We live in an age of breathtaking advances in the life sciences. Achievements in sequencing, or plotting the genetic blueprint of an organism, have been astounding, and may lead to great benefits in public health and medicine. But biological research can be dual-use: that which improves the lot of mankind can also be flipped around to create disease.
Mother nature does this through mutation. But how serious is the threat that a person would deliberately create a dangerous agent, and harm others with it? Do terrorists, or nations, harbor the intention, and can they summon the capability?
While some diseases occur easily in nature and are highly contagious, others require sophisticated work before they can be used as a weapon, and are probably too difficult for today's terrorist groups, although not for nation-states. The Aum Shinrikyo cult in Japan tried to make a biological weapon but failed. During the Cold War, the Soviet Union clandestinely build a massive biological weapons research and production complex. In 2001, five letters carrying anthrax spores were put in the U.S. mail, at least 22 people were sickened and five died. According to the FBI, it was the act of a lone insider in a U.S. military biological defense laboratory. (For a look at bioweapons over the last century, see this article by Milton Leitenberg, senior research scholar at the Center for International Security Studies, University of Maryland.)
Two recent events have rekindled long-standing questions about how far we should go to prevent the deliberate creation and spread of biological agents for use in war and terrorism. There aren't easy answers.
The first event is the just-completed review conference in Geneva for the Biological and Toxin Weapons Convention. Signed in 1972 and put into force in 1975, the treaty bans the development, production, acquisition, retention, stockpiling and transfer of infectious disease agents and natural poisons (toxins) for hostile purposes, and the weapons or other delivery systems for them. Unfortunately, the agreement has never had a serious verification mechanism. The treaty failed to stop the Soviet Union, South Africa and Iraq from attempting to build illicit biological weapons programs.
Every five years, a treaty review conference is held in Geneva. On Dec. 7, Secretary of State Hillary Rodham Clinton became the first U.S. Secretary of State to address a review conference. She declared that the risk of a bioweapons attack is "both a serious national security challenge and a foreign policy priority" for the United States. "A crude, but effective, terrorist weapon can be made by using a small sample of any number of widely available pathogens, inexpensive equipment, and college-level chemistry and biology," she declared.
But at the same time, the United States has abandoned efforts to put legally-binding verification measures into the treaty. The argument is that scientific research has advanced so swiftly that traditional arms control measures are obsolete. In 2001, the Bush administration scuttled a negotiation over the previous six and a half years aimed at creating a protocol for improved verification and transparency. President Obama has not changed this position. Clinton told the review conference "it is not possible, in our opinion, to create a verification regime that will achieve" the goal of bolstering confidence that all nations are complying with the treaty. Instead, she called for some "other steps" such as revising the annual reporting system in which countries are supposed to be transparent about potentially dangerous biological activities.
Judging by some preliminary reports from those who attended, the review conference made little or no progress in strengthening the treaty. Five countries -- Pakistan, Russia, India, Iran and China -- largely blocked any major progress. As a result, the conference outcome was to once again kick the can down the road to future meetings.
Consider this: a three-person staff, known as the "Implementation Support Unit," is assigned to work on treaty issues in between the review conferences. A proposal to expand the staff to five people failed to gain support in Geneva. In contrast, the Organization for the Prohibition of Chemical Weapons, which oversees the 1993 chemical weapons treaty, has a staff of about 500 people. That pact contains tough verification provisions.
How dysfunctional is the biological weapons treaty? There is a reporting system, created in 1987. Each year, nations are supposed to submit a report known as a Confidence Building Measure detailing research, disease outbreaks, legislation and past activities, among other things. In the last year, fewer than 40 percent of signatories to the treaty even bothered to submit the forms. If nations can't lift a finger to do the paperwork, how much effort are they going to put into watching out for abuses?
At the review conference, there was renewed discussion about focusing on the rapid changes in life sciences. Sounds good. But there seems to be little willpower, either in the United States or elsewhere, to do anything about the fact that the biological weapons convention is a toothless tiger.
The second recent event was caused by a laboratory experiment. Researchers led by Ron Fouchier of Erasmus Medical Center in Rotterdam modified the H5N1 virus, better known as avian influenza or bird flu. Up until now, the virus has been quite lethal in humans, with a fatality rate of about 60 percent in confirmed cases, but it has not been very transmissible among people. The researchers under Fouchier introduced a number of mutations into the virus that could make it highly transmissible through the air, and they demonstrated this in ferrets, which are considered a good stand-in model for humans in testing influenza strains. The experiment was carried out in a special, high-security laboratory, but it raised a terrifying prospect -- if the modified strain got out, or was created somehow by a person with malevolent intent, it could lead to a devastating pandemic. In announcing his results, Fouchier said he wanted to help prevent just such a deadly crisis: “We now know which mutations to watch for in the case of an outbreak and we can then stop the outbreak before it is too late. Furthermore, the finding will help in the timely development of vaccinations and medication.”
