When disease hit close to home, these clinicians tackled the problem head on.
When Alan Braverman, MD, FACC, was given his first stethoscope in medical school he took it home and immediately began listening to his family members’ heartbeats. What he found would alter his life forever.
“There are six kids in our family,” explains Braverman, now a medical professor in the cardiovascular division at the Washington University School of Medicine in St. Louis. “I discovered a heart murmur in my older brother, David. When an echocardiogram showed an enlarged aorta and mitral valve prolapse, we recognized that David had Marfan syndrome.”
Braverman also realized that his late father, who died in 1977 from an acute aortic dissection, had also been afflicted with Marfan syndrome, unaware that he had the condition. Perhaps more importantly, those events put Braverman on a career path to not only learn as much as he could about the genetic disorder, but to positively impact the way Marfan is diagnosed and treated.
And Braverman is not the only physician to combat a disease that has touched them personally. Mark Lewis, MD, a hematology/oncology fellow at the Mayo Clinic in Rochester, Minnesota; Douglas Dieterich, MD, a professor of medicine in the Liver Diseases Division at Mount Sinai Medical Center in New York City; and Stanley Nelson, MD, a professor in the Department of Human Genetics at the UCLA Jonsson Comprehensive Cancer Center, are all waging a personal vendetta against diseases that have hit too close to home.
Putting Marfan on the map
Marfan syndrome is a genetic disorder affecting one in 5,000 people, meaning that it is rare enough that physicians often misdiagnose it. That’s problematic because Marfan can also be fatal if unrecognized and untreated. The symptoms include disproportionately long arms and legs, elongated fingers or loose fingers, and a tall and lanky frame. Braverman’s brother David was 6-foot-4, considerably taller than the rest of the family. David underwent life-saving aortic surgery in 1985, and has done very well since. But David’s son (Braverman’s nephew) also has Marfan syndrome, and is monitored regularly.
When Braverman came to St. Louis as a general cardiologist he learned of a local chapter for the National Marfan Foundation (NMF). He attended a meeting, immediately became involved with the local chapter, and later on became active on a national level. Today, he’s not only director of the Marfan Syndrome Clinic at Washington University Medical Center, he is also chair of NMF’s Professional Advisory Board. “So much of what has happened regarding Marfan syndrome is because of interested researchers and the incredible passion of the National Marfan Foundation,” Braverman says. “What the foundation tries to do is educate physicians, medical students, residents, physical educators, parents, teachers, and patients. It’s a wide net to try to cast to continue to have awareness in education. It’s an ongoing challenge, but there’s no question that in the last 20 years people have become more aware.”
To help address that challenge, Braverman and his colleagues created a scoring system to help physicians diagnose Marfan syndrome. The system, which is based primarily on a multi-system clinical examination, also provides patients with a more accurate diagnosis and better medical management.
“There are many conditions with features which overlap with Marfan syndrome,” Braverman explains. “The new diagnostic criteria assist clinicians with the approach to the diagnosis and evaluation of these conditions.”
Braverman also praises the work being done by researchers on the gene that affects Marfan syndrome and other related disorders. He himself is currently involved with a major study funded by the National Heart, Lung, and Blood Institute on a potential treatment for aortic enlargement in Marfan syndrome that is opening doors to potential treatments for the life-threatening problems associated with the condition.
“The work being done has led to translational research on medications which prevent Marfan syndrome in the animal model,” Braverman says. “And that has led very quickly to human studies. There are simple compounds that are blood pressure medicines that might change the natural history of Marfan syndrome. So, we are part of ongoing trials that are looking at these medications, and hoping they will make a difference.”
When attorneys have a personal relationship with individuals in a legal matter, they are required to recuse themselves from the proceedings. Braverman, however, says that having a family connection with Marfan syndrome has been one of the most positive things about his career. Often, patients are initially unaware of that connection.
