September 29, 1995

Dianne Feinstein, California.  co-chair Connie Mack, Florida.  co-chair

Testimony of:

Brad Margus

President, A-T Children's Project, Boca Raton, FL

Audio exerpts .au (14 Mb) / .ra (1.8 Mb)

My name is Brad Margus. I am from Boca Raton, Florida, and I am here today only because a rare genetic disease interrupted my family's perfect life and changed it forever.

Just over two years ago, I thought my wife and I had a perfect family. I ran a thriving business, I had a beautiful, intelligent wire, and together we had three little sons who seemed perfectly healthy. Whenever I took my little boys to a park or to a store on weekends, people would stop men and make jokes about how we seemed to be staring our own basketball team. People seemed to envy our happy family, and my wife and I dreamt of our little boys growing to be strong, healthy men someday.

Then, about two years ago, two of my young sons were diagnosed with a rare, brutal disease called Ataxia-Telangiectasia, or "A-T" for short.

A-T is an inherited disease that has the same incidence in all races, sexes and countries. It's recessive, which means that both my wife and I had to carry a defective copy of the same gene in order to be able to have a child with this disease. My wife and I are not related, and we had no way of knowing that we were both carriers of this rare, defective gene. so what happened to us could easily have happened to anyone-even one of you. Believe me, I have wondered many times what might happen is a U.S. Senator were to have a child with this disease! If you can, please try now to imagine it yourselves...

Try to imagine at least a couple of your children having a disease that combines the most commonly know aspects of muscular dystrophy, cancer and cystic fibrosis,and you'll have an idea what A-T is like. Although normal at birth, around the age of two, your children would start losing the ability to control their arms and legs, as they first seemed a little bit wobbly and had slurred speech. But the loss of muscle control would be unrelenting. Your children with A-T would be wheelchair dependent by the age of eight or ten, and as brain cells continued to die, their speech and eye movement would even become difficult.

Besides this horrible neurological deterioration, your A-T kids would also be about one thousand times more likely than normal kids of developing terminal cancer, especially leukemia and lymphoma, and because their bodies would be extremely sensitive to radiation, many typical cancer therapies would kill them. As if these symptoms were not enough, your A-T kids would also have very weak immune systems, and frequent respiratory infections could eventually become life threatening. Your A-T children might even experience premature aging and diabetes.

Senators, even if they were spared the cancer, your children would eventually be killed by this terrible disease by their late teens or early twenties.

For my wife and me, this is not imagined. It's become real.

My son Jarrett is now six years old, and Quinn is four. It took almost two year and thousands of dollars to diagnose them properly, and that final diagnosis was a devastating blow to us. Even though he boys are still very young, we know that their health will deteriorate quickly. The clock is ticking. If they don't develop cancer, as about 35% of A-T kids do, then they will certainly be severely disabled in a few more years.

Everyone responds to a personal crisis differently, and our response was to learn al we could about this new enemy that had taken control of our family. So immediately upon learning of the diagnosis, I struggled to learn the basics of molecular genetics and neurobiology, and at the same time, contacted research teams around the world working on A-T. I had no scientific or medical credentials, but I wanted to learn enough to figure out what I could do. I began by having a PhD tutor me at nights on molecular biology and genetics. Next, I started meeting the people who were doing the research.

As I contact and visited the few A-T researchers, it became clear to me that this disorder was an extremely rare "orphan" disease, and research for a cure or treatment had been tremendously limited because of a lack of funding. It seemed as though there was also no way to know whether the people who were working on A-T were effective scientists, or how rigorous their efforts were. But I had to find out. Of course, at first, I assumed that I'd find everyone eagerly trying to help us.

You see, when a family like mine is diagnosed with a brutal disease, the usual tendency is to trust the doctors and to trust the system. We always assume that someone else is well-informed, someone else is pushing forward with research, someone else is trying new ideas, and someone else is doing everything they can to help people like us. But families who are diagnosed with a rare, obscure disease soon learn that people are not necessarily fighting for you. In fact, your family's problem may not be receiving any attention at all, or may only be worked on by a few people who don't have the resources to get a lot done.

But it seemed to us that regardless of how rare the disease was, our sons and all A-T kids deserved to have world-class researchers employing first-rate science to solve the A-T problem, with objective, brilliant scientists and physicians overseeing the process. Therefore, we formed a non-profit organization ourselves to raise funds to accelerate and elevate scientific research aimed at finding a cure. We name the foundation the A-T Children's Project, and we recruited respected experts to advise us. We set up a clinical center for A-T patients at John Hopkins and a cell- bank to ensure that all researchers would have free access to patient materials. While we frantically raised money, we also organized and sponsored four conferences where scientists from diverse fields helped us plan our strategy.

