Case Shakes Theories Of Aids Origin
ST. LOUIS — Long before Robert R. finally entered the hospital, his body had begun to fail him in many ways.
For nearly two years his lower legs and genitals had been swollen. Since then the black teenager had grown thin and pale, fatigued and short of breath, and now his bloodstream swarmed with the microbe called Chlamydia.
Just when Robert`s condition seemed to have stabilized, his breathing became more labored and his white blood cell count began to plummet. He developed a fever, went into a convulsion and died.
The parade of doctors who examined the young man in life, who poked and prodded and photographed him for their archives, agreed that Robert`s immune system had somehow ceased to function. But none of them could offer a clue as to why.
None, that is, until Dr. William Drake, the pathologist who performed the autopsy, discovered something odd: a small, purplish lesion on the boy`s left thigh, and several similar growths in the soft tissue inside his body.
In his autopsy report, Drake concluded that the lesions were a malignant tumor called Kaposi`s sarcoma, a rare brand of cancer once confined mostly to elderly Jewish and Italian men.
According to contemporary diagnostic criteria, Kaposi`s sarcoma in a patient younger than 60 is almost certain to signal a case of acquired immunodeficiency syndrome. But on May 16, 1969-the day that Robert died-nobody had ever heard of AIDS.
The doctors who attended Robert R., (and who agreed to talk about the case in exchange for an agreement to withhold his last name) and for whom his case has presented a continuing puzzle, now believe the 15-year-old youth from the St. Louis ghetto was infected with the same human immunodeficiency virus
(HIV) that has since been linked to AIDS.
If they are correct-and laboratory evidence obtained just last week indicates strongly that they are-it means the AIDS virus has existed in this country for at least two decades, a full 10 years before the first cases of AIDS-related Kaposi`s sarcoma began showing up in white, male homosexuals in New York City.
The implications of such a conclusion are profound, for the length of time that the AIDS virus has been present may not only determine how many Americans have been exposed to it but reveal much that so far is unknown about the past and future course of the disease.
At the moment, however, the case of Robert R. raises more questions than it answers. From whom did he acquire the AIDS virus, and how? To whom might he have passed it? Most important of all, when did the AIDS virus arrive in this country, and where did it come from?
Before he died, Robert was unable to contribute much to the solution of the mystery that surrounds him. “He was the typical 15-year-old who is not going to talk to adults, especially when I`m white and he`s black,“ said Dr. Memory Elvin-Lewis, a microbiologist at Washington University in St. Louis who followed Robert`s decline for more than a year.
“He was not a communicative individual. He knew the minute I walked into the room that I wanted something more from him-more blood, more lymph fluid, more something.“
Between extractions and injections, Robert did tell his doctors a few key facts: that he had been born in St. Louis and had never traveled outside the Middle West, much less the country. Nor, he said, had he ever received a blood transfusion.
He also admitted having had heterosexual relations; according to his autopsy report, “the patient dated his physical disability from an instance of sexual relations with a neighborhood girl.“
Robert was never asked about the possibility of homosexuality, but circumstantial evidence suggests that he may have been the recipient of anal sex, the variety of intercourse believed most likely to transmit HIV.
“We knew from the very first that he wouldn`t let us do a rectal examination on him,“ recalled Dr. Marlys Hearst Witte, a professor of surgery at the University of Arizona who was closely involved with the case of Robert R.
“We knew that he had genital edema and severe proctitis, which is an unusual problem in a 14-year-old boy-the stigmata, almost, of homosexuality. At autopsy he had Kaposi`s sarcoma of the rectum and anus, which is an unusual place for Kaposi`s sarcoma to be.
“So if you`re asking me, do I think this boy lived in an environment or engaged in practices that one would now associate with transmission of AIDS, I would say I think that was rather likely. He could have been a male prostitute. He certainly lived in the environment where that was possible.“
However Robert acquired the virus, he must have gotten it from someone, since no viruses can exist for long outside the human body. And whether he passed it on or not, the presence of HIV in this country as early as 1968 raises important questions about the current thinking on the genesis of AIDS. Most researchers now believe that HIV assumed its present shape somewhere in Central Africa and arrived in this country during the middle 1970s. The theory is bolstered by the discovery, two years ago, of HIV antibodies in a blood sample dating from 1959 in Kinshasa, the capital of Zaire.
Because the incidence of AIDS in Haiti is high, and because some of the first cases in this country occurred among Haitian emigres in Florida, it has been assumed that the virus probably passed through that island nation on its way from Africa to the United States.
One theory suggests that French-speaking Haitians, imported to Zaire and other French-speaking African nations as servants during the 1960s and 1970s, brought the virus back to Haiti, where it was picked up by vacationing American homosexuals in the mid-1970s.
Another holds that HIV first came ashore in south Florida with the successive waves of Haitian boat people who began landing there in 1978.
But however it is constructed, there are a number of gaps in the Africa-Haiti theory. One is that the per capita incidence of AIDS in other Caribbean nations, including the Bahamas, Barbados and Bermuda, is even higher than in Haiti.
Another is the question of why, since nearly equal numbers of Haitian men and women appear to be infected with HIV, the virus was not also acquired by heterosexual American tourists in Haiti-or, for that matter, in Miami.
If some other explanation for the passage of HIV to the United States must be constructed on the strength of Robert R`s case, an explanation will also have to be found for the fact that white male homosexuals, who make up two-thirds of all AIDS victims, did not begin to sicken and die in large numbers until the late 1970s.
