Dogs, bees in gene-mapping contest (2002)

 

 

Dogs, bees in gene-mapping contest - Race is on to determine which creatures to decode next (2002)
Laurie McGinley

The Wall Street Journal
Navasota, Texas,
Feb. 28

Danny Weaver, a fourth-generation beekeeper, wants to breed a better queen bee. For help, he has turned to the Human Genome Project.

It isn't so far-fetched. The genome project, which last year published a draft of the human genetic code, will wrap up much of its work on the human, mouse and rat genomes in the next year or two. Many of its DNA-sequencing machines, which determine the precise order of the chemical units that make up the genetic code, will be available even earlier.

Lobbying for species
Now, the National Human Genome Research Institute, the arm of the federal National Institutes of Health that funds much of the sequencing in the U.S., must decide which creatures to decode next. To get advice, it is conducting a novel contest in which scientists and industry groups make pitches for their desired species.

The honey-bee advocates, which include several prominent scientists as well as bee breeders such as Mr. Weaver, are some of the busiest. They argue that decoding the bee — considered the social butterfly of the insect world — would provide crucial clues to human learning and behavior. Besides, Mr. Weaver says, “We’ve got a long way to go to get a perfect bee.”

But the bee faces competition from an array of other beasts. Sequencing the chimpanzee would help define “humanness,” say backers of one of man’s closest relatives. Platypus partisans say the furry egg-layer would provide clues on the evolution of mammals. Fans of the rhesus macaque tout its wide use in biomedical research. Cow researchers say the bovine genome might pinpoint genes that contribute to disease resistance and meat tenderness.

Other contenders include the chicken, the dog, the sea urchin, the freshwater turtle and a pond-dwelling protozoan called Tetrahymena.

“We all have our favorite genomes,” says James Womack, a professor of veterinary pathobiology at Texas A&M University in College Station, Texas. “I like cows. Other people like pigs. But there are so many thousands of species of animals that you can’t do every genome.”

The NHGRI set off the competitive scramble in October by announcing it would accept 10-page nominations for species three times a year. By Feb. 10, the first deadline, the institute had received about a dozen nominations. An institute task force will rank the proposals for an advisory panel that will make final selections in May. The panel could choose more than one creature for sequencing, but hasn’t set a specific number. More nominations are due in June.

Bee price tag? $5-10 Million
The winnowing is necessary because the demand for sequencing is likely to outstrip funding. For example, getting a draft of the chimp genome could cost $80 million, while a high-quality, finished version could cost triple that. A draft of the chicken genome carries a price tag of about $30 million. Even the humble honey bee would cost $5 million to $10 million. The NHGRI is currently spending about $90 million a year on decoding organisms other than the human.

The selections could have important implications for human health. Even with last year’s draft of the human genome, with its 25,000 to 35,000 genes, “we still don’t know how many of those genes function, how they came to be and why they are arranged the way they are,” says Stephen O’Brien, a researcher at the National Cancer Institute who would like to see the cat genome sequenced. He and other experts say that comparing genomes from a variety of species may help explain the human genetic code, yielding insights into everything from evolution to the molecular causes of cancer.

More than just science is at stake. The selections could boost careers and businesses, too. Data from sequenced genomes will be made public, handing a windfall to researchers who focus on an organism that has been decoded. The data should help scientists secure more grants and even start spinoff companies capitalizing on the genomic discoveries.

“A lot of us have invested a scientific career in specific genomes,” says Dr. Womack, the cow expert at Texas A&M. 

The National Cattlemen’s Beef Association thinks a decoded bovine genome would produce gene discoveries that would lead to “a consistent, palatable eating product for the consumer,” says Elizabeth Dressler, the group’s associate director for research and technical services.

Pork producers want more genomic information to help them produce disease-resistant hogs. And companies that specialize in canine health products, from food to antibiotics, think sequencing a dog could help them.

