COLUMNS RELATING TO CHEMICAL AND BIOLOGICAL WARFARE BY

JOSHUA LEDERBERG

[From the Washington Post, Sept. 24, 1966]

A TREATY PROPOSAL ON GERM WARFARE

(By Joshua Lederberg)

(The author is Professor of Genetics at the Stanford University School of Medicine, and a recipient of the Nobel Prize for Medicine in 1958.)

On Sept. 19 a distinguished group of my scientific colleagues released the text of a petition to President Johnson concerning U.S. policy on biological and chemical warfare. They point to the encouragement for the wider commitment to these weapons that our own actions in Vietnam might generate.

According to news reports, we are making extensive use of defoliating chemicals not only against forest cover but also against crops purportedly available to the Vietcong. At some times, tear gas has also been used in military and occupation missions.

The United States has vehemently denied the military use of any biological weapons or of any lethal chemical weapons. However, research on these weapons has continued through and from World War II The Army has a wellknown research facility at Fort Detrick, Md., and a testing station at Dugway, Utah. The aggressiveness with which these activities have been publicized may be laid to intra-service competition for funds to expand a line of work whose actual military utility is highly controversial.

CBR (Chemical, Biological, Radiological Warfare) can easily evoke a highly emotional response, attracting the most vehement emotions on the inhumanity of war. The focus on boycott demonstrations against napalm production shows this; aircraft manufacture or steel production would be far more consequential to the roots of military homicide. The petitioners do not allude to the specific inhumanity of CBR, but it is undoubtedly involved in the stringency of their reactions.

Can we be "rational" about the inhumanity of one class of weapons as against another? It is hard to imagine more inhuman methods of homicide than explosion or suffocation in a collapsed building or starvation, the most widely practiced techniques of contemporary warfare. Humanitarian opposition to CBR is altogether irrational, except as it is directed to war itself. It can be argued, however, that man's proclivity to warfare must be contained through his social institutions, and any breakdown of traditional limitations in the way war is practiced is one more step of degradation of the species.

The petition suggests that minor uses of CBR will lead to escalation. However, since tear gas is already rationalized for other social purposes, the lumping of Chemical, Biological and Radiological warfare may be especially confusing, and could exacerbate the chances of escalation. Biological warfare should be carefully set apart, particularly for the initiative in international negotiations, for several reasons:

Its development is closest to medical research, therefore conveys the most intense perversions of the human aims of science.

It is the most dubious of military weapons.

Its effects in field use are most unpredictable, with respect to civilian casualties, and even retroactive on the user.

The large scale deployment of infectious agents is a potential threat against the whole species: mutant forms of viruses could well develop that would spread over the earth's population for a new Black Death. Chemical weapons, however potent, at least do not produce equally or more virulent offspring.

One approach to the control of biological warfare should be a nonproliferation treaty. Biological warfare development is within the potential resources of the smallest nations, and the weapons liable to the most irresponsible use. On the other hand, no vital interests of one nation are now committed to biological warfare: the powers can afford to limit their sovereignty in this area.

A nonproliferation treaty in this area could be a constructive precedent for other areas of arms control; the more narrowly it is defined the greater the likelihood of its adoption.

The treaty could dedicate all biological and medical research to human welfare. In this light, no research on living organisms could be classified. M.D.'s and Ph.D.'s in life sciences would be registered and expected to report periodically on their current research activity to an international organization. Ideally, these registrants should have the right of free travel, if necessary, for the purpose of reporting violations of the treaty. Special provisions are needed for proprietary interests, e.g., the drug industry, but with stringent time limits set for confidentiality of its information. A world data center for life sciences would have many human benefits, in addition to centralizing the surveillance of treaty obligations. The future of the species is very much bound up with the control of these weapons. Their use must be regulated by the most thoughtful reconsideration of U.S. and world policy.

