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| THE McKNIGHT LEGACY |
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A program with a proud history continues to support research at the leading edge of neuroscience.William L. McKnight, who gave part of his estate to establish The McKnight Foundation, was deeply interested in brain disorders that affect mental functions such as memory. To acknowledge his interest, The McKnight Foundation began supporting neuroscience research in 1977. Beginning with support for the activities of a single institution in Florida in the early 1970s, the Foundation went on to develop a widely acclaimed national program that has supported hundreds of outstanding young and established neuroscientists.
In the late 1970s, Fred Plum, a distinguished professor of neurology at Cornell Medical School, and Julius Axelrod, a Nobel-Prize winning neuroscientist at the National Institutes of Health in Bethesda, Maryland, organized McKnight's initial efforts in neuroscience through a series of committees that reported to the board of directors. In the late 1980s, the Foundation made a permanent commitment to neuroscience research by establishing The McKnight Endowment Fund for Neuroscience, with a separate board and officers. This provided for more autonomy and a continuous stream of funding from the parent foundation. Funding has grown to $4.4 million per year.
Forging a Mission: Basic Research
Since its inception, a major goal of The McKnight Foundation's neuroscience program has been to support basic research that would ultimately increase our understanding of brain diseases, especially those affecting memory and other cognitive problems of aging. The McKnight Foundation initiated the McKnight Awards in Neuroscience in 1976 "to support fundamental research in neuroscience, especially as it pertains to memory and its biological substrates." This emphasis continued into the 1980s and 1990s.
The board of the McKnight Endowment Fund for Neuroscience wanted to fill special needs that were not being met adequately by other funders. Specifically, the board sought to nurture the best and brightest young scientists, to identify the most creative and innovative ideas within its areas of interest, and to seek out ways to fuel paradigm shifts and technological advances.
To this end, the neuroscience board established three award programs. Scholar Awards supported the very best young scientists just starting their own independent laboratories. Development Awards supported neuroscientists in mid-career, enabling them to take risks and try new approaches. Finally, Senior Awards identified a few superb senior scientists who could use seed funding from McKnight to introduce new techniques and approaches into their laboratories and new perspectives to their work. In many cases, this led to key insights that represented the culmination of years of effort.
Initially, the board concluded William L. McKnight's interest was best served through basic research, because the only way to make progress in understanding memory and its diseases and disorders was first to understand the fundamental, basic mechanisms of nerve cell development, signaling, circuits, and plasticity. More than a decade before the field fully realized that common mechanisms are used during the development of the nervous system and later during adult learning and plasticity, the board supported research in both areas.
The McKnight neuroscience program served the field well for two decades. During the 1980s and 1990s, McKnight neuroscience program funds represented less than 1 percent of the total funding of the field in the United States. But the impact was enormous on individual careers and contributions, progress in neuroscience in general, and, more specifically, insights into the biological substrates of memory.
The program nurtured the most creative and innovative minds and ideas at a stage in the history of the field in which such an effort had a major impact on the direction of brain science. Many of the pilot projects supported with modest funds from McKnight later became mainstream projects supported by National Institutes of Health (NIH). Of the few dozen leading senior neuroscientists chosen to receive large-scale funding from the prestigious Howard Hughes Medical Institute (HHMI) as HHMI Investigators, many had help during their formative years from the McKnight neuroscience program.
In 1994, The McKnight Foundation commissioned Abt Associates (Center for Science and Technology Policy Studies in Cambridge, Massachusetts) to evaluate the neuroscience program. The results were extremely satisfying to everyone involved with the program over the previous two decades. Abt Associates made recommendations about revising the program, most of which were embraced, but also applauded its focus on supporting a balanced mix of fundamental neuroscience and specific memory research.
One outside referee wrote: "The McKnight program has funded a significant proportion of
the most talented investigators, particularly younger investigators, in U.S. neuroscience
over the period under consideration."
Abt Associates reported that McKnight funding "was cited as especially important in helping young researchers to establish productive research programs early in their careers, and in allowing established researchers to explore new directions." They concluded that "McKnight funding has been associated with many of the most important developments in fundamental neuroscience in recent years."
As a result of the Abt evaluation, the board made the Development and Senior awards accessible to all applicants, as the Scholar Awards always had been. Previously, investigators had to be invited to apply.
Refining a Mission: Integrative Research
In the mid-1990s, the board began discussing how to encourage more research at the systems and cognitive end of neuroscience. This reflected the new technologies that became available in the 1990s for studies of brain function. These discussions coincided with another of the Abt Associates' recommendations: to place "greater emphasis on integrative research."
