Biotech Battlefield: Profits vs. Public
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Sunday, February 21, 1999
Biotech Battlefield: Profits vs. Public
Private companies are refusing to share the genetic code
of a deadly staph bacterium. They say it cost them millions
to discover, but officials say the data are needed to avert a
public health crisis.
By MARLENE CIMONS, PAUL JACOBS, LA Times Staff Writers
WASHINGTON--The first reported case was in
1996. A Japanese baby nearly died of a
raging infection, despite treatment with one of the
most powerful antibiotics in existence. Over the
next two years, there would be at least three more
cases--including the first death, that of an elderly
New York man struck down last year.
One of public health officials' darkest
predictions had come to pass: A strain of
Staphylococcus aureus, the most common source of
life-threatening bacterial infections in hospitals,
had arrived that was resistant to every antibiotic
known to medicine.
But scientists working to divert a potential
medical disaster have run into a significant
roadblock from the most unexpected of places:
their fellow scientists.
Biotechnology and drug companies have spent
huge amounts of money decoding the genome--the
genetic blueprint--of staph, with the hope of
designing new drugs to challenge it. But they are
unwilling to share that crucial knowledge with
government and university scientists, a stance that
many researchers believe is critically stalling the
pace of scientific progress.
As a result of the private sector's refusal to
collaborate, federal health officials have been
forced to strike out on their own, duplicating the
work at a cost of millions to taxpayers.
What might have been a triumph of modern
science over a looming public health crisis has
become a clash between the needs of companies to
seek a return on their investments and the desires of
academic scientists to put basic genetic information
into the public domain.
This is not the first such confrontation in this
new age of commercialization of biological
science, nor is it likely to be the last. Private
companies and federally funded labs, for example,
are similarly competing to complete the much
larger human genome over the next few years. And
private and public researchers have collaborated in
the past--most notably in the 1980s on AIDS drug
studies--resulting in considerable friction
concerning patent rights.
But in the case of staph, public scientists argue
that profit margins should be secondary to fighting a
common public health enemy and that it is difficult
to imagine a conflict where the stakes could be
higher: fighting a possible outbreak of an
untreatable infectious disease.
The delay in making the data public has "slowed
research by four or five years," contends Dr. Olaf
Schneewind of UCLA, a leading staph investigator,
who understands the industry's position but is
unsympathetic to it. "From the perspective of
industry, you can view this as a market," he says.
"At the same time, there is a humanitarian issue."
"Not having this information is a big obstacle
for the scientific community," says John La
Montagne, deputy director of the National Institute
of Allergy and Infectious Diseases. "Without this
information, we don't have the insights we need. . .
. It's like keeping the map of the city of Washington
The companies argue that they've spent all this
money to get the data--why should they give it away
for free? It will only remove their incentive to do
The three biotechnology companies that are
known to have deciphered the staph genome
maintain that selling their data to big
pharmaceutical companies gets the information to
precisely those who are best at developing new
drugs to keep staph in check.
"Their business is to develop new products,"
said Gerald F. Vovis, a senior vice president of
Genome Therapeutics in Waltham, Mass., which
has a $43.5-million deal with Schering-Plough to
provide genetic information from disease-causing
bacteria, including staph. "They feel the pressure.
The ultimate solution is going to come from
The Problem of Resistant Bacteria
Staphylococcus aureus accounts for at least
500,000 cases annually of pneumonia and infected
incisions in the United States alone. The bacterium
is extremely common, and typically harmless unless
it enters the body through a cut or wound. It is also
seen outside hospitals, as a cause of meningitis and
infections of the skin, heart and bones.
For many years, staph and other bacteria were
kept under control by such "first-line" antibiotics as
penicillin and ampicillin. But in recent years many
organisms have developed a resistance to these
drugs. Even newer-generation antibiotics are far
less effective against it; nearly a third of hospital
staph cases worldwide are now resistant to the
The potent antibiotic vancomycin is the drug of
last resort and "right now is the only thing standing
between us and unremitting Staphylococcus aureus
infections," La Montagne says.
Microbes have an uncanny ability to adapt to
compounds trying to kill them: Expose them to an
antibiotic and a few may survive--the ones that
have genes that can protect them from the drug the
next time they encounter it.
And because bacteria multiply very quickly--as
fast as once every 20 minutes--just a few microbes
with these resistance genes can become a colony of
millions overnight, all with the ability to resist
antibiotics. Worse still, scientists have shown in
laboratory studies that resistance genes are able to
transfer from one kind of bacterium to another.
