A Darwinian view of AIDS

This is the story of the rabbit and the virus.

Rabbits were never meant to live in Australia. But a 19th-century game hunter thought otherwise and imported the creatures. Over the decades, they did what rabbits do best: multiplied and multiplied, until they became a major nuisance.

So, in the 1950s, Australian authorities introduced a viral disease called myxomatosis in a bid to eradicate the rabbits. And it worked -- but only briefly. In a matter of years, rabbits acquired the ability to resist the virus.

It is a classic tale of evolution -- a story that unspools again and again in animals, people included. The march of human civilization, measured both by survival and suffering, is framed in many respects by how well we compete with microscopic organisms.

By exploring how humans evolve to win the battle with diseases and how they are sometimes vanquished by those pathogens, scientists hope to find drugs that can mimic successes and stave off the worst that viruses and bacteria can produce.

''It's a constant race between humans and their capacity to create new drugs and pathogens and their ability to evolve," said Dr. Daniel Cohen, an infectious disease researcher at Fenway Community Health in Boston, which specializes in AIDS treatment.

But before researchers can develop new drugs, they must understand the evolutionary nature of individual diseases and how viruses and bacteria, in turn, shape the evolution of humans and other animals.

Scientists have long known, for example, that in regions where malaria is common, most notably Africa, humans have developed an intrinsic defense against the parasitic illness. And that defense, which involves a change in red blood cells, has proved to be a good thing for many Africans, making them less susceptible to the disease. But the same trait has proved to be a bad thing for their descendants in the United States and other malaria-free areas, because it results in sickle cell disease, a condition that robs organs of oxygen, causing debilitating bouts of pain and sometimes death.

There are vital history lessons, too, when it comes to HIV.

As researchers unlocked the secrets of HIV, they found a gene mutation they suspect may protect against the virus that causes AIDS.

Human cells have locks on their surface -- scientists call them receptors -- and a virus must insert its key into these locks to gain entry. One of those is called CCR5, and HIV needs to unlock it to be able to infect cells. But scientists in recent years discovered that 5 to 10 percent of people in northern Europe don't have CCR5 receptors.

''And that's where the story gets interesting," said Dr. Calvin Cohen, research director for Community Research Initiative of New England, which conducts trials of AIDS drugs.

In contrast, people in Africa and Asia universally possess CCR5. So researchers theorized that lower HIV rates in northern Europe might be due in part to some people lacking the cellular lock.

But why don't they have it? Right now, it's only an informed hunch, but scientists suspect that the mutation exhibited by northern Europeans may be an artifact of the bubonic plague. The theory goes like this: As the plague swarmed Europe starting in the 14th century, it wiped out people who possessed CCR5 but spared those who lacked it.

''What we're talking about is a Darwinian process," Harmit Malik, who specializes in the study of genetic conflict at the Fred Hutchinson Cancer Research Center in Seattle. ''What was a really rare mutation was what survived. Everyone else had fallen prey to this particular pathogen."

And the thing is, people who lack CCR5 receptors appear not to suffer any consequences.

''So we have an ideal combination," Calvin Cohen said. ''HIV needs it, but we don't. What an ideal target for drug development."

That's why drug companies have developed experimental medications designed to block CCR5 so that HIV cannot enter cells. Cohen's Community Research Initiative is currently involved in a study of a Pfizer Inc. medication, with several patients enrolled in Boston.

This and other efforts to use evolution as a weapon against HIV are an acknowledgment that even with more than two-dozen AIDS medications now available, that's still not enough. The AIDS virus is especially adept at evolving to escape drugs -- an evolutionary process that can take place in weeks and months.

''It is essentially an organism that is an example of evolution at light speed, constantly, constantly changing," said Warner C. Greene, director of the Gladstone Institute of Virology and Immunology at the University of California at San Francisco.

Bringing the evolution story full circle, scientists continue to explore the history of the viral cousin of HIV carried by other primates. They know that HIV is an example of a virus that leaped from animals -- monkeys, in this case -- to humans. They also know that, with the passage of time, the virus ceased to harm monkeys, in part to allow its own survival. (So did the virus that attacked the Australian rabbits, by the way, evolving to be less harmful so more of its hosts could survive.)

''HIV coming fairly recently into the human population has not had a chance to evolve that way," said John M. Coffin, a leading AIDS researcher at Tufts University.

''Some day it will, but it's a long time away, and none of us should want to be a part of that evolutionary process."

Stephen Smith can be reached at stsmith@globe.com.