Biotech Firm Founder on Quest for Life
Brad Margus was making a killing in the shrimp business and living happily in South Florida with his wife and three young boys. Then his two youngest were diagnosed with a fatal genetic brain disorder that’s as rare as it is unpronounceable.
It’s called ataxia-telangiectasia, better known as “A-T,” and it afflicts about 500 youngsters in the United States.
Since doctors told Margus in 1993 that his toddlers, Jarrett and Quinn, would soon be using wheelchairs and probably would die before they were old enough to vote, the Harvard Business School graduate has been on a mission to save the boys.
In the process, he has become a self-taught genetics expert, a lobbying fixture on Capitol Hill and head of his own start-up biotech company, making him a learned colleague alongside the field’s leading scientists.
Margus has helped raise $17 million for the nonprofit patient advocacy group he created called the A-T Children’s Project, and he sits down for an occasional television interview with the likes of Barbara Walters.
“It really is like a ‘Forrest Gump’ story in that this shrimp guy with no science background started to get to know a lot of people who today are luminaries,” Margus said.
Perhaps most important, his quest led him to sell his South Florida shrimp-processing plant and launch Perlegen Sciences Inc. in 2000. Margus is chief executive of the Mountain View biotechnology company, which is in the vanguard of the “personalized medicine” movement.
Personalized medicine adherents are attempting to create treatments tailored to individual genetic makeups.
Humans’ DNA is composed of 3 billion chemical bits called nucleotides. Each of the 25,000 or so human genes are typically made up of about 1,000 nucleotides.
Some 99.9% of the nucleotides are identically arranged in all of us. It’s the 0.1% difference that makes each of us unique -- and causes disease in some.
One vital gene in Margus, for example, is missing one nucleotide found in nearly every other human on the planet. His wife has a similar defect. Two of their children ended up with each parent’s mutant gene -- and A-T. (A fourth son, born after the A-T diagnosis, dodged the genetic bullet and is healthy).
Personalized medicine’s goal is to find and exploit these genetic quirks to better develop drugs beyond the pharmaceutical industry’s one-size-fits-all system.
This approach has been kicked around for decades, but the field remained a scientific backwater until President Clinton announced in 2000 that every gene in the human body had finally been mapped.
Almost overnight, dozens of companies backed by enthusiastic venture capitalists popped up, all promising to soon use the human gene map to make personalized medicine the norm.
But the bottom fell out of the field almost as soon as Clinton finished his Rose Garden speech proclaiming a new era in genetics. The dramatic breakthroughs didn’t come as quickly as hoped -- or hyped -- and most of the start-ups are either gone or have changed their focus.
That’s because making tailor-made drugs isn’t as simple as it initially seemed.
Take the stricken Margus boys, now 16 and 14. Researchers funded by Margus’ nonprofit found the gene that causes A-T in 1995, yet they are no closer to a cure today. The average A-T patient dies by 17.
“Even though I’m CEO of Perlegen, I’m not going to try to convince anybody that when you have a disease gene you are close to a cure or a treatment,” Margus said.
Like amyotrophic lateral sclerosis, known as Lou Gehrig’s disease, A-T is robbing the Margus boys of their motor skills while their intellect remains intact. They’ve been in wheelchairs for years. Breathing and talking are becoming increasingly difficult.
“It’s hard as a parent to know that they have a lot of potential. Jarrett can beat most adults in chess, but he’s trapped in his body that continues to shut down,” Margus said. “The reality is that Jarrett and Quinn are deteriorating.”
Five years of incremental advances have brought personalized medicine back to respectability. Scientists at Perlegen recently published 1.6 million genetic differences gleaned from the DNA of 71 Americans of European, African or Chinese ancestry. Now the trick is to determine what those variations mean.
The company’s persistence through the false starts and bad times has made it the sector’s leader. Its investors have quietly poured $206 million into the company over the last five years, and they are expected to reap handsome profits if Perlegen goes public by next spring, as Margus hopes.
The Food and Drug Administration officially endorsed the technology this year when it issued formal guidelines to encourage pharmaceutical companies to collect and give it detailed genetic information amassed from clinical trials.
Perlegen is collecting a steady stream of fees and royalties from nearly all the giant pharmaceutical companies to help them identify which patients do and don’t respond to their drugs. That’s important because drug makers write off millions in research costs each year when they drop development of drugs after a small but significant group of patients have bad reactions.
Perlegen is working with Pfizer on depression drugs and AstraZeneca on heart disease treatment. It has received a $2.8-million grant from the Michael J. Fox Foundation to investigate Parkinson’s disease and a $6-million grant from the National Institutes of Health to develop its genetic mutations map.
The company isn’t specifically investigating A-T, which is all right with Margus.
“Even if Perlegen can’t do anything directly on A-T, just being in the middle of the worlds of biotech and pharma help me see if there’s anything else that can be applied to A-T,” he said. “And that’s a big thing.”
