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FREDERICK GOODWIN, M.D., Center for Neuroscience, PETER WHITEHOUSE, M.D., Ph.d., Alzheimer's Research ERIC ZILLMER, Ph.D., Department of Psychology, PAT LEVITT, Ph.D., Department of Neurobiology, University of Pittsburgh School of Medicine Todd Goren, Federal Filings Business News Robert Cook-Deegan, National Academy of Sciences Shannon Penberthy, Nat'l Assoc. of Epilepsy Center Jennifer Zeitzer, Alzheimer's Association Innovations in Pharmaceutical Science: Breakthroughs in Neuroscience commenced at 12:18 p.m. in SC-5 of the Capitol, Daniel Shostak, IAF Project Manager and Director of the Foresight Seminars on Pharmaceutical Research and Development moderating . . .
Shostak, the Project Manager with the Institute for Alternative Futures and Director of the Foresight Seminars on Pharmaceutical Research and Development.
Let me welcome you to the 5th of our 6 1996 Foresight Seminars. Today's program will be looking Foresight Seminar you've attended. So I would like to give you a brief introduction. This year we're having six Foresight Seminars, and this is our 18th year of having Foresight Seminars up here on the Hill. It is IAF, the Institute for Alternative quickly approaching its 20th anniversary, and many of you will be invited to our upcoming celebration. Do look for your mail. The Institute is an educational nonprofit organization in Alexandria, Virginia where our clients include international agencies, organizations and companies, national and local governments and agencies, nonprofit and community groups, including the Arlington County Library incorporating 22 of the Fortune Global 100.
packages that you have on your seats. The packages contain additional information on the Institute. It also contains copies or summaries of today's additional pieces of information that I would like Neuroscience's "Brainwaves Newsletter." This newsletter is very interesting because on the inside it has a very nice and succinct summary about recent news and scientific innovation in neuroscience. It also has a nice, lovely summary about the impact of neuroscience and neurodegenerative diseases on the The second newsletter we've also been able to include is from the Dana Alliance for Brain Initiatives, an alliance of neuroscientists and brain I would like to draw your attention to the third page, which is a lovely graphical summary of both how we think about neuroscience and about medications both in development and reaching the Finally, the Institute is very pleased to be able to provide to you, and will be able to provide additional copies if you like, the most recent "Prescription Medications and You: A Consumer Guide." This is a joint project of the Agency for Health Care Policy and Research and the National Council on Patient Information and Education. The Institute, AHCPR and NCPI are very committed to wide distribution of this pamphlet, and if you or your organizations require additional materials we'll be your package if the lavender evaluation form. Please do me the honor of completing the evaluation on your way out today so that we can continue to improve the program and get feedback to our speakers, to our The Institute for Alternative Futures has a specific mission: To help communities and organizations more wisely choose and create the futures they prefer. Our seminar goal building off that mission statement is to provide foresight on health to Congress, communities and the public.
foresight as a tool for public policy-making, and I'll spend a couple of minutes doing that in a preferred forecast, to summarize some of the research that we've done at the Institute or information that we've collected in a forecast about a preferred alternative future. The emphasis is on preferred, and that means that we stress the best possible future we can believe could occur. I hope part of our discussion today will be in fact about how to our program is the discussion element. We start our discussion element with topical presentations, and then after the topical presentations hopefully we'll engage you in our question, answer and discussion revealing unintended consequences of public policy. The whole idea here in our foresight discussion is that foresight includes revealing unintended consequences preferably before they happen. forecast about the implications of neuroscience and their recent breakthroughs, then our discussion about some of these breakthroughs, and then I hope to generate a discussion today about the partnership between government and industry and academics and between public and private organizations in fostering this type of innovation and avoiding the pitfalls of program, which is discuss foresight. The Institute has been defining government foresight as the application of futures research and methods to current policy issues by doing three things: model for the policy question in hand, to understand the stakeholders, what they bring into the system, what they want out of the system and how that system revealing unintended consequences, and we'll talk identifying emerging issues. In our first four seminars this year we talked about what futures research is, seeing the big picture and identifying emerging issues. Today we'll talk about revealing I went around the office the other day and said what in one minute could I say to help people be better at revealing unintended consequences, and we came up with five points to encourage you to use in your policy analysis or policy development function.
