Field of Science

On the absurdity of classified information

The problem with keeping information secret is not that secrecy is never warranted, it's that it is always easier to classify something as secret than not, and this leads not just to the withholding of potentially important information from the public but also to all kinds of absurd contradictions. Imagine a bored low-level bureaucrat whose job is to stamp national security documents as secret. It is always going to be easier for him to not take the trouble to go through every line in the document and decide whether to redact it or not; it's far easier to mark everything as secret and stash it away in the archives.

One of the absurdities of secrecy was illustrated by Freeman Dyson a few years ago in a review of the book "David and Goliath" in the New York Review of Books. Dyson was talking about a report called Project Oregon Trail written by academic historians during the Vietnam War that analyzed the results of 'asymmetric wars' in which a larger adversary is fighting a smaller one. The report especially focused on the kinds of conflicts in which a large colonial or imperial power is fighting a small country. It concluded that when the imperial power spends most of its resources on military means, it usually loses. When it spends most of its resources on civilian measures intended to win the hearts and minds of people, it usually wins. The Vietnam War which was then not going well was clearly going down the first road; the disastrous Iraq War went down the same road forty years later, as did any number of attempts by large powers to defeat small insurgent groups using purely military means. The powers in charge did not want to hear the inconvenient truth that they were adopting the wrong strategy. 

There was another report at the same time, published by the RAND Corporation, which analyzed potential conflicts between the two countries using game theory. This was a valuable study which was legitimately classified as secret. But to avoid embarrassment and prevent the results of Project Oregon Trail from being released to the public, the government bound the two reports together and stamped both of them as secret. The valuable, purely historical, Project Oregon Trail is still secret fifty years later. Dyson appealed to the government to release the historical study. I submitted a FOIA request for it more than two years ago, and I am still waiting.

Even legitimate secrecy can sometimes make it embarrassingly easy to let someone with the time and effort know what you are hiding. The nuclear weapons expert Carey Sublette put together a detailed archive of supposedly classified data on nuclear weapons by looking at different classification sources that had redacted the same document in different parts, subjectively exposing and redacting sections of the document according to whim; thus, what one source left out another source disclosed. By looking at a specific document from multiple sources, Sublette was essentially able to reconstruct entire classified papers.

Sometimes it is the omission of information that can alert an adversary to valuable secret information. At the end of the Manhattan Project, the Smyth Report was published to give a general description of the atomic bomb to the lay public. The first edition of this report contained an important fact about the poisoning of nuclear reactors with fission byproducts; it was a problem that had frustrated scientists and taken them quite a while to surmount. When General Leslie Groves who was the head of the project saw this included in the Smyth Report, he ordered it taken out in the next edition. When the Soviets read the second edition and compared it to the first one, they knew exactly what was so valuable and secret.

In the London Review of Books, the physicist and writer Jeremy Bernstein who worked closely with Dyson, Robert Oppenheimer, Hans Bethe and others talks about his own take on the absurdity of secrecy. In 1958 he was invited by Dyson and others to work on a spaceship powered by hydrogen bomb explosions. This was an audacious scheme which several brilliant scientists and engineers seriously worked on for a few years. One of the key calculations in exploring this idea involved using the opacities of elements; the opacity of an element gives us an idea of its capacity to absorb or repel electromagnetic radiation. As Bernstein puts it:

"A couple of physicists at Los Alamos had had the idea that small nuclear devices could be used as propellants for space travel. They would be dropped from the bottom of the ship sequentially and the detritus from the explosions would act as an efficient propellant. Dyson had gone to La Jolla to work on the design of the ship. There was to be a large flat metallic plate, known as the ‘pusher’, attached to the body of the ship by springs that would absorb the shocks of the explosions.
The question was whether the pusher would ‘ablate’ away under the influence of the successive bombs. This depended in large measure on the opacity – the capacity to absorb radiation – of the materials involved. They were to be relatively light elements. At the time I didn’t appreciate the importance of this limitation. Any information, theoretical or experimental, on the opacity of any element heavier than lutetium was and is classified. This includes gold, platinum and lead. To compute an opacity is a problem in quantum mechanics and atomic physics. Anyone can try to do it, but if you do it for lead, the result is classified. Is anything more absurd? Dyson had an idea for a ‘super Orion’ with a pusher made of uranium, which might have been used as fuel for, say, a return trip to Mars. But the opacity of uranium was classified, though it might be an interesting project for a graduate student."
Fifty years later, I did a  Google search and am still not sure whether there is a reliable public source listing the opacities of heavy elements. This is in spite of the fact that many graduate students could now accurately calculate and measure these numbers using a variety of techniques.
Finally, no system of government or private enterprise is foolproof, and secrecy is always thwarted when there are either spies or leakers. Sometimes these spies work against the common good (as in the case of Soviet spy Klaus Fuchs), sometimes they work in its favor (as in the case of American spy Edward Snowden). Bernstein describes how Fuchs was ferrying atomic secrets out of Los Alamos on a daily basis.
"In autumn 1945, Enrico Fermi gave a lecture at Los Alamos on Edward Teller’s hydrogen bomb, the Classical Super. Fermi concluded that he did not see how it could be made to work. The audience was all Q-cleared and the lecture was classified. One of the people in the audience was Klaus Fuchs, who turned the lecture over to the Russians. I am not sure they learned anything they did not already know. But the lecture remained classified by the US government even after the Russians had put it on the web. You can download it at your leisure."
I have not looked for this lecture online but we can be sure of two things: firstly, that it exists in the public domain, and secondly, that the government will never acknowledge its existence. The ultimate absurdity of secrecy arises when the government refuses to deny that something is secret even when it is out for all the public to see. The distinction between classified and unclassified itself becomes classified.

Why technology won't save biology

Carl Woese, who saw an integrated view for 21st century
biology; from molecules to communities
Starting today, I will be writing a monthly column for the outstanding website 3 Quarks Daily. My first post deals with the limitations of the technological zeitgeist in understanding biology.

There seems to be no end to biology's explosive progress. Genomes can now be read, edited and rewritten with unprecedented scope, individual neurons can now be studied in both space and time, the dynamics of the spread of viruses and ecological populations can be studied using mathematical models, and vaccines for deadly diseases like HIV and Ebola seem to hold more promise than ever. They say that the twentieth century belonged to physics and the twenty first belongs to biology, and everything we see in biology seems to confirm this idea.

There have been roughly six revolutions in biology during the last five hundred years or so that brought us to this stage. The first one was the classification of organisms into binomial nomenclature by Linnaeus. The second was the invention of the microscope by Hooke, Leeuwenhoek and others. The third was the discovery of the composition of cells, in health and disease, by Schwann and Schleiden, a direct beneficiary of the use of the microscope. The fourth was the formulation of evolution by natural selection by Darwin. The fifth was the discovery of the laws of heredity by Mendel. And the sixth was the discovery of the structure of DNA by Watson, Crick and others. The sixth, ongoing revolution could be said to be the mapping of genomes and its implications for disease and ecology. Two other minor revolutions should be added to this list; one was the weaving of statistics into modern genetics, and the second was the development of new imaging techniques like MRI and CT scans.

These six revolutions in biology resulted from a combination of new ideas and new tools. This picture is consistent with the general two-pronged picture of scientific revolutions that has emerged through the ages: a picture consisting in equal parts of revolutions of ideas and revolutions of technology. The first kind was popularized by Thomas Kuhn in his book "The Structure of Scientific Revolutions". The second was popularized by Peter Galison and Freeman Dyson; Galison in his book "Image and Logic", and Dyson in his "The Sun, the Genome and the Internet". Generally speaking, many people are aware of Kuhn but few people are aware of Galison or Dyson. That is because ideas are often considered loftier than tools; the scientist who gazes at the sky and divines formulas for the universe through armchair calculations is considered more brilliant than the one who gets down on her hands and knees and makes new discoveries by gazing into the innards of machines.

