'THE DEMON IN THE FREEZER': A TERRIFYING MICROBE



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Last Updated

10 Nov 2002

Source: New York Times, November 10, 2002.

BOOK REVIEW

'The Demon in the Freezer': A Terrifying Microbe

By HAROLD VARMUS

Ever since the publication in 1994 of ''The Hot Zone,'' a factual account of a barely averted disaster with accidentally imported Ebola virus, Richard Preston has been increasingly lionized as our troubadour of troubling microbes. In his new book, ''The Demon in the Freezer,'' the spotlight shifts to another kind of microbial disaster, one that would be intentional and potentially much more lethal -- a bioterrorist attack with the smallpox virus.

No human being is known to have been infected by smallpox for close to a quarter of a century. Yet in a world sensitized to the dangers of terrorism, talk of smallpox is on every front page and at every dinner table. Because infection is often lethal, because the virus is easily transmitted between people and because the discontinuation of routine vaccination three decades ago has made us highly vulnerable, it is not difficult to imagine an attack -- it could be as simple as the undetected arrival in the country of recently infected, suicidal terrorists -- that is truly terrifying.

Policy analysts, public health officials, reporters and many citizens have been imagining such attacks and considering ways to blunt them with the tools of antiterrorism and with medical science -- renewed vaccinations, new medicines, swifter diagnoses. But few of the resulting news reports and books, however informative, portray the immediacy of our predicament with the passion of Preston's new work.

In an afterword he calls the book the third in a ''trilogy on Dark Biology.'' Throughout his trilogy, Preston has used a highly effective technique that seems simple but is artful and informed. He combines extraordinarily vivid descriptions of the pathological effects of infectious agents -- including gruesome but fascinating visits to the autopsies of afflicted people and animals -- with homely accounts of the ordinary routines of people who experience the infections and those who investigate them. With these methods, which blend terror, technology and trivia, he has probably done more than any other writer to establish a nation-wide imperative to think about infectious agents as global threats and potential weapons.

''The Hot Zone,'' the first in the trilogy, is a factual account that reads like a novel. Despite its frightening aspects, the outbreak of Ebola virus in monkeys imported by a research facility in Reston, Va., was not devastating, because the virus strain, now known as Ebola Reston, was unable to infect other hosts efficiently. Thus the outbreak was confined largely to the monkey colony. The second volume, ''The Cobra Event,'' is a fiction that reads like fact, an account of mysterious deaths from a fabricated infectious agent. Buttressed by detailed accounts of the real history, politics, technology and bureaucracy of bioterrorism, it had widely reported effects on national policy. After reading it, President Bill Clinton convened experts and government leaders to discuss its implications, and then readjusted his federal budget proposal to augment defenses against biological weapons.

In this third installment, Preston returns to nonfiction to address what almost all analysts would argue is the most dangerous of the known biological agents. He teaches his readers about the chemical properties of the smallpox virus; how a single infected person (like a returning traveler in Meschede, West Germany, in 1970 -- but read bioterrorist in the post-9/11 world) can set off an epidemic; and what this horrendous disease can be like (in ''flat hemorrhagic smallpox,'' the skin ''darkens until it can look charred, and it can slip off the body in sheets''). We learn how the disease was eliminated by an international vaccination campaign in the 1970's; why there are reasons to believe that the Soviet Union grew staggering quantities of the virus, allegedly in part to arm intercontinental missiles; and how the virus might now be used by others as a ''strategic weapon'' (one that can cause enormous damage to a society without great effort or expense).

Even without evidence that smallpox virus has been used as a weapon in the modern era, concerns about it have sharpened because we have recently witnessed a real episode of bioterrorism within our boundaries: the dissemination of anthrax spores through the mail in the fall of 2001, causing five deaths from inhaled anthrax, several other cases of cutaneous anthrax infection and much panic and confusion.

Apparently for this reason, Preston has chosen, with only partial success, to draw readers into his stories about smallpox through the prism of our experience with anthrax. The book opens with material that is familiar, if ingeniously handled: the first anthrax death, the letters to Senator Tom Daschle and news media figures, and the often clumsy official efforts to understand these incidents and respond. We also get some startling examples of Preston's basic technique. A few pages after being told that a Florida photo retoucher likes to file the barbs off his fishing hooks, we watch pathologists leave their anthrax-contaminated instruments in his body cavity after an autopsy.