“I’ll tell patients that my brother has Marfan syndrome, and all of a sudden there’s a total change in the way the person I’m speaking with interacts with me and thinks about me,” Braverman explains. “Because they now know I’m not just a doctor. I have a very personal interest in this, and in their well-being. And when they hear that my brother’s first surgery was 25 years ago and he’s still doing fine, that gives them a new appreciation for what they can expect; that they can live a long and fruitful life with this condition. That’s been a source of tremendous gratification.”
Hepatitis C victory made sweeter
Immediately after Mount Sinai Medical Center’s Douglas Dieterich, MD, accidentally stuck himself with a needle that had been used on a patient who was a drug user, the 4th year medical student knew he was in trouble. But with an upcoming funeral for his grandmother, he pushed the incident to the back of his mind. Six weeks later Dieterich became very ill and was completely exhausted. He was tested, then told that he had non-A, non-B hepatitis, and that there was nothing the doctor could do for him.
“I guess it was frustrating, but I was so sick at the time when I first got it that it never even occurred to me that there might be something to do,” Dieterich says. It was only later when his condition became chronic and he had to take time off from his residency that the frustration came to the surface. Dieterich clearly recalls the turning point.
“I remember walking with my dog, because I was home from residency, and thinking, damn it, well, if I can’t do anything for myself, the least I can do is maybe work on doing something for somebody else,” Dieterich explains.
He switched his specialty from ophthalmology to GI, and began learning about immunology and virology. Woefully, he says, there was little research being done in hepatitis. Compounding the problem was that his liver was getting worse. He was treated with interferon in 1991, and again in 1997 before he was finally cured.
“I took the medicine every day for 18 months,” Dieterich recalls. “That was before they had the once-a-week stuff, so it was pretty brutal. But I continued to work; that was my answer. I wanted to be doing something constructive.”
Dieterich admits that he takes the battle with hepatitis C “too personally” sometimes, but is not concerned about its impact on his approach to treating patients—many of whom are as determined as he was to get cured, no matter what it takes.
“We have pretty concrete stopping rules, so we follow those,” Dieterich explains. “So as much as we hate to give up, sometimes we have to because we’re kind of torturing the patients unnecessarily, and I know how much they suffer when they take this medicine. So, if it’s not working, it’s not working, and we stop.”
He and his colleagues are heartened, however, by the fact that there are many new medications in the pipeline. “If what we’re doing right now doesn’t work, there are 30 or 40 other medications that are under clinical investigation now for hepatitis C. So it’s sort of okay; it’s not like it’s the last resort.”
Going forward, Dieterich says it’s important for work to continue on two fronts: education and awareness, and research and clinical trials. In particular, he says, education is critical.
“In the US, 75 percent of the patients who have hepatitis C don’t know they have it,” Dieterich says. “And even if we were to identify those people through screening, we still have to get the boots on the ground and treat them. And that’s a daunting task.” Nevertheless, his message to patients is one of hope, not despair. “I tell patients that it’s a really good time to have hepatitis C, compared to when I had it. And it’s a good time to be treating hepatitis C too, because there are so many wonderful things we can do.”
Battling Duchenne muscular dystrophy
It was clear something was wrong. UCLA’s Stanley Nelson, MD, and Carrie Miceli, PhD, noticed that their 2-year-old son Dylan was having both language difficulties and motor movement problems. What followed was a diagnosis of Duchenne muscular dystrophy, a rare and fatal neurodegenerative disease that affects approximately 1 in 3,500 boys. The ensuing nine years have changed their lives.
“Once we recovered from the shock of the diagnosis, which was pretty substantial, it was a major change in our expectations for Dylan’s life and future that fundamentally changed our career paths,” Nelson says. “We were going to be invested in learning as much as we could about Duchenne and what ways we might be able to alter the disease course, and how to optimize his care.”
Miceli, who is a professor in the department of microbiology immunology and molecular genetics, says that Dylan’s diagnosis completely changed the focus of her research lab. “I never worked on muscle, I never worked on Duchenne, and now the bulk of my lab works on those two things.” In addition, Miceli believes that as both parents and scientists, she and Nelson are able to offer a unique perspective.
