An Idea Born In 1941 Hawaii
By Alice Keesing
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Honolulu, 1941. The sirens screech over Honolulu, sending 14-year-old Herbert Nagasawa and his Washington Intermediate classmates scrambling for the bomb shelters, donning their gas masks.
The war in Europe is a remote reality, but Nagasawa and his fellow students are drilled in the possibilities of invasion, including a deadly chemical attack. Gas masks on, they wait, crowded into the shelters, until the all-clear sirens sound and they can get back to their normal teenage lives.
Nearly half a century later, it was those haunting wartime memories that prompted Nagasawa to start his work on an antidote for cyanide - work that now promises to protect large numbers of Americans in the event of a terrorist attack or industrial accident.
Last month, University of Minnesota and VAMedical Center researchers announced that the antidote Nagasawa discovered far outstrips existing antidotes in ease of use and performance.
“It works faster and it can be administered quicker than the existing antidote,” says principal investigator Steven Patterson. “The advantage in that is that emergency responders are able to save more lives.”
It all started with an idea that Nagasawa had back in the early 1990s - an idea that nearly ended up in the trash.
We should point out here that Nagasawa is not only an Island boy - “McKinley High, ‘45,” he says by way of introduction - but the uncle of MidWeek publisher Ron Nagasawa.
Drafted into the Army after high school, Nagasawa trained as a Japanese language interpreter, but the war ended before he could be deployed. Taking advantage of the education available to him under the GI Bill, Nagasawa eventually wound up as a graduate student at the University of Minnesota, after which he joined the nearby VA Medical Center as a medicinal chemist. Over the years, he has worked on drugs to treat Parkinson’s and alcoholic liver disease. He still has an iron in the fire with an antioxidant supplement that promises to protect against all kinds of environmental toxins - but that’s another story.
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It was in 1991 that Nagasawa first turned his attention to cyanide.
“In the first Gulf War I’m seeing these soldiers donning gas masks, and of course I remember this as a kid,” he says. “That shook me up.”
It also got him thinking - with his years of experience, he quickly saw a new and faster way of treating cyanide poisoning. He sought funding, but the government wasn’t interested, so Nagasawa filed the proposal away. Cleaning out an overcrowded desk drawer one year later he came across the proposal and nearly threw it out - but at the last minute he placed it on an inaccessible top shelf, where it sat for 10 years.
Then the second Gulf War began and Nagasawa was again shaken by the images of soldiers in gas masks and talk of chemical warfare. He dusted off his proposal and tried for an Army grant. No luck. Luckily, at this point, the head of the University of Minnesota Center for Drug Design recognized the promise in Nagasawa’s work and gave him enough money to get the project rolling.
“The first two years were difficult,” Nagasawa remembers. “The chemistry was difficult, but at the end of the second year we finally hit it - and we hit it right square on the head. We checked it out and it was very, very good.”
The drug, which is called sulfanegen, is made from 3-mercaptopyruvate, or 3-mp, a substance the body naturally creates to rid itself of small amounts of cyanide.
Existing antidotes have to be injected into a vein and can take as long as 30 minutes to work. Those are 30 long minutes during which cyanide can kill or cause irreversible neurological damage.
But tests of sulfanegen in mice and pigs show it works in as little as three minutes. It is also effective over a wider time window and can even be given in advance. Researchers also are working on skin patches or dissolving tablets that can be given to a patient who is already comatose from the poison.
Both Nagasawa and Patterson speak passionately about the very real need for the antidote. While you might think that cyanide is something found only in old detective novels, they are quick to point out that it’s all around us. Cyanide naturally occurs in stone fruit such as apricots. (Don’t worry: Your body produces that 3-mp to detoxify it.)
Cyanide also is routinely used in a large number of industrial processes from metallurgy to plastic production to photography.
“There are hundreds of tons of cyanide floating around in industrial areas,” Nagasawa says. “This is what scares us. We talk about securing atomic energy places but we don’t secure the (places where cyanide is readily available).”
The new antidote offers a new line of defense to people who work in these industries, as well as to firefighters who can become poisoned by inhaling the burning materials.
A more sinister threat comes from the fear of terrorist attack. Released into an enclosed area such as a shopping mall, cyanide gas could be particularly deadly.
“While we hope it never happens, there is a very real threat,” Patterson says. “There are reports, some with varying degrees of reliability, that terrorists have tried to use cyanide alongside other agents in terrorist attacks ... terrorists are well aware of cyanide, and it’s relatively easy to use.”
Last year, the National Institutes for Health poured $2.5 million into the project, and it’s encouraging the researchers to get the drug into human trials and onto the market as soon as possible.
Nagasawa retired and moved to California in 2004, but his retirement is relative. Now 80 years old, he still consults on the project and stays in touch daily with Patterson, who took over the lead role.
“It’s so important to solve this problem,” he says. “My philosophy is that if you have anything to provide to push this problem forward intellectually, then you are morally obligated to get it done.”
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