Field of Science

Einstein's wonderful letter to David Hilbert: A message for our times

David Hilbert (born today in 1862) was one of the greatest mathematicians of the 20th century. He made incisive contributions to a remarkable range of mathematical fields, published a best selling textbook on mathematical methods in physics, laid out a famous list of twenty-three unsolved problems which still challenge the field's practitioners and was a kind of philosophical godfather to at least two generations of mathematicians. Under his influence German mathematics reached its zenith before it was scattered apart by the rise of totalitarianism.

Perhaps less known is Hilbert's friendly and sometimes not-so-friendly rivalry with Einstein. Einstein's two most serious mathematical competitors were Hilbert and Henri Poincare. Poincare came close to discovering special relativity. Hilbert came close to discovering the equations of general relativity. Unlike Einstein, both were men of prodigious mathematical talent. Einstein's own mathematical shortcomings are well known; he had to learn most of the mathematics he needed for cracking open general relativity from friends and colleagues, most notably Marcel Grossmann.

In 1915 Hilbert came very close to publishing the equations of general relativity before Einstein did. Einstein had given a lecture in Berlin on his tentative attempts at formulating the equations. Hilbert was in the audience and doubled his efforts to find the right formulas. In the end Einstein ended up finding the correct form of the equations just a few days before Hilbert. It's quite likely that Hilbert would have gotten there first had Einstein gotten stalled for some reason.

However this story may paint a false picture of why it was Einstein and not Hilbert who ended up inventing general relativity. The short answer is that it was not mathematics but physics that was at the heart of relativity theory. Hilbert was the greater mathematician among the two, but Einstein's physical insights and visualization of thought experiments were unparalleled in the history of physics. Like a select few scientists - Feynman, Faraday and Fermi come to mind - he saw the physics first and then dragged the math behind him later. He had already viewed gravity as a field of spacetime which could be deformed and pulled by the time he started thinking about the equations. Hilbert, like more traditional physicists, tried to solve the equations first and get to the physical picture later. 

Generally speaking, truly great and successful physicists are ones who see the physical picture first, and Einstein was in the front rank of this group. Thus even if Hilbert had gotten to the equations first, Einstein would still have won the day. His 1915 paper on relativity contains not only the equations but all kinds of amazing physical insights that would lead to observations on the bending of spacetime and the expansion of the universe.

The last word belongs to Einstein, not because he was a great scientist but because he was a great human being. After the whole nail-biting race was over, he wrote a sensitive letter to Hilbert that exuded generosity, acknowledged his own flaws and sought reconciliation and friendship. 

The letter is a role model for competition and disagreement, and should be a must read in this era of political disagreement and conflict. Ultimately Einstein showed that while physics is important, being good human beings is even more important.

Gertrude Elion: Nobel Laureate, inventor of lifesaving drugs, woman in science

It's Gertrude Elion's birthday today. Below is one of hundreds of typical letters of gratitude that she received when she was awarded the Nobel Prize for Physiology or Medicine in 1988.

The prize - one of a select few recognizing drug discovery - was awarded to her, George Hitchings and James Black for the discovery of life-saving medicines for cancer, organ transplantation, viral diseases and stomach ulcers. She was only the fifth women to get it.

Elion repeatedly used to say that such letters and the saved lives of their recipients had long since made up for any formal honors or degrees that she might have lacked. One such degree was the PhD. When Elion applied to PhD programs after graduating with high honors from Hunter College in New York City in 1938, in the middle of the Great Depression, fifteen colleges refused her scholarships or fellowships because she was a woman. Until then Elion, who had been raised in a strongly egalitarian household by a generous-minded father, never thought that her being a woman would make a difference. But in 1938 in did, and Elion persisted and succeeded against such odds.

If some men held her back, others like her father, her fiancé and George Hitchings pushed her ahead. Her fiancé was a young man with a promising career in statistics whom she fell in love with as a student at Hunter College. His death due to a bacterial infection that could be completely cured just a few years later by penicillin cemented two desires in Elion: to stay married to her work and to devote her life to curing human disease and misery. Throughout her life, when she was approached by men either with proposals of marriage or bewilderment that she was a female scientist, she cheerfully dismissed such overtures and simply moved on without holding grudges; her work would speak for itself.