Government and academic scientists argue very
strongly that basic genetic information should be
publicly available. The massive,
government-funded human genome project--which
is undertaking to decipher all of the genes in the
human body--has a policy of publicly posting its
"I believe science moves forward in
unpredictable ways, and with something as basic as
the instruction book of organisms, the more people
who have a chance to look at it, the better the
likelihood that a key insight will occur," says Dr.
Francis Collins, director of the National Human
Genome Research Institute. "The question we ought
to be asking is, 'What is good for the public?' I'm
not sure that all this gold rush is going to serve the
public's needs very well in the long run."
Responding to the frustration of academic
scientists, NIAID last year committed almost $3
million to decode the staph genome's "sequence,"
the bug's basic chemical configuration.
"We were interested in getting these grants
funded precisely to be sure that the sequence
information on the genome of this organism would
be publicly available," La Montagne says.
Last year, the research agency spent more than
$17 million for work on the genomes of more than
20 disease-causing microbes, including several that
have become resistant to standard treatments. In
cases of resistant organisms, scientists look at the
genes of both resistant and nonresistant bugs in
order to understand the differences.
Private companies were already offering their
commercial customers the genetic detail of at least
six of these organisms, among them Mycobacterium
tuberculosis, which causes TB, and enterococcus
faecalis, second only to staph as a cause of
potentially life-threatening hospital infections.
Under proposed federal rules endorsed this
month by an advisory panel, partial results of the
NIAID-funded work must be publicly posted on a
Web site of the researcher's choice at least monthly
for anyone to download.
"We recognize that sharing this data is of vital
benefit to vast numbers of scientists," says Michael
Gottlieb, a program officer with NIAID. "We
consider it a unique research resource and want to
make it as widely distributed as possible,
especially since it was funded with U.S. tax
But why did the federal government wait so
"People were being optimistic" that the work
would be available for everyone, said Clare
Fraser, director of the Institute for Genomic
Research, a nonprofit laboratory that is now
completing work on one strain of staph and a
number of other bacteria. "Why spend $1 million or
$2 million to duplicate what was done in the
The High Road vs. the Income Stream
Publicly traded corporations' first obligation is
to their shareholders, says Dana Wheeler, of Incyte
Pharmaceuticals in Palo Alto.
Incyte sells its staph genome data to some of the
world's biggest drug manufacturers, including Eli
Lilly, Abbott Laboratories and Johnson & Johnson,
and refuses to share it free with academic
researchers. Incyte's extensive database now
includes genetic blueprints for at least 40
"We are a commercial enterprise in funding this
work ourselves and going after it at a very
high-quality pace," Wheeler says.
Unlike its competitors, Human Genome
Sciences of Rockville, Md., is willing to share its
data with publicly funded scientists--but only those
who sign agreements protecting the company's
The company believes that discoveries should
be publicly available to "further the goal of
improving human health," company spokeswoman
Kathryn de Santis says. But if the researchers' work
results in a product, "the intellectual property rights
will reside with Human Genome Sciences," a
restriction that several scientists say would mean
giving up rights to their own discoveries.
As yet, no researchers have taken the company
up on its offer.
More than four years ago, John Iandolo, then at
Kansas State University, gave Human Genome
Sciences the staph DNA it needed to begin
decoding the microbe's genome. He said he did so
assuming the company would make the information
public when it was finished.
"When it became clear they were not going to
share this, we decided to get into the genome
business ourselves and make it clear we would
share it with everybody," says Iandolo, who is now
at the University of Oklahoma, leading the
government-funded $1.4-million effort to decode
"I feel that industry doesn't care as much about
[public health] scares as they do about making a
buck," he says. "When it comes to public health,
you'd think the companies would take the high
The staph research involves isolating copies of
the bacterium's genome--circles of DNA tucked
away in every microbe--and randomly breaking its
DNA into tiny pieces to decipher the chemical
structure. Using computers, scientists are able to
produce a detailed map of the entire genome. This
process is called sequencing, decoding the order in
which four basic chemicals occur in the genome,
giving an organism its unique characteristics.
The staph genome includes between 2,000 and
4,000 separate genes, each one carrying
instructions for a different protein important in the
bug's life cycle. By understanding how these
proteins work, researchers will have new targets
for potential therapies--for example, block one
protein, and the bacterium may be unable to attach
itself to the cells of its human host. Disable another,
and it may not be able to multiply.
