David R. McClay Awarded 2016 Developmental Biology-Society for Developmental Biology Lifetime Achievement Award

By Marsha E. Lucas

David R. McClay, Jr., the Arthur S. Pearse Professor of Biology at Duke University, received the 2016 Developmental Biology-Society for Developmental Biology Lifetime Achievement Award for his outstanding and sustained research and mentoring contributions to the field of developmental biology. McClay is being recognized for his distinguished body of work uncovering the mechanisms underlying cell fate specification, patterning, and morphogenesis in the sea urchin embryo. His discovery that nuclear β-catenin specifies vegetal fates proved to be of great significance as it is critical for endoderm specification in numerous vertebrate and invertebrate species. His group established the role of Notch signaling in secondary mesenchyme induction and has been a leader in unpacking sea urchin gene regulatory networks.

McClay earned his Bachelor’s degree in zoology at Penn State University in 1963 and his Master’s degree in zoology at the University of Vermont in 1965.

However, it wasn’t until he was a graduate student at the University of North Carolina, Chapel Hill (UNC), that he was first introduced to sea urchins. McClay took an embryology course at the Bermuda Biological Station (now the Bermuda Institute of Ocean Sciences) the summer after his first year of graduate school.

“We collected out in the reef everyday and went diving and snorkeling for animals,” he said in a July interview. “I came back from that experience and decided that Bermuda was a great place to do research. So, I dreamed up a problem and managed to do much of my doctoral research in Bermuda.”

McClay studied cell adhesion in sponges under the mentorship of his graduate advisor, H. Eugene Lehman. “Gene Lehman at Chapel Hill was wonderful, and at 96 remains wonderful to my life,” he said.

McClay graduated from UNC in 1971 and headed to the University of Chicago to do a postdoc with Aron A. Moscona. There, he began working on cell adhesion in chick and mouse embryos. Within five months, McClay had an offer from Duke University to become a faculty member in the Department of Zoology. The work he carried out in the mouse and chick earned him his first grants as an independent investigator. They were not, however, the only biological systems on his mind.

“When I got to Duke, I decided that at least a small part of my research would be looking at the sea urchin embryo because it’s so simple and perfect for an experimental embryologist like me,” McClay said.

Sea urchin embryos are transparent, develop rapidly, and are easy to manipulate, he said. “You can ask a lot of questions. And because their rate of development is so fast, you can get answers fairly quickly.”

What started out as a summer project took over his entire lab and in 1980, McClay was awarded his first NIH grant to study sea urchin development. Some thirty-six years later, he still has that sea urchin grant.

McClay has been described as “THE world’s expert in manipulation of living sea urchin embryos.” He says this came about primarily as a defense mechanism. At Duke, he was teaching, running a lab, serving on study sections, and taking on more administrative responsibilities.

“Life is full of choices and my choice was I did not want to vacate the laboratory. I decided to look around and try to figure out what I could do that would be useful to the laboratory that no one else in the lab was really interested in doing. I took on the objective of doing microsurgery and I’ve just gradually become better and better at it. ... I’m in there [almost] everyday ... and it allows me to collaborate on every project with students.”

McClay has trained nearly 6o graduate students and postdocs in his long career. When asked about his mentoring philosophy, he said, “There’s no single formula for doing it. But, I try to work with students in such a way that allows them to identify their strengths—and go with them. I don’t know how good I am, but my students have been pretty darn successful. So, I’m proud of them all.”

Since his days as a graduate student, McClay has rarely been home during the summer. He continued to go to Bermuda up until the mid-1980’s when it became more important to have time with his children. The Marine Biological Laboratory in Woods Hole offered a much more family-friendly opportunity. In 1989, he became an instructor in the MBL Embryology course and co-director of the course with Eric Davidson and Michael Levine from 1991-1996.

McClay now spends his summers in the South of France at the Villefranche-sur-mer Developmental Biology Laboratory located within the Marine Observatory at Villefranche-sur-mer.

“They’ve been very gracious in allowing me a little bit of space to set up and do my work,” he said.

Interestingly, the work he is doing in France is based on work first discovered by Theodor Boveri (co-discover of the chromosomal theory of heredity along with Walter Sutton). Boveri, while visiting Villefranche in 1901, discovered that the Paracentrotus sea urchin egg has a pigment band that surrounds it below the equator separating the animal and vegetal poles of the egg.

McClay wants to understand how those initial asymmetries in the egg are established.

“For a long time, we were building gene regulatory networks along with Eric Davidson’s lab and other members of the sea urchin community. And, for me, the whole rationale behind that was to allow us to identify transcription factors that drive specific processes in development. And that’s mostly what I do, to look at what drives gastrulation, what drives different cell movements. But, I was always puzzled because... the gene regulatory network we were working with started at the 16-cell stage. But, you know there’s something there earlier.”

It is now known that “the vegetal area of the egg harbors factors that are necessary for specification of endomesoderm and the animal pole region harbors factors that are necessary for part of neurogenesis,” he said.

McClay has learned that you can chop off portions of the egg, and as long as it has a nucleus, it will develop. If he cuts off the egg below the pigment band, cells will divide and divide, but won’t make endomesoderm. As a result, he now has an assay where he can add specific maternal factors back to try to rescue endomesoderm.

“So it turns out,” he said, “if you add back members of the Wnt pathway, you can rescue endomesoderm. If you add back, one of the Wnts, you can rescue endoderm.” He has done this experiment with the animal pole as well and been able to rescue neurons by adding back certain not-yet-published maternal components.

When asked about his most significant discovery to date, McClay said it is the discovery he’s going to make tomorrow. “The size of [the discovery] isn’t so important, it’s just finding something new.”

His scientific journey has not been a solo endeavor. He expressed his gratitude for several individuals in his life.

“I very much appreciated Eric Davidson because he not only was brilliant and stimulating, but he was a provocateur. I mean, he would provoke you—make you angry. But, you would constantly try to say, ‘I’ll show that guy.’ So, while he was a good friend, he was also a great provocateur. Eric was important. Another person that was really important was John Trinkaus at Yale who when I was younger, was really terrific in encouraging me and applauding the efforts that I was putting into looking at morphogenesis, which is what I’ve been interested in all my life.”

McClay is a Fellow of the American Academy of Arts and Sciences. He served as SDB President from 1992-1993 and SDB Treasurer from 2003-2004. He continues to serve as an instructor for the MBL Embryology Course, as well as director for the MBL Gene Regulatory Networks Course. He reflected on being awarded the DB-SDB Lifetime Achievement Award.

“It’s an award that really is earned by the students of somebody who’s been in the business as long as I have because they are the ones who over the years have produced most of the work. And so, I tell people that, and yet they say, oh come on, you’re just deflecting. But, I’m not. It’s true.”

“...Getting an award like this means that you haven’t done everything in a complete vacuum. And that’s nice. I’d like to think that what I’ve done has been relevant and useful in advancing knowledge. And to get an award like this means that some other people are in agreement and that to me means a lot.”