Elion found a job at the company Burroughs Welcome (which later became Glaxo Smithkline) by sheer chance, when her father who had seen an ad in the paper asked her to reach out to them. She asked if she could interview there on a Saturday since she was attending classes for graduate school on weekdays. Fortunately the company said yes, and fortunately George Hitchings was also working there on a Saturday.

Hitchings was interested in the application of chemistry to medicine. At that point in history, all medicines had been discovered by trial and error, with the latest example being sulfa drugs. Scientists typically sifted through thousands of molecules like dyes and petrochemicals with the hope that one of them would show interesting activity against diseased cells. Antibiotics hadn't been invented yet. Hitchings wanted to make drug discovery more rational, and his hypothesis was that one should do this by looking at the difference between normal cells and abnormal cells such as cancer cells. He had worked on nucleic acids before and he knew that cancer cells used much more nucleic acid for growth and metabolism. Why not try to look at the structures of nucleotides and modify their chemical structures in order to "trick" cancer cells into using the wrong material?

Hitchings's idea gripped Elion and she spent the rest of her life exploring its manifestations in a spectacular manner. Hitchings never held her back from going out on her own and made sure she was always listed as an author on all the important papers. There was another woman in the lab named Elvira Falcon; she was both Elion's scientific partner and opera partner, and the two enjoyed regularly watching leading operas at the Met. For some time Elion kept on working part time on her PhD, but she finally decided to forgo an official degree because the dean would no longer let her work part time; he dismissed her by saying that surely she must not be serious about becoming a scientist if she was interested in only working on her degree part time. Elion's lack of a PhD shows both the burdens of the PhD system as well as the prejudice against scientists without PhDs.

Among half a dozen others, Elion discovered at least three breakthrough drugs which were the first of their kind and which are still used in diverse areas of medicine. She was a pioneer in both chemotherapy and antiviral therapy. In 1950 she made 6-mercaptopurine which cut the rate of death from acute childhood leukemia in half. Although it brought temporary remission, it could be combined with other drugs to increase lifespan. Elion was only thirty two when she discovered 6-mercaptopurine. Much more important than the specific drug was the new paradigm she unveiled; cancer could now be attacked by looking at chemical differences between molecules used by normal and cancerous cells. It's an approach that is at the heart of cancer drug discovery even today.

Another compound made by Elion was azathioprine. Azathioprine dramatically reduced the immune response and became the first immunosuppressant. Until then organ transplantation had been a nightmare, with violent rejection of kidneys, livers and other organs dooming patients to early deaths. Azathioprine made organ transplantation possible. Doctors who used it were heralded as miracle workers and received Nobel Prizes. The icing on the cake for Elion and Hitchings was being able to see and talk to patients whose lives they had played a direct role in saving, a rewarding experience that organizations really should confer on their scientists. The third important drug which Elion discovered was acyclovir, used against the herpes virus. This drug was discovered on the same basis as the anticancer drugs, by assuming that a compound similar to that used by the virus in its own metabolism would thwart its growth. Acyclovir is still used at the frontline when it comes to fighting viral diseases, not just for herpes but also against chickenpox, shingles and other infections. I quickly benefited from it myself when I came down with chickenpox.

Elion kept on working until the end of her life and died in 1999. It is difficult to overestimate how many lives she saved with her discoveries, and the steady stream of letters of gratitude she received were the best testaments to her work. She was working in a golden age of drug discovery where relatively cheap research would yield important medicines, FDA regulations were slim and drugs could be easily tested on patients. But the powerful paradigm she unearthed will always be a model for drug discovery. Today the pharmaceutical industry has largely supplanted the logic used by Elion with random screening of synthetic and natural molecules. Perhaps it's time to again refocus on Elion's paradigm and look for molecules that are similar to those used by diseased cells and tissues. Fortunately the field of cancer metabolism and cancer immunology are partly based on such thinking. The flame that Elion and Hitchings lit is still alive and seems to be aglow with new hopes and promises.

