November 26, 1999
Biological Products Raise Genetic Ownership Issues
Who Owns Genetic Resources?
By ANDREW POLLACK
or generations, tribesmen in the Amazon rain forest have used
secretions from the skin of a frog to make poison blow darts. Now
Abbott Laboratories is developing a painkiller modeled on the
active chemical in the frog secretion that seems as effective as
morphine but without damaging side effects.
This does not sit well with the government of Ecuador and local
environmental groups. With the American drug company standing to
make millions of dollars if the new drug is successful, they say
the country that is the source of the frog and the indigenous
people who discovered the secretions should get a share of the
A special report.
Angry that they have not profited from the animal and plant life
within their borders, Ecuador and many other developing countries
have begun restricting the freedom of scientists to collect
biological samples and demanding compensation in exchange for
permits. Some scientists warn that scores of research projects that
might lead to breakthroughs in medicine and agriculture, as well as
to the study and preservation of endangered species, are being
impeded or abandoned.
"Ultimately, things on certain species will never be done
because they'll be extinct before the countries can do it
themselves," said John Daly, the scientist at the National
Institutes of Health who isolated the Ecuadoran frog chemical. He
now has great difficulty getting permits. It took him three years
to get clearance from Panama to collect frogs with a cardiac
stimulant in their skin. He gave up on Venezuela.
Projects around the world have been caught up in controversy,
including a study of genes for longevity in China, a search for
cancer fighting chemicals in Southeast Asian marine life, the
breeding of new rice strains from South Asian varieties and the
development of a powerful sweetener from a West African berry.
Earlier this month, the U.S. Patent Office overturned a patent held
by an American entrepreneur on a plant from the Amazon rain forest.
Once considered the common heritage of mankind, wild animals,
plants and crops were taken without asking or freely exchanged. Now
wildlife is increasingly viewed as a "genetic resource," the raw
material of the biotechnology era, just as oil and iron were in the
The Convention on Biological Diversity, forged at the Earth
Summit in Rio de Janeiro in 1992, established that nations have
sovereignty over their genetic resources and are entitled to "fair
and equitable sharing of the benefits."
Since then, the Philippines, Costa Rica and the Andean Pact
countries of Bolivia, Colombia, Ecuador, Peru and Venezuela have
adopted laws controlling access to genetic resources and requiring
compensation. Dozens of countries, including Brazil and India, are
considering legislation or using existing authority to regulate
While the Clinton administration supports the biodiversity
treaty, the U.S. Senate has never ratified it, in part because of
fears it would hurt the biotechnology industry. Nevertheless, the
United States has begun seeking compensation for collection of
micro-organisms in national parks. While many scientists support
compensating source countries, they say unreasonable demands and
red tape are threatening research.
"What's really happening is a tremendous slowdown in the amount
of material that's crossing borders," said Geoffrey Hawtin,
director general of the International Plant Genetics Resources
Institute in Rome, an institute under the auspices of the World
Bank. "Genetic resources for agriculture as a public good, freely
available, are now becoming suddenly unavailable, locked up for
In an effort to preserve the world's food security, the Food and
Agriculture Organization of the United Nations is conducting an
international negotiation to ensure that seed exchanges continue
for important crops.
Limiting exchanges could imperil agriculture, Hawtin said.
Varieties of wheat important to the Green Revolution, which
increased crop yields in previous generations, share ancestry with
as many as 30 countries.
Natural products are also vital as pharmaceuticals, although
some drug companies are de-emphasizing natural sources in favor of
Of the world's 25 top-selling drugs in 1997, seven, with a
combined $11.6 billion in sales, were derived from natural
products, according to "The Commercial Use of Biodiversity," a
new book. These include Merck's Mevacor for lowering cholesterol,
derived from a fungus on a Japanese golf course, and Novartis'
cyclosporine, for fighting transplant rejection, derived from a
Norwegian mountain fungus.
Plants and animals are not the only focus of tension. Some
tribesmen and others are reluctant to give samples of blood and
tissues for medical research.
"We really can no longer get access to some of the most
valuable resources because of the issue and the suspicions," said
David P. Beck, president of the Coriell Institute for Medical
Research in Camden, N.J., the world's largest repository of human
cell lines. Such cells have been used to find genes that cause
illnesses like Huntington's disease and cystic fibrosis.
Last year, the government of China halted a project, partly
financed by the National Institute of Health, that sought clues to
longevity by studying the genes of 10,000 elderly Chinese. The
project resumed after organizers promised that the samples would
stay in China and local scientists would share in patents and
Jeremy Rifkin, the biotechnology critic, said efforts by
countries to restrict access to wildlife, however understandable,
were pushing the world in the same direction as the biotechnology
companies -- toward private ownership of genetic resources.
"You'll have gene wars in the 21st century if we begin to
enclose the gene pool," he said.
HISTORY'S LESSONS: PAYING THE PRICE FOR PAST MISTAKES
he countries controlling access say that their resources have
been used without compensation, acts they call "bio-colonialism"
They point to two cancer drugs, vincristine and vinblastine,
developed by Eli Lilly & Co. in the 1950s and 1960s from the rosy
periwinkle of Madagascar. The drugs have helped dramatically reduce
deaths from testicular cancer and childhood leukemia and netted
Lilly hundreds of millions of dollars.
