'Guerilla scientist' kicks ALS research in the pants

Man's quest to cure his dying brother yields promising results

By Peter Woodford

James Heywood in the upcoming PBS Frontline documentary So Much So Fast

When James Heywood found out his kid brother Stephen had amyotrophic lateral sclerosis (ALS), his reaction was just what you'd expect: despair, anger, helplessness.

But after James dug a little deeper and found out that ALS — more commonly known as Lou Gehrig's disease — gets relatively little attention from the medical research community, he added outraged to the list. He quickly decided he could do better. "I knew nothing about ALS before Steve was diagnosed," he admits. Heck, he hadn't even seen the famous Lou Gehrig story, The Pride of the Yankees, starring Gary Cooper. But the MIT-educated engineer with only a smattering of medical knowledge was convinced that the research establishment wasn't going to do much for this orphan disease — a condition where outcomes have improved little since the days of baseball great "Iron Horse" Gehrig.

James quit his job as a mechanical engineer and set up the "guerilla research" ALS Therapy Development Foundation (www.als.net) to speed up the search for better treatments. Driven by his brother's decline, he wanted to try things that would give hope to living patients — like testing combinations of drugs that were approved for use in other illnesses and rapidly publishing study data on the internet . His basement initially served as the lab and headquarters. Today, the Foundation has a budget of $12 million US and a staff of 35 including some very eminent medical minds and has earned praise worldwide for its innovative murine studies. And now the story of James and Stephen Heywood and their family's quest for an ALS cure is the subject of a riveting documentary called So Much So Fast which will air on the PBS programme Frontline on 3 April at 9PM EST (it can also be viewed on Frontline's website after the broadcast).

AN AGE OF UNREASON
"A reasonable man adapts himself to suit his environment. An unreasonable man persists in attempting to adapt his environment to suit himself. Therefore, all progress depends on the unreasonable man." The famous George Bernard Shaw syllogism is a favourite of James's.

"I was definitely unreasonable," he admits now. "I think I was probably unfair in the beginning thinking that the research field didn't recognize the problem very well. However, without that unfair characterization I probably wouldn't have gone so far."

Stephen Heywood courageously battled ALS

A FALLEN WARRIOR
Tragically, Stephen Heywood passed away in November after his respirator failed. His widow Wendy, who works at the Applied Physiology lab at Harvard, says the Foundation proved to be an enormous support — both therapeutic and moral — while he was alive. "We really went to Jamie and listened to things that were going on at the Foundation, it involved testing things that were already on the market — the way drugs interacted with each other," she says. "For us it was an amazing relief to have this place that was testing all this stuff and we trusted them. They were amazing scientists and hardworking people. Thanks to them, any move we made I felt totally safe with."

"I think it was a wonderful thing. It was very empowering for all of us — a great idea," she recalls. "Nobody knew where it would go but we knew we were going in a positive direction. This is not a family that sits down." Stephen Heywood did, by necessity, sit down — but only in his heavily tricked-out wheelchair. So Much So Fast showcases some of the amazing devices he and his brother dreamed up to maximize his mobility and communication. "It's a sad thing to me that most of the devices for the handicapped today are very badly engineered and don't serve needs very well," says James. "Stephen had a quality of life that literally no-one at his level of incapacitation had — ever."

The Heywood family's passionate quest for an ALS cure could also be trying. "Sure, it was stressful at moments — we used to joke it was all ALS all the time," recalls Wendy. In fact, that stress partially led to the breakdown of James's marriage. Adding to the charged atmosphere was the fact that the Foundation tended to attract researchers whose families were also affected by ALS. "It's a double-edged sword having people with a heavy emotional attachment," says James. "I can be pretty harsh because I don't believe good intentions get you very far so I had to ultimately let go of a couple people who were really connected to the disease."

THE FUTURE
Stephen Heywood's death didn't dampen his brother James' passion for finding a cure for ALS. "What I'm most excited by now is the fact that — I think — we're in a paradigm shift of how research and discovery is going to be done," he says. "There are a few things that are coming together right now — profiling technology like gene chips and proteomics combined with advances in the ability to use the genome more efficiently mean that there's a moment now where a very small research team can do things that just weren't possible before."

The medical establishment has been sceptical of James's project. "What we're criticized for is not following the traditional academic process of grants and publication but what we're not criticized for is the quality or the quantity of work we've produced," he says. "I think the reason we're able to operate with the quality and the efficiency that in ALS is unrivalled is because we're not following rules that would prevent us."

In So Much So Fast there's a scene that nicely illustrates this butting of heads. At the annual meeting of the Society for Neuroscience, Jeff Rothstein, a leading ALS researcher, lambastes him for violating the tenets of peer review, saying "Okay, you want to be an anarchist, you can." Then the film cuts to the next day with Dr Rothstein going back to James to apologize for his kneejerk reaction. "I really like what you've done with the animals a lot. It's a really good job and I actually do think it's better than anything we do," he said.

James points out that he's proud of the fact the European Clinical Trials Group has just adopted the Foundation's standards for how mouse studies are run as a requirement for using the data in trials. "There was a time where we were the cowboys outside the rules a bit and all of a sudden we're the gold standard," he says. "You could blink and miss it."