[From the Washington Post, Mar. 30, 1968]

CONGRESS SHOULD EXAMINE BIOLOGICAL WARFARE TESTS

(By Joshua Lederberg)

The ethics of biological experimentation has become a subject of legislative interest in the last few months. This concern started from the publicity given to important advances like heart transplantation. It may now have a much more pointed application to experiments laden with global hazards, conducted in great secrecy, and outside the reach of any tradition of medical ethics. The news that provokes this observation comes from Skull Valley, Utah, near the Dugway Proving Grounds of the Army Materiel Command.

A few thousand sheep have died, suddenly and mysteriously. At this writing. the Army is still investigating the incident; earlier news reports quoted some military spokesmen as quick to deny the possibility that some experiments at Dugway had misfired.

An independent investigation is clearly out of the question in such a securitysensitive area. Under these circumstances, it is difficult to see how a credible account can be obtained, whatever the facts.

If the incident had no ramifications beyond the accidental release of a potent chemical weapon; if the hazard were limited under any circumstances to a few thousand people, it might be put down to the fortunes of war. The incidental risks would not be fundamentally different from those of high-explosive munitions, casually transported on a large scale.

Sadly, one of the insanities of the chase after military security is a world-wide competition in research and development on biological warfare. Because the Russians or the Chinese might be investigating exotic bacteria and viruses, the argument goes, we must do the same in self-defense. And of course the Russians and the Chinese have exactly the same reaction to our own secret programs.

These activities are aimed at practicing the large-scale deployment of the most contagious enemies of man that he can discover or invent. Our personal security must then depend on the depth of the technical competence of the men responsible for the research. This is impossible to judge from outside the secrecy barrier. However, it is almost certain that the technicians willing to work in this area are self-selected for peculiar nonchalance about it. Who else would? Without other objective surveillance, we have to be unforgivingly harsh in our judgment of mistakes and leaks that do come to public notice.

Is anyone competent enough to play with these matches, which are designed to ignite "controlled pestilence"? According to a paper in the December 8, 1967, issue of Science magazine, the American Public Health Association has a file of 2700 cases of virus infections contracted by workers in medical laboratories. These included 107 fatalities. This file is probably not complete; we have no way of

knowing the completeness with which such cases are reported from military research laboratories. I do know that one of my late colleagues in microbial genet ics died of a plague infection contracted in the British laboratories at Porton. And he dies in town.

In the midst of the global arms race, it would be futile to demand a unilateral abnegation of research on biological weapons. A Congress interested in biological ethics should, however make insistent demands for efforts, which do not now exist, to find formulas for international control of species-suicidal research. For his own personal security, every Congressman should also seek his own assurance-less readily available to the common citizen-that the internal surveillance of experiments with contagious weapons is prudent enough to suit him and his family.

[From the Washington Post, Aug. 17, 1968]

SWIFT BIOLOGICAL ADVANCE CAN BE BENT TO GENOCIDE

(By Joshua Lederberg)

The phrase "germ warfare" evokes a moral revulsion which is not strictly justified. War is already awful; how nice it would be to bypass its blood and guts and evoke some clean, almost symptomless disease instead.

From a military standpoint, the ideal agent for BW (biological warfare) would be a completely nonlethal but highly contagious virus that merely stupefied its victims for a few hours or days and for which the good guys had a reliable antidote or preventive antibody. This hypnovirus is a logically plausible ideal, just as is the thought of using mind-altering drugs as chemical warfare agents. (LSD was in fact studied by the U.S. Army long before the hippies discovered it.)

Having the hypnovirus would, however, make very little difference to the maneuverings of the great powers, with their highly automated nuclear missile systems. Could we persuade the Kremlin to exclude biological attack from the threats it intends to retaliate against? The impact of hypnovirus on smallcountry politics, and on the "policing" of the world by the major powers, would be another matter, one that deserves a more leisurely discussion.

For the moment, hypnovirus is a pipedream. Most BW research is claimed to be defensive. That is, it seeks to anticipate the worst horrors an enemy might develop, then beat him to it so as to know how to defend the population. Needless to say, there is no more ingenious device to ensure the rapid escalation of offensive capabilities.

