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Bioterrorism and the University

The threats to security--and to openness

November-December 2003

There can be few higher privileges for the scientific community than to contribute to the security, freedom, and well-being of our nation and of people around the world. It is precisely that freedom and security that make possible the pursuit and transmission of knowledge—the fundamental mission of the university in society. Yet we live in a world in which much of the science that can contribute to improving life for millions on the planet can also be misused by terrorists to destroy millions of lives. This paradox creates the fundamental tension under which universities and the scientific community now live. The challenge is to ensure, to the extent possible, both the security of our nation and the openness that is critical to the vitality and progress of science. We need to find the means to prevent bioterrorism without crippling biomedical research essential for developing drugs and vaccines to protect not only our population but people everywhere. Unfortunately, in the wake of September 11 and the subsequent anthrax attacks, our ability to fulfill both these vital goals may be at some risk.

To understand why that is so, it may be useful to review how federally funded scientific research related to security has been conducted in the past, and to have some insight into how bioterrorism differs from nuclear threats. During the Cold War—when the major concern was the threat of nuclear attack—the government developed policies that were, to a remarkable extent, successful in making it possible during the past 40 years to maintain openness in fundamental science while protecting national security in the realm of physics. In 1985, President Ronald Reagan codified this arrangement when he issued National Security Decision Directive 189, which states that "No restrictions may be placed upon the conduct or reporting of federally funded fundamental research that has not received national security classification, except as provided in applicable U.S. statutes." In other words, the mechanism to assure security for militarily sensitive research is to define certain research a priori as classified, generally before the work is funded. To allow both types of research to proceed, the directive stipulates that a tall wall must be built between fundamental research and applied research that could be used for military purposes, and that the latter must be classified research.

That directive stimulated much introspection in academic communities on the centrality of intellectual openness in the life of the university. To preserve the principle of free and open intellectual scholarship, Harvard and many major research universities, including MIT, forswore doing such classified research. Some, like MIT, have developed mechanisms for contributing to classified research on military-funded projects at separate, and separately staffed, facilities, such as Lincoln Laboratory, located in the suburbs, or the Draper Labs, a federally funded research institution adjacent to the campus. All have encouraged members of their faculties to serve as advisers to the government when asked.

Biological versus Nuclear Defense

Bioterrorism poses unique challenges for security, related to intrinsic differences between biology and physics, that make it much more difficult to draw the line so neatly. That poses real difficulties for universities and for the basic research so critical to advancing knowledge in the life sciences and for human health.

First there is the conundrum of asymmetry. During the Cold War, the ultimate restraint on the use of nuclear weapons was "mutual assured destruction": if they use nuclear weapons on us, we will retaliate—and both nations will be bombed back to the Stone Age. Remarkably, in 1969 President Nixon unilaterally forswore the use of biological weapons for "hostile purposes or in armed conflict" by the United States. That commitment was later confirmed in the Biological Weapons and Toxins Convention (BWC), in which this country and 163 other signatories undertook "never in any circumstance to develop, produce, stockpile or otherwise acquire or retain: 1. biological agents, or toxins...; and 2. weapons or means of delivery of such agents for hostile purposes or in armed conflict." This was the first of the international weapons conventions signed by the United States, in 1972; it was ratified in 1975. It should be a source of great pride to the University that one of the great intellectual forces contributing to the development of the convention was Matthew S. Meselson, currently Cabot professor of the natural sciences. Although the BWC has worked remarkably for established nations and superpowers, it has no provisions for verification or enforcement of violations (although Meselson has proposed that it be modified to criminalize use of biological weapons). In current scenarios of war and terrorism, an asymmetry would exist in a conflict with rogue states—or even more likely, small groups or even individuals—who might choose to develop biological weapons and use them without compunction, knowing of our commitment not to retaliate in kind.

A second unique challenge posed by biological agents is the "dual-use" nature of knowledge and technology in the biological sciences. In contrast to nuclear weapons, which require complex equipment and facilities that can usually be detected, biological agents can be manufactured with ordinary catalog items, like fermentors and milling machines, which are legitimately used to produce chemicals, pharmaceuticals, and beer. Producing biological agents is relatively easy—one doesn't have to be a rocket scientist to learn how to do it—but predicting attacks is enormously difficult.

A final characteristic that sets bioterrorism apart is that distinguishing an introduced infectious disease from a naturally occurring or emerging infectious disease is very difficult. Ironically, the fact that natural pathogens have survived thousands of years of evolution implies that the best bioterrorist agents are probably those found in the environment, rather than genetically engineered organisms whose stability and transmissibility have not been selected for in the real world.