picture model. If you don't have a systems model of the question at hand try to develop one or try to find one that may already exist, and then work through the problem through your model to see if it makes sense. The model may need changing or the other arguments. Needless to say, not all opponents of your position are saying things that aren't true.
More importantly, they may be revealing things about your systems model that may need to be incorporated in your model to further refine your policy proposal.
A third proposal to help reveal unintended consequences is examine historical analogies. It's kind of funny to hear a futurist talk about history, but in fact much of the future still comes from our history. Bosnia may be one of the prime examples of that in current contemporary politics. Finding the appropriate historical analogy is difficult, but it is an important task to incorporate in your policy advocate. As you develop your policy proposal begin to say what's wrong with it, be aggressive about taking positions and tearing it apart. It is a good exercise, it's a wonderful way to build teams and policy analytical organizations, but, most importantly, it will improve your policy analysis.
agrees on in our office that has to be remembered is Murphy's Law - What can go wrong will go wrong, and one of the best ways to revealing unintended consequences is simply begin asking yourself how many things can go wrong and how many different ways they We tried to summarize a futurist Murphy's Law yesterday and it came out something like this: consequences, but that doesn't mean you shouldn't.
neuroscience, but often people say well where do these forecasts come from. So I use this slide to help people understand that we don't really pull them Our forecasts are built upon identifying: many of you work on day in and day out here in the Capitol and around government and organizations, -- Forces, and these are long-term social organizational forces that may be affecting the environment, but not necessarily policy or politics; Some of these are general principles about overall systems, and some of these are more specific Alternative Futures is very much committed to what we call vision, asking ourselves what are the people in power or what are the stakeholders particularly interesting in accomplishing, what is their vision for the future and how do their actions affect the forces, principles, trends or issues.
At the bottom of your screen you'll see a note on wildcards, and this is the thing that we use to remind ourselves that not everything is predictable or forecastable. Sometimes things happen that you cannot foresee, but you need to remember that that can occur when you begin to do a forecast, for today. Let's move on to our topic.
neuroscience and all that it contains, and we'll talk about that in a moment, will lead to profound changes in human consciousness, health, society and therefore the neuroscience you're about to discuss is going to have a profound impact on our future. It may in fact be transformative in terms of our culture and the way we relate to people in this room, in this community disorders is large and growing. One in six private research dollars goes into CNS research right now. Why would that be? That's because 1 in 20 Americans suffer from developmental disorders of the nervous system. Brain related disorders account for the majority of our nation's long-term costs, and brain and psychiatric disorders combined account for more hospitalization than all other diseases in this 2020 the burden of central nervous system and related disorders will rise by 50 percent worldwide. That will be equal to 190 million disability adjusted life years lost in that year alone. The disability adjusted life year loss is a metric to account for that people with these diseases will be alive but unable to contribute productively in some way to society. Nearly 14 percent of these daily adjusted life years lost will be due to CNS related disorders of the total. Major unipolar depression will become the second leading cause of life year loss in 2020.
