In November of 1992, a group of distinguished scientists and Dana Foundation members convened at Cold Spring Harbor Laboratory to discuss the need to increase public understanding of brain-related diseases, disorders and research. Hosted by Nobel laureate, James D. Watson, Ph.D., the group laid the groundwork for the Dana Alliance for Brain Initiatives and set down a vision for their organization, including their goals, strategy, and tools.
Alliance vice-chairman and Nobel laureate James D. Watson at the press conference announcing the formation of the Dana Alliance for Brain Initiatives in April 1993.
Imagine a world . . .
- In which Alzheimer's, Parkinson's, Lou Gehrig's (ALS) diseases, and retinitis pigmentosa and other causes of blindness are commonly detected in their early stages, and are swiftly treated by medications that stop deterioration before significant damage occurs.
- In which spinal cord injury doesn't mean a lifetime of paralysis because the nervous system can be programmed to re-wire neural circuits and re-establish muscle movement.
- In which drug addiction and alcoholism no longer hold people's lives hostage because easily available treatments can interrupt the changes in neural pathways that cause withdrawal from, and drive the craving for addictive substances.
- In which the genetic pathways and environmental triggers that predispose people to mental illness are understood so that accurate diagnostic tests and targeted therapies - including medications, counseling, and preventive interventions - are widely available and fully employed.
- In which new knowledge about brain development is used to enhance the benefits of the crucial early learning years and combat diseases associated with aging.
- In which people's daily lives are not compromised by attacks of depression or anxiety because better medications are being developed to treat these conditions.
Although such a vision may seem unrealistic and utopian, we are at an extraordinarily exciting time in the history of neuroscience. The advances in research during the past decade have taken us further than we had imagined. We have expanded our understanding of the basic mechanisms of how the brain works, and are at a point where we can harness the healing potential of that knowledge.
We have already begun to devise strategies, new technologies, and treatments to combat a range of neurological diseases and disorders. By setting therapeutic goals, and applying what we know, we will develop effective treatments - and, in some instances, cures.
For all that has been learned in neuroscience recently, we are learning how much we do not know. That creates the urgency to continue basic research that looks at the broader questions of how living things work. This will help to formulate the complex questions that lead to scientific discovery.
The coordinated work of thousands of basic and clinical scientists in multiple disciplines, ranging from molecular structure and drug design to genomics, brain imaging, cognitive science, and clinical investigation, has given us a pool of information that we can now use to build into therapeutic applications for all neurological diseases and disorders. As scientists, we will continue to move forward not just as individuals, exploring our particular areas of interest, but also in concert with colleagues in all areas of science, mining opportunities to collaborate across disciplines.
Public confidence in science is essential if we are to be successful in our mission. To this end we recognize that dialogue between researchers and the public will be essential in considering the ethical and social consequences of advances in brain research.
The Dana Alliance for Brain Initiatives and the European Dana Alliance for the Brain represent a community of neuroscientists willing to commit to ambitious goals, as seen in 1992 in Cold Spring Harbor, New York where an American research agenda was set forth and again in 1997 when the newly formed European group followed suit with its own goals and objectives. Both groups now are moving the goalposts to capitalize on the gains that have been made. We are setting new goals to guide what can be achieved in the near term, and project even further into the future. By allowing ourselves to imagine what benefit this new era in neuroscience is likely to bring, we can speed progress toward achieving our goals.
(Clockwise from top left) Francis S. Collins, W. Maxwell Cowan, Fred Plum, and Guy M. McKhann make remarks at the Alliance press conference in April 1993.
Combat the devastating impact of Alzheimer's disease.
In Alzheimer's disease, a small piece of the protein, amyloid, accumulates and is toxic to nerve cells. The mechanism of this accumulation has been worked out biochemically and in genetic studies in animals. Using these animal models, new therapeutic drugs and a potentially powerful vaccine are being developed to prevent the accumulation of this toxic material or enhance its removal. These new therapies, which will be tried in humans in the near future, offer realistic hope that this disease process can be effectively treated.
Discover how best to treat Parkinson's disease.
