Bio-terrorism & SARS.

In the weeks that the "allied forces" were wreaking destruction and death in Iraq to hunt down Saddam Hussein and his elusive "weapons of mass destruction," a SARS epidemic has been criss-crossing continents carried by air-passengers and spreading like molecular cluster bombs that explode to liberate further millions of infectious particles soon after a target is struck.

SARS--Severe Acute Respiratory Syndrome--is a completely new infectious disease spread by human contact, and kills about 4% of the victims. The epidemic originated in Guangdong Province, South China.

The disease first struck in November 2002. In March 2003, Liu Jianlin, a 64 year-old medical professor who was involved in treating patients, went from Guangdong to Hong Kong to attend a wedding. He was taken ill soon after arrival and admitted to a hospital. He asked to be put into quarantine, but was ignored, nor did the hospital warn his contacts. As a result, nine guests in the hotel where he stayed caught the disease and carried it to Singapore, Canada, Vietnam and other hospitals in Hong Kong.

On February 10, news of the disease was posted on ProMed, an international e-mail notification service for infectious diseases outbreaks. By April 8, there were 2671 confirmed cases of SARS in 19 countries, and 103 deaths.

A palpable sense of panic gripped the health authorities around the world. "Mother nature is the ultimate terrorist," says an editorial in the journal Nature. "Powerless to stop the spread," says New Scientist magazine.

Eleven laboratories around the world participated in the hunt for the disease agent, a collaborative effort organized via teleconferencing, since March 17, by virologist Klaus Stohr at the World Health Organization (WHO) headquarters in Geneva.

Malik Pieris of the University of Hong Kong was the first to identify coronavirus (which causes colds and pneumonia) just four days later. This finding was replicated in other laboratories. The virus and antibodies against the virus were detected in many, though not all infected patients, but were not found in more than 800 healthy controls tested.

There is some remaining doubt, however, whether the coronavirus is the complete story. John Tam, director of virology at Prince of Wales Hospital in Hong Kong, found another virus, the human metapneumovirus in 25 out of 53 SARS patients, as have laboratories in Canada and Germany.

Metapneumoviru belongs to the family Paramyxoviridae, which includes viruses responsible for parainfluenza, mumps and measles.

Could it be that both viruses are bystanders of the disease while an as yet unidentified virus could be responsible for SARS?

The coronavirus was atypical. It rapidly infected cells in culture dishes, something that other human coronaviruses do not do. Viruses from the lung tissue in Toronto patients readily infected monkey kidney cells, and no known human coronavirus infects that cell line.

More detailed analysis using polymerase chain reaction (PCR) indicate that the new virus is not closely related to any known virus at all, human, mouse, bovine, cat, pig, or bird.

Furthermore, the virus was isolated from cell cultures only, and not from the tissues of patients. The PCR fragments of the new coronavirus were not detected in any healthy subject tested so far. But not all patients with SARS tested positive for one of the PCR fragments. Where did this new virus come from?

Genetic engineering super-viruses

While the epidemic has still to run its course, a report appeared in the Journal of Virology, describing a method for introducing desired mutations into coronavirus in order to create new viruses. A key feature of the procedure is to make interspecific chimera recombinant viruses. It involves replacing part of the spike protein gene in the feline infectious peritonitis virus (FIPV)--which causes invariably fatal infections in cats--with that of the mouse hepatitis virus. The recombinant mFIPV will no longer infect cat cells, but will infect mouse cells instead, and multiply rapidly in them.

These and other experiments in manipulating viral genomes are now routine. It shows how easy it is to create new viruses that jump host species in the laboratory, in the course of apparently legitimate experiments in genetic engineering.

It is not even necessary to intentionally create lethal viruses. It is actually much faster and much more effective to let random recombination and mutation take place in the test tube. Using a technique called "molecular breeding," millions of recombinants can be generated in a matter of minutes. In other words, geneticists can now greatly speed up evolution in the laboratory to create viruses and bacteria that have never existed in all the billions of years of evolution on earth.

Controlling bio-terrorism

John Steinbruner, University of Maryland arms control expert, has been calling for mandatory international oversight of inherently dangerous areas of biomedical research--specifically, an international body of scientists and public representatives to authorize such research.