In 1999, the board drafted a proposal to The McKnight Foundation reflecting changes in the field. The Foundation board endorsed a new approach to fuel creative ideas and paradigm shifts, galvanize interactions between disciplines that traditional funding does not support, and push the field forward into a renewed focus on the interface between basic neuroscience and diseases of the brain.
Our vision for the future of the McKnight contribution to the neurosciences focuses on four
areas: three award programs and a revised annual meeting.
The programs are:
- McKnight Scholars Award
- McKnight Technological Innovations in Neuroscience Award
- McKnight Neuroscience of Brain Disorders Award
- Annual McKnight Neuroscience Conference and Workshop
These programs are united in their emphasis on creativity and innovation. Each also strives to bridge the gap between basic neuroscience and neurological disease.
McKnight Scholar Awards: The goal remains to support young scientists as they first emerge as independent investigators—recognizing, however, that the scientific horizons are immeasurably broader than they were 20 years ago. Molecular biology has had an impact on neuroscience that few would confidently have predicted. In addition, advances in the understanding of the principles of nervous system development have revealed common developmental programs in widely divergent animals. The approaches available to systems neuroscientists are also vastly richer. Collectively, these advances have led to a maturation of the field, both conceptually and clinically.
In supporting young scientists, the McKnight Scholar Awards attempt to balance the best in basic research with an emphasis on those areas of greatest clinical importance. The aim is to select problems that, if solved at the basic level, would have immediate and significant impact on clinically relevant issues such as learning and memory.
McKnight Technological Innovations in Neuroscience Award: Brain studies are being held back by limits in our technology. The field is in desperate need of new ways to visualize the details of brain function. The purpose of these new methods is to monitor brain activity in awake behaving animals in great detail and to record the activity of ensembles and circuits of neurons. At the same time, the field needs new ways of monitoring and manipulating gene expression in the developing and functioning brain, so that we can learn which genes and proteins are involved in a particular brain function.
Many of these technological advances will come from scientists in other fields (e.g., physics, chemistry, engineering) in collaboration with neuroscientists, or alternatively from neuroscientists who themselves ventured into these other areas. The McKnight Technological Innovations Awards push the field forward at the interface between neuroscience and other scientific disciplines.
In the first year of these awards, 1999, the committee received preliminary proposals from 130 research laboratories. Clearly, the existence of this award stimulated new thinking and brought together scientists from different areas. The McKnight Technological Innovation award has a unique mission to catalyze the invention and development of new ways of approaching brain function.
McKnight Neuroscience of Brain Disorders Award: When the McKnight neuroscience program started more than 20 years ago, the founders looked forward to a time when basic neuroscience research could be applied to the diagnosis, prevention, and treatment of brain disorders, especially those that affect cognition and memory in old age. Such applications were not possible then. But now, as more and more is learned about brain molecules and functions, the time has come to apply this knowledge to human disease.
A good example is Alzheimer's disease. Twenty years ago all that was known about Alzheimer's was that brain cells of many older people became sick and died, resulting in loss of memory and mental deterioration. Over the years it was found that parts of a specific brain protein (amyloid precursor protein) accumulated in these sick brain cells. Discovery of this protein was based, in part, on tools developed by scientists supported by the McKnight program.
Based on our growing understanding of how this protein may lead to the degeneration of nerve cells, pharmaceutical companies are trying to develop drugs to stop the accumulation of the parts of this protein involved in the progression of the disease, in hopes of treating and preventing Alzheimer's. Also of great benefit would be the development of genetic tests that can identify people who have this inherited vulnerability to develop Alzheimer's disease.
Of course, the McKnight Neuroscience of Brain Disorders Award, first given in 2000, goes beyond diseases of memory attributable to neurodegeneration. It also extends to other disorders that can be illuminated by basic neuroscience discoveries—such as spinal cord injury, stroke, drug addiction, schizophrenia, and mood disorders. With modern tools of genetics, molecular biology, physiology, and functional imaging in hand, it is now possible to systematically dissect and understand brain disorders and elucidate causes. The Neuroscience of Brain Disorders Awards will encourage many of the best neuroscientists to turn their attention to diseases and disorders of the brain.
Annual McKnight Neuroscience Conference: Each year, awardees come together for a meeting and workshop that focuses on both their science and on selected topics picked by the board. The conference is designed to educate McKnight awardees and to foster new interests and collaborations. These four aspects of our program—three awards and an annual conference—have a common goal: to focus the best minds in neuroscience on solving the problems of diseases and disorders of the mind. The McKnight Foundation has been doing just that for 25 years, and its support for research has served society well. McKnight has played a strategic role in bringing science closer to the day that preventions, treatments, and cures for neurological diseases are found. The McKnight Endowment Fund for Neuroscience is dedicated to continuing this important quest.
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