Field of Science

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 (http://omicsomics.blogspot.com/…/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.

Oppenheimer's folly: On black holes, fundamental laws and pure and applied science

On September 1, 1939, the same day that Germany attacked Poland and started World War 2, a remarkable paper appeared in the pages of the journal Physical Review. In it J. Robert Oppenheimer and his student Hartland Snyder laid out the essential characteristics of what we today call the black hole. Building on work done by Subrahmanyan Chandrasekhar, Fritz Zwicky and Lev Landau, Oppenheimer and Snyder described how an infalling observer on the surface of an object whose mass exceeded a critical mass would appear to be in a state of perpetual free fall to an outsider. The paper was the culmination of two years of work and followed two other articles in the same journal.

Then Oppenheimer forgot all about it and never said anything about black holes for the rest of his life. 

He had not worked on black holes before 1938, and he would not do so ever again. Ironically, it is this brief contribution to physics that is now widely considered to be Oppenheimer’s greatest, enough to have possibly warranted him a Nobel Prize had he lived long enough to see experimental evidence for black holes show up with the advent of radio astronomy.

What happened? Oppenheimer’s lack of interest wasn’t just because it was published on the same day on which World War 2 was launched. It wasn’t because he became the director of the Manhattan Project a few years later and got busy with building the atomic bomb. It also wasn't because he despised the freethinking and eccentric Zwicky who had laid the foundations for the field through the discovery of black holes' parents - neutron stars. It wasn’t even because he achieved celebrity status after the war, became the most powerful scientist in the country and spent an inordinate amount of time consulting in Washington until his carefully orchestrated downfall in 1954. All these factors contributed, but the real reason was far more mundane – Oppenheimer just wasn’t interested in black holes. Even after his downfall, when he had plenty of time to devote to physics, he never talked or wrote about them. The creator of black holes basically did not think they mattered.

Oppenheimer’s rejection of one of the most fascinating implications of modern physics and one of the most enigmatic objects in the universe - and one he sired - is documented well by Freeman Dyson who tried to initiate conversations about the topic with him. Every time Dyson brought it up Oppenheimer would change the subject, almost as if he had disowned his own scientific children.

The reason, as attested to by Dyson and others who knew him, was that in his last few decades Oppenheimer was stricken by a disease which I call “fundamentalitis”. Fundamentalitis is a serious condition that causes its victims to believe that the only thing worth thinking about is the deep nature of reality as manifested through the fundamental laws of physics.

As Dyson put it:

“Oppenheimer in his later years believed that the only problem worthy of the attention of a serious theoretical physicist was the discovery of the fundamental equations of physics. Einstein certainly felt the same way. To discover the right equations was all that mattered. Once you had discovered the right equations, then the study of particular solutions of the equations would be a routine exercise for second-rate physicists or graduate students.”

Thus for Oppenheimer, black holes, which were particular solutions of general relativity, were mundane; the general theory itself was the real deal. In addition they were anomalies, ugly exceptions which were best ignored rather than studied. As Dyson mentions, unfortunately Oppenheimer was not the only one affected by this condition. Einstein, who spent his last few years in a futile search for a grand unified theory, was another. Like Oppenheimer he was uninterested in black holes, but he also went a step further by not believing in quantum mechanics. Einstein’s fundamentalitis was quite pathological indeed.

History proved that both Oppenheimer and Einstein were deeply mistaken about black holes and fundamental laws. The greatest irony is not that black holes are very interesting, it is that in the last few decades the study of black holes has shed light on the very same fundamental laws that Einstein and Oppenheimer believed to be the only thing worth studying. The disowned children have come back to haunt the ghosts of their parents.

Black holes took off after the war largely due to the efforts of John Wheeler in the US and Dennis Sciama in the UK. The new science of radio astronomy showed us that, far from being anomalies, black holes litter the landscape of the cosmos, including the center of the Milky Way. A decade after Oppenheimer’s death, the Israeli theorist Jacob Bekenstein proved a very deep relationship between thermodynamics and black hole physics. Stephen Hawking and Roger Penrose found out that black holes contain singularities; far from being ugly anomalies, black holes thus demonstrated Einstein’s general theory of relativity in all its glory. They also realized that a true understanding of singularities would involve the marriage of quantum mechanics and general relativity, a paradigm that’s as fundamental as any other in physics.

