SINCE the end of the Cold War, the Western world has been experiencing an
unaccustomed respite from the fears of large scale violence. No longer do two
superpowers appear ready to bury civilisation under a barrage of nuclear
missiles. Strategic bombers, once perpetually on patrol, are parked in their
hangars. The threat of Armageddon has faded. We ought to be safer.
Safer, perhaps, but not safe. Military analysts warn that we should now be on
our guard against a new type of savagery that kills civilians but spares their
homes and offices, strikes without warning, and against which there may be no
defence. What is more, although this threat requires no radically new
technology, the laboratories of academia and the biotech industry indirectly
contribute to its development. The threat is bioterrorism.
A few hundred kilograms of a properly “weaponised” bacterial preparation,
carefully dried and milled to a precise particle size, has the potential to wipe
out the inhabitants of an entire city in a single strike. A nuclear bomb in the
hands of a deranged person has long been the stuff of nightmares, but the
materials needed to make such a device are hard to obtain and exceedingly tricky
to assemble. Biological weapons are not nearly so difficult to manufacture.
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Many experts say that it is no longer a question of whether a major
bioterrorist attack will occur, but when. “It is really a matter of time,” says
microbiologist Raymond Zilinskas of the University of Maryland Biotechnology
Institute in College Park, who participated in the UN’s hunt for Iraq’s
biological weapons after the Gulf War. “I don’t understand why it hasn’t
happened already.”
Two factors make the threat of a bioterrorist attack greater than ever
before, says Kyle Olson, a chemical and biological weapons analyst at TASC, a
firm of defence consultants in Arlington, Virginia. First, the unspoken taboo
that previously dissuaded terrorists from using chemical or biological weapons
against civilians has now been broken. On 20 March 1995, the nihilistic Japanese
cult Aum Shinrikyo unleashed nerve gas on the Tokyo subway, killing 12 people
and hospitalising five thousand. Aum was also developing biological weapons.
Second, with the explosive growth of basic biological research and
biotechnology, what was once regarded as esoteric knowledge about how to culture
and disperse infectious agents has spread among tens of thousands of people.
Grim reality
“People must recognise that the threat of bioterrorism is not a curiosity,
but a grim reality as we enter the next century,” says Olson. Most importantly,
argue Olson, Zilinskas and others, public health authorities and emergency
services must start planning now to cope with the aftermath of a variety of
biological attacks.
Biological weapons have been with us for half a century or more, but military
commanders consider them too unpredictable and slow-acting, preferring the
touch-of-a-button reliability of explosives. What is more, the international
condemnation that the use of biological weapons would provoke gives any rational
military strategist pause. Biological weapons are also an unlikely choice for
most politically inspired terrorist organisations. “Traditionally, political
terror groups are trying to get a seat at the table and to establish the
legitimacy of their cause,” says Brad Roberts, a biological weapons expert at
the Institute for Defense Analyses, a think-tank in Alexandria, Virginia. That
goal would not be met by resorting to bioterrorism.
Nonetheless, terrorist experts fear that the probability of a surprise
biological attack on an unprotected city is higher today than ever before. Many
point to a new brand of terrorism—epitomised by Aum Shinrikyo—that
lacks the restraints imposed by a political agenda. “There are new actors
appearing, individuals and small organisations that don’t seem to care about
establishing legitimacy, but just want to strike a blow in anger and kill as
many people as possible,” says Roberts. “For them, the calculation of the right
level of violence seems to have no upper bound.”
In addition, the number of trained biologists is soaring. Life science PhDs
awarded in the US increased by 30 per cent between 1975 and 1991 to more than
5700 a year. By 1994 England alone had 5700 biology graduate students. American
industry now employs around 60 000 life scientists. There are over 1300
biotechnology companies in the US and about 580 in Europe; 25 years ago there
were none. Moreover, many less developed countries, including Iraq, have their
own biotechnology industries.
The threat does not come from the fictional mad scientist engineering a
deadly new germ, says Zilinskas, although the technology to create a Satan bug
may soon be within our grasp (see “What if . . .”). Instead, the widespread use
of the basic tools of industrial biology has put the power to create
“traditional” biological weapons in the hands of tens of thousands of people.