“Things that may not occur to other people just in terms of study design or even just the logistics of certain things, you have a very different perspective because you know [the disease] in a different way,” Miceli explains. “And I find that our colleagues are very thankful for that, and it’s inspiring to everybody.”
Dylan, now age 11, is “engaged in life” says Nelson, noting that there have been a lot of positive changes since the youngest of their two sons was first diagnosed. “The disease is not a fatalistic diagnosis,” Nelson says. “More so, it’s a diagnosis that requires a very well organized team—collaborating neurologists, cardiologists, pulmonary specialists, along with steroid treatments. And I think that was just starting to get organized when Dylan was diagnosed. I think that’s become fairly routine and accepted, and the clinicians themselves are doing it much better than they were nine years ago.”
Nelson and Miceli have been active writing grants and gaining funding for new research projects. One of their major efforts led to the opening of a Duchenne muscular dystrophy clinic at UCLA in 2010. The clinic, which serves approximately 350 boys, has grown substantially in two short years, and is now one of the largest clinics in California. Perhaps the most significant accomplishment of late is that the clinic has been given status as a California Children’s Services Special Care Center for pediatric neuromuscular diseases.
“The work’s not done yet by any stretch of the imagination,” Nelson cautions, “but the accomplishments so far are really quite impressive.”
Miceli adds that the biggest change in the field of DMD since Dylan was first diagnosed is that the multidisciplinary approach has become the standard mode of care. “It’s a mind change. And you can gather data from the literature that says multidisciplinary care extends life 10 years. That’s pretty powerful in terms of progress.”
A ticking time bomb
Many public figures, from Albert Einstein to Michael Jordan, have commented on the ability to turn a negative situation into a positive one. For Mayo Clinic hematology/oncology fellow Mark Lewis, MD, living those words has been the story of his young life.
Lewis’s father, a lifelong non-smoker, died of lung cancer at an early age. Watching his father undergo treatment drew Lewis to oncology, but initially not in a positive way.
“When I was young all I could see was the negative, and I was quite angry at whatever force was responsible,” Lewis recalls. “But out of that came what I would call a personal vendetta against cancer.”
Lewis pursued that vendetta, but when he began his fellowship at the Mayo Clinic, he was diagnosed with multiple endocrine neoplasia type 1 (MEN 1), a rare and familial tumor syndrome that forecasts a predisposition to tumors in the endocrine organs, specifically the pituitary gland, the parathyroid glands, and the pancreas. The discovery that he had a high calcium level, similar to what his father experienced, sealed the relationship link. But out of that negative, too, came a positive.
“It seemed like a dark time, but I think it really deepened my relationships with my patients, and I hope it makes me a more effective communicator with them,” Lewis says. “I think it gives me a lot of meaning and drive, but it can be a Pandora’s Box when you look at it more thoroughly.”
Lewis, who says the tumors that currently reside in his pancreas are stable for the moment, further explored Pandora’s Box recently when he had his two children tested. The inheritance pattern, he says, is a flip of a coin, 50-50, and those odds played out exactly where his children are concerned. His 4-year-old daughter does not have the syndrome, which is brought about by a defect in a protein called menin, but his 1-year-old son does.
“I think what has troubled me more than anything is the knowledge that I’ve given him an inherited disease,” Lewis says. “But sometimes not knowing is worse. I may not be able to do anything right now with that information, but I think forewarned is forearmed.”
Lewis admits that he is the “farthest thing from a basic scientist,” but is excited about the prospects of strides that can be made to better understand MEN 1—specifically through establishing a national or international database.
“Rather than facilities just looking at the patients they’ve seen within their walls, it would be nice to share that experience across the globe,” Lewis says. “And that way it might be easier to see certain trends.”
For now, Lewis is focused on patient advocacy. “I always hope to be involved with patients.” And because MEN 1 has implications for families, he believes it’s particularly important that people understand genetic illnesses; that they’re not a death sentence for their children. The more they know, the less scary it seems. “If nothing else, what I’ve tried to do by sharing my own story is I want awareness of this condition to be raised. That’s my own personal mission.”