However, this fondness for theory versus experiment paints a false picture of scientific progress. Machines and tools are not just important for verifying theories; they are more often used to discover new things that theory then has to catch up with and explain. In physics, the telescope and the particle accelerator have been responsible for some of the greatest revolutions in our understanding of nature; they haven't just verified existing theories but uncovered the fundamental composition of matter and spacetime. In chemistry, the techniques of x-ray diffraction and nuclear magnetic resonance have not just opened new windows into the structure of molecules, but they have led to novel understanding of molecular behavior in environments as diverse as intricate biological systems and the surfaces of distant planets and galaxies. There is little doubt that new experimental techniques have been as or even more responsible for scientific revolutions as new ideas.

As one example of the primacy of tool-driven revolutions, four of the six milestones in biology noted above can be considered to have come from the development or application of new tools. The microscope itself was a purely technological invention. The structures of cells, bacteria and viruses was made possible by the invention of new forms of microscopy – the electron microscope in particular – as well as new dyes which allowed scientists to distinguish cellular components from each other. The structure of DNA came about because of x-ray diffraction and chemical analysis. The minor revolution of imaging was made possible by concomitant revolutions in electronics and computing. And finally, the revolution in genomics has engendered by chemical and physical methods of rapidly sequencing genomes as well as powerful computers which can analyze this data. The application of all this technology has been a windfall of data which hides gems of understanding. The new science of systems biology promises to tie all this data together and lead to an improved understanding of biological systems.

And this is where the problem begins. In one way biology has become a victim of its success. Today we can sequence genomes much faster than we can understand them. We can measure electrochemical signals from neurons much more efficiently than we can understand their function. We can model the spread of populations of viruses and populations much more rapidly than we can understand their origins or interactions. Moore's Law may apply to computer chips and sequencing speeds, but it does not apply to human comprehension. In the words of the geneticist Sydney Brenner, biology in the heyday of the 50s used to be "low input, low throughput, high output"; these days it's "low input, high throughput, no output". What Brenner is saying is that compared to the speed with which we can now gather and process biological data, the theoretical framework which goes into understanding data as well as the understanding which come out from the other end are severely impoverished. What is more serious is a misguided belief that data equals understanding. The philosopher of technology Evgeny Morozow calls this belief "technological solutionism", the urge to use a certain technology to address a problem simply because you can.

Consider a field like cancer where gene sequencing has come to play a dominant role. The idea is to compare the genome sequences of cancer cells and normal cells, and therefore understand which genes are malfunctioning in cancer cells. The problem is that if you sequence a typical cell from, say, a lung cancer patient, you will find literally hundreds of genes which are mutated. It is difficult to distinguish the mutant genes which are truly important from those which just come along for the ride; the latter are a necessary part of the messy, shotgun process of cancer cell evolution. It is even more difficult to know which genes to target if we want to keep the cancer from growing. For doing this it is important to have a better theory for understanding exactly what genes would be mutated in a cancer cell and why, and what function they serve. While we have made strides in developing such theories, our understanding of the basic causal framework of cancer is far behind our capacity to rapidly sequence cancer genomes. And yet millions of dollars are spent in sequencing cancer genomes, with the expectation that someday the data alone with lead to a quantum leap in understanding. You look for the keys not where they are but where you can easily see them, under the bright light.

A recent paper from the neuroscientist John Krakauer said the same thing about neuroscience. If biology is the science of the twenty first century, neuroscience is probably the cherry on that cake. No other field promises to deliver fundamental insights not just into major mental health disorders but into the very essence of what it means to be human. To understand the brain better, scientists and government launched the Brain Map Initiative a few years ago. The goal of this initiative can be stated very simply: it is to map every single neuron in the brain in space and time and to understand the connections between them. The belief is that understanding the behavior of neurons will lead to an understanding of human behavior. At the heart of the initiative are new methods of interrogating neuronal function, ranging from very precise electrical recording using advanced sensor techniques to studying an inventory of the proteins and genes activated in neurons by modern recombinant DNA technology. These methods will undoubtedly discover new aspects of the brain that were previous hidden. Some of them well lead to groundbreaking understanding. But we do not know whether they will allow us to understand human behavior. As one example, the paper by Krakauer talks about mirror neurons, a specific class of neurons that caused a great stir a few years ago. As their names indicate, mirror neurons in one brain fire when the same class of neurons is activated in another brain. These neurons have thus been proclaimed to be the basis of diverse human emotions, including empathy; understanding them is considered to be integral to understanding social behavior; delicate imaging studies can track their activation and deactivation. But as Krakauer notes, many experiments on mirror neurons have been done on monkeys, and in those cases, little attention if any is paid to the actual behavior of the monkey when the mirror neurons fire. Thus, we seem to know what is going on, but only at the level of the neurons themselves. We do not know what is actually going on in the mind of the monkey in terms of its behavior when the neurons are activated.

To understand why these limitations of technology can hamper our understanding of complex biological systems, we must turn to one of the great philosophical foundation stones of science: the paradigm of reductionism. Reductionism was the great legacy of twentieth century science, and a culmination of everything that came before. It means the breaking up of complex systems into their simpler parts; the idea is that understanding the simpler parts will enable us to understand the whole system. There is little doubt that reductionism has led to spectacular successes in all of science. The entire edifice of twentieth century physics – exemplified by relativity and quantum mechanics – rose from the reductionist program of understanding matter and spacetime using its most basic components; particles and fields. Molecular biology similarly was created when biological matter started to be unraveled at the molecular level. Most of these advances became possible because powerful new technology like particle accelerators and spectrometers allowed us to break and study matter and living organisms at their fundamental level.

But as science overturned one obstacle after another in its confident reductionist march, it became clear that all was not well with this approach. One of the first salvos in what came to be called the "reductionism wars" was from the physicist Philip Anderson who in 1972 wrote an article titled ‘More is Different'. Anderson did not deny the great value of reductionism in science, but he pointed out that complex systems are not always the sum of their constituent parts. More is not just quantitatively different but qualitatively so. Even simple examples illustrate this phenomenon: atoms of gold are not yellow, but gold bars are; individual molecules of water don't flow, but put enough of them together and you get a river which has features that are not directly derived from the molecules themselves. And consciousness may be the ultimate challenge to reductionism; there is absolutely nothing in a collection of carbon, hydrogen, oxygen and nitrogen atoms in a human brain that tells us that if you put enough of them together in a very specific configuration, you will get a human being who would be writing this essay. Rivers, gold bars, human brains; all these systems are examples of emergent phenomena in which the specification of the individual components is necessary but not sufficient to understand the specification of the entire system. This is top-down as opposed to bottom-up understanding.

Why does emergence exist? We don't know the answer to that question, but at least part of it is related to historical contingency. The complexity theorist Stuart Kauffman gives a very good example of this contingency. Consider, says, Kauffman, the structure and function of the human heart. Imagine that you had a super-intelligent demon, a "superfreak" who could specific every single particle in the heart and therefore try to derive the function of the heart from string theory. Imagine that, starting from the birth of the universe, this omniscient superfreak could specify every single configuration of atoms in every pocket of spacetime that could lead to the evolution of galaxies, supernovae, planets, and life. He would still fail to predict that the most important function of the human heart is to pump blood. That is because the heart has several functions (making beating noises for instance), but the function of the heart about which we care the most is a result of historical accident, a series of unpredictable circumstances on which natural selection acted before elevating the pumping of the blood as the quintessential property of the heart. Some of the pressures of this natural selection came from below, but others came from above; for instance, the function of the heart was sculpted not just by the molecules which make up heart muscle but by the functions of the physiological and ecological environments in which ancient heart precursors found themselves. The superfreak may even be able to predict the pumping of blood as one of the many properties of the heart, but he will still not be able to determine the unique role of the heart in the context of the grand tapestry of life on earth. The emergence of the human heart from the primordial soup of Darwin's imagination cannot be understood by understanding the quarks and cells from which the heart is composed. And the emergence of consciousness or the brain cannot be understood merely by understanding the functions of single neurons.

