David Da-I Ho

Molecular biologist David Da-I Ho (born 1952) has dedicated his career to identifying a cure for acquired immune deficiency syndrome (AIDS). His greatest contribution to the worldwide battle against AIDS came in 1996 when he combined state-of-the art AIDS medications in a way that stopped the progression of the human immunodeficiency virus (HIV), which leads to the deadly AIDS condition.

AIDS researcher David Ho was the fourth scientist to identify the cause of AIDS as a virus that attacks the body's immune system. Now chief executive officer and scientific director of the Aaron Diamond AIDS Research Center (ADARC), Ho has been at the forefront of the worldwide battle against the AIDS epidemic and remains hopeful that HIV can be eradicated.

A Strong Work Ethic

Ho was born on November 3, 1952, in Taichung, a small town in Taiwan where transportation was by means of bicycle and the only form of communications technology was a small radio. His parents, Paul and Sonia Ho, were poor but proud; they lived in a small four-room house bordering a ditch that served as an outdoor toilet. Ho's father, an engineer, had high hopes for his family. Reflecting Paul Ho's optimism, he named his first child Da-I, meaning "Great One," then boarded a freighter for the United States in 1956. Fluent in English, he enrolled in an advanced engineering degree program at the University of Southern California, Los Angeles (UCLA), determined to make a better life for his growing family. It would be nine years before Paul Ho felt secure enough in a new job to send for his wife and two young sons.

Raised by his mother, Ho showed an early aptitude for math and science, staying after school for advanced class work and transforming the family garage into a scientific laboratory. He also exhibited the same penchant for comic books and sports as many boys his age. It was clear to all that the young boy was following the family tradition; many of his relatives were involved in science-related jobs.

In 1965 Ho arrived in the United States, where his father had established a home. David and younger brother Philip were joined by another brother, Sidney, as they settled into their new residence in an African American neighborhood in central Los Angeles. Wanting to assimilate into his new country and inspired by his Christian beliefs, Paul Ho renamed his children, and Da-I became David. While his father had spent nine years adapting to American language and culture, 12-year-old David spoke only Chinese and without even a basic knowledge of the English alphabet, the language of math became his refuge. Putting all his energy into his schoolwork, he showed the same determination as had his father. "People get to this new world, and they want to carve out their place in it," he told a Time contributor. "The result is dedication and a higher level of work ethic. You always retain a bit of an underdog mentality."

During his first year at school in Los Angeles, Ho was looked upon as an outcast because he never talked with his classmates and never participated in class discussions. Within six months he had mastered the English language enough to break down his social barriers, and his grades shot up. A daily dose of television also aided in his eventual fluency in spoken English, and the game of basketball provided him with friends. By the end of high school, Ho's transcript reflected his hard work, and the decision to go to college became clear.

Deciding to go into physics, Ho applied to the best schools and ultimately enrolled at the Massachusetts Institute of Technology (MIT). Unhappy on the east coast being so far from home, he returned to California to finish his bachelor of science degree and graduated summa cum laude from the California Institute of Technology in 1974. Ho was fascinated by the ongoing advances in the area of molecular biology and the cutting-edge technology involved in gene splicing. This fascination prompted him to make a second trip east and earn a medical degree from the Harvard-MIT Division of Health Science and Technology in 1978.

A Series of Mysterious Deaths

In 1981 Ho became a resident in internal medicine at UCLA's Cedars-Sinai Medical Center and advanced to chief resident the following year. He was concerned by the large number of homosexual men who exhibited the same unusual symptoms. Their immune systems were seemingly inoperable; infections that would otherwise be easily overcome such as pneumonia and brain infection (toxoplasmosis) were suddenly proving fatal. Diagnoses ranged all over the map, from allergies to substance abuse to sexually transmitted diseases. Some researchers suspected that it was more likely a parasitic, bacterial, or viral infection that destroyed the body's immune system, and Ho was among them. He decided to make the cause of these deaths his focus. When that cause was eventually determined, it was found to be AIDS.

When the AIDS epidemic became understood in the late 1970s, it drew the best minds from the country's finest research hospitals, both bacteriologists and virologists. Ho worked first from UCLA, moving his research into the existence of a possible virus to Massachusetts General Hospital's infectious diseases unit in 1982, where he worked alongside fellow virologist Martin Hirsch. Ho was the fourth researcher to identify HIV; Paris-based researcher Luc Montagnier of the Pasteur Institute was the first to isolate the retrovirus, followed by American scientist Robert C. Gallo of the National Cancer Institute and Jay Levy of the University of California's San Francisco Medical Center.

