Every scientist’s dream, says researcher Dr. John Rose, is to do something that is really relevant to human health.
But even when you are trying to save millions of lives, it pays to remember that everything has a price tag.
A year ago, Rose, a member of the departments of Pathology and Cell Biology at the Yale School of Medicine, received his first positive results for a potential HIV vaccine.
“It was a very exciting moment,” Rose said. “I called my wife, who is a research associate in my lab, into my office and I said ‘Wow!'”
If proven effective in humans, the vaccine could provide desperately needed help in combating a worldwide AIDS epidemic that has killed 22 million, and infected 36 million more.
That is, if it ever reaches the people who need it most.
Determining the genetic codes of certain viruses has been a goal of scientists for decades. Six years ago, Rose shifted the scope of his research at the Medical School to begin looking at how viruses are constructed.
His theory was simple. Once you know the genetic makeup of a virus, you can alter it to suit your own purposes.
Rose’s investigations came to fruition when he injected an altered version of a common livestock virus, vesicular stomatitis virus, or VSV, into monkeys. The altered virus, while harmless to humans, elicits an immune response that protects the body against AIDS proteins. This allows the immune system to effectively fight off any future infection by HIV.
Soon after AIDS was identified in the early ’80s, scientists across the globe began searching for a vaccine. There are currently about 90 candidates in human clinical trials, but a problem with many of the other vaccines is that they require multiple doses and must be injected.
In many parts of the world, it is nearly impossible for doctors and relief workers to get patients to return for a second or third injection.
Rose’s vaccine is especially promising because it would require just one or two doses, and it may be administered as a nasal spray.
“No one else that I am aware of has an AIDS vaccine candidate that could be delivered intranasally,” Rose said.
Since the initial positive results with just two monkeys, extensive trials have been done in animal models in Rose’s lab, the most recent results of which were published in the Sept. 7 issue of Cell.
Despite animal models being highly predictive, Rose said, he is weary of the long road ahead before anything could possibly be made available to the public. Human clinical trials would not begin for at least another 12 months, said Jon Soderstrom, managing director of Yale’s Office of Cooperative Research. The process, which will take years, will likely not even begin until 2003.
Rose’s vaccine would not be able make it to clinical trials without the help of Wyeth-Lederle, a subsidiary of corporate giant American Home Products.
Such pairings of faculty members with formidable drug-development companies is not uncommon at large research universities.
At Yale, the Office of Cooperative Research handles all of the intellectual property developed through research. The goal of the Office is to take discoveries made within the University and to find suitable companies to further develop and market the findings, Soderstrom said.
The office files a patent whenever a researcher demonstrates innovative work that could lead to a marketable product.
“That’s the only way the things are going to work,” Rose said. “We can discover things at Yale, but we have no way to market them.”
In the case of the work done by Rose’s team, preliminary results with the VSV vector in 1995 looked promising enough to warrant the Office to file patents, Soderstrom said, before any of the HIV work.
Rose suspects that at some point, his research was the most expensive case that the University had running because of its patent costs. Accordingly, the University was heavily recruiting companies to assume that financial load.
“The costs to file patents are very high, and the University looks for a company to take the burden off the University,” Rose said.
Despite the high price tag, large drug-development companies are willing to take on the financial burden.
Wyeth, through its support, gains the exclusive rights to develop and commercialize the VSV vector and its implications as an HIV vaccine, Rose said.
But it is with that patent that the questions move from the realm of science into the arena of public policy, economics and medical ethics.
After his scientific triumph, Rose no longer has any formal control over his discovery.
Doug Petkus, a spokesman for Wyeth-Ayerst Pharmaceuticals, stressed that while Wyeth does control the rights to the vector, “this is a co-development project,” and there is more to be done by Rose in the lab in coordination with Wyeth in development.
Weary of the hype, AIDS activists fear that they have seen this scenario before.
Last year, controversy arose over an AIDS treatment, the drug d4T, which was based on the work of Yale’s own William Prusoff. The rights to develop a drug based on this research were licensed to pharmaceuticals powerhouse Bristol-Myers Squibb.
Prohibitively high prices precluded much of the developing world from taking advantage of this new drug, to the dismay of many here at Yale, students and faculty alike.
“Yale as an institution should do everything within its power to make this vaccine accessible in Africa and Asia where people don’t have the resources to buy it,” said campus AIDS activist Beth Rubenstein ’03. “I think Yale will need some reminding to make sure the vaccine does not end up like d4T and reaches the people it needs to reach.”
Last March, Yale began negotiations with Bristol-Myers Squibb to allow for a generic version of d4T to be produced for use in South Africa.
The previous licensing agreement between Yale and Bristol-Myers Squibb had prevented either party from unilaterally issuing a license to produce a generic drug without the fear of a lawsuit.
After a few weeks of negotiations, Bristol-Meyers Squibb became the first pharmaceutical company to allow other companies to produce generic versions of an AIDS drug for which it has exclusive production rights.
But Rose, Soderstrom, and Petkus all doubt that such a predicament will occur with the proposed vaccine.
Rose believes that his potential vaccine is in a different category than drugs like d4T.
“This is a completely different process than with treatment drugs which have to be taken typically life-long in the case of AIDS, and that costs a fortune just in production,” Rose said. “This is a one-time vaccine and it would be cost-effective for the world to get rid of the plague.”
Rose expects that the World Health Organization, under the United Nations, will “negotiate a price with a company and will turn out billions of doses so people in underdeveloped countries won’t pay more than cents to get the vaccine.”
Rose draws hope from the World Health Organization’s successful effort to eradicate the smallpox virus in the ’70s. After only 12 years, the organization marked the elimination of the virus in all areas of the globe.
“The idea for this vaccine is [the] creation [of a product] for a world market,” Soderstrom said. “Clearly, Wyeth and others are well aware of what’s been going on in terms of some of the controversies over other AIDS therapies.”
But those who have less faith in the benevolence of the pharmaceuticals industry stress Yale’s responsibility for getting the vaccine to underdeveloped nations across the globe.
“The discovery and development of a vaccine is critical to halting the AIDS pandemic,” said Tyler Crone LAW ’03, who has a master’s degree in public health.
“Yale is, and must continue to be, a leader in the fight against global AIDS,” she added. “We are an institution designed to serve the public good and it is our responsibility to do so.”
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