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[PROFILE] Dr. David Ho (AIDS Researcher)

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  • madchinaman
    THE TAO OF HO BY HOWARD CHUA-EOAN DECEMBER 30, 1996/JANUARY 6, 1997 VOL. 148 NO. 29 http://www.time.com/time/special/moy/ho/cover.html If you lean in close,
    Message 1 of 1 , Jan 20 11:41 AM
      DECEMBER 30, 1996/JANUARY 6, 1997 VOL. 148 NO. 29

      If you lean in close, conspiratorially, Sonia Ho may just let slip a
      secret she keeps about her son David. She will speak in a hush, as
      if to elude some spy's eavesdropping from behind the potted palm.
      But she badly wants to divulge her information. Thus, slightly
      abashed but nonetheless proud, she will confide, "He's kind of a
      genius, you know. I'm not supposed to say that, but it's true."

      Mothers are allowed to say these things. But one doesn't have to be
      David Da-i Ho's mother to be aware of his brilliance. He lays forth
      clearly and succinctly some of the boldest yet most cogent
      hypotheses in the epic campaign against HIV; at the same time, he
      operates nimbly through the budgetary and political pitfalls of the
      enterprise. And though he is monumentally tranquil in demeanor, he
      has been known to fling the occasional hot one-liner against
      naysayers--once, "It's the virus, stupid!" to those who insist HIV
      is not the cause of AIDS.

      Genius, however, is a word that originally referred to a guardian
      spirit. Ho cuts too slight a figure to qualify as a force of nature,
      but his spirit is startling: a fierce competitiveness that is
      manifested as a subtle calm, a passionate transcendence. It is
      evident in his gestures. His fine-fingered hands do not punch out
      arguments; rather they escort logic through tangles of confusion,
      gently prodding reason his way. Perhaps Sonia Ho is right to be
      hushed, for her son's genius emanates from the depths of his
      family's experiences, and it is not quite Asian to make a display of
      one's legacies. But she is also right to be proud, for this is
      America, and her son is an extraordinary American success story.

      TIME's 1996 Man of the Year was born in Taichung, Taiwan, on Nov. 3,
      1952. At birth, he was given the name Da-i, two Chinese ideograms
      that literally mean "Great One," a Taoist term of vast cosmological
      consequence. It is a name reflecting great expectations. Taichung,
      however, was a quiet town in the Taiwan boondocks, and the Ho family
      lived in a modest four-room house with a backyard ditch that served
      as a toilet and from which farmers collected fertilizer for their
      fields. To forge a better life for his family, Ho's father took ship
      in 1956, traveling 18 days on a freighter to America. For nine
      years, Da-i would know his father only through letters and parcel

      For Da-i and his younger brother, the years of waiting were filled
      with long school days that included, after a quick stop at home for
      dinner, a 20-minute bike ride to a cram school for extra tutoring.
      As they rode home in the dark through the empty countryside, the
      eerie sounds of frogs and crickets would sometimes scare the
      brothers into frenzied pedaling. Street stickball was a welcome
      interruption. And whenever he could, Da-i would sneak off to the
      neighborhood store to leaf through comic books.

      When his father sent for the family, a seriousness came over Da-i.
      The 12-year-old packed his own bags and stayed awake throughout the
      flight to watch over his mother and his younger brother. They were
      traveling to a land they did not know and whose language they did
      not speak. It would be a place where they would receive new names
      and new identities. Their father, a devout Christian who now called
      himself Paul, had picked the boys' American names from the Bible.
      Thus it came to pass that Ho Da-i became David Ho and his younger
      brother became Phillip. For a few more years, Phillip would refer to
      David by the Chinese honorific for "older brother"; becoming
      American would take time.

      The family initially settled in a black neighborhood of central Los
      Angeles, not far from the University of Southern California, where
      Paul Ho pursued a master's degree in engineering. A translator for
      U.S. troops in China during World War II, he instructed his wife
      that their sons were to stick to Taiwanese and Mandarin Chinese and
      not learn English until they got to America for a better chance of
      speaking it without an accent. As Sonia Ho recalls in careful but
      imperfect English, "When we first come to U.S., we don't know any
      words. David would come home from school and say, 'I don't know what
      they talking about.' I'd say, 'Oh, what are we going to do?'" Says
      David: "We hadn't even learned the ABC's. I remember being laughed
      at by classmates who thought I was dumb."