“Advanced biological technologies have spread all over the world,” says
Zilinskas. “There are many more people who are technically trained, and the
methods for culturing large quantities of bacteria are well worked out and
commonly employed.”
Olson agrees: “A person who is smart, determined, trained in basic
microbiological techniques, and willing to take a few short-cuts on safety and
go at a few technical problems in mildly unconventional ways, could conceivably
do some horrible things.”
Horrible indeed. Bioterrorism is distinguished not only by its mode of
killing, but also by the potential scale of destruction—thousands of times
as many people as could be killed by a typical car bomb. That awesome potential
has caught the attention of the US government. A 1993 report on weapons of mass
destruction by the US Office of Technology Assessment (OTA) lists the diseases
that could be employed as biological weapons. They include plague; tularemia, a
plague-like disease; and botulism, caused by a toxin from the common
food-poisoning bacterium Clostridium botulinum. But the most chilling
reading in the report is the story of anthrax, the original biological warfare
agent.
Low-tech weapons
Anthrax, a disease of cattle and sheep caused by Bacillus anthracis,
can also kill humans. The external form of the disease, which sometimes strikes
people who handle infected fleeces, causes unpleasant sores. The pneumonic form
is far more serious, killing more than 90 per cent of its victims if left
untreated. The key to triggering the second form of the disease is to create and
disperse spore-containing particles of exactly the right size—between 1
and 5 micrometres—to ensure that they are retained in the lungs. As few as
8000 spores per person reliably causes a lethal infection. The spores cross the
epithelial lining of the lungs and travel to the lymph nodes, where they
germinate, multiply, and then spread to the other tissues, releasing toxins as
they go. The first symptoms include vomiting, fever, a choking cough and
laboured breathing. Antibiotics can cure patients in the earlier stages of the
disease. Without antibiotics, death from haemorrhage, respiratory failure or
toxic shock follows within a few days.
The OTA report emphasised that, for the most part, transforming B.
anthracis into a weapon is a low-tech procedure. It also noted that on a
clear, calm night, a light plane flying over Washington DC (similar to the one
that crashed into the White House in 1994), carrying 100 kilograms of anthrax
spores and equipped with a crop sprayer, could deliver a fatal dose to up to
three million people.
Zilinskas emphasises that making an anthrax weapon capable of murder on this
scale is not a trivial undertaking. But while it may be much more difficult than
building a fertiliser bomb, the problems are far from insurmountable. The tricky
part, he says, is not culturing the agent, but processing the crude slurry into
a form suitable for dispersal. “You have to dry it somehow, adjust the particle
size, load it into a canister, and spray it. If you wanted to be sure your
preparation would work, you would also need to test your isolate for virulence,
measure the particle size and perhaps field test your sprayer with a
non-pathogenic bacterium. All the while you have to protect yourself and avoid
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A project of this complexity would require months of systematic effort, the
practical engineering skills of a clever back-yard inventor, and luck. These
barriers, however, are not impossibly high. Basic microbiology
skills—techniques an undergraduate studying the subject would be
taught—should be sufficient to isolate B. anthracis from cattle
pasture in areas where the disease is endemic, such as small areas of the US,
and larger tracts of land in Russia and South Africa. Using this as the starter
culture, a terrorist with a 100-litre culture vessel—about the size of a
home fish tank—could in a few days brew up several kilograms of crude
slurry containing billions of spores. Drying the slurry would be tricky, though
not impossible. Freeze-drying—a procedure in which material is frozen and
put under a vacuum to remove water, and which is used on a small scale
throughout the biotech industry—could be one option. Grinding the slurry
powder into particles of the desired diameter would provide the greatest
challenge, mainly because of the risk of contamination. Indeed, the most likely
glitch all round is that the terrorists become the first victims, or that they
infect their neighbours and give the game away.
Moreover, Zilinskas says a few essential details are not commonly known. “The
Iraqis, as far as we know, never mastered the art of weaponising their bacterial
agents, which included anthrax,” he says. “Most of what the UN investigators
found were crude preparations mounted on conventional bombs and missiles, which
might not have dispersed very well.” But he notes that less ambitious attacks
also pose a threat. For example, a crude slurry of anthrax spores left in the
tunnels of an underground railway system, where wind created by passing trains
would dry them and blow them around, could claim thousands of lives.
