One of the things that became clear, at this panel and more generally through the day, is that we may have become a bit sloppy in our thinking about heritable and environmental influences on human health and behavior. And, if we don’t attempt to form clear hypotheses and demand evidence in support of them, then there’s a chance that we’ll end up accepting things that appeal to our personal biases.

That may sound a bit dry, but it played out in dramatic fashion across the course of the panel, in part because of the prickly presence of James Watson.

Geneticist Mary-Claire King started out by strongly arguing against genetic determinism, or the idea that your genes are necessarily your destiny. Throughout the panel, people pointed out that things like a rich early childhood environment had a profound impact that persists throughout a person’s life. It was also noted that, in some cases, genetic risk factors for diseases like high blood pressure may be significant if a person lives on some cultures, but irrelevant in others, as environmental influences swamp the (relatively minor) predispositions influenced by genes.

If genetic determinism were dead, however, the panel as a whole wasn’t ready to bury it; at the far end of the row of chairs, Jim Watson, co-discoverer of the structure of DNA, was visibly squirming during the opening statements. Watson has a history of inflammatory remarks on this topic, saying that there were genetic differences in intelligence among the races and sexes. Although he skirted those subjects here, he still managed to stir up the panel by saying that the resistance to genetic determinism was partly social, saying, “the middle class does not like to hear they’re limited by their genes.”

Buried within the bombast, though, Watson made a valid point: there’s strong evidence that schizophrenia has a strong genetic component, and we all seem to accept that. Why is there so much resistance to the idea that positive mental attributes can also be inherited?

This was one of the first of several points that King called for more rigor, the generation of specific hypotheses (about either genetic or environmental influences) that we can test. Without them, we’re likely to accept or reject weaker evidence, in part because it supports positions we favor for ideological reasons.

Somewhere in the middle of this, Helga Nowotny (President of the European Research Council) dropped a term that kept cropping up all day: epigenetics. This term refers to persistant changes to DNA that don’t affect the actual sequence of bases; typically, they involve a chemical modification of bases or changes to the three-dimensional DNA packaging. Epigenetic changes can persist through multiple cell divisions and, in some rare cases, be passed on to offspring.

For a number of people, including Nowotny, epigenetics nicely explains how things like early environmental influences can end up looking like stable genetic differences. Again, Watson wasn’t buying it, saying that “epigenetics is used for a lot of crap, and it’s used by people who don’t like genes.” But again, buried in the rhetoric, he had a point, one that other members of the panel were willing to put in more convincing terms.

We simply don’t have any evidence that epigenetics does much in humans, aside from being involved in a few rare mental disorders. We certainly don’t have any evidence that it can lead to the inheritance of an acquired behavior in humans — the closest we come is a single study in rats.

In fact, King suggested that, when it comes to epigenetics, “we have a semantic problem that’s becoming a philosophical problem, and on the verge of becoming a dangerous political one.” Over the past few decades, the definition of epigenetics has broadened. “Epigenetics” was once strictly used for those rare cases where something was inherited across generations without involving a change in DNA sequences. Now, biologists use it for things that can be inherited when a cell divides, and so persist only for the lifetime of a single individual.

Partly as a result, epigenetics has touched on more and more areas of research. But King seemed to be warning that there’s a danger that people are misreading evidence that epigenetics may be involved in things like health and behavior, and jumping to the conclusion that epigenetics explains everything about them. And, if we do that, there will be a temptation to ascribe all sorts of things to epigenetics without evidence. The social consequences of doing so aren’t obvious, but a number of speakers (including, at some points, Nowotny) appeared to be close to doing just that.

But, if so, Nowotny picked up on King’s caution almost instantly, and made a comparison to the public reception to Chaos Theory. That had specific, mathematical meaning as the scientific community understood it, but Nowotny said the public latched on to how the name reflected a lot of their personal experiences, and started applying it to situations where it wasn’t appropriate. (Philosopher John Dupré also seemed to take King’s warning to heart, later joking “I get tempted to generalize about epigenetics, given I’m a middle-class Englishman.”)