      A diffident David did two things: he became an introvert and stuck
      close to the family, and he focused on school and achievement. Says
      Phillip, now a dentist: "He knew what it was he had to do." Sonia
      recalls, "If he got even one question wrong, he'd be very upset with
      himself." It was A's in everything, math, science--and English. Six
      months after starting school, David settled into the language,
      thanks to an English-as-a-second-language program and the miracle of
      TV. "We watched The Three Stooges," Phillip says. "We picked up a
      few phrases here and there and some mannerisms." When their parents'
      third son was born, Phillip and David got to choose the name. They
      skipped the Bible and picked Sidney, after a character in a Jerry
      Lewis comedy.

      Medicine was David's second choice as a career. After high school,
      he attended M.I.T. and Caltech as a physics major. He never let up
      on himself, at work or play. Though short, he was an intense
      basketball player. At Caltech, he took up chess. Characteristically,
      the first time he entered a tournament, he won.

      Ho soon realized that the most glittering prizes in science weren't
      in physics. Molecular biology was the cutting edge, gene splicing
      the hot technology. Medical research, says Ho, was much
      more "tangible." And so he made his way to Harvard Medical School.
      Soon enough, medicine provided the turning point of his career. His
      mother recalls, "He told me he saw a lot of young people die. He say
      that must be some disease, so he want to keep researching to find
      out why." Ho had met up with HIV.

      As he pursued medicine and then the virus, Ho's introversion
      faded. "It took many years to reverse itself," Ho says. At the same
      time, his brothers say, he grew less temperamental and developed his
      legendary tranquillity. When colleagues threw a tantrum, Ho gently
      offered advice from Chinese philosophers. One of his favorites is
      the Taoist sage Lao-tzu, who said, "The softest things in the world
      overcome the hardest things in the world."

      The equanimity deepened as Ho carved out time for his family. Even
      at school, he acted as a second father to his brother Sidney,
      writing constantly with advice and encouragement. Says Sidney, who
      now works for David as operations manager at the Aaron Diamond AIDS
      Research Center: "He would take a late flight and get in past
      midnight, but he would always come to my room and wake me up for a
      brotherly chat." Ho became a father himself. He and his wife Susan
      Kuo, an artist, have three children: Kathryn, 18, Jonathan, 15, and
      Jaclyn, 10. Now and then, Ho sneaks away from his busy schedule to
      surprise his kids at school. This fall, after his picture appeared
      in TIME, he was invited to explain AIDS to Jaclyn's fourth-grade

      As a child, Ho had his math tables drilled into him in Mandarin, and
      to this day he does his calculations in Chinese. "But," he says, "I
      wouldn't even have the vocabulary to give a scientific talk in
      Chinese." He plays down the importance of being Chinese to his
      success--but that is a very Chinese thing to do. Instead, he cites
      immigrant drive: "People get to this new world, and they want to
      carve out their place in it. The result is dedication and a higher
      level of work ethic." He adds, "You always retain a bit of an
      underdog mentality." And if they work assiduously and lie low long
      enough, even underdogs will have their day.

      --Reported by Dan Cray/Los Angeles, Alice Park/New York and Donald


      Dr. David Ho, World-Renowned HIV/AIDS Researcher and Time
      Magazine's '1996 Man Of The Year' to Serve as Senior HIV/AIDS

      PR Newswire, 810 Seventh Avenue, New York, NY 10019 - May 1997.

      LOS ANGELES, May 15 /PRNewswire/ -- Dr. David Ho, world-renowned
      HIV /AIDS researcher, and Time magazine's "1996 Man Of The Year,"
      will be senior consultant for the BENTLEY HEALTH CARE, Inc.
      HIV /AIDS division. Dr. Ho has been internationally recognized for
      his groundbreaking work with protease inhibitors, which in
      combination with standard anti-viral medications has provided a
      dramatic new direction for the treatment of HIV / AIDS patients .
      BENTLEY HEALTH CARE, Inc. is the newly created global health care
      company of Dr. Bernard Salick, the disease-state management
      visionary and former Chairman and CEO of Salick Health Care, Inc.
      Dr. Salick is highly acclaimed for his pioneering approach to
      quality, cost-effective, state-of-the-art outpatient diagnostic and
      treatment centers. He is credited with the development of innovative
      concepts that have fundamentally altered the way cancer care is
      delivered in the United States. He is also recognized as a leading
      expert in managed care and disease-state management.