The second reason why neuroscience may be transformative is that current CNS research is resulting in more knowledge about the brain, the body and society and is improving treatment. Again, 1 in 6 private research dollars go into CNS research today. Nearly a dozen pharmaceuticals were approved for CNS related disorders in 1995, and many, many more are in the pipeline or about to be approved. We'll be hearing about some of that a little bit why neuroscience may be transformative is that neuroscience will revolutionize how we think about ourselves. The fundamental question that these people have been working on and dozens, hundreds, thousands of other researchers are working on is how does the brain work and how does the consciousness and the idea of self come out of how the brain works.
bit about how the brain works at the molecular, genetic and mechanical level, how that generates behavior and how all that knowledge goes into treating mental illness or understanding mental illness and, finally, Alzheimer's disease, the Neuroscientists are asking the fundamental questions that are going to change how we think about thinking. And, finally, going back to history and historical analogies one rule of history in social change is that as the idea of self evolves social one that I find most pressing is the idea of free will. After the Renaissance people began saying we had free will, and if we had free will we did not have destiny and we could choose our future, and within the next two to three hundred years after the idea of free will re-established itself from Western Europe we saw the end of the kings, we saw the colonies splitting and we saw the end of the empirical empires, and there are other examples about how the idea of self changes and leads to social Pittsburgh. He is the new Chair and Professor of Neurobiology at the Pitt School of Medicine. He focuses on how the brain works and how the workings of the brain turn into functional relationships and ultimately into behaviors. He is a neurobiologist by Drexel University. His research focuses on personality and the brain. So we go from the working Director of the Neuroscience, Medical Progress and Social Program at George Washington University. His research focuses on how the brain, behavior, and human values are all linked. He is also a member of the Institute of Medicine, one of five psychiatrists And our final speaker is Peter Whitehouse from Case Western Reserve University and the School of Medicine there. He is the Director of the Alzheimer's Center. Dr. Whitehouse will finish our formal program discussing recent advances in Alzheimer's screening and how those advances provide great new information, but raise very troubling each make a brief presentation, I'll take one clarifying question after each presentation to make sure we're getting it all straight, and then after the final presentation we'll open up for our question With that introduction done, I would like PAT LEVITT, Ph.D., UNIVERSITY OF PITTSBURGH DR. LEVITT: Thank you very much, Dan.
comments were couched in terms of the strategic importance of neuroscience being focused upon the pathological aspects of the nervous system, affective disorders, behavioral disorders and neurological disorders. But when I think about it in some sense I think about how our understanding of how the nervous system works will impact upon normal processes. As we learn how we learn and as we learn how we communicate we will design new strategies I think for educating ourselves and future generations. I think I'll make a forecast or a prediction that in about three weeks the City of Washington, D.C.
will be inundated with neuroscientists. 25,000 neuroscientists will be attending the Annual Society of Neuroscientists Meeting in the City of Washington, D.C. It is the largest biologically associated society in the country and in the world probably with 25,000 members. The only scientific society larger in the United States is the American Chemical Society. So in fact we don't need to make predictions I think about how important neuroscience will be in the future. Scientists in fact have done that for us and there are a number of us in the room minutes now is to provide some baseline information about how we think about cellular processes in how the nervous system forms. I'm a developmental biologist and I do have an inherent bias in that I believe that in order to understand how the central nervous system works and how the brain works you might as well start from the beginning and understand how this is built, how circuits are formed, how cells that comprise the brain are actually produced, how they wire together and how they maintain their capacity to change over our entire life, and what are the mechanisms that drive all of those forces.
you to remember today I think, and there are a number of them, but the one is that we've had a tendency in the past to understand that genes are very important in all biological processes, and we also have an understanding that experience, either by the organism or by cells, is also a major part of driving The problem that we've tended to segregate or separate those in some sense, that is it's either genetic or its epigenetic, and what I would like to show you, and let's have the first slide, is that in If we go back a little bit in history, and this is a slide that was of a schematic that was generated by Paul Vice, a very famous biologist, who back in the 1940s generated this. All I want this to represent is in fact we've come full circle into separating these processes of genes that regulate biological functions and experience that regulates biological functions to an image like this where these arrows that interconnect a number of different processes that occur in development in fact impact example, that the nervous system has 50,000 genes at least or more that are unique to the nervous system itself. No other organ in the organism shares those genes, and by the year 2000 we will have identified 99 percent of the composition as we know it in the favorite experimental model at least preferred by biologists of the mass. So we'll have the substrate in fact of that information by the end of the century, there is no question about it, and maybe even before. The problem is we're still in the infancy of understanding how those genes in fact are regulated to drive a number of different biological last 10 years, and this is from a number of different laboratories, and I'm really not going to talk very much about my own work, that there are genes that are unique to the nervous system that control pattern. That is, there are genes that are expressed in certain parts of the very early brain, and the brain starts out as two, and those genes drive the identity of what those different parts of the brain will become. But we know that the genes are not sufficient to drive that process. So, for example, if you identify that gene, and you identify when that gene is first expressed, and you're looking at a picture in the top right-hand panel, and that purple color is actually the expression pattern of a gene within in a very small segment of the spinal cord and it's expressed in no other part of the brain and it's expressed in no other part of the organism.
