The bundle of non-truths that's Deepak Chopra

You can always trust Deepak Chopra to put a positive spin on pseudoscience and casually pummel straw men and misrepresent facts while he is at it. His latest favorite concerns experiments done by Nobel laureate Luc Montagnier (the co-discoverer of the AIDS virus) who has ventured into highly questionable scientific territory by trying to demonstrate that DNA can imprint its "memory" on water even at great dilutions, which basically boils down to pushing homeopathy. Unless supported by massive evidence, there's no need to take Montagnier's results seriously for now. But as usual for Chopra, this is a resounding victory of what he considers to be the "inconvenient truths" of science. And as usual, Chopra's greatest achievement is the remarkable number of strawmen, non sequiturs, misguided conclusions and plain misrepresentations he manages to include in a single article.

Chopra starts by extolling what he sees as the "fraying of science at the edges" done by scientists themselves.

"What delights me about this controversy, which will be won by the skeptics, naturally, is that conventional science is fraying around the edges, and the fraying is being done by scientists themselves. A decade ago, for example, you couldn't find more than a small handful of physicists and biologists who were willing to consider that the study of consciousness was reputable. This year there will be conventions on the subject with hundreds of participants. This isn't because there's been an outbreak of rebelliousness in labs across the globe. Rather, there was nowhere else for the trail to go. You can't discuss memory, either in the human brain or in water, without explaining consciousness"

First of all, science has been "frayed" at the edges by scientists for hundreds of years; it's called scientific progress. One can argue that any new revolutionary result or theory pushes the envelope and tries to redefine the boundaries of conventional science. But this has nothing to do with Montagnier's experiments or the paranormal and only time will tell if these results will challenge "conventional" science. And of course in Chopra's definition, "unconventional" science is new-age mysticism whereas most scientists define it as new but still concrete and validated results that advance our understanding. Secondly, Chopra is just constructing a straw man with his quip about consciousness. He tries to make consciousness sound like some kind of non-material entity whose existence scientists are now being grudgingly forced to accept. That's just plain wrong. Consciousness has long since been thought to be a function of the basic biology and chemistry of the brain. No scientist worth his salt who is researching consciousness believes that it's supernatural or somehow outside the purview of science. If you doubt this, just read noted neuroscientist Vilayanur Ramachandran's latest book to understand how scientists are boldly tackling consciousness; you will find them all using novel but standard scientific tools like MRI and CT scans. The only "rebelliousness" that Chopra talks about is in the fact that we can now actually tackle the problem of consciousness using modern scientific methods. Most scientists think consciousness is a remarkable phenomenon, but only Chopra thinks that it's remarkable because it's paranormal and outside the boundaries of traditional science.

Further on Chopra cannot help but tar the founders of quantum theory, a discipline whose real understanding he completely lacks and which he himself has done so much to dress up in mumbo jumbo and completely misrepresent.

Popular books like The Tao of Physics and God and the New Physics played an enormous role in the general culture. But their impact on professional physicists has been slight and gradual. That's because physics is based on materialism. Anything that isn't a thing, any phenomenon that cannot be measured, doesn't belong in physics. But the solid, material world vanished a hundred years ago, and almost all the quantum pioneers, such as Einstein, Bohr, Heisenberg and Schrödinger, either became outright mystics or remained baffled by the radical discovery that the universe emerged from a void"

No. The solid, material world did not "vanish" with the advent of quantum mechanics. In fact if anything it became even more fortified because quantum mechanics helped us understand it better. The predictions of quantum theory were taken seriously only because they agreed with measurements in the material world to an outstanding degree of accuracy. And while some of the founders of quantum theory were great philosophers and interested in "mysticism", every single one of them always emphasized that quantum mechanics is only as good as its compatibility with hard experimental data on material objects. As Bohr himself said, "Physics only tells us what we can say about the world". In fact it is a triumph of traditional "materialist" science that some of the most bizarre predictions of quantum theory like entanglement are now being validated through meticulous experiments. By declaring that the founders of quantum theory became outright mystics, Chopra grossly misrepresents and insults their great contributions to science.

Further on Chopra again wants to convince us that the "wall between science and consciousness has broken down". Again, the wall is probably breaking down but only because of hard scientific experiments that are allowing us to actually study the phenomenon, not because of new-age thinking emerging from pseudoscience. I could go on, but what's the point? Deepak Chopra, in Derek Lowe's words, has been a "firehose of nonsense". He wants to portray every scientific development as some kind of maverick paradigm shift which is forcing scientists to re-evaluate material reality itself. Yes, there are paradigm shifts in science, but they come about because there's massive amounts of actual data, not because some isolated experiment whose results are inexplicable require scientists to believe in the paranormal. Chopra is about as misguided as they get.