Physics Nobel Prize winners and second acts: A rare pairing

Luis Alvarez made a major contribution to geology and biology
with his son after winning a Nobel Prize in physics
A while ago I had a discussion with a friend about physicists who did significant work even after winning an honor such as the Nobel Prize. The examples are few but noteworthy; accomplishing one significant piece of scientific work is hard enough, so if you manage more than one it’s quite something. I decided to dig a bit deeper and looked at the list of all Nobel Prizes in physics starting from 1900 and found interesting examples and trends.

Let's start with the two physicists who are considered the most important ones of the twentieth century in terms of their scientific accomplishments and philosophical influence - Albert Einstein and Niels Bohr. Einstein got a Nobel Prize in 1921 after he had already done work for which he would go down in history; this included the five groundbreaking papers published in the "annus mirabilis" of 1905, his collaboration on Bose-Einstein statistics with Satyendranath Bose and his work on the foundations of the laser. After 1921 Einstein did not accomplish anything of similar stature but he became famous for one enduring controversy, his battle with Niels Bohr about the interpretation of quantum theory that started at the Solvay conference in 1927 and continued until the end of his life. This led to the famous paper on the EPR paradox in 1935 that set the stage for all further discussions of the weird phenomenon known as quantum entanglement.

Bohr himself was on the cusp of greatness when he received his prize in 1922. He was already famous for his atomic model of 1913, but he was not yet known as the great teacher of physics - perhaps the greatest of the century - who was to guide not just the philosophical development of quantum theory but the careers of some of the century's foremost theoretical physicists, including Heisenberg, Gamow, Pauli and Wheeler. Apart from the rejoinders to Einstein's objections to quantum mechanics that Bohr published in the 30s, he contributed one other idea of overwhelming importance, both for physics and for world affairs. In 1939, while tramping across the snow from Princeton University to the Institute for Advanced Study, Bohr realized that it was uranium-235 which was responsible for nuclear fission. This paved the path toward the separation of U-235 from its heavier brother U-238 and led directly to the atomic bomb. Along the same lines, Bohr collaborated with his young protégé John Wheeler to formulate the so-called liquid drop model of fission that likened the nucleus to a drop of water; shoot an appropriately energetic neutron into this assembly and it wobbles and finally breaks apart. Otto Hahn who was the chief discoverer of nuclear fission later won the Nobel Prize and it seems to me that along with Fritz Strassman, Lise Meitner and Otto Frisch, Bohr also deserved a share of this award.

Since we are talking about Nobel Prizes, what better second act than one that actually results in another Nobel Prize. As everyone knows, this singular achievement belongs to John Bardeen who remains the only person to win two physics Nobels, one for the invention of the transistor and another for the theory of superconductivity. Both of these developments were singularly important, not just for the physics of the 20th century but for the engineering of the 21st. And like his chemistry counterpart Fred Sanger who also won two prizes in the same discipline, Bardeen may be the most unassuming physicist of the twentieth century. Along similar lines, Marie Curie won another prize in chemistry after her pathbreaking work on radioactivity with Pierre Curie.

Let's consider other noteworthy second acts. When Hans Bethe won the prize for his explanation of the fusion reactions that fuel the sun, the Nobel committee told him that they had trouble deciding which one of his accomplishments they should reward. Perhaps no other physicist of the twentieth century contributed to physics so persistently over such a long time. The sheer magnitude of Bethe's body of work is staggering and he kept on working productively well into his nineties. After making several important contributions to nuclear, quantum and solid-state physics in the 1930s and serving as the head of the theoretical division at Los Alamos during the war, Bethe opened the door to the crowning jewel of quantum electrodynamics by making the first decisive calculation of the so-called Lamb shift that was challenging the minds of the best physicists. This work culminated in the Nobel Prize being awarded to Feynman, Schwinger and Tomonaga in 1965. If the rules of the prize did not limit it to three people, Bethe and Freeman Dyson would almost certainly have received a share of it. Later, at an age when most physicists are just lucky to be alive, Bethe provided an important solution to the solar neutrino puzzle in which neutrinos change from one type to another as they travel to the earth from the sun. There's no doubt that Bethe was a supreme example of a second act.