A question posed by Peter Jahrling, from the Army's Medical Research Institute of Infectious Diseases, one of the federal investigators of the outbreak -- might the anthrax spores have been laced with particles of smallpox virus? -- is intended to serve as a conduit to the heart of the book, several long chapters about smallpox. Since the proposal seems somewhat implausible and the answer -- which Preston gives only much later -- will be presumed by most readers, the book lacks the integrity and dramatic intensity of its predecessors.

But the essays on smallpox have much to offer. As in the two previous books, the style is a stimulating mixture of cinema (fast cuts to change time and place), science journalism (with news that will surprise even some researchers in virology, presented with an admirable clarity) and personal reminiscence (the ordinary events of people facing extraordinary danger and death).

''The Demon in the Freezer,'' like Preston's 1999 New Yorker article that ran under the same title, feeds on an undercurrent of uncertainty about recent decisions taken by the World Health Organization, with the support of the United States government, not to destroy the two known stockpiles of smallpox virus (''the demon in the freezer''), at the Centers for Disease Control in Atlanta and the ominously named Vector Laboratory in Russia. These decisions, still intensely debated, have disappointed many, like D. A. Henderson, who directed the famously successful worldwide effort by the W.H.O. to eliminate smallpox, and who as an adviser to Tommy Thompson, the secretary of health and human services, is a frequently cited guru on bioterrorism. (He is one of Preston's most fully rendered figures.)

The drive to eradicate every vestige of smallpox, even its causative agent, has now been derailed by two considerations. First, there are reasonable, and worrisome, conjectures -- aired abundantly here and even more thoroughly in other recent books -- that active smallpox virus is not just in the two authorized sites but also in the hands of untrustworthy regimes and terrorists. In addition, there is a more welcome prospect: that the stored virus might be used to produce and test safer vaccines and new antiviral treatments for our vulnerable population.

Preston pursues these conjectures and prospects energetically. In his discussion he emphasizes two recent scientific undertakings that exacerbate underlying tensions about the future of the official virus repositories and raise additional questions about the kind of experiments that should be done in this new era, and about whether they should be reported in widely accessible forms.

The first of these is a collaborative effort between the Centers for Disease Control and Army scientists, urged on by Jahrling, to determine whether our stored smallpox viruses can be transmitted to monkeys to establish an animal model for testing antismallpox drugs and vaccines. Because the story has not been reported in the scientific literature, many virologists will read for the first time in this book about the dozen or so crab-eating monkeys who succumbed to experimentally administered smallpox virus in the summer of 2001, even before the terrorist attacks of Sept. 11 and the anthrax outbreak that followed shortly afterward.

Preston is appropriately ambiguous about whether to view such experiments as harbingers of danger or as a sign of hope for a better defense. But the novelty of the findings may be less than he implies. References reporting the transmission of smallpox virus to various kinds of nonhuman primates as early as 1874 can be found in what Preston respectfully calls ''the Big Red Book.'' This is ''Smallpox and Its Eradication,'' by Frank Fenner and others, including Henderson (who is quoted here as saying, before the new experiments, that monkeys can't get smallpox). But regardless of precedents, readers will be unable to tell whether the recent work should be celebrated, feared or ignored.

The other line of work is more provocative. In characteristic fashion, Preston describes two of his scientific informants, Jahrling and an associate, learning accidentally about surprising results from an Australian group while wandering through a meeting of virologists in Montpellier, France. In these studies, now published in a well-regarded journal, a smallpox-like virus of mice (mousepox) was made more potent -- able to grow in mice that are resistant to the normal virus -- by adding a mammalian gene to the mousepox virus. Such genetic engineering is generally believed more likely to impair than enhance viral virulence, so the findings are surprising and interesting. But if the findings can be extended to the human smallpox virus, something we simply don't know, they might be interesting to bioterrorists too. Such speculation prompts other questions: Should such work have been done in the first place? Should it have been published? Should it be followed up? Should the story even be told in this book? Most of us would answer yes to all of these questions, but in these days of Dark Biology, uncertainty reigns.

Such uncertainty and unanswered questions dominate ''The Demon in the Freezer,'' making it as perplexing as the times. It is also a less satisfying tale than its predecessors. As Preston says, with sadness, on the final page: ''All I knew was that the dream of total Eradication had failed... . We could eradicate smallpox from nature, but we could not uproot the virus from the human heart.''

Harold Varmus is the president of Memorial Sloan-Kettering Cancer Center and former director of the National Institutes of Health.