A Machine to Make a Future: Biotech Chronicles

A Machine to Make a Future: Biotech Chronicles

by Paul Rabinow, Talia Dan-Cohen

Paperback(With a New afterword by the authors)

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A Machine to Make a Future represents a remarkably original look at the present and possible future of biotechnology research in the wake of the mapping of the human genome. The central tenet of Celera Diagnostics--the California biotech company whose formative work during 2003 is the focus of the book--is that the emergent knowledge about the genome, with its profound implications for human health, can now be turned into a powerful diagnostic apparatus--one that will yield breakthrough diagnostic and therapeutic products (and, potentially, profit). Celera's efforts--assuming they succeed--may fundamentally reshape the fabric of how health and health care are understood, practiced, and managed.

Presenting a series of interviews with all of the key players in Celera Diagnostics, Paul Rabinow and Talia Dan-Cohen open a fascinating window on the complexity of corporate scientific innovation. This marks a radical departure from other books on the biotech industry by chronicling the vicissitudes of a project during a finite time period, in the words of the actors themselves.

Ultimately, the authors conclude, Celera Diagnostics is engaged in a future characterized not by geniuses and their celebrated discoveries but by a largely anonymous and widely distributed profusion of data and results--a "machine to make a future."

In their new afterword, Rabinow and Dan-Cohen revisit Celera Diagnostics as its mighty machine grinds along, wondering, along with the scientists, "what constitutes success and what constitutes failure?" The pathos of the situation turns on how one poses the question as much as how one answers it.

Product Details

ISBN-13: 9780691126142
Publisher: Princeton University Press
Publication date: 04/02/2006
Edition description: With a New afterword by the authors
Pages: 224
Product dimensions: 6.00(w) x 9.25(h) x (d)

About the Author

Paul Rabinow is Professor of Anthropology at the University of California, Berkeley. His many books include French DNA, Making PCR, and Anthropos Today (Princeton). Talia Dan-Cohen received a B.A. in anthropology from the University of California, Berkeley.

Read an Excerpt

A Machine to Make a Future

Biotech Chronicles
By Paul Rabinow Talia Dan-Cohen

Princeton University Press

Princeton University Press
All right reserved.

ISBN: 0-691-12614-3

Chapter One


Confronted with an apparently deadlocked and frustrating situation, actors have a number of possible courses of action. The economist Albert Hirschman developed an elegant typology of such options. The first is one of "voice": the actors remain in the troubled situation but actively seek to propose alternatives. By so doing, they affirm their fundamental loyalty to the current order of things but express their dissatisfaction with it. By affirming their loyalty, they legitimate their criticisms as being in the interest of the organization, product, or party. A second alternative is to remain loyal to the organization, product, or political party and simply endure the strain of the current situation, hoping that it will change. The third option is "exit." This option usually is chosen only after attempts at voice and loyalty have failed. Exit can be a kind of voice, as it makes a statement of an informed kind, addressed to those who have the power to change things, about what the actors take to be an untenable state of affairs. Exit can even be a kind of loyalty, in the sense that it may well affirm commitment to the fundamental principles or modes of operation that moved the actors to join theorganization, buy the product, or work for the political party in the first place.

The future directors of Celera Diagnostics proceeded haltingly and with much reflective, even agonized, soul-searching, down the paths of voice, loyalty, and finally, exit. In some situations, stasis and patience may well be a plausible option. One can imagine political loyalists waiting through a rough period until better times arrive, but in the domain of genomics there is no such thing as long-term stasis. On the one hand, as the investments, stakes, and pressures are so high, decisions need to be carefully weighed, especially as they are being taken in uncharted waters. (No one knows how to best do genomics.) On the other hand, the investments, stakes, and pressures preclude excessive delay or procrastination. Everything turns, therefore, on what one considers to be "excessive."

In addition to differing judgments as to what constitutes a "reasonable" or "prudent" weighing of options-over which actors might well differ in good faith-there are other factors that affect the dynamics of loyalty, voice, and exit. These include the legitimacy accorded to those making decisions. That legitimacy rests on multiple foundations, from a simple respect for hierarchy to a sense that even decisions one disagrees with are nonetheless being taken in good faith and are being applied in a spirit of equity. When the latter affective or emotional ties are eroded, they become very hard to repair. Honest differences of opinion are easier to adjudicate and overcome than the erosion of trust. Once the latter process advances, the proverbial exit door beckons. Of course, upon exiting one must go somewhere else. Hence conditional planning and increasingly divided loyalties (even if the letter of the law is strictly followed) almost invariably precede leave-taking.