The research raised the question of whether the results should be published. (Another study along similar lines was also performed by scientists at the University of Wisconsin and University of Tokyo.) After a review by the National Science Advisory Board for Biosecurity, the U.S. government took the unprecedented step of recommending that two prominent journals, Science and Nature, withhold key details of the research, so that it would not fall into the wrong hands.
Understandably, this is a thorny problem. Scientists chafe at restrictions which could stifle discovery and innovation, potentially hurting society more than helping it. The results of the Fouchier research could be valuable to those combatting influenza, a virus that mutates rapidly and can pose a real threat to populations. Some experts suggested that it be distributed on a need-to-know basis. The secrecy is worrisome, but it might also be prudent in this case. Paul Keim, chairman of the science advisory board, told ScienceInsider, "I can't think of another pathogenic organism that is as scary as this one." He added, "I don't think anthrax is scary at all compared to this."
Similar worries were touched upon last year by a U.S. presidential commission studying developments in synthetic biology, which involves using engineering techniques to create new biological parts or devices, or re-designing existing ones. More regulation is not necessary at this time, the panel said, but synthetic biology should be watched closely. Separately, efforts are being made in the United States to improve the monitoring of biological research by scientists, companies and government. Yet much of it remains voluntary. What happens if a real rogue actor comes along and breezes right past the voluntary roadblocks?
At the same time, it is impossible to put this remarkable and fast-moving science under lock and key. These are not nuclear warheads. Biological research can be carried out in small laboratories the size of a garage and agents carried in a test tube that fits in a shirt pocket. We need to encourage the science, without forsaking security. It will require new thinking. We're not there yet.
AFP/Getty Images/Kenzo Tribouillard
One of the most remarkable advances against disease and death was the invention of antibiotics, which led to a massive and immediate decline in death from infections. In a paper published last fall in a workshop report of the Institute of Medicine, Brad Spellberg, an associate professor of medicine at UCLA, noted that antibiotics led U.S. deaths to decline by about 220 per 100,000 population over 15 years, from the late 1930s to the early 150s. This period includes the introduction of penicillin.
By contrast, he reported, subsequent medical advances over the next 45 years resulted in only minor further reductions in deaths by infections—about an additional 20 per 100,000 people.
Antibiotics caused a revolution in medicine, and gave hope to millions of people who might otherwise have died from infections. They allowed the conduct of complicated and deeply invasive surgery, and organ transplants, which would not have been possible without effective antibacterial agents to deal with infections.
Spellberg recalls the words of Dr. Lewis Thomas, one of the most prominent physicians of the 20th century, on the arrival of the first antibiotics. In a memoir of his internship, Thomas wrote:
For most of the infectious diseases on the wards of Boston City Hospital in 1937, there was nothing that could be done beyond bed rest and good nursing care. Then came the explosive news of sulfanilamide, and the start of the real evolution in medicine. I remember the astonishment when the first cases of pneumococcal and streptococcal septicemia were treated in Boston in 1937. The phenomenon was almost beyond belief. Here were moribund patients, who would surely have died without treatment, improving ... within a matter of hours ... and feeling entirely well within the next day ... we became convinced, overnight, that nothing lay beyond reach for the future. Medicine was off and running.
But the antibiotic revolution seems to be running out of steam. The number of new antibiotic drugs has dwindled. Meanwhile, microbes continue to evolve, developing resistance to existing drugs. Some of these bacteria, like Methicillin-resistant Staphylococcus aureus, or MRSA, are lethal.
There are economic reasons why the drug pipeline has been drying up. Among them: pharmaceutical companies don’t get as high a return on investment for products taken for just a few weeks, compared to those for chronic disease, so there are not strong incentives to invest the millions of dollars in developing new antibiotics.
Now comes a report of a promising new approach. In a paper just published by Nature Chemistry, [abstract] a team of researchers has developed biodegradable nanoparticles, super-small particles which attack the microbe’s cell membrane “selectively and efficiently,” in effect poking holes in the membrane. They destroy the infection, without hurting healthy cells. In an article in the Wall Street Journal today describing the technology, James L. Hedrick of International Business Machines Corp., one of the researchers, said the destruction of the bacteria renders it unable to develop resistance to the nanoparticles. The paper says the technology can work against many different infections, including MRSA, which is responsible for some 19,000 hospital-stay related deaths per year in the United States. It hasn’t been tested yet in humans, but if further trials and research show it works, nanoparticles could eventually open a new avenue to fight a real and ongoing threat.