The Aum Shinrikyo attack on the Tokyo underground fell into this less
ambitious category—and even that was bungled. Olson, who interviewed cult
members in Japan both before and after the Tokyo incident, says that the attack
was hastily planned, the batch of sarin nerve gas the cult members manufactured
was impure, and the dispersal device was nothing more than a bag punctured with
an umbrella tip. Had the sarin been pure, and the dispersal mechanism slightly
more sophisticated, tens of thousands could have died.
But John Sopko and his colleagues on the staff of the US Senate Permanent
Committee on Investigations, who were asked to look into the attack by Senator
Sam Nunn of Georgia, found that despite the cult’s ineptitude there was plenty
of reason to take notice. In a report presented last November at one of a series
of Senate hearings on terrorism, they wrote that the cult, which had more than
40 000 members in Japan and Russia and one billion dollars in assets, had
recruited hundreds of scientists to assist with its “avowed purpose of plunging
the United States and Japan into a war of `Armageddon’ from which the cult would
arise as the supreme power in Japan.”
Sopko and his colleagues—not the kind of people given to
sensationalism—also noted that “although the findings may initially sound
far-fetched and nearly science fictional, the actions of the Aum . . . create a
terrifying picture of a deadly mix of the religious zealotry of groups such as
the Branch Davidians, the anti-government agenda of the US militia movements and
the technical know-how of a Doctor Strangelove.” A manual on sarin production
included the song Sarin, The Brave with the catchy lines “Prepare
Sarin! Prepare Sarin! Immediately poisonous gas weapons will fill the place.
Spray! Spray! Sarin the Brave, Sarin.”
Ebola expedition
The cult also had a large biological weapons programme, the precise extent of
which remains unexplored to this day. “There is an Aum lab—now
sealed—that was devoted to biological agents, which has not yet been fully
investigated,” says Olson. “As early as 1990 they were trying to aerosolise
botulinus toxin. We think they had anthrax as well. In 1991, [cult leader Shoko]
Asahara led an expedition to Zaire to obtain samples of the Ebola virus. We have
to assume they had progressed since then, but how far they got we don’t
°ě˛Ô´Ç·É.”
The Japanese cult is now out of action. “My concern is [that] new groups will
look at Aum Shinrikyo’s activities and ask: `How could I do this a little
better?’ ” says Roberts. Compared with Sarin gas, he says, “biological agents
might look a lot easier to work with—in terms of access to material, and
the level of expertise needed—and more effective”.
Only time will tell whether the Aum Shinrikyo attack will inspire or deter. But the
Japanese tragedy has sparked concern that greater efforts are needed to prevent and
prepare for a bioterrorist attack. On the intelligence front, the Aum experience
is not encouraging. The Japanese authorities were aware of some of the cult’s
activities, and were poised to move against them. But though the US was known to be
one of the cult’s avowed targets, John O’Neill, chief of the Counterterrorism and
Middle East Section of the FBI, admitted to the Senate that the cult’s activities
“weren’t on our radar screen”.
Apart from acting on intelligence, another defence would be to restrict access to
the tools of bioterrorism, including starter cultures. In March 1995, Larry Harris, a
microbiologist and a member of the Aryan Nations white supremacist group, used a forged
letterhead and his professional credentials to order samples of Yersinia pestis,
the organism that causes bubonic plague, from the American Type Culture Collection, a
clearing house for microbiological samples in Rockville, Maryland. The ATCC dutifully
mailed the samples, but in the nick of time staff became suspicious that Harris did not
have the expertise to handle plague and the vials were recovered unopened. Harris
is being prosecuted for mail fraud—owning plague, it transpires, is not illegal in the US.
In Britain any company that wants to keep lethal pathogens must prove to the government’s
Health and Safety Executive that it has adequate containment facilities. But, according to
spokesman Mark Wheeler, the HSE has no jurisdiction over private citizens. Lindsey French
of the Department of Health confirms that people may keep lethal pathogens at home. But
she says that threats to do harm with those pathogens, transporting or storing them
improperly, or obtaining them by fraud or theft, are illegal. Not that would-be terrorists
need obtain their pathogens through official channels. If you know where to look, many
can be isolated from the wild.