The leaders of Roche Molecular Systems-Kathy Ordoñez, Tom White, and John Sninsky-during 1999 and the first half of 2000 found themselves in a situation that fits Hirschman's typology. To show them facing the fork in the road, we first present a summary of the situation as seen from the outside, including an interview with Michael Hunkapiller, president of Applied BioSystems, and then, two interviews with Tom White, as well as interviews with Kathy Ordoñez and Gabriella Dalisay, White's executive assistant.

Holding Pattern: Turbulence and Stasis

A line of developments with direct consequences for our chronicle took place in 1998 when Hoffmann La Roche acquired a German company, Boehringer-Mannheim. The merger was announced in April 1998 and officially started in April (or May) 1999. Mergers are complex affairs requiring multiple levels of negotiation to bring about and many more steps to bring to fruition. Among the possible complications, and in this case an apparently unanticipated one, is cultural friction between the merging companies: German, Swiss, and American styles of management and personal relations did not blend easily. This cultural friction was linked to the power dynamics any such situation entails. The German representatives jockeyed hard for increased authority and power in shaping and running the new organization, and over time they were making advances in achieving their goal. There is no need to explore here the typical corporate and bureaucratic politics involved, only to underscore that they existed, and that they set other things in motion that do concern us directly. Among these factors was the interpersonal and intercultural dynamics between a company run in an American style and headed by a woman and a more bureaucratically oriented company staffed in its upper echelons by men of a certain age and style.

Thus, for the key players at Roche Molecular Systems, it was during 2000 that future career options became an object to reflect on. Equally, as we have seen, it was during this period that the developments in genome mapping were coming to fruition as the race to finish the initial sequencing accelerated.

We interviewed Mike Hunkapiller at Applied Biosystems on July 7, 2003. He explained the events that led to the departure of Venter, in January 2002, from the company that he had helped make famous and the arrival of Kathy Ordoñez onto the scene.

MH: Celera Genomics was started as an information and bioinformatics endeavor, and its initial goal was to use the sequencing of the human genome to establish a position in that field. It was not just sequencing for sequencing's sake, and it absolutely wasn't to build a huge patent portfolio around the human genome as such. It really was to lay the foundation for an information business, and from my perspective, it got a little bit ahead of itself as being seen as a business built around a proprietary set of information, and it was always intended to be an informatics tools business. The value lay in helping people understand what the human genome was. Celera Genomics had envisioned, even early on, taking some of the information tools applied to the sequence data and pulling out bits of information that they would exploit themselves, either as therapeutic targets or as diagnostic targets. They didn't have the expertise built up To do either because things moved so fast on the sequencing side that the company got ahead of itself.

PR: So Celera's strategy of challenging the public effort worked almost too well?

MH: Almost too well, that's true. They chose to focus initially on the therapeutic side. And partly because that's a long-term research endeavor you do internally, we decided that the best way to do the diagnostics was to create a joint venture between two of us, and that provided a good vehicle for bringing Kathy and her group in.

PR: So there was no resistance from Celera Genomics on any of this?

MH: No, I think Craig would have probably preferred to do a lot of it in Celera Genomics, but he really didn't have the people and the expertise to do it, and if you're going to bring on somebody of Kathy's caliber, they have to have a coequal position in the overall management scheme for the purpose of arguing for resources. So the resistance didn't last for long.

PR: She speaks only glowingly of Venter, which is what one would expect.

MH: [laughs] Well, I mean, Craig has had a history of successfully challenging conventional wisdom as to what's possible scientifically. And he likes to play the role of a maverick in that process, there's no doubt about that; he's been right on many occasions when the traditional wisdom wasn't so correct. While Celera was in the formative mode of really having to challenge what was thought to be the pathway to get the human genome sequenced, Craig was really into that. Once he had to step back into a more traditional, longer-term role of managing a business, he was less well matched for the job and the role in the therapeutics aspect. Being a maverick may sound good but it doesn't work with the FDA or the whole procedure of getting things through a long, drawn-out process. And so he was just less comfortable with doing that. I think it was a natural parting point. Had things moved more slowly in the sequencing, he would have had the time to build up an organization that would have brought in the relevant expertise to take that over, but there wasn't time.