Emergence is what thwarts the understanding of biological systems through technology, because most technology used in the biological sciences is geared toward the reductionist paradigm. Technology has largely turned biology into an engineering discipline, and engineering tells us how to build something using its constituent parts, but it doesn't always tell us why that thing exists and what relationship it has to the wider world. The microscope observes cells, x-ray diffraction observes single DNA molecules, sequencing observes single nucleotides, and advanced MRI observes single neurons. As valuable as these techniques are, they will not help us understand the top-down pressures on biological systems that lead to changes in their fundamental structures.

The failure of reductionist technology to understand emergent biology is why technology will not save the biological sciences. I have a modest prescription to escape from this trap: create technology that studies biology at multiple levels, and tie this technology together with concepts that describe biology at multiple levels. For instance when it comes to neuroscience, it would be fruitful to combine magnetic recording of single neurons (low level) with lower resolution techniques for studying clusters of neurons and modules of the brain (intermediate level) with experiments directly probing the behavior of animal and human brains (higher level). The good news is that many of these techniques exist; the bad news is that many of them exist in isolation, and the researchers who study them don't build bridges between the various levels. The same bridge-building goes for concepts. For instance, at the highest level organisms are governed by the laws of thermodynamics, more specifically non-equilibrium thermodynamics (of which life is an example), but you will not usually see scientists studying collections of neurons taking into consideration the principles of statistical thermodynamics or entropy. For achieving this meld of concepts scattered across different levels of biological understanding, there will also need to be much closer multidisciplinary interactions; physicists studying thermodynamics will need to closely collaborate with geneticists understanding the translation of proteins in neurons. These scientists will in turn need to work together with psychologists observing human behavior or ethologists observing animal behavior; both these fields have a very long history which can inform researchers from other fields. Finally, all biologists need to appreciate better the role of contingency in the structure and function of their model systems. By looking at simple organisms, they need to discuss how contingency can inform their understanding of more complicated creatures.

For a wholesome biology to prosper we need both technological and human interactions. But what we need most is an integrated view of biological organisms that moves away from a strict focus on looking at these organisms as collections of particles, fields and molecules. The practitioners of this integrated biology can take a page out of the writings of the late Carl Woese. Woese was a great biologist who discovered an entire new kingdom of life (the Archeae), and one of the few scientists able to take an integrated view of biology, from the molecular to the species level. He pioneered new techniques for comparing genomes across species at the molecular level, but he also had a broader and more eloquent view of life at the species level, one which he set down in an essay titled "A New Biology for A New Century" in 2004, an essay that expanded biology beyond its mechanistic description:

"If they are not machines, then what are organisms? A metaphor far more to my liking is this. Imagine a child playing in a woodland stream, poking a stick into an eddy in the flowing current, thereby disrupting it. But the eddy quickly reforms. The child disperses it again. Again it reforms, and the fascinating game goes on. There you have it! Organisms are resilient patterns in a turbulent flow—patterns in an energy flow. A simple flow metaphor, of course, fails to capture much of what the organism is. None of our representations of organism capture it in its entirety. But the flow metaphor does begin to show us the organism's (and biology's) essence. And it is becoming increasingly clear that to understand living systems in any deep sense, we must come to see them not materialistically, as machines, but as (stable) complex, dynamic organization."

As the quote above observes none of our experiments or theories captures the science at all levels, and it's only by collaboration that we can enable understanding across strata. To enable it we must use technology, but use it not as master but as indispensable handmaiden. We are all resilient organisms in a turbulent energy flow. We live and die in this flow of complex, dynamic organization, and we can only understand ourselves when we understand the flow.

On Albert Einstein's birthday: How Eddington and Einstein set an example for the international fellowship of science

The world woke up on the morning of November 7, 1919, to an amazing piece of news. A few months before in May, the English astronomer Arthur Eddington had led an expedition to the island of Principe off the west coast of Africa to try to observe one of the strangest phenomena ever predicted in the history of the science: the bending of starlight by the gravitational field of the sun. The phenomena could only be observed during a total solar eclipse, when the sun becomes dim enough to track the passage of starlight past it.

Eddington’s analysis proved that the light was bent by an amount that was twice that predicted by Isaac Newton, often considered the greatest scientist who ever lived. The man who trumped the great Sir Isaac’s prediction had until then been a relatively unknown forty-year-old physicist working in Berlin. His name was Albert Einstein, born on this day in 1879.

The observation of starlight bending was the first prediction of Einstein’s then otherworldly-seeming general theory of relativity: “One of the greatest achievements in the history of human thought. It is not the discovery of an outlying island but of a whole new continent of scientific ideas”, quipped the English physicist J. J. Thomson, discoverer of the electron. It was only the first among a stellar set of experimental observations that validated some mind-bending phenomena and ideas: spacetime curvature, black holes, gravitational waves, an expanding universe. It catapulted Einstein to world celebrity, and made him a household name and a part of the history books.

More importantly for the sake of world peace, however, it underscored one of the finest moments in the history of science diplomacy. The world had seen its first brutal world war end just a few months before, when the guns had finally been silenced in August.  The carnage had been unparalleled: more than 38 million casualties, with 17 million deaths. And in the light of this death and destruction, there was one country on which the world’s anger was focused: Germany. It seemed Germany had started the war and continued it, and it was fanatic German militarism that seemed to have sown the seeds of discontent.

In the middle of all that resentment then, it must not have gone unnoticed that an Englishman had confirmed a seminal prediction of a German’s reworkings of our understanding of the cosmos. In fact it was an exceptional gesture that would go down in history as a measure of the international brotherhood of science. Eddington, a pacifist Quaker who loathed war, joined heart and mind with Einstein, another pacifist who loathed war. At a time when the two countries had just come out of a horrific conflict with each other – a conflict streaked with memories of poison gas, trench warfare, dysentery and hand-to-hand combat - here was singular proof that there could be friendship between them again, that it was possible to forgive and move ahead together. The expedition at Principe confirmed a singular fact about science: that it can go beyond petty and deadly territorial disputes, that its bonds go deeper than those of rank or politics, and that, in the hands of men and women with conscience, it can rise above the fray and be the one shining candle in the dark. Einstein never forgot Eddington’s contribution to relativity and the hand of fellowship that bridged two nations who only a few months before had been sworn enemies. At the end of November, he finally gave in to the constant pleas from journalists and the public to hold forth on his theory and wrote a piece for the London Times on relativity. But he began the piece not with a scientific exposition but a human one:
“I gladly accede to the request of your colleague to write something for The Times [London] on relativity. After the lamentable breakdown of the old active intercourse between men of learning, I welcome this opportunity of expressing my feelings of joy and gratitude toward the astronomers and physicists of England. It is thoroughly in keeping with the great and proud traditions of scientific work in your country that eminent scientists should have spent much time and trouble, and your scientific institutions have spared no expense, to test the implications of a theory which was perfected and published during the war in the land of your enemies. Even though the investigation of the influence of the gravitational field of the sun on light rays is a purely objective matter, I cannot forbear to express my personal thanks to my English colleagues for their work; for without it I could hardly have lived to see the most important implication of my theory tested.” 
Einstein’s message here was clear. No matter what the political environment, science should trudge on, and political differences should not be a reason to squelch scientific collaboration. In fact such collaboration may be the only bond joining two countries together when all others have failed.

Eddington and Einstein’s plea for scientific fellowship has again become relevant, even as irrational nationalism has started to rear its ugly head, in the United States, in Europe and beyond. Demagogues with no understanding of science are trying to stem the flow of scientific talent from other countries, and no nation will be hurt more by this backward policy than the United States. More than any other single country, the United States has been the beneficiary of groundbreaking work by émigré scientists; in fact, the U.S. rose to scientific prominence when Jewish scientists fleeing from fascism in Europe migrated to its shores. It rose to world prominence in diverse scientific fields like astronomy, biomedical research and social science as these European immigrants and their students, along with others who came to the country during the last few decades from Asia, Africa, Australia and other continents, massively contributed to new scientific discoveries and inventions and won a string of Nobel Prizes.

