The Al Qaeda terrorist attack on America was a stunning case of asymmetric warfare. The resources needed to develop the sophisticated weapons owned by many western countries are beyond the capacity of smaller nations and terrorist groups who oppose the global dominance of the US and its allies. The focus of these groups has thus shifted to exploring other means of inflicting great damage at low cost. Foremost among these is biotechnology.
A dauntingly large number of infectious organisms and biological toxins can be used to attack people, animals and plants. The most likely biothreats for humans encompass all branches of the microbial kingdom, including: bacteria (anthrax, plague, brucellosis, tularaemia); rickettsia (typhus, Rocky Mountain spotted fever, Q Fever); viruses (smallpox, influenza, dengue fever, various encephalitis viruses and the haemorrhagic fever agents, Ebola, Marburg and Lassa); fungi (coccidioidomycosis); and toxins (botulinum, Staphylococcal enterotoxin b, shigella, ricin, aflatoxin). The Nato biowarfare defence handbook lists 31 human pathogens of concern. The former Soviet Union (FSU) bioweapons programme accorded priority to 11 of these agents, with smallpox, anthrax, plague and botulinum toxin regarded as the most dangerous. Anthrax (non-contagious) and smallpox (highly contagious) are accorded primacy in the bioweaponeers' arsenal because of their deadliness and ease of manufacture, storage and dispersal by aerosol.
Bioagents can be disseminated in many ways. Aerosols are the most effective for contaminating large areas and achieving high rates of infection. For certain pathogens, lethal doses can be achieved by aerosol deployment as far away as 50 to 100 miles. Contamination of water offers an efficient avenue for spreading certain diseases. The release of infected insects, plants or animals is also an easy way to attack the agricultural sector and the food chain. Some consider it only a matter of time before deliberately infected humans will become the bioterrorism counterpart of the suicide bomber, seeding disease in aircraft, public transport, shopping malls and other venues where people congregate.
The ultimate biothreat lies in infections caused by viruses that can integrate themselves into the genes of their victims to await activation at a later date. This is no longer a dystopian fantasy. Infection with latent agents and their controlled reactivation has already been achieved in animal experiments.
A pervasive sense of vulnerability to unseen microbes is more disturbing to the public psyche than many other potential threats. The five deaths and 18 infections caused by the recent anthrax-by-mail incidents in the US were a fraction of one day's carnage from American traffic accidents, but round-the-clock media coverage fuelled public fear and an over-reaction by legislators. The incidents also revealed the inadequacy of current defence measures in responding to even a minor incident.
ASSESSING THE BIOTERRORISM THREAT
One school holds that the bioterrorism threat is exaggerated on the grounds that bioagents are too difficult to produce and use, terrorists have easier ways of causing havoc, and moral constraints will preclude their use against civilians. The alternative view holds that it is inevitable that bioweapons will be used against the west. Advocates of this pessimistic view argue that there is no instance in history when a new weapon with the potential to transform the balance of political and military power has not been deployed.
Those who argue that bioweapons are too difficult to develop or impractical to use, must know something that the FSU overlooked. Ken Alibek, the Russian bioweapons expert, documents in his 1999 book, Biohazard, how the FSU Biopreparat programme developed massive quantities of bioagents for use against humans, plants and animals. Even with the crude technologies available three decades ago, Biopreparat successfully engineered organisms with enhanced virulence and dissemination capabilities and with increased resistance to drugs and vaccines.
It is true that the Soviet Union had a powerful state machine and vast territory at its disposal, unlike many of those who are currently trying to develop bioweapons. But what has changed the risk calculus in the past two decades is the dramatic progress in biotechnology and the much wider access to its products. The pharmaceutical industry, and numerous bioprocess industries, produce large quantities of micro-organisms and employ genetics to modify microbial properties. It is hard to detect illicit R&D activities and easy to procure samples of many different bioagents from a variety of sources, legitimate or not. In addition, natural outbreaks of anthrax, bubonic plague and other pathogens offer the terrorist the means to obtain seed materials.
Training in genetics, microbiology and biotechnology is now offered in college courses around the world. Huge volumes of information pertinent to bioterrorism are available in non-classified scientific journals and on the internet. The number of trained personnel capable of undertaking sophisticated genetic manipulations has expanded substantially, including in nations viewed as potential sponsors of terrorism. Technological advances allow the cultivation and harvesting of large quantities of virulent micro-organisms virtually anywhere and at minimal expense. A survey of 1,400 US academic institutions revealed that 16 per cent had stocks of pathogens listed in the draft Biological Weapons Convention, 11 per cent had high-level microbiological containment facilities and 3 per cent had large volume bioreactors. Over 2,000 new biotechnology companies have been formed in the US and 1,500 in Europe during the last 20 years, together with a parallel expansion of expertise in genetics and molecular biology within the pharmaceutical sector.
