Harry Kroto (1939-2016): A salesman of science in the best sense of the term

Harry Kroto who sadly passed away yesterday at 76 co-discovered fullerenes and was a passionate communicator of science. After he got the Nobel Prize, he devoted all his time to spreading the excitement of science in developing countries. Among other things he started the Vega Science Trust website which features interviews with and lectures by many famous scientists, from Feynman to Sanger. 

I had a nice chat with Kroto at the Lindau Nobel Laureate meeting in Germany in 2009. At Lindau he gave a sparkling multimedia presentation that was less science and more of a paean for science. After his talk I wrote a post comparing his presentation to savoring a rich parade of treats, and I think this attitude to science characterized his entire post-Nobel career. Below I reprint the post. Harry's zest for science will be missed

When I visit my favorite restaurant for lunch or dinner, I usually order a legitimate food item from the main course. But once in a while, just to indulge, I order a sample platter of appetizers. The appetizers don’t always provide the deep satisfaction that I get from eating a proper, expensive food item. But they provide me with a different kind of unique satisfaction; they give me a glimpse of what’s new, what’s possible. They provide a view of the diversity that can emerge in a plate of bite-sized chunks. And through their frequent novelty, they give me hope that there are new possibilities on the horizon. These appetizers constitute occasional but necessary fodder. Sir Harold Kroto’s talk was one of the most satisfying platter of appetizers I have sampled, and I had not even ordered it.

Harry Kroto exemplifies the British intellectual tradition at its best. He has three passions; science, education and humanism. And in a wonderfully entertaining talk filled with animation, quotes, videos and wit, he exemplified all three qualities. And of course no talk is ever really interesting without being a little provocative, so there was plenty of that too.

Kroto shared the Nobel Prize in 1996 for discovering a chemical structure that has become a cornerstone of our scientific imagination in the same way that DNA has. The fullerenes that he, Robert Curl and Richard Smalley discovered have symbolized scientific discovery. The myriad odd structures emerging from these structures including carbon nanotubes give us the hope of novel technologies in engineering and medicine. Since his discovery of buckyballs in 1985, Kroto has turned toward other endeavors. He has strived to make his beloved science accessible to those who would most benefit from it, namely children around the world. To do this he travels all over the world and organizes local groups in developing and developed countries who teach children about science.

Kroto believes that science should always be presented in an attractive way for it to become truly appealing. To this end his talk reflected this style. Each of the slides was highly pictorial, filled with rapid animation, videos and quotes, exactly the dose of inspiration and fun that a roomful of 500 excited science students and young researchers needed. The talk began with an exposition of “chemistry in 30 seconds”. It must have been a module that Kroto and his team designed for students; starting from simple numbers and figures Kroto derived the periodic table on the screen. The next few slides explored molecular flexibility, an important consideration which is paramount in the biological activity of drugs for instance. Kroto’s own speciality- microwave spectroscopy- examines this phenomenon and was key in the discovery of fullerenes. Kroto’s story is the quintessential story of serendipitous scientific discovery. 

His real interest was the study of molecules found in outer space. One day during this exploration he and his team accidentally discovered a peak in their spectrum, something that they were not looking for. Today a PhD. advisor may severely reprimand a graduate student if he tries to assign a chemical structure to a single signal in a complex spectrum. But Kroto and independently Smalley and Curl investigated this anomaly. As they say, the trick in science consists of seeing what everyone sees, and thinking of what nobody thinks. The rest is history, although Donald Huffman and Wolfgang Krätschmer had to synthesize fullerene in measurable quantities to meticulously characterize it.

After encapsulating chemistry in 30 seconds, Kroto moved on to the topic of science education. Some of the brightest children in the world are the most pressed for access to scientific knowledge. As I write this and look at the young scientists and bloggers around me, I ask myself, “What if we had been born in Somalia, or the DRC, or El Salvador, or a tiny village in China or India?”. We each have to realize that most of us are privileged in doing what we do not just because of our own intrinsic capabilities of learning but because of fortunate circumstances, educated parents and plain old good luck. We should continue to remember that there are kids brighter than us, kids who potentially could make Nobel Prize winning contributions, who don’t have the tiniest chance to climb the ladder of education. We owe it to ourselves to make sure if we can, to invest a tiny amount of effort in our own way to educate those who have not been fortunate to educate themselves.

To achieve this, Kroto has started the Vega Science Trust which seeks to communicate the value of science and common sense thinking to children in poor countries. In this respect Kroto is not a general who dictates from the sidelines. He is a foot soldier who is out there in the field. Photographic evidence of this fact came from several photos of Kroto teaching science to children in Mexico, Florida, China and Africa. The children were wearing t-shirts that were proudly emblazoned with fullerenes. The teaching of science extended to the spiritual; “fullerene meditation” in which children balance fullerenes on their heads while adopting a state of quiet contemplation. Kroto also emphasized the importance of the three bastions of modern information access, Google, Wikipedia and Youtube. All three constitute important forms of information access for millions of people in the future. Especially Wikipedia is a tremendous example of the remarkable wealth of high-quality knowledge and intense interest that individuals have in contributing to it.