If the United States starts appearing as an unwelcome destination for the world’s scientists, doctors and engineers, not only would this be a scientific disaster but it will be a human disaster. Immigrant scientists are often fleeing from persecution, broken economies and shoddy education standards and therefore usually work extra hard to ensure that their work brings success to their adopted countries. They may not all be Christians, but as is clear from the educational attainment and income levels of so many of these immigrant groups, they often live and breathe the Protestant work ethic of hard work, honesty and perseverance. As exemplified by a letter written by the German émigré Hans Bethe to his teacher Arnold Sommerfeld, many of them come to love their country and demonstrate deep loyalty toward it. Einstein himself was of course one of the most important examples of the immigrant experience in this country; when he moved to Princeton in 1933, the center of world physics moved with him. Alienating these people would not just be antithetical to the universal fellowship of science but it would decidedly not be in the United States’ best interests; it is these immigrant scientists and engineers who have started companies worth billions, discovered new drugs, materials and species, and contributed to America's tremendous supremacy in the information age. Supporting these immigrants is in fact putting ‘America First’.

One can have a perfectly reasonable discussion on limits to immigration without keeping talent away from these shores or without alienating potential immigrants who want to succeed in this country through hard work and family values. The current political environment has erased these important distinctions, if not explicitly at least in spirit, and it’s a distinction that we need to all clearly point out. The path ahead will not be easy, but as long as we support and understand each other, as long as we organize panel discussions and conferences and exchange programs which make people appreciate the international nature of science, we will move ahead together. All we need to do is have the Eddingtons and Einsteins among us keep finding each other.

Yuval Noah Harari's "Homo Deus": Sweeping, clever and provocative, but speculative and incomplete

Yuval Noah Harari's "Homo Deus" continues the tradition introduced in his previous book "Sapiens": clever, clear and humorous writing, intelligent analogies and a remarkable sweep through human history, culture, intellect and technology. In general it is as readable as "Sapiens" but suffers from a few limitations.

On the positive side, Mr. Harari brings the same colorful and thought-provoking writing and broad grasp of humanity, both ancient and contemporary, to the table. He starts with exploring the three main causes of human misery through the ages - disease, starvation and war - and talks extensively about how improved technological development, liberal political and cultural institutions and economic freedom have led to very significant declines in each of these maladies. Continuing his theme from "Sapiens", a major part of the discussion is devoted to shared zeitgeists like religion and other forms of belief that, notwithstanding some of their pernicious effects, can unify a remarkably large number of people across the world in striving together for humanity's betterment. This set of unifying beliefs is not just religious or supernatural; even a completely secular concept like human rights refers to ideas which are nowhere to be found except in the human imagination. It is this zeitgeist of beliefs which is partly what jump-started the cognitive revolution that made Homo sapiens so unique. It has created or enriched an almost infinite variety of human institutions and ideas, from money and mating to democracy and disco music. As in "Sapiens", Mr. Harari enlivens his discussion with popular analogies from current culture ranging from McDonald's and modern marriage to American politics and psychotherapy. Mr. Harari's basic take is that science and technology combined with a shared sense of morality and our belief-generating cognitive system have created a solid liberal framework around the world that puts individual rights front and center. There are undoubtedly communities that don't respect individual rights as much as others, but these are usually seen as challenging the centuries-long march toward liberal individualism rather than upholding the global trend.

The discussion above covers about two thirds of the book. About half of this material is recycled from "Sapiens" with a few fresh perspectives and analogies. The most important general message that Mr. Harari delivers, especially in the last one third of the book, is that this long and inevitable-sounding imperative of liberal freedom is now ironically threatened by the very forces that enabled it, most notably the forces of technology and globalization. Foremost among these are artificial intelligence (AI) and machine learning. These significant new developments are gradually making human beings cede their authority to machines, in ways small and big, explicitly and quietly. Ranging from dating to medical diagnosis, from the care of the elderly to household work, entire industries now stand to both benefit and be complemented or even superseded by the march of the machines. Mr. Harari speculates about a bold vision in which most manual labor has been taken over by machines and true human input is limited only to a very limited number of people, many of whom because of their creativity and demand will likely be in the top financial echelons of society. How will the rich and the poor live in these societies? We have already seen how the technological decimation of parts of the working class was a major theme in the 2016 election in the United States and the vote for Brexit in the United Kingdom. It was also a factor that was woefully ignored in the public discussion leading up to these events, probably because it is much easier to provoke human beings against other human beings rather than against cold, impersonal machines. And yet it is the cold, impersonal machines which will increasingly interfere with human lives. How will social harmony be preserved in the face of such interference? If people whose jobs are now being done by machines get bored, what new forms of entertainment and work will we have to invent to keep them occupied? Man after all is a thinking creature, and extended boredom can cause all sorts of psychological and social problems. If the division of labor between machines and men becomes extreme, will society fragment into H. G. Wells's vision of two species, one of which literally feeds on the other even as it sustains it?

These are all tantalizing as well as concerning questions, but while Mr. Harari does hold forth on them with some intensity and imagination, this part of the book is where his limitations become clear. Since the argument about ceding human authority to machines is also a central one, the omission also unfortunately appears to me to be a serious one. The problem is that Mr. Harari is an anthropologist and social scientist, not an engineer, computer scientist or biologist, and many of the questions of AI are firmly grounded in engineering and software algorithms. There are mountains of literature written about machine learning and AI and especially their technical strengths and limitations, but Mr. Harari makes few efforts to follow them or to explicate their central arguments. Unfortunately there is a lot of hype these days about AI, and Mr. Harari dwells on some of the fanciful hype without grounding us in reality. In short, his take on AI is slim on details, and he makes sweeping and often one-sided arguments while largely skirting clear of the raw facts. The same goes for his treatment for biology. He mentions gene editing several times, and there is no doubt that this technology is going to make some significant inroads into our lives, but what is missing is a realistic discussion of what biotechnology can or cannot do, and what aspects of the field are likely to be impacted through gene editing. Similarly, it is one thing to mention brain-machine interfaces that would allow our brains to access supercomputer-like speeds in an offhand manner; it's another to actually discuss to what extent this would be feasible and what the best science of our day has to say about it.

In the field of AI, particularly missing is a discussion of neural networks and deep learning which are two of the main tools used in AI research. Also missing is a view of a plurality of AI scenarios in which machines either complement, subjugate or are largely tamed by humans. When it comes to AI and the future, while general trends are going to be important, much of the devil will be in the details - details which decide how the actual applications of AI will be sliced and diced. This is an arena in which even Mr. Harari's capacious intellect falls short. The ensuing discussion thus seems tantalizing but does not give us a clear idea of the actual potential of machine technology to impact human culture and civilization. For reading more about these aspects, I would recommend books like Nick Bostrom's "Superintelligence", Pedro Domingos's "The Master Algorithm" and John Markoff's "Machines of Loving Grace". All these books delve into the actual details that sum up the promise and fear of artificial intelligence.

Notwithstanding these limitations, the book is certainly readable, especially if you haven't read "Sapiens" before. Mr. Harari's writing is often crisp, the play of his words is deftly clever and the reach of his mind and imagination immerses us in a grand landscape of ideas and history. At the very least he gives us a very good idea of how far we as human beings have come and how far we still have to go. As a proficient prognosticator Mr. Harari's crystal ball remains murky, but as a surveyor of past human accomplishments his robust and unique abilities are still impressive and worth admiring.

Macrocycles, flexibility and biological activity: A tortuous pairing

Here's an interesting paper from the Jacobson, Wells and Walsh labs at UCSF and Stanford that seeks to demonstrate how restricting the flexibility of macrocycles may lead to better inhibition of their targets from an entropic perspective. The authors are looking at a non-ribosomal peptide called thiocillin which inhibits the growth of Gram positive bacteria, especially MRSA.

What they wanted to determine was the effect of point mutations in the peptide on the inhibition. They performed saturation mutagenesis between positions 2 and 9 of the peptide and generated 152 mutants whose activities they tested in a minimum inhibitory concentration (MIC) assay. They found that 8 point mutants especially resulted in more potent analogs.