He has taken the proposal to meetings of the American Association for the Advancement of Science and the World Medical Association in recent months, and in April 2003, to a London bio-terrorism meeting, sponsored by the Royal Society of Medicine and the New York Academy of Medicine.

The oversight system would be mandatory and would operate before potentially dangerous experiments are conducted. Access to results could also be limited to those who pass muster.

Requiring scientists, institutions and even experiments to be licensed "would have a devastating chilling impact on bio-medical research," said American Society for Microbiology (ASM) president Ronald M. Atlas. His answer is self-regulation, already in line with ethical requirements to prevent the destructive uses of biology.

The ASM orchestrated and supports a statement released February 15 by a group of major life sciences editors and authors, acknowledging the need to block publication of research results that could help terrorists. Critics say even the self-censorship espoused by the journal editors and authors group is an impediment to the rapid progress of science, which is the best way to defuse the lethal potential of some biological research.

But Steinbruner fears that self-regulation does not go far enough to head off terrorists.

Both Steinbruner and Atlas agree, however, that any effort to keep good science out of the hands of ill-intentioned people must be international to be effective. And both point to existing efforts to push a treaty making bio-terrorism an international crime.

Steinbruner and his critics, and the critics of his critics are all missing an important point. They have yet to acknowledge that genetic engineering experiments are inherently dangerous, as first pointed out by the pioneers of genetic engineering themselves in the Asilomar Declaration in the mid 1970's, and as we have been reminding the public and policy-makers more recently.

But what caught the attention of the mainstream media was the report in January 2001 of how researchers in Australia "accidentally" created a deadly virus that killed all its victims in the course of manipulating a harmless virus. "Disaster in the making: An engineered mouse virus leaves us one step away from the ultimate bioweapon" was the headline in the New Scientist article. The editorial showed even less restraint: "The genie is out, biotech has just sprung a nasty surprise. Next time. it could be catastrophic." The SARS episode should serve as a reminder of some simple facts about genetic engineering.

In the first place, genetic engineering involves the rampant recombination of genetic material from widely diverse sources that would otherwise have very little opportunity to mix and recombine in nature.

And, as said earlier, some newer techniques will create in the matter of minutes millions of new recombinants in the laboratory that have never existed in billions of years of evolution.

In the second place, disease-causing viruses and bacteria and their genetic material are the predominant materials and tools of genetic engineering, as well as for the intentional creation of bio-weapons.

And finally, the artificial constructs created by genetic engineering are designed to cross species barriers and to jump into genomes, to further enhance and speed up horizontal gene transfer and recombination, now acknowledged to be the major route to creating new disease agents, and possibly much more important than point mutations which change isolated bases in the DNA.

With genetic engineered constructs and organisms routinely released into the environment, we hardly need the help of terrorists. That may be why we are coming up against new epidemics of viral and bacterial diseases with increasing regularity. Mother nature is not the ultimate terrorist, we are.

What needs to be done instead?

It is pointless to control the publication of sensitive scientific results because there is nothing special about the recombination techniques--they are already well known. "The only way we'll ever understand these natural outbreaks is by first-rate science and getting it published," says Lynn Enquist, editor of the Journal of Virology, referring to the creation of a coronavirus that crosses from cat to mouse that's a routine part of a genetic engineering technique.

Open publication is only half of the story. The other half is the importance of biosafety. An international instrument for regulating biosafety already, exists--it is the Cartegena Biosafety Protocol agreed in January 2000, now signed by 43 countries including the European Union; though efforts to undermine it has continued unabated, principally by the United States, allies, and the biotech industry. All we need to do is to strengthen the Bio-safety Protocol both in scope and in substance.

There is also an urgent need for democratic input into the broad areas of scientific research that are to be supported by the public purse. Every sector of civil society has been called upon to be "accountable," even corporations, so why not scientists?

Note:

A long list of sources and references for this article is posted on ISIS Members' website: http://www.i-sis.org.uk/ full/BioTerrorismAndSARSFull.php The Institute of Science in Society, PO Box 32097, London NW1 OXR telephone: [44 20 8643 0681] [44 20 7383 33761 [44 20 7272 56361] General Enquiries [e-mail] Website/Mailing List [e-mail] ISIS Director [e-mail]

Mae-Wan Ho, Institute for Science in Society