A government center for drug discovery?

The New York Times has an article about a new center for drug discovery that the government is going to set up in the face of the declining pace of new drug discovery in the pharmaceutical industry. We all know what's wrong with the industry, with the numero uno factor being the pursuit of short-term profit goals at the expense of basic science and long-term benefit. The question is, can the government make up for this shortfall?

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.

Here's what I think instead. If the center truly wants to do something productive that pharmaceutical companies cannot, let it put together a mini Manhattan Project type team focused on understanding a few specific problems, like how lithium works in the brain. The problems should be picked based both on their medical importance and their potential impact in enabling general understanding of the field. Just like the Manhattan Project did, get together the best people in the country from several disciplines who are experts at multidisciplinary thinking and problem solving. If you want to attack the lithium problem for instance, get together chemists, biologists, neuroscientists, pharmacologists, doctors and perhaps even a few physicists, mathematicians and computer scientists. Put them in a couple of large rooms (and maybe even seclude them in the majestic mountains of New Mexico) and give them enough funds. And then most importantly, give them almost complete freedom to brainstorm about specific problems. Let them consider every possible approach, from running basic biophysical experiments to the most advanced neural imaging techniques. Don't limit yourself to any one philosophy like translational genomics or any other currently fashionable mantra. Genomics can certainly be part of the mix but it should not be put on a pedestal. Combine the oldest tools of classical pharmacology with the newest tools of molecular biology. If the industry has been missing one thing, it's been the presence of bright young people who are given complete freedom to focus on their diverse ideas without strings attached and constant fear of unemployment. The government can give these men and women what industry has taken away from them in recent years.

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.

Phosphorus beats arsenic...by a factor of seventeen powers of ten

For all the implications about little green men and alien bacteria, the real question at the heart of the great arsenic controversy was essentially chemical: Can arsenic substitute phosphorus in the key biomolecules and metabolic processes of life and especially those in the GFAJ-1 bacteria? I and others referred to a classic paper published many decades ago by the eminent Harvard chemist Frank Westheimer which pointed out the instability of arsenates compared to phosphates. This is still the central chemistry-based question in everyone's minds. In a just accepted article in the journal ACS Chemical Biology, researchers in Missouri and Cairo provide a nice overview of the great challenges associated with substituting As in place of P in the backbone of DNA.

They start off by pointing to the similarities between the two elements; similar atomic size, pkA values (which would allow similar acid-base behavior) and electronegativities. These similarities would lead us to believe in the ready replacement of P by As, but that's where they end. From here on the devil is in the details.

Experiments have been conducted with model compounds approximating the phosphate diester backbone in DNA and its putative As counterpart. Firstly the authors note that the phosphodiester backbone is really stable to hydrolysis (the cleavage of the bonds by water), so stable in fact that it's difficult to measure its rate of hydrolysis in DNA because of the slow rate of the reaction. This has led to many studies performed on model compounds where the two linkages to sugars in the DNA backbone have been replaced by suitable alkyl groups. These studies have measured the half-life of the phosphate diester linkage. The half-life of a reaction measures the time taken for half the reaction to finish and is a very convenient tool for quantifying its rate; in case of the phosphate diester compounds, it turns out to be a whopping 30,000,000 years. This is a huge achievement if you consider the very high concentration of water in cells which is 55 M. As the authors say, this means that only two out of the 3 billion base pairs in the DNA from a human cell are expected to undergo spontaneous, uncatalyzed hydrolysis per week. It is a testament to the amazing power of catalytic enzymes that this reaction is brought within reasonable time frames in biological systems. While the results from the model system constitute an extrapolation to DNA, it's a reasonable one since the accessibility of the P to attack by water in the model compounds is similar to that in DNA.

The corresponding arsenic diesters present a scenario that's out of the ballpark. The half-life of the model arsenate diesters is no more than 0.06 seconds which corresponds to a difference of a factor of 10¹⁷ between the two. This is an absurdly large number; as just one comparison, it exceeds the number of cells in the typical human body by a factor of ten thousand. Error bars will do nothing to change it. In fact the hydrolysis of arsenate diesters is so fast that this fact has been used productively by scientists who want to study the kinetics of phosphate containing molecules but who are thwarted by the extremely slow nature of the reaction; substitute the P with As and you get a system which will otherwise be similar but which will transform itself rapidly into the desired products. What biology abhors, chemists can adore.