Now there can be several reasons why the potency went up, but one potential reason is entropy. Macrocycles, while often more rigid than their corresponding linear analogs, are still quite flexible. In fact, my own work with the macrocycle dictyostatin in graduate school showed how flexible even a supposedly constrained molecule can be. What this paper finds out is that in cases where the mutant lost activity, there was a corresponding increase in flexibility and entropy as measured by the number and distinctive nature of conformations from a conformational search technique which they have developed. Particularly striking changes in potency occurred when a single residue was modified from having a planar sp2 carbon to a non-planar sp3 carbon: in that case the saturated analog had many more conformations than the unsaturated one.

As someone who has always been partial to the impact of entropy and conformational flexibility on molecular activity, I like this kind of work. But I am not quite convinced yet that it is decreased flexibility that leads to more potent inhibition. For one thing, inhibition is not direct binding, and there are a variety of factors including changes in cell permeability and off target effects that could lead to the observed changes in inhibitory - not binding - affinity. Secondly, there were 152 mutants, and it's not clear to me how many were tested for flexibility: in other words, I am not sure there were enough controls to determine whether the flexibility-inhibition correlation really holds up. For instance, many of the mutants were inactive: were there instances in which some of these were actually less flexible and challenged the hypothesis? Another way to put it is to ask what the right null model for this dataset is. 

Thirdly, decreased or increased inhibition can be a result of both more conformations as well as conformational selection. For instance, two macrocycles can have similar conformations, but in one case a particular conformation more suitable for binding could be more stable (perhaps because of an intramolecular hydrogen bond) and represented to a higher degree in solution, making it easier for a protein target to pick it out. Lastly, it is not clear whether the improved affinity could simply have been a result of better interactions: although that seems unlikely for the sp2 vs sp3 pair above, it is nonetheless a factor that could be operating in other cases.

Entropy is an important consideration in drug design, but it's also trickier than it sounds to both understand its effects and implement its benefits. To their credit the authors acknowledge that rigidity is a necessary but not sufficient condition for increased affinity, and other studies seem to bear it out. Macrocyclization can also be counterintuitive: for instance in my own studies I found out that dictyostatin which is a macrocycle seems more flexible than its corresponding acyclic counterpart discodermolide. In that case it was fairly straightforward syn-pentane interactions which made the acyclic molecule rigid. In other cases it could be the opposite. In any case, this study serves as an interesting starting point for exploring the impact of flexibility on drug affinity, but it also serves to illustrate how thick the jungle of SAR really is.

An open letter to my fellow industry scientists: Why the March for Science must be led by us

On April 22nd, scientists, science-lovers and people who care about evidence-based reasoning are going to participate in protests and marches around the country. The flagship march will take place in Washington DC, but there are sister marches in Boston, San Francisco, Atlanta and Raleigh, to name a few cities.

There has been a lot of debate and commentary on what the objectives of the march should be, how political it should get and what it generally should or should not do. Some think that scientists should not politicize the march, others think that there is no way the march could not be political. I am participating in the march myself and wish it all success, but one thing is clear to me: the march will not succeed in its objectives if industry scientists do not participate in it in large numbers.

For me, it is very clear why this is the case. First of all, a few words about the motives and reasoning of the march. The objective of the march is to send a resounding message to the politicians and people of this country about respecting scientific facts and divorcing them from political ideology. However the people who need to hear the message about science the most are Donald Trump's supporters, especially ones in the rural areas of this country. If we don't reach them, we would spend the day feeling happy and smug about ourselves, wander around with like-minded people, and come home after patting each other's backs without really having accomplished much, feeling secure in our secure worlds. We would have done almost nothing to change the mind of the average person living in rural Alabama.


The only way to not have our efforts fail is to understand the details of the bridge we need to build to mend our relationship with those who may think differently. We are more similar than we think. Many people who are suspicious of science are far from dumb, but they are suspicious of certain fields of science such as climate science and evolution while being supportive of areas like space exploration. I don't think there is any evidence that the average American is against scientific research as a whole. But those who are suspicious of specific areas think that not only do these ideas infringe on their deeply held religious beliefs, but that they are part of a grand liberal agenda to ram sweeping government policies down their throats. They also think especially of academic scientists as liberal, ivory tower intellectuals who have their heads in the clouds and who don't care about the welfare of the common man. The victory of Trump was in large part a victory against these perceived intellectual elitists.

Firstly, what we need to convince these people is that many of the facts unearthed by science, even in areas like climate change and evolution, are independent of the political beliefs of the people who discover these facts. That means pointing out, first of all, that there are religious and conservative scientists who work in these fields, and that these scientists also support the facts independent of their religious or political beliefs. The continuing head of the NIH, Francis Collins, is a devout Christian for instance who fully supports evolution and important fields like stem cell research. The better we can do in separating scientific facts from the beliefs of the people who find out these facts, the better we will be able to reach the people who need to know them the most. At the same time, we should admit that some scientists do politicize science, and that we need to have an honest dialogue with each other about how we can keep science as neutral as possible. We also need to admit that extreme politicization of science can take place on both the left and the right.

Most importantly, however, we need to convince the people who need to hear about science the most that science is far from being limited to ivory tower academics, and to fields like evolution or climate change. Even if we completely ignored those fields, there is zero doubt that science has had a profound impact on the standard of living of the very people who are suspicious of it during the last few decades. Even if you completely took liberal academics out of the equation, science still pervades every aspect of everyone's lives. The best way to convince them of this is to move away from pure and basic science to applied science.

That's where industry scientists come in. Forget, for a moment, abstract academic matters like dark energy and directed gene evolution and the fine-tuning of computer climate models, forget what Thomas Kuhn said about science, forget what stuffy scientific epistemology and ontology are all about, and focus on one stark fact: Science has directly, immeasurably and irrevocably impacted the lives of rural and urban populations alike through its research into fossil fuels, into agriculture, into infrastructure such as roads and bridges, into oil refining, into plastics and textiles, into improving water and air quality, and into lifesaving drugs and vaccines against cancer, polio and infectious diseases. Most of this innovation was made possible by the creativity and passion of industry scientists, ranging from Wallace Carothers to Gertrude Elion. 

Throughout recent history, companies like Bell Labs, IBM, Lockheed, Ford, GE and Exxon have been fonts of scientific innovation and progress. This kind of science is not just sewn into the fabric of everyday American life from Boston, MA to Savannah, GA, but it should also appeal to his or her patriotic instincts, since it's what has allowed the United States to become a powerhouse of technology and finance after World War 2. Even if you are suspicious of global warming or evolutionary theory, you should be able to appreciate the profound influence science has had on your way of life by bringing you transistors, the Saturn V rocket, nitrogen fertilizer, painkillers, petroleum cracking, nylon, Ford F-150 trucks, Portland cement and the iPhone. These are not liberal or conservative inventions. These are scientific inventions. They are enabling beyond measure. Even if you think they haven't really helped lift you out of poverty, without them your fate would be unimaginable.

It's only by talking about these very practical and amazing innovations that you can convince the average American of the value of science. Whether you are a Clinton supporter or a Trump supporter, a Methodist or an atheist, poor or rich, gun lover or hater, for or against abortion, it is simply impossible for your life or that of your parents and grandparents to not have been radically impacted for the better because of improved medicines, better roads and automobiles, better clothing and housing and better means of communication. At the heart of every single one of these innovations is science, firmly rooted in observable fact and independent of politics and religion. At the same time, this is where we can loop back from these highly applied advances to basic science which may sound very esoteric. For instance, Einstein's relativity is what makes GPS possible. Basic research into organic synthesis is what makes new drugs possible. And it would be impossible to understand cancer and AIDS without understanding evolution. But even if you didn't care about the process that goes into these developments, you can still care about the fruits themselves.