important in driving that gene and specifying that very part of the spinal cord because we can place that piece of tissue into a new micro environment. That new environment contain signals from other cells from other parts of the organism that can in fact expression of gene patterning will eventually be in the formation of the nervous system to defining how the circuits actually form. So that early events at the genetic level that are driven by experiences that the cells undergo as a community and also individually will in fact drive the basic patterns of how the nervous system wires with each other. That's not to suggest that the wiring that occurs during development is immutable. In fact, it undergoes So what you're seeing here is actually new dyes that have been developed over the last 10 years that allow us to actually look at the very specific patterns, the intricacies of circuits, and what you're seeing here in fact is the circuit that's required by the organism to sense something in the environment, a touch, and to perform a motor task circuits and we can identify what happens to those circuits if there is abnormal gene expression. Remember again that gene expression is going to be regulated at every step of the way by influences from the environment, and this just doesn't happen post- natally. This happens prenatally as well.
cells on an individual level as well. We have the tools to do that now microscopically and we also have image analysis, and that becomes very important because in a number of laboratories around the world we're trying to understand at a circuit level what happens when we perturb the normal processes of development or what are normal processes of development, and I'll give you an example.
molecules that are very important in carrying information. They are the chemicals that carry information from one neuron to another, and just imagine this process happening in your head, and 10 to the 14 neurons are doing this, and I always get a headache when I think about it this. But in fact we neurotransmitters, and many of you know about norepinephrine and serotonin, and others on the panel will perhaps speak about those, are in fact molecules that are very important in regulating growth during development. They perform a separate role during critical periods of development before the individual neurotransmitter, dopamine, which we know is involved in affective disorders, can in fact modulate the develop of certain parts of the brain.
The way that we've investigated this, with a number of others, is to actually manipulate the levels of dopamine in the brain, and we've done this in a paradigm that actually has a clinical link to it. That is using an animal model we can expose developing animals to cocaine which directly modulates the levels of this neurotransmitter. Now remember that during early periods of development it's not a neurotransmitter per se, but it's a growth regulating molecule, and when we do that we've identified in fact that we don't grossly change the structure of the brain, but we do modify aspects of cell form and aspects of cell conductivity that have long-term impacts on how the organism cells, that very pretty painting, or it's actually a picture that was generated off of a computer, and it shows you the structure of some seven or eight cells, neurons sitting in the brain in an animal that was exposed prenatally. This animal was an adult when we changes that occurred in the structure.