The fate of the personnel and pathogens from the FSU bioweapons programme is of particular concern. The Biopreparat effort in the civilian sector employed at least 70,000 people in its illicit bioweapons programme. Concern persists that elements of the military programme may not have stopped. There are also reports of FSU scientists working in Iraq, Iran and North Korea. Security at FSU bioweapons facilities is lax and economic pressures have increased the risk that both personnel and biological specimens are available at a price. In spite of these risks, the "loose bug" problem in the FSU has been given far less emphasis than the "loose nuke" problem in the weapons threat reduction programmes being funded by western governments.
In early April, the US administration informed Moscow of its concerns that Russia is not complying with treaties banning chemical and biological weapons. This decision was prompted by Moscow's refusal to share a bio-engineered strain of anthrax developed by its scientists despite repeated promises to do so in the course of assisting the US in investigating the anthrax bioterrorism incident.
UNIQUENESS OF THE BIOTERRORISM THREAT
Life sciences research is being transformed from merely describing biological phenomena to revealing the genetic control networks that orchestrate biological processes. This holds great promise for improvements in medicine and agriculture, but the same knowledge can be exploited for less benign ends in a world full of individual and group hatreds.
Advanced genetic techniques make it increasingly simple to use pathogens as weapons. And on a longer timescale, the risk of even more threatening manipulations must be entertained. These include the use of entirely synthetic genes that enhance microbial virulence or the ability to circumvent protective vaccination. Genetic methods enable the construction of organisms whose purpose is not to cause death and injury by infection but to disrupt critical body functions through uncontrolled hormone production or to trigger the immune system to destroy its own tissues. Non-living targets are also vulnerable. Micro-organisms able to degrade materials such as petrochemicals, plastics, or computer components would quickly compromise military operations and cripple infrastructure.
At least a dozen nations are believed to be engaged in developing bioweapons including Iraq, Iran, Syria, North Korea, Sudan, Israel, China, Libya, India, Pakistan and Egypt. More have the capability for doing so. Bioterror is within the grasp of small, modestly equipped groups or even individuals.
Since 11th September, it has been de rigueur for politicians to refer to the need to improve defence against weapons of mass destruction (WMD). The WMD mantra, lumping together nuclear, chemical and biological threats, implies that they present similar security challenges. This is not true. The "lumping" problem has hindered the development of a coherent defence policy for biological threats. The view is widely held in political and military circles that what has worked well against nuclear threats will serve equally well for biodefence. This is a dangerous delusion. Nuclear, chemical and biological threats each present unique complexities. But the detection and control of biothreats is by far the most complex. These difficulties reflect several unique aspects of the "biothreat."
1. The diversity of the biothreat inventory, the ubiquity of targets and the ability of the attacker to use different routes of dissemination mean that it is impossible to provide a uniform picture of the biothreat problem. Bioweapons can cause widely differing levels of carnage, ranging from transient illness to catastrophes in which millions of people die.
2. In assaults with nuclear and chemical weapons the scale of damage is evident immediately. In contrast, the effects of a bioattack are unlikely to be recognised quickly. Depending on the method by which a pathogen is released and dispersed, initial infection of victims can occur within a few hours (for large airborne releases) or extend over weeks or months (for release by contagious carriers). The initial symptoms of many bioagents are indistinguishable from common infections such as colds and flu.
3. Prevention of bioattacks before they occur is obviously the most desirable situation. Unfortunately, there are substantial shortcomings in current intelligence capabilities. This is reflected in the failure to detect the bioweapons programme in the FSU. This was conducted on a colossal scale for over two decades. Substantial R&D investment has been made by the US since the Gulf war to develop sensors to detect biothreat agents in the environment. However, this is a difficult technical challenge and progress has been slow. The use of environmental sensors to detect illicit production of bioagents is unlikely for at least a decade, and possibly longer. For the foreseeable future, biodefence must rely mainly on faster medical diagnosis and containment of an incident once it has begun.
4. The fragility of current public health capabilities means that the first indication that a bioattack has occurred will come only after doctors report abnormal numbers of ill people who share symptoms. But the diagnostic laboratory tests for many of the anticipated biothreats are either not yet developed or available only in a few specialist laboratories. This makes it difficult to ascertain the full scope of an attack and to guide treatment strategies.
