Jim's cool reception among the British geneticists
Avrion Mitchison

Department of Immunology,
Windeyer Institute of Medical Science
46 Cleveland Street,
London WIT 4JF
Tel: 0044 (0)2076799354
Fax: 0044 (0)2076799357


Jim Watson's travels in the UK during the 1950's brought him into contact with eminent geneticists whom he found disappointing for their lack of enthusiasm for DNA. He mentions Conrad Waddington ( 1905- 1975) in Edinburgh and Cyril Darlington ( 1903-1981) in Oxford. I don't recall him mentioning my uncle JBS Haldane (1902-1964) whom he might also have met, well known among Jim's Cambridge set for having published a book titled The Biochemistry of Genetics in 1954 without mentioning DNA. These were all men whom I much admired, and the reasons for their lack of interest intrigue me. I give the dates to make clear that at that time these were not old dodderers, but rather were at the peak of their activities and influence. Nor were they alone in their unsatisfactory response to Jim's great discovery. Other eminent figures in the landscape of British genetics who would more or less shared have shared their view were R.A. Fisher (1890- 1962) at Cambridge, E B 'Henry' Ford ( 1901 -1988) at Oxford, Julian Huxley ( 1887-1975) then Director of UNESCO in Paris, Michael White (1910-1983) who had by then migrated from Haldane's environment in UCL (University College London) to Texas, and Fisher's ex-colleague Robert Race (1907-1984) still in London. All of them were Fellows of the Royal Society, whose lives and discoveries are written up in the Society's Biographical Memoirs. To catch the tone of that generation I recommend Bryan Clarke's delicious account of 'Henry' Ford.

Why did these men take so cool a view of DNA? It surely cannot be that they were simply too busy with their own tasks the prior-engagement theory of sluggishness; and it certainly was not because they weren't bright enough. My belief is that they differed from Jim more deeply in style of thought and consequently in choice of objectivcs and means of approach. In summary, they were particularists, and Jim is a generalist. Their style of work was to choose a particular problem, to work on it for a limited period of time, and then to move on. In contrast, Jim chose to work on the most general problem in biology, the nature of genetic material. He was lucky to choose DNA to work on, as genes could easily have turned out to be made of- RNA or even protein, and the simplicity and generality would have been lacking. As it is, DNA has turned out to be far the most general material in biology. The ways that it replicates and translates constitute biology's ground rules. They have had a huge unifying effect, cutting across the division of biology into separate areas of animals, plants and micro-organisms. They allow us to think in much the same way about areas as diverse as development of shape, resistance to infection and physical versus cultural inheritance. The structure of DNA has had as broad all impact as Darwin's theory of evolution.

Jim's life work has been to foster these developments. One can only speculate whether it was a generalist character that made him follow this path, or whether it was the other way round, with a choice of subject that moulded his life. Probably a bit of both. Mulling over those British geneticists, one is struck by the influence of upbringing: respect for learning acquired by upbringing in a rectory (Fisher, Ford), late entry in science after a classical education (Ford, Haldane). Late entry seems to be a recipe for subsequent flexibility, the ability to move on from subject to subject.

Let me state my credentials for writing about these men. I was raised in a nest of biologists; grandfather JS Haldane was a physiologist (for further particulars, vide Aldous Huxley's caricature of him in Point counter point), one elder brother became an authority on tuberculosis and the other on the cell cycle. Aldous and Julian Huxley were family friends. From this promising material I early developed an obsessive interest in scientific instances of the human comedy. What is now called a gap year was spent in my uncle's department in University College London, where the principle entertainment in that grey war time was to listen to him and Fisher bashing one another at meetings of' the Genetical Society. Ostensibly they argued about statistical calculations, but really it was about Marxism versus eugenics (Fisher proposed that the family allowance be directly rather than inversely proportional to income!). I assisted White, whom I much admired for his harvesting of elm branches in central London for the sake of the midge that he worked on. Later, at Oxford, I went to Ford's lectures on ecological genetics, which placed evolution at the centre of science, and convinced us that evolution was not just in the past but going on all around us. He must be the last man (and possible the first) to walk through the passages of a science department in full morning dress, announcing that he was required to attend the Privy Council. He brought Darlington to Oxford as its first Professor of Genetics. Starting in research I learned from Race how to type blood, the starting point of immunogenetics. Fisher dined with me in Magdalen College, where the dons were disappointed to find that this giant of the mathematical intellect would admit only to keeping numerous mice. Waddington I knew as a senior colleague in Edinburgh.

A bunch of true English eccentrics, then, that set the tone of the British genetics outside the privileged domain of the Cavendish laboratory where Jim worked. So what do they tell us about sociology of particularism?

1. Vision. Generalists tend to denounce the particularists for lack of vision. In defence the particularlists plead that for from lacking vision, they need a special sort of vision that the generalists lack. They have to be able to pick a worthwhile problem out of the multitude offer-ed by nature. Every important question, they argue, can best be answered by picking the right biological system (this is sometimes called the comparative method). White picked his midge not in the spirit of a stamp collector, but as a test case for how little genetic material is needed to support somatic cell life.

2. Does particularism suit only certain areas or techniques? The happy hunting grounds of particularists are wild nature and medical science. The range of questions offered by the wild and by the human body is curiously similar, and both invite the same sort of case-by-case investigation, witness Race and Fisher on the blood groups of man. Ecological and medical genetics have much in common. Right now mathematics applied to biology is at an interesting stage. Fisher and Haldane tended to developparticular methods for particular problems (the latter more than the former). My guess is that use of the Hoff bifurcation may transcend the particular.

