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Biotech and bioterror: a global dilemma

Experts worry about

House hearing on bioterror
BBC thumbnail of Kenneth Alibek
Roger Brent, molecular scientist
Brent's faculty page
Michael V. Callahan, DARPA scientist
Basement gene tweakers -- Wired article
Professors embroiled in bioterror fears
Bioterrorism: a clear and present danger -- article by federal scientists
Helpful government bioterror info links
Globalization and biosecurity (National Academies)
Biotech and terror (National Academies)
Human genome project's private sector alliance
President's Council on Bioethics
Genome chip technology
About Znewz1

Draft 3

By Paul Conant

Copyright 2006 by Znewz1

JULY 2006--This article is drawn in part from a hearing of the House Subcommittee on Prevention of Nuclear and Biological Attack, which is part of the Homeland Security Committee. The Federation of American Scientists provided a transcript in July 2006. Other sources are National Acadamies reports.

Permission is granted for reproduction of this article.

Could a lone crazed gene scientist or a cell of fanatical "suicide coughers" unleash a global pandemic that kills tens of millions of people?

Such a day is at hand, if it is not already here, say top U.S. biological weapons experts. And U.S. defenses against such attacks are far from adequate, they say.

The specter of Ted Kaczynski, the mathematician now imprisoned in the serial Unabomber murders, is much on the minds of those with an interest in America's biodefenses. Tools and knowledge now available, some of it via the Internet, are just waiting to fall into the hands of such a person, experts fear.

The revolution in biotechnology means that biologists can swap genes in and out of an organism to increase its virulence or resistance to antibiotics. Moreover, they can assemble an entire pathogen -- disease-causing microbe -- from scratch.

Unlike nuclear weapon construction, which is effectively contained by control of fissile materials, bioweapon construction is not nearly so difficult a challenge for terrorists, according to experts testifying before the House Subcommittee on Prevention of Nuclear and Biological Attack.

The Centers of Disease Control have identified 60 pathogens that federal scientists consider dangerous and in need of controls and devlopment of countermeasures, such as vaccines, according to a panel member, James R. Langevin, D-R.I.

Langevin pointed out that supplies, such as DNA and growth media, that might be of use to bioterrorists can be obtained by mail-order.

Government, university and pharmaceutical research programs are involved in a wild scramble to develop biotech in the fight against disease, the engineering of superior crops and livestock and for varied and sundry other industrial purposes. For example, the federal Human Genome Project works hard to pass along a torrent of knowledge stemming from its work to the private sector.

Imposing controls on U.S. biotech research, however, makes little sense in the face of the industry's boom outside America, say experts who are pushing for more international safeguards -- arguing that the biological weapons treaty is inadequate. They note that China -- still straddled by authoritarian communism despite the fond hopes of the U.S. policy of "engagement" -- is a hub of biotech research, much of it intertwined with U.S. business.

Germ war expertise for sale

Nevertheless, regardless of the outcome of claims concerning Iraq biowar capabilities, other Middle Eastern states, perhaps employing ex-Soviet germ war scientists, also have the capability of posing major threats, according to experts. Iran is a central concern.

The Soviet Union ran a vast and dangerous germ warfare research program, known as Biopreparat, and once headed by Kenneth Alibek, who is a now a U.S. biowar consultant. Alibek testified in the July 2005 hearing that in the 1980s his experts were exploiting new discoveries in genetic engineering to create AIDS-type pathogens that were intended to subvert victim immune systems.

Alibek said lawmakers should focus on the fact that a new pathogen, perhaps resistant to antibiotics, can be formed by simple genetic engineering. "This knowledge exists; this knowledge is, let me say, widely published; and there is no significant problem to developing genetically engineered pathogens."

However, once a pathogen is engineered, terrorists still face the problem of brewing up large enough batches, though that problem is not as difficult as it once was, because the boom in genetic technology has resulted in the downsizing of key equipment.

Alibek said that the knowledge and capability is already in place for state-supported groups to produce biowar weapons but he was cautious about the thought that "low-level terrorist groups" might already be capable of such technology.

However, others voiced concerns about the possibility of "garage hackers" producing new biological pathogens rather than computer viruses. Interest in gene-splicing and DNA information is growing among amateurs, according to a July 2006 report in Wired magazine (see link above). Wired also cites the case of two professors caught up in bioterror fears over one's amateur interest.

