Biotech Battlefield: Profits vs. Public
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 secret.”
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 research.
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 pharmaceutical companies.”
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 latest drugs.
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 data.
“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 dollars.”
But why did the federal government wait so long?
“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 private sector?”
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 disease-causing organisms.
“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 interests.
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 staph.
“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 road.”
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 genes themselves.
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 road.”
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 companies.
“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 industry.
“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 unencumbered.”
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 go after.”
Cimons reported from Washington and Jacobs reported from California.
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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 become millions.
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 software.