I was given the chance to pose a question, so I asked about a relatively recent discovery that was further clouding the already blurry boundary between environment and heredity: de novo mutations. We’ve recently discovered a number of cases where individuals have a condition that’s associated with a mutation they carry, but didn’t inherit (this was most prominently discovered with autism). These mutations have apparently occurred either in the cells that produced their parents’ eggs and sperm, as evidenced by the finding that their frequency goes up with parental age. (To bring this full circle, parental age is notably influenced by social factors.)

Rather than focusing on this as being social or genetic, King again called for being careful with how we use our terminology. “Genetic” doesn’t necessarily mean inherited, any more than inherited necessarily means that something is genetic (King cited money as something that’s inherited but not genetic.)

King’s focus on greater rigor and hypothesis testing is the right way to put the science on sounder footing, but it’s clear that society is, in various ways, already responding to the incomplete data we already have. As Nowotny put it, we’re already challenged to deal with differences we’re aware of—they can be enriching, like diversity, or can be a mechanism for marginalizing and excluding people.

Even if reality ends up being closer to Watson’s view, with genes playing a larger role in determining human fates, Dupré said that the “genome is not a puppetmaster, just a single link in a complex chain.” And Bruce Beutler brought the discussion full circle, noting that, although there’s certain to be some level of genetic determinism, we need to focus on what we can—the things emphasized by King at the very start, like education and parental involvement.

The post Getting rigorous about genes vs. the environment appeared first on Nobel Week Dialogue.

We began with two audience polls, a show of hands proposed by Ridley: how many people are in favour of GM foods? An overall majority in favour. Louise Fresco suggested a poll on how many are optimistic we can feed the world in 2050, again a majority. These two questions highlight the main themes of the discussion, that of the base issue of GM acceptance, and the need for which GM will be required to feed a growing population.

Fresco opened by stating the GM debate by highlighting that most of the GM work has gone into herbicide resistance, which ironically has generated the most resistance in another area – society. In recent years Bacillus thuringiensis toxin (Bt) has had a positive effect on health and ebnvironment, it has allowed small farmers in India and China to reduce use of pesticides, with a positive effect on health and environment. Can we extend that same duel benefit to other crops?

However Fagerström raised the more fundamental issue, the question of why is there this resistance in society? Especially given the empirical support for GM not being a problem is very strong. How did we end up here? Nüsslein-Volhard believes the issue is rooted in a resistance against science, rather than GM itself. Why do people not trust scientists? Why are politicians inclined to embrace the more fluffy ‘green’ organisations rather than scientific manifestos? The problem is that there is deeply rooted mis-trust brought about by a lack of education. I could liken it to the issues raised by Helga Nowotny this morning on the fulfilment of promise – genomic technologies meeting a pre-genomic society. After all, we have the genomes for several crops now (e.g. rice) so we actually know what we are changing.

The other issue is that in modern, western farms, farmers are paid whether their crop fails or succeeds; they just don’t need to care about more efficient production. In fact, if they increase production – the surplus just floods (and destablises) the developing countries. However, local action on governments in countries where these technologies are being developed negatively effects the prospects for these products in these developing countries.

Fresco highlighted that in discussing GM people don’t go into the details; there is too much generalisation. Focus on specifics, like perhaps the potato. We’re not talking about wide-crosses here (i.e. jellyfish genes in vegetables), but in fact practise sys-genesis, the back crossing with ancestral Andean types of potato that are resistant to phytophthora blight. We should show that GM can be close to the original, rather than some mutant chimera. Torbjörn agrees, and suggests that GM should be judged crop by crop like anything else. It’s like saying you are against electricity, just because some electrical items can be bad!

Another problem is that societies that most object to GM do not readily feel the tangible benefits of GM. Is the a comparable objection to GM cotton that we wear, or the idea of fast growing GM trees, or transgenic mosquitoes that don’t vector diseases such as Dengue. When we feel the advantage, so our perceptions of ‘risk’ diminish?

Fresco believes this is something that is much more related to our relationship with food, and a lack of knowledge of about the process. Everyone thinks they’re an expert in food; it has moral underpinnings and views (good vs bad) that are commonplace conversations. People have strong views about intensification, multinationals, international food chains, animal treatment, but many of these are centred in highly urban with a loss of connection with the steps embedded in bringing food to the plate. Euros accept modernisation by these routes in many other technologies, but not in food. People like small farms; they think small is better. The GM debate often focusses on quantity and not quality. However GM is not inherrently tasteless, it’s down to the cultivars being developed, as it’s not a big issues to return to old ‘tastier’ varieties, but improve productivity by improving production circumstances.

