SCIENTIFIC COMMUNITY:
Asilomar Revisited: Lessons for Today?

Marcia Barinaga

A conference last month asked whether the "Asilomar process" cou help to
resolve today's biotech controversies

PACIFIC GROVE, CALIFORNIA--The Asilomar conference on recombinant DNA
was the Woodstock of molecular biology: a defining moment for a generation,
an unforgettable experience, a milestone in the
history of science and society. But was it something that could--or even
should--be repeated?

Those were some of the questions on the minds of 55 scientists, lawyers,
historians, and ethicists who gathered here last month
at the Asilomar Conference Center near Monterey to mark the 25th anniversary
of that historic meeting. In February 1975,
140 participants--mostly biologists, with a handful of lawyers and
physicians and 16 members of the press--gathered at the
rustic conference center overlooking the Pacific to tussle with an issue
that had just burst onto the biology scene: the safety of
recombinant DNA research. Known officially as the International Congress on
Recombinant DNA Molecules but remembered
ever since simply as "Asilomar," that meeting was widely hailed as a
landmark of social responsibility and self-governance by
scientists. The participants in last month's conference*--who included 11 of
the 1975 conferees--were not just here to
reminisce. Legal scholar Alex Capron, a participant in the 1975 meeting and
now co-director of the Pacific Center for Health
Policy and Ethics at the University of Southern California in Los Angeles,
assembled the group to discuss what lessons could be
learned from the "Asilomar process" and, specifically, whether there are
situations today in which it might be appropriately
applied.

Asilomar occurred at a unique moment in biology. Researchers had just
discovered how to cut and splice together the DNA of
disparate species and were beginning to contemplate the cornucopia of
experiments this opened up. "Recombinant DNA was
the most monumental power ever handed to us," said California Institute of
Technology president David Baltimore, one of the
organizers of the 1975 meeting. "The moment you heard you could do this, the
imagination went wild." But a number of
scientists at the time raised concerns about whether such experiments might
create dangerous new organisms, microscopic
Frankensteins that could sneak out of the lab undetected on the sole of a
Hush Puppy and threaten public health.

Those concerns triggered a "hectic experience" of scientific soul-searching
that culminated in the 1975 Asilomar conference,
recalled Stanford molecular biologist Paul Berg, another organizer of that
meeting. Participants at a June 1973 Gordon
Conference on Nucleic Acids had published a letter expressing concern about
recombinant DNA research. In response, Berg
led a committee of the National Academy of Sciences that in July 1974 took
the unusual move of calling for a voluntary
moratorium on certain types of recombinant DNA experiments until the hazards
could be evaluated.

Berg and several colleagues organized the Asilomar meeting 7 months later to
bring together "people who were engaged in the
research or were likely or eager to use it." The organizers also brought in
researchers with expertise in bacteria and viruses to
help assess the potential hazards. A sense of urgency pervaded the meeting,
in part because researchers were impatient to put
the new technology to work. Although most of the participants suspected that
there was no real hazard, Baltimore said, the
stakes were clearly "too important to be wrong." The meeting's organizers
decided not to address the ethical issues surrounding
genetic alteration but to stick to safety issues they felt they could
address as scientists. After much haggling, the group settled on
a set of safety guidelines that involved working with disabled bacteria that
could not survive outside the lab. The guidelines not
only allowed the research to resume but also helped persuade Congress that
legislative restrictions were not needed--that
scientists could govern themselves.

The group that convened last month faced a very different set of
circumstances. The technology that seemed like science fiction
in 1975 is now commonplace and has yielded what Baltimore called "a
remarkable harvest" of products and applications, such
as genetically enhanced crops, tests for genetic diseases, and human gene
therapy. Last month's meeting also had less of a
sense of urgency because, for the most part, scientists consider these
technologies safe.

But the public remains hugely concerned about the applications of genetic
manipulation: Witness the recent protests in Europe
over genetically modified crops. And society today is much more insistent on
participating in the debate. "There are no
important risks that scientists alone can assess," said Princeton University
president Harold Shapiro, chair of the National
Bioethics Advisory Commission. "Scientists can make a great contribution,
but they can't decide alone."

What's more, the scientists themselves have changed. Those who gathered at
Asilomar in 1975 represented a research
community that was purely academic in its interests. Today, "there are few
pure academics left" in molecular biology, Baltimore
noted. As genetic engineering has gone commercial, academics have followed,
and today most senior academic researchers
have ties to biotechnology companies that would complicate any attempts at
self-scrutiny.

During the course of last month's 2-day meeting, participants concluded
that, for these and other reasons, it would not be
appropriate now for scientists alone to take on the task of analyzing the
risks of their work while setting aside the ethical issues,
as they did a quarter-century ago at Asilomar. Nevertheless, as they debated
the genetic modification of crops, gene therapy,
and the use of genomic information, the participants identified instances in
which society might have benefited if scientists had
actively contributed to a public debate about the safety of their work.

One of those was gene therapy, the subject of the most intense
soul-searching at the meeting. Gene therapy has been in the hot
seat since the death last September of Jesse Gelsinger, an 18-year-old
subject in a gene-therapy trial at the University of
Pennsylvania. Others in the field knew that the adenovirus vectors being
used in the Pennsylvania trial could cause potentially
dangerous immune reactions, like the one that apparently killed Gelsinger,
said gene therapy researcher Inder Verma of the
Salk Institute in La Jolla, California. "Why didn't we stand up" at meetings
and raise those concerns? Verma asked.