Madagascar did not share in the profits.
Similarly, crossbreeding with barley collected from Ethiopia in
the 1950s saved California's crop from the yellow dwarf virus,
resulting in hundreds of millions of dollars' worth of increased
output, without any return to Ethiopia.
"I'm not saying it was unfair," said Tewolde Berhan Gebre
Egziabher, general manager of the Ethiopia Environmental Protection
Authority. "That was before fairness in this line became an
One factor behind the increased chauvinism about genetic
resources is that the advent of genetic engineering is perceived as
having increased the value of genes by making them easier to
University of Wisconsin scientists, for instance, isolated a
protein 2,000 times sweeter than sugar from a West African berry.
The gene for that protein can now be inserted into other fruits to
make them sweeter. If a table sweetener is developed from the
protein, it will probably be produced in genetically modified
bacteria, eliminating the need for the berry itself.
"The West African plant has been replaced on the international
market," said Joseph M. Gopo, director of Zimbabwe's national
Another factor is the increased patenting of genetically
modified plants and animals in the West. Some developing nations
say that if a company takes a seed from a farmer's field, adds a
gene and patents the resulting seed for sale at a profit, there is
no reason the initial seed should be free.
"It's not until we've had to deal with some of these
intellectual property issues in recent years that we've started to
have problems," said Henry L. Shands, of the Agriculture
Department's research service. It has long collected seeds from
abroad for the nation's seed banks and freely dispenses seeds to
Patents on living things changed by genetic engineering have
been allowed since a 1980 U.S. Supreme Court decision on a microbe
genetically enhanced to consume oil spills. U.S. patents are
granted for chemicals and genes isolated from plants and animals.
They have also been given for many years for plant varieties
developed by breeders.
But many countries do not allow patents on plants and animals of
any kind and view natural products as discoveries, not inventions.
Arguments on patenting of life are being made in the five-year
review of a global agreement known as Trade-Related Aspects of
Intellectual Property Rights. It requires signatory countries to
provide patents on micro-organisms and intellectual property
protection for plant varieties.
Developing countries object that widespread patenting will make
them dependent on Western companies for seeds and drugs. They also
say patents ignore the contributions by indigenous peoples, who
often are the true discoverers of useful plants and animals, or of
farmers who improve crops over the generations.
The negotiation run by the Food and Agriculture Organization is
weighing whether to compensate traditional farmers for work in
improving crops and maintaining different varieties. Malaysia has
proposed an international fund of $3 billion but the United States
Farmers in India last year protested the patenting of a form of
basmati rice by Ricetec, a Texas company with annual sales of about
$10 million. Ricetec obtained a basmati seed, believed to be from
Pakistan, free of charge from an Agriculture Department seed bank.
Through crossbreeding, it developed a form of the long-grained,
fragrant rice suitable for growing in America.
In India, the world's largest producer of basmati rice, farmers
accused the company of usurping the nation's heritage, threatening
its exports and piggybacking on the work of generations of farmers
who developed the crop.
"It's a hijacking of prior innovation," said Vandana Shiva, an
activist on these issues in India.
Ricetec argues that its patent covers only one variety, not all
basmati rice, and that it has no intention of trying to ban imports
Such patents can be challenged. Two years ago, the U.S. Patent
Office overturned a patent awarded to two scientists at the
University of Mississippi for the use of turmeric, a spice, in
healing wounds. The government of India had challenged the patent
on the grounds that this was an old Indian folk remedy, not a new
Earlier this month, the Patent Office issued a preliminary
ruling overturning a patent awarded to Loren Miller, an American
entrepreneur, on a hallucinogenic plant used in religious
ceremonies by Amazon tribes.
One Amazon group challenged not only Miller's patent but also
his life. It declared him "an enemy of indigenous peoples" and
warned that if he or his associates returned to the Amazon it would
"not be responsible for the consequences to their physical
Miller, who lives in Newark, Calif., said he was given the plant
by a tribe in Ecuador in 1974, and built a school in return. He
cultivated the plant in Hawaii, developed a stable variety eligible
for patent, and formed a small company to see if the plant's
compounds were useful in psychotherapy or cancer treatment. Those
efforts, he said, never succeeded and are all but dead.
"Nobody's going to invest in a company that we could all be
killed for," he said.
BARRING ACCESS: RESTRICTIONS SLOW EXCHANGE OF IDEAS
ne of the premises of the Convention on Biological Diversity
was that if countries were compensated for their genetic resources,
they would have an incentive to conserve them.
"If you can't get farmers to recognize that there is a value in
a forest other than for cattle, the outlook is really very grim for
the tropics," said Joshua P. Rosenthal, biodiversity director at
the Fogarty International Center of the National Institutes of
There have been some successes. In an oft-cited model, Merck &
Co. in 1991 paid $1 million to the National Institute of
Biodiversity in Costa Rica for the right to collect plants in its
search for drugs. Both the Fogarty Center and the National Cancer
Institute coordinate collections overseas involving drug companies
and academic institutions. Compensation to source countries can
include upfront payments of tens of thousands of dollars, product
royalties and training of scientists.