A final comment, raised by a question from the floor, was the role of GM policy skepticism; maybe the public is more skeptical of our policy-making apparatus than the technological apparatus. People don’t trust the decision value of politicians, thus don’t trust the application of these technologies. Fagerström suggests that scientific verdict should permeate into policy-making, rather than irrational decision-making.

Final take-home messages

Fresco: we are risk averse in the middle-classes. We learn by making mistaked. People don’t want to make mistakes anymore. Let’s not be afraid of risks. Just as cars were introduced as a death trap, we improve – better cars and licensing.

Pang: Can we take what we have learned about policy decisions in the developed world and apply to developing countries, so the same mistakes are not made.

Nüsselein-Volhard: Try to get the GM to make use of land that is not cultivatable by any other means.

Barton: Education – teach the consumer how this works. Going to need to produce 70% more food than we do today. The next 50 yrs will have to do ciumulatively what we achieved in the last 10,000 yrs. Applying genetics to food is going to be a critical component.

Ridley: In 2013 the vitamin-A enhanced golden rice, a fantastic non-profit technology, will be introduced. All eyes will be on how this is rolled out, and the responses of society.

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Epigenetik verkar alltid skapa en extra elektrisk stämning, i alla fall om det finns personer som James D. Watson i panelen.  Själva begreppet ställer till det; epigenetiska fenomen finns men termen har används för brett och lett till missförstånd, menar Mary-Claire King och resten av panelen håller med henne. Hon betonar att samma vetenskapliga standard måste finnas när både genetiska som epigenetiska effekter kommuniceras. Det måste hållas en hög vetenskaplig nivå och hon jämför med hur det var när människans genom skulle sekvenseras, att en del forskare gick ut med väldigt djärva uttalanden om att sekvenseringen skulle vara lösningen på så mycket. Visst vet vi mer nu när människans genom är sekvenserat, men de svar vi har fått föder nya frågor.

Men visst finns det konstiga exempel som inte kan förstås som annat än epigenetiska fenomen, även om de epigenetiska mekanismerna inte alltid är kartlagda. I experiment med råttor har det visat sig att ungar vars råttmamma slickat dem mycket när de var små också slickar sina ungar. I Överkalix har en medicinsk släktanalys visat att pojkar som svalt i 9-12 års ålder får barnbarn som är friskare än genomsnittet. Mammor som svalt i Holland under nazisternas ockupation fick barn med ärftliga problem. Det verkar finnas ett fönster i unga organismers liv där miljöfaktorer kan påverka framtida avkomma på ett sätts som ärvs över generationer.

Samtidigt är de här exemplen inte huvudfåran för den epigenetiska forskningen som mer handlar om hur celler förändras och specialiseras trots att de bär på samma dna. Det som nu är brutet är dogmen om att ”dna gör rna som gör protein”. Forskare ser på genomet som mycket mer dynamiskt idag.

Själv skulle jag gärna ha hört mer om den roll som rna verkar spela i det här. Forskare som Craig Mello har visat att små rna spelar en avgörande roll i cellens maskineri och om jag får gissa så kommer det komma fler viktiga upptäckter inom det området. Rna har gått ifrån att vara en enkel budbärare, en slags andra klassens dna, till att hamna allt mer i blickfånget; från hypoteser om livets ursprung på jorden till reglering av epigenetiska mekanismer när cellerna specialiseras. Nästa gång jag träffar Craig Mello ska jag fråga mer om det (när det nu kan tänkas bli).

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Nowotny started out by noting that genomics is often mentioned a promising things (like the “promise of genetic medicine” and so forth). But the term promise, she noted, implies a contract, and she did her best to make the details of that contract explicit. And the payoff of getting this contract right in the case of genetics, she suggested, might be a second Renaissance.

Although attempts to understand the natural world have existed in almost every culture, institutionalized science of the sort we practice today only dates back a few hundred years. As it has grown, it’s become increasingly reliant on society for support. In return, Nowotny said, science makes a number of promises. One is the promise of information that’s above the vagaries of political and religious figures.

