety of contributions he made to disparate branches of chemistry: the quantum mechanical basis of chemical bonding, the structure of crystals, the structure of proteins and the molecular basis of genetic diseases to name a few. Some of these contributions do stand out for their depth but the name of the game here is "diversity" which is at the soul of chemistry. Pauling's contributions as well as his status as the leading scientist in his field also highlight the problems with the public perception of chemistry- the fact that the field lacks "big problems" which can be latched on to by the public imagination. For physicists it's the origin of the universe, for biologists it's evolution. But chemistry is usually seen as a utilitarian and enabling science which contributes to revolutions in other fields but lacks deep, defining questions of its own.
However I beg to slightly differ here. There is in fact one problem, as deep and fundamental as any in physics and biology, which is essentially chemical. This problem is the origin of life. Life started out unquestionably as a molecular event. Other disciplines certainly bear on this problem in important ways but the way the origin of life started off constitutes a quintessentially chemical conundrum. Darwin took off where chemistry left off; ironically it is the first step that's still the big mystery while the succeeding steps have been worked out in spectacular detail. More broadly, the origin-of-life problem boils down to the problem of self-assembly which is also important in other applied areas like protein folding and nanotechnology. So if chemists want to really pitch an abiding single problem in their field with important repercussions for the human race to the public, they cannot do better than the origin of life and self-assembly. They could start with origins and end by talking about amyloid, Alzheimer's disease and supramolecular circuits, covering a vast scientific landscape which demonstrates the reach and impact of chemical science.
But back to the greatest chemist ever. At its heart chemistry is an experimental science, more so than physics where mathematical elegance may play roles which are as important as experimental observations. Any list of greatest chemists should include some of the great experimentalists in the field, people whose contributions led to techniques that revolutionized the reach of chemistry. In the list of greats cited by the others, one name seemed conspicuously missing to me- that of Fred Sanger. Not only is Sanger the only person to win two chemistry Nobel Prizes, but the techniques that he discovered- protein and DNA sequencing- underlie all of modern biochemistry and the genomics revolution. If you want to make a case for a chemist fundamentally altering the progress of human life, Sanger is as good a case as any and his absence on the lists is surprising and regrettable. One can also talk about Kary Mullis and PCR, but Sanger's contributions encompass a much wider swathe of basic science.
If chemistry as a science has been driven as much by techniques as ideas, one can also talk about the pioneers of x-ray crystallography and NMR spectroscopy in the list of greatest chemists. However, since these contributions were necessarily group efforts it's not really possible to single out individuals, although people like Perutz, Bernal, the Braggs and Hodgkin are certainly worthy candidates. Chemistry as a science is also uniquely distinguished from other sciences by its ability to make new things, so the inclusion of synthetic chemists like Woodward and Fischer is mandatory and has duly been acknowledged. With exciting developments in protein and nano-material design looming on the horizon, who knows what new creatures would populate this traditional looking roster of synthetic giants in the future.
The fact remains that chemistry is much too diverse to be pigeonholed into narrow "big idea" boxes. But rather than bemoan this fact, chemists should proudly wear it on their lapel since it demonstrates the exhilarating possibilities inherent in chemistry's expanse. An expanse which announced its presence with the origin of life.
Close documents the initial theoretical efforts by Wolfgang Pauli, Enrico Fermi and others to explain atomic processes like beta decay by invoking the neutrino. But the real heroes in the story are the experimentalists who spent their entire careers and gambled their scientific lives in dogged pursuit of this ghost particle. It was Bruno Pontecorvo, a protege of Fermi who realized that one could set up chlorine tanks near nuclear reactors to detect the existence of neutrinos. Pontecorvo also proposed other creative and theoretical ideas to capture and analyze neutrinos. He certainly deserved and would probably have won a Nobel Prize had he lived long enough and not defected to the Soviet Union. After Pontecorvo, the great modern heroes of the neutrino story are Raymond Davis and John Bahcall who spent their lives making heroic efforts to nail down the identity of Fermi's "little neutral one". Davis read Pontecorvo's paper in the early 50s and decided to set up an ambitious experiment with a chlorine tank several kilometers underground in an abandoned mine. The location was necessary to shield out other radiation from cosmic rays and capture only neutrinos, which being massless can travel virtually unimpeded through the earth. At the same time their lack of charge and mass makes their interaction with matter very rare and fleeting. Bahcall was a theoretical wizard who provided increasingly accurate estimates of the rate of capture. Half a century of almost obsessive work by the two men won Davis a Nobel Prize in physics, which he should have shared with Bahcall.
