By Martha Henry
It’s unlikely that you’ll ever meet anyone more focused than Max Essex. A 1986 New York Times profile described him as “mild mannered” with “a thatch of thick hair” and “among those in the forefront of the worldwide effort to find a cure for acquired immune deficiency syndrome.” Today, though his hair is white, that description still fits. Essex, now in his 70s, still arrives at the office by six o’clock most mornings and spends long days planning and improving research projects around the world. He remains, as the Times reporter described, “deeply exercised about the fate of AIDS patients.”
As a young microbiologist, Essex started out studying the relationship between viruses and cancer. He arrived at the Harvard School of Public Health in 1972 as a junior faculty member. He worked to understand how viruses cause leukemia and lymphoma in cats and whether or not similar viruses might cause similar forms of cancer in people.
in 1974, Essex showed that a retrovirus caused immune suppression in cats. A few years later, Dr. Robert Gallo discovered the first retrovirus in humans. As soon as Essex knew that human retroviruses existed, he wanted to know if they could also cause immunosuppression, significantly damaging the body’s ability to fight disease.
The Epidemic Begins
In 1981, Essex read a short report published by the Centers for Disease Control (CDC) that began, “In the period October 1980-May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. Two of the patients died.” This was the first mention in the medical literature of what would later be termed AIDS. Pneumocystis pneumonia is usually found in severely immunosuppressed patients.
As the disease spread, Essex hypothesized that a retrovirus might be the cause of AIDS. He was right. The CDC called to enlist his help. Samples of the virus were sent to his lab. At the same time, AIDS patients began showing up in Boston hospitals. Essex collaborated closely with Dr. Martin Hirsch, an infectious disease researcher and clinician at Massachusetts General Hospital. “In the 1980s, AIDS was a devastating diagnosis to receive,” said Hirsch. “Our hospital was loaded with people dying from this infection.”
People were dying fast from a disease no one understood. Panic and stigma were widespread. Researchers at Harvard and around the world worked impossibly long hours to answer basic questions about the virus.
Essex and his team provided many of the early answers. They determined that HIV could be transmitted through blood to hemophiliacs and transfusion recipients. They identified the specific protein (gp120) that’s used worldwide for AIDS tests and blood safety screening. They provided the first evidence that AIDS could be transmitted by heterosexual intercourse. With collaborators, they discovered the first evidence of simian immunodeficiency virus (SIV), the counterpart of HIV in primates. With Senegalese collaborators, they discovered that a second type of HIV, HIV-2 existed in western Africa and that it was less virulent than HIV-1, the virus found predominantly in the U.S. and Europe.
Dr. Richard Marlink, at the time a research fellow in the Essex Lab, remembers, “It was a time when discoveries were happening almost monthly—major discoveries—with Tun-Hou Lee and Phyllis Kanki and others. They were deciphering and figuring out where this virus came from and how it worked and then how we could detect and, ultimately, how we could treat it.”
Essex and other Harvard researchers made many of the early discoveries about HIV/AIDS. In the late 1980s, Dr. Harvey Fineberg, Dean of the Harvard School of Public Health, proposed creating the Harvard AIDS Institute (HAI) to coordinate and strengthen efforts across the university.“Max Essex was the obvious choice to lead the enterprise,” said Fineberg. “He had the personal connections with the investigators throughout the university and beyond. And by personality, he was a great leader and one that we knew we could count on to make this the enterprise we wanted.”
Crisis in Africa
The introduction of triple-cocktail antiretroviral therapy (ART) in 1996 changed the fate of AIDS patients. People who were expecting to die got better. After years of agonizing deaths, there was suddenly hope, at least for people in wealthy Western nations. The cost of ART was well over $10,000 a year per patient.
It was also becoming increasingly clear that AIDS was devastating Africa. In the 1980s, Essex and Senegalese colleagues had established a study of commercial sex workers in Dakar to investigate the dynamics of transmission and methods to prevent the spread of HIV. New infections in Senegal had been controlled. Something completely different was happening in southern Africa. Essex wanted to know why.
Maurice Tempelsman, a U.S. businessman working in Africa, had been instrumental in helping Essex establish collaborations in Senegal. Essex turned to him again for advice. When Ketumile Masire, the President of Botswana, was visiting Washington, Tempelsman arranged for Essex to meet him. Masire invited the Harvard professor to visit Botswana and welcomed his guidance.
Essex was soon on a plane. He knew that to make the biggest difference, he had to work in the area most affected. Botswana had one of the highest rates of HIV in the world, with over 20% of adults and 37% of pregnant women infected. The purpose of his trip was to explore the possibility of collaborating with Botswana’s Ministry of Health and collect blood samples to analyze in his Boston lab.