In perhaps the most exciting development in the field, Leonard Susskind, Hawking and others have found intimate connections between information theory and black holes, leading to the fascinating black hole firewall paradox that forges very deep connections between thermodynamics, quantum mechanics and general relativity. Black holes are even providing insights into computer science and computational complexity. The study of black holes is today as fundamental as the study of elementary particles in the 1950s.

Einstein and Oppenheimer could scarcely have imagined that this cornucopia of discoveries would come from an entity that they despised. But their wariness toward black holes is not only an example of missed opportunities or the fact that great minds can sometimes suffer from tunnel vision. I think the biggest lesson from the story of Oppenheimer and black holes is that what is considered ‘applied’ science can actually turn out to harbor deep fundamental mysteries. Both Oppenheimer and Einstein considered the study of black holes to be too applied, an examination of anomalies and specific solutions unworthy of thinkers thinking deep thoughts about the cosmos. But the delicious irony was that black holes in fact contained some of the deepest mysteries of the cosmos, forging unexpected connections between disparate disciplines and challenging the finest minds in the field. If only Oppenheimer and Einstein had been more open-minded.

The discovery of fundamental science in what is considered applied science is not unknown in the history of physics. For instance Max Planck was studying blackbody radiation, a relatively mundane and applied topic, but it was in blackbody radiation that the seeds of quantum theory were found. Similarly it was spectroscopy, the study of light emanating from atoms, that led to the modern framework of quantum mechanics in the 1920s. Scores of similar examples abound in the history of physics; in a more recent case, it was studies in condensed matter physics that led physicist Philip Anderson to make significant contributions to symmetry breaking and the postulation of the existence of the Higgs boson. And in what is perhaps the most extreme example of an applied scientist making fundamental contributions, it was the investigation of cannons and heat engines by French engineer Sadi Carnot that led to a foundational law of science – the second law of thermodynamics.

These days there is a lot of valid discussion about how the pursuit of pure science usually leads to unexpected applied results, but sometimes the opposite is also true: the pursuit of what Subrahmanyan Chandrasekhar called “derived science” leads to new horizons in pure science. Derived science consists of exploring the implications and results of pure science, but as the history of science has regularly demonstrated, this investigation can also feed back into the advancement of pure science itself.

Today many physicists are again engaged in a search for ultimate laws, with at least some of them thinking that these ultimate laws would be found within the framework of string theory. These physicists probably regard other parts of physics, and especially the applied ones, as unworthy of their great theoretical talents. For these physicists the story of Oppenheimer and black holes should serve as a cautionary tale. Nature is too clever to be constrained into narrow bins, and sometimes it is only by poking around in the most applied parts of science that one can see the gleam of fundamental principles.

As Einstein might have said had he known better, the distinction between the pure and the applied is often only a "stubbornly persistent illusion". It's an illusion that we must try hard to dispel. 

Seeing the 2016 election through Jonathan Haidt's moral foundations theory

One of the best social science books that I have read is NYU psychologist Jon Haidt's "The Righteous Mind". Recently Haidt has become well known for opposing what he sees as clampdowns on free speech and dissenting views on college campuses, the paucity or suppression of conservative views on these campuses and the coddling of students, but he is still primarily known for his writings on political psychology. As someone who describes himself as a moderate libertarian, I largely agree with Haidt's views on these matters.

The basic premise of "The Righteous Mind" is that liberals, conservatives and libertarians use different moral metrics to judge the veracity and fitness of political candidates and of their world views in general. Their outrage or praise at statements that politicians make depends on how well or badly these statements score on their spectrum of moral values. Haidt's point is that most of the disagreement on political issues between liberals and conservatives boils down to a subset of six moral 'foundations' that they score politics on. 

The six moral foundations are: care/harm, liberty/oppression, fairness/cheating, loyalty/betrayal, authority/subversion and sanctity/purity. Based on several studies conducted by him and his colleagues, Haidt has concluded that in general, liberals value the first three values disproportionately while conservatives value all six values equally. Thus as an example, liberals get very worked up about the oppression of minorities because it scores very badly on the "care/harm" and "liberty/oppression" metrics, while religious conservatives get very worked up by LGBT rights because it scores very badly on their "sanctity/degradation" and "liberty/oppression" metrics. Libertarians view the liberty/oppression axis as being as overwhelmingly important.