But, more frequently, science has been viewed as offering something a bit more nebulous: progress. In this sense, Nowotny noted, genomics is just the latest in a long line of scientific developments that has been promoted as having the potential to usher in a sort of golden age.

But we’re now far past the point, Nowotny said, where we believe in a simple, linear slope of progress, and we tend to focus on the fact that the challenges we face are complex and often overlapping. But that shouldn’t obscure the fact that, in some cases, science really has delivered on its end of the promise. Nowotny showed two graphs, one that showed a rapidly increasing life expectancy, and another showing that the number of hours worked by people in industrial societies has plunged in concert. And her point was inadvertently driven home by Steven Chu’s later talk, which showed how crop yields per acre farmed have also shot up as a result of the application of science to agriculture.

(It’s easy to forget both of these as you work in a high-stress work environment and get bombarded by disease-of-the-week coverage in the news media.)

So, the promise of genomics comes at a time where we’re a bit cynical about the nature of progress and haven’t fully appreciated the promises science have delivered on. But Nowotny mentioned a few additional features that could make the reception to genomics different from past cases of scientific promise. For one, it’s being received by a world that’s now globalized. The knowledge generated by it will be able to rapidly spread to just about every culture. But, at the same time, the risk is that the benefits won’t be, which could exacerbate existing tensions.

Nowotny also referred to the work of Edmund Husserl who, in 1936, proposed the concept of the “life world.” This concept, inspired by quantum mechanics, focused on the growing gap between the world that scientists were describing and the world that’s intuitive and commonly experienced by most people. Genomics and the insights it provides clearly run the risk of creating the same sort of gap between what we learn and our intuitive experiences.

But Nowotny clearly felt that the payoffs of keeping that divide from widening were tremendous. She suggested we had the potential for a “Second Renaissance,” one that also hard a focus on the individual, but now placed that in the context of the similarities we share with all other humans, as well as our similarity with other species. She clearly felt there was a key role for her field (the humanities) to play in keeping the gap between science and the public from widening. But the exact means for doing so appeared to be a subject for a separate talk.

The post Will the genomic revolution produce a second Renaissance? appeared first on Nobel Week Dialogue.

There was a strong focus on the continued need for fundamental science during this afternoon’s session, Human Biology: The Great Deal We Don’t Know and How to Discover It.

The worry about reduced funding for fundamental research was evident during each speakers input to the conversation on the future of research on human biology. Taking this a step further, Christiane Nüsslein-Volhard said that “we need to know more about general biology”.

The moderator, Bruce Alberts, said that much of the funding for biochemical research is by people who have had these diseases e.g. cancer survivors. This has an adverse impact according to the Editor-in-Chief of Science. He often hears people say: “Why should the public tax money pay for scientists satisfying their curiosity?”

Craig Mello added that those very naive curiosities often result in huge discoveries. He mentioned being in awe of the fact that the genetic code is similar across organisms and finding out that the insulin gene can be read by bacteria. I interviewed him earlier this week and he spoke about this: read here.

“Curiosity is a basic must for scientists” said Nüsslein-Volhard. She recommended that if you’re not curious, don’t do science. Here’s a great formula she gave for good research:

Curisosity + Good Problem + Bit of Smartness = Good Basis for Research

Mello said that the reduction can be blamed on the limited resources we now have. Given the choice between funding research that might get into clinics next year or a long-term project that could revolutionize medicine, review panels are choosing the applied clinic-focused research. He said that funding in the United States is flat despite the increased need to understand the new knowledge available. “This is really unacceptable and it really threatens our ability to do the basic science for the next 10 years”.

Asked how we can change this, Steven Chu said that leaders have to be convinced that you have to make investments into the future. This is happening in the United States according to Chu who used the saying “you don’t eat your seed corn”. Mello added that we need to do a better job at communicating with policy makers and scientists must keep track of the impact of their research.

This is yet another conference where this debate is a hot topic. Every Nobel Laureate and prominent scientist that I have heard speak about this thinks there is a problem with fundamental science funding. However, policy makers in many countries think we need more applied science. Perhaps this is a take home message for policy makers!

Maria Delaney tweets @mhdelaney.

