U of M's cyanide research paying off

In the early 1990s, Prof. Herbert T. Nagasawa came up with an idea for a new, fast-acting antidote to cyanide poisoning.

But the University of Minnesota chemist couldn't find anyone willing to pay for the research. So he filed it away.

Now, at age 80, he's finally started to see his idea pay off.

In research featured in today's issue of the Journal of Medicinal Chemistry, Nagasawa and several colleagues found that his discovery, a new type of drug, works faster and may be more effective than existing cyanide antidotes.

It has only been tested in mice, but if they can prove it works in people just as well, it could go a long way toward meeting a Defense Department goal of a "three minute solution" for mass casualties in a cyanide attack.

The scientists said it might save countless lives in the event of a terrorist attack. It could also aid firefighters and industrial workers who may be exposed to cyanide on the job.

"Theoretically, you can take a pill [in advance] and it will protect you," Nagasawa said. Or, if a lot of people are exposed, it can be distributed quickly. Now, cyanide antidotes must be injected into a vein, and they can take up to 30 minutes to work, according to Steven Patterson, who is heading the research as associate director of the university's Center for Drug Design. That's a problem, because "If you have a lethal dose [of cyanide], it can kill you within minutes," he said.

The experimental drug, called sulfanagen, worked twice as fast as conventional antidotes when given to lab mice exposed to a nonlethal dose of cyanide, the study found. In some cases, it worked in as little as six minutes, Patterson said.

Nagasawa, a university researcher for 45 years, retired to California three years ago, but he still spends about half his time on the project. "I like to work, and I think it's very important," he said. "Whatever I can do to accelerate the process, I'd like to do it."

The new drug is made from a naturally occurring substance -- called 3-mercaptopyruvate -- that the body produces to rid itself of small amounts of cyanide, which can be found in some foods such as pitted fruits.

Nagasawa, who joined the university in 1959, tried to get government funding to develop the drug during the first Gulf War in 1991. "I'm watching TV and I'm seeing these soldiers putting on gas masks," he recalled.

But the government turned him down. "So we shelved it," he said.

"Then the second Gulf War comes along. I said, 'Hey, wait a minute.' Again, the same thing: soldiers donning gas masks. I said, 'You know, we have a good cyanide antidote, I think -- at least hypothetically.'"

This time, he sought an Army grant without success. But Robert Vince, a scientist who heads the university's center for drug design, took a gamble and gave him funds to get started.

Within two years, Nagasawa had several versions ready for testing. Last year, the National Institutes of Health poured $2.5 million into the research. "Now it's a big priority," he said.

The researchers hope to start testing the best version of the new drug in people in the next two to three years, Patterson said. After that, it might take another four to five years to get it on the market. "And that's if things go perfectly," he said.

But the scientists say it's worth the effort. "We hope that a terrorist never releases cyanide among the population," Patterson said. "But I think that's something that we need to be prepared for."

Maura Lerner • 612-673-7384