The Vega Science Trust also has a really great website which has free access to interviews with Nobel Prize winners and other scientists, lectures by famous scientists (including a fantastic set of four one-hour lectures by Richard Feynman) and many other science resources. I have listened to several of the interviews and talks on this site and they do an admirable job of inspiring young people to study science.

However, educating children is not just educating them about science, because science itself is not simply about facts but about a process of constant questioning and revision. Sir Harold’s third passion, humanism, firmly rests on the pillars of open criticism and inquiry that exemplify science. Humanism is not necessarily a rejection of religion, but it is an active and relentless emphasis on critical thinking, equality and skeptical thought.

Here is where the talk became provocative because when you start talking about impediments to learning you inevitably have to mention religion. The science-religion controversy is so widespread that you think that everything possible that one can say about it has been said. However Kroto focused on some key aspects. He was categorically clear that children should not be indoctrinated with their parents’ religion and taught that that is the only “right” one. Kroto has spent more than a decade teaching children to be inquisitive, critical and open-minded. Religious indoctrination of children will undo much of what he has been trying to do. But for Kroto the issue goes much further. Religious indoctrination is part of many different environments that the child inhabits. To make his point Kroto showed pictures from the odious creation “museum” in Kentucky, with saddled dinosaurs and with children shown the “evolution” of the earth over the past 6000 years. Even religious moderates should find this spectacle ridiculous. Richard Dawkins has called parents bringing up their children in their own religious tradition as engaging in “child abuse”. While one might debate the merits of such a strong statement, there is no doubt that parents of all stripes must teach their children the value of open exchange and critical thinking.

But why? Why constantly stress the value of scientific thinking? Because otherwise our future generation would not be able to make the contributions that scientists at Lindau have made, and they would not be able to reap the benefits of these discoveries. The current flood of students at Lindau might well dwindle down to a trickle. We depend so intimately on continuous scientific discovery that we largely take it for granted. Too much of the science-religion debate ignores the simple fact that science has led to an enormous reduction in the amount of suffering in our world. As just two examples, Kroto quoted the discovery of anesthetics and penicillin, two discoveries which were watersheds in the amelioration of human disease and suffering. Whatever the positive and negative qualities of religion, the positive qualities of science should be apparent to any person. And it is only through the constant application of critical thinking and healthy skepticism that we have bequeathed the fruits of scientific wisdom.

Thinking about critical thinking and a balanced outlook takes us to the last point that Kroto discussed, and that was the absolutely crucial need for sustainable development. The same rational thinking that has led us away from superstition should also lead us to realize the grave danger that our activities pose to our planet, and the urgent need for prompt and cogent action. If we don’t take care of our planet, we would not be able to take care of ourselves and nothing would matter then; not fullerenes, not education and not the science-religion debate. All that would matter would be the throes of a helpless species which could not prevent its own destruction. For a species which has sequenced its own language of life, sent men to the moon, plumbed the depths of its planet and defied nature by extending its own survival and life-span by leaps and bounds, we owe ourselves more than that.

Albert Einstein once said that “all of science measured against reality is primitive and childlike- and yet it is the most precious thing we have”. This is another profound realization that is frequently lost in the science-religion debate; that science makes no claim to ultimate truths (notwithstanding the utmost self-confidence that some of its practitioners may exhibit) but it has been supremely useful in gradually helping us know and get rid of our biases; as Niels Bohr said, the rather unpretentious goal of science is the gradual removal of our prejudices. To this extent science should be the epitome of modesty. We should be humbled and reminded of our own tiny little space in the universe whenever our eyes stretch across the vast milky way or whenever we view the sheer diversity of the species that populate a rain forest and recognize the deep and intimate relationship we share with these creatures.

At the same time we should feel supremely privileged that science, with the simplest of lessons, has allowed us to transcend our dreams in ways that have been possible for no other species on our planet. Science is not perfect, but the values of open-mindedness and skepticism that it has taught us have not only allowed us to make the world a better place through practical discoveries, but have also engendered the most basic elements of humanity, including a respect for free and open minds that is independent of nationality, gender, race and language. The Lindau meeting proves that science transcends every kind of barrier like no other endeavor. This rare realization, this most unifying of paradigms, is indeed a thing of limitless value. The most precious thing that we have.

Thoughts on personalized medicine

This is a piece I had written up for the annual report of this year's Lindau Meeting of Nobel Laureates. The final version had to be significantly edited because of space limitations so I thought I would post the full version here.

The future of personalized medicine

In this year’s Lindau meeting, the Israeli biochemist Ciechanover expressed great hope for the future of personalised medicine, an age in which medical treatments are customized and tailored to individual patients based on their specific kind disease.