So perplexing was the case of Robert R. that two of the doctors who attended his autopsy took samples of his blood and tissue back to their laboratory freezers, along with the faint hope that science might someday tell them what to look for.
One was Dr. Elvin-Lewis, then a newly minted Ph.D. who had just finished a doctoral dissertation on a little-known sexually transmitted disease named, like the microbe, Chlamydia.
“He was my first patient,“ Elvin-Lewis recalled in a recent interview,
“and I couldn`t believe what I was seeing. He was a bag of producing Chlamydia. His antibodies were so low that nobody could understand it.“
“The case sure was consistent with some kind of virus knockdown of the immune system,“ said Drake, the pathologist, who is now retired. “The Chlamydia, for instance, shouldn`t have been in his blood. Chlamydia should stick to the site where it enters the body.“
Another who watched Robert`s progress with great interest was Marlys Witte, then a young thoracic surgeon who, with her physician husband, Charles, had become intrigued by the apparent obstruction of the boy`s lymphatic system.
“When he died, Marlys and I just stood there and took everything,“ said Elvin-Lewis. “Blood and lymph and tissue and you-name-it.“
For two decades the samples were kept in cold storage, some of them in Elvin-Lewis` laboratory in St. Louis, the others by Witte at the University of Arizona.
The case remained sufficiently perplexing that Elvin-Lewis, the Wittes, Dr. William Cole and some of the others involved reported the enigma in a 1973 medical journal article. And there it might have ended, as the co-authors followed their separate career paths to teaching and research.
Elvin-Lewis became chairman of the microbiology department at the Washington University Dental School. The Wittes moved to Tucson. Cole gave up his post as chief of surgery at Barnes Hospital in St. Louis to open a small- town practice in Sedalia, Mo., and Drake went on doing autopsies.
But the case of Robert R. stayed in the back of Marlys Witte`s mind.
“I`m not someone who`s devoted my whole life to AIDS,“ she said in a recent interview. “This was an incidental patient, coming in with something I deal with on a regular basis-lymphedema. But I have always thought this was an important case, and I did the best thing. I saved everything.“
In 1984, as AIDS was moving to the forefront of American medical research, Witte decided that some of Robert R.`s samples should be thawed and tested.
Antibodies were found to Herpes simplex, Cytomegalovirus and Epstein-Barr disease, three viruses that, along with bacterial Chlamydia, are common among homosexual men, especially those with AIDS.
But there was then no way to test for antibody to HIV, which represents nearly irrefutable evidence of exposure to the virus.
“I thought that I would just sit until techniques were better, so that I would have my best shot at really documenting it,“ Witte said. “We felt we had so little fluid that we were going to save what we had and do everything at once.“
Early last year, after sensitive HIV antibody tests had become available, Witte called Elvin-Lewis to ask whether she had saved any of the samples she took from Robert R.
“She turned out to be as much of a pack rat as I am,“ Witte said. “So I said, `Send me everything you`ve got.` “
In June, Witte sent a half-teaspoon of Robert`s blood and a few specks of tissue to Dr. Arthur Gottlieb, a friend and colleague who heads the microbiology department at the Tulane University Medical School in New Orleans.
“I thought that things were at a stage where, if there was going to be something to be found, we would be able to find it now,“ Witte said.
The decision to test Robert`s remains for HIV was first disclosed by Witte, who is secretary general of the International Society of Lymphology, in the opening address to a special AIDS seminar last month at the 11th International Congress of Lymphology in Vienna.
There she told an astonished audience, “We are currently testing body fluids and tissues preserved for nearly 20 years for evidence of HIV or related retroviruses, to see whether this perplexing case was actually HIV infection before its time. Preliminary determinations are suspicious.“
Antibodies and viruses are mainly made up of proteins, long chains of amino acids that have a biochemical attraction for one another.
In the human body, molecules of antibody produced in response to an invasion by a specific virus fight off the disease by binding themselves to, and then killing, virus molecules in the bloodstream.
If a blood sample is mixed with several of the major proteins that make up HIV, and if the sample contains HIV antibody, the same kind of binding will occur in the laboratory.
At Tulane, the samples from Robert R. were given over for testing to Dr. Robert Garry, an associate professor of microbiology and colleague of Gottlieb.
The test chosen by Garry to search for the presence of HIV antibody was the Western Blot, the most specific and sensitive of the antibody tests now in general use.
The Western Blot is so sensitive that the Pentagon, which is testing millions of new recruits and in-service personnel for AIDS, requires evidence of antibody to just two of the nine main viral proteins before rendering a positive diagnosis. The Red Cross insists on three.
The blood of Robert R. contained antibodies to every one of the nine HIV proteins used in the test. “We found very good reactivity,“ Garry said. “We also got positive reactions to two of the tissue samples from his spleen.“
Gottlieb agreed that “there`s no question that it`s positive,“ but he said the test would be repeated this week out of an abundance of scientific caution.
Steve Alexander, director of immunology for Biotech Research Laboratories of Rockville, Md., the firm that manufactures the test, said positive reactions for all nine HIV proteins made the presence of HIV antibody virtually certain.
“The only alternative would be if someone contaminated the sample,“ he said. But he added that in cases of contamination it was unlikely that antibodies to all nine viral proteins would be detected.
Asked whether the age of the blood sample might make the possibility of a false positive more likely, Dr. Alexander said he had used the Western Blot on some 15-year-old blood samples “and as long as they`re preserved, they`re okay.“