I therefore want to issue an open appeal to my colleagues in industry. To scientists from Exxon, Dow, Pfizer, Kraft, GM, Raytheon, Genentech, GE, Monsanto, Coca Cola and the umpteen number of small startups doing research in pharmaceuticals, food science, agriculture, electronics and tech; don't just participate but lead the March for Science. Show up with your families. Come out in large numbers; it's a Saturday so you don't even need to take a day off. Since academia is a niche, show the country that you and your colleagues actually constitute the majority of scientists in this country. Leave aside your political differences and come together to show everyone how your work and that of your intellectual forefathers has profoundly changed the average American's life for the better, and how it has turned his nation into the most technologically advanced civilization on earth. Forget about politics for a moment and remember the joy that each one of you feels in the shared moment of scientific discovery, a moment completely divorced from your political beliefs. It certainly helps that unlike leading academic centers, the leading industrial research centers you work in are more uniformly distributed throughout the country and not just limited to the coasts. A strong showing of industry scientists would thus automatically disperse the science march over a much wider area. 

My fellow industry scientists, here is our chance to try to convince our fellow countrymen, and especially ones with whom we have strong political disagreements, that irrespective of what they think about its political trappings, science is a fantastic truth-finding practical tool that influences and will keep influencing their way of life through its contributions to the most practical matters related to energy, transportation, housing, and healthcare. Here is our chance to convince the average American how she could be a part of this revolution, and how you are ready to do what you can to communicate not just the wonders of science to her but to enable her to participate in its fruits. Reassure her that you are willing to have an honest dialogue about how the government can do more to retrain her for this new technological age, to try to make sure that her kids can go to college and become technically enabled, to become a part of the same adventure that put a man on the moon, helped the United States win World War 2, and ended polio and smallpox. 

Seen from the angle of these practical innovations, science has been the great equalizing force in American life, reaching Americans of every political stripe and disagreement. That is what makes it so special, so important for our future, so much worth fighting for, and most importantly, so much worth sharing with those who we think are so different from us.

I'll see you there.

Darwin Day: A personal offering


Two hundred and eight years ago this day, Charles Darwin was born. The vision of life that he created and expounded on transformed humanity's perception of its place in the universe. After Copernicus's great heliocentric discovery, it was Darwin's exposition of evolution and natural selection that usurped human beings from their favored place at the center of the universe. But far from trivializing them, it taught them about the vastness and value of life, underscored the great web of interactions that they are a part of, and reinforced their place as both actor and spectator in the grand game of the cosmos. Not only as a guiding scientific principle but as an all-encompassing element of understanding our place in the world, evolution through natural selection has become the dominant idea of our time. As the eminent biologist Theodosius Dobzhansky put it quite simply, nothing in biology makes sense except in the light of evolution. Evolution is a fact. Natural selection is a theory that is now as good as a fact. Both evolution and natural selection happen. And both of them owe their exalted place in our consciousness to a quiet, gentle and brilliant Englishman.

Today it is gratifying and redeeming to know how right Darwin was and how much his theory has been built upon, and frustrating to keep on realizing how those professing religious certainty threaten to undermine the value of his and others' careful and patient discoveries. Especially in the United States evolution has become a bizarre battleground of extreme opinions and mudslinging, a development that seems to be in step with the tradition of coloring any and every issue with a political hue. In this country, it seems today that you can hardly utter an opinion without attaching a label to it. You cannot simply have an opinion or take a position, no matter how grounded in fact it is; your position has to be Republican, Democrat, Libertarian, Neo-Conservative, Socialist or Atheist. If none of these, it has to be Centrist then.

When it comes to evolution, attaching the label of "Darwinism" has obscured the importance and power of the theory of natural selection. On one hand, those who defend the label sometimes make it sound as if Darwin was the beginning and end of everything to do with evolution. This is simply untrue; in his creation of the theory of natural selection, Darwin was a little like Martin Luther King. The Civil Rights movement owed an incalculable debt to King, but King was not the Civil Rights movement. On the other hand, those who oppose the Darwinist label make it sound like all of us who "believe" in evolution and natural selection have formed a cult and get together every weekend to worship some Darwin idol.
Unfortunately both these positions only serve to obfuscate the life and times of the man himself, a simple, gentle and brilliant soul who painfully struggled with reconciling his view of the world with prevailing religious sentiments and who thought it right to cast his religious views aside in the end for the simple reason that his findings agreed with the evidence while the others did not. Darwin Day should be a chance to celebrate the life of this remarkable individual, free from the burdens of religion and political context that his theory is embroiled in today. Because so much has been said and written about Darwin already, this will be more of a personal and selective exposition. Since I am a lover of both Darwin and books, I will tell my short story of Darwin as I discovered him through books.

When you read about his life for the first time, Charles Darwin does not evoke the label of "genius", and this superficial incongruence continues to beguile and amaze. His famous later photographs show a bearded face with deeply set eyes. His look is gloomy and boring and is not one which elicits the image of a sparkling, world-changing intellect and incendiary revolutionary taking on an establishment steeped in dogma. Darwin was not a prodigy by the standards of his English contemporaries William Hamilton or Lord Kelvin, nor did he particularly excel in school and college. He went to Cambridge, of course, but most well educated Englishmen went to Cambridge or Oxford. At Cambridge, although he studied religion, Darwin had one overriding quality: curiosity about the natural world. He consummately nurtured this quality in field trips and excursions; as one famous story goes, Darwin once held two beetles in two hands and popped one of them in his mouth so that he could free one hand for catching a third very attractive one which he had just noticed. He indulged in these interests much to the chagrin of his father who once said that he would not amount to anything and that he would be a disgrace to his family.

As is well-known, Darwin's story really begins with his voyage of the Beagle when he accepted a position on a ship whose melancholic, manic-depressive captain Robert Fitzroy wanted an educated, cultured man to keep him company on a long and dangerous voyage that circumnavigated the world. For Darwin this was a golden chance to observe and document the world's flora and fauna. One of the best illustrated expositions of Darwin's voyage is in Alan Moorhead's "The Voyage of the Beagle" which is beautifully illustrated with original drawings of the wondrous plants, animals and geological formations that Darwin saw on the voyage. Darwin's own account of the voyage is characteristically detailed and modest and depicts a man enthralled by the beauty of the natural world around him. By the time he set off on his historic journey, young Charles had already been inspired by his teacher Charles Lyell's book on geology that talked about geological changes over vast tracts of time: in time, “Principles of Geology” would become a seminal text and a touchstone of the Great Books program. As is also rather well known, evolutionary ideas had been in the air for quite some time by then (as marvelously documented in Rebecca Stott's recent book "Darwin's Ghosts", which traces evolutionary thinking back to Aristotle and even before), and Darwin certainly was not the first to note the rather simple fact that organisms seem to have changed over time, a view that nonetheless and naturally flew in the face of religious dogma. Most importantly, Darwin was well aware of Thomas Malthus's famous argument about the proliferation of species exceeding the resources available to them, an idea whose logical extension would be to conjecture a kind of competition between species and individuals for finite resources. The "struggle for survival", taught today in school textbooks, a phrase that became much maligned later, nonetheless would have been obvious to a man as intelligent and perceptive as Darwin when he set off on his voyage.

Biology, unlike mathematics or physics, is a science more akin to astronomy that relies on extensive tabulation and observation. Unlike a theoretical physicist, a biologist would be hard-pressed to divine truths about the world by armchair speculation. Thus, painstakingly collecting and classifying natural flora and fauna and making sense of its similarities and differences is a sine qua non of the biological sciences. Fortunately Darwin was the right man in the right place; endowed with a naturally curious mind with an excellent memory for assimilation and integration, he was also unique and fortunate to embark on a worldwide voyage that would enable him to put his outstanding faculties to optimum use. Everywhere he went he recorded meticulous details of geology, biology, anthropology and culture. His observation of earthquakes and rock formations in South America and his finding of fossils of giant mammals lend credence to his beliefs about organisms being born and getting extinguished by sometimes violent physical and planetary change. His observation of the Pacific and Atlantic islanders (especially the ones on Tierra del Fuego) and their peculiar customs underscored the diversity of human life along with other life in his mind. But perhaps his best known and most important stop came after several months of traveling, when the ship left Ecuador to dock at the Galapagos Islands.