The magnitude of the problem is driven home by the calculation that with this rate of hydrolysis, half of all the arsenodiester linkages in the DNA of the GFAJ-1 bacterium would be cleaved in less than a tenth of a second. In addition there are other problems with As. As the authors note, As can also change its oxidation states more easily compared to P. The oxidation state of As and P in the DNA backbone is +5. But unlike P, As can undergo ready enzymatic conversion to a +3 oxidation state. Compounds containing As +3 are even more unstable than those containing As +5.

Now does this mean that organisms substituting As for P cannot exist? No. But as basic chemistry demonstrates, this would present very great challenges of stability. As indicated, there could be possible solutions to this problem such as dehydrating conditions containing very little water or the presence of special proteins that stabilize DNA and shield it from water. But it's clear that any such extremely novel ideas would be speculative at best until supported by evidence.

I hate quoting Carl Sagan all the time but his statement about extraordinary claims requiring extraordinary evidence is a cliche because it's true.

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

How can we make the International Year of Chemistry successful?

2011 has been designated by the UN as the "International Year of Chemistry". As a community of chemists, for us the question is simple: What can we do to make this year successful and enhance the public's appreciation of chemistry? Here are three core aspects of chemistry which I think should be constantly highlighted:

1. Explain to the public the essential nature and unique philosophy of chemistry: As a field, chemistry is inherently more challenging to pitch to the public compared to physics or biology. If you are a physicist and you say to a layman that you are investigating the Big Bang, you don't have to say anything more to get his or her attention. A biologist who works on human evolution will get similar nods. But what about chemists? One of the reasons for the relatively dim public appreciation of chemical science was mentioned before; it is because the field apparently lacks "big ideas" that people can instantly latch on to (but see below). But what chemistry may lack in terms of the grand picture, it more than compensates for in terms of its identity as a "central science" and the sheer number of explanations and applications that it lends to almost every other discipline, from physics and biology to art and engineering. No other field does this in such a palpable way. In this sense chemistry is akin to engineering, but much more fundamental.

The chemist more than any other kind of scientist is a discerning arbiter of patterns and a patterner of chaos. One of the most striking manifestations of this quality is in the beautiful structures that chemists draw and encounter every single day. Chemists look at structures the way artists look at mosaics of colors and architects look at geometric patterns of tiles. What other kind of scientist spends his or her professional workday doodling and evaluating lines, rings and their myriad intersections? In its ability for visualization and pattern analysis, chemistry comes closer to art than any other science, and the public needs to appreciate this supremely important aspect of the discipline.

But it is in its ability to make new things which never existed before that chemistry is wholly unique. In the last few years synthesis and especially total synthesis have taken some flak as somewhat self-serving activities geared toward factory-style publication and the nurturing of slave labor, but it cannot be denied that synthesis is what makes chemistry different from all other disciplines. No other science can boast the creation of new substances that have improved every facet of human life, from the conquest of disease to the feeding of the poor. Of course chemistry also led to poison gas and nerve gas but this was true of other disciplines too. The fact remains that chemistry has modeled and sculpted the material world familiar to the layman more than any other science. Other fields provided valuable input to the principles behind synthesis, but the end products were those of chemistry alone, shining examples of the very ability of human beings to create, manipulate and improve. In the future chemistry promises us improved materials for alternative energy and designer drugs and biomolecules for treating disease. Convince the layman of the enduring centrality of synthesis, and you would have convinced him or her of the essential value of chemistry.

2. Push the origin of life as chemistry's "big idea": We mentioned above that chemistry seems to suffer from a lack of big ideas as compared to physics and biology and that this is partly responsible for its lackluster public perception. But as I indicated in my last post, there is actually a problem as big as any other which is primarily within the domain of chemistry. This is the origin of life within its broader framework of self-assembly. God must have been a molecular self-assembler, because without self-assembly the first components of life could not bond to each other and the first cells could not form and segregate their cargo, sparking the interactions and reactions that led to replication and metabolism. Darwin solved the second problem of what happens when life gets started, but not the first one of how it all began. Again, other sciences will continue to contribute to the unraveling of this problem, but the first step was uniquely chemical. A narrating of the origin of life as a quintessentially chemical question would also lead to a general exposition on self-assembly (important in diseases caused by protein misfolding) as well as a spirited homily on the central importance of weak interactions and hydrogen bonding.

