Scary Near-Miss Shows Bioterrorism Vulnerabilities

By Laurie Garrett

Council on Foreign Relations, February 16, 2005


Shortly before Christmas, some genetic data was--as a matter of routine--posted with GenBank, a mammoth, publicly accessible computer repository located at Los Alamos National Laboratory in New Mexico. No special phone calls were made, no alarms sounded. But the GenBank posting looked like the genetic code for a new, manmade killer influenza that was infecting pigs in South Korea. Fingers seemed to point to Pyongyang.

Before you have a heart attack, let me assure you that, two months later, it looks like the nightmare of weaponized super-flu did not happen this time. But the scenario that played out is probably pretty close to what might unfold in a genuine bioterrorism incident, and it reveals critical weaknesses in our global security system--or lack thereof.

In December, somebody from one of South Korea´s veterinary schools did what hundreds of virus-hunters do the world over: he or she e-mailed to GenBank the genetic details of newly identified viruses. In this case, the posting said, six new strains of influenza had been found in local pigs. Each of the strains were genetically manipulated and contained genetic bits of an avian virus unlike those now prompting separate bird flu concerns.

Worse, there were large segments of a flu bug dubbed WSN/33, a human flu virus altered in 1933 in a laboratory by infecting mice, resulting in a strain that kills mouse brain cells. The original 1933 human virus was related to that which caused the 1918 pandemic flu, killing an estimated 50 million people. Nothing even remotely like the WSN/33 flu has circulated in the world since 1956, and this particular WSN-avian flu combination is not known to have ever occurred naturally, so most of the global population would have little or no immunity to the virus. Since neither the particular bird flu strain nor the WSN/33 flu were known to exist outside of laboratories, one Internet journal concluded that "these sequences could represent a military experiment that resulted in an unplanned release. Moreover, at this point, bioterrorism cannot be ruled out."

The World Health Organization´s (WHO) influenza branch responded later in December, convening a teleconferenced meeting of flu experts to analyze the GenBank information and exchanging a flurry of e-mails. They concluded somebody had made a lab error. On January 27, the South Korean government confirmed a laboratory error had been made and promised to send samples of the six viruses to WHO´s Hong Kong collaborative lab.

But at press time the South Koreans had not sent the promised samples. Internet chatter about possible North (or South) Korean bioweapons experiments persists. This is dangerous.

What happened? Nobody, except perhaps the silent South Koreans, knows for sure. But there are two general hypotheses, WHO says. Someone in the South Korean veterinary lab may have innocently pulled the wrong computer file of genetic sequence data into an e-mailed transmission to GenBank, resulting in the display of this potentially terrible viral code. The lab in question may have contaminated its research samples. Or the South Korean lab is working on a flu vaccine, using the WSN/33 human sequence from 1933 as a basic template and deliberately scrambling it with various animal flus. In such a scenario, the scientists accidentally created these disturbing influenza strains in the lab in their vaccine production effort. I cannot accept the vaccine idea: why in the world would anybody be making a vaccine against a type of human flu that hasn磘 circulated on earth for more than 70 years? If lab contamination or data input error are the problem, I am left to fret about a host of recent lab accidents that, in some cases, have allowed dangerous microbes to leak, including SARS and tularemia.

If we are seriously concerned about the possibility that nefarious individuals or groups might make bioweapons using state-of-the-art genetic manipulations, the chain of events leading to recognition that such experiments were under way might look very much like what occurred with these Korean swine strains. The WHO would be under pressure--by international agreement under the Bioweapons Convention of 1972--to definitively prove, or disprove, allegations. Does WHO have sufficient funding, manpower, and clout to do this job at this time? No. The core budget of WHO is a mere $400 million and only two scientists are employed full time to monitor new epidemics and rumors of bioterrorism. An additional handful of full-time staff leads efforts to monitor flu strains around the world.

Many within WHO and the global health community are uncomfortable with the prospect of building a significantly larger bioweapons verification and surveillance program at the Swiss-based United Nations agency, fearing it will undermine the organization´s ability to open doors in its 192 member nations to work on HIV, tuberculosis, measles, and other diseases that, combined, kill tens of millions of people every year. They are right to be worried. We are therefore in a credibility Catch-22: Overemphasis on weapons threats could undermine the credibility of WHO´s primary mission, but no other organization has sufficient credibility worldwide to referee and investigate bioweapons claims. Guy Roberts, head of the U.S. delegation to biological weapons negotiations, publicly confirmed in August that the Bush administration supports WHO´s prime role.

It is likely that future claims will, as was the case in this Korean incident, focus on hotspots of geopolitical tension. In such an environment, even an unproven claim could have serious political consequences. Indeed, one can imagine "evil-doers" deliberately posting false virus information on GenBank in order to discredit a given country or cause unjustified panic. How can we tolerate such imprecision in our post-9/11 world?