Another outstanding example is Enrico Fermi, perhaps the most versatile physicist of the twentieth century, equally accomplished in both theory and experiment. After winning a prize in 1938 for his research on neutron-induced reactions, Fermi was the key force behind the construction of the world's first nuclear reactor. That the same man who designed the first nuclear reactor also formulated Fermi-Dirac statistics and the theory of beta decay is a fact that still beggars belief. The sheer number of concepts, laws and theories (not to mention schools, buildings and labs) named after him is a testament to his mind. And he achieved all this before his life was cut short at the young age of 53.

Speaking of diversity, no discussion of second acts can ignore Philip Anderson. Anderson spent his entire career at Bell Labs before moving to Princeton. The extent of Anderson's influence on physics becomes clear when we realize that most people today talk about his non-Nobel Prize winning ideas. These include one of the first descriptions of the Higgs mechanism (Anderson is still regarded by some as a possible contender for a Higgs Nobel) and his firing of the first salvo into the "reductionism wars"; this came in the form of a 1972 Science article called "More is Different" which has since turned into a classic critique of reductionism. Now in his nineties, Anderson continues to write papers and has written a book that nicely showcases his wide-ranging interests and his incisive, acerbic and humorous style.

There's other interesting candidates who show up in the list. Luis Alvarez was an outstanding experimental physicist who made important contributions to particle and nuclear physics. He also designed the detonators for the bomb dropped over Nagasaki. But after his Nobel Prize in 1968 he re-invented himself and contributed to a very different set of fields; planetary science and evolutionary biology. In 1980, along with his son Walter, Alvarez wrote a seminal paper proposing a giant asteroid as the cause for the extinction of the dinosaurs. This discovery about the "K-Pg boundary" really changed our understanding of the earth's history and is also one of the most exemplary examples of a father-son collaboration.

There's a few more scientists to consider including Murray Gell-Mann, Steven Weinberg, Werner Heisenberg, Charles Townes and Patrick Blackett who continued to make important contributions after winning a Nobel Prize. It's worth noting that this list focuses on achievements after winning the prize; a "lifetime achievement" list would include many more scientists like Lev Landau, Subrahmanyan Chandrasekhar and Max Born.

Neither is research necessarily the epitome of a scientist’s career. It's also important to focus on non-research activities that are still science-related and in which many physicists excelled with zeal. A list of these achievements would include teaching (Feynman, Fermi, Bohr, Born), writing (Blackett, Feynman, Bridgman, Weinberg), science and government policy (Bethe, Compton, Millikan, Rabi) and administration (Bragg, Thomson, de Gennes, Rubia). Bonafide research is not the only thing at which great scientists excel; they do not rest on their laurels and keep on exploring multiple aspects of their chosen path until their last breath.

Infinite in All Directions: Freeman Dyson at 93

The author with Freeman Dyson at his 90th birthday celebration
One afternoon when I was in college, classes were getting characteristically dull, so I decided to step into the library for my weekly random stroll through the stacks. There, lying on the floor and covered with dust and neglect, was a book named "Disturbing the Universe", by an author I had never heard of before. Taking the book home, I was almost startled by the sheer range of the mind that wrote it and tore through it in one night. There was talk of nuclear weapons, and extraterrestrials, and T.S. Eliot, and number theory, and Yeats, and a life-changing ride with Richard Feynman, and space colonization, and growing up in wartime England. But it wasn't just the intellect that shone through. The prose flowed like silk, often glowing with eloquence, humanity and poignancy without sentimentalism. It ranged across the entire landscape of science, technology, politics and history, lovingly presenting ideas both big and small. How could a scientist write like this? The author also seemed to be friends with some of the greatest scientists of the twentieth century - Robert Oppenheimer, Hans Bethe, Feynman, Francis Crick. Whoever this Freeman Dyson was, I decided that he must be a very special person.

My first correspondence with him was in 2005 when the great physicist Hans Bethe who was Dyson's advisor at Cornell University died at the ripe age of ninety eight. Bethe who was one of the truly great minds and human beings of the 20th century continues to be a hero of mine. I sent Dyson a letter about Bethe which I had gotten published in the magazine Physics Today, and he immediately replied with warm appreciation. Much later when I was living in New Jersey, I realized that Dyson lived and worked only a half an hour or so away from me at the famed Institute for Advanced Study in Princeton. With some trepidation I decided to ask him for an audience. Knowing that even in his 80s he was a busy man who wrote books, traveled around the world giving talks and consulted with the government, I certainly did not expect a quick reply, if at all. In keeping with one of his signature habits, not only did he reply to my email almost instantly but invited me over for lunch and a conversation in his office. So began a memorable correspondence. Like countless friends of his around the world, I soon started addressing him as Freeman.