"Select Agents," "Sensitive" Research

Because of the inherent difficulties in distinguishing between naturally occurring infectious diseases and biological weapons, building the firewall is more difficult in the realm of biological research. Most scientists recognize the need for research on prevention of infectious diseases, and study of biological and chemical agents for defensive purposes, and hence respect the need for classified research. But, as noted, it has long been a principle at many research universities, such as Harvard and MIT, that it is essential to a university for all knowledge and research to be open to all students and faculty members and, as a consequence, the university will not carry out classified research. Harvard's policy further stipulates that "sponsors may not have, nor appear to have, the right to exclude specific individuals or groups from participating in research on account of their beliefs or backgrounds."

In multiple ways, that policy now puts Harvard and other universities in potential conflict with the new regulatory regime put into place in the wake of September 11. The USA PATRIOT Act of October 26, 2001, stipulates that it is a crime for "restricted persons" to possess, use, or transport "select agents" per se. And the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (the "Bioterrorism Act") requires any person who possesses, uses, or transfers a select agent to have a background check and register with the U.S. Secretary of Health and Human Services (HHS). That is to say, whole categories of materials and people are now regulated in ways that go far beyond former definitions of defense classification, with potentially wide and overlapping effects on research that is being conducted for reasons of legitimate, fundamental science.

"Select agents" are currently defined as toxins, viruses, bacteria, and fungi now listed by the Centers for Disease Control and Prevention, the number of which has expanded in the past couple of years from seven to 82. A small number are exempted from the regulations. "Restricted persons" include people who have been convicted of crimes, who are fugitives from justice or unlawful users of controlled substances, who have been judged mentally defective, or have been dishonorably discharged from the U.S. armed forces—categories not likely to have much impact on universities. But the final category excludes from access to select agents "aliens and nationals from a country that the Secretary of State has determined supports terrorism (currently Iran, Iraq, Cuba, North Korea, Syria, Sudan, and Libya)." Universities are further constrained by a new law which requires not only that institutions that possess select agents must register and be certified by the secretary of HHS, but also that individuals with access to such agents must have a "legitimate need and bona fide" research purpose and be registered and checked against federal databases.

Although scientists at several Harvard schools are engaged in research relating to countering bioterrorism, the School of Public Health is the only faculty within the University that actually houses and does research directly on select agents. The school has fully complied with the law, but as dean I have to be concerned about who will make the determination whether there is a "legitimate need" for the research we do, and whether it is "bona fide" research.

Moreover, in October 2002, President George W. Bush issued his Homeland Security Presidential Decision Directive (PDD-2), which stipulates that "the Government shall...prohibit certain international students from receiving education and training in sensitive areas, including areas of study with direct application to the development and use of Weapons of Mass Destruction." This formulation creates a vague and undefined category of "sensitive"—not classified—research, a category which was abandoned 40 years ago in physics as counterproductive and, in my view, may be potentially more harmful to science and national security in the realm of biological sciences. PDD-2 can delay or deny publication of research findings after the research is done, the inevitable result of which will be to discourage bright students from undertaking study and research on biological or chemical agents that could at any point be declared "sensitive."

This is not a hypothetical fear, and it strikes at the foundation of scientific research. Earlier this year, Science published a paper on production of infectious poliovirus from chemicals in the laboratory. In essence the scientific achievement was to have created from simple chemicals and enzymes a form of life, a fully infectious virus, completely in a test tube for the first time—not a bad day's work for a scientific group. But it also provided a basis, should someone wish to do so, for inserting genes for toxins or other poisons into poliovirus, making it an even more devastating pathogen and potential bioterrorist agent. Were the paper submitted today, it might not be published, because the editors of 32 major biological science journals, including Science, have recently agreed that "an editor may conclude that the potential harm of publication outweighs the potential societal benefits." This is a chilling example of the impact of terrorism on the freedom of inquiry and dissemination of knowledge that today challenges every research university.

Undermining Security

Do the current laws and PDDs significantly limit academic freedom? The answer must be yes, in that they restrict the free exchange of ideas; restrict the ability of any student to pursue all areas of knowledge and to participate in any ongoing area of research or study; and selectively discriminate against students—who are accepted as being of a quality to merit university admission—on the basis of their country of origin.

But do these laws and presidential directives really help to protect our country significantly? To this second question, I would argue that as applied to the major research universities, many of these new restrictions are unlikely to add to the security of our country—and, in the long run, they may actually be detrimental. As Oklahoma City and probably the anthrax attacks demonstrate, one doesn't have to have been born in a "restricted country" to become a terrorist. Nor does restricting access to "select agents" prevent a biology student from learning the key principles of genetic engineering: the technology critical to genetically engineering microorganisms can be acquired much more readily by studying the standard lab organism, E. coli (not considered a "select agent," and the basis of all molecular biology), rather than a more difficult organism such as anthrax or Ebola virus. Moreover, experimenting with this standard organism would keep such individuals out of the government's spotlight. Thus, these recent restrictions are not likely to filter out as much danger as intended.

