The future of animal health

When Dr. Peter Johnson of the USDA's National Research Initiative talks about the possibilities of microbial genomics, he uses the example of Neisseria meningitidis, which causes meningitis in humans.

By sequencing N meningitidis—identifying all the genes in the bacteria's DNA—researchers at the Institute for Genomic Research took just a year and a half to develop two potential vaccines, now in clinical trials. Using more traditional methods, it could have taken them years or even decades to get to that point, Dr. Johnson said.

Genomics holds the same promise for animal pathogens, he said. With this technology, scientists can develop improved diagnostics and new vaccines by targeting proteins responsible for the microbe's pathogenesis, virulence, and other fundamental qualities. But compared with human disease-causing agents, few animal microbe-sequencing projects have been funded, and most by countries other than the United States.

"We want to stay at the forefront, and there is a definite concern and real possibility that the United States is falling behind in this area," Dr. Johnson said. "I hear it over and over again from multiple sources, and then I just observe it—the United States is not the leader in genomics for veterinary pathogens."

Using an electronic forum, veterinarians and others in the agriculture field have produced proposals aimed to change that, however.

On Jan 31, the USDA Microbial Genomics Workshop—a panel of 26 investigators with backgrounds in many species—released a report containing eight recommendations for how the USDA can take a leading role in this type of research, and a list of 15 priority microbes that should be sequenced first.

"What we've done is to put forth our plan, so to speak, of how it is that we're going to be spending the next four to five years in improving animal health through a basic understanding of the genetic makeup of these microbes," said Vivek Kapur, PhD, BVSc, one of three workshop co-chairs.

The group not only wants to bring the United States up to speed with other countries' efforts to sequence microbes that cause disease in animals, it also wants veterinary microbial genomics to catch up to its human equivalent.

"If these recommendations were all put in place, what it would result in is elevating the USDA—or elevating agriculture, elevating veterinary medicine—to a level comparable to the National Institutes of Health in terms of what they are able to do for human health," Dr. Johnson said.

The conference, held entirely via e-mail, also gave nonpanelists the chance to participate. Those from industry and veterinary groups, including the AVMA and the associations of bovine, equine, and swine veterinarians, were invited to submit comments to a separate e-mail listserver. The comments from both the selected panel and the other stakeholders were collected between May and June of 2000.

"I think that we all, as the AVMA, as the veterinary profession, or people interested in animal health, ought to take some pride in this effort," said Dr. Brad W. Fenwick, professor of pathology at Kansas State University and workshop co-chair.

The list of priority microbes will be updated as more sequencing projects are undertaken, and organisms from a second-tier list will be moved up to replace those that are completed. The panelists also recommended the formation of an international review group to revisit the entire list at least once a year.

The final eight recommendations for the USDA included a dollar amount for the near future of genomic research. To truly keep pace, the panel advised, the USDA would have to spend a minimum of $90 million in the next five years.

"Those numbers are very helpful to the USDA," Dr. Johnson said. "They begin to give us a gauge as to how well we're doing."

The panel recommended that the USDA spend $15 million on sequencing animal pathogens in the first year—a formidable increase from the $2.3 million the agency devoted to this research last year.

Most of the other recommendations, including the development of community access databases, increased educational outreach, and expanded genomic training programs for veterinarians and other biologists, are dependent on those resources. And although Dr. Johnson said he thinks this report will help convince USDA administrators of the importance of this research, panelists said cooperation from other stakeholder groups would also be necessary to achieve the ambitious goals the workshop laid out.

"The message is not just to the USDA, it's to the whole industry," Dr. Fenwick said. "We're hoping that commodity groups, animal interest groups, will take this report and put it on their research agenda or their funding agenda to partner, to try to do some of those [sequencing projects] in addition to just relying on the USDA."

Co-chair Dr. Kapur, an associate professor of veterinary pathology at the University of Minnesota and director of its Advanced Genetic Analysis Center, received such industry support when he led a team of researchers in sequencing Pasteurella multocida. The sequencing, which was recently completed and published in the March 13 Proceedings of the National Academy of Sciences, was funded in part by the Minnesota Turkey Growers Association and was the first such project to receive competitive USDA funding.

Analysis of the data continues, Dr. Kapur said, but the animal health community will soon be reaping the benefits. He and his team have identified a molecule that could potentially be used as a vaccine for diseases caused by this pathogen.

"Now that we know every gene of this organism, we actually have a fairly good indication of how this organism works," he said. "Slight, subtle changes in its genome structure may have very large consequences on its ability to cause disease. Now, with this background information, we're able to monitor those changes at a level of discrimination that we were heretofore not able to."

This intimate knowledge will be possible for each microbe sequenced, and could also lead to new and novel classes of antimicrobial agents and vaccines, Dr. Kapur said—especially valuable given current debates over veterinary antimicrobial use and its effects on human resistance.

"My sense is that, in terms of combating these diseases—that's either preventing them or treating them more effectively—we have essentially gone as far as we can using traditional techniques," Dr. Fenwick said. "Without applying the molecular biology techniques of sequencing organisms and looking at these organisms' abilities to cause disease at the molecular level, we're not going to make any more progress than where we stand today."

The final report, as well as correspondence from panelists and other stakeholders and a complete list of sequencing projects already underway, is available at genome.cvm.umn.edu.