Merck Funds Basic Research
Biotechnology firms and their pharmaceutical
company partners are applying for patents for some
of those promising protein targets as well as for the
Government officials and academic scientists
worry that the companies' staking claims to the
staph genome--and delaying the release of genetic
information until patents are secured--will
discourage independent investigators from studying
an organism at all.
"At the end of the road is a product that will
benefit the public," Collins says. "All this secrecy
being applied is putting a lot of tollbooths on that
However, Collins also acknowledges that patent
protection can serve as an incentive to get new
antibiotics and vaccines to the market.
"My happy medium would be to get all the
sequencing into the public domain, and if people
want to claim intellectual property rights, it has to
be based upon [discovering] the function or utility
of a sequence, instead of claiming the sequence
itself or hiding it," he says. "Then what we would
reward would be a discovery of how it works."
While the law is not entirely settled, U.S. patent
officials say that scientists must indeed show the
utility or usefulness of a discovery before they will
be issued a patent. But some legal scholars observe
that patents are being given for most basic
discoveries, and they worry that this will hamper
further research, as Collins fears.
Standing virtually alone in the drug industry, one
company--Merck Research Laboratories--has been
supporting efforts to share basic gene-sequencing
information for the human genome, as well as staph
and other organisms with all scientists, even those
working for its competitors.
Through its nonprofit Merck Genome Research
Institute, the company has awarded grants to the
University of Oklahoma and the Institute for
Genomic Research to finish their work on two
separate staph strains.
In fact, one of Merck's conditions for all of its
grants is that the results be "shared in a rapid and
customary fashion via publications, presentations,
and submission to public databases."
The company insists that having the staph
genome publicly available will spur basic research
by academic researchers and result in whole new
classes of antibiotics being developed by drug
"About 95% of the fundamental discoveries that
point you in the right direction come out of basic
science funded by government and not-for-profit
sources," says Dr. C. Thomas Caskey, president of
Merck's research institute, and a senior vice
president of the company. "About 98% of products
and vaccines come out of the pharmaceutical
"It's a diversion of [the private sector's] money
to be trying to make the fundamental discoveries
and a diversion of [the government's] money to
make drug products," he says. "Our overriding
philosophy is to make the [genetic information]
available to all investigators electronically and
To be sure, access to the staph genomic
sequence and its various strains won't instantly or
by itself lead to new ways to attack infections.
But it is seen as a critical first step--and one that
should be available to the best minds in science,
academic researchers say.
"The irony of the whole thing is, you're much
more likely to find interesting things if you allow
free access," says Richard Novick, a researcher at
the New York University Medical School. "You'll
understand the organism better, and learn what to
Cimons reported from Washington and Jacobs
reported from California.
* * *
A Dictionary of Terms
Biotechnology companies have spent millions to
decode the genetic blueprint of the bacterium that
causes the most serious staph infections. But
because they are not sharing the information with
government-funded scientists, the National Institute
of Allergy and Infectious Diseases is spending
millions of taxpayer dollars to duplicate the work
on staph and a number of other organisms. Here are
some of the key terms and concepts:
Staphylococcus aureus. One of several types of
staph bacteria, this one causes half a million
hospital infections a year, most often entering the
body through surgical incisions.
Antibiotic resistance. Bacteria are able to
develop resistance to antibiotics because they
evolve so quickly. They multiply rapidly--two or
three times an hour. That's as many as 72
generations in a day, which for humans would
require more than 1,500 years. The bacteria with
genes that protect them from antibiotics survive the
exposure. Overnight, a few resistant microbes can
Genome. All the genetic material of an
organism. In the case of staph, the genome is a
circle of 2.8 million chemical structures, the basic
building blocks of DNA. The genome is the genetic
blueprint, divided into smaller units called genes,
which guides the microbe through its life cycle. The
staph genome is about one-thousandth the size of
the human genome.
Sequencing. The reading out of the genome, in
order, chemical by chemical, using the four letters
that represent the DNA code--G for the chemical
guanine; T for thymine; A for adenine; and C for
cytosine. This was once a slow and laborious
process. Today, scientists break up multiple copies
of the entire genome into small pieces and then use
high-speed, automated machines to do the readouts.
Reassembling the information is like taking several
copies of a novel that have been cut up randomly
into sentence fragments, searching for overlapping
words and phrases, then piecing the book back
together. The job requires sophisticated computer
Copyright 1999 Los Angeles Times. All Rights Reserved