A pox on Smallpox

Smallpox is a severe viral disease that claimed hundreds of millions of lives during the course of history. A uniquely human affliction, it killed a third of its victims and left the survivors disfigured with pockmarks and sometimes blind. From 1966 to 1977, a global vaccination campaign under the auspices of the World Health Organization (WHO) eradicated smallpox from the planet in one of the greatest public health achievements of the 20th century. Since then, the absence of the disease has saved an estimated 60 million lives. In a dark irony, however, eradication created a new vulnerability with respect to the potential use of the smallpox virus as a biological weapon.

Smallpox—The Death of a Disease is an authoritative behind-the-scenes history of smallpox eradication and its aftermath by D. A. Henderson, the U.S. physician who directed the global campaign. At its best, Henderson’s memoir is a compelling human story about overcoming adversity in pursuit of a noble cause. The reader vicariously experiences the deep emotional lows and exhilarating highs of participating in a hugely ambitious international effort whose ultimate success depended on the vision, dedication, and teamwork of a relatively small group of individuals. Although the technical recounting of the eradication program is at times overly detailed for the general reader, the book provides valuable lessons for anyone interested in global health or the management of large and complex multinational projects. Those seeking a balanced, objective treatment of smallpox-related issues should look elsewhere, however. Henderson pulls no punches in assigning credit or blame where he considers it due and in conveying strong personal views on a variety of controversial topics.

The book weaves Henderson’s personal history with that of the smallpox virus. An Ohio native, he attended Oberlin College and then went to medical school at the University of Rochester. In 1955, he was drafted for two years of military service and offered a position with the Epidemic Intelligence Service of the Communicable Disease Center (CDC), later renamed the Centers for Disease Control and Prevention. Although Henderson had no particular interest in infectious diseases, tracking down outbreaks sounded more interesting than doing routine physicals, so he accepted the offer. At the CDC, he was trained in “shoe leather epidemiology,” or the investigation of epidemics by collecting data and interviewing patients. Eventually, he became deeply engaged by public health and decided to devote his career to it.

At the time, smallpox imposed a major burden of illness and death on the developing world. Although the last case in the United States had been in 1949, the CDC considered it almost inevitable that a traveler from a country where smallpox was endemic would reintroduce the disease. Several aspects of smallpox made it theoretically susceptible to eradication, including the easily diagnosed facial rash and the lack of an animal reservoir. In 1958, the Soviet Union had persuaded WHO to launch a smallpox eradication program, but it was seriously underfunded and made little headway.

After Henderson was promoted to section chief at the CDC, he submitted a proposal to the U.S. Agency for International Development for a five-year program of smallpox eradication and measles control in 18 countries of West Africa. Unexpectedly, President Lyndon Johnson decided to fully fund the project in late 1965 and later expanded it. This U.S. engagement tipped the balance in favor of a decision the following year by WHO member states to launch an intensified global smallpox eradication program, although the resolution passed by only two votes. Because the WHO director-general believed that eradication was impossible, he insisted on putting an American in charge so that when the program failed, the United States would be held responsible for the debacle. Henderson was chosen as the sacrificial lamb, and in October 1966, aged 39 and with only 10 years of experience in public health, he flew to Geneva to lead what looked to be a quixotic effort.

At that time, smallpox was endemic in 31 countries, was being routinely imported into 12 more, and was causing between 10 and 15 million cases a year, with 2 million deaths. At WHO Headquarters, the smallpox program was housed in three modest rooms and given a small staff and a shoestring budget. In addition to a skeptical boss, Henderson faced a dysfunctional WHO bureaucracy with six passive and uncooperative regional offices. To overcome these obstacles, Henderson had to be resourceful, pragmatic, and wily, circumventing the regional offices when it was necessary to get things done. He also recruited a small but talented group of epidemiologists with the determination to persevere against great odds.

Smallpox— The Death of a Disease describes the myriad political, logistical, and organizational challenges that the WHO eradication campaign had to overcome during its 11-year history, including wars, floods, refugee crises, and unresponsive governments. Despite repeated setbacks, the team of public health practitioners from several countries persisted in their efforts, inspired by the goal of conquering an ancient scourge and buoyed by an ethos of collegiality and teamwork. A major theme of the book is the improvisational and unorthodox way in which Henderson and his colleagues worked around technical and bureaucratic obstacles. Even so, the ultimate success of the campaign hung in the balance until the last moment.

Two technological advances were essential to the success of smallpox eradication: the development of a stable, freeze-dried vaccine (containing the related but benign vaccinia virus) that did not require refrigeration in tropical countries, and a simple but elegant method of inoculating the vaccine into the recipient’s skin with a bifurcated needle. The basic strategy also evolved over time. The initial approach was mass vaccination, designed to reach at least 80% of the population. But epidemiologists soon discovered that the rapid detection of smallpox outbreaks, followed by the isolation of patients and the vaccination of family members and other contacts in the immediate vicinity, created a “firebreak” of immune people that halted the further spread of the disease. This discovery led Henderson to augment mass vaccination with a targeted strategy called “surveillance-containment.” Because national health ministers had known only mass vaccination, however, they found the new approach hard to accept.

