In 1999, Tommy Nilsson, Rainer Pepperkok and Brian Storrie published results about protein export in cells they obtained by using shiga toxin. One month later, Nilsson (a group leader at the European Molecular Biology Laboratory in Heidelberg, Germany) received a request for the plasmids that his laboratory used to produce non-toxic fragments of the toxin. As a scientist, Nilsson shares his published knowledge and material with every colleague who asks for it. But one aspect of the request for the toxin constructs made him hesitate. The letter came from North Korea. After considering the request and discussing the matter with other colleagues, Nilsson decided not to send these plasmids to a country labelled as a ‘rogue’ state. ‘You have to think about what consequences might arise from this,’ he explained, ‘because the material might fall into the hands of people working on biological weapons.’ Indeed, he did not make his decision easily. ‘I felt pretty bad about not sending it,’ he said, ‘because you are obliged to send out material after you have published it—–that’s the norm. And you must pay particular attention to requests from third world countries where any material, be it an antibody or a plasmid, may be of great help.’
Nilsson made his decision because he was uncertain about legal aspects and the possibility of abuse. And without knowing about these details, he was right, as Germany is one of the countries that have passed laws to control the export of material that could be used for the development of weapons of mass destruction. But many scientists, when sending strains or genetic elements to a colleague, do not give a second thought to such consequences. They are simply not aware of those laws or the fact that some strains or genetic material could be turned into a weapon. And given that preparing a terrorist attack using bioweapons would be relatively easy, scientists should be made aware of the potential abuses of their knowledge and materials.
‘Black biology’, the research on bacteria, viruses and toxins for the purpose of creating weapons of mass destruction, is the nightmare of security experts in western countries and is also beginning to capture the attention of scientists and politicians. Although the possibility of a biological attack wiping out Washington, London or Paris is rather small, bioweapons have become the ‘poor man’s nuke’ for states and terrorist groups that do not have the means to build nuclear weapons. Among the countries that are suspected of developing biological weapons are those that have tried to build or acquire nuclear weapons, including North Korea, Libya and Iraq. Indeed, for a terrorist group to extinguish a metropolis like New York City, an atomic bomb would certainly not be the weapon of choice. The huge facilities required to produce bomb-grade plutonium or uranium cannot be hidden and are easy targets for a preventive attack. Furthermore, a nuclear warhead is too bulky to fit into a plane’s storage bin, and it does not have enough power to annihilate all of New York’s five boroughs. A well-designed bacterial or virus strain, in contrast, can be produced in a garage hidden from spy satellites, transported in a thermos flask, and, theoretically, has the potential to wipe out whole cities.
But the main advantage of biological weapons is the fact that they are easy to manufacture. The know-how to produce a toxin, increase the virulence of a bacterial strain or design a deadly virus is only a few mouse clicks away on the World Wide Web. The raw material—plasmids, bacteria and viruses—can be obtained by simply asking the scientists who work with them. Indeed, this is common practice among scientists, as most journals even require them to provide material on request after publishing their results.
But this practice, when it concerns materials that could be turned into a biological weapon, runs counter to international treaties designed to ban weapons of mass destruction. These treaties are based on the ‘United Nations Convention on the prohibition of the development, production and stockpiling of bacteriological and toxin weapons and on their destruction’, which came into force on 26 March 1975 (http://www.state.gov/www/global/arms/treaties/bwc1.html). Those countries that signed and ratified the convention committed themselves to opposing the production of biological weapons. Particularly important for scientists is article III of the convention, which obliges the countries ‘not to transfer to any recipient whatsoever, directly or indirectly, and not in any way to assist, encourage, or induce any State, group of States or international organisations to manufacture or otherwise acquire any of the agents, toxins, weapons, equipment or means of delivery […]’.
Since then, nearly all countries, including Iraq, Iran and Libya, have signed and ratified the convention. Interestingly, North Korea is one of the few countries that has not even signed it. Many of the signatories have passed additional export control laws in order to regulate the export of material or equipment that could be used to create biological weapons. Based on the UN convention, these countries compiled lists of strains and toxins for which export regulations apply (see sidebar, p. 300). Most countries have even expanded the UN convention by introducing the ‘dual use’ definition: goods that have the potential for both military and civil uses. Consequently, export control laws also regulate the export of genetically modified organisms and genetic elements ‘that contain nucleic acid sequences associated with pathogenicity’ or ‘coding for any of the toxins’ specified in their lists [UK Export of Goods (Control) Order, No. 3092, 1992]. Under these laws, it would be illegal for a scientist to send a colleague in Iraq or Libya a plasmid containing a gene for a surface protein from whitepox virus, for instance. Frank Bonaldo, a spokesperson for the German Federal Ministry of Economics and Technology, confirmed that scientists who wish to send such material to designated states must seek approval from the relevant German authorities. ‘If one works in such a sensitive area,’ he said, ‘one has to be aware that there are regulations’. But most scientists have never heard of these laws. ‘I had no idea about these international laws and treaties,’ Nilsson said, ‘I had never come across this issue before’. His decision not to send shiga toxin constructs to North Korea was based mainly on his concerns about the legality and possible abuse, he explained.
