A powerful pain reliever called ziconotide, which serves as an alternative treatment to opioids, is derived from an unusual source: the venom of cone snails.
The roots of the discovery of ziconotide stretch back to the Philippines in the 1970s. However, “we weren’t aiming to develop a pain compound,” said researcher Michael McIntosh.
Studying cone snails was initially a detour for researchers Baldomero Olivera and Lourdes Cruz. Olivera, who was splitting his time between the United States and the Philippines, found his research on DNA synthesis hampered by a lack of access to equipment and supplies in Manila. He found inspiration in his childhood interest in shell collecting. Cone snails are abundant in the Philippines, and their venom, which they use to trap fish, worms, and other mollusks, could be a rich avenue for research.
A number of breakthroughs emerged from the multidecade, multinational collaboration begun by Olivera and Cruz, which was bolstered by access to raw materials in their Philippines lab and leading-edge technology for analysis of the venom at their University of Utah lab. Among their findings: determining that the venom itself was made of peptides—very small, tightly bound proteins.
Building upon this work were other researchers, including McIntosh and Craig Clark, both of whom joined the lab as undergraduates. Pursuing his interest in brain science, Clark injected different combinations of cone snail venom peptides directly into the brains of lab mice to a surprisingly wide range of results: Some combinations caused shaking, others made mice lethargic, others made them excitable. McIntosh homed in on the particular peptide that caused shaking—purifying it, identifying its chemical structure, and dubbing it omega-conotoxin.
Over the years, the lab, in partnership with collaborators, uncovered more about omega-conotoxin and its effects—including its use as a potent pain reliever for patients with chronic illnesses. Observing the effects of conotoxins in animals has also helped researchers find new ways to map the body’s nervous system.
Now, the researchers have been recognized with the 2022 Golden Goose Award, which honors federally funded research that unexpectedly benefits society.
Funding from the National Institute of General Medical Sciences of the National Institutes of Health as well as the Department of Defense was indispensable to their discoveries, the researchers acknowledged.
“It wasn’t that easy to analyze small amounts of proteins at the time,” said Olivera. “But the fact that we finally got an NIH grant, that I would say was what really allowed us to discover things that were unexpected.”
“Tiny Snail, Big Impact: Cone Snail Venom Eases Pain and Injects New Energy into Neuroscience” was one of three Golden Goose Award–winning research projects recognized at the 14 September ceremony hosted by the American Association for the Advancement of Science. In attendance at the Washington, D.C., ceremony were Olivera and McIntosh, who continue to work together at the University of Utah, and Cruz, who was named a National Scientist of the Philippines in 2006. (Clark passed away in 1994.)
“This is that wonderful time of year when we shine a light on the unforeseen yet completely predictable major impacts of federally funded scientific research,” said Sudip S. Parikh, chief executive officer at AAAS and executive publisher of the Science family of journals, in remarks at the ceremony. “AAAS is proud to be a Golden Goose Award founding organization and to have the opportunity to share with all of you the stories of these incredible scientists whose research went in amazing and valuable directions that will benefit all Americans.”
This year’s award comes weeks after Congress’s passing and President Biden’s signing of the bipartisan CHIPS and Science Act, which reauthorizes the key federal agencies whose projects will propel the very innovations honored by the Golden Goose Award.
The award was launched in 2012, but like much of the research it recognizes, its inspiration emerged much earlier. In the 1970s and 1980s, the late Senator William Proxmire (D–WI) bestowed the dubious honor of the Golden Fleece Award. His awards were intended to highlight wasteful government spending, and basic scientific research was often in his crosshairs. Representative Jim Cooper (D–TN), however, recognized that esoteric, often silly-sounding scientific research can yield significant impacts. To recognize and celebrate the scientists pursuing federally funded research with often unexpectedly beneficial results, Cooper’s vision was brought to life by a coalition of businesses, universities, and scientific organizations, including AAAS.
Since its inception, the award has honored more than 70 researchers for breakthroughs deriving from sources as wide-ranging and seemingly obscure as horseshoe crab blood and rat massage.
Also joining the ranks of honorees with the 2022 Golden Goose Award are two more teams of researchers.
Manu Prakash of Stanford University and Jim Cybulski of Foldscope Instruments, Inc., earned the award for creating the Foldscope—an innovative new microscope made of folded paper. Powerful enough to magnify 140 times, inexpensive to manufacture, and accessible in conditions where a bulky yet delicate and expensive microscope might not be practical, the tool was born of Prakash’s fieldwork in a Thai rainforest studying infectious disease diagnostics, where a standard microscope was going unused.
To develop an accessible microscope that could be toted anywhere, Prakash’s lab received support from NIH, while Cybulski received the NIH Fogarty International Center Global Health Equity Scholars Fellowship and a National Science Foundation grant allowed them to manufacture and distribute Foldscopes.
A multinational team consisting of Tibor Juhasz, Ron Kurtz, Detao Du, Gérard Mourou, and Donna Strickland also received the Golden Goose Award for paving a path to bladeless LASIK eye surgery.
The serendipitous results stem from Mourou and Strickland’s research on short, intense laser pulses—their development of the optical technique known as chirped pulse amplification earned them half of the 2018 Nobel Prize in Physics.
When Du was a graduate student in Mourou’s lab—the Center for Ultrafast Optical Science at the University of Michigan—he accidentally lifted his goggles and exposed his eye to a stray beam. While Du had no visible damage to his eye, Kurtz, then a medical resident, checked his eyes to find a series of perfectly circular laser burns on his retina. The damage was not serious, but the laser left much more precise marks than the lasers in medical use at the time. Along with Juhasz, they collaborated to pursue clinical uses for these femtosecond laser pulses. Their research was supported by funding from the Department of Energy and NSF.
Today, this laser approach has supplanted the precision scalpel for surgery to improve patients’ vision, from which millions have benefited.
Cooper—the award’s “Father Goose”—retires this year after 32 years of service in Congress, but his vision of recognizing and celebrating that serendipitous science can change lives persists.
Said Cooper at the award ceremony, “Tell me a fact, and I may remember it. Tell me the truth, and I may believe. But tell me a story, and I will carry it in my heart forever. And that’s what Golden Goose is all about.”
Meredith Asbury, Gwendolyn Bogard, and Haylie Swenson contributed to this report. It first appeared in the Sept. 29, 2022, issue of Science.