Dissecting 2008: The stories behind the science

Dissecting 2008: The stories behind the science

Oh, 2008. How we will miss thee. You brought us a historic and entertaining presidential election, a record-breaking Olympics and, of course, the near collapse of the economy (we'll try not to hold that one against you). It was a good year for science too. UF researchers began testing gene therapy to treat blindness in humans and reported numerous findings that someday could help patient's battle cancer, obesity and other diseases. The POST brought you these headlines each month, but what about what we didn't tell you, the stories behind the science? For every research discovery, there's a story of how it happened or what's happened since then. So, as 2008 ends, we bring you a few of the tales we found in labs across the HSC this year.

Research on a roller- coaster

After two years of experiments, tests, frustration, revised experiments and more tests, UF researchers were finally decoding the worm-to-worm signals the microscopic nematode Caenorhabditis elegans sends its potential suitors. That's when UF biochemist Art Edison, Ph.D., read an abstract and realized his lab may have been scooped.

Written by Frank Schroeder, Ph.D., a Cornell University researcher whom Edison had invited to speak at UF, the research abstract detailed a chemical structure strikingly similar to the one Edison and his researchers had recently identified. But Edison's lab was trying to find the first mating pheromone in the tiny worm — one of the most simple multicellular organisms and a model research subject — while Schroeder's lab was looking for what's known as Dauer pheromones, chemical signals that control the worm population, not expand it.

While Schroeder was in town for the talk, Edison asked him to review his lab's most recent nuclear magnetic resonance spectroscopy results, data that detailed, atom by atom, the chemicals in the fraction of the worm they were studying. Looking at the results, called a spectrum, Schroeder spotted it, C6, the Dauer pheromone he had discovered. It was very similar to the chemical UF researchers had identified as a mating pheromone.

"I was on a roller-coaster at that point," Edison says. "We had been working on this for two years and either we had been scooped, or C6 did a lot more than Frank had known before."

Working in collaboration with Paul Sternberg, Ph.D., a scientist at the California Institute of Technology whose research sparked Edison's interest in the mating pheromone, the researchers learned they had identified the same chemical — the only difference in chemistry was a sugar attached to UF's molecule, Edison says. And it did, in fact, have two distinct purposes, working basically as a population monitor. It opens the door for mating when the pheromone signal is very low, and if the signal gets too strong, it shuts the worms' system down, sending them into hibernation mode.

"It's like a bell-shaped curve," says Edison, who along with his collaboraters reported the findings in Nature in July. "It only works within a certain range. A lot of pheromones act like that.

"This is something I'm going to be thinking about for years. It does make sense that the same molecules have dual purposes. The other caveat is we're certain the story is more complicated. There are more signals we haven't identified."

So why all the fuss to understand how worms communicate? Researchers have learned almost everything there is to know about cells, human or animal, by first discovering it in a nematode or a fruit fly, Edison says. Because nematodes are actually the most common animal on the planet, understanding C. elegans could help scientists combat worms that threaten human health, too.

And, as any researcher will say, C. elegans is easy to study.

"You can grow large amounts of C. elegans in a culture mixed with bacteria," Edison says. "It sounds disgusting, but it's not. They're actually very pretty worms." — April Frawley Lacey

Vision in sight?

Surprisingly, they could see better in the dark.

Each of the first three patients who volunteered to test the safety of an experimental gene-transfer technique to treat blindness said their vision had improved, but a portion of that improvement was not readily evident.

The UF and University of Pennsylvania scientists conducting the phase 1 clinical research study here in Gainesville were startled to learn that after treatment the volunteers could see best when they woke up in the morning.

"When someone walks into a dark movie theater from the sunlight, it takes a few moments for their eyes to adjust. This process is termed ‘dark adaptation.' But for some people, dark adaptation takes much longer, if it occurs at all," says William Hauswirth, Ph.D., an eminent scholar, professor of ophthalmology and member of UF's Powell Gene Therapy Center. "When our patients told us they could see better after they had been in the dark for hours, it became clear that some of their restored visual function was hidden by a defect in their rate of dark adaptation."

