SEARCHING FOR DR. HO
By Colman Jones
Now On 1997
Colman Jones goes to Washington to track down the most famous (and controversial)
WASHINGTON, DC -- There's tension in the posh lobby of the U.S. capital's
Sheraton Hotel, where security guards are nervously adjusting their wireless
A strange situation, considering that this is supposed to be a mild-mannered
medical affair. The Fourth Conference On Retroviruses And Opportunistic
Infections is the only major scientific forum on AIDS in North America
this year. With all the recent hoopla surrounding the prospect of "eradicating"
AIDS with new combinations of high-tech drugs, thousands have descended
upon this hotel to get all the latest updates. Among them are a few people
with AIDS who aren't on the guest list but who are determined to get in
all the same.
At the centre of the storm stands David Ho, Time magazine's Man of the
Year for 1996, the virologist who has become the disease's latest cause
celebre. Ho, director of the prestigious Aaron Diamond Research Centre
in New York, is credited not only with figuring out how HIV works inside
the body but also with discovering a series of drugs that appear to make
it go away -- at least for now.
In the midst of all the media accolades, some scientists are voicing
caution about the reports coming out of Ho's lab. Although the new protease
inhibitor drugs appear to be helping many people with AIDS (see NOW, January
9-15), no one is sure exactly when to start using them, which ones to use
or how long their benefits will last.
Other critics argue that Ho's theory of HIV dynamics -- the virus locked
in a pitched battle with the immune system from day one -- is nothing but
a hypothetical construct that in turn is based on complex mathematical
modelling that may not hold up in the real world.
Bob Gallo, the original AIDS pioneer credited with co-discovering HIV
in 1984, has little use for Ho's novel ideas about how the virus behaves
inside the body.
"I've never read his model, and I never would," says Gallo,
the U.S. government's senior AIDS researcher in the 1980s. "There's
no new paradigm to me. I just think it's a lot of noise."
Gallo's skepticism about Ho's theories is shared by other scientists,
like Jay Levy, another veteran HIV researcher at the University of California
in San Francisco. But these dissenting voices are largely absent from this
meeting, which is organized by an elite club of scientists who govern AIDS
research in North America.
Indeed, hundreds of doctors and researchers have been turned away from
the event that some charge is "in the hands of a few self-selected
individuals whose views and preferences dominate every aspect of the program,"
to quote Martin Delaney, founder of San Francisco's Project Inform, one
of the oldest AIDS service organizations around.
Delaney's group is part of a coalition of U.S. AIDS groups using the
opening day here to launch a public campaign designed to persuade the organizers
to radically rethink the design of their gathering. Now that the international
conferences are only held biannually, activists want this meeting expanded
in order to make more room for people with AIDS and broaden its scientific
Conference organizers reject accusations of scientific favouritism,
but there's no denying this meeting's overarching emphasis on fighting
AIDS through expensive cocktails of high-tech drugs, a strategy that holds
little relevance for the vast majority of the world's infected populations.
I'm here to find out how AIDS research has arrived at this latest juncture
in its development, and to unlock the secrets behind the man who's now
the centre of attention -- David Ho.
* * *
I enter the gigantic hotel ballroom for the opening evening session,
which features a keynote lecture by Ho, who's introduced by conference
chair Douglas Richman. Taking a cue from the Time magazine spread, Richman
shows us grainy snapshots of the Ho family as he recounts the young Taiwan-born
researcher's climb to the upper echelons of AIDS research. Ho then takes
the podium, his round and boyish features amplified by a massive array
of speakers and TV screens.
The short, mild-mannered father of three appears ill at ease with his
newfound status as AIDS celebrity, expressing his hesitance at being singled
out as Man of the Year, insisting the coveted honour be shared among his
colleagues. He then recites the now-familiar data that has tantalized the
world for months in a talk entitled Can HIV Be Eradicated From An Infected
The answer to that question, Ho admits, isn't known, and won't be known
until doctors feel confident enough to take people off the new drugs, at
which point the virus could still return with a vengeance, as has already
been seen in some cases. He's quick to caution that this apparent eradication
of HIV, achieved in the first few months of infection, may not necessarily
be possible in people who've been infected for years.
My attempts to set up an appointment with Ho before heading down to
Washington were unsuccessful, Sidney Ho -- David's brother and the centre's
operations manager -- insisting that no interviews were being granted.
But when I spot the diminutive scientist in a hallway here at the conference,
I can't help but amble over to see if I can quiz him for a few minutes.
He can't talk now, he says, but instructs me to call his hotel room later,
though he's visibly unenthusiastic about yet another round of Q & A.