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Gene-environment interactions was a hot topic during the first part of Stream A in the panel discussion on The Promised Land of Genomic Medicine: Where Can the Science Take Us?

The moderator, Göran Hansson, posed the question: How far are we from understanding these interactions?

Eric Lander raised a really interesting point that the general public perceive genetics as risk factors of disease. He disagreed with this impression saying “genetics is here to understand mechanism”. It seems that geneticists need to portray as Lander said that “genes and environment works inextricably together”.

Using lung cancer as an example, Lander said that we can understand the genes involved but we need to address the huge environmental factor: smoking. He added that we need to communicate science better to get people to stop smoking and understand this obvious environmental effect.

In some diseases, I thought it was brilliant that this panel of geneticists were willing to question the focus on genetic research. Joe Goldstein said “we have to deal with patients with diseases that have strong familial components”. He cited colon cancer as an example where a colonoscopy is much better than getting your genome sequenced.

If you look at cancers in a population, the hereditary impact varies between 3 and 10%. Using breast cancer as an example, Mary Claire King said that by working with families that are severely affected by the disease, they were able to isolate the genes involved: BRCA1 and the many others found since. She said Europe was better at testing for these mutations but the United States needed to improve. If these mutations are tested in women, these cancers can be prevented. I think this is true for many new technologies involving genetics – governments are slow to adopt them which to me seems short-sighted given the costs involved downstream for treatment.

This short-term focus was also raised by Bert Vogelstein who said that “we, as a society, are so focused on curing these advanced cancers that we don’t see other ways to tame the beast”.

This was such an fascinating discussion. Now that we know so much more about the genetic mechanisms, it seems that looking towards the impact of the environment is more possible. Göran Hansson  summed this up saying “we are probably in for a new era of diagnostics”.

Maria Delaney tweets @mhdelaney.

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Moderna människor och neanderthalare har en gemensam förmoder för 500 000 år sedan, men det var inte sista gången de hade sex med varandra. Många av dagens människor bär med sig det genetiska resultatet av sexuella realationer som skedde när människor mötte neanderthalare, troligen på Arabiska halvön, för runt 70 000 år sedan. Men det har funnits fler människoarter som tidigare moderna människor hade sex med. I en grotta i östra Sibirien har forskare hittat ett lillfinger från en hittills okänd människoart som har fått sitt populära namn från grottan där finger hittades – Denisovagrottan och denisovamänniskan. Människor i sydöstasiatiska övärlden bär fortfarande på gener från dem.

Frågan är vad de genetiska resterna i oss från de sexuella relationerna utanför artgränserna spelar för roll idag. Vi vet inte än, enligt Svante Pääbo, men det finns spännande indikationer på att delar av genomet som härstammar från neanderthalare kan påverka immunförsvaret. Men kanske ännu mer spännande: eftersom vi har hela neanderthalarnas och denisovanernas genetiska sekvens kan vi nu börja fråga oss vad det är som gör oss till moderna människor.

Ingen annan art har (haft) vår teknologi eller vår konst. Vi har spridit oss över hela världen på ett sätt som ingen annan art har lyckats göra. Det finns unika mutationer som bara finns hos oss moderna människor, som saknas hos schimpanser och neanderthalare. Det är totalt 100 000 förändringar, men vilka av dem betyder något?

Några av de här förändringarna vet vi vad de betyder och av dessa är 23 proteinkodande gener som är unika för människan. Fyra gener påverkar huden, sex gener påverkar synen, två påverkar nervsystemet, två påverkar nervsignaler, två är kopplade till autism – men vi vet ännu inte vad de här förändringarna lett till. Kan de ha gett en fördel hos våra släktingar i Afrika för runt 200 000 år sedan? Hur gör genomet egentligen en människa? De frågorna saknar fortfarande svar.

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Nowotny asks what does a social scientist do in the land of genomic promise? The promise (or contract) that binds science and scientists together is the expectation that the public have from scientists, and the scientists aspiration to produce something useful. The pursuit was one of laws, the laws of natural philosophy, but with the concept of ‘law’ as a term taken from society. Yet the aim to supersede the laws of society; science promised access to the kind of laws that could not be bent by kings or rulers – they provided truths above the arbitrariness of the rules of society. For the early scientists, Francis Bacon et al. the promise was the affecting of all things possible, using the experimental method and practical objectives, for the betterment of humankind.