PR: And therapeutics is sexier than diagnostics too?

MH: Well, I'm not sure I would argue that that's the case-some people might. It has bigger payoffs associated with it in some cases, but I wouldn't argue it's any more valuable or interesting scientifically. But Craig hadn't done the diagnostics either. He just hadn't built the biology up commensurate with the science associated with generating large amounts of information, which is what the expertise of Celera Genomics was initially-bioinformatics. And they had begun to do a little bit on the protein side, mostly from the perspective of coming up with protein targets for therapeutics. But it was still research, not research directed toward specific disease indications. It was kind of broad: How do you generate a lot of data and then begin to pick the cream off the top of that? So when he left, Tony [White] looked to bring in a seasoned pharmaceutical executive who could mesh the research endeavor and engine that was there with the opportunities in therapeutics. In the end he decided that maybe that wasn't the best position for us to be in, because it's a rough road-it may be sexy, but it's also risky, and the failure rate is very high. Is there a way that we can take advantage of the fact that we've got a pretty successful beginning to a genetic diagnostics business and the right team there in Alameda running it? So we decided to try doing the clinical diagnostics and the clinical therapeutics development together in areas where there could be synergy between the two.

PR: So it was very intense?

MH: Sure. Celera had taken advantage of the big spike in market capitalizations to go out and do a secondary offering and raise money. We had the resources there. We didn't want the resources sitting idly. PR: And then, given that thinking, it was, as you say, natural that Kathy and her people would be a good choice?

MH: Well, Kathy was brought in to run the diagnostics business before Craig left. Although they're separate entities, having Kathy oversee both of them could maximize the synergy between the two.

Initial Plans: Interview with Tom White, October 15, 2001 TW: Today is the anniversary of the date I accepted the job offer from Applied Biosystems. The same applies to Kathy and John. Four to six weeks later we left Roche and joined Applied Biosystems.

The first few months were spent analyzing the AB technologies; we were somewhat familiar with them as AB was Roche's partner in the research field. We spent close to three months working together by driving down to Foster City a lot. We would meet in the morning at Kathy's house from eight to ten until the traffic died down, then head across the bridge and try to leave there by three o'clock, when the traffic got impossible. So it was a chance to look at things without the encumbrance of having the Roche business going. We were essentially developing a strategy for analyzing what we were going to do. At Roche we were so busy we were not able to devote the extensive time to do this analysis.

We began with a clean slate about AB and then developed a plan about what to analyze. The existing molecular diagnostic business in infectious disease tests is Roche's business, and that is the one we built; we know the competitors (Abbott, Bayer). They are still thinking about how to take Roche's business away from them today rather than thinking about how to proceed over the next ten years. They have had trouble competing against Roche, rather than leaping into a completely unknown area. This is not a good strategy since Roche's competitors had not done well in the infectious disease area. Other companies approached us because they had been competing against us at Roche, and they were now thinking it might be useful to work with us as a way to compete against Roche. For us it was more a question first of figuring out what we wanted to do. We didn't want any more encumbrances; we felt that those companies' limited success in this field was not a plus. We left to do something really different. We are focusing on molecular diagnostics, a totally new field that is still only a small part of the diagnostics field as a whole, which is mostly clinical chemistry. Molecular methods have increased to about a billion dollars a year over the last ten years, but that is only 5 percent of the diagnostic product market. There are only four or five companies that are in that. Since those companies also offer the full range of diagnostic tests, a new, small company can't really compete in hospitals, medical centers, and big labs unless it offers the full range of products. That is the flaw of most of the biotech companies; they think, "We have hot new technology or a hot new test for a specific thing," but they don't realize how diagnostics are delivered to the worldwide medical system. Even when we were at Roche, we had R&D, manufacturing, regulatory, et cetera, but we did not actually sell to customers; we sold to another unit of Roche. We wanted to discover what was useful medically, develop it, and then have someone else sell it. And then we can go on to the next medically important thing. We felt that we don't want to get into the end stage business of marketing and sales to customers. This meant we had to partner with one of the big companies like Roche or Bayer or Abbott, BioMerieux, GenProbe, or Johnson & Johnson. It was always an element of our strategy to figure out who was the best company to distribute the things that we develop. Because of our past relationship with Roche, our former employers, we were not inclined in that direction. At the same time, they own more than half of the molecular diagnostic business and they are more than five times more powerful than any of the other second choices. We wanted to explore the thoughts of the other companies; by the end of the year 2001 we intended to finish our discussions. So that is the strategy of establishing the downstream part of the business that will allow us to feel more comfortable about focusing on what we are calling "the front part."

