Early Research Days of AIDs: Fighting an unknown killer

Guest Blogger: Tom Folks, Ph.D.

 

Dr. Tom Folks is recognized as one of the world’s preeminent HIV researchers. He became involved with the disease in the early 1980s—even before its origin had been determined.  In, fact, it was Dr. Folks, who was one of the first few scientists to grow the virus in a lab, which paved the way for serious research to begin. Here, he recounts the events during those early days of identifying the virus and beginning the fight.

In the 1980s, an HIV diagnosis was considered a death sentence.  A healthy 20-year-old diagnosed with the disease could expect to live just 12 years.  Treatments were only slightly effective (if at all), and side effects often made patients sicker.  Physicians were still bewildered by this new malady.

 

1983:  A Mystery Illness.  And Some Red Herrings.

I was primarily trained as an immunologist.  While I was a post-doctoral fellow at the National Institutes of Health, my lab director approached me about a new disease emerging that primarily was affecting homosexuals. The only laboratory information at the time about these patients showed they were losing their T lymphocytes and becoming susceptible to many types of infections.

Since I had experience growing human lymphocytes from my previous pre-doctoral work, I was recruited to culture patients T cells and determine if any unusual changes were taking place.  By the methods I was using, I didn’t notice anything unusual about the cells, except the cells died earlier than normal in culture.

We analyzed the culture media used to grow the cells and found an unusual fungus only from the cultures of the patient’s cells and not from the normal controls.  Of course, this was exciting and urged us to further analyze the fungus.

Interestingly, the fungus was very rare and could not be isolated from the room or other areas that might have contaminated the cultures.  We were never able to isolate the fungus from any other patients—ruling out this as a possible etiology.

Looking back, we theorized that the first patients from whom we identified the fungus were from the same location, and being treated with an experimental drug. This drug was most likely the source of the contamination. Since we were so focused on determining the etiology of the new immunodeficiency disease, we chose not to pursue the fungus issue any longer.

 

Dr. Thomas Folks

Dr. Thomas Folks

1983-1984:  Finding The Virus—In A Refrigerator

At this time in my career, I was pursuing every avenue, looking for the cause of this newly emerging immunodeficiency disease.  Bacteria from dogs and viruses from cats were not out of the realm of possibility.  We followed every lead brought to us.  All were dead ends.

One afternoon, I was approached by one of the lab chiefs, an expert in virology. Since I was one of the scientists in the National Institute of Allergy and Infectious Disease at the NIH who was growing and investigating T cells in humans, he asked if I could work with his lab to attempt to isolate a newly-discovered virus. He indicated that it had come from Dr. [Luc] Montagnier’s lab in France—and that it purportedly grows in human lymphocytes and had come from patients exhibiting immunodeficiency.  (Dr. Montagnier is credited, along with Dr. Robert Gallo, as a co-discoverer of the AIDS virus. Dr. Montagnier was awarded a Nobel Prize for his work in 2008.)

Of course, as a young scientist who was pursuing every lead possible, I said yes.

The lab chief said he would bring it in the next day, since he had just returned from France the night before and had it in his freezer at home.  After several days of culture, a detectable virus grew and was detected by a crude enzyme test (Reverse transcriptase).  The excitement was overwhelming!

This did turn out to be the virus that causes AIDS, first called LAV (Lymphadenopathy Associated Virus) and later to be renamed HIV (Human Immunodeficiency Virus).

 

1985-86:  Creating Cell Lines—And Discovering HIV’s Insidious Latency

As I became fully entrenched in the field of AIDS and the study of how the virus caused disease (pathogenesis), my expertise grew in the area of viral culture and cell biology. I developed a technique of immortalizing the virus in cancer cell lines such that it could infect the cells without killing them. The cells could be cloned and distributed for research purposes.

This provided an opportunity to work with the virus to researchers who did not have access to patients or isolation techniques.

Two cell lines that I developed were 8E5 and U1.  The first cell line, 8E5, had the virus integrated into its genome (DNA) and continuously expressed a mutant non-infectious virus.  This provided an ability to work with the virus and not fear its infectious nature. And, by growing the cells in large quantities, it also provided a source to mass produce the viral components for use in diagnostic assays.

The second cell line, U1, was a special—and intriguing—cell.  We discovered that although it was infected with the virus, it did not express or release it. However, when we treated the cell line with cytokines (cellular hormones), it would then amazingly express and secrete large quantities of virus.

This was the discovery of viral latency in AIDS and provided the next big challenge in AIDS research and patient management.  We now understood that once the virus had entered the host, it would always be there, and possibly lie dormant until the right signal came along to wake it up.

The virus was dynamic and resourceful.  So we began to understand that our research and treatments would have to be just as resourceful to keep up.

HIV diagnoses peaked in the late 1980s and early 1990s, and have decreased as education on prevention has reached more people.  For a 20-year-old with HIV, the average life expectancy of 12 years after diagnosis in the 80s has now risen to 49 years, with proper treatment. This doesn’t take into account new treatments that are being researched, nor vaccines that could prevent new infections. We haven’t cured AIDS.  But we are making significant progress.