THE CASE OF THE GHOST MOLECULES

A French immunologist says he has unveiled the mystery of molecular memory, but a
team of ghostbusters disputes his claims.

The apartment, on a quiet cul-de-sac overlooking Paris' Montparnasse cemetery,
is a curious mix of sheer affluence and cheerful jumble-a bathrobe thrown
carelessly over an expensive Italian leather couch, a chaotic pile of papers and
photographs crowning an antique mahogany desk. The apartment's owner is a study
in contradictions. too.

A respected and much-cited immunologist, Dr. Jacques Benveniste directs the
Immunopharmacology of Allergy and Inflammation unit at INSERM (the French
National Institute of Health and Medical Research). But he has also taken a
walk on the wild side. Traveling down what many of his colleagues call the path
of destruction, he has conducted a series of controversial new experiments on a
weird and disputed phenomenon known as molecular memory. This memory works, he
says, when water molecules store and release information in a previously
undetected way: through a subtle electromagnetic language that enables one
molecule to record the ..essence" of a second, much like a tape recorder records
a sound. If confirmed, Benveniste's work would vindicate the discredited field
of homeopathy, which holds that disease can often be treated and cured using
infinitesimal amounts of medicine diluted in water. More important, says
Benveniste, his research could lead to "the medicine of the future," in which
doctors tap into the electromagnetic molecular communication system to perform
surgery without knives, prevent diseases without using vaccines, and effect
cures without drugs.

"Take a simple example," Benveniste explains. "You have a toothache. Then you
take a gram of aspirin, and it invades your entire body. It upsets your stomach,
it blocks your blood coagulating mechanisms, so if you cut yourself an hour
later you're in trouble. But if we understand the body's electromagnetic
language, we could send the tooth the signal for aspirin instead of taking a
pill."

These are radical assertions, and they leave most mainstream scientists cold.
"A delusion," says John Maddox, editor of the respected scientific journal
Nature, which published some of the first reports of Benveniste's work.

"Bizarre," says Henry Metzger, Director of Intramural Research at the National
Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda,
Maryland. "If Benveniste were right, the French wine industry would be
distraught, because all you'd have to do is put a drop of wine in a glass of
water and you'd have burgundy."

But a few scientists remain agnostic. "It's a little hard to believe," says
James A. Scott, a specialist in nuclear medicine at Massachusetts General
Hospital in Boston, "but that doesn't mean it's not true." And at least one
researcher is supportive. "There are interactions at the molecular level that
are not chemical, and we don't know very much about them," says Robert Becker, a
researcher at Upstate Medical Center at the State University of New York in
Syracuse. "I'm sure that Benveniste is on the right track."

Right or not, Benveniste's work has already generated one of the noisiest and
most bizarre controversies in the history of modern science. That controversy
began in 1988 when Nature, the august British scientific journal, published the
results of Benveniste's experiments on "water memory." The controversy
culminated-but did not end-when Nature sent a team of "ghostbusters," including
the famous iconoclast-magician James Randi, to Benveniste's laboratory to
investigate his claim. During the ensuing mud fight, the Nature team accused
Benveniste and colleagues of everything from shoddy science to delusional
thinking. Benveniste responded with loud screams of "witch hunt." In the end,
the shouting damaged the reputations of both parties and left Benveniste
fighting not only for his job, but also for his scientific life.

It is an unlikely controversy, and Benveniste himself seems somewhat unlikely in
the role of crusading scientist. Now 57, he is an elegant Frenchman with a full
range of Gallic expressions, at least one of which makes him look very much like
Marcello Mastroianni. Indeed, there is an unmistakable (and unscientific?) dash
to his presence-the balance of his wardrobe tips heavily toward suede and
leather, and when he arrives to pick up a reporter at a Paris hotel, it is in a
pristine vintage Jaguar.

Yet the experiments began quietly enough when, in the early Eighties, Benveniste
was approached by a young doctor at INSERM. Recalls Benveniste, "This young man
said to me, 'You know, I am a homeopath.' I said, 'is that some kind of sexual
disease?"' Although Benveniste thought homeopathy was "a bunch of baloney," he
gave the doctor permission to conduct a few experiments "as long as it didn't
interfere with his real work."

The experiments that followed were based on a few simple scientific facts:
During human allergic reactions, allergens-dust, for example, or pollens-bind to
an antibody called Immunoglobulin E, or IgE for short. The allergen-IgE
combination then triggers white blood cells called basophils, causing them to
release some of their contents, a process known as degranulation.

Exploiting this basic biology, the researchers created their own allergen in a
serum composed of an antibody to IgE (or anti-IgE) in a solution with water.
They took this solution through a series of five progressive dilutions so that
little or no anti-IgE serum was left. They then exposed white blood cells to
this highly dilute solution. Though the amount of anti-IgE in serum was
negligible, they reported, measurable degranulation had occurred.

"As soon as I saw this," Benveniste says. "I understood that the degranulation
could not be due to molecular activity because it normally takes millions of
molecules of anti-IgE to produce a reaction. It had to be something else."