Early promises that have been realised in society include the reduction in working hours with the concomitant provision of more free time, which ironically we fill with the products of other scientific promises, those of technology – mobile phones, TV, travel. As we consider the impact of genomic science, the genomic promise is a global promise where investment flows globally and through decentralised networks. Is genomic science now in the position to take the promise of human enhancement/betterment to a new level?

Nowotny quotes Richard Powers –  ”People want everything, that’s their problem”

With genomics we may be entering a second renaissance. Like the original renaissance that put the individual at the centre of the political and cultural world, genomics offers the opportunity to recognise and discover our own individual uniqueness in a deep sense together with our relatedness to each other and to other species.

However, we need to be careful with promises we make, and not betray them. The worry is that we arrive in a situation where post-genomic science ends up meeting a ‘pre-genetic society’ that isn’t ready for it. There need to be bridges that enable society to be ready for these new technologies; these could include citizen science projects. Create space for people’s everyday experience and integrate it as experiential evidence. One such project is personal genomics – allowing people to interface with and explore the question, ‘who am I?’

Nowotny highlights discussion points that will be explored in the afternoon sessions.

From my own perspective, and reflecting on Nowotny’s ideas of promise and ‘betrayal’, it’s worth reflecting on that fact that the human genome project was funded off the back of such a promise – that benefits would be delivered upon its completion.

That we needed the genome sequence goes without saying, but the fact that most scientists knew the answers would not (could not) be immediate was probably known to scientists in a way that it was not clear (or not made clear) to society, or the politicians ratifying the funding. Although we could ponder on whether a government would have provided the funding it did had it known it wouldn’t get immediate results.

If the promise of science in society is one of expectation, I think it’s probably important to be careful managing those expectations. These begin with education about how science works, it’s pace and the absolute need to establish the fundamentals before we seek to apply discoveries to society.

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One of the major reasons why Judson’s book is unlikely to be surpassed is simply because he was a man who was both lucky and prescient enough to discover his life’s work at a time when almost all the protagonists in his drama were alive. In the preface he lists at least a hundred names who he interviewed, often multiple times, and these names constitute probably ninety-nine percent of the most important molecular biologists of the twentieth century. Crick, Watson, Perutz, Pauling, Bragg, Sanger, Brenner, Meselson, they are all there. Now many of them are gone, and anything anyone wants to say about them will have to come from second-hand sources. One suspects that the most commonly accessed second-hand source will be Judson’s book.

James Watson and Francis Crick in an interview with Horace Freeland Judson

Thanks to the Nobel Week Dialogue, we now have access to another unique historical source, an interview conducted by Judson with James Watson and Francis Crick in 1993, forty years after the discovery of the structure of DNA and twenty-five years after Watson’s memoir “The Double Helix”. It’s been presented today at the Nobel Week Dialogue and it was definitely worth hearing what they have to say. Please find the link to the video here.

Judson starts by asking Watson and Crick about their educational background and what influence if any it had on their famous work. It’s worth recalling that the precocious Watson started college at the University of Chicago at age fifteen, at a time when the president of the university, Robert Maynard Hutchins, was stressing the virtues of broad and mandatory education in both the sciences and the humanities. Part of this education involved reading the “Great Books”, classics of science in their original form. This broad education instilled in Watson a tendency to seek out facts even if they turned out to be from disparate sources. Crick on the other hand considered himself an overage physicist in his mid-thirties whose work was interrupted by the war. He too had been to an English public school which provided an unusually good and broad education in the sciences. Unlike Watson, he also had a firm grasp of the mathematics of x-ray diffraction