I remember the date - November 10, 2010. The leaves were still changing color as I parked my car and made my way to the brickstone building, struck by the serenity that had drawn Einstein, Gödel, Oppenheimer and von Neumann to the place. I walked into an office on the second floor and saw an elfin-looking man sunk deep in his chair, staring intently at a document on his computer screen. So intently that when I called out his name he did not hear it. The second time I called it out he jumped about two inches in his chair, and I immediately felt guilty about interrupting his reverie. But this was Freeman Dyson after all, a man whose powers of concentration were the stuff of cafeteria banter.

Like many others who have met him, I was immediately struck by his slight but impressively energetic frame, honest cackles of laughter, studied powers of concentration and most of all, his striking and intent gray-blue eyes full of endless curiosity and wonder. His brilliance combined with his deceptive frailty made him look like a wizard from an enlightened world. What followed was a uniquely memorable meeting lasting several hours. Talking to him was like taking a random walk around an exotic garden filled with intellectual treats. I struggled to keep up with both his quick stride and his nimble mind as we walked to the cafeteria. Once we got our lunch trays, our conversation ranged over a huge spectrum of topics ranging from politics and family to physics and biology. He was pointedly opinionated but also consummately cordial. I told him about modeling water molecules in proteins, he told me about his belief that it might be impossible to observe single gravitons. I told him about my father's intense love of books which he passed on to me, he told me about his father's notable contributions to music, conceived even as bombs were falling on London. I told him about my sister's family in Tasmania, he mentioned strolling through a forest in Tasmania that was the densest he had seen. Discussions about science were punctuated by warm reminiscences about colleagues and fond stories about his grandchildren - all sixteen of them. The meeting told me what I had already learnt from his books; Freeman Dyson is one of the most human of all scientists and thinkers, imbibed with an even greater concern for the well-being of humanity as for the mysteries of the universe.

By any definition he's one of the great thinkers and polymaths of the twentieth century. He was a founding father of quantum electrodynamics, was elected to the Royal Society at age 30, made important contributions to everything from quantum mechanics to spaceship design, became a professor at Cornell with no more than a B.A. but has received more than twenty honorary PhD degrees, contributed enough as a consultant to the defense establishment to receive the Fermi Award and contributed enough to the dialogue about science and religion to receive the Templeton Prize. He is a mathematician who is as adept at calculating continued fractions and shock absorber stresses as the energy levels in atoms. Even if you consider his purely technical ideas, his range is astonishing; at his 90th birthday celebration, his colleagues spoke of at least half a dozen major contributions in fields as diverse as solid state physics and astrophysics which had opened new areas of research and engaged scores of researchers for a decade or more. At 93 he continues to be active; only two years ago he wrote a controversial and highly cited paper on game theory. He has won every award except the Nobel Prize, and regarding that omission he wryly quotes Jocelyn Bell Burnell, another omitted Nobel Laureate: "It's better that people ask me why I did not win it rather than why I did".

What truly sets Dyson apart though is his command of the English language and his understanding and concern for human problems. The prose is spare and simple and yet luminous; as one of the reviews of his book described it, "full of no little blood and fire". These are qualities that are extremely rare among scientists, and especially among physical scientists. Dyson is as equally at home talking about the S-matrix and about diplomacy with the Soviets as he is mulling over T. S. Eliot's "Murder in the Cathedral". In his writing he offers at least as many original ideas in various fields as in his research. His vast imagination roams across ideas ranging from clever to preposterous and yet semi-serious; over the years he has invented Dyson spheres (featured in an episode of Star Trek) and has proposed that life could thrive better on comets than on distant planets. He has penned endearing - and enduring - portraits of his close friends Richard Feynman, Robert Oppenheimer, Hans Bethe and Edward Teller and demonstrates a rare grasp of the value of human imperfection. His reviews of books for the New York Review of Books are simply an excuse to hold forth on the human condition.

