Lab culture

July 26, 1996

What is an anthropologist doing in a genetics lab? Jon Turney asks Paul Rabinow to explain.

If I was patient enough, I always learned something from things they didn't like." So says Paul Rabinow about his study of scientists at work. The comment suggests one reason why an anthropologist may have something to contribute to accounts of how scientists do what they do.

What they were doing in this case was developing the technology of molecular genetics, working in particular on polymerase chain reaction, the crucial trick used to amplify tiny samples of genetic material - DNA. Rabinow, professor of anthropology at the University of California at Berkeley, has just published a study of how this tool was fashioned by his scientific neighbours at biotechnology company Cetus.

He originally intended to carry out a more general study of the new human genetics, and the focus on the polymerase chain reaction, known to biologists as PCR, came about partly by chance. In spite of the dollars earmarked by Congress for study of the implications of the human genome project, he could not get any grants to actually look inside the laboratory. He was told that the ethical, social and legal studies mandated did not mean studying the scientists. "Ethics and social consequences mean the scientists discover the truth and the ethicists worry and the sociologists worry about the effects. And the idea that you would actually go and look at the emergence of the social conditions in which these things got invented was strictly ruled out."

Fortunately, as a Californian academic, he did not need to go far to find scientists in the lab, and he embarked on a study of genome work at the Lawrence Berkeley Laboratory. But this foundered because of political disputes in the institution. By then he was attracted to the flourishing local biotechnology industry. "Something new was taking shape there, and that intrigued me."

He became particularly intrigued by the Berkeley-based Cetus Corporation. Cetus, and its development of PCR, was already well-established in biotech folklore. Self-styled maverick Kary Mullis, a synthetic chemist, had dreamed up the rudiments of PCR in 1983. At that time, many Cetus scientists were preoccupied with how to increase the sensitivity of tests for detecting infinitesimally small quantities of DNA, tests which might be turned into lucrative diagnostic products. But Mullis realised that there was a way to solve the problem by the back door: amplifying the DNA in the sample, rather than improving detection.

He saw it could be done by a clever combination of specially made short stretches of DNA, "primers", and use of the well-known natural enzyme DNA polymerase. In fact, if you could engineer a repeated series of steps - making DNA, then separating the two strands and getting the enzyme to stitch a new, matching strand alongside both of them - you could amplify the original exponentially. Voil : PCR.

The rest was history. The reaction worked "the first time I tried it", Mullis wrote. The first papers on PCR appeared in the journal Science in 1985. By December 1989, its worldwide impact in laboratories led Science to choose it as its first "Molecule of the Year". In 1991, Hoffman-LaRoche bought the rights to PCR for a reputed $300 million. A few years later, a Nobel prize for Mullis appeared to set the seal on his claim to be the brains behind a scientific and commercial success story with few parallells.

On the other hand, science is not made (solely) by brilliant individuals, least of all in the hurly-burly of start-up companies frantically trying to bring complicated products to market. And reactions this complex never work first time out. Mullis undoubtedly originated the concept of PCR, but many others were involved in turning it into a working system, and finally a saleable package that would work as well in London, Paris or Boston as in San Francisco. And the volatile Mullis, never a team player, left the company in 1986. So who really gets the credit for making PCR?

That was the question Rabinow set out to answer. Having got involved with Cetus, and especially with its former research director Tom White, Rabinow decided he had "a certain historical responsibility for telling at least one version of what went on". Now he has done so, in an unusual book, written with academic restraint but aimed at a general audience. He deliberately avoids the conventions of science journalism, mostly eschewing drama and, as is the current anthropological fashion. "letting the scientists talk much more".

He was very conscious of the hype surrounding the genome project, from supporters who saw it solving all known health problems and from critics who insisted it was a short-cut to eugenic horrors. And he wanted to portray the way it looked to the researchers actually making the project move. "This was an attempt to work with scientists, who are sympathetic and open, to try and create some kind of a space where we weren't just shouting at each other, or denouncing each other, or admiring each other: we were working together." It was an ethnographer's approach, he says: "take the native's point of view as a starting point. I'm not out to denounce them or uncover their dirty laundry, or something. I want to be critical and balanced, but the point is, actually, to create something between us."

With the exception of Mullis, who has told his story many times, Rabinow interviewed all the key players and they reviewed the results. The final version of the book tells "the story of how PCR was conceived, invented, coddled and pushed into becoming a workable technology", as he wrote recently. But it is also a snapshot of the creative life of a particular scientific milieu - West Coast venture capital biotech in the 1980s. All the people involved were highly gifted, in their different ways. All had taken big risks, the scientists when they left their academic careers to take industrial posts, the managers when they staked their careers (and cash) on a new company. The result is an intriguing, composite picture of a form of life, as he puts it.

That picture contradicts several stereotypes - especially of pure, academic science versus grubby commercial enterprise, and of inspired genius fighting the forces of reaction. Many of the Cetus scientists left academe because of what they saw as endemic infighting, in the hope that a company united around clear objectives would foster some real collaboration and teamwork. And one is left with a strong impression that Mullis alone, for all his fecundity of ideas, would never have brought PCR to fruition.

The blending of hitherto separate cultures is also a feature of Rabinow's latest study, of the leading French genome centre, the Centre d'Etude du Polymorphisme Humaine, in Paris. He managed six months' fieldwork there two years ago, just after they had produced the first complete, if crude, physical map of the human genome. It was a great success, but also a crisis point. What would they do next, and who would pay for it? Rabinow, partly at the behest of the centre's director Daniel Cohen, decided to track the decisions which followed. When we meet, he has just made a further visit to Paris, tying up loose ends: "I'm starting the book next week." The working title is French DNA, from a remark made by the doctor son of former President Pompidou that French DNA should never be sold to the United States. But that still does not explain what an anthropologist is doing in a genetics lab.

"The human genome project couldn't be more central to anthropology," he suggests. "It is going to change what 'man' is." And it is of more particular interest to him, an expert on Foucault and an investigator of modernity. For Rabinow, the advent of the genome project emphasises the crucial aspect of modern science: "Our way of understanding is through technological manipulation - to do things with it - and that's how we found out how genes work, and now we're expanding that."

In the end, he is interested in the effect of new genetic information on the way we define our identities. His overall vision is that the whole collection of genetic technologies now being assembled will establish what he calls "biosociality", basically a world in which the groups individuals identify with are defined by biological information. As we can tell people more and more about their particular variant genes, "older cultural classifications will be joined by a vast array of new ones, which will cross-cut, partially supersede and eventually redefine the older categories". We have only hints of this so far, indeed it may not be highly noticeable until after the genome project is complete. It is not often realised, he says, that the project is finite, and doesn't have all that far to go. "Once the genome is mapped, in ten years or so, then the fun really begins".

Plenty of scope, too, for more work with the scientists busy inventing the technology. "I think there's a lot of demand among a range of different scientists to think more about what they're doing". As one who went into anthropology because he did not want his philosophical interests to lead him to a lifetime in the library, he relishes the prospect.

"Anthropology is experimental for me - that's the reason for doing it as opposed to doing philosophy. I enter into these things as an experiment, and I don't know what's going to happen. I'm not primarily trying to prove some theory about science. That isn't my goal. I was interested in getting involved with these people, to learn from them, and also to see their limits, and see what it would do to me." So far, what it has done is made him more interested in the science, and in the complexities of the milieux from which it emerges, complexities which the new book begins to uncover.

Jon Turney is a Wellcome fellow in science and technology studies, University College London.

Making PCR: A Story of Biotechnology, University of Chicago Press.

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