The volunteers have a type of hereditary blindness called Leber congenital amaurosis type 2, a condition where photoreceptor cells cannot respond to light because a gene called RPE65 does not properly produce a protein necessary for healthy vision.

Each received a subretinal injection to replace the nonfunctioning gene in small, selected regions of the retina. And the therapy is working.

The results, reported in September in the Proceedings of the National Academy of Sciences, are the first to show that gene therapy can improve both day and night vision in patients with LCA. Restoration was localized to the area of treatment. While day vision improved as much as 1,000-fold, night vision improved as much as 63,000-fold.

But the restored night vision of the volunteers took as much as eight hours to adjust to darkness compared with about 20 minutes in normal eyes.

"This is not a bad thing, because what we've given them is some vision in daylight and lots of vision after dark, and we've only treated a very small portion of the retina," Hauswirth says.

Since the first three patients were treated, two additional ones have received the therapy. The sixth is expected to be treated in January.

"So far, so good," Hauswirth says. "The results are already spectacular. We have one more patient to go in this round. We'll then watch for any side effects and if everything continues to be OK, we'll decide whether or not to move forward in children. LCA2 is considered a childhood form of blindness, and patients are usually functionally blind before age 10. We think the younger the patient, the more vision they can potentially gain back."— John Pastor

A sound idea

It all began when Lee Krause started asking his audiologist, Alice Holmes, Ph.D., questions. Krause, a computer engineer from Melbourne, Fla., was frustrated with the fine-tuning process after he received a cochlear implant at Shands at UF in 2002.

"I realized during the tuning process that I was never going to achieve my objective of being able to better understand speech," Krause says. "I knew there had to be a better way."

After cochlear implant surgery, audiologists "fit" the patient's cochlear implant processor by manipulating implant settings, a process that often takes multiple clinic visits and many months to complete. Several million combinations of device parameters make it impossible to evaluate a patient's performance for every possible combination.

"Lee came in to me one day while we were doing programming and said ‘This doesn't make sense. Why are you having me listen to beeps when I want to listen to speech? Why don't you test me doing speech and we can program it that way?'" recalls Holmes, a professor in the College of Public Health and Health Professions' department of communicative disorders. "I told him there were some problems with that and I gave him a couple of chapters to read thinking that that was probably going to answer his questions. And he came back the next week and said ‘No I really think we can do this.'"

Krause and Holmes, along with Rahul Shrivastav, Ph.D., an associate professor in UF's College of Liberal Arts and Sciences, and Purvis Bedenbaugh, a former UF professor, set out to develop a better system for cochlear implant tuning. The resulting software program, known as Clarujust, quickly analyzes the patient's speech comprehension to determine the best cochlear implant settings for a particular patient. In a pilot study, the researchers found that the new program resulted in improved performance in all outcome measures, including speech perception and the ability to hear over background noise.

The new software program has the potential to improve the quality of life for thousands of cochlear implant recipients, Holmes says.

"This is the most exciting research project I've been involved with in my career," she says. — Jill Pease

No money, no problem

After Linda Bartoshuk, Ph.D., and her students discovered an unexpected correlation in their research database, she was delighted, in a sense, when the National Institutes of Health gave her only the nominal amount of $50,000 to further her research.

Although $50,000 was a mere fraction of what she would have needed to gather more data for her study, all was not lost. Instead, the NIH pointed her in another, less costly but just as effective direction.

The NIH requires researchers to allow access to databases created with NIH grant monies. So the NIH put Bartoshuk in touch with researchers at several U.S. academic institutions that had databases with the same types of general health information she was collecting. The other groups mined their databases, some of which cost millions to create. The results showed the same correlation that Bartoshuk's team had seen in their database — a connection between childhood ear infections and adult obesity.

Bartoshuk, a professor in the UF College of Dentistry who studies taste and smell, had discovered that ear infections damage taste, which alters eating habits and can lead to obesity.

"In a time of budget constraints, it was delightful to create a collaborative effort between institutions that weren't vying for control or money, just interested in furthering knowledge," Bartoshuk says. — Karen Rhodenizer