When the Biological and Toxin Weapons Convention was first signed in the 1970s, it was hailed as a step forward in disarmament. There was no effective enforcement mechanism, but at least the major powers had agreed to outlaw germ warfare. In the years since, it has became clear that the lack of enforcement left gaping holes. The agreement failed to prevent the Soviet Union, aparthied-era South Africa and Saddam Hussein's Iraq from pursuing secret biological weapons programs. Jonathan B. Tucker, the author of Scourge and War of Nerves, and professor at Darmstadt University of Technology in Germany, says the treaty “lost a good deal of credibility."
Tucker has written a thorough and illuminating piece for Arms Control Today about the next review conference of the treaty, due this December. He points out that suspicions persist about noncompliance. The State Department's 2010 report to Congress noted that China and Russia have been less than full in disclosing past biological warfare programs, and suggesting that offensive programs may exist in Iran, North Korea, Russia and Syria. Also, the treaty has only 163 member states, compared to 189 for the Nuclear Nonproliferation Treaty and 188 for the Chemical Weapons Convention. Tucker also says that fewer than half of the members participate in the annual confidence-building declarations. These forms were supposed to help boost transparency, since there is still no mandatory inspections or effective verification. But the confidence-building forms haven't even been revised since they were first instituted in 1991.
In the late 1990s, there was an effort to stiffen the treaty with a more forceful, legally-binding inspection procedure. This fell apart in 2001 when the Bush administration rejected it and the talks collapsed. The Obama administration has also shied away from the legal approach, and instead offered a "strategy" document on biological threats. Tucker criticizes the measures as "conceptually flawed or too weak to make much of a difference."
But Tucker says there is a chance to improve the treaty and make a difference at the review conference. He urges the United States to take good advantage of it, and offers a useful list of ideas. The treaty entered into force 35 years ago, and looks dog-eared. Not only has it been repeatedly violated with impunity, but the rapid pace of change in biotechnology is making it seem less and less relevant. Can it be saved?
Getty Images/Dimas Ardian
Earlier this year, scientists at the J. Craig Venter Institute reported in the journal Science that they had designed and created a synthetic chromosome which they transplanted into a living cell. The living cell created new cells which are controlled only by the synthetic chromosome. The experiment was another reminder of the possibilities of synthetic biology, and its complexities.
The revolution in the life sciences is filled with promise for improvements in health, medicine, energy, and the environment. Yet the field known as synthetic biology is relatively new, and many hurdles remain. Turns out it is a lot easier to synthesize some bits of genetic material than it is to make them work inside the body. For an interesting look at the difficulties, see this piece from Nature, in January.
The knowledge of biology is dual use: that which can make our lives better can also be used for ill. With this in mind, President Obama last May 20 asked his new Presidential Commission for the Study of Bioethical Issues to undertake a study of synthetic biology, looking at the “potential medical, environmental, security, and other benefits of this field of research, as well as any potential health, security or other risks.” He asked for the study to be complete in six months.
Last week, The Scientist published an interview with Amy Gutmann, president of the University of Pennsylvania, who is the chairman of the 12-member commission.
Gutmann says the benefits of the new field could range from “better production of vaccines to environmentally friendly biofuels to developing, in the near term, semi-synthetic anti malarial drugs.” But there are risks, she added, all in the future. The primary risk “that needs to be overseen is introducing novel organisms into the environment, [and] how they will react with the environment.”
She says the panel will recommend some kind of middle ground between unfettered scientific discovery and stopping all scientific research until the risks are known.
Can biological science police itself? This is the question Amy E. Smithson has asked in a new article for the journal Survival. Smithson, a senior fellow at the James L. Martin Center for Nonproliferation Studies, Monterey Institute, says recent experiments have sparked a debate over the need for increased oversight, whether by scientists themselves, or by the government, or others. The article gives a good overview of the options. Smithson concludes that we haven’t found the best answer yet, and both government and those outside it need to do more to find the right mix of oversight. While the government can’t leave it all to the private sector, Smithson says the biotech industry is not likely to tolerate those who would misuse biology for malevolent purposes. “Companies do not want to see products designed and produced for legitimate purposes hijacked for malign ones,” she writes, “if only because such misuse could cause a company’s fortunes to plummet.”
A related phenomenon is the rise of the do-it-yourself bio community. According to another recent piece in Nature, potential “bio-hackers” around the world “are setting up labs in their garages, closests and kitchens—from professional scientists keeping a side project at home to individuals who have never used a pipette before.” For now, they are weekend hobbyists, the article says, but there have been security concerns raised about dabbling in dangerous pathogens. The FBI has taken a sort of “neighborhood watch” approach to the hobbyists, relying on the biohackers to monitor their own community and report any behavior they find threatening, the article says.
David E. Hoffman is a Pulitzer Prize-winning author and a contributing editor to Foreign Policy.