In other writings he has shown himself sympathetic to religion, thinking it to be as necessary to hope and survival as the tools of science. Unlike the so-called "New Atheists" Dyson believes that religion, with all its evils and flaws, has demonstrated itself at the very minimum to be a useful glue that binds human beings to each other in times of adversity. He is a non-denominational Christian who values religion for the sense of community it fosters. Taken as a whole Dyson's thoughts and writings are primarily about science as an instrument of human progress, but they are also equally about the role of history, poetry, literature and politics in making sure that science functions responsibly; when I was a somewhat zealous student of science in college, he was the first scientist who made me appreciate how important it is for a scientist to educate himself in the humanities. And never one to descend into unproductive hand-wringing, his writings glow with optimism and project a bright future for the human species, no matter how dismal the future might occasionally appear. I agree with his biographer Philip Schewe that far and beyond, Dyson will be best remembered as an original essayist.

Over the past few years Dyson has become much more well-known in the public eye for his skepticism regarding climate change, a view made popular in a lengthy 2009 New York Times magazine profile. This was always unfortunate. Both his views and the article were blown out of proportion. In reality, as can be readily judged when you talk to him, Dyson's opinion of climate change is mildly proffered, moderate to a fault and in the best tradition of the same skepticism that has guided science since its inception. He disapproves of faith in computer models and of the zealous dogmatism exhibited by some climate change activists, and both these points are extremely well taken. Ultimately Dyson is saying something simple; that science progresses only when there is a critical mass of skeptics challenging the status quo. It's not about whether the skeptics are right or wrong, it's about whether their voices are drowned out by the consensus. One of his favorite quotes is the motto of the Royal Society, an institution established by freethinkers in the shadow of a heavy-handed monarchy: "Nullius in verba" - Nobody's word is final.

Since our first meeting we have kept up a warm correspondence in person and over email. Every year when I meet him he inevitably invites me to have lunch at the Institute for Advanced Study and gives generously of his time; every meeting provides me with inspiration and ideas. He has recommended rare and underappreciated books by J. B. S. Haldane, H. G. Wells and P. M. S. Blackett which offered unique insights into science, war and the human condition. Among others, I in turn have gifted him books by Andrea Wulf on Alexander von Humboldt and by Peter Conradi on the tragic and brilliant wartime poet Frank Thompson, a fellow Winchester College student who he knew during his time there.

As a role model of science and humanism, I hope Freeman continues to offer us his wisdom and insights, and I look forward to congratulating him on his next milestone. Happy Birthday, Freeman!

Drones, Silicon Valley and biology: The future isn't here yet

There is an illuminating article in the WSJ that lays out the problems with routine drone delivery that have been plaguing companies like Amazon and Google. Turns out it's one thing to make drones fly, quite another to make them deliver well defined objects in even better defined locations.

Most of the problems with drone delivery that the article highlighted are not too surprising when you think about them. The drones have problems landing smoothly, their GPS has problems pinpointing the precise locations of homes and distinguishing obstacles from landing spots, and they can get caught in or destroyed by any number of obstacles, from power cables to flying birds. There are also some interesting social problems involved: for instance the engineers have to worry about whether people might be scared by drones or, conversely, be too enamored of them and try to steal them. The bottom line is that landing drones on a routine basis in heavily populated residential areas is a messy and unpredictable process that has turned out to be far more challenging than what it seemed to be.

It seems to me that the problems with landing drones could serve as a metaphor for Silicon Valley attempting all kinds of things beyond its core areas of expertise, most notably biology. Just like residential areas, the interiors of cells are crowded, messy and wet environments with water molecules, proteins and small molecules sloshing around against each other. Just like the drone GPS has a problem with resolution, cracking problems in the heart of the cell also suffers from a lack of resolution in terms of how much we can actually see at the atomic level; even our best techniques like NMR spectroscopy and x-ray crystallography are acutely limited with limited to both resolution and dynamics. And just like a drone can be stolen or feared, the complex machinery inside a cell can interact very unpredictably with an intruder from outside, like a small molecule drug; it can chew up the drug or turn it into something toxic. Finally, the regulatory hurdles that drugs have to face are orders of magnitude bigger than those faced by drones.