But perhaps the most neglected area of planning is the medical response to an attack.
“The scenario changes with the agent used,” says Philip Russell, former commander of
the US Army Medical Research and Development Command in Fort Detrick, Maryland.
He is now president of the Sabin Foundation, an organisation based in New Canaan,
Connecticut, which promotes vaccine use against natural diseases. “Plague
is different from smallpox, which is different from anthrax. We need a group
of folks to go through different scenarios and think about what could be done other than
counting the bodies.” For example, he says, plans are needed to ensure that large amounts of
antibiotics, and properly trained and equipped people, can be rushed to the scene.
In the US, these responsibilities fall to the Federal Emergency Management Agency and
the Office of Emergency Preparedness of the Department of Health and Human Services,
both in Washington DC. At the moment, although these agencies have adequate plans to
cope with floods, earthquakes, and the occasional car bomb, OEP head Frank Young told a
Senate hearing on 1 November 1995, “there is no co-ordinated public health infrastructure
to deal with the medical consequences of terrorism”. This is not to say there are no
plans at all. Last June, President Clinton told government agencies—including the
military—to improve their planning for a massive terrorist strike. But at the
most recent Senate terrorism hearing, on 27 March, several key witnesses, among them
P. Lamont Ewell, president of the International Association of Fire Chiefs, questioned
whether the new plans were adequate and whether they had been sufficiently well rehearsed
to cope with a real attack. In Britain, the Home Office takes ultimate responsibility for
preventing bioterrorism and for preparing to deal with its aftermath. It is
characteristically enigmatic. Robert Smith of the Home Office has “contingency plans drawn
up, and they are ready to be used”. But he refused to give any details to New
Scientist because “that would defeat the object of the exercise”.
In the wake of a major bioterrorist attack, undoubtedly the contingency plans would
be rapidly and publicly overhauled. Meanwhile, consider this.
The mid-morning radio news reports an odd outbreak of a respiratory disease on the fringes
of London. It rapidly becomes the top news story, first locally, then nationally, as more
cases show up during the afternoon. Hundreds of people turn up at hospitals across the
city gasping for breath. Doctors begin to suspect, and quickly confirm, that the bizarre
disease is anthrax. An extended evening bulletin gives it saturation coverage. Experts
from the Department of Health try to figure out where the spores came from and in which
direction they are spreading. It all takes time—time they don’t have. Rumours are rife
that supplies of antibiotics have run out. The authorities caution against panic. You know
that you and your family have been exposed…
* * *
What if . . .
The human race suffers many ills, but a lack of scientific creativity is not
one of them. This century alone, the creative output of disciplines from
astronomy to zoology, computer science to communications has, like a flock of
startled birds, soared and spread in every direction. Modern biological sciences
are arguably the most creative of all.
That, and the fact that most technology has sooner or later been turned to
the art of war, made me wonder whether the biological sciences had the power to
enhance the already impressive killing capacity of microorganisms. With these
thoughts in mind, I approached several scientists who study disease pathogenesis
and asked them a disagreeable question: could the tools of biotechnology,
coupled with our exponentially expanding understanding of microorganisms, be
perverted to create pathogens even worse than those nature throws at us?
The answer I got was reassuring—to a degree. Creating a “Satan bug” or
an “Andromeda strain” would be extremely difficult and would probably require a
colossal group research effort, rather than the tinkerings of a lone,
psychologically disturbed postdoc. But when pressed, none of the scientists I
spoke to would rule out the possibility. Like much of modern biology, the
ability to create a Satan bug would depend less on specialist equipment and more
on powerful ideas. And they agreed that the knowledge base on which those ideas
are built is expanding rapidly. Most also agreed that few developments,
including the deliberate construction of a devastating new bug, are outside the
realms of possibility.
