Shots in the Dark: The Wayward Search for an AIDS Vaccine

  • Jon Cohen
W. W. Norton: 2001. 440 pp. $27.95

With 22 million dead from AIDS and the threat of countless millions more to follow (current infection rates are estimated at 100,000 people per week), the search for a vaccine against the human immunodeficiency virus (HIV) is one of the most urgent and important priorities facing biomedicine. This quest has been followed by the science writer Jon Cohen since its beginnings in the early 1980s, and is now documented in Shots in the Dark. The title and its subheading — “The wayward search for an AIDS vaccine” — give notice that this is a critical account. Jon Cohen has been reporting on AIDS for the journal Science for some ten years and is very highly regarded by researchers in the field.

His book is a long one, totalling more than 400 pages, and is woven from two main strands. The first is a detailed account of the principal events and characters of AIDS- vaccine science and politics, from the first brash announcement in 1984 that there would be a vaccine within three years, to the present day. The second strand is the author's own search for why we still lack a vaccine, where he considers we have gone wrong, and how we could do better. The historical account is fascinating, very well researched and sourced, and should be required reading for anyone wishing to understand the efforts to develop an AIDS vaccine. From White House press secretary Larry Speakes' joking about gay cruising and AIDS in 1982, through to the present controversy about testing subunit vaccines in the United States and Thailand, Cohen presents an authoritative, highly readable and objective narrative.

The author's search within a search is provocative, but in my opinion somewhat less persuasive. Let me not overreach here. Cohen struggles constantly to deal fairly with difficult issues and never resorts to cheap shots or preaching. He focuses on two themes. One is the suggestion that AIDS-vaccine research has lacked central direction (for which the National Institutes of Health (NIH) is criticized). Cohen calls for a 'Manhattan' project, analogous to the concentrated effort of scientists from many subdisciplines to develop the atomic bomb. The second theme is the struggle between 'empiricists', who favour early and many clinical trials, and 'reductionists', who desire more information before committing to large-scale trials.

The call for a Manhattan project has some merit and there have been increasing moves in that direction, particularly from the International AIDS Vaccine Initiative. One needs, however, to temper all criticisms of the NIH, given that this organization is one of the great success stories of the twentieth century. AIDS research in all areas has been built on the rock of NIH funding, and most HIV vaccine research has been, and will continue to be, funded by the NIH. Certainly, the organization suffers from the inflexibility inherent in a large federal bureaucracy and mistakes have been made, but it is not responsible for a 'wayward search' for an AIDS vaccine. The author sometimes sees the problems of AIDS-vaccine development too much in terms of human bungling and not enough in terms of the quirky properties of the virus itself, which has evolved a formidable arsenal of strategies for avoiding immune responses — thereby presenting major problems for vaccine developers.

The empiricism versus reductionism argument is a complex one, sometimes unhelpfully simplified by key protagonists in the book. The late Jonas Salk, for instance, lamented scientists who “mainly seek answers to the most basic questions — dissecting the squirrel to see why it climbs the tree — and there is no detectable push to translate those data into experimental vaccines”. This notion of scientists in ivory towers is more and more a myth. If altruism does not provide the necessary push, then surely, in the modern age of biotechnology, the profit motive will.

Others accuse the NIH culture of undervaluing applied research, but then many scientists would argue that there must be something worthwhile to apply. In AIDS-vaccine research, until recently, there have been very few data of sufficient promise to support a vaccine efficacy trial. In 1995, a meeting was organized at which the assembled scientists “all understood that Thailand urgently needed to try something — even something that had only an outside chance of working”. Is it wise to spend millions of dollars on clinical trials that have only an outside chance of working?

To return to empiricism versus reductionism, all science has a strong empirical component. Every experiment is something of a shot in the dark: if we knew what the result of an experiment was going to be, we wouldn't need to do it. Nevertheless, we constantly make judgements about the worth of following a particular path or taking a particular shot in the dark. Not all shots can or should be taken. It would seem that Cohen joins the contingent who believe that judgement in the HIV-vaccine field has been made too often in favour of restraint. Some of us disagree — arguing that at least the gun should be loaded with live ammunition before shooting in the dark — but doubtless the controversies will continue.

As a scientist, I had a number of other different perspectives from the author. Sometimes I wanted to plead with him that it is not only the guy frenetically running around organizing, planning and talking about vaccine programmes, but also the bench scientist working to solve some crucial problem, who is making big contributions. I was irritated at times by his tendency, Hollywood-style, to embrace mavericks, some of whose work has not stood the test of time. I was also puzzled by the omission of any reference to the solution of the structure of the virus surface protein gp120, which I believe will eventually be seen as a major milestone on the route to an HIV vaccine. But, reservations aside, my emphatic overall conclusion is that this is an excellent book which demands to be read.