Ho relocated to Cambridge, Massachusetts, from 1982 to 1985 to serve as a Harvard University research fellow in medicine before returning to UCLA in 1986. With the HIV virus now isolated, he was able to provide others colleagues in the battle against AIDS with much-needed information about the disease, including its neurological complications. "He was the first to show that it grows in long-lived immune cells called macrophages," a Time reporter explained, "and was among the first to isolate it in the nervous system and semen." Ho was also able to subdue a public scare by verifying the fact that there not sufficient HIV virus in human saliva to transmit AIDS on drinking glasses or eating utensils or while kissing. Other scientists also added pieces to the AIDS puzzle, and within a few years researchers had discovered that the virus destroys the immune system by entering T-cells, cells that help keep disease from taking hold by attaching and unlocking the CD4 receptor proteins on the cells' surface.

Research Setbacks Reoriented Search for a Cure

AIDS researchers believed that injecting AIDS patients with massive doses of CD4 protein could intercept the virus and prevent it from attaching to those CD4 receptor proteins located on the surface of T-cells. Ho and Robert Schooley of the University of Colorado Medical Center in Denver tested soluble CD4 in over 20 AIDS patients, but the results were disappointing: some HIV strains, termed "wild viruses," are able to distinguish the real CD4 proteins from the CD4 decoy particles.

Frustrated at this failed effort to stop HIV's rampage, Ho decided to start at the beginning and study the onset of the virus. Using as subjects four homosexual men who displayed the flu-like symptoms of an early HIV infection, he discovered through research that millions of infected particles are present in a patient's blood stream, even at the early stage of the disease. In fact, the level of virus particles remains a high constant during the course of the disease, resulting in its rapid spread. Ho's results mirrored those of fellow researcher Dr. Robert W. Coombs, affiliated with the Unversity of Washington School of Medicine, in proving that the virus directly damages the immune system and actively reproduces even in early stages and does not at first lie dormant as was previously believed.

In addition to his research, Ho established a teaching career, beginning as assistant professor in 1986 and rising to the post of associate professor of medicine at the UCLA Medical School three years later. In 1990 he was named chief executive officer and scientific director of the new Aaron Diamond AIDS Research Center (ADARC), the largest privately funded AIDS research center in the world, established by philanthropist Irene Diamond and based in east Manhattan, New York. He left UCLA and relocated his career as an educator at New York University, becoming professor of medicine and microbiology at the university's medical school and co-director of its Center for AIDS Research. In 1996 he moved to the Rockefeller University and a new professorship. Despite the fact that his work had increasingly taken him away from the "front line" of AIDS, the clinics, the emergency rooms, the hospitals, Ho remained dedicated to fighting the disease on a personal level. As he told Judy Woodruff in an interview with CNN: "I think everybody who's involved in patient care in the AIDS field has been personally affected in many different ways. We've seen too many tragedies, too many deaths, due to this virus. There's no question that myself and all of my colleagues who have cared for AIDs patients have been touched in a very deeply emotional way."

Attracting many top-notch AIDS researchers from around the world, ADARC quickly became a heavy hitter in the battle against AIDS. In addition to testing a wide variety of AIDS treatments, including herbal remedies used by AIDS patients, Ho and his team continued to focus on ways the virus might be contained and worked closely with the Centers for Disease Control in tracking the spread of AIDS. Through work at ADARC, Ho revealed that the presence of white blood cells, a byproduct of a functioning immune system in HIV patients shows that the immune system responds in combating the virus early on. Then why does the virus level in AIDS patients become so high so quickly? One possibility, Ho reasoned, was that in the earliest stages of the virus the immune system sets to work killing off viral particles; because the HIV virus replicates immediately upon infection, the disease progresses rapidly, causing the over-taxed immune system to quickly give out and the production of virus particles is then allowed to continue unabated.

"Cocktail" Therapy Proves Effective

In 1994 those battling AIDS were handed a new weapon in the form of non-nucleoside protease inhibitors, protease being an enzyme component of HIV that breaks down the proteins in the virus so that an infectious particle is formed. Developed by drug researchers, protease inhibitors stop the breakdown, bringing to a halt the replication of HIV unlike AZT, the first drug to show effectiveness, which only slows the spread of the virus. Within the year Ho and his team at ADARC had devised an experiment utilizing protease inhibitors and two other drugs, reverse transcriptase inhibitors, administering these to patients in the early stages of the disease in a "cocktail." The results were dramatic and were quickly disseminated around the world: through combination therapy Ho had halted the AIDS virus in its tracks. Even better, he showed that once the HIV is halted, the body's immune system is able to reduce viral particles to undetectable levels. And Ho's use of a combination of drugs reduces the chances that virus particles will mutate and become resistant to the drug therapy.

