Friday, August 27, 2010

Guest Post - Eliminating Smallpox

by Robert L. Wallace

For several decades a mass murderer has waited on death row. As with other scheduled executions, this one is not without controversy, but the final decision to execute will not be made in the courts, nor will it be made by popular vote. Further, this murderer is not a person. It is the smallpox virus, and the last portions of this killer known to science are held in special vials within the cold storage chambers of two high-tech microbiology laboratories. One set of samples, numbering some 450 units, is held in Atlanta at the Centers for Disease Control and Prevention, commonly known as the CDC. The other samples (about 150 units) are in Moscow at the Institute for Viral Preparations. This execution has been delayed and rescheduled—only to be delayed again. The World Health Organization (WHO) will again consider its destruction next year.

The human battle with smallpox (a.k.a., variola or varida) is an ancient one, dating back at least 2,000 years. However, with mortality rates ranging from a low of 1% to a depressing 50% depending on the strain, the effect of this scourge on humanity has never been the same in all societies. Nevertheless, if not a killer, smallpox usually left evidence of its presence in the form of deep scars or pockmarks on the survivors.

Unfortunately, throughout much of history our arsenal against smallpox was limited. Progress, therefore, in overcoming this disease was very slow. The earliest records of combating smallpox come from the 10th century. These accounts chronicle early attempts to control epidemics by a practice called variolation. In China variolation was done by having people inhale dust that had been produced by crushing the dried scabs collected from the pock scars of people with variola. In the Middle East a variation of this practice was done. Here scab material or fresh fluid was ingested by, or inoculated into, a disease-free person.

To some, variolation seems to be a silly idea, but the concept was sound. Rather than waiting for an epidemic to come along, entering a population where few people were immune, a small epidemic was started. In this way the terrible scourge of an epidemic was controlled as a negligible outbreak: negligible, but only to those who did not become seriously ill. In immunological terms, variolation relies on a phenomenon known as herd immunity; the more people in a community (the herd) who are immune to an infectious disease, the less chance there is for the disease agent to establish a full-blown epidemic.

Lady Mary Wortley Montague, spouse of the British Ambassador to Turkey, introduced variolation into England in 1718 and the practice was used in England until the end of that century. Even Washington had his troops protected in this way. Variolation worked best when the milder strain of smallpox, variola minor, was used. Unfortunately, when a more virulent strain of the disease was used, variola major, the case-fatality rate could exceed 50%.

Although probably part of folk-wisdom for centuries, the knowledge that previous infection with cowpox imparts protection against smallpox was first applied as a prophylactic two decades before Edward Jenner’s celebrated attempt (Cartwright & Biddiss, 2000, pdf). These early attempts notwithstanding, modern treatment for smallpox really developed from the work of Jenner in the late 18th Century. Like those before him, Jenner noted that dairymaids in rural England usually did not carry the characteristic smallpox scars seen on those who had survived their bout with smallpox. Jenner formulated a hypothesis that the dairymaids had contracted cowpox and that this conferred immunity to variola. Cowpox generally causes little problems to humans or even to cattle for that matter. Working on this insight Jenner inoculated the arm of James Phipps with the pus from cowpox scabs from the hand of Sarah Nelmes. Then a scant three weeks later injected the boy with material from smallpox victims. Common knowledge at the time held that the boy would come down with at least the mild case of smallpox, but he did not. Thus was born the practice of vaccination, the procedure of conferring immunity against a certain disease through inoculation with a specific substance. The word vaccination is derived from the term used for the cowpox virus, vaccinia (Latin, vaccin-, of a cow).

Jenner's prophylactic for smallpox was hardly without controversy. Political cartoons at the time predicted that those inoculated with cowpox scabs would grow the heads of cows from their arms or other parts of their bodies. As vaccination proved effective its practice became widespread, but not universally. In the U.S., a modern form of vaccination was rigorously applied so that smallpox epidemics were rare in the 20th century. Eventually, the need for immunization in the U.S. declined and, except for the armed forces, it has not been possible to get a vaccination of smallpox for many years. So in the U.S. smallpox vaccination became a thing of memory even before epidemic smallpox was eliminated from the world. The elimination of routine vaccination explains the rarity of vaccination scars on the arms of people younger than about 40 years of age. At one time a large percentage of the world’s population was immune to smallpox, either through a natural active immunity (i.e., surviving the disease) or artificial active immunity (i.e., vaccination), but, of course, the level of immunity is dropping.