In some ways personalised medicine is already here. Over centuries of medical progress, astute doctors have fully recognized the diversity of patients who are suffering from what appears to be the same disease. Based on their rudimentary knowledge of disease processes, empirical data and experience, physicians would then prescribe different combinations of medicines for different patients. But in the absence of detailed knowledge of disease at the genetic and molecular level, this kind of approach was naturally subjective; it continued to rely on extensive personal experience and ad hoc interpretations of incompletely documented empirical data.

This approach saw a paradigm shift in the latter half of the twentieth century as our knowledge of DNA and genetics revealed to us the rich diversity and uniqueness of individual genomes. Concomitantly, our knowledge of the molecular basis of disease led us to recognize molecular determinants unique to every individual. We are already taking advantage of this knowledge and harnessing it to personalize therapy.

Take the case of the anticancer drug temozolomide for instance. Temozolomide is prescribed for patients with a particularly pernicious form of brain cancer with poor prognosis. The drug belongs to a category of compounds called alkylating agents, a common class of anticancer drugs in which a reactive chemical group is transferred onto DNA in cancer cells, rendering them incapable of efficient cell division and causing their death. The problem is that because of its key role in sustaining life processes, DNA division is tightly controlled. Any kind of modification of the kind caused by temozolomide is treated as DNA damage and- for good reason- life has evolved multiple mechanisms to reverse such damage. In this case the body produces an enzyme that strips DNA of the reactive functionality attached by the drug. Thus the body unwillingly helps cancer cells by reversing the drug’s action. The understanding of this mechanism has led doctors to personalize temozolomide treatment only for individuals who have low levels of the drug-resisting enzyme. For other patients that produce high levels of the enzyme, temozolomide will unfortunately not be effective and doctors will have to turn to other drugs.

We will undoubtedly witness the proliferation of such advances in personalizing individual treatments in the future. But what appears to be an even more promising approach is to start at the source, at the fundamental genomic sequences that dictate the phenotypical changes associated with enzymes and proteins. The deciphering of the human genome has opened up exciting and promising new avenues for mapping differences in individual genomes and harnessing these differences in drug discovery. The most important strategy has been to compare genomes of individuals for single nucleotide polymorphisms (SNPs) which are changes in single base pairs in the DNA sequence. In fact much of the genetic variation between individuals and populations arises from these single nucleotide changes. SNPs have been of enormous value in tracing genetic diseases and generally categorizing variations in our species. They are typically utilised in genome-wide association studies in which the genomes of members of a certain homogeneous population with and without a disease are compared. Knowing the differences can enable scientists to pinpoint genetic markers responsible for the disease. These genetic markers can then be linked to phenotypes like enzyme overproduction or deficiency that are more directly related to the disease. In addition SNPs are unusually stable and remain constant between generations, providing scientists with a relatively time-invariant handle to study genetic disorders. One of the most notable instances of using SNPs to determine propensity toward disease involves the so-called ApoE gene in Alzheimer’s disease. Two SNPs in this gene lead to three alleles- E2, E3 and E4. Each individual inherits one maternal and one paternal copy of the ApoE gene and there is now solid evidence that the inheritance of the E4 allele leads to a greatly increased risk of Alzheimer’s disease.

In the long run, SNP’s may provide the foundation for much of personalised medicine. This is because SNPs also often dictate individuals’ propensity toward drugs, pathogens and vaccines. Thus in an ideal scenario, one might be able to predict a patient’s response to a whole battery of drugs using knowledge of specific SNPs associated with his or her disease.

Unfortunately this ideal scenario may be much farther than imagined. For one thing, we have still only scraped the surface of all possible SNPs, and there are already an estimated three million out there. But more importantly, the difference between knowing all the SNPs and knowing their causal connections to various diseases is almost like the difference between a list of all human beings on the planet on one hand and everything about their lives on the other; their professions, origins, hobbies, political views, family lives. Knowing the former is far from understanding the latter.

In this sense the problem with SNPs illustrates the problems with all of personalised medicine. In fact it’s a problem that plagues scientific research in general, and that’s the dilemma of separating correlation from causation. The problem is even more acute in a complex biological system like a human being where the ratio of extraneous unrelated correlations to genuinely causative factors is especially high. Simply knowing the SNP variations between a healthy and diseased individual is very different from being able to pinpoint the SNP that is directly connected to the disease. The situation is made exponentially more complex by the fact that these putative determinants usually act in combination with each other. Thus one has to now account not only for the effect of an individual SNP but also for the differential effects of its combination with other SNPs. And as if this complexity were not enough, there’s also the fact that many SNPs occur in non-coding regions of the human genome, leading to even bigger questions about their exact relevance. Sophisticated computers and statistical methods are enabling us to sort through this jungle of data, but as of now the data itself clearly outnumbers our ability to intelligently analyse it. We need to become far more capable at distinguishing signal from noise if we are to translate genetic understanding into practical therapeutic strategies.