The story also has amusing side-lines, such as when a group of physicists called a nearby nuclear power station to correct their calculations for antineutrinos produced by the reactor. Not knowing what an antineutrino was, the reactor personnel assumed that the particle was harmful and that the physicists were environmentalists, and they tried to assure the scientists that "no antineutrinos were being produced" which would have been impossible and violated some fundamental laws of physics. One of the most intriguing discussions in the book documents the resolution of the so-called "solar neutrino problem". The generation of neutrinos in the processes that produce solar energy had been described by Hans Bethe and others. But the actual rate of detection turned out to be far less than the theoretical postulated rate. Something was missing and this caused a lot of angst for several decades. Bahcall and Davis gambled their entire careers on this paradox. A lot of creative, Nobel Prize caliber work by many scientists involving the decay of other novel particles like muons and pions finally revealed that the neutrinos emitted by the sun were actually changing their identities between two "flavors" called electron and muon neutrinos. This process was termed neutrino oscillation. The underground detectors could detect only one flavor of neutrino, explaining the discrepancy between theory and experiment. It was one of particle physics's resounding triumphs and revealed among other things that neutrinos have a vanishingly small but finite mass.
The tremendous work with neutrinos in the 20th century has led to the flourishing of a branch of astronomy called "neutrino astronomy" in the 21st. The study of the types, numbers, directions and flavors of neutrinos can shed valuable light on astrophysical processes taking place inside exotic objects like supernovas millions of light years away. Some of the facilities set up to detect neutrinos involve football field sized underground detectors filled with hundreds of tons of material located in some of the most extreme environments on the planet like the South Pole in order to avoid interference from other sources. Neutrino astronomy has turned physicists into intrepid explorers traveling to the far reaches of the planet. Their work is ensuring that we now have an additional window into the workings of the farthest and deepest reaches of the cosmos. But as Close excitingly documents in this slim volume, the foundation for all these exciting developments was laid by the theoreticians and experimentalists who participated in some of the most exciting races and pursuits of particle physics during the twentieth century. It's a story that's as rousing as any in science.
For doing this it’s extremely valuable to turn the question around and ask what we would do if we were to announce our presence. What kind if messages would we send to a potential ET listener? This line of questioning is valuable but it always includes the significant pitfall of suffering from anthropocentrism. It’s all too easy to believe that ET thinks just the way we do. Nonetheless, thinking from a human perspective opens the way toward understanding various potential forms of communication. So with the caveat that we should not constrain ET to fit our shoes too well, it’s worth pursuing this direction of thinking.
Assuming that the listening civilization is at least as advanced as ours and possibly more and assuming that they are actively listening and sending, the central requirement is that the message should be unambiguously construed as ‘artificial’ and not of natural provenance. The message should thus clearly seem artificially ‘designed’. This requirement is harder to satisfy than it seems. As we are well aware, there are numerous examples of natural entities which suffer from the ‘illusion of design’. Seashells, snowflakes, the myriad anatomical structures inside organisms and life itself all suffer from the illusion of design. No wonder that creationists and intelligent design proponents have seized on all of these and declared them to be the work of an intelligent designer. In fact, if we didn’t know better about the process of evolution and natural selection that has fashioned these complex structures, we too would think of them as designed, and indeed we did until Darwin came along and produced his great piece of work. Thus, when selecting a message to transmit, we need to be careful that it can be clearly distinguished between one which is natural but creates an illusion of design and one which must be actually designed by intelligent beings like ourselves. This requirement for making sure that a message looks designed has led the radio astronomy camp to suggest sending out messages that communicate prime number sequences. If after waiting for some time, we receive a message containing the next prime number in the sequence, we could be almost certain that the message was sent by beings who had discovered mathematics and factorization and who therefore could be considered ‘intelligent’.