Again, much has been written about the Galapagos Islands and about Darwin's Finches (most notably by Jonathan Weiner in his “The Beak of the Finch”). The truth is subtler, both simpler and more interesting than what it is made out to be. Darwin had mistaken his famous finches for other species of birds. It was only after coming back that his friend, the ornithologist John Gould, helped him to identify their correct lineage. But finches or not, the birds and the islands provided Darwin with a unique opportunity to study what we now know as natural selection. The islands were separated from each other by relatively small distances and yet differed significantly in their geography and flora and fauna. On each island Darwin observed similar plants and animals that were yet distinct from each other. As in other places, he also observed that species seemed to be adapted to their environment. Geographic isolation and speciation were prominent on those hot, sweaty and incredibly diverse landmasses.

After five years of exhaustive documentation and sailing Darwin finally returned home for good, much changed both in physical appearance and belief. His life following the voyage has been the subject of much psychological speculation since he settled down with his cousin Emma and never ever left the British Isles again. He also seemed to have been stricken with what today is noted by many authors as a kind of psychosomatic illness because of which he was constantly ill with abdominal and other kinds of pains. After living in London for some time, Darwin retired to Down's House in Kent where he peacefully lived the rest of his life with a kind and loving wife, playing with his children, taking walks along the path at the back of his house named the "Sandwalk", corresponding with intellectuals around the world and constantly interrupting his research with salutary visits to spas and resorts for "natural" treatments that were often of dubious value.

But peaceful as his life was, psychologically Charles Darwin was fomenting a maelstrom of revolution that was to have earth-shaking implications. Another fact that is frequently emphasized in contemporary discourse is his hesitation to not publish his ideas for another twenty-five years. Darwin was planning to write it for a while, but was finally jolted into writing it when he received a letter from an obscure young naturalist named Alfred Russell Wallace who was living a hard life of science and natural history exploration in Indonesia. Wallace had read some of Mr. Darwin's papers and manuscripts and had been struck by the similarity of his ideas to his own. Would Mr. Darwin comment on them? Darwin finally realized that he had to act to prevent getting scooped but characteristically credited Wallace in his published work.

In my mind however, Darwin's procrastination and its story sounds much simpler than the mystique and psychological speculation that sometimes envelop it. As we noted earlier, Darwin was a highly trained biologist and scientist of the first caliber. He knew that he would have to exhaustively document and classify the windfall of creatures, plant and rock specimens that he had collected on his voyage. Apart from thinking and writing about his Beagle collections, Darwin also maintained an astonishingly comprehensive and detailed research program on marine invertebrates and barnacles. More tellingly, he did experiments to find out if seeds are viable even when dispersed over long distances over salt-water. He visited gardens and zoos, and quizzed pigeon breeders about their profession. Much of this was in preparation for the grand act that was to follow. In case of the barnacles and marine creatures, Darwin's research was second to none. He published several extremely detailed books on the minutiae of these organisms; some of these had titles which would have put anyone to sleep.

And yet the level of detail in them reflects the extraordinary patience, power of observation and meticulous hard work that characterized the man, characteristics crucial for developing the theory of natural selection. Darwin was also very fortunate to have had several friends and colleagues who were experts in areas that he was not, who helped him classify and name all the material. Foremost among his correspondents were Charles Lyell and Joseph Hooker to whom he confided not just his scientific questions but also his emerging convictions about the interconnections and implications that were emerging from his research and writing. Also as noted above, John Gould accomplished the crucial task of reminding Darwin that his Galapagos birds were finches. With help from these collaborators and his own studies and thoughts on his observations, thoughts that filled literally dozens of rough drafts, scribblings and private diaries, Darwin finally began to glimpse the formation of a revolutionary chain of thought in his mind.

But Darwin did not rush forth to announce his ideas to the world, again for reasons that are obvious; Victorian England was a hotbed of controversy between science and religion, with many distinguished and famous scientists there and in other countries not just fervently believing in God, but writing elegant tomes that sought a supernatural explanation for the astounding diversity of life around us. Cambridge was filled with intellectuals who sought a rational framework for God's intervention. Darwin would have been quite aware of these controversies. Even though Darwin's grandfather (a more pugnacious character) himself had once propounded an evolutionary view, Darwin was finely attuned to the sensitive religious and social debate around him. Not only did he not want to upset this delicate intellectual and spiritual balance and get labeled as a crackpot, but he himself had not started his voyage as a complete non-believer. One can imagine the torment that he must have faced in those early days, when the evidence pointed to facts that flew in the face of deeply held or familiar religious beliefs. One of the factors that dispossessed Darwin of his religious beliefs was the stark contradiction between the observation of a cruel and ruthless race for survival that he had often witnessed first hand, and the image of an all-knowing and benign God who kindly reigned over his creations. As the evidence grew to suggest relationships between species and their evolution by the forces of natural selection that preserved beneficial characteristics, Darwin could no longer sustain two diametrically opposite viewpoints in his mind.

Opponents of evolution who want to battle the paradigm not from a scientific viewpoint (because they can't) but from a political one frequently raise a smokescreen and proclaim that evolution itself is too complex to be understood. The tricksters who propagate intelligent design further attest to the biochemical complexity of life and then simply give up and say that only an omniscient God (admittedly more complex than the systems whose complexity they are questioning) could have created such intricate beauty. The concept of a struggle for survival has also been hijacked by these armies of God who proclaim that it is this philosophy that would make evolution responsible for genocide, fascism and the worst excesses of humanity. This is a deeply hurtful insult to natural selection and evolution as only the most dogmatic believers can deliver.

One thing that constantly amazes you about evolution is its sheer simplicity. Stripped down to its essentials, the "theory" of evolution can be understood by any school child.
1. Organisms and species are ruthlessly engaged in a constant struggle for survival in which they compete for finite resources in a changing environment.
2. In this struggle, those individuals who are more adapted to the environment, no matter how slightly, win over other less adapted individuals and produce more offspring.
3. Since the slight adaptations are passed down to the offspring, the offspring are guaranteed to preserve these features and therefore are in a position to survive and multiply more fruitfully.
4. Such constant advantageous adaptive changes gradually build up and, aided by geological and geographical factors, lead to the emergence of new species.

It's almost like a simple three-step recipe that when followed keeps on churning out culinary wonders of staggering complexity and elegance. In my mind the beauty of evolution and natural selection is two-fold; firstly, as Darwin emphasized, the slightest adaptation leads to a reproductive advantage. Such slight adaptations are often subtle and therefore sometimes can sow confusion regarding their existence; notice the debate between driver and passenger mutations in fields ranging from evolutionary biology to oncology. But the confusion should be ameliorated by the second even more striking fact; that once a slight adaptation exists, it is guaranteed to be passed on to the offspring.

As Gregor Mendel hammered the mechanism for natural selection in place a few years after Darwin with his discovery of genetic inheritance, it became clear that not every one of the offspring may acquire the adaptation. The exact pattern may be complex. But even if some of the offspring acquire it, the adaptation is then guaranteed to confer reproductive fitness and will be passed on. This fact should demolish a belief that even serious students of evolution, and certainly laymen, have in the beginning; that there is something very uncertain about evolution, that it depends too much on "chance". The key to circumvent these misgivings is to realize the above fact, that while adaptations (later attributed to mutations) may arise by chance, once they arise, their proliferation into future generations is virtually certain. Natural selection will ensure it. That in my mind is perhaps Darwin's greatest achievement; he finally found a mechanism for evolution that guarantees its existence and progress. As for the struggle for survival, it certainly does not mean that it results in non-cooperation and purging of other individuals. As examples in the living world now document more than convincingly, the best reproductive fitness can indeed come about through altruistic leanings and cooperative behavior.

Every one of these factors and facts was detailed and explained by Darwin in "The Origin of Species", one of the very few original works of science which remain accessible to the layman and which contained truths that have not needed to be modified in their basic essence even after a hundred and fifty years. It was readable even when I picked it up as a callow young college student. No one who approaches it with an open mind can fail to be taken with its simplicity, elegance and beauty. One of the most extraordinary things about Darwin and something that continues to stupefy is how right the man was even when he lacked almost all the modern tools that have since reinforced basic evolutionary ideas. As one of Darwin's intellectual descendants, the biologist E O Wilson says, it is frustrating for a modern biologist to discover an evolutionary idea through his work, and then go back a hundred and fifty years and discover that the great man had hinted at it in his book.