But there's a specific reason I want to talk to Ho. It centres on a
key piece of research he published back in early 1995, one that has guided
the consensus view of HIV infection and its treatment.
Ho's team, along with one in Alabama, claimed to show much more HIV
activity in people with AIDS than was previously thought, with the virus
attacking the critical CD4 cells of the immune system from the first moment
of infection. According to Ho, HIV and the cells of the immune system are
constantly regenerating at high rates, with 1 billion new CD4 cells being
produced every day to fight off the equally prolific virus.
HIV finally wins the battle, the theory goes, and kills more cells than
the body can produce, leading to immune collapse. Ho uses a colourful analogy,
comparing the loss of CD4 cells in advanced HIV infection to "a sink
containing a low water level, with the tap and the drain both equally wide
But major questions have been raised about this new construct of HIV
pathogenesis, both in the scientific literature and at other conferences.
For example, a series of letters by other HIV researchers appeared in Nature
following the publication of his 1995 paper, questioning the mathematical
models used in calculating the numbers of cells and viruses.
More recently, a study published in Science magazine last November by
a team of researchers in Holland appears to contradict one of Ho's chief
claims, namely, that the critical CD4 cells of the immune system undergo
a rapid rate of renewal during early HIV infection.
Every time a cell divides, it loses a fragment from the extreme ends
of its chromosome, known as telomeres. The Dutch researchers analyzed cells
taken from HIV-positive men over a period of several years. They found
no evidence that the telomere lengths of the cells were shortening over
time, implying that cells were not in fact replicating at anywhere near
the rates claimed by Ho and his colleagues.
Frank Miedema, a leading immunologist at the Netherlands Red Cross Blood
Transfusion service, insists that "There is no more cell turnover
than we have in a normal individual.
"There is no exhaustion of the immune system at all," says
Miedema, in an interview from Amsterdam. "At this point in time, David's
sink model is out. All the data argues against it."
But Miedema is reluctant to confront the big guns in the U.S. "I
was not at the Washington meeting, but if the guys had had the guts to
invite me, I would have presented the data.
"If people find it interesting to have this debate, they would
invite people to do that, and it didn't happen." Why not? "The
dogma that is now out there in HIV infection is David Ho's dogma,"
He notes that these questions about how the immune system breaks down
in AIDS bear great relevance to future treatment. "This is the most
critical question in AIDS pathogenesis. If you want to understand the underlying
mechanism by which people die from AIDS, this is not academic -- this might
be very critical."
Miedema is quick to add that he considers Ho's work otherwise outstanding.
"He has a done of lot of things, he has organized a good laboratory,"
he concedes, "but sometimes these people can be wrong."
I'm eager to press Ho for a response to these scientific challenges.
But when I call at the appointed time, Ho isn't in his room, I'm told by
his brother Sidney, who answers the phone. Interviewing the Man of the
Year isn't going to be easy, I'm discovering.
Ho wasn't always top gun in AIDS research, of course. Bob Gallo once
dominated AIDS conferences like this one, but the retrovirologist has since
been relegated to the sidelines by Ho and the new generation of AIDS whiz
I walk up to Gallo after his session and introduce myself, reminding
him of a telephone conversation we had some years ago. He invites me to
the hotel bar for a drink with his friends.
As we sit down, I ask Gallo what he thinks of Ho's much-talked-about
"open-sink" model. The elder AIDS scientist shrugs his shoulders.
"The tenet that you treat against a microbe as early as possible was
there ever since we knew HIV caused the disease," Gallo says. "You
don't need fancy models. David is a good investigator, he seems competent
as far as I know. The rest of it is hoopla -- that's all I can say."
Hoopla perhaps, but Ho's findings are nonetheless being taken as a cue
by many doctors here to treat people with HIV as early as possible with
a combination of powerful drugs, using measurements of virus activity --
known as viral load tests -- to gauge how well the treatment is working.
In San Francisco, Jay Levy, who's cared for people with AIDS since the
beginning of the epidemic, cautions that levels of HIV in the blood are
only one factor in making treatment decisions. "I have tremendous
reservations about using numbers to decide on therapy. We will consider
the viral load, but we look more at the immune response and we certainly
consider the basic clinical condition of the patient. If the immune system
is doing its job, just having the virus floating around -- most of it noninfectious
-- is not a major factor."
As with AZT years ago, concerns are being raised about rushing people
onto combinations of drugs whose long-term effects remain unknown. "(Ho
and Richman) believe that you should start treating right away -- I don't,"
Levy states bluntly. "Once you use therapy, you've committed that
person to therapy for a lifetime."
