More info on Dr. Lo:
From the New York Times
January 16, 1990
THE DOCTOR'S WORLD
THE DOCTOR'S WORLD; Unusual Microbe, Once Dismissed, Is Not Taken More Seriously
By LAWRENCE K. ALTMAN, M.D.
EVIDENCE suggests that a mysterious microbe, whose discovery three years ago was dismissed as a finding of no significance, can cause disease among AIDS patients and even kill people not infected with the AIDS virus. Laboratory tests hint that several antibiotics could control the microbe, but this and other findings need to be confirmed.
Dr. Shyh-Ching Lo, a scientist at the Armed Forces Institute of Pathology in Washington, discovered the microbe in 1986 but first thought it was an unknown virus.
Now, after more research in collaboration with scientists at the National Institutes of Health, Dr. Lo says the microbe is a mycoplasma. Discovered a century ago in plants, mycoplasmas are the smallest and simplest free-living organisms. They are classified between bacteria and viruses, but are closer to bacteria. Members of the mycoplasma group are known to cause pneumonia and other infections. Dr. Lo calls his microbe Mycoplasma incognitus and says it closely resembles M. fermentans, which has only rarely been reported to cause human infection. French researchers are now trying to determine whether the two are truly different.
After Dr. Lo's earlier reports, several experts said they believed he had found a mycoplasma, not a virus. But the scientists dismissed its importance, suggesting that it was a harmless organism that had somehow contaminated laboratory samples. Some scientists still believe the findings reflect a contaminant.
Dr. Lo has published several papers on the microbe in The American Journal of Tropical Medicine and Hygiene, some after other journals rejected them.
In an interview, Dr. Lo said his team almost dropped the research because of frustration, criticism and a lack of Government support. But last month, prompted by Dr. Lo's latest reports and criticism that it was ignoring his work, the National Institutes of Health held a meeting in San Antonio to listen to Dr. Lo.
''We have an open mind and we are trying to see if we can settle this one way or the other over the next several months,'' said Dr. Anthony S. Fauci, who heads the National Institutes of Allergy and Infectious Diseases. ''If it is an important pathogen, then let's see what we can do about it. And if not, let's move on.''
The meeting was led by Dr. Joel B. Baseman, a mycoplasma expert at the University of Texas Health Sciences Center at San Antonio. He said the participants were ''very impressed with the quality of science that Dr. Lo's group displayed.''
''The pathology data was solid and convinced us that the agent is in the tissues,'' Dr. Baseman said. The ability of M. incognitus to cause a fatal wasting disease in monkeys and mice persuaded most participants that the microbe ''has the potential to cause disease in humans,'' Dr. Baseman said, although solid proof is lacking.
From autopsy specimens in 22 of 32 AIDS patients, Dr. Lo's team found evidence that M. incognitus damaged the brain, liver and other tissues. The microbe was detected in the placentas of two mothers with AIDS.
Dr. Lo also reported finding M. incognitus in samples from six military personnel from different geographic areas who were not infected with the AIDS virus. The men and women, who were from 29 to 40 years old, died one to seven weeks after developing a flu-like illness and persistent fever. In each case, military physicians were unable to identify the cause of death.
But Dr. Lo later discovered the mycoplasma in samples from the patients and determined that it was probably the cause of death.
Unlike most other infections, the one apparently caused by M. incognitus does not strike a particular organ but affects many tissues. For unknown reasons, the body does not mount its usual immune response, perhaps because of special biological properties of the microbe. No simple, practical test exists to detect M. incognitus infection in blood and other specimens. In particular, M. incognitus cannot be grown in cultures using specimens from sick people, the way staph and other microbes are. Dr. Lo said one reason he did not initially believe his microbe was a mycoplasma was because he had trouble growing it with standard methods.
Dr. Baseman said Dr. Lo never would have picked up the agent without a new technique known as polymerase chain reaction. By vastly multiplying fragments of nucleic acids from a microbe in a few hours, the technique can identify microorganisms that otherwise would be impossible to detect.
Because of the microbe's elusiveness, researchers are finding it difficult to confirm the findings and to determine whether the microbe is an important cause of illness in the general population.
Dr. Lo was criticized earlier this year when he did not release key substances involved in his experiments to other scientists. But Dr. Lo explained that about a year ago he learned that what he had been calling a virus was probably a mycoplasma. To give the substances to other investigators then would have compelled him to tell them that the microbe was probably a mycoplasma, a disclosure he did not want to make until it was reported in a scientific paper then waiting to be published. He said he has since distributed the substances to investigators. Researchers have begun organizing studies in several centers to determine how often M. incognitus occurs among people infected with the AIDS virus, those with other illnesses and healthy people. An important question is at what stage of an AIDS infection M. incognitus appears.
If infection occurs early, it could suggest that the microbe helps, or even causes, the progression from a symptomless infection with the AIDS virus to disease. If the infection develops after other AIDS symptoms appear, it could indicate that it is a secondary invader that causes an opportunistic infection.
Doctors also hope to develop a preventive treatment, as they have for pneumocystis pneumonia, another opportunistic infection in AIDS.
Laboratory tests show that M. incognitus fails to respond to erythromycin, an antibiotic commonly used to treat other mycoplasma infections. But M. incognitus appears susceptible to tetracycline and other antibiotics in test tubes. Studies are needed to determine if antibiotics work in people infected with M. incognitus.
Another goal is to learn what factors apparently allow M. incognitus to cause widespread infection without provoking a response from the immune system. If the factors can be identified, therapies might be developed to boost the immune response.
No one knows how M. incognitus is spread. Family members and people in close contact with infected individuals did not themselves become infected. The interest now being shown in M. incognitus is vindication of sorts for Dr. Lo. The controversy over his findings stems largely from the way he originally identified the microbe, using a technique known as transfection. The technique involves taking DNA from a microbe and then using electrical devices, chemicals and other methods to insert the genetic material into a cell, where it undergoes replication.
The technique is often used to detect viruses, but generally does not work for bacteria. Dr. Baseman said it remains a mystery why the technique worked for mycoplasma.
Dr. Lo developed immunological techniques tailored to detect the organism that he found by transfection. He also used the immunologic techniques to help identify the microbe in the autopsies. In addition, he identified it using electron microscopy. For unknown reasons, Dr. Lo's team can grow in cultures the M. incognitus obtained by transfection.
Asked if M. incognitus by itself could cause a disease resembling AIDS, if not AIDS itself, Dr. Lo said: ''That's a good question. I don't know, and it will take a lot more work and time to answer it.''
Photos: Dr. Shyh-Ching Lo of the Armed Forces Institute of Pathology discovered a microbe and later determined it was a mycoplasma. (Armed Forces Institute of Pathology); An electron micrograph of Mycoplasma incognitus in the empty extracellular space in tissue taken from the liver of a person with AIDS.