Gene-splicing knowledge abounds

Increasing numbers of people have access to such information, according to witness Roger Brent, director of the Molecular Sciences Institute and a Pentagon consultant. Research into recombinant DNA is more than 30 years old, and the genetic technology revolution is proceeding exponentially, analagous to the accelerating pace of computer efficiency, he said.

As a consequence, Brent said, great potential benefits for humanity are clouded by the fact that there are tens of thousands of people who have the knowledge to engineer drug-resistant anthrax, or who could remake the savage SARS virus, or who might augment existing organisms to make them more deadly. Though the 2001 anthrax attacks showed the hand of an experienced scientist, biowar knowledge is no longer the province of a few shadowy specialists, witnesses said.

Brent aired the scenario of a group of militants who inflict themselves with a highly contagious disease, such as reformulated SARS, who cough on people with the consequence of millions of deaths.

The threat from cult terrorists, who might not be concerned with preserving a particular population, is illustrated by the cult Aum Shinrikyo, which killed 20 people in a Japanese subway using the deadly toxicant Ricin in 1995. The group turned to Ricin after experiments with microbial warfare succeeded only against cult members, it has been reported. But another cult might prove more successful.

James Watson, co-discoverer of the double helix encodement of DNA, has said that the perils of genetic engineering were foreseen in the 1970s, but money pressures eventually broke the moratorium on such research. Watson eventually broke ranks and joined those who favored experimentation.

Other experts have warned that the recombinant DNA genie is already having unknown, but far-reaching consequences in the global ecology, as genetically modified plants and animals escape into the wild and, following classical environmental pressures, mutate and diversify. Some experts say there is no way to know whether such a mutant will eventually lead to a major extinction event that could include the human race (though this fear also applied prior to genetic engineering).

Brent said there is no easy solution to the biodefense problem, but warned that programs to stockpile vaccines are likely to be ineffective in that germ war specialists would simply design a pathogen that circumvents the vaccine. Specifically, anthrax can be modified to sidestep the current vaccine, he said.

The anthrax threat is still with us

Genocidal weapons are not the only concern. In 2001, Alibek noted, a relatively small amount of weaponized anthrax -- 5 to 7 grams -- sent through the mails resulted in months of uncertainty and large sums of money spent to defuse public anxiety and counter the contamination.

Anthrax, which does not easily spread from one person to the next, could still be aerosolized and sprayed into, for example, subway tunnels. The effect on the public would be so great as to perhaps warrant the permanent closure of the underground system, Alibek said.

Michael V. Callahan, an expert on biodefense and mass casualty care who in July 2006 was employed by the Defense Advanced Research Projects Agency, or DARPA, warns of 200 laboratories in sub-Saharan Africa, a number of them in the hands of Islamic fundamentalists, which have the capability to isolate and purify anthrax and plague pathogens. These laboratories run across these organisms in normal veterinary and medical work, he said.

Disseminaton of products -- called reagants -- for amplifying such pathogens must be monitored, he said, though such technology is easy to get. Callahan also cited a test whereby experts found that they could produce 14 million lethal doses of anthrax for a reagant cost of less than $100.

The people who ran the bioterror test obtained all their information from open sources, including the U.S. Patent Office and out-of-date microbiology books, Brent emphasized. Much DNA information has been patented by genetic technology businesses.

In what he called an "exciting" development, Callahan, who has assisted in the decommissioning of Biopreparat operations, noted that the Soviet bioweapons program had included development of recently disclosed countermeasure drugs that strengthen the immune system.

Possibilities are getting worse

However, Callahan reported that the world of bioterror has, if anything, grown grimmer since the collapse of the Soviet Union and its germ war program. "Our scientific understanding of microbial metabolism and the improved efficiency of automated small scale fermenters have increased the amount of vegetative bacteria that can be produced with minimal resources," he said. Very troubling is the growing availability of small-scale fermentation systems which reduce the need for skilled technicians and a major support structure, he said.

"Potentially, a former weapons scientist from Stepnogorsk could travel to a country in the Middle East and reconvene a weapons capability from available veterinary, agricultural and clinical microbiology resources," he said.

The witnesses did not address the issue of Iraq's purported program for weapons of mass destruction, though Callahan's testimony indicates that Saddam Hussein would have had little trouble in implementing such a program, had he wished. Hussein's biowar stocks appear to have been destroyed after the first war with the United States though President Bush has said he was convinced that Hussein was hiding such weaponry prior to the second war with the United States. However, U.S. military authorities made little effort to find the purported germ war stocks in the immediate aftermath of the invasion.