While Ho's initial results have generated a lot of hope within the AIDS
community, everyone is waiting to see what the future holds. "It's
very exciting, but he hasn't proved anything yet," notes Jose Sousa,
an AIDS activist with the Community Treatment Advocacy Council in Montreal,
who's among those refused admission by conference organizers and left to
wander the halls and piece together information from the sessions unfolding
To Sousa, Ho's findings are no cause for celebration. "Right now,
he's putting out a lot of false hope, which is not there for those of us
who have been infected for years. So why is he Man of the Year?"
According to Nancy Kearney, public affairs manager for Time magazine
in New York, it's because Ho is "the person who has made the most
impact on the news. As the article clearly points out, his treatment is
not a cure," Kearney is quick to add, "but it was a breakthrough
year in AIDS research, primarily because of his work."
Meanwhile, the conference is abuzz with new statistics released by the
New York City health department indicating that deaths from AIDS in that
city have plummeted sharply in the last year, a drop credited to the introduction
of the new treatments. Clearly, something is happening, but AIDS advocates
-- like John James, editor of the widely read newsletter AIDS Treatment
News -- warn that it's too soon to break out the champagne.
"There has been a major advance in the last year," James notes,
"but it doesn't work for everybody. And even when it does work, we
don't know for how long. There is intolerance to the drugs, there's drug
resistance, there are compliance problems, interaction problems -- there
are all sorts of problems, and we don't know what the outcome is going
Another concern centres on whether the simple increases in CD4 cell
counts that have been documented with the new medications represent a true
reconstitution of the immune system. Mervyn Silverman, former president
of the American Foundation for AIDS Research (AMFAR), notes that "Even
though you get a buildup in CD4 cells, they may not be the old ones you
lost -- they may just be more of the same that you have. And that may mean
you may not be able to fight off certain opportunistic infections."
According to several scientists I spoke to -- including some who weren't
invited to this meeting -- there's too much emphasis here on the virological
aspects of the disease and not enough attention paid to the immune system
and how it regulates itself.
"The best way you control an infectious agent," Levy insists
from his office in San Francisco, "is through the immune system."
Clinical immunologist Jeffrey Laurence, director of Cornell University's
AIDS lab and a senior scientist at AMFAR, agrees that research into the
immune aspects of AIDS is long overdue. "These conferences, because
they've mainly been based on infectious disease experts, have historically
concentrated on finding a new drug," Laurence points out, "and
the immune therapy side has been ignored."
I go looking for a response from Richman, the conference chair, whom
I eventually find in the poster area chatting with colleagues. He has to
rush off to a meeting shortly, he tells me, but agrees to chat briefly
as we walk down the hall, his bodyguard following close behind.
Richman insists that space constraints prevented admitting more people
to the meeting. "It's limited capacity, and we tried to set up as
fair and balanced rules as we could to let people in according to the time
of submission and other things. This is a standard thing -- there are lots
of meetings with limited scientific capacity."
Richman grows upset when I confront him with the activist groups' press
release, which he labels "trash" and "demagogy." He
vigorously denies charges of scientific elitism, insisting that "If
Jay Levy isn't here, it's for other reasons." He then abruptly cuts
me off and walks away toward another group of scientists, anxious to get
away from the prodding.
Reached later by phone in San Francisco, Levy is quick to point out
that "This is the fourth year they've decided not to have my views
on the program, because Ho and Richman run the conference. It's gotten
to be a political event again.
"It's like a narrow little corner here," Delaney says. "Everything
is protease inhibitors and viremia (virus production), and I just think
that's a trap. It's a trap we've fallen into before, and it's dumb of us
to fall into it again, however attractive the bait may look."
Back in the spacious ballroom, I move toward the front to discover Ho
surrounded by a flock of journalists, microphones in hand. While patiently
awaiting my turn, I'm accosted by a security guard, however, who forcibly
insists that I accompany him out of the area. "The doctor is too busy
for any more interviews," I'm told.
I attempt to stand my ground, citing his earlier willingness to talk,
but within seconds Ho is whisked out a side entrance by his entourage.
I know which direction they're headed and try to outrun them. After a mad
dash across the hotel complex, I finally manage to intercept the doctor,
his brother and another colleague as they head down a hall toward the elevator.
It's clear in an instant that Ho hasn't the slightest intention of talking
to me, and my requests for an interview fall on deaf ears. Sidney hustles
his star brother away, turning only to bid me goodbye as the trio disappears
down the hall.
Ho's unwillingness to be challenged is both frustrating and unsettling,
in the face of all the unknowns surrounding his research. Whether he and
his colleagues will continue to dominate the field will largely depend
on how well these new drugs pan out in the long run. But a groundswell
of opinion is slowly emerging that views the contribution of Ho and his
colleagues as only one -- perhaps small -- part of a much larger AIDS puzzle.