Maverick scientists think they've found a bug in the HIV-AIDS connection

EAST LANSING, MICH. — EAST LANSING, Mich. -- Robert Root-Bernstein is the first to admit it: He likes to find faults. When all those around him are nodding their heads, his instinct is to say, "But wait a minute . . ."

Mr. Root-Bernstein's training as a scientist compels him to take a theory, kick it around in his mind, test other possibilities and then explain why things may not gel.


Lately, the Michigan State University professor has been doing just that, kicking around the almost universally accepted premise that HIV, the human immunodeficiency virus, is the single cause of acquired immune deficiency syndrome or AIDS.

Most other heads are nodding. But for Mr. Root-Bernstein, it doesn't gel.


"The more I looked into the HIV theory, the more I kept finding holes," he said.

The professor thinks that HIV may be a relatively peaceful virus -- necessary, but not sufficient, to trigger AIDS. The way he sees it, HIV needs a crucial assist, probably from one or more other infections, dubbed co-factors.

Mr. Root-Bernstein's beliefs -- detailed in a book, "Rethinking AIDS," scheduled for publication by a division of MacMillan later this year -- are rejected strongly by nearly all AIDS specialists and public health officials.

"HIV causes AIDS. There's no serious question about that," said Dr. Peter Drotman of the Centers for Disease Control. Co-factor theories "have precious little evidence to support them," he said.

But there's enough evidence, at least to some eyes, for scientists such as Mr. Root-Bernstein and Luc Montagnier, the French virologist heralded for discovering HIV in 1983, to keep saying, "Wait a minute. . . ."

Mr. Montagnier, in June 1990, claimed a second discovery that hasn't gotten a hundredth of the attention of his HIV find. He declared that HIV needs help to cause AIDS, from a co-factor he identified as a mycoplasma -- a tiny bacterium.

Mr. Root-Bernstein believes he understands how some in the medical research establishment can reject such findings, given the years and billions of dollars invested in the premise that HIV is an inevitable line to AIDS.

"The problem is that we have people committed completely to HIV research," he said. "They have put, in many cases, more than a decade's worth of their lives into HIV only. To have that pulled out from under them is more than they can stand."


Mr. Root-Bernstein, who has given speeches to scientists and doctors around the country in the past year, has been riddled with an arsenal of adjectives -- stubborn, reckless, contentious, naive, stupid. He has even been called a liar.

"That's when I start losing my cool," said Mr. Root-Bernstein. "I'm not getting up and saying, 'I'm right!' I'm getting up and saying, 'Let's look at these things.' The most important thing is to get at the heart of the matter."

In 1981, at age 27, Mr. Root-Bernstein won one of the MacArthur Foundation's "genius grants," a no-strings pile of money to do research or write without worry of financial backing. From 1981 to 1984, he studied immune disorders in the California laboratory of Jonas Salk, inventor of the polio vaccine.

Now 38, Mr. Root-Bernstein teaches physiology at MSU. He said he was vexed by serious doubts about HIV in 1988 while planning an introductory lecture for MSU students about the causes of diseases.

The lecture would discuss four rules that German scientist Robert Koch formulated more than a century ago -- rules still taught to students of epidemiology today -- for proving that a specific agent causes a specific disease.

Mr. Root-Bernstein planned to apply those rules to HIV and AIDS. But the virus failed on at least two counts.


According to Koch, if a germ causes a disease, the germ must be found in every case of the disease. In a very small percentage of AIDS cases, no evidence of HIV is found.

Mr. Root-Bernstein said his research showed as many as 5 percent of AIDS cases in that group.

However, Dr. Celine Hanson of the CDC said the current percentage was below 1 percent and that in many cases where HIV wasn't found, the explanation was simple: There was no HIV test. Or a bad HIV test. Or an incorrect AIDS diagnosis.

Even so, Dr. Hanson admits that there is a very small number of befuddling cases in which a person appears to have AIDS but not HIV.

HIV also violates Koch's rule that the disease-causing agent, when injected into a healthy host, must produce sickness.

For obvious reasons, no one has injected HIV into a healthy human being. But the virus has been pumped into the bloodstreams of many species of animals, including monkeys, and the virus alone has not triggered anything in these animals resembling human AIDS.


One popular explanation is that certain diseases are specific to certain species and AIDS afflicts only humans.

Mr. Root-Bernstein doesn't buy it.

He said when he listens to scientists defend the HIV theory, he hears them making too many exceptions and allowances for the virus.

"If you now start to look at all the features HIV is supposed to have," he said sarcastically, "it is the most unique virus in the world."

For instance, many people who die of AIDS have only a tiny amount of the virus in their bodies. Mr. Root-Bernstein has not yet heard what he considers an acceptable rationale for how so little virus does so much damage.

Also, HIV is actually spreading less quickly than originally anticipated, the explanation being that it is an exceptionally difficult virus to transmit.


Finally, when HIV infects the body, it rarely produces serious illness immediately. It just sits there quietly until one day -- maybe a year later, maybe 15 years later -- it turns vicious, attacking cells in the immune system.

This is bizarre behavior for a virus, Mr. Root-Bernstein said.

Last year, he and about 35 other scientists in the United States and Europe created an informal committee to share ideas and to argue, mostly through scholarly journals, for a reappraisal of the accepted wisdom that HIV alone causes AIDS.

Unlike Mr. Montagnier, Mr. Root-Bernstein and many other HIV doubters aren't certain what the co-factor of HIV might be. Perhaps it's another virus -- hepatitis B, herpes, Epstein-Barr, the cytomegalovirus -- all of which frequently are found in AIDS patients.