Curious, Benveniste decided to go further: He diluted the original solution ten
times. "At ten times dilution," he explains, "there is no mathematical chance
that even one molecule of anti-IgE will be left in the solution. At ten times
dilution, it's just water." Yet even at ten times dilution, Benveniste says, 40
to 60 percent of the basophils degranulated, reacting to what Benveniste says
was now "plain water" as if it still contained the anti-IgE serum.

In 1984 Benveniste and immunologist Elisabeth Davenas, then a student in his
lab, repeated the experiments and got similar results. Benveniste wrote up his
findings in a scientific report, which he submitted to Nature in 1986. When the
journal asked for confirmation of the results, he farmed the experiments out to
research teams in Italy, Canada, and Israel. According to Benveniste, these
teams reported findings similar to his, and he included them in his own report
to the journal.

Nature says it never saw all the results of these trials but nonetheless sent
Benveniste's report to a team of expert referees. "The referees," Maddox says
now, "couldn't see anything wrong with the experiments, but they didn't believe
the results." This left Nature somewhat reluctant to publish Benveniste's
report, but with no good reason not to. At the same time, Maddox says, reports
of Benveniste's unusual findings were about to appear in the French press.

On the horns of a dilemma, Nature decided to publish the report, but with two
unusual conditions: First, the published report would be accompanied by an
editorial reservation noting the "incredulity" of the referees in the face of
experimental results for which there was "no physical basis." Second, after the
report was published, Benveniste would allow a team of investigators recruited
by Nature to visit his lab and witness the experiments themselves.

Benveniste agreed, and on July 4, 1988-almost a week after the report was
published-the Nature team arrived at Benveniste's INSERM 200 laboratory in
Clamart, a suburb 15 minutes south of Paris. The three-man team, later dubbed
"ghostbusters" by the press, was as unusual as the report it came to
investigate. There were no immunologists on the team and only one practicing
scientist. One of the investigators was Maddox himself. Another was Walter W.
Stewart of the National Institutes of Health in Bethesda, Maryland, who had been
one of the paper's referees and who had made a reputation as a sort of
scientific sheriff, pursuing a number of research fraud cases. The third member
of the team was James Randi, a celebrated magician, MacArthur Foundation Fellow,
and self-appointed skeptic who is perhaps best known for his ongoing and highly
public battle to expose and discredit psychic Uri Geller.

This strange amalgamation of ghostbusters spent a week in Benveniste's lab. The
process started quietly enough, with the Nature team watching four repeats of
Benveniste's experiments. Beneviste says each of these yielded positive
results. But the Nature team did not agree. In fact, Stewart declared all the
results "valueless." His reason: As far as he was concerned, adequate scientific
controls had not been in place.

Next came a series of three more trials with the Nature team taking
extraordinary measures to ensure results could not be manipulated. At one point,
Randi wrapped the code for the experiments-designed so that no one could know
which test-tubes were yielding which results-in aluminum foil. He folded the
foil into a specially sealed envelope and then taped the envelope to the
laboratory ceiling.

The results of these experimental runs were negative. To Benveniste, this was
not especially surprising-there were many instances, he said, in which basophils
had not reacted to the anti-IgE solution at high dilutions.

But as far as the Nature team was concerned, the investigation had put an end to
Benveniste's assertions. As Maddox put it, Benveniste's results had been
"delusions" to be accounted for by sloppy experimental procedures and bad
counting.

On July 28, Nature published the ghostbusters' findings. In the same issue,
Benveniste wrote an emotional reply, labeling the investigation a "Salem witch
hunt" and a "McCarthylike prosecution" and issuing a ringing appeal to other
scientists: "Never, but never, let anything like this happen [to you]," he said.
"Never let these people get in your lab."

These amounted to the opening shots in what soon became a worldwide and highly
public gunfight. For the next six months the pages of Nature, Le Monde, and
even Time bristled with opinions, suggestions, accusations, and
counteraccusations. While few scientists believed that the results of the
high-dilution experiments were valid, many found Nature's tactics distasteful
and even dangerous. "Demeaning to the scientific process," wrote Mark Johnson
of MIT "A three-ring circus," said Mass General's James Scott. "Confirmation of
what I always suspected," wrote biochemist Keith Snell of the University of
Surrey"Papers for publication in Nature are refereed by the editor, a magician,
and his rabbit."

The Nature team stands firm. "Had we known how poor the evidence was," says
Stewart, "Nature would never have published the paper, and we would not have
gone to France."

"We would do it the same way again," says Maddox. "It was the only way to flush
it out."

All the publicity hurt. Up for evaluation by his bosses at INSERM, Benveniste's
job seemed to hang in the balance. In the end, two evaluating committees
suggested that Benveniste stop investigating molecular memory. But INSERM
director-general Philippe Lazar decided Benveniste could proceed, and in 1989,
the high-dilution experiments were quietly resumed. Repeating his original
trials with anti-IgE, Benveniste says he's gotten similar results.