5. A mere few hundred casualties requiring intensive care would overwhelm the hospital network in many cities in America or Europe. Health facilities would not only have to diagnose and treat victims of the attack while still providing care for those ill from natural disease, but they would also be confronted with a tidal wave of "the worried well" who believe they are victims. In addition, there is the prospect of "defections" by health staff and the illicit diversion of scarce medicines and vaccines for use by themselves and their families.
6. Management of a bioincident would be complicated by a lack of drugs and vaccines. Current stockpiles of the few drugs and vaccines which are currently approved for use against biothreats are insufficient if a bioincident required treatment of many thousands of people. Second, little investment has been made to develop new drugs and vaccines against the biothreat agents for which no meaningful medical interventions exists. This reflects the longstanding neglect of the "bio" problem and the lack of financial incentives for the private sector to develop products for pathogens in the absence of government purchase guarantees. Recent decisions by the US government to expand antibiotic stockpiles and expand the vaccine supply for anthrax and smallpox are welcome. In the short term, however, large shortfalls in drugs and vaccines will exist.
7. Actions to limit the consequences of a bioattack require swift action by public health, military and law enforcement authorities in concert with multiple private sector entities. These groups may have little or no prior experience of working together. Decision-makers would be confronted with unfamiliar and complex technical issues that have the potential for catastrophic outcomes if the wrong judgements were made. National leaders would have to decide whether to impose martial law, ban trade and travel and authorise emergency seizure and diversion of private assets. Those involved in the containment of infection would also be forced to make hard decisions regarding rationing of drugs and vaccines, the mandatory testing and treatment of people without their consent, imposition of quarantine and other constraints on freedom. They would also be required to maintain essential services and to address the problem of mass disposal of corpses. Recent US experiences from field exercises involving the simulated release of plague and smallpox in US cities demonstrated that even when disaster plans and management structures were in place, they collapsed quickly due to turf battles, compounded by inadequate training.
Mass psychological trauma would be aggravated by any perception, real or imagined, that a bioincident was being mismanaged or was out of control. The near certainty of irresponsible actions by the media would contribute to public panic and civil disorder.
HOW TO STRENGHTEN BIODEFENSE
Strengthening defences against bioterror must not be played as a zero-sum game. The building of new intelligence capabilities should not be bartered against funds to develop new diagnostic tests and computerised epidemiological networks for faster detection and containment. In turn, these investments should not come at the expense of R&D initiatives to discover new drugs and vaccines or urgently needed investments to strengthen medical and public health infrastructures. However, the timelines required to make these elements a practical reality vary enormously.
The most immediate gains can be made by improving the training of healthcare staff to recognise and manage bioattacks and in strengthening public health and medical resources to improve the speed of incident detection and containment. Vigorous action could achieve these goals in two years. A focused research programme to create new diagnostic tests based on the genetic profiles of biothreat pathogens could fill the current gap within five years. In contrast, the discovery of new drugs and vaccines is more complex and will likely require at least a decade.
Building new intelligence gathering capabilities is the most formidable task in the biodefence agenda. In monitoring the clandestine production of nuclear weapons the intelligence services enjoy the luxury of telltale signatures that enable them to detect and track illicit materials. Equivalent signatures do not exist to allow the remote monitoring of biopathogens. Illicit biological activities can be hidden easily in institutions that have legitimate interests in microbiology and genetics. Monitoring of biothreat production still depends primarily on the "on site" acquisition of samples as in the case of the Unscom detection of Iraq's bioweapons effort. Technical solutions to devise signatures for improved remote monitoring of bioagent production and the emergence of novel methods for covert sampling will take time. Moreover, the historical focus of the intelligence and defence communities on non-biological threats means that these organisations lack the technical expertise needed to analyse the new challenge.
The political response in Washington since September 2001 has been to throw money at the problem. An extra $11 billion has been allocated for biodefence without clear priorities or objectives. The situation is reminiscent of previous Congressional enthusiasms in launching the war on cancer, the quest for an Aids vaccine and the human genome project. In each case, massive funds were allocated with no subsequent accountability for the relatively meagre results achieved.
What is needed? The current vulnerabilities in biodefence must be quantified, together with a stringent technical analysis of how these could be best addressed and the time periods in which solutions might be expected. There is also a need for people who can distinguish worthwhile R&D efforts from purely opportunistic bidders, as government laboratories, universities and private companies seek their share of the new billions allocated to bioterror defence. By funding the many over-hyped projects that are flooding the granting agencies-backed by Congressmen keen to ensure that projects are funded in their own districts-there is a high probability that huge sums will be wasted with few gains.