Whether work is actively proceeding in BW laboratories on producing a hypnovirus, I do not know. They have, however, published abundant reports showing their preoccupation with plague, anthrax, rickettsia, tularemia, encephalitis virus and other equally unpleasant and highly lethal disease agents.

The most chilling thought is that GW research has only just begin to tap the potential offered by chemical genetics for the systematic construction of new disease agents. The announcement of the artificial replication of a virus DNA last December was followed by some rather premature talk about the moral problems of replicating, and altering human DNA. We have a much more immediate concern for the moral problems of the engineering of virus DNA for military purposes.

These anxieties have provoked considerable bitterness in the scientific community and even demonstrations pointlessly misdirected at the Army's biological research laboratories at Ft. Detrick, Md. In recent years, this installation has concentrated on the technology of handling dangerous, infectious materials for research purposes. Its experience is quite valuable for public health work and has been openly published.

Nevertheless, even these positive contributions have a seamier side. The hazards of dealing with dangerous viruses is one of the few discouragements to keep a smaller country from starting its own BW program. As we develop and publicize this technology, we make easier the proliferation of the darkest arts throughout the world.

The makers of policy in Washington, not the technicians at Ft. Detrick, are the just targets of criticism. And they should be chastised less for any malevolent motives in this field than for mere inertia, for technical unfamiliarity, for blind

ness to the pace of biological advance and its accessibility to the most perilous genocidal experimentation.

The U.N. has had a long history of abortive attempts to start discussions on the control of BW.

Now, the British delegation has introduced new initiatives for BW controls and, evidently with some reluctance, the U.S. State Department for the first time agreed to substantial technical studies. Time is running out, and too little is left to let BW remain merely another minor pawn whose disposition is incidental to other settlements.

[From the Washington Post, Aug. 31, 1968]

THE INFAMOUS BLACK DEATH MAY RETURN TO HAUNT US

(By Joshua Lederberg)

In mid-14th century, the Crimean seaport of Caffa (now called Feodosia) was an important fortified outpost of Genoese traders. For the previous 50 years, Genoa had been in intermittent conflict with Venice, and with factions of the Mongel Golden Horde. The famous Travels of Marco Polo were written while this Venetian adventurer was a prisoner-of-war in the hands of the Genoese.

In the year 1346, Caffa was again besieged by the Mongols. During this same time, a vast epidemic of bubonic plague had rapidly spread through the Mongol empire. In the words of Gabriel de Mussis, a contemporary chronicler, "The Tartars, fatigued by such a plague and pestifrous disease, stupefied and amazed, observing themselves dying without hope of health, ordered cadavers placed on their catapults and thrown into the city of Caffa, so that by means of these intolerable passengers the defenders died widely."

After this bacteriological attack, the survivors abandoned the city and returned to Genoa as best they could. By 1348, the Black Death had devastated Europe. Dr. V. J. Derbes of Tulane Medical School, writing in the Journal of the American Medical Association (April 4, 1966), pointed out that the plague would undoubtedly have reached Europe by trade routes, regardless of this incident. Nevertheless, what is known of the spread of the Black Death, starting from the Italian seaports, is consistent with attaching it to the return of the Genoese ships from Caffa with a heavy cargo of infected rats and fleas.

Plague is still with us. It is usually associated with tropical, rat-infested environments, and indeed it was again killing a million people a year, mostly in India, at the time of World War I. Since World War II, vigorous rat-eradication programs have succeeded in holding plague deaths down to a few hundred. The disease has, however, gradually spread to native, wild rodents throughout the world, where it smolders, only to break out in an isolated case or small epidemic of "sylvatic" or forest-living plague. The deprivations of war, as in Vietnam, also foster new outbreaks of plagues.

As far as we know, these outbreaks are caused by the same bacillus that spread the Black Death. However, the organism does show considerable variation under laboratory conditions. An epidemic of the Black Death may have reflected the evolution of some especially virulent and contagious form of the bacillus. Fortunately, streptomycin and a few other antibiotics are remarkably effective. Nevertheless, human ingenuity is quite capable of wasting the good fortune of the human species. Mutant strains of the bacillus that are indifferent to antibiotic therapy are easily cultured.

