AIDS Research Yields Bounty of Science Advances
This winter, when the nation is in the achy, feverish throes of its annual influenza epidemic, Americans will have a new drug to ease their suffering.
Just approved by the Food and Drug Administration, the flu medicine is the first in a new generation of drugs that owe their development to a massive federal investment in AIDS, the deadly disease that attacks the body’s immune system.
Fueled by almost $15 billion in federal funds and the energy of thousands of researchers around the world, scientists have waged an intense and unprecedented campaign to unravel the mysteries of AIDS, which has killed 411,000 Americans.
From the beginning, those scientific efforts--supported by the gay and minority communities hardest hit by the disease--have come under attack from advocates for spending research money on other diseases that kill or afflict more people.
AIDS commands a federal research investment of $1.5 billion a year. By contrast, Alzheimer’s disease gets $400 million annually, even though it affects 4 million Americans, three times the number of AIDS cases.
In the latest salvo, the New England Journal of Medicine suggested in a study reported in June that federal funding should reflect “the burden of disease on society.”
Now, AIDS researchers are fighting back, arguing that, in fact, their work has produced a bounty of unexpected--and unappreciated--scientific advances well beyond the scope of AIDS.
Drug companies need no convincing. They are already lining up at the lab door, eager to turn discoveries into profits. In the next few years, scientists hope that new insights from AIDS research will allow them to develop drugs to combat everything from cancers to the common cold. In the meantime, drug companies and researchers alike are taking heart from new treatments--thanks to AIDS research--for chronic viral diseases, historically among the toughest to cure.
In eight months, a new drug for hepatitis B has become the most valuable treatment for that liver-destroying disease, which afflicts 1 million Americans. Made by Glaxo Wellcome Inc., lamivudine, also known as 3TC, got its start as an AIDS treatment.
The flu medicine is not a vaccine, giving doctors a new weapon to treat flu: a drug to be administered after the illness occurs.
And Dr. Robert C. Gallo, who with French scientist Dr. Luc Montagnier discovered the human immunodeficiency virus, hopes to begin human testing soon on a new drug that destroys cancers in the laboratory and shows potential against certain blood disorders.
“AIDS brought an amazing level of scientific brain power . . . that has brought benefits way beyond HIV,” said Jeffrey Levi, a longtime AIDS policy analyst who is an assistant research professor at the George Washington University School of Public Health here.
“Scientists were excited,” he added. “A lot of them wanted to find the cure and win the Nobel Prize. It stimulated a whole lot of new research.”
In studying AIDS, researchers set out to explore the insidious way in which HIV infects cells and erodes the immune system, unleashing a range of illnesses from pneumonia to blindness to cancer. This track--looking for patterns in how the virus operates--has led to a wealth of scientific information applicable to numerous fields, including virology, microbiology, neurology, genetics and, of course, immunology.
“It has been the real coming of age of immunology,” said Dr. Anthony Fauci, one of the country’s leading AIDS researchers.
One key scientific discovery of the AIDS epidemic was that doctors could slow the progress of the disease by interrupting the virus at different stages of reproduction, suppressing its growth. AZT, approved in 1987, worked by curbing HIV’s production of a key enzyme, reverse transcriptase, needed to help the virus integrate itself within human cells.
As they began to accumulate more knowledge about how HIV worked, researchers discovered that the more such “hits” a virus took during different stages of replication, the better the chances to slow or halt its spread and resulting damage. This led to the development of powerful protease inhibitors and other drugs that deliver a one-two punch at different phases in HIV’s cycle.
Now, the same principle is being applied to other viruses, often with surprising success.
AIDS “gave us the confidence to try,” said Dr. Vicki Sato, a scientist with Vertex Pharmaceuticals, of Cambridge, Mass., a firm involved in research on drugs to combat hepatitis C. “Before, many drug companies were scared off.”
Both hepatitis C and hepatitis B are prime candidates for this drug approach and with a huge potential market. More than 1 million Americans are infected with hepatitis B; nearly 3 million Americans carry the hepatitis C virus. Over time, a chronic infection with either results in liver damage, liver failure and a deadly form of liver cancer.
Like HIV, hepatitis C makes a protease enzyme that is necessary for viral replication. And hepatitis B makes an enzyme that is similar to HIV’s reverse transcriptase.
Vertex Pharmaceuticals also is studying the workings of another hepatitis C enzyme, helicase, with the hope of finding new compounds to inhibit it.
The same approach recently has been applied to viruses that cause acute infections. Even with these, the idea of disrupting the action of the virus shows big promise.
The newest flu drug, for example, Relenza (zanamivir), which was approved by the FDA in July, inhibits an enzyme produced by the two major flu virus strains. Called neuraminidase, the enzyme is vital to the flu virus’s ability to spread through the body.
Although the drug offers only modest improvement--it shortens the duration of illness by about 36 hours--it “opens the door to better drugs that will do the same thing,” Fauci said.
Fauci, who is director of the National Institute of Allergy and Infectious Diseases, said that scientists always had believed in theory that viruses could be attacked where they replicate. But that there was little enthusiasm for investing in that approach before the AIDS epidemic. Most medical researchers now believe it is the way to go, he said, now and in the future.
“We thought that in theory it could be done--but few people were doing it,” he said. “It was almost a cottage-type industry before AIDS. AIDS really jump-started the field.”
Beyond treatment for chronic viral infections, researchers arelooking to other areas for future breakthroughs. Among those thought to be the most promising: blood disorders, autoimmune disorders, genetic conditions and cancers where both viruses and the immune system are believed to play a role, such as cervical cancer, non-Hodgkins’ lymphoma and Kaposi’s sarcoma.
Gallo, now director of the Institute of Human Virology at the University of Maryland, has found several naturally occurring substances produced by the body’s immune system that he believes fight HIV and possibly other illnesses.
He found one such substance while studying Kaposi’s sarcoma. One of the curiosities of Kaposi’s, a form of skin cancer, is that it afflicts many more men than women. In trying to figure out why, Gallo found a protein in the urine of pregnant women, produced early in pregnancy, that kills cancer cells.
Dubbed “Maternin,” the substance has not yet been tested in humans, although Gallo said that he hopes clinical trials can begin by the end of the year. If it is found to be effective, Maternin could be used to help fight blood disorders and some cancers.
The progress in converting the lessons learned from AIDS research to other diseases is unlikely to quiet the periodic complaints of those who believe AIDS has been singled out for special funding attention over the years.
For example, AIDS research funds currently dwarf those for such diseases as breast cancer, which strikes 180,000 women a year and has a federal research budget of $380 million, one-fourth that of AIDS.
But the New England Journal of Medicine study also acknowledged that “different measures of the burden” can yield “different conclusions” about spending decisions.
Many AIDS researchers have insisted all along that AIDS research would produce benefits beyond the treatment of this disease. In the early days their predictions “were as much based on hope as on sound experience,” Levi said. “But, in this case, they turned out to be right.”
