Daniel Doberer measured proteins yesterday during research at Beth Israel Deaconess Medical Center. The hospital believes it has found protective properties in carbon monoxide. (Pat Greenhouse/Globe Staff

Carolyn Y. Johnson 

Boston Globe Staff

October 16, 2009

For more than a century, carbon monoxide has been known as a deadly toxin. In an 1839 story, Edgar Allan Poe wrote of “miraculous lustre of the eye’’ and “nervous agitation’’ in what some believe are descriptions of carbon monoxide poisoning, and today, cigarette cartons warn of its health dangers.

But a growing body of research, much of it by local scientists, is revealing a paradox: the gas often called a silent killer could also be a medical treatment.

It seems like a radical contradiction, but animal studies show that in small, extremely controlled doses the gas has benefits in everything from infections to organ transplantation. Research is now beginning in people, who are given the gas at very low concentrations, and while many doctors remain skeptical, the National Institutes of Health recently gave the idea a vote of confidence: The federal agency awarded a $1.4 million grant to a researcher at Beth Israel Deaconess Medical Center to study the underlying biology of how the gas works.

“Carbon monoxide essentially suffocates the red blood cells - that’s the way we learned it in school,’’ said Dr. Patty J. Lee, an associate professor of internal medicine at Yale School of Medicine, who has done work with the gas. Scientific opinion of the idea has “gone from completely skeptical to moderately skeptical. . . . Therapeutically, I think it has incredibly great potential.’’

Much of the driving force behind scientific interest in carbon monoxide has come from Leo Otterbein, an associate professor at Beth Israel Deaconess who first began considering the possibility that the gas was beneficial a decade ago, as a graduate student.

Otterbein was studying an enzyme that plays a critical protective role in the body, but worked in unknown ways. That helpful enzyme breaks down a substance in the body and creates carbon monoxide as a byproduct, so Otterbein began working on experiments to see whether the gas was providing a benefit.

Positive experimental results began to trickle in, but Otterbein faced skeptics.

“I went to a conference and said, ‘Wait ‘til they see this data, they’ll be amazed.’ Guys stood up and made an absolute fool of me,’’ said Otterbein, who said he persevered anyway, relying on the accumulating data and ignoring the gut reactions of colleagues. “It’s been a hard sell, but in 10 years it’s evolved dramatically.’’

Since that time, Otterbein and other scientists have found that breathing the gas for an hour at about 5 to 10 percent of a fatal exposure has beneficial effects in animals with a range of illnesses, from malaria to cardiovascular disease. While its actions are only partly understood, the gas seems to play a role in controlling inflammation, regulating cell death, and promoting repair and renewal.

The most research has been done with organ transplantation. In one study, carbon monoxide showed promise in reducing organ rejection in rats given heart transplants from mice. In unpublished research on kidney transplants in pigs, the gas was found to improve the function of transplanted kidneys immediately after surgery.

Such findings paved the way for low doses to be administered to 31 kidney transplant patients. Results have not been disclosed and the trial was put on hold for a review, but there were no negative effects, said Otterbein, a consultant to the gas company, Ikaria Holdings Inc.

Dr. Jerzy W. Kupiec-Weglinski, director of the Dumont-University of California, Los Angeles Transplantation Research Center, said that the research might explain anecdotal reports from the 1980s that kidney transplants seemed to work better in smokers than expected, since cigarette smoke contains carbon monoxide.

But given the deeply entrenched fear of carbon monoxide as a toxin, he said it is unlikely that the gas would be directly given as a therapy to many people. Instead, research into the mechanism by which carbon monoxide works could allow scientists to design a drug that could act in the same way.

That is the thinking behind Alfama, a company with its US headquarters in Cambridge that is working on a drug to release carbon monoxide into the body. Otterbein also is a consultant for Alfama.

Dr. Claude A. Piantadosi at Duke University Medical Center has administered the gas to a small group of healthy people and found that it increases the activity of genes involved in making mitochondria, the cell’s power plants. But Piantadosi said sick people may respond differently.

He and other scientists cautioned that their work is at an extremely early stage, and that it should not encourage people to think of carbon monoxide casually.

“Carbon monoxide is a deadly poison. . . . It scares physicians like myself, and I’ve treated a lot of carbon monoxide poisonings,’’ Piantadosi said. “But it’s also made normally by the body. . . . So the issue is how does that all work.’’

In Boston, Otterbein hopes the grant will help him answer that question. His research will look at whether the gas binds to DNA to regulate which genes are active in the body.

When he proposed the idea, he said it seemed so far out, he was sure it would be laughed at instead of funded.

But Michael Bender, a program director at the National Institute of General Medical Sciences, said it was an innovative and risky hypothesis that, if true, could transform current thinking. He pointed out that it follows in the footsteps of Nobel Prize-winning work showing that nitric oxide played an important signaling role within the body.

Understanding this gas has led to drugs that are not inhaled, including Viagra, that work on the same biological pathway.

“It’s probably a risky kind of science to do,’’ Bender said. “It is a novel idea. . . . But what’s been amazing to me is, even though many basic biological processes are very well worked out, there are still surprises to be found.’’