The following chart neatly illustrates these differences:


Haidt also refers to these moral foundations as sacred values, considering how intensely liberals and conservatives often cling to them. Seen through this lens of sacred values, it's very interesting to look at the Giant Conflagration of 2016 (otherwise known as the 2016 US election). When Trump said all those obnoxious things about Hispanics or women or Muslims, he scored very low on liberals' main moral values (the three on the left): by insulting certain racial or demographic groups, he was showing that he did not care about them, he was purportedly infringing on their liberties and he was also not being fair to them. As the chart shows, concern for the care and liberties of victims of oppression is liberals' most sacred value, although it is also valued highly by conservatives. Minorities and women are often thought to fall in this category, and so the violation of this value disqualified Trump in the eyes of liberals right away.

What they failed to realize was that he was still scoring very high on the three conservative values on the right. Many conservatives who supported him disavowed his words, but that wasn't why they would have a big problem supporting him. He was clearly showing loyalty to disgruntled working class whites, he was being an authority figure to them, and in some sense he also seemed to be preserving the sanctity of their way of life. It's not that conservatives didn't care about the left three values, it's just that all the supposedly disqualifying things he said still made him score very high on the values on the right. On balance he thus still scored favorable.

The mistake liberals made was in thinking that his words would be as important to conservatives as they were to them, but because those words didn't really affect the three major values on the right that conservatives found important, they didn't matter much to them. It's a good case of missing the forest for the trees, and hopefully liberals won't make the same mistake next time. All six foundations are important, however, so liberals cannot be faulted for being angry at Trump's shoddy treatment of the three on the left; as Haidt says, even conservatives value these foundations.

The next four years are going to be a giant experiment in testing all these moral foundations. If the worst that everyone thinks about Trump comes to pass, this country will be in bad shape. That would be because he would have failed on all six foundations: for instance, if he does not deliver on promises to bring jobs to the white working class, the moral foundation of betrayal/loyalty and authority/subversion which they have largely staked their support for him on would take a potentially existential hit. He would have then failed both liberals and conservatives. If on the other hand, he manages to actually follow up on the positive promises that he has made, especially regarding job creation, and also manages not to significantly hurt the other moral foundations on the chart, who knows, perhaps everybody would have been wrong about him after all. For now the best strategy is the one recommended by the Zen Master: "We'll see".

Richard Feynman on our difficult times: "Whatever else is going on, we've always got our physics."

At this unfortunate moment, one of the best things I can think of is an anecdote about Richard Feynman from Stephen Wolfram's new book "Idea Makers". Wolfram was a graduate student with Feynman, and he recounts an episode from one of his visits to Feynman's place.
"If there's one moment that summarizes Richard Feynman and my relationship with him, perhaps it's this. It was probably 1982. I'd been at Feynman's house, and our conversation had turned to some kind of unpleasant situation that was going on. I was about to leave. And Feynman stopped me and said, "You know, you and I are very lucky. Because whatever else is going on, we've always got our physics."
To which I may add, we also have friends, family and our hobbies. Whichever direction the maelstrom of political winds blows our ship, we may take solace in these relative constants of our life. 

It does not mean that we lose ourselves in them to the extent of completely withdrawing from the larger national dialogue - the next few years more than any others demand our participation in that dialogue - but it's very reassuring to know that a carbon-carbon bond, or a supernova, or a protein molecule, or a semiconductor, or an equation, simply don't care who the president of the United States is. Moreover, as Einstein once said, time itself is no more than a "stubbornly persistent illusion", and if time might be illusory, then politics is a vanishingly transient ghost in the grand scheme of things.

I find cool succor in this pristine, untouched domain of science and ideas, and I hope most of us will in the difficult days ahead.

BAGIM event on computational chemistry careers

I want to note an event organized by BAGIM - a Boston area group that organizes talks and discussions on computational chemistry and related topics. It's being held on November 10th and will feature a panel discussion on careers in computational chemistry.

The event should be of special interest to postdocs and graduate students. It's a topic that's interesting partly because it's kind of tricky. It's tricky because computational chemistry is a very interdisciplinary field and its practitioners come from a variety of backgrounds - most commonly from organic and physical chemistry but also increasingly from biology and computer science. 

These days the definition of the field has also greatly expanded to include analysis of large-scale data and bioinformatics. What part you exactly need to know and what employers are looking for are facts that you would probably know only after talking to a few people in the field.

That's why I think these kinds of panel discussions might be useful, especially for people who are just getting into industry and academia. It's worth checking out if you are in the area.

Lise Meitner's 48 Nobel Prize nominations

It's Austrian physicist Lise Meitner's birthday today. Meitner was one of the most remarkable scientific figures of the twentieth century. After doing massive scientific work in radioactivity, she figured out the mechanism of nuclear fission with her nephew Otto Frisch in the depressing winter of 1938, after her colleagues Otto Hahn and Fritz Strassmann observed uranium improbably breaking up into barium.

