Chicago Tribune (CT) - THURSDAY September 15, 1988 Edition: SPORTS FINAL Section: NEWS Page: 1 Word Count: 1,173
Ronald Kotulak and Peter Gorner

The successful transplantation into animals of the defense system that protects people was announced Wednesday by two California research teams. Other researchers hailed the experiments as a major advance that could end the logjam that has stymied the search for a cure for AIDS.

The biologically engineered mice also could lead to new ways of diagnosing and treating cancer and other diseases, and solve the problem of rejection in organ transplants.

"It's great, exciting," said Dr. Howard Streicher, a leading AIDS authority at the National Cancer Institute in Washington, of the reports by the two teams. "It opens a tremendous possibility for studying the human immune system in a controlled environment."

AIDS researchers have been frustrated in their efforts to understand and control the illness because the AIDS virus does not cause disease in any other species except humans, and humans cannot be experimented on in the laboratory.

The main targets of the deadly AIDS virus are the white blood cells that make up the immune defense system. By transplanting this functioning system into animals, a goal that was once thought to be impossible, scientists have a powerful new tool for tracking the course of acquired immune deficiency syndrome.

"We now hope to be able to understand how the AIDS virus works in a living animal, and we will also be able to look systematically for therapies that are effective in a living system," said Joseph M. McCune, an infectious diseases specialist at Stanford University Medical Center in Palo Alto, Calif., one of the two groups that announced the developments.

"This is a far step forward from test tube studies, the best strategy available to date," McCune said. "With a small animal model, we can figure out what happens, from the time of infection by HIV (the AIDS virus) until the time of death. What does the virus do? What does the human immune system do? How can things be changed? What therapies will work, and which ones won't?"

Researchers at the Medical Biology Institute in La Jolla, Calif., a nonprofit biomedical research laboratory, reported similarly successful results.

"It is now possible to study the effects of a variety of substances, such as therapeutic drugs, vaccines and toxic compounds, on the human immune system in the body of a living animal prior to performing such tests in human subjects," said Dr. Donald Mosier, leader of the research team at La Jolla.

Both teams are attempting to infect their transformed animals with the AIDS virus.

"If we're enormously lucky and the infection takes, then we can develop ways to immunize the animals against the AIDS virus, thereby developing a vaccine," said Irving Weissman, a leading cancer biologist who heads the Stanford team.

Both teams used genetically defective mice that were born without immune systems. These mutant animals, known as severe combined immunodeficient or SCID mice, were discovered in 1983 by biologist Mel Bosma of the Institute for Cancer Research in Fox Chase, Md.

The Stanford mice developed the ability to make both human blood-forming and immune cells after they were given liver, thymus and lymph node cells obtained, under strict guidelines, from aborted human fetuses, according to a report that is scheduled to appear next week in the journal Science.

These mice were able to fight infections that would normally kill them and remain alive for as long as 15 months, three times the lifespan of other immunodeficient mice.

The fetal liver contains so-called "stem" cells, the progenitors in the body that produce all of the various red and white blood cells. Thymus and lymph cells are necessary to instruct white blood cells how to carry out their roles as soldiers in the body's fight against disease, Weissman said.

The Stanford experiments began before last March, when the National Institutes of Health placed a temporary ban on the use of human fetal tissue for research.

The government agency is holding hearings in Washington about possibly lifting the ban, as a result of new findings indicating that transplanting fetal tissue into patients may be able to correct a number of serious disorders, including Parkinson's and Alzheimer's diseases and juvenile diabetes.

The White House, however, is drafting an executive order that would ban the use of human fetal tissue.

"If the executive order goes through banning (the use of) fetal tissue, it would handicap major medical research efforts," said Weissman. "It would end our research, and such research could not go on anywhere except outside the U.S. or in private institutions that do not depend on government funding."

Researchers at the Medical Biology Institute did not use human fetal tissue in their mice. They report in this week's issue of the British scientific journal Nature that they produced fully functioning human immune systems in mice by transplanting white blood cells from normal human donors.

These cells multiplied in the immune-deficient mice, giving them protection against infection, said Mosier. When the animals were given the tetanus vaccine, they developed antibodies against this acute bacterial infection just as a normal immune system does, he said.

By using these biologically engineered mice, it may be possible to produce protective antibodies against all kinds of infectious agents that could be used to treat humans, Mosier said.

Dr. David Baltimore, a Nobel laureate who directs the Whitehead Institute at the Massachusetts Institute of Technology, said the Stanford research represents a new way of doing human biology that may extend beyond the immune system.

"This model represents an opportunity to study diseases of the immune system, as well as normal human immune function, in an experimental way that's never before been possible," Baltimore said.

Both California teams said they were "very hopeful" their new animal model would end the controversial practice of trying to use captive chimpanzees as animal models for AIDS.

CAPTION: Graphic: How to make an SCID-hu mouse.

1. A mouse born without an immune system, or severe combined immune deficiency (SCID), is given a human (hu) immune system.

2. The mouse receives two types of human cells: Stem cells, which carry the instructions for creating all blood and immune cells, and cells from the thymus and lymph nodes, which are organs that "educate" the stem cells on how to protect the body from disease.

3. The stem cells migrate through the thymus, which produces the T- cells attacked by the AIDS virus, and through the lymph nodes, which create the immune system's B-cells or antibodies.

4. Mature immune system cells are then free to circulate in the blood and begin the immune response of fighting disease in the mouse.

5. The resulting SCID-hu mouse can be used in the testing of vaccines, drugs and diagnosis of human diseases, including AIDS and cancer. Chicago Tribune Graphic; Source: Stanford University.

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