Drugs that act on dopamine pathways in the brain have had significant success in treating the motor abnormalities of Parkinson's disease. Unfortunately, this therapeutic benefit wears off for many patients after 5-10 years. New drugs are being developed to prolong the action of dopamine-based treatments and to slow the selective loss of nerve cells that causes this disease. For those in whom drug therapies fail, surgical approaches, such as deep brain stimulation, are likely to be of benefit. Newer forms of brain imaging have made it possible to determine if these treatments are rescuing nerve cells and restoring their circuits back toward normal.
Decrease the incidence of stroke and improve post-stroke therapies.
Heart disease and stroke can be strikingly reduced when people stop smoking, keep their cholesterol levels low, and maintain normal weight by diet and exercise, and detect and treat any occurrence of diabetes. For those with strokes, rapid evaluation and treatment can lead to dramatic improvement and less disability. New treatments will be developed to further reduce the acute impact of stroke on normal brain cells. New rehabilitation techniques, based on understanding how the brain adjusts itself following injury, will result in further improvement.
Develop more successful treatments for mood disorders such as depression, schizophrenia, obsessive compulsive disorder, and bipolar disorder.
Although the genes for these diseases have eluded researchers over the past decade, the sequencing of the human genome will reveal several of the genes for these conditions. New imaging techniques, along with new knowledge about the actions of these genes in the brain, will make it possible to see how certain brain circuits go awry in these disorders of mood and thought. This will provide the basis for better diagnosis of patients, more effective use of today's medications, and the development of entirely new agents for treatment.
Uncover genetic and neurobiological causes of epilepsy and advance its treatment.
Understanding the genetic roots of epilepsy and the neural mechanisms that cause seizures will provide opportunities for preventive diagnosis and targeted therapies. Advances in electronic and surgical therapies promise to provide valuable treatment options.
Discover new and effective ways to prevent and treat multiple sclerosis.
For the first time, we have drugs that can modify the course of this disease. New drugs, aimed at altering the body's immune responses, will continue to decrease the number and severity of attacks of multiple sclerosis. New approaches will be taken to stop the longer-term progression caused by the breakdown of nerve fibers.
Develop better treatments for brain tumors.
Many types of brain tumors, especially those that are malignant or have spread from cancer outside the brain, are difficult to treat. Imaging techniques, focused-radiation treatments, different forms of delivery of drugs to the tumor, and the identification of genetic markers that will assist diagnosis, should provide the basis for development of innovative therapies.
Improve recovery from traumatic brain and spinal cord injuries.
Treatments are being evaluated which decrease the amount of injured tissue immediately after an injury. Other agents are aimed at promoting the rewiring of nerve fibers. Techniques that encourage cellular regeneration in the brain to replace dead and damaged neurons will advance from animal models to human clinical trials. Electronic prostheses are being developed that use microchip technology to control neural circuits and return movement to paralyzed limbs.
Create new approaches for pain management.
Pain, as a medical condition, need no longer be woefully undertreated. Research into the causation of pain and the neural mechanisms that drive it will give neuroscientists the tools they need to develop more effective and more highly targeted therapies for pain relief.
Treat addiction at its origins in the brain.
Researchers have identified the neural circuits involved in every known drug of abuse, and have cloned major receptors for these drugs. Advances in brain imaging, by identifying the neurobiological mechanisms that turn a normal brain into an addicted brain, will enable us to develop therapies that can either reverse or compensate for these changes.
Understand the brain mechanisms underlying the response to stress, anxiety, and depression.
Good mental health is a prerequisite for a good quality of life. Stress, anxiety, and depression not only damage peoples' lives, they can also have a devastating impact on society. As we come to understand the body's response to stress and the brain circuits implicated in anxiety and depression, we will be able to develop more effective ways to prevent them, and better treatments to lessen their impact.
Take advantage of the findings of genomic research.
The complete sequence of all the genes that comprise the human genome will soon be available. This means that we will be able, within the next 10 to 15 years, to determine which genes are active in each region of the brain under different functional states, and at every stage in life - from early embryonic life, through infancy, adolescence, and throughout adulthood. It will be possible to identify which genes are altered so that their protein products are either missing or functioning abnormally in a variety of neurological and psychiatric disorders. Already this approach has enabled scientists to establish the genetic basis of such disorders as Huntington's disease, the spinocerebellar ataxias, muscular dystrophy, and fragile-x mental retardation.