fact, there are very specific parts of the brain, those that have to do with cognitive tasks, intentional tasks and learning tasks, again relating to structure and function for certain parts of the brain that are more focused on performing certain tasks than others, that are altered and are altered long-term. This just highlights some of those areas on the human brain, and this has been shown again in experimental animals. It clearly shows the power of how the environment, the cellular environment, the environment of the organism can really drive early developmental phenomena that eventually end up -- next slide -- with changes that we can measure as were exposed to cocaine only prenatally, when we assessed their behavior postnatally, that is once they're adults, they behave by and large very normally. But if you challenge them with a specific task, for example an intentional task where they were required to attend to a stimulus and then respond to that with a specific behavior, they can do it, but it takes them a long time to learn how to do that, and in fact in some instances they never quite reach that and more of these systems is to begin to identify brain structural relationships as they relate to how the nervous system first forms, and that in fact will have an impact in terms of understanding the molecular and cellular basis of how we learn and how we behave, and I hope in the discussion we'll talk about what impact that can have on how we generate policy in the broadest sense, and not just health neuroscience is going to tell us a lot more about possible education policy right off the top because if they know how the body develops and learns they are maybe the people who should be setting education Is there any clarifying question for Pat? Zillmer, Professor of Psychology at Drexel University. He focuses his work on personality and the brain. He is also the recent author of a new book on the psychology of Nazis, and has a new book coming out in '97 on the brain itself.
ERIC ZILLMER, Ph.D., DEPARTMENT OF PSYCHOLOGY, I'm going to use my time with you just to touch on three issues briefly, brain research in the past, which I call the scientific search for the soul, brain research in the present, which I call the decade of the brain, and then brain research in the Why is it important to focus on the past? I think for two reasons. I think our history will be our future. In addition, we've made mistakes in history that we should not make in the future, and Most of our history in brain research has been stuck in the dichotomy between I think therefore I am, the kind of idea that brain processes are mysterious and that the soul somehow arises from the brain in a mysterious way, and another concept, sort of a dichotomy, that there is no ghost in the machine and that the brain functions very much like a We are still stuck in the summary you may have seen in the Washington Post this morning that sort of embraced evolution a little bit but he did say that the soul is not part of this and it remains believe now, or we know actually that for every behavior, whether it's a reflex or whether it's religion, there is a neurological correlate. We've accepted that, and now we're trying to find out how research in the past may have affected what we're doing now. It wasn't long ago, 40 years ago, locally that a physician named Walter Friedman pioneered what's known as the transorbital lobotomy, in which he knew that behaviors in schizophrenics was related brain processes. He thought that somehow these neurons were tangled up, and one way you can undo them was to cut them, and he proceeded to do so in This was done in the 1940s and 1950s, and we look back on this now and we say outrageous. This was outrageous. Well I want to impress upon you that when we're in 2020 we're going to look back on how we're treating schizophrenia right now or other mental illnesses that have a biological component, panic disorder or obsessive compulsive disorder, and we're going to say the same thing, outrageous.
we've learned about the brain, 90 percent of it, we've learned in the last 10 to 20 years. In the 1940s and '50s we thought that half of our brain, the right hemisphere, was a reserve hemisphere. I don't know if you drive Jaguars, but they have two tanks, you know, one tank and then you switch over to the only in our understanding of the brain, but also in looking at it, imaging the brain based on an MRI. Well we can do that and target specific structures in the brain and quantify them, the white being the corpus porosa next to the two hemispheres, and the blue being the ventricular system, and we can look at them and look at, for example, differences in men and women on certain strategic structures. We can also see how these brains are working while somebody is doing something and we can superimpose that on the structure. So we're really on the threshold of a new science in terms of how we understand our own behavior and our differences in men and women, young tremendous advances. Children watch Pinky and the Brain, they go to stores called Zainybrain, they have alternative bands called Cerebral Fix, Bad Brains and Spinal Tap, and I don't know if they know anything about neurosciences, but the public has embraced a dreaming is a brain process. We know now that children who develop reading problems or dyslexia have different brains than those who do not. We know that people, who I work with a lot, PTSD, post-Gulf War, the Vietnam and Korean Wars, their brains have changed because they have witnessed a catastrophic event. We also know that now there are some medications that are very refined. We know that there are about 14 receptors just for one neurotransmitter, serotonin, the mysterious chemical that plays a role in mood, depression and anxiety, and we can pinpoint these receptors much better.