And yet as Darwin himself would have acknowledged, there is much in the book that needed to be modified, there was much that he could not explain. Darwin had no inkling of genes and molecular biology, nor could he come up with a convincing mechanism that explained the sheer age of the earth required for evolutionary processes to work their charm (the mechanism was found later with the discovery of radioactivity). The exact mechanism of passing on adapted characteristics was unknown. Major fossils of primates and humanoid ancestors had yet to be discovered. Quite importantly, random genetic drift which is completely different from natural selection was later discovered as another process operating in evolution. The development of viral and bacterial resistance in causing diseases like AIDS finally brought evolution to the discomfort of the masses. It was only through the work of several evolutionary biologists and geneticists that Darwin finally became seamlessly integrated with the understanding of life in the middle twentieth century. Genomics has now proven beyond a shade of doubt that we truly are one with the biosphere. But in the absence of all these developments, it is perhaps even more remarkable how many of Darwin's ideas still ring true.

There is another factor that shines through in "The Origin"; Darwin's remarkable modesty. One would have to search very hard in history to find a scientist who was both as great and as modest. Newton may yet be the greatest scientist in history, but he was nothing if not a petty, bitter and difficult man. Darwin in contrast was a symbol of kindly disposition. He doted on his children and told them stories. He loved and respected his wife even though their religious views gradually grew more distanced. His written correspondence with her was voluminous and fond. His correspondence with his collaborators, even those who disagreed, was cordial and decent. Never one for contentious public debates, he let his "bulldog" Thomas Henry Huxley fight his battles; one of them with Bishop Samuel Wilberforce ended in a famous showdown when the Bishop inquired whether it was through his father or mother that Huxley had descended from an ape, and Huxley countered that he would rather descend from an ape than from the Bishop. Darwin stayed away from these entertaining confrontations; as far as he was concerned, his magisterial work was done and he had no need for public glory. To the end of his life this kind and gentle man remained a wellspring of modest and unassuming wonder. His sympathetic, humane and sweet personality continues to delight, amaze and inspire reverence to this day.

In the later stages of his life Darwin became what he himself labeled as an agnostic but what we today would probably call an atheist. His research into the progression of life and the ruthless struggle that it engenders made it impossible for him to justify a belief in a paternal and loving deity. He was also disillusioned by popular conceptions of hell as a place where non-believers go; Darwin's father was a non-believer and yet a good doctor who treated and helped hundreds of human beings. Darwin simply could not accept that a man as kind as his father would go to hell simply for not believing in a version of morality, creation and life trotted out in a holy book. Probably the last straw that convinced Darwin of the absurdity of blind faith was the untimely death of his young daughter Annie who was his favorite among all the children. According to some accounts, after this happened, Darwin stopped even his cursory Sunday trips to church and was satisfied to take a walk around it while not at all minding his wife and children's desire to worship inside.

The second fact is also in tune with Darwin's kind disposition; he admittedly had no problem reconciling the personal beliefs of other people with his conviction about their falsity. Darwin's tolerance of people's personal faith and his unwillingness to let his own work interfere in his personal life and friendships is instructive; to the end he supported his local parish and was close friends with a cleric, the Reverend John Innes. Darwin's example should keep reminding us that it is actually possible to sustain close human bonds while having radically different beliefs, even when one of these is distinctly true while the other one is fantasy. Nurturing these close bonds with radical scientific ideas that would change the world for ever, Charles Darwin died on April 19, 1882, a content and intellectually satisfied man.

To follow, nourish and sustain his legacy is our responsibility. In the end, evolution and Darwin are not only about scientific discovery and practical tools arising from them, but about a quest to understand who we are. Religions try to do this too, but they seem to be satisfied with explanations for which there is no palpable evidence and which seem to be often contradictory and divisive. It is far better to imbibe ourselves with explanations that come from ceaseless exploration and constant struggle; the very means that constitute these explorations are then much more alluring and quietly fulfilling than any number of divergent fantasies that can only promise false comfort. And these means promise us a far more humbling and yet grand picture of our place in this world. Especially in today's age when the forces of unreason threaten to undermine the importance of the beautiful simplicity in the fabric of life that Darwin and his descendants have unearthed, we owe it to Charles Darwin to continue to be amazed at the delightful wonder of the cosmos and life. We owe it to the countless shapes and forms of life around us with whom we form a profoundly deep and unspoken connection. And we owe it to each other and our children and grandchildren to keep rationality, constructive skepticism, freedom and questioning alive.

LITERATURE ON DARWIN:

I don't often write about Darwin and evolution here for a simple reason; there is literally an army of truly excellent authors and bloggers who pen eloquent thoughts about these subjects and the amount of stuff published about him will fill up entire rooms. You could probably put together a thousand-page encyclopedia simply listing works on Darwin. His original work as stated above is still very readable. Every aspect of his life and work - the scientific, the psychological, the social, the political and the personal - has been exhaustively analyzed. I have certainly not sampled more than a fraction of this wealth of knowledge, but based on my interest in Darwin and selected readings, I can recommend the following.

For what it's worth, if you want to have the best overview of Darwin's life after he came home from his voyage on the Beagle, I think nothing beats the elegance of language and wit of David Quammen's "The Reluctant Mr. Darwin". Quammen has exhaustively researched Darwin's post-Beagle life and work, and no one I have come across tells the story with such articulate enthusiasm, fondness and attention to detail in a modest sized book.

Janet Browne's magisterial biography of Darwin is definitely worth a look if you want to get all the details of his life. Browne pays more attention to the man than the science, but her work is considered the authoritative work, and there are nuggets of eloquence in it.
As a student in high school I was inspired by Alan Moorehead's "The Voyage of the Beagle" noted above which combines an account of Darwin's life and voyage with beautiful and full page illustrations.
Geting to evolution now, there's an even bigger plethora of writings. Several books have captured my attention in the last many years. I don't need to extol the great value of any (and indeed, all) of Richard Dawkins' books. If you ask me which ones I like best, I would suggest "The Selfish Gene", "The Extended Phenotype", "Climbing Mount Improbable" and "The Blind Watchmaker". For a journey into our ancestral history, Dawkins' strikingly illustrated "The Ancestor's Tale" is excellent. Speaking of ancestral history, Neil Shubin's "Our Inner Fish" charts a fascinating course that details how our body parts come from older body parts that were present in ancient organisms. So does his recent book "The Universe Within". Shubin provides scores of interesting tidbits; for instance he tells us how hernias are an evolutionary remnant. Another great general introduction to evolution is Carl Zimmer's "Evolution"; Zimmer has also recently written excellent books on bacteria and viruses in which evolution plays a central theme.

No biologist- not even Dawkins- has had the kind of enthralling command over the English language as Stephen Jay Gould. We lost a global treasure when Gould died at age sixty. His books are relatively difficult to read and for good reason. But with a little effort they provide the most sparkling synthesis of biology, history, culture and linguistic exposition that you can ever come across. And all of them are meticulously researched, although Gould’s political ideology sometimes has to be watched out for. Out of all these I personally would recommend "Wonderful Life", and if you want to challenge yourself with a really difficult unedited original manuscript written just before he died, "The Hedgehog, the Fox and The Magister's Pox". His collections of essays - "Full House" and "Eight Little Piggies" for instance - are also outstanding.

I don't want to really write about books which criticize creationism since I don't beat that horse much, but if you want to read one book about the controversy that rips apart intelligent design proponents' arguments, read Ken Miller's "Finding Darwin's God" which makes mincemeat out of the usual "arguments from complexity" trotted out by creationists which are actually "arguments from personal incredulity". He also has a book covering the Dover Trial. I have only browsed it but it seems to be equally good read. What makes Miller a tough target for creationists (and puzzling for evolutionists) is that he is a devout Christian.

This is an updated and revised version of a post originally written on Darwin's 200th birthday.