In addition, while a certain kind of SNP may be able to determine disease tendency, there are also many false positives and negatives. Only a small percentage of SNPs are typically linked to a condition, especially when it comes to complex conditions like cancer, diabetes and psychological disorders. Many SNPs may simply be surrogate SNPs that have little to do with the disease themselves but which have come along for the ride with other SNPs. It is a difficult task to say the least to separate the wheat from the chaff and hone in on the few SNPs that are truly serving as disease determinants or markers. In such cases it is instructive to borrow from the example of temozolomide and remember that ultimately we will be able to untangle cause and effect only by looking at the molecular level interaction of drugs and biomolecules. No amount of data sequencing and analysis can really be a substitute for a robust study designed to directly demonstrate the role of a particular enzyme or protein in the etiology of a disease. It’s also worth noting that such studies have always benefited from the tools of classical biochemistry and pharmacology, and thus practitioners of these arts will continue to stand on an equal footing with the new genomics experts and computational biologists in unraveling the implications of genetic differences.

Finally, there’s the all-pervasive question of nature versus nurture. Along with genomics, one of the most important advances of the last decade has been the development of epigenetics. Epigenetics refers to changes in the genome that are induced by the environment and not hard-coded in the DNA sequence. An example includes the environmentally stimulated silencing or activation of genes by certain classes of enzymes. Epigenetic factors are now known to be responsible for a variety of processes in diseases and health. Some of these factors can even operate in the fetal stage and influence physiological responses in later life. While epigenetics has revealed a fascinating new layer of biological control and has much to teach us, it also adds another layer of complexity to the determination of individual responses to therapy. We have a long way to go before we can perfect the capability to clearly distinguish genetic from epigenetic factors as signposts for individualized therapy.

The future of personalised medicine is therefore both highly exciting as well as extremely challenging. There is much promise to be had in mapping the subtle genetic differences that make us react differently to diseases and their cures, but we will also have to be exceedingly careful in not leading ourselves astray with incomplete data, absence of causation and confirmation bias. It is a tough, but ultimately rewarding problem which will lead to both fundamental understanding and new medical advances. It deserves our attention in every way.

Image source

Lindau 2011: What do you want me to translate now?

In 1969, one of the more memorable incidents in the public advocacy of science took place. The American physicist Robert Wilson was asked to testify before Congress in support of the construction of the Fermi National Accelerator Laboratory, known as Fermilab. For Wilson, building this huge machine had been a labor of love and nobody had a better background for it. He had worked on the Manhattan Project where he was the youngest group leader in the experimental division, and after the war he had become a professor at Cornell University.

Wilson was a first-rate amateur architect who saw accelerators as works of art. He lovingly designed Fermilab with his own hands and, in order to add to the aesthetic appeal of the place, turned the surrounding acres into a wilderness housing bison and geese. His efforts paid off; Fermilab would become the largest accelerator in the United States and CERN's primary competitor. In 1969 Wilson was asked to justify the expenditure for the multi-million dollar laboratory in front of Congress. The Cold War was raging, most research and especially physics research was being viewed in the context of national security, and Wilson was specifically asked what contribution the new laboratory would make to national defense. He replied in words that should be etched on the foundation stone of every center of basic research. The research, he said, had no direct bearing on national defense. Instead,

It has only to do with the respect with which we regard one another, the dignity of men, our love of culture. It has to do with: Are we good painters, good sculptors, great poets? I mean all the things we really venerate in our country and are patriotic about. It has nothing to do directly with defending our country except to make it worth defending.

It has nothing to do directly with defending our country except to make it worth defending. In saying these words, Wilson was appealing to the heart of what makes any country great. It is not the fancy cars, the shiny malls, the great financial houses and the cornucopia of industrial food that truly contribute to a country's progress. At one point or another in history, Athens, Florence, Takshashila, Baghdad, Oxford, Gottingen, Copenhagen and Philadelphia were primarily known not for their wealth and the splendor of their monuments but for the unmatched wealth of ideas about science, art, economics, politics, freedom and human dignity that their citizens generated. These ideas are now the bedrock of much of modern civilization. Many of these ideas were solutions to practical problems, but most only sought to explore and push the boundaries of human creativity, curiosity, passion and tolerance. The creators and dreamers of these ideas were less concerned about their practical application and more concerned about their ability to answer questions about human origins and nature, our place in the cosmos and our relationship to other human beings.

Why am I retelling the story of Robert Wilson? Because I believe it strikes at the heart of what these days is fashionably called "translational research". Just like physics research was being viewed through the lens of national defense in the 60s, basic biomedical studies run the risk of being viewed through the lens of translational research in the 2010s. The approach is clearly not popular among leading researchers. In 2009, Nobel Laureate Martin Chalfie gave a talk at Lindau in which he described the great satisfaction he had had from doing non-translational research (in fact Chalifie was going to give a talk about this very topic this year at Lindau but unfortunately could not attend). Chalfie is not alone; as just another example, a few months ago I attended a lecture by another Nobel Laureate, Thomas Steitz, also at Lindau this year. Steitz who won the prize for his exploration of the structure and function of the ribosome proudly announced at the beginning of the talk that "the only kind of translation I have worked on is that orchestrated by the ribosome".