Advances in understanding of lung airflow that have benefited numerous respiratory patients are also available to designers of anthrax borne on aerosols, Callahan warned. Specially coated anthrax spores would penetrate lungs after the fashion of the new class of lung medications, he said.

He also pointed out that biowar pathogens can be engineered that evade vaccines.

Development of such superbugs, however, is not necessarily cost-effective. A military biowar unit might find that coming up with an effective contagiously spread pathogen is too time-consuming. Merely because a pathogen is initially virulent doesn't mean it is stable after many replications. It might have a tendency to peter out, to mutate into something relatively innocuous. However, a group of terrorists might be willing to try an untested organism and, against the odds, succeed at killing millions, experts say.

The Kaczynski factor

Concerned about this point, subcommittee Chairman John Linder, R-Ga., asked whether someone with a "modicum of talent in this business" might genetically alter the SARS virus and "make it more virulent, spread faster and make it more difficult to treat?"

The "short answer is yes," replied Brent, though the recombinant virus might actually be weaker than the original.

Still, resynthesized SARS spread by suicidal coughers is a real concern, said Brent.

Anthrax, though not contagious in humans, is the more serious threat, said witnesses, Callahan noting that "you don't have to store it, it lives forever, and you don't have to feed it." The pathogen is also easy to obtain because the disease afflicts animals in many places, he said.

However, Callahan put avian influenza -- bird flu -- as a top concern because of its extreme mortality in humans. If a mutated bird flu pathogen becomes contagious among humans and remains extremely deadly, it could kill some 50 million people worldwide, experts have said. Artificial alteration of the pathogen is a severe worry, Callahan testified. Still, "new inhibitor" drugs are available against bird flu, and biowar experts might face obstacles in getting past these defenses, he conceded.

Another big concern is the possibility that smallpox, once considered eradicated, might be bred from some old Soviet stash. Treatment of smallpox is difficult.

Other pathogens potentially subject to terrorist manipulation include famine-inducing microbes, such as Glanders and zoological agents, that might wreak havoc among livestock and agriculture, said Callahan. Another top concern, he said, is the engineering of microbes resistant to light, making them difficult to decontaminate.

Of keen interest to microbiologists are the thermophiles, microbes that thrive in extreme heat. Other microbes consume metals and are of interest to the military as a means of weakening enemy infrastructure.

Porous biodefenses

Though the United States has drastically improved security of biohazard stocks, said Callahan, such safeguards are "easily circumvented by the novel engineering of a new agent" and "getting a new anthrax strain out of Texas, South Dakota or Maine" can be accomplished within a few days, he said.

Not only is intentional terrorism a worry, but a new concern is adolescent hackers, who maliciously send out deadly bugs without fully realizing what they are doing.

One lawmaker worried that "already the technology exists to resynthesize small viral genomes," a technology that might easily fall into the hands of DNA hackers.

Callahan expressed alarm at the easy availability of biotech knowledge that is spreading like wildfire as biotech businesses and research surges. He said that in the first third of last year, "there are 19 papers that have been produced which provide heavy, excellent answers for the challenges facing a biological weapon scientist" working in some mountain cave lab.

Callahan said the rate of open-source publication of biotech papers was outpacing the Homeland Security Department's ability to monitor them to assess the threat of the published information. "We are just picking up the big stuff, and we are probably about a year behind. We have received several red alerts this month for publications that will show up next month."

Additionally, amateurs and potential "garage hackers" have increasing access to biotech information and new portable equipment, he said.

Brent told lawmakers that he was unconvinced that there were any good means of choking off terrorist access to germ war technology.

Though experts seem wary that DNA-tech savvy teenagers pose an imminent threat, there is the 1995 report of the Detroit Boy Scout building a nuclear reactor at home, using local pitchblende ore and components available at Home Depot. And a National Aacademies report said that high school students routinely do recombinant DNA experiments.

Problems of surveillance

Such worries have undoubtedly strengthened the hand of those who argue that the Bush administration's use of extraordinary surveillance measures is well justified. In particular, the use of network theory might help monitors to zero in on threats, though mathematicians are not unanimous on the efficacy of such programs. The problem of "false positives" may put monitors in the position of "crying wolf" too often.

Callahan suggested that a new technology was needed, whereby detection equipment was not focused on a single pathogen, but on changes in various pathogens. Callahan is currently heading DARPA research into biowar countermeasures.