3. Emphasize the crucial connections of chemistry with medicine and materials science again, and again and again...: It's official. The biggest practical contributions of chemistry to the betterment of human life have undoubtedly been in the discovery of new drugs and new materials. It is remarkable that every one of us benefits from these tangibles at every moment of day and night and yet fails to recognize the essential role that chemistry played in their creation. Since almost all of us know someone who has been afflicted or taken by a terrible malady, one would think that the public would be singing chemistry's praises for saving lives. Yet most people seem to think that it's doctors who discover new medicines. Quiz people about great medical advances and they would enthusiastically tell you about Alexander Fleming and Jonas Salk, but not about Gerhard Domagk or Gertrude Elion. This perception has got to change. Chemists are as responsible as doctors, if not more, for most of the live-saving drugs developed in the past century and will be responsible for many more in the coming one. The era of rational drug discovery was essentially ushered in by chemistry, and it will likely bring us novel advances in the form of designer proteins and small molecules as selective drugs against new threats. The public needs to know this crucial function of chemistry, and it can only be accomplished by drilling the facts into the public's mind eloquently and ad nauseam.

The other field where chemistry promises world-changing discoveries is in materials science and nanotechnology, especially as applied to energy. With climate change looming on the horizon, the next generation of breakthrough solar cells or other technologies may change the lives of millions, dramatically reduce our carbon footprint and impact the international geopolitical landscape. A central player in this seismic shift will undoubtedly be chemistry. The public now thinks very highly of nanotechnology but very few people realize that chemists have been practicing nanotechnology since their discipline gradually emerged from the shadows of alchemy. Polymers have revolutionized our lives as much as anything else. In the future polymers will contribute in novel ways such as drug delivery vehicles and smart materials in electronics engineering and space science. Organic electronics is another lucrative area of polymer science which will pay huge dividends in improving communications technology, leading to improvements in everything from healthcare to education. As the world inches closer to potentially devastating climate change and its global and social repercussions, chemistry will undoubtedly play its important role in saving the planet.

By bridging all other disciplines, enabling human progress and knitting the tapestry of the material universe, chemistry encircles the world. This is our chance to let everyone know.

Image source

The "greatest" chemist ever, and the nature of chemistry

Let's kick off the International Year of Chemistry with one of those somewhat pointless but endearing and endlessly entertaining questions: Who was the greatest chemist ever? Paul@Chembark and the Nature Chemistry crowd have dived into the discussion by conducting informal polls.

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.

Ye olde physicists

"When I try to explain chemistry to outsiders, I have three main audiences: the person in the street, fellow academics in the humanities and physicists. All three audiences are equally ignorant of chemistry, but the most difficult audiences are the physicists, because they think they understand, but they don't."

-Roald Hoffmann

Ouch.

What mad pursuit...

These days we are all excited about the Higgs boson, but as Frank Close reminds us in his lucid and comprehensive yet succinct book, the real heroic efforts in particle physics of the twentieth century were in pursuing and hunting down the elusive neutrino. The neutrino is copiously produced by solar processes and every second billions of neutrinos astonishingly pass through our bodies, yet the particle has no charge and for a long time was postulated to have no mass, which made its detection difficult to put it mildly.

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.

Better extraterrestrial communication through chemistry: What do aliens want?

The search for extraterrestrial intelligence has traditionally hinged on detecting electromagnetic waves, most commonly radio waves but also infrared and x-ray radiation. But in the absence of knowledge about the specific nature of extraterrestrial civilizations, we need to explore all sources of communication possible and not just ones based on electromagnetic waves. Thus the message we would send or receive could and should include everything from symbolic signals to actual physical samples of material signifying the presence of intelligent life. SETI is an endeavor fraught with such momentous potential significance that it would be foolish to hinge it on physics alone. We need to employ other sciences in its service.

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.

That is when it hit me that we could make a good case for an unambiguously designed message by transmitting molecules that have all or many of their hydrogen atoms replaced by deuterium. Recall that deuterium (D) and tritium (T) are the two isotopes of hydrogen. But they are spread out exceedingly thin among the major isotope of hydrogen (H) that we all know and love. Hydrogen is the most abundant element in the universe but deuterium comprises 1 atom in about 6000 of hydrogen and amounts to only 0.02%, while tritium is even scarcer. These isotopic abundances of D and T are constrained by the fundamental laws of physics governing nuclear stability and are extremely unlikely to be different under any circumstances anywhere in the universe. Given the universal low abundance of D, the probability of, say, a molecule of benzene containing only D being synthesized naturally in the universe under any conditions is vanishingly small. On the other hand, organic chemists can and do make molecules containing D using their bag of chemical tricks. Thus, the discovery of a deuterated molecule in outer space should point almost unambiguously to an artificial origin. The molecule need not even be fully deuterated since even partial deuterium enrichment is very unlikely to occur naturally. Full replacement by deuterium would cinch the evidence, however.

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.