But perhaps greater than these influences was a little book by Erwin Schrodinger called “What is Life?”, written during the hopeful year of 1944 when Schrodinger, driven partly by Nazism and partly by his unconventional views on marital harmony, had settled in Dublin, Ireland and asked to give a series of lectures at Dublin’s Institute for Advanced Studies. Schrodinger who was as much of a philosopher as a physicist, was interested in biology and believed that genes, not proteins were at the center of the puzzle of heredity. In his book he stressed the idea of complementarity. It was a viewpoint that made a striking impression on many physicists drawn to biology, including Crick and Maurice Wilkins. The German-American physicist Max Delbruck was mentioned in the book: Delbruck who had trained as a physicist at Niels Bohr’s institute had been inspired by both Bohr and Schrodinger to study bacteriophages, or viruses which infected bacteria. As a physicist, Delbruck knew that the study of the simplest atom, hydrogen, had been immensely helpful to physicists in exploring the applications of quantum mechanics. Perhaps something similar could be done with biology in the form of its own “hydrogen atom”, the bacteriophage. Delbruck teamed up with the Italian emigre Salvador Luria who employed both phages and bacteria in demonstrating the presence of random mutations in genes. This was very important work which would get Delbruck and Luria the Nobel Prize. By a stroke of luck Watson turned up at Indiana University where Luria was on the faculty. Having read Schrodinger’s book, he quickly became enamored of Luria and Delbruck’s work and from then out his eye was fixed on the gene as the unit of heredity.

At this point in his career, after a not particularly glamorous postdoc with Herman Kalcker in Copenhagen, Watson could have had two choices; the Pasteur Institute in Paris or the Cavendish in Cambridge. The venerated Pasteur Institute had been the site of major discoveries in infectious diseases, but their focus was mainly genetic. The Cavendish on the other hand had been led by William Bragg since before the beginning of the war, and as a pioneer of x-ray diffraction, Bragg’s focus had always been on structure. That Watson chose the Cavendish over the Pasteur in spite of his background in genetics is a testament to his wisdom in picking structure as the enabler of genetics. He realized that while genetics was going to be what the gene was all about, without knowing anything about the structure of DNA, you couldn’t really make any headway. This was the spark that lit the flame.

Thus both Watson and Crick were primed to attack the structure of the gene when they had their fateful meeting at the Cavendish. The two hit it off right away. Each one discovered in the other a kindred mind that was inquisitive, fearless and eager to gather facts from every possible source. The confluence of factors that made the discovery possible has been discussed in a previous post. In Judson’s interview, Crick dispels the belief that he and Watson brought a knowledge of physics and biology respectively to the problem. As was seen earlier, the key discipline in understanding DNA was chemistry and the two main protagonists both had the wisdom to gain enough chemical knowledge to make a difference. Much of what they needed to solve the problem was really learnt on the fly.

The role of Rosalind Franklin

The interview then moves on to a sensitive topic; the role that Rosalind Franklin played in the discovery. Watson and Crick both acknowledge that in terms of data, Franklin probably came the closest to unraveling the structure. Asked by Judson what held Franklin back, Crick replies that her problem was that while she was a first-rate experimenter, she lacked the expansive theoretical understanding that would allow her to make sense of the diffraction pattern and tie together the disparate bits of data. And she wouldn’t talk to others about her work, partly because of the difficult relationship she had with Maurice Wilkins. A more contentious question concerns possible institutionalized sexism at King’s College, London, where Franklin and Maurice Wilkins worked. Watson’s own account “The Double Helix” was later accused of hints of benign sexism, although all three men seem to agree that there was no overt sexism in either of the institutions.

It should be remembered however that at this time women were still a minority in the world of science. Just ten or twenty years earlier there was a much more explicit and official bias against the inclusion of women in research and the life stories of many outstanding scientific women – Gertrude Elion and Gerty Cory being merely two of them – testify to this state of affairs. Dorothy Hodgkin was a rare example of a success story. The fact is that while the post-war environment had started to gradually recognize the status of women as equals, women still very much faced an uphill battle in being recognized as peers in academic circles. Franklin must undoubtedly have faced these obstacles, and whatever her other flaws, there is no doubt that she doggedly persevered in this environment and became an outstanding experimentalist. It’s a tragedy of her life that, for whatever reasons, she did not seek out people to talk to. In the interview both Watson and Crick thought that if she had started talking to Crick (who was known as a garrulous conversationalist who was eager to talk to anyone who might listen), history might have been quite different.