      As Senior HIV /AIDS Consultant, Dr. Ho will provide BENTLEY HEALTH
      CARE with strategic advice in the areas of practice guidelines,
      outcomes measurements, and treatment protocols which will be used in
      the development of a data base for capitated and other types of
      managed care products. He will head up the HIV /AIDS scientific
      advisory group that will advise Dr. Salick in the development of
      affiliated networks of basic science and clinical treatment centers
      throughout the world.

      Upon announcing the affiliation, Dr. Salick stated, "I am very
      pleased that a physician and researcher of Dr. Ho's stature and
      accomplishments has decided to be a key member of the Bentley Health
      Care consulting team and will provide such a critical range of

      Dr. Ho, whose ingenious combination anti-viral "cocktail" treatment
      has captured worldwide interest, has been performing landmark
      investigation of HIV infection since the mid-1980s. His research has
      produced a wealth of vital information on how HIV attacks and
      eventually overwhelms the immune system . His experimental work,
      alone and in cooperation with others, has expanded the frontiers of
      knowledge regarding HIV and AIDS and opened exciting new directions
      for treatment.

      BENTLEY HEALTH CARE, Inc. is a Beverly Hills-based global health
      care company that will provide diagnostic and therapeutic services
      to patients with catastrophic illnesses requiring sophisticated long-
      term care in cancer, AIDS, kidney failure, and organ
      transplantation. It will also enter into negotiations with state,
      federal and local governments both here and in Europe in the areas
      of Medicare, Medicaid, Champas and other government health plans,
      Managed Care and the E.C. Nation Health Service. The company is
      dedicated to advancing the field of disease-state management,
      offering innovative and unique solutions to patients, physicians and
      payees seeking quality patient care and cost-effective disease-state
      program management.

      CONTACT: Ron Wise of Bentley Health Care, 310-248-3300


      Dr. David Ho: A Scientist's Perspective
      on the AIDS Epidemic
      By Robyn Page

      Dr. David Ho is the scientific director and chief executive officer
      of the Aaron Diamond AIDS Research Center in New York City, and a
      professor at Rockefeller University. He was named Time
      magazine's "Man of the Year" in 1996 for his leadership in the field
      of HIV/AIDS research. Vision contributor, Robyn Page, recently spoke
      with Dr. Ho about the challenges facing scientists as they develop
      new AIDS drugs and search for a vaccine.

      RP You've been involved with AIDS since the beginning of the
      epidemic over twenty years ago. Did you expect the epidemic to
      unfold the way it has?

      DH Absolutely not. I don't think anyone expected to have an epidemic
      like the one we're facing. In those days it was an interesting
      curiosity, something obviously new, something with scientific
      importance. But no one could have imagined that this would turn into
      a worldwide pandemic, one that threatens the entire world.

      RP Did you feel a sense of helplessness as you watched the epidemic

      DH Oh, for a long time. Despite identifying the virus, proving that
      HIV was the causative agent of AIDS, developing blood tests, and
      many other advances on the basic science front, there was a sense of
      hopelessness because the patients continued to die with minimal
      impact from our intervention. By 1986 or 1987, there was one drug,
      AZT, which slowed the disease by only a few months, so the sense of
      despair was pervasive. Really, it wasn't until more drugs were
      available, by around 1994 or 1995 that a bigger impact was made.
      That was the first time we had any hope that we could at least win
      one battle against this virus.

      RP The development of these antiretroviral drugs has dramatically
      improved patients' quality of life, but now we're hearing reports of
      drug resistance, which can potentially compromise their treatment
      options. Why is drug resistance happening?

      DH In an ideal world, if antiretroviral drugs are being properly
      administered and there is proper compliance, the appearance of
      resistance is uncommon. However, we live in the real world where a
      lot of issues complicate adherence to a drug regimen. There is no
      doubt that when you look at a population, in New York City for
      instance, who are taking antiretroviral drugs, you will find
      individuals harboring viruses that are resistant to one or several
      drugs. These resistant viruses are capable of spreading in the same
      way as the "wild type" virus [the most common form of HIV]. Just as
      we have seen with antibiotic resistance, over time you will find
      that a greater and greater percent of the circulating viruses are
      drug resistant. Right now, only about five percent of the new HIV
      infections are due to drug resistant strains.

      RP Is there anything scientists can do to minimize drug resistant
      HIV strains?