At the same time, he launched a series of new experiments to see if highly
dilute solutions could provoke reactions not just in cells, but in whole organs.
In these experiments, he inoculated guinea pigs with egg albumin from hens. He
then removed the guinea pigs' hearts, suspended them in a glass cylinder, and
kept them "alive" and beating. Finally, he used tubes to drip highly dilute
solutions of egg albumin into the disembodied hearts. If the disembodied hearts
recognized the egg albumin, Benveniste knew, they would have a typical immune
reaction: The coronary arteries would dilate, and blood flow would increase.

Even though the solution of egg albumin was so dilute that not a single molecule
of the albumin remained, the blood vessels of the heart appeared to respond:
They dilated slightly, and blood flow through the heart registered a detectable
increase. In other words, the heart seemed to be reacting to what was now plain
water as if the egg albumin were still there.

Benveniste quietly presented these results at the April 1991 meeting of the
Federation of American Societies for Experimental Biology in Atlanta. With the
exception of reports in the Journal of the French Academy of Sciences and New
Scientist magazine, the press did not take note.

The storm over his work temporarily at bay, Benveniste is free to ponder. the
basic questions posed by his curious experimental results. How could a living
system-a human cell or an animal organ-react to something that isn't there? How
could water "remember" a substance that's gone?

After much reflection, Benveniste could have the answer. He believes that
molecules communicate via electromagnetic radiation instead of by exchanging
chemicals. Like the signals transmitted by a radio station to a receiver, these
electromagnetic signals have different and specific frequencies, each one
prompting a different and specific biochemical reaction. "What my experiments
show, in a terribly clumsy way," he says "is that when you highly dilute a
solution, you separate the molecule from its electromagnetic message contained
in the water."

The medium for these electromagnetic messages, according to Benveniste, is
water. This powerful communication, he says, has been demonstrated in his
experiments again and again. Whether you're talking about anti-IgE or egg
albumin, Benveniste notes, the original molecule modulates waves originating
from water molecules, causing them to emit electromagnetic signals-and to
continue emitting them even after the original reagents are gone. "The message
remains in the water," he declares, "just as your voice remains on a tape
recording even when you're no longer talking." In other words, in Benveniste's
mind, the whole vast dance of chemistry, of biology-of life itself-is
orchestrated by electromagnetic signals passing through water.

Though the idea is controversial, to say the least, evidence from other
researchers has begun to fall into place. Scientists such as T. Y. Tsong, a
University of Minnesota biochemist whom Benveniste likes to cite, for instance,
have shown that many cellular functions-including enzyme activity and synthesis
of DNA and RNA-are stimulated or suppressed by electromagnetic fields. Tsong
thinks that future research will show that electromagnetic radiation may indeed
constitute what he calls "the language of the cell." Tsong, of course, is not
entirely comfortable with Benveniste. "My work is based on principles that we
already know," he says, "and his is based on things we don't yet understand."

Robert Becker adds, "Bioelectromagnetics is still beset by an enormous amount of
uncertainty, but there has to be some kind of energetic reaction to explain
molecular communication, and the obvious candidate is electromagnetism."
Benveniste's work, he says, is a beginning, "somebody asking what if?"

And what if Benveniste is right? What if biochemical reactions can indeed be
prompted by electromagnetic signals recorded in water? "Once you're able to pick
up the signal," says Benveniste, "you have a whole new biology. You can digitize
the message, you can make drugs from it. You won't need the physical substance,
be it ordinary aspirin or AZT, but simply the signal that constitutes its code."

Benveniste also thinks the electromagnetic language could be used to do
non-invasive tests. "You stick your finger in a machine that uses an
electromagnetic field to analyze your blood," he explains, and you could even
use the body's own code to perform non-invasive surgery, in which a defective
heart, for example, "is repaired by sending the appropriate electromagnetic
signals to heal its damaged cells." Killer diseases like cancer or AIDS could be
prevented or cured by jamming the electromagnetic signals that turn normal cells
cancerous or that enable the AIDS virus to find the immune system cells that it
targets and eventually destroys.

Some critics think that this sort of speculation-indeed, all of Benveniste's
high-dilution work-shows that the once-respected immunologist has taken leave of
his scientific senses. Even Nobel laureates, notes Eugene Garfield, "have gone
off the deep end in pursuit of private passions."

On the other hand, his few supporters think this kind of research may presage
the dawn of nothing less than what Becker calls "a new scientific revolution" in
which "present dogmatic theories of how the universe works will be replaced." In
the meantime, Benveniste continues to work, refusing to let go until someone
proves him wrong to his satisfaction. "My enemies say a true scientist doesn't
pay attention to erratic data like this," he says. "Even my friends tell me to
drop this because I am going to kill myself. But if it's true that we can have
molecular activity without molecules, then we have discovered a fundamental
process of life.

"I have no private passions," he concludes. "All I have are these data. What
am I supposed to do with them, put them back in the drawer?"