Further, the regulations may actually undercut security. Restrictions on research and training, and the surveillance and tracking of international students, are likely to discourage not only foreign students from research on "select agents," but Americans as well. If research on an important global disease can, at the whim of the secretary of HHS, become "sensitive" and subject to censorship and to a ban on publication of research or theses tomorrow, why would any discerning student risk studying infectious diseases, or choose to become an expert on one of the major pathogens?

Restrictions imposed on certain international students within a university set up a painful and unacceptable division of students into "foreign" and "American," implying that international students from certain places are intrinsically threatening and more dangerous than native-born students. That circumstance alone undermines the international and collegial nature of a university. At Harvard, 7 percent of undergraduates and 24 percent of graduate students are international, coming from 130 countries. Science and scholarship are global. We all know that many of the greatest contributions to science made in this country during the past century have come from faculty members and students born abroad. International students from the widest range of countries are essential in this global era to foster understanding not only of science and other academic subjects, but of different traditions, cultures, and perspectives.

There is yet another way in which security laws, regulations, and editorial constraints will probably be ineffective at protecting against terrorism, while perhaps discouraging crucial basic research. Which editor or government official is smart enough to know how any fundamental scientific discovery is likely to be used, or misused? I cite three examples remote from bioterrorism. Would it have been obvious a half century ago that a study of sex in bacteria, ridiculed at the time as a frivolous use of public funds, would become the basis for all recombinant DNA, the genetic revolution, and the biotechnology industry? Would it have been suspected that studying why certain tiny viruses that infect only bacteria are able to grow in some strains and not others would provide the tools to clone DNA and sequence the human genome? Would most people have cared whether fusing a cancer cell to a white blood cell producing antibodies extinguished the blood cell's ability to produce its specialized product? That is the experiment that created monoclonal antibodies, used every day in diagnostics, in tumor treatments, and in creating vaccines against HIV and other diseases.

In a sense, the poliovirus story cited above is the kind of obvious experiment that might well have been censored. That research paper wasn't censored, presumably because a decision was made that its misuse would better be prevented by having the entire scientific community made aware of the scientific finding and its potential misuse, than by keeping it secret and risking that only terrorists would carry out similar experiments clandestinely.

Advancing Openness

It is my view that anyone here for training, from any country, who is bright enough and promising enough to be admitted to Harvard or any major research university, and who is cleared by the government agency that has been set up to screen applicants and approve visas for study in the United States (the Student and Exchange Visitor Information System, SEVIS), ought to be able to pursue any area of study and research under faculty supervision in the university. That principle is succinctly stated by MIT as "No foreign national granted a visa by the U.S. government should be denied access to courses, research, or publications generally available on campus." (Harvard has constituted a committee to develop policies that balance the University's educational and scholarly missions and its academic principles with the needs of national security.) Moreover, it is the obligation of all of us in the academic community to defend the principle of openness for all students who are admitted, and to all ideas and knowledge within the university. That means that the leaders in higher education should seek to meet with representatives of the administration and Congress to seek modifications of existing regulations and legislation, including the USA PATRIOT Act, that will encourage the training of international students and protect the openness of universities as well as the security of the nation.

The threat of terrorism is real. The threat to the openness of universities is also real. Engaging the brightest science students in problems that protect people against major infectious diseases, naturally occurring or introduced by terrorists, is essential. Clearly we need a much wider, more thoughtful debate of the real costs and advantages of the policies that have now been imposed on university research in biological sciences.


To get a feel for some of the challenges that will be involved in thinking through these issues, let me ask you to put yourself in the place of the editor of a scientific journal. You have to decide whether to publish a new and most unexpected finding. The paper reports that when a gene that is known to enhance normal immune responses is genetically engineered into mouse pox virus (a member of the same family as smallpox virus), it not only failed to enhance the immune response to the virus, it caused the virus to kill all the mice. We know that smallpox vaccine protects humans quite well against smallpox infection, but here the recombinant mouse pox virus killed even mice that had been previously vaccinated. If humans were to respond in the same way as mice, smallpox virus or smallpox vaccine expressing this gene might be even more lethal—capable even of killing people previously vaccinated. The experiment has indeed been done. Would you publish the paper?


Barry R. Bloom is dean of the School of Public Health and professor of immunology and infectious diseases. He is a former consultant to the White House on international health policy and cochaired the bioterrorism panel for the National Academy of Sciences.