So what is translational research? Many definitions seem to abound and Wikipedia seems to be as good a guide as any: "Translational research is a way of thinking about and conducting scientific research to make the results of research applicable to the population under study and is practised in the natural and biological, behavioural, and social sciences". The goal of translational research especially in medicine seems to transform basic biomedical research discoveries from "bench to bedside".

In the last few years this kind of thinking has has swamped the public discourse on science. New centers are being founded and funded whose mandate is to translate basic research into products directly benefiting humanity. The NIH, the largest biomedical research agency in the world, has also embraced a new National Center for Advancing Translational Research. The director of the NIH, Francis Collins, has not tired of pointing out the exciting advances in discovering new drugs which would be made possible by harnessing data from the human genome project. Not surprisingly, the press has eagerly jumped on the bandwagon, with reports pitching translational research and personalized medicine regularly appearing in the nation's leading papers. Echoing leading scientists, the press seems to be telling us that we should all look forward to supporting translational research in its various guises.

All this makes the idea of translational research sound promising. And yet there must be a good reason why distinguished Nobel Prize winners like Chalfie and Steitz bristle at the mention of translational research. The reason is actually not too hard to discern. The problem is not with applied research per se. Nobody can doubt that applied research especially done by the pharmaceutical and biotechnology industries has saved innumerable lives in the last one hundred years. As Pasteur said, "there is science and the applications of science", and he saw them lying on a continuum. No, there is nothing wrong with trying to turn basic ideas into applied products.

What is wrong is that translational research is being seen as a panacea that will address the flagging rate of new biomedical advances. The thinking seems to declare that if only more people were given more money and deliberately focused on direct application, we would suddenly see a windfall of new therapies against disease. This thinking suffers from two major problems.

The first problem is that history is not really on the side of translational research. Most inventions and practical applications of science and technology which we take for granted have come not from people sitting in a room trying to invent new things but as fortuitous offshoots of curiosity-driven research- the kind that Chalfie and Steitz have dedicated their lives to. Penicillin was discovered through serendipity by a most alert Alexander Fleming who was trying to plate bacterial cultures, not one trying to actually discover the next breakthrough antibiotic. Nuclear Magnetic Resonance was discovered by physicists who were tinkering with atoms in magnetic fields, not ones who were trying to find a method for determining the structures of organic and biological molecules. The discovery of most drugs built upon basic discoveries about human physiology and anatomy made by physicians and researchers who were simply trying to find more about how the body works. The new class of drugs inhibiting protein kinases for instance ultimately owe their development to the discovery of phosphorylation, a fundamental discovery by this year's Lindau attendee Edmond Fischer that was a result of purely basic scientific thinking about how chemical signals are communicated by cells. Similarly, Steitz's ribosome and Chalfie's green fluorescent protein are lending themselves to drug discovery and medical advances in ways which they never planned.

If the history of science teaches us anything, it is that curiosity-driven basic research has paid the highest dividends in terms of practical inventions and advances. Tinkering, somewhat aimless but enthusiastic exploration of biological and physical systems and following one's nose have been the ingredients for some of the key inventions that have transformed our lives. Radar, computers, drugs, detergents, plastics and microwave ovens were all made possible not because someone sat down and tried to discover them but because they arose as fortuitous consequences of elemental, pure research. The hype of translational research not only deflects attention from curiosity-driven basic research but also creates the illusion that asking people to discover new things is the best way to generate new ideas. In fact, trying to discover new things by forcing people to discover them will only siphon off funds from those who have the actual capability of discovering these things.

The second more practical but equally important problem with translational research is that it puts the cart before the horse. First come the ideas, then come the applications. There is nothing fundamentally wrong with trying to build a focused institute to discover a drug, say, for schizophrenia. But doing this when most of the basic neuropharmacology, biochemistry and genetics of schizophrenia is unknown is a great diversion of focus and funds. Before we can apply basic knowledge, let's first make sure that the knowledge exists. Efforts based on incomplete knowledge would only result in a great squandering of manpower, intellectual and financial resources. Such misapplication of resources seems to be the major problem for instance with a new center for drug discovery that the NIH plans to establish. The NIH seeks to channel the new-found data on the human genome to discover new drugs for personalized medicine. This is a laudable goal, but the problem is that we still have miles to go before we truly understand the basic implications of genomic data. It is only recently that we have started to become aware of the "post-genomic" universe of epigenetics and signal transduction. We have barely started to scratch the surface of the myriad ways in which genomic sequences are massaged and manipulated to produce the complex set of physiological events involved in disease and health.

And all this does not even consider the actual workings of proteins and small molecules in mediating key biological events, something which is underlined by genetics but which constitutes a whole new level of emergent complexity. In the absence of all this basic knowledge which is just emerging, how pertinent is it to launch a concerted effort to discover new drugs based on this vastly incomplete knowledge? It would be like trying to construct a skyscraper without fully understanding the properties of bricks and cement.