The Front Part We began by thinking about what were the areas that Roche had not analyzed. Roche has described their genetic projects in a number of areas, such as heart disease and certain inflammatory diseases that are tied to Roche's pharmaceutical interests. Since founding Celera Diagnostics, we have analyzed over two hundred complex diseases for unmet diagnostic needs. It is the most comprehensive analysis I have ever seen. To my knowledge, no other diagnostics company anywhere has done this kind of analysis. The quality of the analysis is pretty amazing in terms of what we have selected to do. So there is no reason to not just forge ahead and do it. We are not like Incyte, Genaissance, DNA Sciences, or little biotech companies trying to raise money by claiming they can do everything. We are prepared to methodically set up this massive thing to do disease association studies on the same scale as Celera Genomics sequenced the genome.


Excerpted from A Machine to Make a Future by Paul Rabinow Talia Dan-Cohen Excerpted by permission.
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Table of Contents








Chapter Seven: SUMMER 2003 169

Illustrations 187


Notes 191

Glossary 195

What People are Saying About This

Nadia Abu El-Haj

A Machine to Make a Future is an insightful and creative contribution to the literature—both scholarly and journalistic—on contemporary genomics. By 'experimenting' with narrative genre, the authors hope to generate different insights into the world of genomics and biotechnology than ones generally presented in existing accounts. They succeed at that goal, providing an account that is ethnographically rich and analytically open to a world whose structure, implications, and outcomes are very much in the making.
Nadia Abu El-Haj, Barnard College, author of "Facts on the Ground"

George Marcus

This impressive book provides an accessible, frank, behind-the-scenes look at what is really likely from the much-hyped hope-inspiring mapping of the genome. Led by the brilliant questioning and set pieces Rabinow and Dan-Cohen have devised, the reader gains, on the one hand, a heartening view of collective scientific talent, ingenuity, and cunning at work. On the other hand, through their interviews the authors show what is really different about this work of scientists—the talented work under the shadow of the profit motive, risk, opportunity, markets, and the brutality, sometimes, of the verdicts of their capitalist patrons. All of this is ingeniously explored in this chronicle, in an involving and engaging way. I gained much from reading it both as an anthropologist and as a middle-aged general reader, like many others, interested in the imminent promise of genetics for medical care.
George Marcus, Rice University, author of "Ethnography through Thick and Thin"

Sarah Franklin

This fascinating book opens up a huge number of questions about how social scientists, anthropologists, or science studies practitioners write about science, scientists, technology, and innovation. It offers some of the most sophisticated and detailed accounts to date of the complexity, serendipity, and unpredictability of the very kinds of scientific innovation that are often described as being deliberately planned to serve specific interests or normative values. It is packed with very original data, its analytical style and argument are very provocative, and it makes a very timely contribution to the field. I have never read anything like it.
Sarah Franklin, author of "Embodied Progress: A Cultural Account of Assisted Conception"

Roger Brent

The stresses caused by the rapid growth of biological knowledge and capability will sorely test democratic societies in the coming decades. A first step in coping with these strains must involve expanding the discussion of the issues and the pace of change beyond the tiny circle of biologists and businesspeople now involved. Enter Rabinow and Dan-Cohen, whose investigations of Celera Diagnostics, a company at the forefront of research in human genetic differences, open the concepts, practices, and institutions of this revolutionary world to broader public scrutiny. Imagine if Tracy Kidder had written The Soul of a New Machine about a genomic diagnostics company, and informed it with deep, scholarly insight into science, business, and leadership, and you begin to get the scope of this book.
Dr. Roger Brent, Director and President of The Molecular Sciences Institute

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