accepting that the brain constitutes a major aspect of who we are. Evolution has placed the brain in a very critical position. It's the only organ that sustains our own existence, and because of its importance it has been completely surrounded by a protective tissue, the skull. Is the brain the source of all behavior? Well we think so.
next millennium, and this is an opportunity for me to introduce to you my two graduate students, Amy and Terry, and I hope there are some radiologists in this group who are going to see some pathology in this concepts about the brain and how will they relate to society? I think that what's going to happen is that we're going to reinvent how we perceive ourselves. We're going to go away from this dualism based on a mind/body dichotomy, and brain based explanations Nobody is surprised any more if they pick up a newspaper and find out that truancy has a biological component. That would have been outrageous 20 or 30 years ago. There will be no distinction made between medical illnesses and mental illnesses. Most, if not all, mental illnesses have Think about the stigma that we are living under. Think about calling into work for one moment and over the phone you say I can't come into work today, I have a mental illness. Think about filling out a job application where it says health and you say I had a bout with mental illness but I got over it. We don't treat mental illness the same way we deal with pneumonia, but I'm suggesting to you in the future schizophrenia will be dealt with just as if somebody had pneumonia. Personality and mental illness will be understood as being both related to brain processes, and it will be okay to call in sick The policy implication is that we have to overcome our two-tier insurance system where we have medical illnesses and we have mental illnesses. If they're all biological illnesses, then we should have one health plan for both types of illnesses. There will be no differences in the health coverage on view the insanity defense. There will be more appropriate biological models of free will and responsibility. The Mcnaghten rule and the American Law Institute rules of responsibility and free will are outdated. I think there will be reform in terms of how we accept and think about responsibility.
We will accept, and we already have, that in the brain hardware as well as software is always changing. Just by me speaking to you I hope that something will change in your hardware and software chemically so you will remember the things that we're telling you today. This becomes very obvious by seeing somebody who goes through a catastrophic event with a post-traumatic stress disorder where they're trying to forget a memory when in fact they can't do The public will be very sensitive to brain injury. It will be understood that we are born with a certain number of neurons and that regeneration of neurons is not possible, even though we're working on it. Just as we have adopted seat belts, more and more air bags will appear in the cars to protect the head. There was a study that showed clearly that football and soccer was dangerous to your well-being, and we will have children not punting the ball with their head until they mature developmentally and neurologically. So the public will embrace this concept that the brain is a very important organ and changes will be such that neuroanatomy, neurosciences and the neurological paradigm will be embraced in education starting with elementary school with neuroanatomy, in grammar school students will learn brain behavioral relationships, in high school students will look forward to examining neuroanatomy and having brain autopsies, and in college students will embrace a new science of the brain.
Let's not go back in how we looked at the brain in the past. I would like to say that brain research has had a long past, but a short history. From the beginning of humanity we have been interested in how the brain works. In pre-Columbian times in Peru it was thought, although there is a controversy whether this was a surgery, that by drilling a hole in somebody's head, and this hole was not drilled into a knee cap or into the elbow, but something mysterious was working inside the head, and they knew this and they thought somehow evil spirits could be released and the sunshine could come in and heal. Let's not make those mistakes again, and let's not try to oversimplify what's going on. There is much about brain research we still don't understand.
Here is a more recent picture of a patient with mental illness confined, and I think this is sort of an old virtual reality kind of device where this person is going through sensory deprivation.
when we look back to 1996 we can be proud of how we're dealing with our mental patients and with how we develop educational systems that are in sync with Is there a clarifying question for Dr.
the brain out of context of life style and the mind.
