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A Private research foundation in the US has stunned the scientific community
by inoculating AIDS patients with blood containing live HIV. The experimental
treatment is intended to thwart the course of AIDS by introducing a supposedly
‘harmless’ strain of the virus into the body to overthrow the patient’s
own virulent strains. But scientists have condemned the experiment as unethical,
unscientific and dangerous,

‘If I was on an ethical committee I would not approve this for monkeys,
let alone humans,’ said John Moore, a virologist at the Institute of Cancer
Research in London. Simon Wain-Hobson at the Pasteur Institute in Paris
called it ‘Walter Mitty stuff’.

But Aaron Klug, director of the Medical Research Council’s Laboratory
of Molecular Biology in Cambridge, said the theory was valid and deserved
further research.

Eleven severely ill AIDS patients in California received the inoculations
almost ten months ago. Since then, say the researchers, four of the patients
have improved, three have shown a ‘mixed response’, three have deteriorated
and one has died. The donor of the blood is a man who has probably been
infected with HIV for more than a decade, yet remains healthy. The team
believes that the man harbours a strain of HIV that is nonpathogenic, or
harmless. Because his previous lifestyle exposed him to many other strains,
they argue, this strain appears to be a successful one that can out-compete
others in the body.

The team says that antibodies specific to one protein fragment from
the donor strain ‘increased strikingly in all patients who improved’, and
all ten survivors had an improved immune response.

Michael Scolaro, a private physician at the Los Angeles Oncologic Institute,
and George Pieczenik, a molecular biologist at Mount Sinai Medical Center,
New York, set up a foundation called Immuvax for the experiment with Roy
Durham, a lawyer. They say they did not need the approval of an ethical
committee for the research because the patients, the funding and the physician
are all private. The patients gave informed consent, says Durham.

Pieczenik is adamant that the experiment was ‘compassionate’ and morally
justifiable. ‘There wasn’t much difficulty ethically,’ he said last week.
‘The strain of HIV is ‘clearly not pathogenic’, says Pieczenik. He said
the patients were all terminally ill and unable to tolerate antiviral drugs.

‘I can’t imagine an ethical committee passing (this experiment),’ said
Jonathan Weber, professor of communicable diseases at St Mary’s Hospital
in London.

There are several major scientific objections to the experiment, say
its critics. First, HIV is a notoriously variable virus that may mutate
over time and when it passes from one host to another. A strain that is
quiescent in one patient may become virulent in another.

Secondly, researchers question the assumption that a strain of HIV is
harmless just because its host has not yet developed AIDS. HIV can remain
latent in cells for a decade or more without doing any damage, then may
suddenly attack. ‘The scientific community is deeply divided on the basis
of pathogenicity,’ says Wain-Hobson. ‘To assume this strain is not pathogenic
is the most primitive of assumptions imaginable.’

Scolaro and his colleagues say they have ‘characterised’ the virus in
the laboratory, but they give no details except to say that its growth in
culture is ‘uncharacteristically slow’. This unqualified statement is meaningless,
says Thomas Schulz at the Institute of Cancer Research. The speed at which
a strain of HIV grows in the laboratory is affected by many factors. Pieczenik
says the strain did not kill T cells in culture.

The way the research was published – as a short letter in the back pages
of The Lancet – has also angered scientists. The letter emerged unnoticed
three weeks ago (vol 377, p 731) and gives virtually no data, stating that
these are available from Immuvax or the journal. ‘For something of this
importance, it’s outrageous by its lack of detail,’ says Wain-Hobson.

The Lancet asked the team to condense a paper into the short letter
that was published, says Pieczenik. David Sharp, letters editor at The Lancet
said it was not the journal’s policy to discuss its reasons for publishing.

Pieczenik says other researchers do not understand his theory of ‘genotypic
selection’, which he first published 10 years ago. He would like a journal
to publish the theory and the experiment together. The team has fuller,
unpublished papers. Science and Nature have both rejected these.

Pieczenik believes that mutations affecting only a single nucleotide
of HIV’s genetic material can determine how pathogenic a strain is. Some
mutations may not affect the structure of the virus’s proteins but only
its RNA, he argues. The main precedent for this is the polio virus. A weakened,
or attenuated strain of this virus forms the basis of polio vaccine. Å®ÉúСÊÓƵs
know that on rare occasions a very minor mutation may cause this polio strain
to turn into a pathogenic one, resulting in disease. ‘But with HIV the story
is likely to be much more complicated,’ says Schulz.

In monkeys, there are strains of immune deficiency virus that do not
cause disease. But Geoffrey Schild at the MRC said it was premature to test
the theory in humans.