The interview ends with Watson and Crick telling Judson what their current work was about. After his memorable time at the Cavendish, Watson briefly led a lab at Harvard after which he assumed responsibility of the Cold Spring Harbor Laboratory, where for the next thirty years he guided the work of outstanding young biological scientists. He was also the leader of the Human Genome Project during its early years when he famously clashed with Craig Venter. All this time, Watson was as well-known for being a fair mentor who never co-authored a paper if he hadn’t done the actual work as he was for occasionally making candid and controversial statements about any subject that caught his fancy. But no one can accuse him of not being honest with his opinions.

Crick on the other hand became the intellectual leader of molecular biology, serving the kind of role that Niels Bohr did in theoretical physics. More than anyone else he always had a grasp of the broader picture, and he made important contributions to the genetic code and to a host of other minor but important topics in the field. During his later years he moved to the Salk Institute in La Holla (where he was joined by fellow genetics pioneer Sydney Brenner) and turned to the overwhelming problem of the brain and human consciousness. He teamed up with the neuroscientist Christof Koch (who has narrated their adventures in his recent book “Consciousness”) to explore the basic differences in brain structure between conscious and unconscious states.

Picking the right field

In the last few minutes of the interview, Watson and Crick stress the virtues of being in a new field at a time when there are few people and the discoveries are ripe for the picking. Part of this is pure luck, being in the right place at the right time, but part of it is undoubtedly having a nose for the right question and the opportunity to answer it. DNA in 1953 offered such opportunities. While molecular biology still holds great surprises, it’s no longer a new field of interest to a few; by his own estimate, Watson counted a quarter of a million researchers working in the field even in 1993. Since then the number could only have grown exponentially.

The brain on the other hand is a much newer field where great fundamental discoveries are still lurking, and this is what led Crick into the field. Although there are many researchers working in the area, we have only now gotten our hands on the tools which would allow us to explore the fundamental features of memory, learning and consciousness. When it comes to the brain, we are still waiting for our Watson and Crick. Perhaps we will find them among those who watch this interview.

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Craig Mello fick nobelpriset i medicin 2006 för upptäckten av rna-interferens, en mekanism som är en del av cellens kontrollsystem för att ha rätt mängd av proteiner. Interferensen kan också upptäcka och förgöra en del virus. Det är tydligt att Mello gillar sitt rna och det tror jag han gör helt rätt i. Mycket av det vi ännu inte till fullo förstår när det kommer till genetiska mekanismer verkar ofta handla om just rna.

Det finns inte högre eller lägre livsformer, påpekar Mello. Allt levande som finns på jorden idag har en lika lång evolutionshistoria på runt 3,8 miljarder år eftersom livet på jorden har ett gemensamt ursprung. Därför är det också rimligt att studera den maskliknande varelsen som kallas nematod, Craig Mellos experimentorganism som han verkar påtagligt förtjust i. När han visar bilder på nematoders äggstockar och pratar om de epigenetiska faktorer som behövs för att fosterutvecklingen fungerar så ser han en tydlig parallell till människan. I själva verket så delar en stor del av våra gener ett gemensamt ursprung med nematoderna. Det beror på att våra gemensamma förmödrar, våra och nematodernas, överlevde den stora påfrestning som det innebar när nästan hela planeten vad djuptfryst som en gigantisk snöboll för runt 800 miljoner år sedan. De gener som den gemensama förmoder hade då är samma gener som ligger till grund för våra och nematodens. Livet är uråldrigt på den här planeten, påpekar Mello. Det har funnits en fjärdedel av den tid som universum existerat. Livet är äldre än de yngsta stjärnorna.

Lika länge som livet funnits har informationsålden rått på jorden. Cellen har ett minne genom epigenetiska mekanismer, information som hela tiden ska underhållas och cellen gör det i en fantastisk hastighet. Inne i cellkärnan skickar dna iväg information till ribosomen med rna där tre genetiska bokstäver i rna-sekvensen kodar för en aminosyra. Aminosyrorna bygger upp proteiner. Ribosomen kan läsa av 20 stycken tripletter av baspar i sekunden. När Mello visar animationer på cellulära mekanismer påpekar han upprepade gånger – det här går MYCKET fortare i verkligheten. När det går så fort är det viktigt att alla kontrollsystem fungerar och ett kontrollsystem är rna-interferens. Det är en mekanism som funnits i celler under miljarder år. Det är en mekanism som vi kan lära oss använda.

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