Picking up on Verma's remark, Baltimore urged that "it is absolutely
necessary" for gene therapists to slow down and
reexamine the standards for when to begin trials on human subjects. "There
are times when some things shouldn't happen," he
said. Gene therapy vectors "that weren't working in animals are going into
humans. A lot of us are saying what the hell are
[doctors] doing putting these into people?" The Gelsinger death and the
publicity it has generated are sure to raise public
suspicion, said Maxine Singer, president of the Carnegie Institution of
Washington: "It will be difficult to repair the damage that
has already been done to biomedical research and gene therapy research."

Some participants also suggested that the huge public backlash against
genetically engineered crops might have been averted if
scientists, both commercial and academic, had taken a more active role in
analyzing risks--not only as they perceived them but
also as society was likely to--and perhaps exercised restraint until those
uncertainties could be resolved. What made Asilomar
unique was that the scientists "gave other people's perspectives some
standing," said Shapiro. "Here is a case where
commercial interests are suffering a great deal from not having confronted
these problems in this way."

But with substantial U.S. acreage--for example, one-third of the corn and
half of the cotton and soybeans--planted with
genetically modified crops, it is too late to go back to a
scientist-controlled process of self-regulation, said Rebecca Goldberg
of New York City-based Environmental Defense. Indeed, it is naïve to think
that any controversial issue can, or should, be
resolved by scientists alone, said sociologist Dorothy Nelkin of New York
University. She pointed out that public fears about
the safety of new genetic technologies often mask deeper societal concerns.
In the case of genetically modified crops, for
example, "when the French talk about risk, they are talking about
McDonald-ization of France and the plight of the small
farmer. When the British talk about risk, they are worrying about the
alteration of nature. Even if it could be demonstrated that
the risks were acceptable, the controversy would continue."

Although it may be too late to influence the debate on genetically modified
foods, at least some of the conferees thought an
updated Asilomar-like analysis of scientific risks could still make an
important contribution in two areas: germ line engineering
and xenotransplantation. Gene therapy that alters germ line cells is an
ethical minefield, as such alterations would be transmitted
to future generations. "At Asilomar [in 1975], people said they would draw
the line at germ line gene therapy," said science
historian Charles Weiner of the Massachusetts Institute of Technology (MIT).
Now, although germ line therapy in humans is not
actually being done, "it's on the table" as an option, said Weiner. Weiner
and others worry that techniques developed to correct
genetic diseases may eventually be used to engineer desired traits into
children.

In addition to those ethical concerns, the group debated scientific risks..
Geneticist Arno Motulsky of the University of
Washington, Seattle, argued that germ line therapy could "lead to reduction
of genetic disease" and so should not be dismissed
out of hand. But physician and geneticist Paul Billings, co-founder of
GeneSage, a San Francisco Internet-based genetic
information and health company, countered that germ line therapy is not
necessary, given other options such as prenatal or
preimplantation diagnosis of genetic defects. What's more, he said, the
altered genes, especially if they insert randomly into the
germ line genome, may have unpredictable and potentially very subtle
negative effects on health or intelligence. Although difficult
to detect, such effects could be "quite significant" to individuals and
their descendents, said Billings. To MIT molecular biologist
Phillip Sharp, debate such as this emphasizes the need for an Asilomar-like
"attempt at evaluation and consensus in the scientific
community" concerning germ line therapy.

As for xenotransplantation, the transfer of organs from nonhuman species
into humans, there are concerns that the procedure
could endanger public health by transferring animal viruses to humans. Other
countries are considering or have instituted
moratoria on the procedure, said Lana Skirboll, director of the Office of
Science Policy at the U.S. National Institutes of
Health, but the United States has done nothing. "We need a scientific
assessment," she said.

At the end of last month's meeting, Berg reflected on the differences
between 1975 and 2000 and what they might mean for the
resolution of scientific controversies. One factor that made the first
meeting work, he said, was the "suddenness of the issue."
Because molecular biologists weren't yet heavily invested in recombinant DNA
technology and the public knew little about it, "it
was much easier to get people to agree on a course of action," Berg told
Science. Most of the issues discussed at last month's
conference are "chronic," he noted. And "once an issue becomes chronic,
positions become hardened, and consensus is much
more difficult to achieve." What's more, Berg and others noted that
consensus might never have been reached if the scientists at
Asilomar had not agreed to put aside the ethical issues and stick to
biological hazards. In 1975, that process worked, and the
research not only went on safely but won the public trust. Today "we are in
a very different world," said philosopher Stephen
Stich of Rutgers University in New Brunswick, New Jersey, where that public
trust is not so easily won.

But that in no way diminishes the need for scientists to reflect on the
impact of their work on society, said Susan Wolf, a
professor of law and medicine at the University of Minnesota, Minneapolis..
What was unique about Asilomar was that "a group
of scientists was convened to reflect upon how their work affected other
people's lives," said Princeton's Shapiro. And that, he
and others agreed, is something that scientists owe society as they move
toward whatever the next scientific revolutions might
be.