The potential of plague for biological warfare (BW) is obvious in the light of the historic precedents. Any intelligent program of BW research, especially if its main mission were "defensive," would have to develop aggressive, drugresistant bacilli in order to evaluate them as a military threat. BW research must also be concerned with the factors that encourage the airborne spread of pneumonic plague.

The Black Death of 1346 probably could have been contained with the resources of modern medicine. When hostile bacilli have been augmented by human intelligence, however, any confidence that they can be contained is a delusion.

The disastrous course of present-day Soviet militarism makes it vastly harder to attempt a world settlement for the surveillance and control of BW agents. But BW can add nothing to the strategic power of nuclear-armed states. If in

nothing else, we should be able to find a common cause in protecting ourselves from a recurrence of pestilence. Or must we console ourselves with the recollection that the Black Death helped pave the way to the Rennaissance?

[From the Washington Post, Sept. 7, 1968]

MANKIND HAD A NEAR MISS FROM A MYSTERY PANDEMIC

(By Joshua Lederberg)

In the aftermath of the six-day war in the Middle East last summer, direct air transport from Uganda to Germany and Yugoslavia was disrupted. Shipments of "green monkeys" for use in preparing vaccines were diverted to London airport before transshipment.

In the process, a group of at least eight monkeys acquired a disease heretofore unknown to medical science. The disease remains unnamed but might be called Marburgvirus, for it infected at least 32 people and killed five of them in Marburg, Germany, and infected two in Frankfurt.

Twenty-seven of the infected cases were among laboratory workers who handled the monkeys or their organs. Five were secondary cases, nurses or doctors who attended the primary ones and were in direct contact with the patients' tissues or secretions. In a brief review in Nature magazine, Dr. C. E. GordonSmith, director of the British biological warfare research laboratory at Porton, also alludes to the transmission of Marburgvirus as a venereal disease, but this is perhaps conjectural.

There is, however, no doubt that Marburgvirus is extraordinarily contagious and rapidly lethal in a distressingly high proportion of cases. It is found in the blood, throat secretions and urine of infected animals and men and direct contact is the only known medium of transmission. What might have been an epidemic of world-shaking dimensions was contained by the sheer good luck that it did not spread to man at London airport but first appeared in the medically knowledgeable environment of the laboratory destinations.

The Porton laboratory was involved when the unusually contagious character of the new disease was first realized by the German physicians. As its director remarks, "The facilities for the study of infectious diseases are of a kind probably unmatched in Western Europe; there is a strict code of safety and specially designed apparatus to cope with hazardous operations. Elaborate precautions are taken to prevent the escape of infective material and a research section is devoted solely to the study of laboratory hazards."

Its scientists were then especially prepared for the further experimental study of the new disease. They soon showed that the Marburgvirus was quite distinct from any previously known disease agent and quite unresponsive to every antibiotic tried.

The virus is also under study in Johannesburg and in the United States Public Health Service researchers at the Communicable Disease Center at Chamblee, Ga., have confirmed that it is a new virus though possibly related to the vesicular stomatitis of cattle.

The origin of Marburgvirus is unknown. It may be indigenous to green monkeys in Africa: it may have been acquired by contact with other animals in whose company the monkeys were held during transshipment through London.

The threat of a major virus epidemic—a global pandemic-hangs over the head of the species at any time. We were lucky on this occasion, but it was a near miss. It could easily have established a very large focus of infection in countries like India or China or South Vietnam, and in our present knowledge of virology we would have been ill-equipped to stop it from dominating the earth, with a halfbillion casualties.

We have also seen the irony of the constructive role played by a BW laboratory in containing the virus. But we cannot blind ourselves to the knowledge that biological warfare now has one more potential weapon in its repertoire. Furthermore, a great deal of scientific ingenuity is dedicated to "improving" such agents, the most suicidal of human enterprises today.