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...

Share story

MOUNTAIN VIEW, Calif. — 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, known as A-T, and it afflicts about 500 youngsters in the United States.

Ever since doctors told Margus in 1993 that his toddlers Jarrett and Quinn would soon have to use wheelchairs and would probably be dead before they were old enough to vote, the Harvard Business School graduate has been on a mission to save them from their genetic fate.

He has become a self-taught genetics expert, a lobbying fixture on Capitol Hill and head of his own startup biotech company, making him a learned colleague alongside the field’s leading scientists.

He helped raise $17 million for the nonprofit patient-advocacy group he created, the A-T Children’s Project.

“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.

His quest led him to sell his South Florida shrimp-processing plant and launch Perlegen Sciences in 2000. Margus is chief executive of the Mountain View, Calif., biotechnology company, which is on the vanguard of the “personalized medicine” movement.

Creating treatments

Personalized-medicine adherents are trying to create treatments tailored to individual genetic makeups.

Humans’ DNA comprises 3 billion chemical bits called nucleotides. Each of the 25,000 or so human genes comprise about 1,000 nucleotides.

Some 99.9 percent of the nucleotides are identically arranged in all of us. It’s the 0.1 percent 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 about for decades, but the field remained a scientific backwater until President Clinton announced in 2000 that every gene in the human body had been mapped.

High interest

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 soon. The dramatic breakthroughs didn’t come as quickly as hoped and most of the startups are either gone or have changed their focus.

That’s because making tailored-made drugs isn’t as simple as it initially seemed.

Take the stricken Margus boys, now ages 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 age 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,” he 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.”

Yet five years of incremental advances have brought personalized medicine back to respectability.

Company scientists have recently published 1.6 million genetic differences sussed from the DNA of 71 Americans of European, African or Chinese ancestry. Now the trick is to determine what those variations mean.

Persistence pays off

Perlegen’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 earlier this year when it issued formal guidelines to encourage pharmaceutical companies to collect and share detailed genetic information amassed from clinical trials.

Perlegen is working with Pfizer to develop depression drugs and Astra Zeneca on heart disease. It has a grant from the Michael J. Fox Foundation to investigate Parkinson’s disease and a National Institutes of Health grant to develop its genetic-mutations map.

The company isn’t specifically investigating A-T, which is OK 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,” Margus said. “And that’s a big thing.”