At first blush, the idea of engineering a virus or bacterium to be meaner
than normal sounds straightforward: isolate the genes that enable one organism,
a virus for example, to cause a particularly devastating disease, and then use
standard genetic engineering techniques to clip them into another organism that
is spread rapidly through the air—the flu virus, perhaps. After all,
bacterial and viral genomes are routinely manipulated in the biochemistry lab.
“Just dreaming up and making a genetic construct is easy: some first-year
molecular biology grad student gone berserk could do that,” confirmed Frederick
Murphy, a virologist at the University of California at Davis who, using an
electron microscope, was the first person to see the Ebola virus.
But Murphy added the reassuring caveat that there is little chance that such
an organism would perform as its creator intended. If anything, the engineered
bug would end up less dangerous than the original pathogen. First, evolution is
likely to have already honed the most virulent pathogens that are possible,
without exterminating so large a proportion of the human population that the
pathogens die too. Second, virulence depends on complex and delicate
interactions between the microorganism, the human body and their environment.
These interactions are determined by myriad different genes, many of which have
yet to be discovered.
Less reassuringly, Murphy and others I spoke with conceded that the
evolutionary pressure on an engineered bug not to destroy its host population
may only come into play after significant numbers have died. They also
acknowledged that huge strides have been made towards achieving a coherent
“system wide” understanding of the genetic basis of virulence. For example, last
year a team of researchers from the Institute for Genome Research in Rockville,
Maryland, and Johns Hopkins University in Baltimore sequenced the entire genome
of Haemophilus influenzae, a bacterium that causes respiratory and ear
infections, and meningitis in children. Since then, paediatrician and molecular
biologist Richard Moxon and his colleagues at the University of Oxford, have
used the sequence to identify dozens of genes that control the bacterium’s
virulence.
Surface molecules called lipo-polysaccharides (LPS) are the key to the
disease-causing capabilities of H. influenzae and other gram-negative
bacteria. The bacterial biochemistry required to manufacture LPS molecules and
transport them to the surface of the bacteria is complex and requires the
combined effort of numerous genes, said Moxon. But the whole genome sequence
allowed them to identify candidate genes whose products are involved in these
processes, knock them out, and test the effect on virulence in animals. During
these experiments, for example, Moxon’s team found genes that enable the
bacterium to alter the shape of the LPS molecule to evade the host immune
system—a sure-fire way for a bacterium to enhance its virulence.
Of course, Moxon’s team is applying its knowledge to decrease the bacterium’s
effective virulence by creating vaccines that could save millions of young
children around the world who each year die from H. influenzae
infection. And Moxon, like Murphy, argued that it would be hard to beat these
ploughshares into swords, either in H. influenzae or in the other
pathogens whose gene sequences are currently pouring out of laboratories. “You
can remove some of the things that are essential for the optimal virulence and
make an attenuated pathogen,” said Moxon. But increasing virulence is more
tricky, because you would have to tinker with numerous genes without
compromising the microbe’s viability.
Paul Ewald, an evolutionary microbiologist at Amherst College, Massachusetts,
made the point that even if engineering a supervirulent microorganism is
possible, it would require a sustained effort by a small army of very smart and
highly trained people, who would have to test the fruits of their labour in
humans. Such a programme would be hard to conceal. Creating a Satan bug, said
Ewald, would probably be harder even than gene therapy which, despite the best
efforts of thousands of scientists, remains elusive.
William Haseltine, chairman and chief executive officer of Human Genome
Sciences in Rockville, Maryland, gave me another, less comforting, reason to
stop worrying about a lone scientist engineering a particularly mean bug. “You
could do so much harm with pathogens that occur naturally,” he said, “why bother
to engineer something new?” Matthew Meselson, a molecular biologist at Harvard
University in Cambridge, Massachusetts, who has worked for 30 years to limit the
global spread of biological weapons, agreed wholeheartedly, but added that
biological weapons still pose a terrible threat.
Unlike Meselson, the majority of scientists I approached were intensely
uncomfortable with my question, some to the point of refusing to discuss the
issue. Many said that they feared that any public discussion of the risks would
undermine support for biology. Meselson had little time for such reticence.
“Biologists need to remember that our species has turned every technology to
war, going all the way back to alloying metal and shaping stone.”