The $64m helix

The Golden Helix - Genetic Engineering
February 23, 1996

The first things venture capital bought from biotechnology were the words. Biogen, Galagen, Genentech, Metrigen, Genzyme. Sometime in the mid-1970s, smart movers started registering all the combinations of hitherto scientific syllables they could think of. Registering a corporate name in California only costs five dollars a throw.

Many of the names never left the register. Some briefly identified small companies that never shipped a product. Others grew into flourishing enterprises. By the end of 1993, there were over 1,200 American biotechnology companies, employing 80,000 people.

Arthur Kornberg's memoir of this period tries to show why some turned scientific promise into commercial success, while others went broke.

One key to the success of a biotechnology company is the quality of its science. So starting one that works depends on persuading young scientists to quit university. Just remind them what life there is like: "What must you go through to start a new project? How many grant applications, how many forms, how many approvals? The department chairman? The university resources committee? . . . A brilliant man can't squander time with forms and committees. Life is too short, and DNA too long."

In Michael Crichton's Jurassic Park the brilliant young geneticist hears the message. In the real world of Kornberg's biotech ventures the goals are worthier than cloning dinosaurs, but the approach is similar: "Unencumbered by teaching loads, committees and bureaucratic obstructions, given access at all levels to a lean, responsive administrative staff, afforded excellent salaries, benefits and bonuses, DNAX scientists are largely freed from immediate financial concerns and the diversion of seeking or weighing offers from other institutions."

This beguiling prospect was put to prospective recruits not by a venture capitalist but by Kornberg himself. His book is in part a chronicle of how a remarkable generation of biologists those with successful university careers in the United States when the techniques for cutting and recombining DNA were put together in the mid-1970s were drawn into a new world. Once content to be eminent professors, they almost all became founders, shareholders, or advisers to companies trying to apply the new techniques to generate marketable products: hormones, growth factors, modulators of the immune system, neurotransmitters.

Kornberg is relatively little known among the pioneers of DNA technology. But his services were in great demand when biotech fever hit Wall Street. For although all the new business prospects hinged on DNA, the possible products then were not pieces of genetic material, and neither were the crucial tools. DNA does not actually do anything. To accomplish the kind of molecular splicing and pasting that now set investors' pulses racing, you needed command of a large battery of enzymes. Back in the mid-1950s, a mere two years after Watson and Crick proposed that DNA was a double helix, Kornberg had isolated the most important of them all, DNA polymerase. Twenty years and a Nobel prize later, he probably knew more about the enzymes that help living cells keep their genetic storehouse in order than anyone alive.

He was already an adviser to Alza, founded in the 1960s by a remarkable Uraguayan scientist, entrepreneur and drug company executive Alex Zaffaroni. Alza was bought out by Ciba-Geigy, and Zaffaroni's search for a new challenge led to the foundation of DNAX, christened the DNAX Research Institute of Molecular and Cellular Biology Inc, to denote its dedication to science.

Kornberg, along with the equally distinguished Paul Berg and Charles Yanofsky, agreed to join Zaffaroni's scientific advisory board. The rest is a tale of DNAX's success, contrasted with the failure of many other, similar ventures, which Kornberg describes with some relish. His success, he argues, lay in forging a commercial culture in which scientists enjoyed all the advantages of academe and none of the disadvantages.

They worked in groups, in close touch with academe, and were free to publish and to pursue their own research as long as it conformed broadly with the company's goals. The results were spectacular, most notably in the discovery of Interleukin-10, an important regulator of the immune response. According to Kornberg, "The discovery of IL-10, at the time it was made, could have come only from DNAX. The prompt coalescence of all the scientific resources of the institute to exploit the discovery would have been possible nowhere else. Such sharing of knowledge, resources and effort would never happen in a university setting, where each research group is discrete, self-contained, and jealous of its own status and security."

While other companies, their founders variously distracted by spending vast paper profits, hampered by commercial secrecy, or tied down by uncomprehending corporate managers after cheap take-overs, went off the boil, DNAX produced spectacular science. More surprisingly, the founders managed to preserve their style after the firm became a subsidiary of Schering-Plough.

The older company was clear what it was buying: "a first-class team . . . which could not be recruited into our, or a competitor's, industrial laboratory." Kornberg in effect made it easier for the pharmaceutical industry to buy some very talented academic scientists.

This is fine by him. He sees the role of the industry as expediting the benefits to be had from the remarkable new science biologists now have at their command. Although he is consistently coy about numbers of dollars, these ventures have plainly made him a wealthy man. But his main satisfaction seems to be in building enterprises - the neuroscience company Regeneron is another to benefit from Kornberg's advice - that bring new health-care products on stream. He is clear that they only exist by exploiting a large base of publicly-funded research.

Indeed corporate strategies down Kornberg's way build in future as well as past university work. At Regeneron, openness with new discoveries was always part of the plan. That way, when nerve growth factors were identified by the company, "Regeneron could distribute them widely and thereby enlist the entire academic neuroscience community in revealing their physiological functions and clinical potential". No need to give all of them a shareholding, presumably, as they were doing what they would want to do anyway.

Kornberg's book assumes that the problem is to exploit the science to best effect. But his impressive account of the dynamism of American capital must now be read in the context of a new generation of technologies. The names of the companies are changing again: GeneMedicine, Somatix Therapy, Viagene, GenVec. These are among the companies dedicated to developing gene therapy. They and ten or so others already represent a billion-dollar investment, although none yet has a product. How far do we wish to leave these techniques in private hands, when almost all the technical experts have a company interest to consider?

For that kind of question, one must turn to a different kind of book, and Enzo Russo and David Cove admit many of these wider concerns into their popular account of the new genetics. They join a growing list of geneticists who want to tell the public about the extraordinary promise of the new developments in molecular biology and to invite them to ponder its implications. Their treatment of the science is fairly standard for such books, assuming no previous knowledge and moving from cell biology through DNA to gene therapy.

Where they differ is in devoting more space to ethical and other issues raised by the new technologies. In particular, they have rather more to say about the history of eugenics, perhaps because one author, Russo, works at the Max Planck Institute for Molecular Genetics in Berlin. They certainly emphasise the involvement of geneticists in the development of eugenics under the Nazis.

Although as convinced as any of the promise of the technology, they end with problems, rather than solutions. How to prevent genetic discrimination? What might be the risks of releasing genetically modified organisms? What are the limits of genetic modification of humans? They give the complete beginner a good basis for starting to think about the problems, as well as the promise. But Kornberg reminds us of one point which the two European academic authors hardly touch on - that all these technologies will be driven by commercial potential as well as clinical need. Jon Turney teaches science communication in the department of science and technology studies, University College London.

Although he has already produced a scientific autobiography, The bright young researchers Kornberg and his colleagues recruited made it the most cited institution in the world for research in immunology between 1986 and 1980.

By creating an institution where academic scientists could enjoy the traditional benefits of a scholarly community without having to chase grants, deal with students, or with unimaginative college adminstrators, , and enriched his family - one of his sons runs a laboratory design company.

- and he is almost exclusively concerned with new drugs Kornberg's fellow scientists than books by working scientists normally do , which even managed to bring some profitable products to market from DNAX discoveries.

A far cry from Crichton's solitary genius spirited away to work in secrecy, t in chapters which are competent if not always inspired It is not too hard.

The Golden Helix: Inside Biotech Ventures

Author - Arthur Kornberg
ISBN - 0 935702 32 6
Publisher - W. H. Freeman
Price - £24.95
Pages - 287

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