The Nipah virus that has apparently spread from pigs to humans highlights the increasing evidence that disease-causing microbes are breaking þspecies barriersþ as they cross over from animals to people. This process is now thought to be caused by þhorizontal gene transferþ which must be more properly understood if we are to prevent the outbreak of more new diseases.

by Martin Khor

It is now confirmed that the epidemic causing brain damage and death in Negri Sembilan and Perak is mainly caused by a newly discovered virus, named the Nipah virus.

This has similarities with the Hendra virus and distinctly different from the Japanese encephelatis virus. Whilst the latter is spread via the culex mosquito, it is not clear how the Nipah virus is spread.

What seems certain is that the Nipah virus is transferred from pigs (some of which have in the affected areas also been afflicted with a similar disease) to people who have been involved in handling pigs.

The virus attacks the brain, causing many of the victims to go into a coma and some to die.

In Australia, the hendra virus was apparently spread from the fruit bat to horses, and from horses to a few people who handled the horses.

The deaths and sickness caused by the Nipah and hendra viruses underline public concerns about the rise of new diseases as well as how infection-causing microbes have found ways to cross over from surviving in one species to another. For example, viruses that used to inhabit animals such as pigs, monkeys or cows, can also now affect human beings. This "breaking of species barriers" has emerged as a critical part of the chain of events causing the global rise in infectious diseases. In many cases, specific viruses, bacteria and other microbes exist only in specific organisms (plants, marine life, insects, animals or humans). Thus, a microbe is often "host-specific", surviving only within one or a narrow range of life-forms, and unable to transfer to or live within other organisms. But some new diseases have emerged as viruses that used to only inhabit animals were able to "cross species barriers" and infect humans. It is widely believed that the crossing of the HIV virus from monkey to humans led to AIDS whilst the crossing of a virus from an animal (yet to be identified) to humans is believed to be the source of the Ebola disease, which first appeared in 1976.

In the case of the so-called "Mad Cow Disease", this infection is believed to have originated in sheep, then transferred to cows, causing BSE (bovine spongiform encephalopathy). It is then passed via an infectious agent, known as a prion protein, through beef consumption to humans to cause CJD (Creutzfeldt-Jakob Disease). Microbes which used to exist in one or a narrow range of host organisms are broadening their host range, and when this includes humans, the result is the emergence of new diseases or new varieties of existing diseases which are harder to treat. The process is known as "horizontal gene transfer" or the transfer of gene by infection, between species that do not interbreed and are unrelated. This has been known to occur among bacteria and viruses for at least 20 years. It used to be thought that horizontal gene transfers could not involve humans because there are genetic barriers between species, according to Dr Mae-Wan Ho, a scientist at the Open University in the United Kingdom. But in recent years the full scope of horizontal gene transfer has come to light. Dr Ho says the evidence shows that transfers occur between very different bacteria, between fungi, between bacteria and protozoa, between bacteria and higher plants and animals, between fungi and plants and between insects.

"There is even a report of a gene that has jumped from fruitflies to humans where it causes a neurological wasting disease," said Dr Ho. The genes can be transferred through conjugation (or the mating process); transduction (transfer with the help of viruses); or transformation (direct uptake of DNA by the bacteria). Horizontal gene transfers have occurred in the past but they were relatively rare among multicellular plants and animals. A new fear by some scientists and ecologists is that genetic engineering could greatly accelerate gene transfers. In a paper, Dr Ho and Dr Beatrix Tappeser (from the Institute of Applied Ecology in Germany), explains that genetic engineering technology is designed to enable genes to cross species barriers.

"It recombines genetic material in the laboratory between species that have very little probability of exchanging genes otherwise." Drs Ho and Tappeser explain it is not easy to transfer genes naturally between species, as there are cellular mechanisms to excise or inactivate foreign genes. Genetic engineering is designed to break these natural barriers so that a gene from one species can be transferred into another. The technology uses artificially constructed parasitic genetic elements including viruses as "vectors" to multiply copies of genes and in many cases to carry and smuggle genes into cells (of the target plant, animal or human being) which normally exclude them.

Thus, transgenic organisms are made carrying the desired transgenes. The vector is used to enable the gene to more easily cross the species barrier successfully. "Vectors are now increasingly engineered to overcome the cellular defence mechanisms, thus further undermining the ability of the species' system to resist invasion by exotic genes carried on such transgenic vectors," said Drs. Ho and Tappeser.

"Many unrelated bacterial pathogens, causing diseases from bubonic plague to tree blight, are now found to share an entire set of genes for invading host cells, which have almost certainly spread by horizontal gene transfer. "There is sufficient evidence that horizontal gene transfer is responsible for the emergence of both old and new pathogens, and for the evolution of multiple antibiotic resistance. "We certainly do not need any more releases of transgenic organisms that would provide yet more vehicles for horizontal gene transfers." Dr Ho said that there is no evidence (at least not yet) that genetic engineering has been responsible for the spread of drug resistance in bacteria, or for creating new pathogens. She stressed, however, that genetic engineering is inherently a technology that increases the likelihood of horizontal gene transfer and thus has the potential of spreading resistance and contributing to new diseases. Of topical interest to Malaysians (given the Nipah virus) is Dr Hoþs concern about research being conducted to make "transgenic pigs" with organs suitable for transplanting to humans. The pigs are genetically engineered so that the pig organs would not be rejected in humans after transplantation. "This is worrying because the there is a possibility that pig viruses may then be able to cross species barriers to affect human beings." Dr Ho said that a laboratory experiment had shown that if pig viruses were cultured in human cells for only one generation they would already be able to infect human cells. She called for a moratorium on environmental releases of transgenic organisms and the marketing of transgenic foods to be imposed until the possibility of horizontal gene transfer and its consequences can be fully assessed.

Martin Khor is the Director of Third World Network.