Chalfie, Steitz and others like them are also right to criticize the frenzy that translational research generates in the popular press. We live in an age when buzzwords are eagerly generated and lapped up by the media. These buzzwords usually run roughshod over subtleties and ambiguities and the press seldom has a taste for indulging these in the first place. Needless to say, committing national resources and public attention to translational research when most of the basics are still to be understood is an endeavor fraught with great risk and uncertainty. It would be far wiser to bolster basic research that can bring us to the brink of real application. There are places where such research is conducted. They are called universities.

Ultimately, the importance of basic research goes back to what Robert Wilson said to Congress. It has to do with the same reasons that we created the Mona Lisa, painted the Sistine Chapel, built Chartres Cathedral, wrote The Love Song of J. Alfred Prufrock and composed the Goldberg Variations. Da Vinci, Michelangelo, T. S. Eliot and Bach were all trying to find the essence of man's soul and his relationship with the universe and with his fellow men. So were Einstein, Newton, Faraday and Darwin. They were not trying to invent a better mousetrap, but the world did beat a path to their door. Similarly, once our basic understanding of biological systems is firmly in place, translation will willingly follow.

The next researcher, when asked to comment on the relevance of his or her basic studies in cell biology to translational research, should echo Wilson: "It has nothing to do directly with translational research, except to enable it".

Lindau 2011: What do scientists do after winning the Nobel Prize?

Most of us know about the prize-winning work of this year's Lindau Nobel Laureates, but how many of us keep track of what they did after winning the coveted honor? Scientists' lives after the Nobel Prize change dramatically. As former Lindau attendee Richard Ernst put it, they are now expected to be oracles on everything from international politics to religion, even when their knowledge of most other things is as limited as that of other people. There is no common thread; after winning the Prize, scientists' lives become as varied as those of all of us and in some cases a little more interesting. Here's a short portrait of life after the Nobel Prize illustrated with a select few examples...

Read the rest of the post on the Lindau blogs site...

Lindau 2011: From designing airplanes to designing proteins

An inspiration from the birth of aviation

A few weeks ago I visited the small coastal town of Kitty Hawk in North Carolina. Kitty Hawk is where the Wright brothers made their epoch-making first powered flight. Big stones mark the start and end points of the flight. There is a huge monument on top of a hill where they took off and then there are three stones at varying distances at ground level. The three stones indicate the distances covered on every flight; the brothers clearly got better at flying on every attempt.

The Wright brothers' story is inspiring not only because of the watershed in human history which they orchestrated but also because it shows the evolution of a technology at its best. The projects which the brothers undertook cost a few hundred dollars and should serve as a beacon of inspiration in this era of "big science" involving hundreds of millions of dollars. The brothers had a bicycle workshop in which they fashioned many of the components of their infant gliders. They drew inspiration from Otto Lillienthal who had been the first aviation pioneer to make successful glided flights; tragically, Lillienthal was killed on one of his flights, but not before saying "Kleine Opfer müssen gebracht werden!" ("Small sacrifices must be made!").

One of the most important lessons that the Wrights learnt from Lillienthal's adventures was the great value of building 'toy' models. Toy models start from the simplest possible systems which retain the essential features of a phenomenon and then work their way towards greater complexity. This philosophy has been used by many other pioneers of technology, including the scientists and engineers who made the moon landings possible...

Read the rest of the entry at the Lindau blogs website...

Lindau 2011: The beginning

This year I am privileged to be invited again to write for and attend the 61st Meeting of Nobel Laureates in Lindau, Germany. This year's meeting is dedicated to Physiology or Medicine and the list of attendees provides a glimpse of the diversity and impact of biomedical research. These men and women have made enormous contributions to our understanding of biological systems, from elucidating structures and pathways to providing tools of inestimable value. My first post just went up and I will be linking to others as I write more. Here's the first one.

From messy to magical: Preparing for the future of medicine

In the early 1940s, as war raged over the continent, the British mathematician Freeman Dyson and the Indian physicist Harish Chandra were taking a walk in Cambridge. Harish Chandra was studying theoretical physics under the legendary Paul Dirac while Dyson was getting ready to spend a depressing time calculating bombing statistics at Bomber Command.

“I have decided to leave physics for mathematics”, quipped Harish Chandra. “I find physics messy, unrigorous, elusive”. “That’s interesting”, replied Dyson. “I am planning to leave mathematics for physics for exactly the same reason.” Leave their respective disciplines the two did, and both of them had highly distinguished careers in their new fields at the Institute for Advanced Study in Princeton.

I narrate this story because I can imagine almost exactly the same conversation taking place today between a biomedical researcher and any other kind of natural scientist. In fact it’s interesting to compare the status of medicine today with the status of physics when Dyson and Harish Chandra had their conversation. By 1940 physics had underwent a great revolution in the form of quantum mechanics and relativity. Yet there was much to be done and the “second revolution” was in the making. In retrospect it’s clear that very little was known about the strong and weak nuclear forces and nothing was known about the particle “zoo” that would be uncovered in the next few years. It took the efforts of many brilliant individuals to unify crucial concepts and make the whole structure look more consistent and complete.