The Human Genome Project, an international effort overseen in the U.S. by the NIH and the Department of Energy, is expected to produce a final sequence of the human genome by April 2003, 50 years after the DNA’s double-helix structure was discovered. Other creatures that have been decoded or are being decoded include widely used laboratory organisms such as yeast, E. coli, the nematode, the fruit fly, the zebra fish and the pufferfish.

Big investment
Meantime, the federal government has a big investment in $300,000 DNA-sequencing machines, mostly at three big university-affiliated centers: Baylor College of Medicine in Houston, Washington University in St. Louis, and the Whitehead Institute in Cambridge, Mass. Gesturing at one of Baylor’s 75 sequencers — which resemble industrial washing machines — George Weinstock, co-director of the facility, says, “It’s our most expensive piece of equipment. You don’t want this sitting around idle.

While there was broad agreement on which projects to do in the past, researchers, industry groups and the sequencing centers have a long and varied wish list for what could come next. And they’re not relying solely on dry scientific arguments in lobbying for their favorites.

Maynard Olson, a University of Washington researcher who favors the chimp, put in a plug for it while addressing a conference in December attended by NHGRI director Francis Collins. Elaine Ostrander of the Fred Hutchinson Cancer Research Center in Seattle highlighted her canine-genetics research during a talk in New Orleans last year. “To see a big puppy flash up on the screen, it was a highlight, you bet,” she says.

Sean Eddy, a researcher at Washington University in St. Louis and a member of the priority-setting task force, says low-key politicking often occurs during social hours at conferences. “People will be sitting around drinking, and say something like, ‘I think the platypus should be next.’

Some groups are looking to Congress. A new advocacy group, the Alliance for Animal Genome Research, is pressing for increased funding of genomic research involving livestock animals, such as pigs and cows, and pets, such as dogs and cats. Members include the National Pork Producers Council, the cattlemen’s association, crop-biotechnology company Monsanto Co. and agribusiness giant Cargill Inc. The dog advocates have hinted that they will appeal to lawmakers if the canine genome isn’t made a top priority.

Watson's support
The dog is likely to be nominated later this year. It has the additional support of DNA pioneer James Watson and of the American Kennel Club’s Canine Health Foundation, which spends $1 million a year on genetics studies. Those studies already have uncovered genes for certain types of canine blindness. “Dogs get 350 inherited diseases, many of the same ones as humans,” Dr. Ostrander says. Because of that, Dr. Watson believes that decoding the dog genome could help pinpoint genes important to human health.

Keith Killian, a Duke University researcher, is pushing the duck-billed platypus, a web-footed mammal that is sometimes called a living fossil. Because it is so distant from humans, from an evolutionary standpoint, any DNA sequences found in both genomes probably would be “highly significant,” Dr. Killian says. But there’s a complication: Because it’s very difficult to raise platypuses in captivity, tissue must be acquired from scientists in Australia and Tasmania, who collect samples when the animals are hit by cars or attacked by dogs.

Scientists focused on the top of the evolutionary scale prefer the chimpanzee, with a genetic code that is believed to be almost identical to the human one. Comparing chimp and human genomes could help explain “one of the major transitions in evolution,” the emergence of humans, says Ajit Varki, a researcher at the University of California at San Diego. But even some primate researchers think the chimp may be too close to the human to disclose much new information.

Danny Weaver, 42 years old, whose family has been keeping bees in rural Texas since 1888, says decoding the honey bee would benefit both beekeeping and human health. “No other genome project will deliver more bang for the buck than the honey bee,” he says. “It’s a sweet deal.”

For the industry, he says, it would accelerate the breeding of superior bees resistant to parasites and disease. Exotic mites, including the bloodsucking Varroa destructor, have wreaked havoc on the industry since arriving in the U.S. in the 1980s.

Mr. Weaver, a top queen breeder who owns B. Weaver Apiaries Inc. with his father, Binford, has had thousands of dollars in bees destroyed by the pests. So have the Weavers’ customers-hobbyists and professional beekeepers who buy bees by the pound.