Could we be making the same mistake that you were talking about in your last slide, and that it needs to be put in a platform of the consumer, the way they live, their nutrition all those things rather than DR. ZILLMER: I think that we could make a mistake. Like Dr. Levitt talked about, you can change your brain by changing your environment. So it's much more systemic than just focusing on one organ, but the matter of the fact is that's where the information processing occurs and that's where it even occurs at the cellular level throughout our body, the innate wisdom of the body. I mean that's a big issue right now, and to tag it all to brain you important point. I mean the biology is telling us something about the brain because, as I mentioned before, there are things, molecules, genes present in the brain that exist nowhere else in any other organ many things can modulate the function of the organism, and I think what neuroscientists are saying is that that begins in changes and processes at the molecular and cellular level in the nervous system and then is expressed by the body in some outward Goodwin, Director of the Center on Neuroscience Medical Progress in Society at George Washington University, and the former Director of the National Institute of Health and the National Institute on CENTER ON NEUROSCIENCE MEDICAL PROGRESS IN SOCIETY, reminds me more of my earlier career in philosophy spent the last 30 years in research, but also seeing sick people, people with major depression and manic depression illness, and a lot of my perspectives and biases, if you will, come 30 years as a clinician.
Dr. Zillmer was referring to this, we're faced with myths about mental illness, but I have a slightly different take on how to deal with these myths because I think some of the stigma that the public has is based on concerns the public has which are legitimate and which when we call everything a no- fault illness we're overstating a little bit. It is different to have pneumonia and to have an illness which affects your behavior which affects other people, and that's I think the nub of the education think should be done away with are that it is not definable, that it is not treatable or that everything sort of works for everything with non- specificity, or that they are so pervasive that everyone has a little bit of it and you would break deal of responsibility for this one because we go around saying 22 percent of the population has a mental disorder, and the taxi driver says well if 1 in 5 people have a mental disorder if you covered it In fact, only 9 percent of the population have a disorder with any significant dysfunction. I mean half the population has a respiratory disorder every year, and that doesn't mean we all go off to the doctor every time we have the flu.
The most important one, and I keep hearing this even from psychiatrists and psychologists, is this issue of diagnostic reliability. If you actually look at mental disorders and the percentage of time that independent observers can agree with one another about a diagnosis, independent observers now, that's .72, and for major affective disorders it's .8, and also for schizophrenia it's .8, our two more important subgroups of major disorders.
clinicians to tell a woman whether she has a malignancy based on a mammogram, 67 percent, or the ability to tell from an exercise EKG whether you have a heart problem, 30 percent. That's essentially guesswork. Nobody would think of not covering an exercise EKG in insurance, and nobody would think about covering a mammogram, and yet these are not nearly as precise in terms of reliability as the diagnosis of mental illness. So the old Woody Allen image of mental health, mental illness has to be put don't work or they are sort of non-specific again is based on the older sort of non-specific analytic model which may have been useful in certain cases, but not certainly for the major number of things This is a review that we prepared at NIMH for the Health Care Reform Task Force looking at the efficacy of treatments for the five major mental disorders, schizophrenia, panic disorder, bi-polar or manic depressive illness, obsessive compulsive disorder and major depression, and it took a one-year time frame to look at substantial recovery of function at one year measured by a functional recovery score, not a symptom score, but a functional life function recovery score, and using that same score looking at those studies in the cardiovascular literature, which had done the same thing, we looked at angioplasty, arthrectomy and anti-hypertensive medication. The one-year efficacy rates came in at between 40 to 50 percent, whereas in the five major mental disorders it was 60 to 80 percent.
efficiency basis of the rates of efficiency of treatment you would put the mental illnesses before the cardiovascular illnesses. We used cardiovascular illness as a comparison because the net cost to cardiovascular illness is into the country, that is health care as well as lost productivity equals the net cost of mental disorders. They're both in the range of $160- to $170 billion a year.
treatment, and we could review all the wonderful medications if we had time, but let's remember that one of the striking things that is being demonstrated today about psychosocial treatments, about psychotherapies is that the biggest effect of psychotherapy is now demonstrable in the sickest patients. It's exactly the converse of the common wisdom. The key is of course, unlike the classical trials of psychotherapy alone, is that here we're talking about psychotherapy combined with effective has now been replicated several times. The medication effect, this is neuroleptic medication in schizophrenia, our most difficult to treat and most devastating illness where these by the age often of 20 have essentially disconnected from life to a degree that it's hardly enough to call a normal life see a relapse rate, and this is a one-year follow-up, a relapse rate of nearly 40 percent, 36 percent in one year with medication alone. Now I'm sure that may get a little better with some of the newer medications, Clozerile and Lanthropine, and I think it will get better, but nevertheless this is considered a good result with medication alone.