The greatest challenges of the eradication campaign arose in India and Bangladesh because of the high population density and the mobility of migrant laborers and refugees. During the fall and winter of 1972–1973, a massive smallpox epidemic broke out in three impoverished states of northern India with a total population of 189 million. WHO’s strategy was mass vaccination combined with intensive surveillance-containment, including monthly searches for smallpox cases in thousands of villages. This effort involved up to 150,000 health workers and required eight tons of forms and other documentation.

In 1974, as the outbreak in northern India continued to spiral out of control, the program staff faced a deeply discouraging period when it seemed that all their efforts would come to naught. Henderson describes a meeting at which the country team members were exhausted, having worked seven-day weeks for several months in sweltering heat. Four had serious medical ailments, yet “the only problem they would discuss was where to find the additional resources to keep the program going.” They persisted, and gradually the number of smallpox outbreaks began to wane; the last case in India was found in May 1975.

The final battles of the eradication campaign took place in Ethiopia and Somalia, where health workers faced armed villagers who resisted vaccination, uncooperative government officials who suppressed information about outbreaks, and widely dispersed groups of nomads who had to be tracked down and vaccinated. A 30-year-old Somali cook named Ali Maow Maalin was the world’s last case of natural smallpox, the endpoint in a continuing chain of transmission extending back at least 3,500 years.

The remainder of the book is devoted to the post-eradication period, including the painstaking two-year process of verifying that no cases of smallpox remained hidden in some remote corner of the globe. Henderson also addresses the contentious debate over whether to destroy the remaining laboratory stocks of the smallpox virus. After eradication, WHO gradually reduced the number of labs worldwide that possessed the virus from 75 to 2 authorized repositories: 1 in the United States and 1 in Russia. Although the U.S. government initially supported a plan to destroy the smallpox virus stocks, in late 1994 the Pentagon began pushing to retain the live virus for the development of improved defenses against its possible use as a biological weapon. Driving this concern were reports from Soviet defectors that Moscow had maintained a vast clandestine biological warfare program in violation of international law, including the production of smallpox virus as a strategic weapon—a shocking betrayal of the goals of the WHO eradication campaign. Other countries, such as North Korea and Iran, were also suspected of retaining illicit stocks of the virus. Because the routine vaccination of civilians against smallpox had ended in the early 1980s, the world’s population was increasingly vulnerable to a deliberate attack, yet only limited supplies of smallpox vaccine were available.

In the mid-1990s, Henderson reengaged with smallpox issues on a number of fronts, including efforts to train physicians and public health experts about the diagnosis, treatment, and control of the now-unfamiliar disease. After 9/11 and the anthrax letter attacks, the Bush administration appointed him to direct a new office of public heath preparedness, where he spearheaded a crash program to procure 200 million doses of smallpox vaccine by the fall of 2003. Henderson disagreed with a plan proposed by Vice President Dick Cheney to vaccinate the entire U.S. population against smallpox, arguing that the risk of serious side effects from the vaccine far outweighed the low probability of a military or terrorist attack with the virus. Over his objections, the White House proceeded with the voluntary vaccination of some 450,000 front-line health workers, but the program collapsed when fewer than 40,000 agreed to be vaccinated.

Henderson discusses at length his opposition to research with the live smallpox virus for the development of medical countermeasures such as antiviral drugs, which began in 1999 at the two WHO-authorized repositories and has continued since then. He questions the value of such research, noting that in tests with infected animals, no drug candidate has been effective when administered after the appearance of fever and rash. In his view, destroying the known stocks of the smallpox virus would set a powerful moral standard for the international community. Although it would be impossible to verify that no hidden caches still existed after the known stocks had been destroyed, WHO member states could formally agree that any scientist or country found to possess the smallpox virus would be deemed guilty of a crime against humanity and subjected to severe sanctions. Proponents of defensive research with the live virus consider Henderson’s proposal dangerously naïve and believe that the development of anti-smallpox drugs is both necessary and feasible. In an effort to resolve this policy debate, WHO is conducting a major review of the smallpox research program for discussion at the next annual meeting of member states in May 2010, with a final resolution of the issue scheduled for the subsequent annual meeting in 2011.

Henderson is also skeptical about the current WHO campaigns to eradicate Guinea worm and polio (launched in 1986 and 1988, respectively), neither of which has succeeded after more than 20 years of effort. “At this time, I don’t believe we have either the technology or the commitment to pursue another eradication goal,” he writes. “More useful and contributory would be to build and sustain effective control programs that are adapted to the social and public health needs of each country.” This view conflicts with that of WHO Director-General Margaret Chan, who recently affirmed that polio eradication remains one of the organization’s top priorities.

Although his critics portray Henderson as a curmudgeon, no one can deny the sincerity of his opinions or the magnitude of his achievements. Indeed, his powerful intellect, unbending will, impatience with bureaucratic ineptitude, and contrarian nature, all of which are on display in this intriguing memoir, were key to the success of the smallpox eradication campaign.

Jonathan B. Tucker ([email protected]) is a senior fellow specializing in biological and chemical weapons at the James Martin Center for Nonproliferation Studies and the author of Scourge: The Once and Future Threat of Smallpox (Atlantic Monthly Press, 2001).