For years, the Weavers have used traditional breeding techniques, including artificial insemination, to raise stronger queens. But the process sometimes results in unwanted traits such as reduced honey and brood production. Mr. Weaver says sequence information could help identify specific genes for more precise breeding. “Getting the honey-bee genome could revolutionize bee breeding in three to five years,” says Mr. Weaver. For bee breeders and keepers, that could mean higher quality product with fewer losses and lower costs.

Mr. Weaver’s campaign for the genome began in earnest last spring, after he met Gene Robinson, a leading entomologist at the University of Illinois at Urbana-Champaign. The two shared a passion for bees and genomics, and began exchanging e-mails and phone calls about getting the honey-bee sequence.

Serious Science
Dr. Robinson had become enthralled with bees in 1974, when he worked for a commercial beekeeping operation in Israel after high school. “I fell in love with bees, and they led me into biology,” he says. Over the years, he grew fascinated by their “prodigious feats of learning,” in spite of their having tiny brains.

“They learn where they live, how to navigate back to hives from the environment, how to scout for food,” says Dr. Robinson, whose laboratory focuses on honey-bee genetics and social behavior.

In June 2000, he organized an international meeting for scientists interested in honey-bee genetics in Bellagio, Italy. The experts agreed that the highly social insect could help researchers understand the genetic basis of interaction in other species, including man, and could provide information on infectious diseases and allergies.

When Mr. Weaver joined the effort, the base broadened to include the bee industry, including the American Beekeeping Federation, an industry group based in Jesup, Ga. Mr. Weaver, who did postgraduate work in molecular biology at the University of California at Berkeley, could keep up with the researchers. He also knew how to generate buzz. To win government support for sequencing the genome, he thought, the backing of one of the big federally funded sequencing centers would be crucial. Nearby Baylor, which was focusing on the human and the rat genomes, seemed to be the logical place to turn.

He cold-called Richard Gibbs, director of Baylor’s Human Genome Sequencing Center, set up a meeting and sent a batch of information. At the Sept. 13 meeting, “We just sat across the table from one another, and Richard said, ‘OK Danny, tell me about the honey-bee genome,’ ” Mr. Weaver recalls. “My first job was to show that this wasn’t a moronic pie-in-the-sky idea, but has serious science behind it.”

By the end of the session, Dr. Gibbs and the center’s co-director, Dr. Weinstock, were on board. Baylor later committed not only to do the sequencing of the honey bee but also to take a first crack at comparing it with other genomes, such as the rat’s and the fruit fly’s. That’s an initial step in figuring out the genes’ functions.

In October, after NHGRI requested nominations, the honey-bee advocates mobilized. To accompany a white paper nominating the insect, Dr. Robinson lined up letters of endorsement from such scientists as Thomas Cech, the Nobel Prize-winning president of the Howard Hughes Medical Institute, and Gerald Rubin, a prominent fruit-fly researcher.

Both Dr. Robinson and Mr. Weaver played a role in getting a letter of endorsement from Edward O. Wilson, the influential Harvard sociobiologist. Mr. Weaver’s late uncle, Nevin Weaver, was a friend of Dr. Wilson’s, and Dr. Robinson previously had discussed the honey-bee project with Dr. Wilson. In his endorsement letter, Dr. Wilson wrote that the bee genome is likely to yield data “that have application to the understanding of human social behavior.”

At the same time, Baylor officials were working with Dr. Womack about sequencing the bovine genome. Shortly before Christmas, advocates for both the honey bee and the cow met at Baylor to finalize plans for their white papers. “We call it the milk-and-honey meeting,” Dr. Weinstock says. He urged both groups to focus on human-health implications. Baylor officials also talked to people supporting the rhesus macaque and sea-urchin genomes and joined forces with them, too. A day or so before the Feb. 10 deadline, they embraced freshwater turtles as well. All the projects are worthy, they say.

The Baylor people say they are confident that the honey bee will be viewed as a high priority for sequencing by NHGRI, and have started preliminary work on the bee, using DNA supplied by Mr. Weaver.