PARTNERSHIP IS ESSENTIAL FOR ADVANCING ANIMAL GENOMIC RESEARCH

For Roger Wyse, Managing Director of Burrill & Company, and Chairman of the Alliance for Animal Genome Research, the strongest approach is to involve a number of different entities in domestic animal genomics research programs. “It's quite clear that what we're talking about here is not a standalone initiative, but rather one that needs to be integrated across agencies to take advantage of their structure and strengths.” Although it will be more complicated to coordinate efforts in such a broad coalition ranging from government to the private sector, it is in practice the only viable option. For example, scientists then can consider their research priorities and decide which governmental agency is most appropriate for working with them, instead of concentrating on an agency first and trying to present their research in such a way that it fits the agency's agenda.

Presently, the role of the federal government in genomics research remains important with respect to the opportunities that it offers for competitive research grants. Most of the support for basic research into domestic animal genomes, such as determining the billions of individual base pairs that make up the genetic sequence of each mammal, is likely to come from research grants, said Wyse, and most of those grants will come from the federal government. This type of funding has two important functions, Wyse said.

“We think it is very important to have the funding to increase the knowledge base,” he said. So determining the cattle genome, for instance, is valuable in itself. However, Wyse also noted the importance of securing human resources, stating that “…it is equally important to get a competitive grants program to allow us to build the human resources that are necessary for not only doing the science, but commercializing the science.” The benefits of increasing human resources in this field will be broad ranging, and spread across different types of institutions, Wyse said. “If you are a small company now in the animal genome space and you are looking to hire really good people, there aren't very many out there. It is going to be important that we populate our universities with research funds so that we can train that next generation to do research in this area.”

THE ROLE OF FEDERAL AGENCIES

The issue of which federal agencies most likely would provide the basis for research on domestic animal genomes generated a great deal of discussion at the workshop. Most of the federal funding for sequencing the human genome came from two agencies, the National Institutes of Health (NIH) and the Department of Energy (DOE). The NIH was interested in the human genome because of its importance to medicine and improving human health, while the DOE's genome effort stemmed from its long interest in the threat that radiation poses to human health—particularly its ability to cause genetic mutations. From one perspective, the NIH and DOE are well positioned to oversee research into domestic animal genomes, for they already have strong support for genomics, some of which could be applied to domestic animal research. On the other hand, NIH and DOE traditionally have focused on humans and on animals, such as the mouse, that serve as traditional laboratory models for disease, and domestic animals traditionally have not been part of their domains.

By contrast, the U.S. Department of Agriculture (USDA), with its mission for improving agricultural productivity in the United States, would seem to be appropriate for initiating further sequencing of domestic animal genomes, but its budget requests and allocations traditionally have not accounted for increased genomics research. Thus, workshop participants discussed the best ways to match their research objectives to the goals and missions of these various government agencies.

Wyse suggested, for instance, that the USDA has a number of existing programs that could be oriented toward research on domestic animal genomes. However, “ we have not really used the competitive advantage of the structure of an organization like USDA. For example, you have in it the Agricultural Research Service, which is an in-house research unit and has the necessary structure and budgets, has the ability to assign people to projects, and, most importantly, has a rewards system that allows it to do directed kinds of activities that can be both long-term high-risk or programs like managing germplasm. I think we ought to take advantage of some of the structures that we've got in place…Also at USDA is a competitive grants program that could be used to move into (research determining) gene functions that are important in applications in agriculture.”

On the other hand, as Jerry Dodgson of Michigan State University pointed out, the USDA budget cannot accommodate genome programs for farm animals. “We are talking about three mammals and the chicken, so we are talking $340 million by today's dollars. Unless we take a chunk out of the farm subsidy pot, that becomes a big constraint.”

For that reason, one audience member suggested NIH as the most appropriate starting point. “In light of NIH calling for proposals, I think what we do is work very hard to get NIH to see the value in sequencing farm animal genomes.”

As for companion animals, such as dogs and cats, the USDA Agricultural Research Service is not authorized by law to fund research on them. In this case, there is no choice but to consider other non-agricultural agencies such as NIH.

“As we think about the sequencing that needs to be done,” Wyse said, “we need to establish the criteria and the rationale” and then engage the “various agencies, whether that's NIH, DOE, National Science Foundation (NSF), or USDA. So an important part of this is thinking through what we want to do and then using the competitive strengths and the missions of the various agencies to appropriately support it.”

THE ROLE OF THE PRIVATE SECTOR

In order to address the later stages of basic research achieved through competitive grants, Wyse said that participation by the private sector must be considered as the research moves closer to commercial applications. He then mentioned the role of venture capital and funding from corporations interested in agriculture and human health.

“A lot of the fundamental knowledge that is going to be developed is really to develop the knowledge on which you can form small companies that people like us (venture capitalists) can invest in.” Wyse noted that venture capital is fairly new to agriculture, but made it clear that it is important because these small companies become the source of moving basic knowledge towards commercialization. Agricultural biotechnology represents a small fraction of the amount invested by venture capitalists in U.S. companies. Still, Wyse said, venture capitalists are just discovering agricultural biotechnology, and the amount they invest in it should grow. “I would argue that it's going to be critically important in the future.”