The whole process of gene discovery and its use in clinical diagnosis promises to transform neurology and psychiatry and represents one of the greatest challenges to neuroscience. Fortunately the availability of microarrays or "gene chips" should greatly accelerate this endeavor and provide a powerful new tool both for diagnosis and for the design of new therapies.
Apply what we know about how the brain develops.
The brain passes through specific stages of development from conception until death, and through different stages and areas of vulnerability and growth that can either be enhanced or impaired. To improve treatment for developmental disorders such as autism, attention deficit disorder, and learning disabilities, neuroscience will build a more detailed picture of brain development. Because the brain also has unique problems associated with other stages of development such as adolescence and aging, understanding how the brain changes during these periods will enable us to develop innovative treatments.
Harness the immense potential of the plasticity of the brain.
By harnessing the power of neuroplasticity - the ability of the brain to remodel and adjust itself - neuroscientists will advance treatments for degenerative neurological diseases and offer ways to improve brain function in both healthy and disease states. In the next ten years, cell replacement therapies and the promotion of new brain cell formation will lead to new treatments for stroke, spinal cord injury, and Parkinson's disease.
Expand our understanding of what makes us uniquely human.
How does the brain work? Neuroscientists are at the point where they can ask - and begin to answer - the big questions. What are the mechanisms and underlying neural circuits that allow us to form memories, pay attention, feel and express our emotions, make decisions, use language, and foster creativity? Efforts to develop a "unified field theory" of the brain will offer great opportunities to maximize human potential.
Dana Foundation director and Alliance member Steven E. Hyman at the August 2000 meeting to revisit the Alliance's mission and goals.
Adult nerve cells cannot replicate themselves to replace cells lost due to disease or injury. Technologies that use the ability of neural stem cells (the progenitors of neurons) to differentiate into new neurons have the potential to revolutionize the treatment of neurological disorders. Transplants of neural stem cells, currently being done on animal models, will rapidly reach human clinical trial status. How to control the development of these cells, direct them to the right place, and cause them to make the appropriate connections are all active areas of research.
Neural repair mechanisms
By using the nervous system's own repair mechanisms - in some cases, regenerating new neurons and in others restoring the wiring - the brain has the potential to "fix" itself. The ability to enhance these processes provides hope for recovery after spinal cord injury or head injuries.
Technologies that may arrest or prevent neurodegeneration
Many conditions, such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and ALS are the result of degeneration in specific populations of nerve cells in particular regions of the brain. Our present treatments, which modify the symptoms in a disease like Parkinson's disease, do not alter this progressive loss of nerve cells. Techniques that draw on our knowledge of the mechanisms of cell death are likely to offer methods to prevent neurodegeneration and, in this way, stop the progression of these diseases.
Technologies that modify genetic expression in the brain
It is possible to either enhance or block the action of specific genes in the brains of experimental animals. Mutated human genes that cause neurological diseases such as Huntington's and ALS, are being used in animal models to assist in the development of new therapies to prevent neurodegeneration. Such techniques have also provided valuable information about normal processes such as development of the brain, learning, and the formation of new memories. These technologies provide an approach to the study of normal and abnormal brain processes more powerful than there has ever been available before, and in time, may be used clinically in the treatment of many brain disorders.
Advanced imaging techniques
There have been remarkable advances in imaging both the structure and the function of the brain. By developing techniques that image brain functions as quickly and accurately as the brain does, we can achieve "real-time" imaging of brain functions. These technologies will allow neuroscientists to see exactly which parts of the brain are involved as we think, learn, and experience emotions.
Electronic aids to replace non-functional brain pathways
In time it may be possible to bypass injured pathways in the brain. Using multi-electrode array implants and micro-computer devices - which monitor activity in the brain and translate it into signals to the spinal cord, motor nerves, or directly to muscles - we expect to be able to offer the injured hope for functional recovery.
Novel methods of drug discovery
Advances in structural biology, genomics, and computational chemistry are enabling scientists to generate unprecedented numbers of new drugs, many of which promise to be of considerable value in clinical practice. The development of new, rapid screening procedures, using "gene chips" and other high through-put technologies, will reduce the time between the discovery of a new drug and its clinical evaluation, in some cases, from years to just a few months.