There have certainly been honest attempts to tackle the complexity of biology recently, most significantly through machine learning and simulation approaches. But what the problems with drone delivery indicate is that some humility is in order here: one would have thought that Amazon Drone Delivery would have been right on the heels of Amazon Prime 1-Day Delivery. The basic issue is the distinction between code and the physical world. Code is clearly human created, cities are community created and bodies are crafted by four billion years of evolution. With code you know exactly where everywhere is, and there are clearly well known guidelines for debugging. If you don't like it you can redesign it from the ground up; try doing that with either cities or flesh and blood. In case of cities and even more so in case of biology, we don't even know where the bugs are, let alone how to debug them. It's a brave new world where we very much make the rules as we go along.

Clearly the drone delivery goal turned out to be deceptively simple, and the idea of applying software to drug discovery and biochemistry will be even more so. That does not mean progress won't be made (in both drone delivery and computational biology) and it certainly does not mean that software engineers should give up on trying to "solve" drug discovery, but it does mean that they need to be in for a long haul filled with blind alleys, sunk capital and plenty of heartache.

As the article says, coders who moved from the messy world of atoms into the clean world of code are now being confronted with addressing the messy, daunting world of atoms again. And there is no assembly of atoms conceivably more complicated that the one typing these words. From one flying jumble of atoms to another typing jumble, Palo Alto has a long way to go and I wish them luck.