The largest problem facing the national security apparatus is that the relevant skills in biotechnology reside largely outside government. This contrasts with the evolution of nuclear defence policies in which much of the leading edge science was either conducted in government laboratories or could be accessed via symbiotic links with the defence industry.
A further requirement in biodefence strategy is organisational. Today, over 40 US government departments and agencies have assigned or claimed responsibilities in biodefence. The appointment of Governor Tom Ridge to oversee "Homeland Security," without the resources needed to implement radical reform and integrate government biodefence responsibilities within a common command structure, was a lost opportunity.
the biological weapons convention
In November 1969, President Nixon issued National Security Memorandum 35 declaring that the US would renounce all methods of biological warfare and limit its R&D activities to defensive purposes. US biological and toxin stockpiles were destroyed and production facilities dismantled. Nixon also endorsed a British proposal to prohibit the development, production and possession of biological weapons that led to the 1972 Biological Weapons Convention (BWC), which sought to establish international rules to prevent the spread of bioagents and facilitate action against violators. In contrast to the Chemical Weapons Convention, which established formal verification mechanisms to ensure compliance, the BWC had no legally binding requirement for declaration of compliance and no provision for inspections. In 1994, efforts were launched to redress these deficiencies. In late 2001, the proposed revisions were rejected by the Bush administration on the grounds that they would do little to ensure compliance and that the measures to protect the interests of legitimate commercial companies which might be subject to inspection were inadequate. The debacle of the UN inspection effort in Iraq was cited as an illustration of the ineffectiveness of enforcement measures, albeit compounded by the complicity of Kofi Annan in brokering a deal that undermined his own inspection teams and allowed Iraq to retain key elements of its chemical and biowarfare programmes.
The US counter-proposals to the BWC protocol included the need for signatory countries to "sensitise scientists to the risk of genetic engineering" and to establish "national oversight of high-risk experiments." Life sciences researchers can no longer ignore the national security implications of their work and must participate in limiting the proliferation of new modes of bioterror. (The USA Patriots Act passed in October 2001 imposes security background checks for scientists working with those pathogens deemed most likely to be used by bioterrorists.)
Three examples of academic research which is already in the public domain illustrate the problem: the genetic codes of devastating pathogens such as bubonic plague, smallpox, and the 1917 pandemic strain of influenza which provide critical insights into how to manipulate the virulence of such organisms and to generate modified forms that resist drugs and vaccines; the use of gene shuffling methods to create viruses with altered modes of spread; and the construction of viruses with genes to paralyse the body's immune defences.
The issue is not whether areas of "forbidden knowledge" should be defined in which research is prohibited. Rather, it is about defining boundaries for "constrained knowledge" whereby freedom of research enquiry is not impeded, but access to certain forms of research data would be limited to those with bona fide credentials. Freedom of intellectual enquiry must be protected. Researchers in physics, chemistry and engineering have long had to accept constraints on public domain knowledge. Biology and medicine cannot escape the same responsibilities.
In 1975, at the dawn of the biotechnology era, scientists were concerned that new gene splicing methods and cross-species transfer of genes might convert harmless microbes in the body into virulent pathogens or produce long-term genetic damage. These concerns stimulated the Asilomar conference which led to a voluntary moratorium on certain forms of genetic manipulations until the risks were evaluated. Asilomar is a model for how science can independently regulate its own enquiries. This ethos must now be reawakened.
are we doomed?
It is certain that the number of discoveries in the life sciences that present complex dual-use dilemmas will increase at an accelerating pace. The basic rules of biological design that are now being discovered will create a new catalogue of designer biothreats that target specific molecular control networks in the body. Of particular concern is the prospect of novel biothreats that affect human brain function.
The convergence of biotechnology, nano- technology, robotics and computing offers a further menu of emergent biothreats. And as in the nuclear age, there is the real danger of accidental catastrophe. Bill Joy, chief scientist at Sun Microsystems, in his well publicised essay "Why the future doesn't need us" feared that man-made production of self-replicating molecular and nano-devices that would neither need, nor respond to, human intervention could damage irrevocably the molecular structure of our world. Numerous technical rejoinders have been offered to Joy's essay, but these are secondary to the question that Joy and others (including Martin Rees in the January 2002 Prospect) are rightly raising about whether our current institutions and policies are adequate to address the perplexing issues being generated by contemporary technology.
The west enjoys military, economic and technological strengths that have immunised it against security threats and natural disasters. Those strengths can also breed complacency. The debate about the nature and scope of biosecurity and the adequacy of current institutions and policies to analyse and respond to the emerging threats has barely begun. It is destined to move to centre stage.