Meitner continues to be one of the most notable scientists not to have won a Nobel Prize. The omission stands out especially because Hahn won it in 1945. By all accounts Meitner and Hahn enjoyed a very productive working relationship for almost thirty years before the tide of fascism tore their lives apart. Their relationship was warm and friendly, but still formal; both were after all products of the rigid and hierarchical German society of their time.

Meitner's lack of a Nobel Prize is stark not only because of the seminal importance of nuclear fission, but because a search of the Nobel Prize nomination database reveals a striking fact: Meitner was nominated for the Nobel Prize in physics or chemistry no less than 48 times between 1937 and 1948 alone. That's almost five nominations a year. Other great scientists have also received dozens of nominations - for instance the chemist R. B. Woodward had 92 before he finally won - but Meitner's is certainly on the higher side. The database runs to 1965, and it's rather curious to see no nominations after 1948.

The list of scientists nominating her is a roster of the who's who of twentieth century physics: Max Planck, Niels Bohr, Werner Heisenberg, Arthur Compton and Max Born all nominated her multiple times. Hahn nominated her once. Curiously, Albert Einstein who thought highly of Meitner does not seem to have nominated her even once; given Einstein's freethinking views and liberal persona this is rather strange.

Given the number of prominent personalities advocating her work, Meitner's omission from a Nobel Prize will continue to be a blot on the history of the prizes. This hole stands out even more because Meitner was otherwise highly decorated and publicly recognized, receiving for instance the prestigious Enrico Fermi Award from the United States Atomic Energy Commission. A combination of factors likely contributed to the failure of the prize committee. Sexism, certainly, but I don't think sexism played as prominent a role as it did in the careers of some other deserving female scientists. Part of the reason why I don't think it played an overriding role is that nuclear physics was the only field until then in which two women - Marie Curie (who shares a birthday today with Meitner) and Irene Joliot-Curie - had received Nobel Prizes. The physicist Maria Goeppert Mayer would very soon become only the second woman to win a physics Nobel Prize, again for nuclear physics. Also, Otto Frisch and Fritz Strassmann who were instrumental in both discoveries also did not receive the prize, and their omission of course cannot be ascribed to gender discrimination.

The real reason remains muddy and is likely a collage of fuzzy factors. Some have speculated it was anti-semitism, although given the number of Jewish prize recipients until then it would appear to be a minor determinant. Others think that the relatively low opinion of her work held by some prominent members of the Nobel committee might have contributed. Personally I also think it might have been an honest albeit misguided view of the contributions of the four scientists involved in discovering fission: Hahn's work might have been regarded as a proper "discovery" while Meitner and Frisch's might have been regarded as a mere "explanation". Strassmann could have been omitted because he was presumably Hahn's "assistant" (which he wasn't).

All these factors likely played a role, and no single factor might have been dominant. At the very least, Meitner's lack of a prize is as disappointing as Frisch and Strassmann's. In fact I always think that if there is an underappreciated hero of the nuclear fission story, it's not Meitner but Fritz Strassmann. This quiet and industrious man did much of the tedious grunt work that was key to solving the puzzle of the breakup of uranium. The kind of craftsmanship that he exhibited is too often overlooked, by the public as well as by prize committees. Morally too he was a hero; during those perilous years he hid a Jewish friend in his apartment for many years at considerable risk to his life. 

Meanwhile, Frisch was instrumental in helping his aunt work out the exact mathematics of the fission process and then performing the first fission experiment outside Berlin. Working with Rudolf Peierls in Birmingham, he later established the first value for the critical mass of a bomb and helped convince key members of then slow-moving Manhattan project that nuclear weapons were possible. He also fine tuned this critical mass value at Los Alamos by performing dangerous experiments which were christened 'tickling the dragon's tail'.

Niels Bohr rightly suggested that the physics Nobel Prize should have been split between Meitner and Frisch, the chemistry prize between Hahn and Strassmann. But the prize is a human institution after all, and a fallible human committee created by fallible human beings does not always obey the logical dictates of history. Hahn and Meitner are now largely remembered, Strassmann and Frisch are now largely forgotten. But Meitner stands out, for her brilliance and experimental acumen, for her perseverance and doggedness, for her stoic will during tumultuous and painful times, for great personal fortitude. She may not have won a Nobel Prize, but her 48 nominations provide a tribute to her remarkable personality as a scientist and human being. She deserves to be constantly remembered and celebrated.