|Killer virus sparking biotech fears
by Martin Khor, Third World Network
The potential hazard of applying genetic engineering for medical purposes was dramatically publicised last week when Australian scientists revealed they had accidentally created a killer version of the mousepox virus that killed all the mice in their experiment.
If the same method had been used on the smallpox virus (which is similar to mousepox), it may have resulted in a more dangerous form of that virus that can destroy the immune system and thus be extremely lethal to humans.
Hundreds of experiments are taking place around the world in which scientists genetically modify viruses and bacteria. As the Australian case has shown, it is possible for new dangerous viruses to be created, with or without the intention of the scientists, and with potentially catastrophic health consequences.
Last week's revelation is likely to spark a major controversy on the need to strictly regulate genetic engineering research, experiments and use in animals and humans.
In recent there have been serious concerns, and many public protests, regarding genetic engineering. However, they have mainly focused on its use in agriculture and on the safety of genetically-modified foods.
The Australian mousepox case can be expected to cause similar concerns on the use of genetic engineering in medical applications and purposes, or for biological warfare and acts of terrorism.
The scientists who carried out the experiment have themselves publicised the dangers that can arise from it, warning that terrorists could without much difficulty use their method to develop a new lethal strain of smallpox to carry out biological warfare.
"We discovered that if we modified this virus in a particular way then suddenly animals were dying that would normally be resistant to the virus," said Bob Seamark, the head researcher, according to an AFP news report.
"It was a concern that this same modification could be made to human viruses and this would enhance their virulence or at least strengthen their ability to kill people."
Seagate and the Cooperative Research Centre issued a global warning to guard against misuse of their research.
Another scientist, Annabelle Duncan, called for the tightening of the Biological Weapons Convention to make it "very, very hard" for terrorists to use the results of scientific research to create deadly new weapons.
Duncan is molecular science chief at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) which helped create the virus, and was formerly deputy leader of a United Nations team that investigated bio-warfare agents in Iraq.
Whilst it is right for the researchers to warn about the misuse of scientific data by "bio-terrorists", equal attention should also be paid to the hazards posed by scientific research and experiments, including those like the Australian case, that may be perfectly legal but nevertheless potentially harmful.
What if the new lethal mousepox virus escapes from the laboratory and moves freely about? And, worse, what if genetically-modified viruses that can cause more lethal versions of life-threatening human diseases (such as smallpox) or even new diseases.
The Australian case was first reported in the New Scientist magazine last week, and then was publicised worldwide through the BBC and major news agencies.
The New Scientist report began dramatically as follows: "A virus that kills every one of its victims, by wiping out part of their immune system, has been accidentally created by an Australian research team. The virus, a modified mousepox, does not affect humans, but it is closely related to smallpox, raising fears that the technology could be used in biowarfare."
The researchers were trying to make a mouse contraceptive vaccine for pest control, and did not intend to produce a killer virus.
Two scientists, Ron Jackson of CSIRO and Ian Ramshaw of Australian National University inserted into a mousepox virus a gene that creates large amounts of a molecule, interleukin 4 (IL-4), that is naturally found in the human body. The molecule was supposed to stimulate antibodies against mouse eggs, and thus make the mice infertile.
The mousepox virus was used as a vehicle to transport the egg proteins into mice to trigger an antibody response and the gene for IL-4 was added to boost antibody production.
"The surprise was that it totally suppressed the cell-mediated response--the arm of the immune system that combats viral infection," says the New Scientist report.
Mice normally suffer only mild symptoms from mousepox, but with the added gene, it killed all the mice in nine days. "It would be safe to assume that if some idiot did put human IL-4 into human smallpox, they'd increase the lethality quite dramatically," said Jackson.
Moreover, the modified virus is unusually resistant to vaccine as the vaccine applied to the mice to protect them against mousepox worked in only half the mice exposed to the killer version. If a human version of the virus is created, vaccination programmes would be of limited use.
In light of the incident, the New Scientist report poses a vital issue: "Is it possible that research into new vaccines against cancer and other diseases could inadvertentl create lethal human viruses? Many of the most promising modern vaccines depend on viruses to transport genes into the body, and contain genes that directly alter the immune response.
"But researchers have not been too concerned because the evidence until now suggested that changes in the genetic make-up of viruses invariably makes them less virulent, not more."
Meanwhile the researchers decided to go public with the results of their experiment.
"We wanted to warn the general population that this potentially dangerous technology is available," said Jackson. "We wanted to make it clear to the scientific community that they should be careful, that it is not too difficult to create severe organisms."