Medicine in the year 2011 is like physics in the year 1940. Just like physics it has had a recent revolutionary past in the advent of molecular biology. Just like physics there is much of it that is “messy, unrigorous, elusive”. And it’s exactly these qualities that make it a field ripe for another revolution. The future beckons for medicine and biology today as it did for physics in 1940.

Read more at the Lindau blogs website...

Lindau: The teachings of the savants

Marie Curie once said that "Science is about things, and not people". While this statement is true and profound, the fruits of science are unmistakably linked to their human origins, postmodernist relativism notwithstanding. The scientists who make discoveries are human beings, and they shoulder their share of foibles and successes, petty rivalries and forthcoming generosity, despair and triumph. Their life displays cycles that any young researcher will go through in his or her future career...

...more

Lindau: Who is the joke going to be on?

When the controversial and talented physicist Edward Teller was doing a PhD. with the great Werner Heisenberg at the University of Leipzig, the question asked at the end of every group meeting that focused on a complex sequence of problems was "Wo ist der Witz?", supposed to be translated as "What is the point"? but more correctly translated as "What is the joke?". The joke part of it consisted of turning a wry eye at the world, donning the hat of the court jester who laughs even as the fire that he predicted would engulf the world rages on. The question about global warming that we ask is also "Wo ist der Witz"? and we only hope that the joke is not upon us and we can actually still get the last laugh. Whether we might was the topic of discussion of a panel on global warming on the final day of the 59th Meeting of Nobel Laureates at Lindau...

...more

Lindau: From fullerenes to global education

When I visit my favourite restaurant for lunch or dinner, I usually order a legitimate food item from the main course. But once in a while, just to indulge, I order a sample platter of appetizers. The appetizers don't always provide the deep satisfaction that I get from eating a proper, expensive food item. But they provide me with a different kind of unique satisfaction; they give me a glimpse of what's new, what's possible. They provide a view of the diversity that can emerge in a plate of bite-sized chunks. And through their frequent novelty, they give me hope that there are new possibilities on the horizon. These appetizers constitute occasional but necessary fodder. Sir Harold Kroto's talk was one of the most satisfying platter of appetizers I have sampled, and I had not even ordered it...
...more

Lindau: The way dinner should be

When you first meet Aaron Ciechanover, he appears to have the distracted air of a man who feels slightly inconvenienced to be in whatever situation has been apparently imposed on him. But this preoccupied demeanor belies a mind which is ready to hold forth on a disparate variety of topics with infinite verve and enthusiasm and which is not reluctant to be politically incorrect, provocative and utterly honest. And it hides a broad smile which is very readily revealed at the mention of a favourite incident or fact.

If there is one word to describe the Israeli doctor, biochemist and Nobel Laureate it's passion, and this passion is pronounced no matter what the topic of discussion; from protein degradation to languages and traveling, from politics to history. Whether we were talking about protein structure or Israel-Palestine relations, Ciechanover's thoughts were always opinionated, honest, cogent, provocative and without a dull shade in them. This is the kind of stimulating person that you always want as a dinner companion...

...more

Lindau: the glowing joy of discovery

Last year's chemistry Nobel Prize was one of the most softball predictions ever made for the Nobel Prize. The Green Fluorescent Protein (GFP) has become so widely used in chemistry, biology and medicine that it is easy to forget that someone had to discover it and develop the technology. Every year Roger Tsien's name used to be on everybody's favorite candidate list along with Martin Chalfie's and Osamu Shimomura's. Then last year, he along with Shimomura and Chalfie finally put the tortuous process and spilling of ink to rest.

A post about GFP is a writer's dream for indulging in pretty pictures. I will restrict myself to two. GFP has become a poster boy for the science of biotechnology. Its barrel shaped ß-sheet structure shown above has become iconic in the scientific world. This is most emblematic in the odd and many varieties of glowing animals that now grace the covers of everything from scientific journals to websites and children's textbooks. If as some have predicted, we happen to "domesticate" biotechnology in the next few decades, it is very likely that one of the first things that our children would do would be to produce glowing pet rabbits, dogs, mice and cats. Along with a few other icons like DNA and the fruit fly, the image of glowing animals and fluorescent proteins is now deeply ensconced in our imagination as an example of what humans can do by manipulating biological systems. Perhaps one day our children can become friends with transgenic, green, glowing human beings, without the hulk-like physique and temper tantrums...