Possibly, Mr. Root-Bernstein said, the co-factor is not a specific agent but a chronic behavior or condition -- drug abuse, alcoholism, malnutrition -- that suppresses the immune system and renders it vulnerable to assault and ultimate defeat by HIV, or by HIV and another bug egging each other on.

Whatever the case, the renegade theory that HIV alone cannot cause AIDS has powerful implications, both positive and negative.


On the good side, it offers some hope to people with HIV.

Many of the possible co-factors being mentioned are viruses or organisms that are sexually transmissible, such as some mycoplasmas. A person with HIV may be able to avoid them through protected sex, Mr. Root-Bernstein said.

Also, if the development of AIDS relies on immune suppression independent of HIV infection, perhaps an infected person can fend off AIDS by keeping his or her immune system in perfect shape -- through sobriety, good nutrition and protected sex.

Perhaps, said Mr. Root-Bernstein, "HIV is not a death knell -- it's a two-minute buzzer," and an infected person can turn the game around and win.

Finally, if HIV requires a co-factor, then researchers and doctors may have a second front on which they can attack AIDS. While they haven't found anything to stop HIV, perhaps they can find medicines to foil its accomplice.

But there's a scary side to the dissent of Mr. Root-Bernstein and others.


The holes they try to punch in accepted medical wisdom about AIDS suggest that researchers still haven't solved some essential puzzles of the disease.

Researchers know what is probably the most important thing -- that something called HIV is involved in all this and that people must protect themselves from HIV infection.

But if HIV is not the whole picture -- if there are co-factors, or even ways to suppress the human immune system without HIV -- then perhaps a lot of time and money has been squandered on research that's on the wrong track.

Mr. Root-Bernstein is particularly intrigued by the time lag between HIV infection and the onset of AIDS, which suggests to him that the virus is benign until something else comes along and "turns it on."

The average time span between HIV and AIDS is 10 years, the CDC said. But Mr. Root-Bernstein thinks it's a poorly substantiated figure -- and should be at least several years longer.

The figure comes primarily from a test group of gay men in San Francisco who participated in a hepatitis B study between 1978 and 1980. Their blood samples were kept and years later, when the AIDS epidemic emerged, the samples were tested for HIV. Hundreds came up positive.


For more than 500 of the men testing positive, researchers were able to determine probable infection dates. They then watched the men to see when HIV became AIDS. By the 10-year mark, about half had developed AIDS; half had not.

But Mr. Root-Bernstein believes an HIV-infected person in otherwise good health would fare much better than the men studied, because the men all had been treated for sexually transmitted diseases (STDs), which he said can batter the immune system even before HIV infection.

The notion of a co-factor might explain not only the lag time before AIDS but the widely varying rates at which infected people develop the disease, Mr. Root-Bernstein said. He also believes that the presence or absence of co-factors could determine whether or not a given person, in given situations that expose him or her to HIV, becomes infected with the virus or not.

Specialists don't know why two different people can be exposed to HIV in the same way and one can end up infected while the other doesn't.

The answer may be genes -- different susceptibilities to sickness. It may be sheer chance. Mr. Root-Bernstein, however, wonders if the answer may be that the person who gets infected has a co-factor.

He also wonders if a person experiencing some level of immune suppression may be particularly vulnerable to HIV infection.


Drug users clearly are immune-suppressed, he said.

So, possibly, are gay men who are the passive partners in unprotected anal intercourse. There's some evidence that when sperm enters the bloodstream -- more likely in anal than vaginal intercourse -- it suppresses the immune system.

Blood transfusions, through which many people became infected before blood donations were screened for HIV, are often immune-suppressing, he said.

These categories, of course, don't explain the many cases of HIV and AIDS in people who never have abused substances, never been the passive partners in anal sex, never gotten a blood transfusion.

But maybe they've taken prescription drugs that have immune-suppressing effects, Mr. Root-Bernstein theorizes. Maybe they're experiencing some level of malnutrition, not getting minerals or vitamins crucial to immune function.

Mr. Root-Bernstein thinks more thorough studies need to be done into the lifestyles and health of those who have progressed from HIV to AIDS vs. those who haven't.


He wants to know: What's special about long-term survivors of HIV infection who haven't developed AIDS?

What's going on in those people who have AIDS, or at least something very much like it, but not HIV?

For example, the CDC has identified 20 to 30 young gay men who are not infected with HIV but have come down with Kaposi's sarcoma (KS).

KS is a skin cancer so rare in this country that when it began afflicting gay men in the early 1980s, doctors concluded that there must be some new, drastic level of immune deterioration in these men.

That was a clue to the discovery and definition of AIDS. KS is one of 23 specific illnesses signaling a battered immune system and the onset of AIDS.

The 20 to 30 cases of KS without HIV -- though a small number -- still is higher than health officials normally would expect, said Dr. Thomas Peterman, a medical epidemiologist at the CDC.


Is there a cause of KS that doesn't require HIV? If so, how can we be sure HIV is the key villain in the cases of KS where the virus is present and a person is diagnosed with AIDS?

Did these 20 to 30 men develop a state of immune suppression similar to AIDS without HIV? If so, what caused it and could that cause turn out to be a co-factor that usually works with HIV but also can work without it?

Mr. Root-Bernstein said the lingering questions, the faults he sees in the HIV premise, are signals that the whole truth isn't known.

If the faults are looked at more seriously, and more kinds of research are done, "it may very well prove that HIV is the cause of AIDS," he said. "That's fine."

But, he added, "If there's reason for doubt, we better figure out what the doubt is so we can figure out a way to get rid of the doubt. We cannot afford -- in terms of human lives, research and manpower investment -- to be wrong.

"Unfortunately, we may be."