3. The Darwinian tradition. British geneticists pride themselves on following in the tradition of "treasure your exceptions". They dilate on the beauty of the English countryside, and the rich opportunity offered by the flora and fauna of its hedgerows, meadows and streams. Henry Ford directed his ashes to be spread over his beloved Cotswold butterfly meadow. You hear the same sort of thing in the USA, although wild nature is altogether more formidable there.

4. Personality. As mentioned above, the Genetical Society used to be a quarrelsome place. My view is that particularist research is an excellent occupation for really difficult personalities, as the damage that they can do there is limited. They are no good in generalist areas, as there they need to inspire a team. Those British geneticists had little use for new techniques, and were by no means in the habit of ringing one another up to find out how to do this or that.

5. Life on the plateau. These personality traits are highly adapted to working in a part of science that has reached a funding plateau. The particularist takes one student at a time, so needs less money, and does not leave a trail of jobless post-docs. Most of the papers published by those British geneticists had no more that two authors. A generalist operating at full tilt can be quite destructive.

6. Periodicity. Do periodic events spur fresh outbursts of generalism? One has in mind new developments like the bond angles and lengths that made possible the CrickWatson approach to DNA, or the sequencing methods that have changed the face of genetics. Possibly, but my guess is that "breaking the paradigm" has more to it than that.

7. Junk. Senior faculty do not welcome the prospect of their. ideas being relegated to the attic, particularly when their junior's mission of simplifying the subject strikes them as a cheap trick to know the students.

The contrast with the Jim that I knew at Cambridge was enormous. What struck me were the warmth and enthusiasm, the lack of boastfulness, and the vision of where the miraculous structure of DNA would take biology. At the same time I found it hard to imagine anyone among all those eminent geneticists who would share that enthusiasm, particularly as I walked past Henry Ford's closed door back in Oxford. All my family liked Jim a lot, but found him something of an innocent abroad, interested in British life but a bit baffled. Later we were amused by his efforts in The Double Helix to paint himselt, quite misleadingly, as a villain.

Let me mention a specific difficulty that Waddington and Medawar had with DNA. In those days both of them were keen on plasmagenes. These were imagined to be some kind of cytoplasmic genetic material that would be inherited from cell to cell, which could explain long-term differentiation of proliferating cells. Medawar thought they could explain cell-to-cell spread of pigmentation in guinea pig skin. The model was Sonneborn's killer-determinant particles in Paramecium.
I too loved this idea, and decided to post-doc with Sonneborn, with encouragement from Jim who had enjoyed his time in Indiana University. .The model collapsed when Ruth Dippel found DNA in the killer-determinant particles, after which they were relegated to the status of parasitic bacteria. The collapse of plasmagenes was a disappointment, although for me knowing Sonneborn, experience with Paramecium and life at IU was all well worthwhile.

Waddington had a second preoccupation, with the canalisation of development and its counterpart "genetic assimilation". The later term has a sinister ring of Lamarkism, but that wasn't what Waddington meant. He was testing the hypothesis that gross perturbation, for instance growing Drosophila on semi-toxic salt concentrations, might shake embryos out of their normal strictly regulated development and reveal new genetic possibilities, a possibility of practical importance in animal breeding. He made some progress, but the real breakthrough occurred only recently, when knockout of heat shock proteins in Drosophila was found to reveal new evolutionary possibilities (Anne Mclaren, Trends in Genetics 1999). I wonder whether Jim missed out on something during his visit to Edinburgh, although admittedly Waddington required patience in the listener.

Where in Europe might Jim's ideas have found a warmer welcome? In Paris, chez Monod, goes without saying. A more challenging questions concerns Germany, where Norbert Hilschmann (now at Goettingen) and H-J Rheinberger (Berlin) have told me the history. Adolf Butenandt ( 1903-1995) became Director of the KWI (Kaiser Wilhelm Institut) for Biochemistry in Berlin in 1936, a feat that reflects his Nazi sympathies at that time He was a steroid chemist who received the Nobel Prize for Chemistry in 1939 for the structures of androsterone and progesterone. His achievements in molecular biology are less widely known. At the KWI he started work together with Alfred Kuhn on the one gene one protein rule, taking a pigment polymorphism in the eyes of the moth Ephestia as material. They showed that the ommochromes obey the one-one rule, prior to the wonk of Ephrussi and Beadle in neurospora. Another line was to start work on TMV (Tobacco Mosatic Virus), which led on after the war to the structure of TMV protein as determined by Schramm and Braunitzer. In the same period NW Timofeeff-Ressowsky at the KWI for Brain Research in Berlin-Buch, jointly with Lise Meitner., and KG Zimmer and Max Delbruk at the KWI for Chemistry in Berlin, used radiation mutagenesis to estimate by target theory the size of the gene. Taken together this work represents a root of molecular biology as valid as the bacteriophage genetics that Delbruk started in the USA; in both cases the aim was to determine the complete structure of a minimal genetic organism. Jim began his research career in phage genetics, and there is some irony in the fact that he never got around (so far. as I know) to visiting molecular biology's other starting place.

The story has at happy ending. Now that DNA technology is so widely used to explore evolution, the schism between DNA-based generalism and Darwinian particularism is closing. As al participant in this enterprise, it is a pleasure to note that genetics is now again a unified subject.