“I think he was overwhelmed by what he saw. I can remember how quiet he was as he absorbed the pain and suffering by patients when we walked him through the medical ward,” said Dr. Joseph Makhema, then an internist treating AIDS patients at Princess Marina Hospital in Gaborone, Botswana’s capital. “Bed occupancy was greater than 120% and floor beds were the order of the day. Mortality was high and staff morale was low. It was common to have five to ten deaths per day.”
Essex helped Makhema collect blood samples. At the time, Botswana had no access to antiretroviral drugs. Doctors could only treat their patients’ opportunistic infections and keep them as comfortable as possible.
Essex returned to Boston. Flying to and from Botswana would soon become commonplace for him. That same year, 1996, the Botswana Harvard AIDS Institute Partnership (BHP) was established. Essex was given space in a trailer on the grounds of Princess Marina Hospital. A small lab was created in a nearby storage shed.
The best model for collaborations, Essex had learned, was to have the host country determine priorities and set the research agenda. Meetings took place with the Ministry of Health and others.
In 2001, the Botswana–Harvard HIV Reference Laboratory opened. The 25,000-square-foot research center has become one of Africa’s leading scientific institutions and also serves as headquarters for the BHP.
As a leading AIDS researcher, Essex was able to win competitive grants from the U.S. National Institutes of Health. The first big clinical trial in Botswana was on the prevention of mother-to-infant transmission of HIV. Other important studies have followed, in areas including HIV treatment, acute infection, AIDS pathogenesis, cost-effectiveness of ART, genetics of susceptibility to HIV, AIDS in children, and cancer and HIV.
With guidance from the BHP, the Government of Botswana established a national ARV program in 2002 to provide free treatment to any citizen in need. For the first years of the program, drugs were donated by the Bill & Melinda Gates Foundation and the Merck Foundation.
In 2015, the BHP employed over 300 people, mostly Africans. Makhema, the doctor who worked with Essex in 1996, is now the C.E.O.
The Next Generation
Makhema credits Essex’s “ability to attract quality loyal and dedicated staff” as one reason for the BHP’s success. Essex considers teaching and mentoring to be high priorities, especially training young Africans in hopes that they’ll return to Africa. A two-way flow of trainees between Harvard and the BHP helps bolster projects at both places.
Dr. Pride Chigwedere was a young doctor treating AIDS patients in Zimbabwe when he met Essex. “Max was doing work on AIDS in southern Africa, my interest area,” said Chigwedere. “I had no dreams of coming to Harvard. Max reached out and sponsored me.”
Chigwedere earned his doctorate at Harvard. He currently works as a Senior Advisor to the UNAIDS Office to the African Union. “Max remains my mentor. I keep asking for his guidance and support,” said Chigwedere.
Preventing New Infections
In the past decade, preventing new HIV infections has been a major focus for Essex. He and his team have had success in determining how best to prevent pregnant HIV-positive women from transmitting the virus to their children. Transmission rates in Botswana, once as high as 30%, have been reduced to 1% in clinical trials.
Preventing adult HIV infections is a more difficult challenge. As a Senior Principal Investigator for the Botswana Combination Prevention Project (BCPP), Essex currently spends much of his time troubleshooting problems. The ambitious clinical trial he and his team designed is now entering its second year in 30 villages.
As hope for an AIDS vaccine dims, Essex sees the use of antiretroviral therapy, which has been shown to nearly eliminate transmission in trials conducted in discordant adult couples, as the best strategy to prevent new infections and eventually end the epidemic.
“I don’t believe for a minute that AIDS is going to disappear as a disease in the next 50 years,” said Essex. “I think it’s impossible that will happen, or near impossible. I think, on the other hand, that it could be reduced to a very rare disease when transmissions would be thought of as very unusual.”
Making AIDS “very unusual” is what still motivates Max Essex.
“He continues to work extraordinarily hard,” said his old friend Marty Hirsch. “The current studies that he’s doing on trying to prevent spread at a local level are extremely important. Exactly what the results of these trials are going to be, of course I don’t know, but one way or another, they are going to significantly influence our efforts to control infections in areas like Botswana.”
Joe Makhema says the same thing in a slightly different way: “Max is a stellar scientist and human being driven by commitment and passion to end human suffering from the
Title photo by Dominic Chavez
Martha Henry is the Director of Communications for the Harvard T.H. Chan School of Public Health AIDS Initiative.