Leroy Hood and the tool-driven revolution in biology

The Galisonian view of science - named after historian of science Peter Galison - says that science is driven as much or even more by new techniques and instruments as by new ideas. Sadly most people have always placed theoretical ideas at the forefront of scientific revolutions, a view enforced by Thomas Kuhn's famous book "The Structure of Scientific Revolutions". But a study of the history of science shows that new tools have been as instrumental in opening up whole new areas of science as new ideas. In fact one may argue that ideas allow you to largely explain while novel tools allow you to largely discover new things.
From the viewpoint of tool-based science, scientists like Faraday, Rutherford, Woodward, and Lamb are as important as Newton, Dirac, Heisenberg and Pauling. To this list of tool-builders and users must be added the name of Leroy Hood. Hood is one of the most important pioneers of the genomics revolution. Seeing far ahead of most biologists in the 1980s when he was at Caltech, he invented four tools that were to revolutionize the theory and practice of genomics: the protein sequencer, the protein synthesizer, the DNA synthesizer and the DNA sequencer. At a time when most biologists positively looked down upon technology development and engineers, Hood blazed new paths in combining chemistry, instrumentation and biology. His tools not only allowed biologists to do things better, but allowed them to discover new things which they hadn't imagined before.
Luke Timmerman has written a valuable biography of Hood which would be of interest to anyone interested in the recent history of the gene. I picked it up encouraged by Keith's favorable review (…/veteran-biotech-reporter-l…) and am glad I did. My only reservation is that Timmerman could have done a much better job embedding Hood's inventions in the bigger story of genetics and molecular biology. There were parts of the book where I thought the science could have been fleshed out much more, so if you are looking for a concomitant work of popular science along with a biography, this is not really it.
Hood's essential qualities were ingrained during a vigorous upbringing in rural Montana. His father was a peripatetic telephone engineer who did not give praise easily. He and Hood's mother taught their children to be self-reliant, resilient and hard-working. Throughout his career Hood has been a force of nature, displaying these qualities to an unprecedented extent and leaving behind some of his more talented competitors by sheer tenacity and dedication. As he recounts, the most valuable class for him in high school was not math or science but debating. He was also his high school's star quarterback. Even now, at the age of 75, he runs 3 miles every day and does a hundred push ups. He has also combined great scientific talent with a passion for public speaking and entrepreneurship; through these skills he has raised hundreds of millions of dollars from universities, funding agencies and wealthy philanthropists and made millions of his own. He has given generously to the cause of middle and high school education. No obstacle has been daunting for him, and by any of the usual metrics his career has been stunningly successful; as his website points out, "in addition to his ground-breaking research, Hood has published 750 papers, received 36 patents, 17 honorary degrees and more than 100 awards and honors, and has founded or co-founded 15 biotechnology companies including Amgen and Applied Biosystems."
Hood got his undergraduate and graduate degrees from Caltech along with an MD from Johns Hopkins. Caltech sought him out as an assistant professor right after graduation. Hood's early contributions were to immunology where he figured out the basis of antibody diversity. But soon he began to broaden his horizons and became one of the first biologists to truly appreciate the impact of new technology on biology. He had an amazing talent to spot big picture problems, drive himself mercilessly to crack them and recruit world class people to solve them. Using his unique skill set he built the first protein sequencer and DNA sequencer and licensed them out to the company Applied Biosystems. The DNA sequencer is at the very heart of the genomics revolution. Gene sequencing is no longer just a tool for faster and more efficient molecular biology, but it has transformed itself into a formidable instrument to explore stunning new domains of biology, from the creation of new organisms to the cracking of the genetic code for all kinds of diseases to the exploration of the world's biodiversity. Hood's work showed that not only can technology enable science but it can actually give rise to new science.
Unfortunately Hood's grand visions and the size of his lab and research projects (at one point his lab numbered more than a hundred people) soon ran afoul of Caltech's desire to stay a small, tightly knit school. Very soon he had a falling out with the faculty. One of his students who is now the head of research at Merck was then a professor at the University of Washington. He persuaded the medical school at UW to invite Hood for a few lectures. The chairman of the department in turn persuaded Bill Gates to attend those lectures. Gates who had started taking an interest in biology in the late 90s was entranced by Hood and immediately agreed to endow a $12 million dollar faculty position at UW for Hood. Hood's moved to UW was accompanied by breathless press releases proclaiming that his appointment was one of the most momentous events in the history of the university.
At UW Hood became the father of a new science: systems biology. He was no longer content to just explore genes and whole organisms, instead he wanted to bring about a completely unified view of biology by connecting atoms to molecules to cells, all the way to whole organisms and ecosystems. It was a grand vision, and one which only someone like Hood could pull off. Systems biology is now a mainstay of cutting edge biological science, bringing together biologists, mathematicians, computer scientists and other. But Hood got there first, being one of the first scientists to bring together interdisciplinary subject experts.
Sadly it was here that Hood's failings become clear, and Timmerman pulls no punches in narrating them. Hood was a big picture thinker, not a detail-oriented person. He left the day to day running of his labs to postdocs and research associates. More importantly, he was terrible at interpersonal relationships. He almost never took interest in his students' lives, never picked up the check when he "took them out" for lunch and regularly played favorites. He was not an unkind person, but he was simply too busy, driven to succeed and tone deaf to the everyday human relationships that make any endeavor successful. He was not above claiming credit for others' discoveries, not intentionally but because of his relentless drive to finish that simply left him clueless about such things. He rubbed people the wrong way at Caltech and UW and found even the generous support at UW insufficient for his systems biology vision. Predictably enough, when some of his key allies passed away, he had a falling out at UW too after he tried to sell them a plan for an independent new institute. Confident that his friend Bill Gates would fund it, he went to see Gates at Microsoft, only to be turned away with an icy dismissal (Gates: "I never fund things that I think are going to fail."). Undaunted, Hood poured $5 million of his own money into the institute. Personally too he faced a tragedy: his wife Valerie who he had married out of college succumbed to Alzheimer's disease.
Since then, the Institute for Systems Biology in Seattle has become a thriving research institute that is at the forefront of investigating both basic and applied genetics. Hood continues to be a powerhouse, crisscrossing the world giving talks about how biology is going to revolutionize human life. The system's research may or may not help discover new cures for important diseases, but what's more important is the vision and accomplishment of one man in achieving all that: Lee Hood. Hood is a fantastic example of what happens when passionate tenacity for a cause, a deep appreciation of the impact of technology on science, a passion for entrepreneurship and a relentless pursuit of the big picture come together to create an explosive mix. In the DNA sequencers that are humming softly in hundreds of thousands of industrial and academic laboratories and hospitals around the world, reading and rewriting the code of life, Lee Hood's legacy keeps humming on too.