I am reminded of a bioweapons meeting I attended in Geneva several years ago during which Pakistan and India exchanged charges that each had released germs aimed at the other´s crops. There was no evidence to support these claims, but the respective countries could make things "true" merely by constant repetition. To this day, there are prominent political figures and news organizations in India that insist the country´s 1994 pneumonic plague outbreak was the result of a genetic engineering experiment carried out in Kazakhstan by the CIA, under the supervision of the American Ambassador to Delhi--a bizarre, patently false concept. A recent poll of African Americans revealed more than half believe HIV is a virus designed by the U.S. government to kill black-skinned people--a sentiment echoed by the recipient of the 2004 Nobel Peace Prize. Even as I write these words, I worry that my efforts to dismiss the current Korea allegations could backfire, fueling conspiracy fires. Clearly, this is an unacceptable dilemma.

We desperately need timelier, directed means of global--not just American-- surveillance and verification against bioterrorism. But investment in poor and middle income countries?disease surveillance is abysmal-to-nonexistent. Though President Bush´s proposed FY2006 budget would devote $4.2 billion to bioterrorism preparedness, nearly every penny would be spent inside the United States, and the Centers for Disease Control would, overall, take steep cuts. The lion´s share of the funding would go to the National Institutes of Health for research on diagnosis and treatment of likely bioterrorist diseases.

I hope that Senate Majority Leader Bill Frist (R-Tenn.), who last month called for a "something that even dwarfs the Manhattan project" for bioterrorism, is paying attention. The problem right now is not a few billion dollars worth of fancy technology. It is much more basic than that, costs a lot less to fix, and isn磘 inside Fortress America.

Recombinomics Commentary
February 22, 2005

>>  If we are seriously concerned about the possibility that nefarious individuals or groups might make bioweapons using state-of-the-art genetic manipulations, the chain of events leading to recognition that such experiments were under way might look very much like what occurred with these Korean swine strains. The WHO would be under pressure--by international agreement under the Bioweapons Convention of 1972--to definitively prove, or disprove, allegations. Does WHO have sufficient funding, manpower, and clout to do this job at this time? No. <<

As more and more announcements on the looming flu pandemic hit the news services and the public realizes that pandemic preparedness in 2005 is not much better than it was in 1918, the issue of bioterrorism preparedness is again being raised. The bird / human  flu situation in South Korea is being cited as a "scary near miss" to show how unprepared the US is for bioterrorism.

However, the characterization of the WSN/33 situation in pigs on farms in South Korea is clearly not in the "near miss" category at this time.  The situation is unresolved and although several explanations have been offered, the likelihood of the explanations being correct is very close to zero.

The WSN/33 are clearly on deposit at GenBank and Los Alamos and publicly available.  They were deposited at GenBank on Oct 24, 2004 and were publicly available at the end of November.  WHO was notified in early December about potential public health issues, and the possibility of Bioterrorism was also publicly raised in early December.

It is now 2 1/2 months later and the location and existance of the viruses is unresolved.  The Korean lab that isolated viruses and deposited the WSN/33 sequences says the sequences are in many pigs on many farms in Korea.

The human portions of the Korean swine sequences at the databases are clearly WSN/33 related and present in reassortants, which have human and avian influenza genes as well as recombined genes.

South Korea is calling the sequences a lab error and claiming that the WSN/33 sequences exist only in cyberspace and the sequences they generated point to yet another virus as the source of the human sequences.

Clearly someone is mistaken, but no one at this time can say who.

The South Korean official explanation certainly would fall into the "least likely" category.  There were six sequences on eight genes that were deposited at GenBank last year.  Of these 48 sequences, 30 are over 99% homologous to WSN/33 and virtually all are slightly different than WSN/33 and slightly different than each other.  Moreover, these differences are not random sequencing errors.  They are differences consistent with well defined rules of influenza evolution.

Since the Korean lab has indicated that it does not have WSN/33 growing in the lab, and the viruses were isolated in chicken eggs, it is hard to see how any WSN/33 would contaminate the viruses or the data.  Thus, at this time there is no credible data refuting the presence of these combinations in pigs.

The existence and location of the sequences is not an academic exercise.  WSN/33 is quite lethal in mice and two of the sequences are H1N1 which would be readily transmissible from human-to-human.  Since these sequences are from 1933, most people would be immunologically naive to these proteins, so infections in humans could have severe consequences.  Moreover, the sequences indicate the isolates have reassorted and recombined genes and recent data of 2003 isolates shows extreme genetic instability in South Korean isolates.  Not only were H9N2, H3N2, and H6N1 subtypes identified, but some of these genes were also recombinants.

Since South Korea is saying that there are no WSN/33 sequences in pigs and the data are lab errors, the source of these swine sequences is not being investigated.

Thus, the existence of the sequences in swine has not been resolved four months after they were placed on deposit at Genbank.

Bioterrorism and Pandemic Preparedness are interesting concepts, but avian influenza continues to evolve and gain pandemic potential as governments spin wheels, issue warnings, and hope for the best.