In addition to competitive grants from the federal government, and venture capital, Wyse discussed the role of corporations interested in agriculture and animal health. To date, he said, these companies have done relatively little. The animal health industry, he said, “has been the weak sister of the big pharmaceutical companies, and there hasn't been a lot of funding or initiative on their side to develop new things on their own.”

According to Wyse, this is about to change. For example, “There is a whole group of companies in the germplasm development area. Those folks are probably the furthest along in (terms of) thinking about genomics and how it can be used to help them select superior animals. But the issues for them are the profit margins that they have and the cost of doing both the basic work and some of the assays that would be used in marker assisted breeding or gene-expression profiling.”

THE ROLE OF A PUBLIC-PRIVATE PARTNERSHIP

To help define the roles of the public and private sector in domestic animal genomics research, Wyse suggested a public–private consortium in which private companies and research universities worked together. If the consortium had well-defined goals and limited itself to precompetitive research (work where companies or institutions are not averse to their competitors having equal access to the results of their efforts), it would have a good chance of success. Wyse believes that food and agricultural industries are prepared to be strong partners in an alliance, because the companies are interested in developing the technologies that they can apply. In particular, Wyse noted, the companies that process food animals are “poised and ready to participate. I would think that if we constructed the right kind of consortium, there might be an opportunity for a public partnership across that sector.” It also is likely, he said, that various special-interest groups would support or help fund such a consortium. Wyse identified the Canine Health Foundation as a prime example of a special interest group that has accomplished a great deal with a relatively small amount of resources and would be quite amenable to forming a consortium.

Kevin Schultz of Merial supported the idea of such a consortium. “One of the things that we've done as a company is to make a decision to do a lot more external interactions, rather than do everything internally. In fact, the shareholder companies Aventis and Merck, who own Merial, have made similar kinds of decisions. And so I think that there will be partners. It's clearly an expensive venue and we've got discussions ongoing with certain companies along those lines.”

Albert Paszek of Cargill showed support for the idea of a consortium as well. “When it comes to animal genomics activity, everything is outsourced anyway, and the major strategy that we operate under is massive collaboration and sponsorship of projects at public institutions, including universities.”

Max Rothschild of Iowa State University added that, historically, consortia have been successful in the agricultural research area. “There's some good evidence in the swine business that there have been good consortiums if it's precompetitive. There was one in Europe at the start of the 1990s. I helped organize one for QTLs in the mid-1990s.”

Finally, Wyse said, those interested in furthering domestic animal genomics should consider highlighting the ultimate value of this research to drugs and other human medical products. “ Part of the strategy will be playing up the fact that the biotechnology companies that take the information you generate and apply it to agriculture are actually going to build value in the human health care market.” Because returns are higher in human than in animal healthcare, and because the human healthcare market is much larger than its animal counterpart, the applications that animal genomics research has to human health will be an important consideration.

ALLOCATING WORK IN ANIMAL GENOMICS RESEARCH

In reflecting on the roles of government and the private sector, workshop participants focused on one major question with respect to the role of academia and its importance in creating a strong genomics research community: How much of the sequencing and other routine work should be conducted outside of an academic setting?

Over the past several years, for instance, several private companies have begun to offer sequencing services. One such example is The Institute for Genomic Research (TIGR), which is a nonprofit research institution located in Rockville, Maryland. With banks of automated sequencing machines, such centers can determine DNA sequences more quickly and cheaply than most university sequencing projects. A number of workshop participants found it sensible to use these specialized centers performing parts of the genomic research that mostly are a matter of technique.

Several workshop participants agreed that a number of the routine aspects of genomic research such as constructing BAC libraries or sequencing should be contracted out to these specialized facilities while researchers and students spend more of their time investigating “more interesting things” such as looking at gene function and gene expression and how those relate to the important traits, phenotypes, or diseases that we are interested in, be they in agriculture or in human health.

Others argued, however, that a university setting could be beneficial for carrying out sequencing. “One of the downfalls of outsourcing all sequencing activity,” said one audience member “is the fact that you cannot encourage small laboratories to train the next generation of scientists. You also discourage people from using those data because they don't feel ownership or a tie to it. I understand the efficiencies of outsourcing, but there needs to be a happy medium.”

A second audience member concurred. “Some of these species that we are talking about—cattle and pigs included—don't really have a community of people built up who are working with these things. There needs to be a balance between outsourcing and how much you give to academic institutions to encourage that community development in graduate students, post-doctoral fellows, and the like. There needs to be some recognition of the fact that the community is not widely developed, and it's in everyone's best interests that the community be developed.”

But, said Claire Fraser, president and director of TIGR, there does not necessarily have to be a choice between high efficiency and training new scientists. “What's been set up at Baylor (College of Medicine) and what's been set up at Washington University represent excellent examples of how you can create high-throughput facilities to get this work done at the most efficient cost yet, at the same time, train students and train post-doctoral fellows. I don't think it's an either/or situation.”

Ultimately, Wyse concluded, those calling for a centrist approach seem to have a valid argument. “There is a balance between doing routine sequencing in an academic setting with faculty and graduate students and post-docs, versus contracting it out to TIGR or someone else.”

But for the parts of the project with more intellectual content, most seemed to agree that it makes sense to use university researchers. “It's been my philosophy,” Wyse said, “that universities are better positioned to do the competitive-grant functional-genomics work and the like, as opposed to the basic sequencing. It seems to be a better fit with the university environment as well as its reward system.”