...more

Wine, wisdom and wish-fulfillment at Lindau

This cannot get any better. There's everything here; the opportunity to interact with dozens of Nobel prizewinners in a very informal setting, spectacular views of the alps bordered by three countries (Germany, Switzerland and Austria), nice bicycle rides, a charming hotel to stay in, polonaises to dance to, great banquets with varied food and drink and a festive atmosphere, really nice people to interact with (my co-bloggers are super-friendly and helpful) and dinner with small groups of students and Nobel laureates. I could not have asked for anything more. Here's me with my wunderbar fellow bloggers. I also ran into Bora and PZ Myers and had a nice walk with them around town. Both of them are attending and vigorously blogging as usual and Bora was also part of a panel discussion on open science access.



This year India is a partner country and has sent the third-largest delegation of students, about 43. Guests included the minister for human resources Kapil Sibal and the minister for science and technology S. E. Chavan. As a partner country India hosted a wonderful banquet yesterday with lots of Indian food, followed by an Indian dance performance. This was followed by a Lindau tradition; a polonaise in which the ladies and the gentlemen form lines and ascend the stage from both sides. The gentlemen pick up a flower and present it to whichever lady happens to be in front of them in the center of the stage. The polonaise then breaks into a waltz, and the dancing continues late into the night. There is purportedly ghastly photographic evidence of a certain individual trying to waltz.

Most importantly, you cannot help but be taken in by the picture of hundreds of students from every possible country interacting so enthusiastically with each other, underscoring the global nature and brotherhood of science. Indians interact with Belorussians, Americans interact with Poles, Chinese interact with Russians, Zambians interact with Germans. And Nobel Prize winners participate in the dances and interact with everyone else. The atmosphere is truly international and sparkles with verve.

Today I had the opportunity to conduct an informal interview with Prof. Peter Agre whom I had also met last year. But this year it was one-on-one for 40 mins and was truly enjoyable since Prof. Agre is an exceptionally witty and nice person. You can read about the interview here.You can find the rest at the official Lindau blog, including all my posts (my name is right below each). Updating will continue all week long. Keep watching that spot for more!

Blogging from ground zero: day zero

I have finally arrived in Lindau, Bavaria to offer my thoughts on the meeting of minds between 500 students, 23 Nobel Prize winners in chemistry and the handful of acting scientific journalists such as myself. The journey itself was uneventful but very long. It took me almost the same time to get from Frankfurt to this little island as it took me to get from New York City to Frankfurt. I had to change trains twice, first at Mannheim and then at Stuttgart. Plus I think I am still to savor the punctuality of German transport since my train was delayed by more than half an hour at Stuttgart and then twice more at miscellaneous stops. However I have to admit that this still beats driving or any form of personal transport.

I cannot yet offer my thoughts on the environment Lindau provides, but one thing stuck out as I passed over a bridge; a spectacular view of the Alps on the other side of the Bodensee. Again, I have yet to see around, but an island at the base of the alps which is located in Germany, Austria and Switzerland cannot exactly be dull and ugly, can it?

I have already started blogging on the Lindau blog website and I would prefer not to cross-post that material in other places. Here is the link to the website and to my first three posts:

Lindau blogs website

Exemplifying apprenticeship; The Lindau meetings

Diversity of talks; diversity of science

Surfaces, ammonia, ozone and scientific destiny

Live-blogging starts tomorrow! Here is the program for tomorrow:

The 2009 Lindau Nobel Laureates Meeting

It is a great privilege for me to be invited to live-blog and write about the 2009 Lindau Nobel Prize Winners meeting in the scenic Bavarian town of Lindau, Germany. Since 1951, dozens of Nobel laureates have been joined every year by about 500 carefully chosen students from around the world for a full week of informal discussions, seminars, lunches and lectures where students and Nobelists mingle with each other and one can find at least one laureate on every square foot of the floor no matter what direction he looks.

This year's focus is on chemistry and an august list of no less than 22 Nobel Prize winners in the subject is going to gather in this scenic town. I am honored to be invited because of my background in chemistry and blogging and relish the opportunity like nothing else. I am supposed to be on a small team of 7 journalists and bloggers blogging the event for scienceblogs.com and scienceblogs.de. Along with Matthew Chalmers who is an editor and writer for several publications like New Scientist and the Times, I will largely be responsible for writing about the event in English for Scienceblogs.com. The writing will include both general observations about the meeting as well as descriptions of the talks and seminars. Hopefully I can bring it all together.

Nobel laureates have long been a particular interest of mine. People interested in this kind of a thing collect Nobel statistics like sports and stock market statistics; it was only when exploring facts about youngest, oldest, tallest, most awarded, famous father-son duos, and most neglected non-winners that I realised the allure of cricket or sensex figures.

Calling the list of scheduled speakers at Lindau stellar is a futile and redundant effort because every one of them has won the highest honor in his or her field. Many of the names are familiar and not only have I long admired these people, but I have even directly and indirectly used their work in my own research, as have thousands of scientists and students around the world. Now we will all experience a connection to our work like no other.

In any case, this is as magnificent a concatenation of minds as you can expect to find and I am immensely looking forward to it. The meeting is going to be held from June 28 - July 3. 22 Nobelists in one of the most beautiful parts of the world. It does not get better than this. I will naturally keep on updating.