San Francisco Chronicle (SF) - THURSDAY, December 1, 1994 Edition: FINAL Section: News Page: A2 Word Count: 836
Charles Petit, Chronicle Science Writer

The AIDS virus directly attacks the human immune system. The scientists reason that if the immune system of a person with AIDS were replaced with corresponding cells from baboons, which appear impervious to most forms of the AIDS virus, the patient may be able to battle back against the infection.

The experiment, which could start within a year, is driven by frustration at the failure of standard medicine to provide breakthroughs against HIV, the virus that causes AIDS. It also is fraught with potential dangers.

The strategy is the brainchild of Dr. Suzanne Ildstad, a transplant surgeon and director of the division of cellular therapeutics at the University of Pittsburgh, a center of pioneering research into transplant procedures.

She has teamed up with Dr. Steven Deeks, an AIDS specialist at the University of California at San Francisco. They expect the first experiments to be conducted on volunteers from patients on the AIDS ward of San Francisco General Hospital.

"The easy solutions have not worked," Ildstad said during a recent visit to the Bay Area. She said a baboon cell transplant is a natural extension of other efforts, by several research teams, to genetically modify human immune system cells to resist HIV infection. "It is a natural form of gene therapy," she said. "If one is considering genetically modifying human cells to be resistant, why not use a naturally resistant cell?"

The idea is being reviewed by the 13-member UCSF Committee on Human Research, which has asked Deeks and Ildstad for more information on their proposal before deciding whether to permit it. A source on the committee said "we have a very long list of questions. This is a complicated experiment and I don't think we are going to give it approval any time very soon."

Deeks, however, said he hopes to have answered the review committee's questions by early next year. If he is given the go-ahead, he will immediately begin recruiting volunteers. Until that happens, however, people interested in taking part should not try to sign up. Only four volunteers are expected to be treated in the first year or so.

Among the concerns is that the grafted monkey cells could carry hidden viruses of their own that would only add to the medical problems of people infected with HIV.

It is also possible that the implanted monkey immune system would attack the human host. In addition, preparing people with advanced AIDS for the procedure involves first deliberately weakening their own immune systems, potentially compounding problems caused by HIV. Moreover, the treated person would probably remain infected and a potential source of disease to others. But if it works as well as some studies suggest, the specially purified baboon cells would take root in the bone marrows of their human host and multiply to assemble a new, AIDS-proof system for fighting disease. It would take over the job from patients' own immune systems collapsing from the assault by HIV.

Although HIV often infects tissues other than those of the immune system, it is hoped that a vigorous baboon immune system would then stem progress of the disease throughout a patient's body.

Effective immune systems must respond quickly to invading organisms, such as viruses or bacteria, while not attacking normal tissues of the host organism. "The charm of this new technique," Deeks said, "is that the bone marrow of humans and baboons can learn to recognize each other as `self,' so they don't attack one another."

Ildstad came up with the idea as part of her leading role in a major multi-institutional effort to find ways to use animal organs -- with baboons and pigs the leading contenders -- for human transplant. After several failed efforts in the past 15 years, many scientists now believe that improved methods of controlling rejection of alien tissue make the time ripe for a new round of experiments. New AIDS-proof immune systems are just examples of techniques that may provide new hearts, kidneys, or other organs.

Ildstad made a key discovery that paves the way for moving immune systems among different species. Within the bone marrow, she found, are two separate populations of cells that must be transplanted together. For years, scientists have known that so-called stem cells provide the raw material for growth of a wide range of disease-fighting cells in the bloodstream, including the T-lymphocytes ravaged by HIV. Ildstad recently discovered a second line, called facilitating cells, that must accompany stem cells if they are to set up shop in a new host.

Already, she and other groups have shown that immune systems from mice can be put into rats, and vice versa, two species more different than humans and baboons. She also has established human-derived immune systems in baboons without apparent ill effect on the animals.

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