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Boyd Haley: Tagging Toxins for Better Health

by Jeff Worley

Why do we eat? Simple hunger? Because our favorite foods taste so good? Nope. According to Boyd Haley, the reason we eat is to make ATP.

ATP—adenosine triphosphate—is nature's energy conversion compound, energy that's used for all the processes that keep us alive. Some of these processes occur continually, such as the metabolism of foods, and other processes occur only at certain times, such as muscle contraction and other cellular movements, says Haley, a professor of medicinal chemistry at UK since 1985. "When you clench your fist, you're contracting muscles and that movement burns up this important biological molecule."

Photo of Boyd Haley

Haley, who is currently chairman of UK's chemistry department, has had a lifelong professional interest in ATP, a focus that directed his graduate work 30 years ago and led him eventually to invent a chemical compound analogous to ATP that can be made to be radioactive. Using a light-activated form of radioactive ATP, scientists can pinpoint areas of binding activity in body tissue. Haley patented this compound and subsequently formed a company that has sold it to researchers, dentists and physicians from all over the world.

But this synopsis gets us ahead of our story. Let's first roll back the years and follow Haley on a scientific journey that started with a tantalizing string of trout.

"When I was just getting out of the army in the early '60s, I got this brochure from the University of Idaho," Haley recalls. "The cover featured a beautiful woman holding a string of trout in front of this canoe by a lake with a gorgeous mountain behind it." Like the trout, Haley was hooked. He wrote to the university, which encouraged him to come for his advanced degree, and a week and a half after he got out of the army Haley was setting up his rack of test tubes in a University of Idaho chemistry lab.

He loved it there but when his mentor left, Haley went even further west, to Washington State, for his doctorate in chemistry. There, he was able to combine his strong background in organic chemistry with the expertise of the scientist he worked for, a biochemist. And this is where his interest in ATP began.

"At the time a major chemical question was, where does ATP bind on a protein molecule in order to make it contract? The guy I worked for at Washington State was a muscle biochemist. We worked together to make chemical modifications on ATP to try to identify how and exactly where ATP binds to cause muscle movement," explains Haley. We were not successful but did make some important research compounds. I moved to Yale University for a postdoctoral with a physiologist and continued to work on this project and published the first successful use of these compounds in 1974, the year he joined the Department of Biochemistry at the University of Wyoming. There, he continued this ATP research, almost single-handedly carving out the new field of photoaffinity labeling, pioneering work that had been continuously supported by the National Institutes of Health for 27 years.

The purpose of "labeling" ATP is so that researchers can see which proteins it binds to in tissue—they can also pinpoint the location on the proteins it binds to when it does its work. The compounds, or probes, that Haley develops are chemical modifications of natural ATP, chemical "act-alikes." He combines radioactive ATP with a photosensitive group, which renders the probe photoactive. When these photoprobes are exposed to ultraviolet light, they bind to the active site of the protein, allowing it to be permanently tagged with radioactivity for isolation and identification.

"The probe behaves just like ATP in the absence of light," Haley says. "It's a mimic of the natural compound in your body that converts the chemical energy of ATP into mechanical energy, causing your muscles to contract.

"What this technology does is extremely important," says Haley. "Using this, you can take a piece of normal tissue, brain tissue, for example, and compare it with brain tissue from, say, someone with suspected Alzheimer's. And by using these probes you can see the biochemical differences between the two tissues." This lead to a proposed diagnostic test for Alzheimer's disease that was published by Haley and a graduate student in the Proc. National Academy of Sciences in 1992. Currently, a company called SynXpharma with Johnson & Johnson are using this technology to develop a "chip technology" for testing patients with regards to early diagnosis of Alzheimer's disease using serum and cerebrospinal fluid.

Realizing the scientific importance and diagnostic potential for his probes, which Haley has patented through UK's intellectual property office as he has developed them, he formed a company to market the substances in 1994. Bioproducts Inc. was one of the first start-ups in UK's Advanced Science and Technology Commercialization Center.

"The major backer was a lab supply company owner from Chicago, who put half-a-million dollars into the company," Haley says, "and we were off." Though sales were good, even early on, Haley's partner pulled out after three years because "he thought he'd get rich quick and made good money selling our synthetic schemes to another company." There was a silver lining, however: the ex-partner had to leave behind all the major lab equipment that was radioactive.

During the existence of Bioproducts, Haley continued to refine his invention and also work to extend its usefulness. Drawing on his background in biological chemistry and toxicology—Haley was a faculty member in the UK College of Pharmacy from 1985 to 1997 before he came to the chemistry department—he began thinking about how his photoaffinity probes might work to identify the presence of toxic compounds.

"There was a very convincing article in JAMA [the Journal of the American Medical Association] not long ago on the linkage between microbe produced toxins in the human mouth and all kinds of diseases—strokes, low birth weight babies, late onset diabetes, cardiovascular disease, high blood pressure, dental implant infections, arthritis, and blood infections," Haley says. So with Curt Pendergrass, a Ph.D. student who had chosen to do his doctoral work under Haley, a protocol was developed that can readily detect the presence of these toxins through a seven-minute test-tube procedure. Dr. Pendergrass named the procedure TOPAS (Toxicity Prescreening Assay).

Haley and Pendergrass then presented their findings to a small conference of dentists and physicians. One of the dentists was so convinced of the validity of the link between oral infection and serious disease that soon after the meeting she sent them some patients' samples for analysis. She also sent Haley and Pendergrass a check for $2,600.

"We made the decision then and there," Pendergrass says. "I'd become a full-time entrepreneur and Boyd would remain a 'lab rat,' and we'd try to make this thing work as a for-profit business."

So Haley literally picked up the pieces in his old lab in ASTeCC and started over. "This was in '97," Haley explains. "I put in 10 grand out of my pocket into what we decided to call Affinity Labeling Technologies (ALT), and initially we focused on making the probes that we knew sold best."

But ALT quickly outgrew the lab space as the orders for testing kits and analyses poured in. In less than three years ALT purchased a home—an office building near campus, where Haley and Pendergrass, along with their wives, put aside their analytical lab skills for much more basic skills: painting, dry-walling, installing cabinets and countertops, and transforming the concrete block shell into a working biomedical lab with offices.

ALT has incrementally increased its sales in each of the years since, without the benefit of any publicity or marketing efforts, except the launching of its Web site ( by Dr. Pendergrass, Haley says. The company now has five employees: Pendergrass, who serves as president; Dr. Anjan Bhattacharyya, radiochemicals laboratory director; a medical technician, a business manager, and a staff member. "I don't go there at all— I'm only the scientific advisor," Haley says.

"A major goal, along with the testing services we provide, is to raise the level of awareness among the public and health-care professionals concerning the proven relationship between good oral health and everyone's simple well-being," says Haley.