Many scientists think that these laws will not stop the development of bioweapons at all. ‘I have very little confidence that regulations will work’, Hidde Ploegh, a pathologist at Harvard Medical School, said. ‘My experience tells me that if things are feasible they will be done,’ he said. ‘The system is too leaky.’ Ploegh also sees no sense in regulations that include only a small number of organisms and toxins without regulating the export of other technologies that could be equally dangerous. ‘Should we equip the North Korean military with all the sophisticated biochemistry without giving them the toxins?’ He questioned the ‘dual use’ definition. Furthermore, prohibiting the export to certain countries would also be a form of scientific discrimination. A scientist cannot know whether a Libyan colleague will use his or her plasmid containing the gene for a whitepox virus surface protein to design a bioweapon or to develop a vaccine against the virus.
Export control laws might even be useless, as the knowledge is already available to everybody. For instance, the last stocks of smallpox—at least the ones the public knows of—are stored in Atlanta and Moscow, but the full sequence of variola is public knowledge. So, Internet access, a gene assembler and recombinant technology are sufficient to create a bioweapon based on the variola sequence. Some scientists therefore argue that certain research should not be carried out if the potential dangers that would come with abuse are too large. ‘In fact, the problem is that as soon as someone has got the information, it will be available,’ Antoine Danchin, a bacterial geneticist at the Pasteur Centre of Hong Kong University, said. ‘So I think there is knowledge that should not be obtained.’ Consequently, he considers the sequencing of variola and publishing the sequence to be an error. ‘Now the sequence is available on the World Wide Web and nobody knows who’s using it,’ he said. ‘I think it’s stupidity.’ To prevent the construction of bioweapons based on public information, Danchin would like scientists to refrain from some areas of research that are considered to be dangerous.
Ploegh, who was a member of the committee on the assessment of future needs for smallpox virus and came out in favour of not destroying the remaining stocks, disagrees. Scientific knowledge per se should not be suppressed or destroyed, he argued, as nobody is capable of making a realistic assessment of its dangerous or useful potential. ‘Today we might see the destruction of smallpox as desirable but we might look at it differently 20 years hence,’ he said, citing the development of new antivirals as an argument in favour of preserving and studying the virus. Furthermore, Ploegh thinks that nobody should be able to make decisions to suppress basic research or the dissemination of knowledge. ‘These things are very difficult to regulate, even by scientists,’ he said.
In the end, the decision not to send biological material comes down to the moral values of an individual scientist, as in Tommy Nilsson’s case. ‘I wholeheartedly agree with Nilsson,’ Ploegh said. ‘It’s a personal issue and people should decide according to the standards they can set for themselves.’ But to make such a decision, a scientist must know about the possibility of abuse as well as about existing laws designed to prevent it. ‘As scientists, we are not always aware of or care about the potential implications,’ Nilsson explained. He, therefore, would like to see governments educate biologists about the legal situation, probably as part of their education. Danchin thinks that biologists should be educated in ethics to ‘push the considerations of the human sciences into natural science’. But more important than passing laws or educating scientists would be a public discussion of the potential dangers of abusing scientific research. Such a debate would be a good way of showing scientists the dark side of science rather than regulating their work. ‘I’m interested in a debate about these issues,’ Nilsson said, ‘to answer the question: “Where do you draw the line between scientific freedom and responsibility?”’
Some bacterial and virus strains and toxins whose export is regulated in various countries. This incomplete list is based on the UK Export of Goods (Control) Order.
Bacteria
Bacillus anthracis
Clostridium botulinum
Francisella tularensis
Vibrio cholerae
Yersinia pestis
Chlamydia psittaci
Brucella abortus
Brucella melitensis
Brucella suis
Pseudomonas mallei
Pseudomonas pseudomallei
Salmonella typhi
Shigella dysenteriae
Viruses
Variola
Ebola, Marburg
Dengue
Hantaan
Lassa fever
Rift Valley fever
Whitepox
Yellow fever
Junin
Lymphocytic choriomeningitis
Machupo
Chikungunya
Equine encephalitis viruses
Toxins
Clostridium botulinum toxins
Clostridium perfringens toxins
Conotoxin
Ricin
Saxitoxin
Shiga toxin
Staphylococcus aureus toxins
Tetrodotoxin
Verotoxin
Microcystins