Neuroscientist Corey Goodman, a longtime researcher at the University of California, Berkeley, who went on to start numerous biotech companies and, most recently, co-founded a venture capital firm, has been awarded the 2020 Gruber Neuroscience Prize.
Goodman, a UC Berkeley adjunct professor at the Helen Wills Neuroscience Institute (HWNI), shares the prize with Stanford University President Marc Tessier-Levine and Friedrich Bonhoeffer, emeritus director of the Max Planck Institute for Developmental Biology in Germany.
All three are known for showing how neurons make the proper connections in the growing body, so that our muscles, eyes, brain and everything else work properly. They focused on the signposts that guide axons, which all neurons send out like the growing roots of a tree, to find other cells that are their targets.
“All three of these neuroscientists were instrumental in breaking open the field of axon guidance,” said Susan Amara, scientific director of the National Institute of Mental Health and chair of the advisory board to the prize. “Their discoveries have fundamentally changed our understanding of how neural circuits are formed and have led to greater insights into a wide range of neurological disorders and injuries.”
The prize, which includes a $500,000 award, will be presented to the three scientists on Oct. 25 at the annual meeting of the Society for Neuroscience. Goodman has donated his share of the prize to HWNI.
“It’s a tremendous honor,” Goodman said. “Since I have been out of the field for so many years, it was very touching to have my colleagues honor me, along with Marc and Friedrich, for the work our three groups did, largely, in the 1990s. I was so touched by their recognition.”
Though Goodman closed his UC Berkeley lab in 2004 to focus on identifying new drug strategies to treat disease, eventually becoming founding president of the Biotherapeutics and Bioinnovation Center at the pharmaceutical company Pfizer, he retained his affiliation with UC Berkeley and the neuroscience institute he co-founded and once led. He has co-founded and led seven biotech companies, many of which have produced treatments approved by the FDA. The venture capital firm he launched in 2011, venBio, already has three approved drugs.
“Corey’s arrival at Berkeley ushered in our modern era of neuroscience,” said Ehud Isacoff, current director of HWNI and a UC Berkeley professor of molecular and cell biology. “This was one of the key steps in actualizing the reorganization of biology (begun by the late Daniel Koshland at UC Berkeley). Corey brought together molecular genetics, physiology, systems and cognitive and computational neuroscience and founded the Helen Wills Neuroscience Institute as an even broader cross-campus unification that brought in engineering, psychology, chemistry, public health and vision science.”
The logic of the nervous system
Building a complex organism like a human body seems mind-boggling, if you realize that our genome contains fewer than 30,000 genes, far too few to encode step-by-step instructions. Scientists like Goodman looked for the simple molecular logic that applies to all cells in the body and guides development with a modest set of initial instructions. He focused on perhaps the most complex organ, the brain.
“You’ve got the most incredible computational machine located in your brain, with billions of connections,” Goodman said. “And even though we are all different, we are all fundamentally built from the same wiring diagram that helps us move, think, see, perceive and do all the things we do. The questions have always been: Where is the wiring diagram? Where are the genetic instructions to wire up the brain?”
Using fruit flies as models, he pioneered the use of genetic screens to find the signals that set up this wiring diagram. Using chemical mutagens, his lab created tens of thousands of fruit fly mutants and searched through them for ones in which early development was affected. He and his colleagues were particularly interested in mutant flies with a disruption in connections between the left and right sides of the nervous system, which, in the fruit fly, are organized in mirror symmetry on each side of the midline, in the equivalent of a vertebrate’s spinal cord. This led Goodman and his colleagues to a signaling molecule, called slit, that repelled neurons away from the midline. They subsequently discovered a receptor for slit, which they called roundabout (robo), on axon growth cones, and a gene that they called commissureless (comm), which regulates the dynamic expression of the robo receptor, helping to coordinate growth toward, across and then away from the midline.
At the same time, Tessier-Levine, then at UC San Francisco, used biochemical techniques to isolate a molecule, netrin, that attracted growth cones to the midline. He and Goodman showed that netrins, slit proteins and another family of signaling molecules, sempahorins, which Goodman had discovered, all had counterparts in mammals, helping to establish the wiring of the spinal cord.
Bonhoeffer independently showed that the interplay of repulsion and attraction helped neurons in the eye send axons to the correct part of the brain. He dubbed one of the signaling molecules he discovered ephrin.
The group’s work established the four major families of axon guidance molecules – netrins, slits, semaphorins and ephrins – and revealed the logic of how they functioned to wire up the developing nervous system. Signaling molecules attract growing axons to one place in the body, but when the axons get close, other signals ramp up to repel them, diverting the growing axons to a new branch point. The repeated pull of attractants and push of repellants coordinates the setup of complex neural connections.
“Taken together, the work of these three scientists comprises one of the greatest success stories in developmental neuroscience,” said Joshua Sanes, Harvard University professor of molecular and cellular biology and director of its Center for Brain Science, who is a member of the prize selection advisory board.
Goodman received his B.S. from Stanford in 1972 and his Ph.D. from UC Berkeley in 1977. Following a postdoctoral fellowship at UC San Diego, he joined the Stanford faculty in 1979. He moved back to UC Berkeley in 1987 as a professor of molecular and cell biology, a Howard Hughes Medical Institute investigator and head of the Department of Molecular and Cell Biology’s Division of Neurobiology. He has published more than 200 scientific papers and is a member of the National Academy of Sciences, American Academy of Arts and Sciences and American Philosophical Society. He has won many prestigious awards, including the National Science Foundation’s Alan T. Waterman Award, the Canada Gairdner Award for biomedical research and the March of Dimes Prize in Developmental Biology.
He co-founded Exelixis in 1994 to pursue cancer treatments; Renovis, which he led as president and CEO in 2000, to attack neurological disorders; and five other biotechnology companies to help find cures for various forms of cancer, blindness, gut diseases and chronic migraines. He is a former chair of the National Research Council Board on Life Sciences, which advises the federal government, and the California Council on Science and Technology, which advises the governor and state legislature.
The Gruber Foundation, based at Yale University in Connecticut, was established in 1993 by the late Peter Gruber and his wife, Patricia Gruber. The foundation inaugurated the Gruber International Prize Program in 2000 and currently awards prizes in he fields of cosmology, genetics and neuroscience. UC Berkeley’s Mu-ming Poo won the Gruber Neuroscience Prize in 2016.