Biological weapons are not new. Their use by armies has taken place for centuries. Take the Plague, for example. The pandemic was reportedly first introduced to Europe during the siege of the Genoese trading port of Kaffa in Crimea by the Golden Horde army of Jani Beg in 1347. It decimated 30 percent of the European population. Paradoxically, the resultant labor shortage and lack of faith in the prevailing order helped end the Dark Ages and launched the Renaissance in Europe. Another agent, smallpox, caused the deaths of 90 percent of the Mayas and Aztecs, enabling the Spanish to conquer the New World.
Between World War I and the ratification of the chemical and biological weapons treaty, it is estimated that at least 20 countries had a biological weapons program. The reasons are not hard to understand. Biological agents are easy to make, merely requiring a laboratory on par with what is found in most universities today and can be created by any graduate student. They are not resource-intensive, and most ingredients are easily available. This is in marked contrast to nuclear weapons, which are very expensive to make, require radioactive precursors that are under the tight supervision of international agencies, and demand technology that is not easy to come by. This is why, despite intense efforts, only a few countries in the world possess nuclear weapons.
Biological weapons have additional attractiveness, as they can be tailor-made based on the requirements of the “manufacturer”. In order to understand this point, it is important to differentiate between bioterrorism and biological warfare. The former includes agents designed to spread terror but with a limited number of deaths. A perfect example of this is the ‘anthrax scare’ of 2001, where the amount of mass fear far exceeded the number of those affected. In contrast, biological warfare uses agents such as smallpox that have the potential to cause a large number of deaths, numbering in the hundreds of thousands or millions.
Thus, a perpetrator of bioterrorism would choose diseases such as anthrax and botulism, with agents that are not self-replicating (so as to limit spread) but have high lethality (to increase fear). Think of it as a “biological Unabomber.” While dangerous to those exposed, this is thankfully a limited threat.
In contrast, those advocating the use of biological weapons for warfare would use a self-propagating agent (to increase spread) that was inhaled (to increase dispersal) and one that was made resistant to antibiotics (by recombinant technology, to increase mortality). Two kinds of people would use such weapons. The first could be nihilists and anarchists, who find all aspects of modern society despicable and feel we need to start all over again. Such a person(s) could create a recombinant agent (such as a virus) that could literally destroy society as we know it. Unfortunately, such an agent would not be hard to create. For example, HIV-1 could easily be inserted into Adenovirus (after removing the dispensable E3 gene of the latter) creating inhaled AIDS. Needless to say, such a creation would be devastating.
The 20th century saw seven countries by known count — Britain, France, Germany, Iraq, Japan, the Soviet Union, and the US — embark on programs to identify, manufacture, and weaponize killer agents. But the next generation of biological weapons may exploit knowledge about genomes, with a calamitous effect. A couple of years from now, there may be as many as 70 pathogens whose genetic code has been cracked. The genomes of cholera, leprosy, the plague, and tuberculosis are already in the public domain, as is Staphylococcus aureus, which is becoming resistant to antibiotics. There is fear that a bioterrorist with lots of money and a good laboratory could use this readily available data, inserting or swapping genes in bacteria and viruses to create new, horrifyingly virulent agents.
There are at least two documented cases in which biologists have created doomsday bugs. One was a strain of the common intestinal bug Escherichia coli that was 32,000 times more resistant to the antibiotic cefotaxime than conventional strains. The superbug’s creator was Willem Stemmer, chief scientist with Maxygen, a California pharmaceutical research firm, who was exploring the function of resistance genes in bacteria. The technique used, DNA shuffling, involves shattering multiple copies of a gene and then reassembling them. The process produces a range of daughter genes with the fragments stitched together in subtle but new ways. The enzymes involved in the re-assembly are prone to errors, leading to mutations, and therefore greater diversity. The daughter genes can then be re-introduced into the bacteria and the resultant bacteria with the desired strains (such as those good as biological agents) selected. Fragments from different bacteria can be mixed and matched by this technique. Needless to say, the potential of this in the wrong hands is enormous. In response to an appeal by the American Society for Microbiology, the E. coli created by Stemmer was destroyed.
In another example, Australian scientists Ron Jackson and Ian Ramshaw unwittingly created a vicious strain of mousepox, a cousin of smallpox. They were attempting to control the population of mice by altering the genes of mousepox to make it more lethal. To create their mouse contraceptive, they took a relatively benign strain of mousepox and added genes for proteins carried on the surface of mouse eggs. The idea was that cells infected by the viruses would churn out egg proteins, causing female mice to produce antibodies against their eggs. To maximize the vaccine’s effectiveness, Jackson and Ramshaw also engineered the virus so that it contained the gene for interleukin 4, a cytokine that boosts antibody production. The IL-4 gene also shut down the mice’s cellular immune response, so they were unable to fight off the virus. The effect was lethal, with mice that were previously immunized against mousepox dying within days. The implications for smallpox are obvious and profound – what would happen if the gene for IL-4 was introduced into the smallpox virus? Would the present vaccines even work? When the Australian scientists realized the implications of their creation, they destroyed the virus and then went public with their findings to draw attention to the potential abuse of biotechnology.
The other perpetrators of biological warfare could be terrorists, domestic or foreign. Groups like this could gamble that even though biological warfare would hurt them in the end, it would level the playing field where they have the long-term advantage. Agents that could be created to fit such a scenario include putting the cholera toxin gene into the tuberculosis bacteria along with an antibiotic-resistant gene to cause fatal, rapidly acting, and antibiotic-resistant pneumonia (details on how such an agent could be created are in Germs of War). A tactic a foreign terrorist could use is to select agents to which they are relatively immune while the Western world is relatively naïve. This can be created by the insertion of antibiotic-resistant genes or genes that selectively attack certain racial groups (in another article, I will show how such agents can be created). Given the jihadi mentality, such groups will consider their own mortality as martyrdom while those of the enemy (us) as the ultimate goal.
It is important that the public be aware of the potential pitfalls so corrective and preventative actions can be taken.
Ketan Desai is a physician executive.