T H E   N I H    C A T A L Y S T      M A R C H  –  A P R I L   2006

Marriage of the Minds


by Karen Ross

Branch Mates: Alexander Wilson and Joan Bailey-Wilson, co-chiefs of the Inherited Disease Research Branch, NHGRI, at Baltimore's Bayview campus. She heads the Statistical Genetics Section, and he heads the Genometrics Section.

Alexander Wilson and his wife Joan Bailey-Wilson have two families: their two children at home and the 20-odd students, postdocs, and research staff who make up the Inherited Disease Research Branch (IDRB) at NHGRI.

The pair, who were recently named co-chiefs of the IDRB, use statistical methods to tease out which genes contribute to complex disorders such as cancer and depression.

So far, one of the most challenging aspects of their new position has been coping with the attention that their status as married co-chiefs has brought. In addition to this article, the Baltimore Sun featured Wilson and Bailey-Wilson in its Health and Science section, just before Valentine's Day, where the couple's story shared space with a large photograph of a chocolate bar.

For the junior scientists in the group, it was an irresistible opportunity to poke fun at their leaders.

Professionally, Wilson and Bailey-Wilson have different, but complementary, interests. Both of them examine family and population data to find patterns in the transmission of thousands of markers, small regions of DNA sequence that are scattered throughout the genome.

"The markers are our little signposts along the sequence,"  says Bailey-Wilson. When a marker shows up more often in individuals with a particular disease, a gene that lies near that marker is likely to contribute to that disease.

Some diseases—cystic fibrosis, for example—are caused by defects in a single gene, and the causation between the gene and the disease is very clear.

The diseases that Wilson and Bailey-Wilson study, however, are probably caused by a confluence of many genes, and the effect of any one gene may be quite modest.

Therefore, they rely on sophisticated statistical methods and heavy computer power. To get the large sample sizes they need, they collaborate with investigators from institutions around the world.

'Qualitative' Lung Cancer,
'Quantitative' Depression

Their work diverges when it comes to the diseases they study. Wilson jokes, "Joan and I divided the world a long time ago into qualitative disease and quantitative traits. 

Bailey-Wilson focuses on diseases such as cancer for which the diagnosis is qualitative—the patient is either affected or unaffected. Wilson studies diseases such as depression that have quantitative measures of severity and response to treatment.

One of Bailey-Wilson's main interests is lung cancer, a disease that appears to have a fascinating tangle of genetic and environmental causes. "We know smoking is the most important risk factor,  she says.

However, some families have disproportionately high rates of lung cancer even after smoking is taken into account, strongly suggesting a genetic contribution. "It may be a genetic risk where you need the smoking to see the risk due to the gene,"  she says.

She and her collaborators have recently identified a region of the genome that is linked to a high incidence of lung cancer. The region contains hundreds of genes, so they are now doing a finer- scale analysis to figure out which gene is the culprit.

Bailey-Wilson hopes that giving affected families the knowledge that they are high risk "will be the motivation needed to keep young people from starting to smoke and that extra motivation needed to help people quit." 

In addition to her lung cancer work, Bailey-Wilson is also investigating the genetic basis of several other types of cancer and other disorders, including nearsightedness.

Before You Know It . . . .

In collaboration with Francis McMahon and other investigators at NIMH and at the University of Texas Southwest Medical Center at Dallas, one of Wilson's projects has recently led to the discovery of a marker in the 5HTR2A serotonin receptor on chromosome 13 that affects how well depressed patients respond to a particular antidepressant medication.

"Fifteen years ago I wrote a paper reporting a linkage between depression spectrum disease and the esterase D [ESD] marker on chromosome 13 and noted that the 5HTR2A receptor was quite close to the ESD marker. Fifteen years later, we find an association with a marker in the 5HTR2A gene and replicate it—twice," says Wilson.

He is also pursuing projects with two sets of collaborators at the Johns Hopkins University School of Medicine in Baltimore—one on the effects of low-dose aspirin therapy on circulatory system disease and the other on scoliosis.

Neither Wilson nor Bailey-Wilson can really say what effect the overlap in their personal and professional lives has had on their careers or their family. It's hard to say, says Wilson, because they have no basis for comparison. "This is what we do; it's not what we chose to do; it's just what we do," he says. Besides, if they ever did things differently, they "would have to do it 100 times  to get good statistics, he continues.

Bailey-Wilson notes that it is nice to have a colleague at home to talk to but that the kids can get bored when the dinner conversation turns to technical genetics issues.

At work, she says, they are neither competitors nor collaborators, but their accomplishments are "mutually beneficial." As Wilson puts it, their individual progress "is good for the branch, and because we are married, it's not only good for the branch, it's good for us." 



A team on the homefront and the workfront, Alexander Wilson and Joan Bailey-Wilson enjoy what they believe is a unique arrangement, co-chairing a NHGRI research branch dedicated to uncovering the genetic and environmental components of inherited diseases

The personal and professional relationship of NHGRI's husband-and-wife researchers Alexander Wilson and Joan Bailey-Wilson spans more than three decades.

They met as undergraduates while working with the sole genetics faculty member at Western Maryland College (now called McDaniel College), a small liberal arts college in Westminster, Md. One thing led to another, and they ended up attending graduate school together at Indiana University, where they studied medical genetics sprinkled with a healthy dose of mathematics and computer science.

They were married in 1978, and two years later they received their doctorates and went to Louisiana State University Medical School in New Orleans to work with Robert Elston. Elston is one of the leading figures in statistical genetics, a then-emerging field that draws on elements of epidemiology, genetics, molecular biology, computer science, and statistics. They entered LSU as postdoctoral fellows and stayed for 15 years, each ultimately reaching the rank of full professor.

When Elston left LSU for Case Western Reserve University in Cleveland in 1995, Wilson and Bailey-Wilson decided to relocate as well—to NHGRI.

Initially they were in separate branches—Wilson in the Genetic Disease Research Branch led by Robert Nussbaum and Bailey-Wilson in the Medical Genetics Branch led at the time by Clair Francomano. However, their work was so different from that of the other more traditional bench scientists in their branches that they posed an administrative challenge.

"We don't purchase supplies; we make contracts for data collection. When we buy computers, it's not laptop computers, it's big servers,"  explains Wilson.

So two years later, Wilson and Bailey-Wilson became a branch unto themselves—the IDRB. Because NIH's anti-nepotism rules prohibit one spouse from supervising the other, Nussbaum was appointed acting chief of the branch. Over the years, Nussbaum gradually taught Wilson and Bailey-Wilson the administrative aspects of the chief's job; thus,  they were well prepared to take over this year. "He trained us up,"  says Wilson.

Co-branch chiefs are rare at the NIH; married co-chiefs are even rarer. To their knowledge, Wilson and Bailey-Wilson are the only ones.

Karen Ross




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