But many experts say countries and companies have reached fewer
"bio-prospecting" deals than expected, in part because of mutual
"When the world mentality was that natural resources were
common ownership, then there was a fertile utilization of natural
resources for drug discovery," said William Fenical, director of
the Center for Marine Biotechnology and Biomedicine at the
University of California in San Diego. "The Rio convention
Fenical said it had taken him four years to get further access
to an Australian coral that contains what appears to be a potent
He also said he had negotiated for two years for a permit to
sample marine organisms in the Philippines, to look for chemicals
toxic to cancer cells. While he was on the plane there last year to
begin his work, he said, the government revoked his permit and
added demands like payments of about $600,000 from Bristol-Myers
Squibb, which was to follow up leads produced by the initial
"They went ballistic about demands and we walked away," he
The Philippines in 1995 became the first country to enact a law
in response to the biodiversity convention. It requires
compensation and collaboration with local scientists and informed
consent from indigenous tribes in areas where the sampling will
Many scientists say the rules are extremely restrictive.
According to a Columbia University study, only two of 37
applications have been approved.
Althea Lota, a Philippine government environmental manager, said
that getting a permit is "not really that hard" but that the
government intends to streamline the process. Fenical's permit was
revoked, she said, because "they did not go through the whole
Colombia rejected an application filed by Andes Pharmaceuticals
four times. The Washington-based company was started in response to
the biodiversity convention and formed a joint venture with a local
citizen so that some profits would go back to Colombia. But
Colombia said the application was not specific enough in stating
which species would be sampled and how much cash would be paid.
Problems may continue after samples are collected. David
Spooner, a botanist with the Agriculture Department and the
University of Wisconsin, has been unable to bring back samples of
wild potatoes he gathered in Peru earlier this year. Britain's
Portsmouth University was pressed to return 120 bottles of marine
fungi obtained in Thailand several years ago.
Controversy has dogged the first bio-prospecting agreement in
the United States. In 1997, for a $100,000 payment and royalties
ranging from a half of 1 percent to 10 percent, the Diversa Corp.
of San Diego won the right to collect microbes from Yellowstone
National Park's geysers for five years.
The Park Service entered the profit-sharing agreement because it
had already lost out once. In the 1960s, a microbe discovered in a
Yellowstone hot spring yielded a heat-resistant enzyme that is now
key to a DNA-amplification process. Hoffmann-LaRoche, which owns
the patents, gets about $100 million a year from them. Yellowstone
But some opponents of biotechnology, arguing that these genetic
resources should not be commercialized, sued and won a temporary
suspension of the Diversa agreement.
ROUGH TRANSITION: NO GOING BACK TO THE OLD WAYS
cientists say a major obstacle to bio-prospecting is that many
countries overestimate the value of raw genetic resources. Drug
companies may need to invest $500 million to develop a drug over 15
years. How much should a country get merely because a plant happens
to live within its borders?
The chances of finding a big drug are remote. The National
Cancer Institute has collected 50,000 plant samples from 30
countries since 1986 and has only one drug in clinical trials.
Drug companies like Abbott and SmithKline Beecham, have cut back
natural drug discovery programs. A new technology called
combinatorial chemistry allows them to generate thousands of
synthetic compounds quickly. Some companies still doing natural
drug research focus on micro-organisms and fungi, which can be
found all over the world, not just in the tropics, and can be
reproduced in vats.
Valuing raw genetic resources can be difficult when the link
between drug and source is indirect, as with Abbott's painkiller.
The company said it owes no compensation to Ecuador because it
merely got the inspiration for its drug by reading a scientific
paper about the frog chemical.
"We've never seen the frog," Michael Williams, a vice
president, said. "We've never touched the frog."
In any case, Ecuadoran officials acknowledge that they have no
legal right to compensation because no rules were in effect when
the frogs were collected by Daly in the 1970s.
Some experts say the problem is not that payments are too high
but too low to encourage conservation.
"The bio-prospecting stuff is turning out to be just a
flimflam," said Ed Hammond of Rural Advancement Foundation
International, a Canadian group. "It's not doing anything for
Nations and tribes can be played off against one another,
weakening their bargaining positions, when plants grow in more than
one area. One NIH project, unable to get into the Philippines, went
to Laos and Vietnam instead.
Some developing countries are becoming more directly involved in
the commercialization of their genetic resources. Brazil is
reluctant to let plant samples be taken to the United States, so
the National Cancer Institute does its drug screening on Brazilian
plants there. The Malaysian state of Sarawak has formed a joint
venture with an American company to conduct clinical trials of an
AIDS drug discovered there.
Some say rough spots are to be expected as the world moves from
free to controlled access of genetic resources.
"I think the realization is coming that this isn't some sort of
'green gold,' and it's going to take a lot of work and a lot of
cooperation to derive the benefits for all parties," Gordon M.
Cragg of the National Cancer Institute said. But, he added,
"There's not going to be a return to the old days when everyone
would just walk in and take things out."