Backed by the NIH, a recent decision by the Institute of Medicine on controversial hepatitis C research could change practices in the lab.
Before new medications and medical procedures can be tested in humans, they are typically tested in animals, who serve as "model systems" to determine their safety and efficacy. The use of animals in research is an understood and, in many ways, integral part of medicine.
But about a year ago, the National Institutes of Health (NIH) commissioned a long-term study by the Institute of Medicine (IOM) to evaluate the necessity of using chimpanzees in medical research. The IOM released their findings last month, arguing that the use of chimpanzees should be significantly curtailed. But the researchers remained undecided on a couple of important issues, one of which was the advisability of using chimpanzees in research testing preventative vaccines for the hepatitis C virus (HCV).
According to the Centers for Disease Control (CDC), about 3.2 million Americans suffer from HCV, with 17,000 new cases occurring each year in the United States alone. The virus can lead to significant liver disease and cancer, and it is the primary cause of liver failure and transplants in the country.
Chimpanzees are our closest genetic relatives, which in some ways makes them excellent stand-ins as research subjects for serious diseases. And, in the case of HCV, they are the only other species that can contract the virus. But there are some concerns, both scientific and ethical, about using them as subjects for HCV research. One issue is that their physiology is just different enough from ours that they actually handle the virus more effectively. In humans, about 20 percent of people are able clear the virus from their bodies spontaneously, meaning that they need no treatment. In chimpanzees, the clearance rate is about three times higher. Because of these physiological differences, Dr. Jeffrey Kahn, who headed the IOM committee, said that "HCV presents somewhat differently in chimpanzees than in humans."
That fundamental problem aside, the committee members remained split on whether chimpanzees should be used in a specific area of HCV research: the development of a prophylactic, or preventive, vaccine. This is one of the two major approaches in HCV research -- the other being how to treat people already infected. The committee agreed on the second issue: Since there are so many humans already infected with HCV, infecting chimps would be unnecessary. "Safety concerns could be addressed by testing new drug candidates in other animal models," Kahn said.
The development of a prophylactic HCV vaccine poses more problems, largely because studies to test the efficacy of such vaccines require what are known as challenge studies, in which animals must be intentionally inoculated with the virus. "Challenge studies for a preventive HCV vaccine aren't ethical in humans," Kahn said. "If such challenge studies are deemed necessary -- and the committee was evenly split on their necessity -- the only alternative animal model at the moment is the chimpanzee."
Since the committee was unable to come to a consensus on this issue -- which is clearly not a minor one -- what will happen? The question is especially relevant since the NIH swiftly agreed to abide by the IOM's recommendations, recently releasing a statement to this effect.
Despite remaining disagreement within the IOM committee over whether the chimpanzee is necessary for HCV preventive vaccine research, the NIH will use the IOM's recommendations to evaluate new research projects. They'll require that proposed studies involving chimpanzees fulfill the following criteria as recommended by the IOM committee:
- That the knowledge gained must be necessary to advance the public's health;
- There must be no other research model by which the knowledge could be obtained, and the research cannot be ethically performed on human subjects; and
- The animals used in the proposed research must be maintained either in ethologically appropriate physical and social environments (i.e., as would occur in their natural environment) or in natural habitats.
Kahn underlines that to ensure the requirements are followed, the NIH will be appointing a new body whose job will be to review research studies proposing the use of chimpanzees. "We looked at areas of research, not specific research projects," he said. "The new committee will be reviewing specific projects and decide whether they fit the criteria we recommended, and which the NIH adopted."
Animal advocates have long been pushing for an end to the use of chimpanzees in research. Whether this development marks the beginning of a trend in the U.S. to reevaluate the use of other animals in medicine remains to be seen.
"Many have asked whether this marks the beginning of a major change in the use of animals or whether it's a one-off case," Kahn said. "Our analysis only considered chimpanzees, but one of the take-home messages of the report is that the necessity for chimpanzees in biomedical research is on a downward trajectory. The committee's criteria set the bar quite high, and fewer studies are going to pass muster. The fact that the NIH has accepted and adopted the recommendations represents a turning point for the use of chimpanzees in research."
Time will tell whether this moment in research history will affect the roles of other animals in scientific research, but this is an important win for chimpanzees.