While many scientists have been quick to point out that Ho's drug treatment is not a cure for AIDS as it does not restore the health of organs already damaged, there is no sense of how long its positive effects will last. There is the chance that the virus may remain dormant in certain body organs, but the treatments ability to stop the advancement of HIV was the first positive news for those infected with the disease. It has also provided other researchers using techniques such as X-ray crystallography with information useful for continued work. Meanwhile, researchers have become split in their goals: some, like Ho, believe that HIV can be eradicated through the use of antiviral drug therapies, while others hope only to control the epidemic. As Ho noted to Woodruff, "We, basically, have, for the first time, staggered the virus, and the new optimism comes from the fact that we now realize maybe, just maybe, this virus is not as invincible as we have previously thought… . This is just a beginning of this battle, and I think we have taken the first step successfully." Overall, Ho maintains, although he continues to refine and improve the effectiveness of his protease inhibitor "cocktail," combination drug therapy is effective only in individual cases in individuals with access to physicians and expensive medicines. In order to protect the world population, the true work is in the area of AIDS prevention: vaccines and education.

Ho continues his work at ADARC, where in 2002 he and his staff of over 100 were investigating a group of antiviral proteins called alpha-defensins that seem to help some individuals remain resistant to HIV infection. He also continues in his role as an educator. In addition to serving in an advisory capacity to such organizations as the scientific advisory board of the National Cancer Institute and the American Foundation for AIDS Research, he continues to author or coauthor scientific articles in journals such as Nature and the New England Journal of Medicine. For his accomplishments in the area of AIDS research, Ho was named 1996 Man of the Year by Time magazine and has been honored for his work in other ways. Among his scientific prizes are the Scientific Award of the Chinese-American Medical Society, the Ernst Jung Prize in Medicine, New York City Mayor's Award for Excellence in Science and Technology, the Squibb Award, and a Presidential Citizen's Medal. Making his residence in Chappaqua, New York, Ho is married to artist Susan Kuo, with whom he has three children: Kathryn, Jaclyn, and Jonathan. He is a member of the Committee of One Hundred, a Chinese American leadership organization, in addition to several scientific groups. Interestingly, despite his high professional profile, his command of the English language, his role as director of a U.S. corporation, and his successful assimilation into U.S. culture, Ho still performs his mathematical calculations in Chinese.

Books

Notable Scientists: From 1900 to the Present, Gale, 2001.

Periodicals

Advocate, July 21, 1998.

Asian American Times, August 2001.

Chemical and Engineering News, September 30, 2002.

Gay Men's Health Crisis: Treatment Issues, May 15, 1991.

New York Times, December 14, 1989; January 31, 1990; September 27, 2002.

Rolling Stone, March 6, 1997; April 29, 1999.

Time, December 30, 1996; August 20, 2001.

Wall Street Journal, December 17, 1996.

Online

"Interview with Dr. David Ho," CNN Interviews: Medical Detectives,http://www.time.com/time/moy/ho.html (February 15, 2003). □

David Da-I Ho 1952-

Virologist, aids researcher

An Immigrant Success Story

Born on 3 November 1952, Da-I Ho was the first child of Paul Ho, an engineer, and Sonia Ho. In 1955, when Ho was three, his father left Taichung, Taiwan, and immigrated to the United States. Da-I did not see his father for nine years. In 1965 Ho left Taiwan with his mother and brother to join his father in Los Angeles. Ho's father renamed him David and his brother Phillip. A third child, born in the United States after the reunion, was named Sydney. In 1996 Ho told Judy Woodruff of the Cable News Network (CNN) that his parents early impressed upon him the importance of getting a good education. Their sacrifices in the effort to make a better life for their family furthered his determination to excel academically. Surmounting his early difficulties with English, which he did not know at all when he arrived in the United States, Ho achieved academic success in high school. After graduation he attended the Massachusetts Institute of Technology (MIT) in Cambridge for a year before transferring to the California Institute of Technology (Cal Tech) in Pasadena. During his undergraduate career, Ho frequented the blackjack tables in Las Vegas, where he became so adept at memorizing and counting cards that several casinos banished him. Ho graduated summa cum laude from Cal Tech in 1974, having changed his emphasis from physics to medical research. He returned to Cambridge and enrolled at Harvard Medical School, earning an M.D. in 1978. After completing his residency in internal medicine at the Cedars Sinai Medical Center in Los Angeles in 1981, Ho served for a year as chief medical resident.