The warning by these scientists poses many questions. What if they had covered up instead? How many other scientists have been involved in genetic engineering research that also resulted in lethal viruses, but who did not publicise the findings, or who did not even know the effects their modified organisms are capable of?
Are there adequate regulations to prevent the production and spread of potentially dangerous modified viruses and bacteria? Do the authorities in each country and in international agencies even keep tabs of the experiments going on?
In view of the seriousness of the Australian case, these questions need to be answered, and extreme caution is required, before an accidental (or even an intentional) release of deadly microbes takes place.
The emergence, spread and effect of the AIDS virus is an outstanding example of the devastation a new virus or bacterium can inflict on human lives and health, in this case a virus that damages or destroys the body's immune system.
Last week's news that a new virus was created in a laboratory that can kill all its victims by wiping out an important part of their immune system should serve as a warning for regulatory action to be taken before it is too late.
New Scientist, January 10 2001
An engineered mouse virus leaves us one step away from the ultimate bioweapon
A virus that kills every one of its victims, by wiping out part of their immune system, has been accidentally created by an Australian research team. The virus, a modified mousepox, does not affect humans, but it is closely related to smallpox, raising fears that the technology could be used in biowarfare.
The discovery highlights a growing problem. How do you stop terrorists taking legitimate research and adapting it for their own nefarious purposes?
The Australian researchers had no intention of producing a killer virus. They were merely trying to make a mouse contraceptive vaccine for pest control. "But it's a good way to show how to alter smallpox to make it more virulent," says Ken Alibek, former second-in-command of the civilian branch of the Soviet germ-warfare programme.
Ron Jackson of CSIRO's wildlife division and Ian Ramshaw at the Australian National University, both in Canberra, inserted into a mousepox virus a gene that creates large amounts of interleukin 4. IL-4
is a molecule that occurs naturally in the body. As part of a study aimed at creating a contraceptive vaccine, they were trying to stimulate antibodies against mouse eggs, which would make the animals infertile. The mousepox virus was merely a vehicle for transporting the egg proteins into mice to trigger an antibody response. The researchers added the gene for IL-4 to boost antibody production. The surprise was that it totally suppressed the "cell-mediated response"--the arm of the immune system that combats viral infection.
Mousepox normally causes only mild symptoms in the type of mice used in the study, but with the IL-4 gene added it wiped out all the animals in nine days. "It would be safe to assume that if some idiot did put human IL-4 into human smallpox they'd increase the lethality quite dramatically," says Jackson. "Seeing the consequences of what happened in the mice, I wouldn't be the one who'd want to do the experiment."
To make matters worse, the engineered virus also appears unnaturally resistant to attempts to vaccinate the mice. A vaccine that would normally protect mouse strains that are susceptible to the virus only worked in half the mice exposed to the killer version. "It's surprising how very, very bad the virus is," says Ann Hill, a vaccine researcher from Oregon Health Sciences University in Portland. If bioterrorists created a human version of the virus, vaccination programmes would be of limited use.
Alibek, who now works on developing novel treatments for anthrax for the defence contractor Hadron in Virginia, says this highlights the drawback of working on vaccines against bioweapons rather than
treatments. "I'd say any vaccine could be overcome by one or another genetically engineered virus or bacterium," he says.
Is it possible that research into new vaccines against cancer and other diseases could inadvertently create lethal human viruses? Many of the most promising modern vaccines depend on viruses to transport genes into the body, and contain genes that directly alter the immune response. But researchers have not been too concerned because the evidence until now suggested that changes in the genetic make-up of viruses invariably makes them less virulent, not more. One way to reduce the risk, says Gary Nabel of the National Institutes of Health, is to use only viruses that cannot replicate. "There are some replication-competent [viral vaccines] around, but there is increasing concern about their use," he says.
Defence experts are also worried about preserving the freedom to publish medical findings while trying to stop the information falling into the wrong hands. According to D. A. Henderson, a former US presidential adviser, and director of the Center for Civilian Biodefense Studies at Johns Hopkins University in Baltimore, what are effectively blueprints for making microorganisms more harmful regularly appear in unclassified journals. "I can't for the life of me figure out how we are going to deal with this," he says.
The Australian researchers consulted their country's Department of Defence before submitting the work for publication, and only decided to go ahead after considerable thought. A report will appear in a February issue of the Journal of Virology. "We wanted to warn the general population that this potentially dangerous technology is available," says Jackson. "We wanted to make it clear to the scientific community that they should be careful, that it is not too difficult to create severe organisms."