The New York Times - October 23, 1984
Lawrence K. Altman, M.D.

That process is known as fulfilling Koch's postulates, and doctors have been doing it over the last 100 years since Robert Koch, the German microbiologist, developed the scientific steps named for him.

Koch's postulates are often summarized in four steps. First, the microorganism is observed in all cases. Second, the microorganism is grown in pure culture. Third, inoculations of the pure culture in susceptible animals reproduce the condition. Fourth, the microorganism is recovered from the experimentally infected animal.

In the case of acquired immune deficiency syndrome, or AIDS, scientists have come tantalizingly close to proving that a retrovirus called HTLV-3/LAV is the cause of the usually fatal syndrome. However, scientists have not yet fulfilled Koch's postulates for AIDS, which has struck more than 6,250 people, according to the latest reports from the Centers for Disease Control in Atlanta.

Nevertheless, AIDS researchers have taken a major step toward fulfilling Koch's postulates by transmitting the HTLV-3/LAV retrovirus to chimpanzees.

The experiments have been done independently by researchers at the National Institutes of Health in Bethesda, Md., and at the Centers for Disease Control by different methods. In one, the injections were made with pure cultures of the AIDS virus. In the other, samples of blood from victims of AIDS were injected into animals.

At the National Institutes of Health, a team headed by Dr. Harvey Alter took plasma from AIDS patients and injected it into three chimpanzees housed at the Southwest Foundation for Biomedical Research in San Antonio. Two of the chimpanzees showed some evidence of AIDS.

A natural response to infections is to form antibodies, the immunological proteins that chemically fight off the invading microorganism. One striking feature of the AIDS syndrome is the development of enlarged lymph nodes throughout the body. Another is the development of an immunological abnormality, depression of the so-called T4-T8 ratio. The T4 and T8 are types of white blood cells known as lymphocytes.

One chimpanzee injected with the AIDS virus developed enlarged lymph nodes as well as laboratory signs of the infection. The chimpanzee also developed antibodies to HTLV-3/LAV and also developed the T4-T8 immunological abnormality.

A second chimpanzee developed antibodies to the AIDS virus but not the two other abnormalities. The third has remained well and shown no laboratory abnormalities.

However, the incubation period is long in AIDS. The incubation period is the time it takes from exposure to the microorganism to the onset of symptoms of the condition it causes. The incubation period of AIDS can be up to five years in humans, and it took several months for the chimpanzees to develop the syndrome under the conditions of the experiment.

Thus, it is not clear whether animals injected with the AIDS virus will develop a more severe form of the disease. Sometimes microorganisms do not produce an illness of the same severity when injected across species barriers. But some researchers have accepted the experimental results as evidence toward fulfilling Koch's postulates.

However, the N.I.H. researchers have not yet succeeded in the final step, recovering the AIDS virus from the experimentally infected animals.

In the experiments that researchers at the disease control centers carried out with colleagues at Emory's Yerkes Regional Primate Research Center in Atlanta, two chimpanzees injected with the AIDS virus developed antibodies against it after four months. The animals developed swollen lymph glands but because they did not develop a clear case of AIDS, they did not fulfill Koch's postulates. However, the researchers did recover the virus from the infected animals.

According to Dr. Alfred S. Evans of Yale, Koch did not recommend the postulates as rigid criteria of causation and they should not be regarded as such today.

The postulates have been refined over the years to reflect advances in techniques and knowledge. Also, doctors have come to realize that the same syndrome can be produced by more than one agent and that one microorganism can produce different forms of illness depending on the circumstances.

Further, although doctors have fulfilled Koch's postulates for scores of infectious diseases, sometimes they have been unable to do so. Instead they have relied on immunological and other experimental evidence to support contentions that a microorganism causes a disease.

At a news conference last April to announce scientific advances concerning the HTLV-3 virus, Dr. Robert C. Gallo of the National Cancer Institute, a major figure in AIDS research, cited such problems. He said scientists might not be able to meet Koch's postulates in the case of AIDS.

In this connection, AIDS researchers have pointed to evidence from two humans who developed AIDS. One was a blood donor. The second received a transfusion of the first individual's blood, which was donated before the donor developed AIDS. The AIDS virus was isolated from both the donor and the recipient.

Although AIDS researchers have not yet fulfilled Koch's postulates, their success in transmitting the infection to chimpanzees is a crucial step toward the ultimate goal of developing a vaccine for AIDS.

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