Brent urged a "greatly beefed-up World Health Organization" that could be used in efforts to monitor possible biowar activities.

Callahan said WHO's bioterror awareness had improved but Alibek cautioned that "the international community" is inadequately involved in biodefense.

Alibek said DARPA was doing sophisticated work in anthrax defense and urged passing on these countermeasures for public use but Brent said a foe would simply strike with something other than anthrax.

The experience of coping with SARS, or severe acute respiratory syndrome, demonstrates that biodefense authorities are not in an easy position, experts said. In Asia in 2003, the SARS virus killed 10 percent of the 8,000 people who were sickened by it.

Another concern is the possible engineering of pathogens that target specific DNA subgroups, informally known as "races." Since some diseases, such as sickle-cell anemia, are specific to racial type, it is a concern that a malicious group might bio-engineer a pathogen intended to wipe out a particular race.

The witnesses did not discuss the possibility of nanotech terrorism. However, as nanotechnology and nanomedicine gain ground, the fear is likely to worsen.

Nano-computers and nano-machines -- devices that are no bigger than a few atoms -- are in the developmental stages. At some point, they may be used in medicine to enter the body to control molecular interactions. Some have foreseen the possibility of self-replicating nano-robots, which, if misused, could swarm through a victim like a microbial infection -- with devastating results.

In May 2006, Anthony S. Fauci, director of the National Institute of Allergies and Infectious Diseases, or NIAID, re-emphasized that "we cannot become complacent" about bioterror threats. Fauci's agency, which is part of the National Institutes of Health, has been undertaking research into vaccines against anthrax and other bioterror threats.

In a Nature article published after the 2001 anthrax attacks -- which killed four people and forced 30,000 others to take antibiotics -- Fauci and fellow agency scientists, pointed out that, in the event of a bio-attack, the appropriate antibiotic regimen and duration of treatment can be uncertain.

The NIAID has identified three categories of potential bioterror agent:

Category A. Anthrax, botulism, plague, smallpox, tularemia ("rabbit fever") and viral hemorrhagic fevers.

Category B. Q fever (carried by livestock), trucellosis, Glanders, ricin toxin and staphylococcus enterotoxin B1.

Category C. Nipah virus, Hanta viruses, tick-borne encephalitis viruses, yellow fever, drug-resistant tuberculosis.

These categories, however, do not adequately address emerging bioterror threats, according to a panel of experts writing for the federally funded National Academies, which focus on science and technology.

Two reports, one in 2004 and another in 2006, by National Academy experts stress the need to develop a comprehensive security structure within the biotech arena, whereby scientists, journal publishers and others continually watch for potential threats from wide dissemination of information.

But, the 2006 report found that censorship is not an easy issue. Commenting on the furor over publication of the method of altering the mousepox virus that made it more vicious and immune to vaccine, the panel said the technology the authors cited -- incorporating the IL4 gene into the mousepox genome -- has been known for decades. Similarly, the panelists said, the synthesis, from scratch, of the poliovirus genome, was accomplished with well-known methods. Though such replication might pose a threat, in this case the poliovirus was considerably weaker than wild strains, probably because of synthesis methods.

Also, the very knowledge that is needed to identify how a pathogen works so that it can be combated is potentially of use to a bioweapon maker, experts say.

The 2006 National Academies report identifies technologies that seek to:

* Acquire new biological or molecular diversity.

* Generate new but predetermined and specific biological or molecular entities via directed design.

* Understand and manipulate biological systems in a more comprehensive and effective manner.

* Enhance production, delivery and packaging of biologically active materials.

Of particular concern are transfer of antibiotic resistance to microbes, modification of a microbe's antigenic properties, modification of a microbe's stability in an environment, and transfer of pathogenic properties to a microbe.

The 2004 National Academies report outlined seven types of experiment that should be watched:

* How to render a vaccine ineffective. A vaccine-resistant smallpox strain could prove devastating.

* How to make pathogens resistant to antibiotic and antiviral drugs.

* How to increase the transmissibility of pathogens, whether within or between species.

* How to alter the range of the pathogen -- that is, making it a danger to more lifeforms.

* How to evade diagnostic testing for a disease, through use of microencapsulation or alteration of gene sequences to change the DNA fingerprint.

* How to enable the weaponization of of a biological agent or toxin. Example: synthesis of the smallpox virus.

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Conant to Reporters Committee for Freedom of the Press