As humans are the only natural host of the virus, WHO saw the possibility of a worldwide immunization campaign against smallpox with the goal of its eradication. The WHO program was not without its political and religious problems, but the goal of universal immunization against smallpox was achieved late in the 1970s. Smallpox was declared eradicated in 1979 by WHO (the publication date was actually 1980) and smallpox is now considered to be a disease of the past.

To close this part of history, we should note that the last case of epidemic smallpox was diagnosed in a Somalian, Ali Maolin, on October 26, 1977; over 30 years ago. The only other case developed as a result of a laboratory accident the following year. That infection resulted in two cases of smallpox and two deaths, but only one from smallpox itself. Janet Parker, a medical photographer from Birmingham University Medical School in England, died of the disease; the other death was a suicide by the head of the smallpox laboratory. So it took about 170 years to move from Jenner’s work in 1796 to the elimination of epidemic smallpox in 1977.

The Debate — So what of the vials of the variola virus that await their fate in those deep freezers? And why is there any debate at all over their fate?

Those who favor the destruction of the smallpox virus maintain that there is no need to keep the virus for a number of reasons. We already have sequenced the genetic code of the major variants and the virus has been divided into several short fragments, which have been inserted into separate plasmids that reside in special strains of bacterial kept in laboratory culture. Thus, there are adequate ways of studying the virus without the possibility of causing an epidemic. The virus produces a relatively slow moving epidemic with easily recognizable symptoms. Therefore, any new epidemic supplied from unknown sources may be contained by quarantine. There is no evidence that there are hidden reservoirs of smallpox. Also there is no evidence that without smallpox there is a kind of empty pathological niche waiting to be filled by a related virus, a virus that will evolve into a new form of smallpox. Further, the nomination of monkeypox, as a candidate for this evolutionary step seems unwarranted. Genomic studies by Douglas & Dumbell (1992) indicate that monkeypox is not the ancestor to smallpox. It is not be necessary to keep stocks of smallpox virus on hand from which we could make vaccine; new epidemics would provide sufficient stock and of the proper variant(s) to produce new vaccines. Destruction of the viral stocks would remove forever the possibility of accidental or deliberate release. The latter could occur from hostile nations engaged in biological warfare or from terrorists. Finally, destruction of this virus will be an important symbol of hope in these days of a different plague, HIV–AIDS.

Those in favor of saving the samples argue that destruction of the samples does not eliminate the threat of additional outbreaks of smallpox. First, new epidemics could come from some unknown active pocket in a remote corner of the world, from a victim buried in the permafrost of Siberia, or from mislabeled samples that may remain in laboratories around the world. Second, an evolutionary change could occur, if not from cowpox or monkeypox, then from some other unknown source. This would permit the emergence of a new poxvirus into the human population. Therefore, smallpox reserves should be retained to permit controlled studies allowing full understanding of the biology of a deadly virus we have yet to completely comprehend. Opponents of the destruction also argue that the study of this virus might provide insights into other important diseases. Finally, they argue that we should not get into the habit of eliminating any life form—even the etiological agents of disease—as we exterminate far too many species already.

Shall science execute this plague virus or not? A morning's work with an autoclave or even a large pressure cooker in two different sites is all that is needed to send this killer to oblivion. A report from WHO scientists was prepared for the General Assembly of the United Nations and the recommendation was made to destroy the smallpox virus. After one stay of execution a second date was set for June 30, 1995, but another reprieve was granted. Now another new date for the destruction of smallpox is approaching, and the question remains: what should we do with the virus?

Humanity has wanted to eliminate this disease since the time of Edward Jenner. While the disease state of Smallpox has been purged from humanity, now we can eliminate the last known remnants of the etiologic agent—or so it would seem. What should we do with the remaining vials of smallpox: keep it or destroy it? I argue for its destruction.

Cartwright, F.F. & M. Biddiss. 2000. Disease and History. Sutton Publishing, Phoenix Mill, UK.

Douglass, N.J. & K.R. Dumbell 1996. DNA sequence variation as a clue to the phylogenesis of orthopoxviruses. Journal of General Virology 77 947–951.

Robert Wallace is Professor of Biology at Ripon College. Versions of this post were published in 1994 in The Oregonian, The Houston Post, St Louis Post-Dispatch, Providence Journal-Bulletin, Valley News, Ripon Commonwealth Press, and The Milwaukee Journal.

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