As it turned out, for a rare disease like A-T, there were not a lot of choices for research strategies aimed at finding a cure. Sure, for common diseases that affect million of people, a major drug company might become interested, and might be willing to spend millions or even billions of dollars to screen thousands of compounds in hopes of randomly coming across one that is safe, and somehow helps. But given the small number of A-T patients, and therefore a very limited market for any drug company, no one was going to come up with the hundreds of million of dollars we would need to screen for drugs using that conventional, random way.

Instead, our only hope was to use an efficient, economical approach that would rationally figure out exactly how the defective gene caused the disease and then come up with a way to correct that defect. Therefore, for A-T families like mine, hope lay in the field of genetics. The A-T Children's Project therefore directed our funds to several research labs, including one in Israel run by Dr. Yosef Shiloh. And just a few months ago, in June, Dr. Shiloh announced that his team, working with Dr. Francis Collins and many other collaborators, had identified the defective gene that causes A-T!

The gene discovery was tremendously exciting to us, because it represented the first major step toward understanding how the gene causes the many terrible symptoms of this disease, and perhaps figuring out ways that we can compensate for what the damaged gene is failing to do. For example, now that they have the defective gene at hand, researchers at the National Center for Human Genome Research in Bethesda are working hard to develop a mouse with the same genetic defect and disease that A-T kids have. Hopefully by January, this mouse will exist and with any luck, it will have the same symptoms that we see in A-T kids. Then, we can begin trying numerous drugs and interventions on these mice in hopes of finding a treatment that works.

The announcement of the A-T gene's discovery this past June, however, turned out to be much bigger news than what you would expect for a little, unknown disease like A-T. Surprisingly, it made the front pages of almost every newspaper in the country, and was covered by every major TV network news. And there is a reason for it. It turns out that there are at least two million "carriers" for this disease in the U.S. alone--individuals who have just one of the two defective genes needed to become afflicted with A-T. If carriers are this common in the population, this means that there are probably several people in this room today, who are unknowing carriers of the defection A-T gene just as I didn't know I was a carrier.

And here is the potentially scary part: these carriers are suspected of being four to five times more susceptible than non- carriers to various forms of cancer, and therefore constitute a numerically important proportion of the population with an elevated cancer risk. For example, a researcher funded by the National Cancer Institute has published that one in six women who have breast cancer is probably an A-T carrier. While this is still a controversial claim, several independent groups have conducted different research studies that have pointed at a higher cancer rate in carriers, and I know that Dr. Klausner and the NCI are now planning many more studies to get to the bottom of this.

Sitting here today I have very mixed feeling knowing that people who are carriers of the A-T gene are more prone to develop cancer. As a father who is desperately trying to save his sons and other A-T children by increasing the level of research on a very rare disease, I am thrilled that this moves our obscure disease into the spotlight. The press coverage means more public awareness. And mainstream cancer researchers are now contacting us regularly to ask about funding, to obtain patient samples, and to collaborate with other A-T researchers. Even the director of the National Cancer Institute himself invited me to Bethesda recently to discuss how we might approach A-T family embers in order to study the subject more thoroughly. In fact, fundraising may even become a little easier, as I can approach people who have never hear about Ataxia-Telangiectasia, knowing that almost everyone has known someone who was touched by cancer.

That's the good facet of knowing and pointing out that A-T carriers are more prone to cancer. On the other hand, it's also a little scary. For one think my wife and I would be worried about who would take care of our kids if either of us were taken by cancer. And, if as suspected, carriers are slightly more sensitive to radiation than non-carriers, we'd need to know what to do about it.

But what is perhaps even more scary for us, is what other people might do who learned that we are more likely to develop cancer. For example, companies who provide health and life insurance would probably look at us differently knowing that we are more likely to develop cancer and therefore cost them money than other people. After all, the insurance business is based on looking at averages and calculating risks, right? It's really not hard to understand how an insurance company would be tempted to raise the rates on or even weed out A-T carriers from those people whom it insures.

In fact, as a businessman myself, I can easily imagine how one insurance company might want to be the good guy, but would fear that its competitor would gain an edge by using this genetic information...

But I also know that if rules existed that everyone had to play with, then companies would still be able to compete profitably. So it's my hope that some of the experts who are here today will help you Senators make the rules that are needed to protect the individual's privacy, and equally important, to forbid discrimination based on one's unchangeable genetic make-up.

Thank you for inviting me to speak here today. I know that there are some very knowledgeable and eloquent experts lined up to speak now. but as a non-physician, Washington outsider who has only recently learned about our medical system because of a very personal reason, I'd like to make one final point:

Please do what you can to make our laws catch up with the rapid scientific advances we are seeing. Even if people are fearful of how all the new genetic information will be used,please do not allow this fear to slow down the pace of biomedical research. We need caution, and we need controls in place that will protect people. But we also cannot afford to slow down research. FOR TODAY, BIOMEDICAL RESEARCH USING MOLECULAR GENETICS IS THE ONLY HOPE WE HAVE OF CURING MANY RARE DISEASES -- AND OF SAVING MY SONS.

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