Based on this background, I asked myself the following question as I drove on a particularly monotonous stretch of interstate highway:
‘As a chemist and especially as an organic chemist, how would I transmit a molecular message to an alien civilization such that the message would almost certainly be construed as designed by an intelligent being?’
Now organic chemists are well aware of differences between naturally occurring and artificially synthesized molecules. Chlorophyll, penicillin and quinine are examples of naturally occurring molecules while nylon, Viagra and LSD are unambiguously synthetic. Thus a chemist’s impulsive reaction might be to suggest sending samples of nylon or LSD out to potential ET listeners as decidedly ‘designed’ entities. But recall what we said about creating the illusion of design. Viagra may be man-made, but there’s really no reason why it cannot be made by nature in principle, even if it may be very unlikely in practice. Nature is wonderfully adept at producing an astonishing variety of molecular structures. For all we know, we might find Viagra someday as a vital communication molecule in some obscure marine sponge. To provide the strongest evidence of artificial design, we need to send a molecular message that is unlikely to be naturally designed not just in practice but also in principle.
Along with radio and infrared waves, we should thus also try to probe the presence of deuterated compounds in deep space. Fortunately we have several spectroscopic techniques to detect deuterium that include sensitive mass spectrometry methods. The problem with deuterium is that it might be hard to detect against the abundant background of normal hydrogen. Tritium could have been possibly used to circumvent this problem since its radioactivity would make it stand out against the background. Unfortunately the half-life of tritium is only 12 years so it’s useless as an emissary of interstellar communication.
For any intelligent civilization, the advantages of sending out deuterated molecules would be many. For one thing, virtually any all-D molecules would do the trick. Simple molecules containing D are as unlikely to have been naturally synthesized as complex molecules. As noted above, even all-D benzene could be a signature of intelligent life. So would all-D methane. Using simple heavy water (D2O) is another option. This wide berth in picking the exact molecular structures frees us up to focus on optimizing other important properties of the molecules like resistance to the rigors of outer space (extreme heat, cold, radiation etc.). Since even simple D containing molecules would serve our purpose, chemists won’t have to go to great lengths in terms of the actual synthesis. Plus as mentioned above, even partial enrichment in D would work.
This strategy of transmitting isotopically enriched molecules could be extended to other elements. What about carbon, the element of life? The most abundant isotope of carbon is carbon-12 (C12). C13 makes up about 1% of the rest while radioactive C14 comprises as little as 0.0000000001%. Just like T, C14 is a potentially valuable but unfortunately useless isotope because of its half-life of 5700 years. That leaves C13 as the ideal candidate. Similar to D, the probability of a molecule naturally enriched in C13 is tiny, and therefore the discovery of a C13 enriched molecule would also strongly suggest an artificial origin. But C13 has other advantages. It is a magnetically active isotope of carbon which can be detected using Nuclear Magnetic Resonance (NMR) spectroscopy; organic chemists use it all the time in deducing the structures of complex molecules by enriching them in C13. A molecule enriched in C13 would not only signify an artificial origin but it would also provide the added bonus of revealing its own identity through NMR spectroscopy. Just like a message containing prime numbers would reveal knowledge of mathematics, a message containing a swarm of C13-enriched molecules would reveal knowledge of chemistry and NMR spectroscopy. Quite adequate for concluding the presence of intelligence.
I propose therefore that the search for extraterrestrial intelligence should include the search for molecules enriched in deuterium, carbon-13 and minor isotopes of other elements in addition to more traditional signals like electromagnetic radiation. If we wished to communicate our existence and intelligence to other civilizations, we would not constrain ourselves to physics and astronomy but would also employ chemistry, biology and every other tool at our disposal. The discovery of intelligent life in the universe is too important to be left to the vagaries of a single or a few approaches. One of the signs of intelligence is the ability to make the most out of diversity. We can only expect other intelligent civilizations to behave accordingly.