Discovery of HIV

During this period Ho began to encounter otherwise healthy homosexual men suffering from infections that ordinarily did not afflict those with functioning immune systems. Soon other patients with similar infections began arriving at the hospital in increasing numbers. They included not only gay men, but also intravenous drug users, hemophiliacs, those who had received blood transfusions, and babies. Each of the cases was distinct, but all had one element in common: whatever was making these people sick attacked the T-cells and destroyed the immune system, making it vulnerable to even the most harmless of infections. From the beginning Dr. Ho suspected a virus was responsible. He was not the first, however, to isolate the virus that causes AIDS. That honor went to Dr. Luc Montagnier of the Pasteur Institute in Paris, Dr. Robert C. Gallo of the National Cancer Institute in Bethesda, Maryland, and Dr. Jay Levy of the University of California, San Francisco. An immunologist at UCLA, Dr. Michael Gottlieb, reported the first documented cases of "gay pneumonia."

Big Breakthrough

Ho, working alone or in concert, altered the way in which scientists and physicians understood HIV and AIDS. His research during the 1980s and 1990s showed how HIV attacked the immune system and how the body combats the infection in its early stages. He thus prompted a major shift in the treatment of AIDS, emphasizing the early instead of the latter stages of the illness. Ho demonstrated that there was no initial dormant stage of infection, as AIDS researchers had once believed. From the beginning the body fights the disease, launching billions of immune cells to counter the threat. As long as doctors thought the virus was not very active in the early stages of infection, it made sense to delay radical treatment until it emerged from hibernation and began to ravage the immune system. Ho concluded, however, that the most effective treatment ought to be administered in the earliest stages of the disease, before it had utterly depleted the natural defense mechanisms.

Daring Experiment

In 1995 Ho, then scientific director and chief executive officer of the Aaron Diamond AIDS Research Center in New York City, began a daring experiment. To treat patients infected with HIV (Human Immunodeficiency Virus), the virus that causes AIDS, he began administering powerful new drugs called protease inhibitors in combination with standard antiviral medications. Other physicians, such as Dr. George Shaw of the University of Alabama at Birmingham, had done the same. Ho's bold innovation was to give the protease-inhibitor medication to patients in the earliest stages of infection. With this approach Ho came tantalizingly close to eliminating the virus from the blood. Within weeks of beginning the treatment the levels of HIV in his patients' blood dropped so low that it could no longer be measured. Ho suggested that if the disease is detected and treated within three months of infection, the patient stands a good chance of being entirely free of infection within two or three years. Ho was quick to caution, however, that his treatment is neither a preventive nor cure for AIDS and that it offers little hope to those suffering from the advanced stages of the disease. In those cases Ho's therapy may temporarily improve a patient's health but does not offer the prospect of long-term recovery. Ho was among the first to point out additional complications. The treatment was expensive, costing approximately $20,000 per year, and was thus unavailable to all but the wealthiest or best-insured patients. For twenty million victims of HIV in the developing world such remedy was out of the question. Moreover, Ho and other AIDS researchers were concerned lest the medication itself inadvertently produce a mutant strain of the virus immune to available drugs and thereby spawn a new and even more devastating epidemic. Yet, Ho's research brought a sense of hope, however tentative it might have been, to those who suffered from HIV For the first time someone demonstrated that HIV was not invulnerable and that AIDS might not be a death sentence. Ho told Judy Woodruff in 1996, "We basically have, for the first time, staggered the virus, and the new optimism comes from the fact that we now realize maybe, just maybe, the virus is not as invincible as we had previously thought."

Sources:

Howard Chua-Eoan and Dan Cray, "The Tao of Ho," Time Australia, 1 (30 December 1996): 44-45.

Philip Elmer-Dewitt, "Time's Man of the Year for 1996: Dr. David Da-i Ho," Time, 148 (30 December 1996): 52-55.

Christine Gorman and Alice Park, "The Disease Detective," Time Australia, 1 (30 December 1996): 36-43.

Miriam Helbok and Sidney Ho, "In-Depth Biography: Dr. David Ho," Click2Asia.com, Internet website.