      DH Well, I think scientists could help in many respects. One way is
      simply to come up with better antiretroviral drugs. More potent
      drugs would help control the virus better and drugs with better
      features could be taken once a day instead of three times a day,
      which would help patients with adherence. Also, because these drugs
      have side effects, scientists need to modify the drugs to retain
      their effectiveness but remove the side effects. Then ultimately we
      can come up with drugs that attack another target within HIV so that
      viruses that are resistant to existing drugs would then be
      completely sensitive to the new drugs. This is what we can do and in
      fact such developments are being made as we speak.

      RP Now that we've discussed some of the challenges faced in
      developing antiretroviral drugs for treating people who are already
      infected with HIV, let's discuss the development of vaccines for
      preventing HIV infection. Why has it been so difficult to come up
      with a vaccine for HIV?

      DH Firstly, HIV is a different virus. It's in a family of viruses
      that we have really not confronted before. Unlike many other viruses
      we have dealt with in the past, HIV is particularly difficult to
      inactivate by antibodies. Usually, the antibodies in the human
      immune system are quite effective at controlling viruses by binding
      to them and inactivating them. Our antibodies are not very effective
      against HIV because much of the surface of HIV is composed of sugar.
      This acts as a kind of shield, which prevents the antibodies from
      attaching themselves and inactivating the virus. Our traditional
      vaccines have been based on the introduction of specific antibodies,
      for example polio or smallpox. But since HIV-specific antibodies are
      not able to bind very well, they are not able to inactivate HIV very
      well. So that's one huge problem confronting us.

      Secondly, we are now forced to use vaccines that that produce a
      different type of immune response, which we call a cytotoxic T-cell
      response. These vaccines require a different method of
      administration or delivery or overall vaccine strategy. We simply
      cannot take the virus, kill it and give it as a vaccine as has been
      done with other viruses. With HIV we have to come up with novel
      strategies like DNA vaccines, line vector vaccines, which involve
      new technologies that we have not used for other vaccines in the

      And thirdly, and this is not necessarily a complete list, because
      HIV has a very high mutation rate it's rapidly changing, so we're
      not dealing with a single virus, we're dealing with a huge
      population of diverse, yet related viruses. It just adds another
      layer of complexity. What we need is a new approach to deal with a
      moving target.

      RP Does HIV mutate more than other viruses?

      DH There are many viruses that mutate a lot, but many of the viruses
      don't continue to mutate day after day. So HIV not only has a
      mutation rate, it also causes a chronic infection. Many RNA viruses
      actually mutate quite a bit, but some of them only infect you and
      replicate for a few days or a few weeks at most. HIV continuously
      replicates for ten-plus years sometimes. In this respect, Hepatitis
      C is similar. So HIV is not the only frequently mutating virus, but
      it's certainly one of the most striking ones.

      RP Realistically, how soon can we expect to see a vaccine for AIDS?

      DH I think scientists are upbeat because there have been some recent
      successes in monkey experiments. There is a greater concerted effort
      to develop a vaccine now, but the timeline is long, because the
      testing process is long. Let's say, for example, you have a very
      good vaccine in your hands today. You would need to take it to the
      FDA [United States Food and Drug Administration] for the initial
      safety testing, and then do additional testing in people to show
      that it would induce the kind of immunity you seek. Lastly, even if
      you successfully overcame those hurdles, you would then have to
      prove that your vaccine protects against HIV infection. So you would
      need to take it to an area where the HIV infection rate is high and
      compare your vaccine to a placebo. You would need to give the
      vaccine to thousands or tens of thousands of people for one or
      several years. So you can see the timeframe. Even if you had the
      vaccine today, it would take about five years to prove it.

      RP I've heard about a type of vaccine that would help boost the
      immune system of HIV-infected individuals. How would this work?

      DH There's a lot of talk of using a preventative vaccine to treat
      infected people. Now, of course, it's probably pointless to
      vaccinate while the virus is replicating and attacking the very
      immune cells you're trying to stimulate. But now that we have better
      drugs to control the virus, there's a school of thought that perhaps
      we could control the levels of the virus with drugs and boost the
      HIV-specific immunity with the vaccine. The hope being that this
      would help control the virus someday without the use of drugs so
      that the patient could discontinue using drugs. There are already
      such experiments going on in people. It could be a reflection of
      this being a first generation vaccine, but we've not seen a great
      deal of success along that line. But it doesn't mean that we should
      abandon the whole strategy should there be better vaccine candidates
      to come.

      For more information on the research being done at the Aaron Diamond
      AIDS research center, go to http://www.adarc.org/
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