Starting a Career in Science: Challenges and Successes
Developing a Corporate R&D Career
Making Chemistry More Accessible
Envisioning Ancient Spaces, Virtually
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Susan J. Hayflick '80 |
As a young clinical geneticist at Children's Hospital in Buffalo, N.Y., Susan J. Hayflick '80 met an Amish family from the western part of the state. Three of their four daughters suffered from a rare disorder with debilitating symptoms, including night blindness, uncontrolled muscle spasms, speech and cognitive problems, and seizures. At that time it was known to be one of several forms of a disorder known as neurodegeneration with brain iron accumulation (NBIA), which is characteristic of many human neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Yet the specific cause of this progressive disorder was unknown, and there was no effective treatment for these children.
Thus, a "gene hunter" was born.
After 10 years and the analysis of perhaps 10,000 gene-sequencing traces in Hayflick's laboratory at Oregon Health and Science University, Portland, and in those of her research collaborators, the gene was discovered.
"At four o'clock on March 13, 2001, I got an e-mail from my collaborator Jane Gitschier at the University of California in San Francisco," Hayflick recalls. "The subject line was ‘hold on to your hat.' We had found a brand-new gene with a compelling mutation. From the gene structure, we could identify the protein it produced. From the protein, we could predict what occurred in a biochemical pathway. Most amazing, we had some ideas for therapies. After a decade of looking, the whole world opened up. It was beautiful."
The gene, called PANK2, is located on the upper arm of chromosome 20. "We discovered that changes in this gene cause abnormalities in an enzyme called pantothenate kinase," explains Hayflick, who is now a professor and vice-chair of the Department of Molecular and Medical Genetics, Pediatrics and Neurology at OHSU. "This is a key regulatory enzyme in the biosynthesis of coenzyme A, which is critical to fatty acid synthesis and energy metabolism."
Because abnormalities in pantothenate kinase cause a significant portion of cases of NBIA, the team named this form of NBIA pantothenate kinase-associated neurodegeneration, or PKAN.
Therapeutic Value
Hayflick earned her medical degree from Pennsylvania State University and went on to a three-year internship and residency in pediatrics at Maine Medical Center, Portland. She had always wanted to become a rural family doctor but, during her second year of the residency program, she discovered she did not really enjoy routine outpatient primary care.
"I tried on different specialties and, with clinical genetics, it was a ‘eureka' moment," Hayflick says. During a fellowship in clinical genetics at Johns Hopkins University, she also became interested in biochemical genetics.
Nevertheless, with a physician's passion for healing, Hayflick came around slowly to the realities of her new specialty. "Clinical genetics is very rich from a diagnostic standpoint, but something of a wasteland from a therapeutic standpoint," she says. "As a clinical geneticist, I cure nothing. It took me a long time to appreciate the therapeutic value of what we do: we provide diagnoses for families who usually have been passed around from specialist to specialist, often over the course of decades, without a diagnosis. And we can often link these families with one another, so they have someone to talk to.
"This is a different type of intervention from prescribing a medication or cutting out a tumor," Hayflick says.
Nevertheless, in the case of PKAN, Hayflick's team initially identified pantothenic acid — vitamin B5 — as a potential therapy for patients with a mild form of the disease. Many patients who have tried it report benefits, although it is not a cure. Hayflick's laboratory has begun testing potential therapies, beginning by screening existing drugs for benefits in mouse and fruit-fly models of the disease.
"Gene therapy is pretty far off in the future, in my humble opinion," Hayflick observes. "Inserting a gene into any cell is challenging. Doing so in a way that is not harmful adds a second layer of challenge. And in the case of a childhood neurodegenerative disorder, you'd have to get the gene into every cell of the brain, which is well protected by the blood-brain barrier.
"Stem-cell therapy is much more likely to be fruitful in my professional lifetime," Hayflick predicts. "What genetics research and the identification of disease genes is useful for is to understand the molecular basis of a disorder."
While continuing her work on PKAN, Hayflick is also working to discover the gene that causes infantile neuroaxonal dystrophy, or INAD, another hereditary neurodegenerative disease.
A Partnership
Besides the intellectual challenge of genetics research, Hayflick says it is the families that help her remain focused during the long hunt for a disease-causing gene. "I have a picture on my bulletin board of an Amish horse and buggy," she says. "This reminds me of why I do what I do.
"Patients take comfort in knowing that someone is working hard to try and figure this thing out," Hayflick says. "They are our greatest allies in the research, both in their participation and fundraising. It's a partnership."
Dorothy Wright contributes news and feature articles on science, technology, engineering and general-interest topics to a variety of publications, including Civil Engineering and Engineering News Record.