http://www.dispatch.com/news-story.php?story=dispatch/news/news02/nov02/1466342.html
 
Breakthroughs mean fewer cats needed in study
Ohio State project on spread of HIV drew many protests for killing animals
Friday, November 1, 2002
David Lore
THE COLUMBUS DISPATCH

Fewer cats than originally planned will be needed to research the impact addictive drugs have on the spread of the AIDS virus in humans, the new chief of the project at Ohio State University said yesterday.

The five-year, $1.68 million project has changed dramatically since the National Institute on Drug Abuse approved it two years ago, said OSU immunologist Larry Mathes, who succeeded Dr. Michael Podell, a veterinary neurologist, this month.

Podell left last summer to enter private veterinary practice near Chicago after being heavily criticized by animal-rights groups.

"I'm not Mike Podell, and I can't do what he did,'' Mathes said yesterday. "If we were only to pursue the original objectives of the grant, I wouldn't have done that.''

The redesign is in part because of dramatic -- and unexpected -- breakthroughs over the first two years of research, he said.

Podell's original plan was to infect up to 120 cats with FIV -- feline immunodeficiency virus, which is an animal model for HIV in humans -- and then addict the cats to methamphetamines to see how the drugs affected the progression of the disease in the brain.

So far, 42 cats have been killed to study brain changes, Mathes said.

But, at least for the next year, no cats will be used because the focus now is on analyzing tissue from those already euthanized and testing viral response to drugs in cell cultures. The cultures, which Ohio State purchases, were cloned from skin or tumor cells from live or dead cats. Using them is one way to reduce the number of live animals required.

Some cats may be used in the fourth or fifth year of the study to verify cell-culture results, Mathes said. But he said far fewer than 120 cats will be needed.

"As these projects evolve, this often happens,'' he said. "I've done animal studies for years, but you don't do them if you don't need to.''

The breakthrough, Mathes said, has been preliminary findings that methamphetamines -- and possibly other addictive drugs, illegal or otherwise -- speed up the spread of the virus in brain cells in cats. The drugs, he said, cause the virus to mutate in a way that allows the infection to move rapidly from cell to cell rather than only through blood or fluids.

"I can't tell you how exciting that is,'' he said. "The potential is enormous, in terms of learning how the virus may be carried to the brain.''

In an addict's brain, the mutant virus "becomes like a bomb -- it explodes and puts the virus out to the next cell and the next and the next,'' said Dr. Maria Hadjiconstantinou-Neff, a co-investigator and expert on the effects of drugs on the brain.

Mathes and Neff say their research already points at new treatments for AIDS.

Once the process is understood, Neff said, it may be possible to block the cell-to-cell transmission of the virus or at least reduce toxic effects enough to save brain cells. That wouldn't eliminate the virus, but it could improve quality of life, she said.

Using animals in research is declining, Mathes said, but often is still necessary because researchers can't control the many differences in the condition of human subjects and the drugs they have used.

Podell became the target of hundreds of e-mails, letters and telephone calls protesting his work, including what he described as death threats.

Protect Our Earth's Treasures, which plans a campus demonstration today, opposes animal research regardless of the numbers involved, said director Rob Russell. "If they really aren't going to use any more cats, they should just come out and say it. No more pussyfooting around.''

The Washington-based Physicians Committee for Responsible Medicine is suing the national institute in federal court to learn more about the OSU project.

Dr. Neal Barnard, president of the group, said he thinks a reasonable compromise would be for OSU to use cell cultures and brain tissue already acquired without killing more cats.

"Clearly they have an alternative on this one,'' Barnard said. "This is giving science a bad name.''

Ohio State has increased security for the scientists, in view of Podell's experience, but Mathes said he does not intend to work behind a barricade.

"Hunkering down is not the way I like to operate,'' he said. "I like to be open and talk about this work.''