If you combine that in a random assignment and double blind way with social skill training for the patients you bring it down, and with family therapy for the families focused on expressed emotion and education about the illness and how to deal with it you bring it down, and if you do the two together, the two psychosocial therapies together you in fact reduce the relapse rate by a factor of four-fold. Now there is nothing in psychotherapy alone which I've reviewed extensively that could ever approach least a reduction in half of the relapse rate. Think how stupid it is not to cover this, and this is a very cheap kind of therapy, by the way, and often a lot of it is done in groups, think how stupid it is to risk an at least doubling of your relapse rate with hospital costs of psychiatry averaging $800 a day, when for a few hundred dollars you could be providing this kind of psychotherapy. This is not get on the couch and tell me how you feel about your mother type of therapy. This is very focused here and now and very practical. Unfortunately, a lot of psychiatrists still, I mean people trained many years ago, may not even know how to do these kind of Dr. Levitt and Dr. Zillman said, and this is a study from UCLA looking at patients who have a very severe form of obsessive compulsive disorder. These are people who have to wash their hands six times, and then when they touch the faucet to turn the water off they've got them dirty so they have to wash them again, and often their lives are so limited. They literally cannot get out of their house they're so limited by this repetitive, stereotyped, meaningless, purposeless activity of obsessive compulsive behavior. I'm not talking about obsessive personalities that many of us have who are doing research, and some of us have the disorder actually, using PET scanning where you can actually reduce your color coding, the relative glucose uptake by the brain and therefore the relative metabolism, you can find very specific areas, pre-frontal areas that are highly active in the OCD patient prior to treatment, and they are different from normal controls. Then post-drug treatment you see the big reduction in this, and then you have the same, and this is slightly different slice, but you have the same reduction in the same area produced by behavioral therapy. So the notion that drugs are working biologically and behavior therapy is working in some etherial material way, you know, the final common Now both Dr. Levitt and Dr. Zillmer talked about neuroscience, and what has happened in neuroscience in the last few years has become much more sophisticated about behavior, and it has become much more able for psychologists to find a common for the environment to change the brain in specific ways, has been referred to and the environmental impact on gene expression. This is not Lamarckian genetics. The environment as far as we know does not affect the DNA, but it does affect the rate at which the DNA is expressed in the RNA and therefore converted into proteins, and there is often more room this whole ability to look at the CNS. It's not a soup any more. It's not like the liver, one cell being the same as every other. It's in fact extremely compartmentalized, and therefore to understand integration you need to be able to image the brain and look at the anatomy of thinking and the An increasing behavioral sophistication is developmental neuroscience, which means that you can do very subtle things now to the brain in animals and to the environment and see long lasting effects that started to say about stigma. Stigma is still real and reflected in those three myths. I agree that there is more public understanding of brain behavior, but 40 percent of the public still thinks that depression is a weakness. Now why do they think that? That doesn't mean that 40 percent of the public is just stupid or prejudiced. What it means is that they sense that people who have a behavioral disorder still have some responsibility to do something about it, and that's what we believe in It's one thing to say it's not your fault that you have severe depression, and let's take, for example, the early onset of alcoholism. From what we know the early onset of alcoholism is purely genetic.
There doesn't seem to be any environmental contribution to getting the early onset of alcoholism. The adoption studies show no impact of the environment on whether you have it or you don't have it. So you inherit something that is not your fault, but it's your responsibility to make sure that you abstain from alcohol and that you get help in The quadriplegic has a clear neurological deficit and it's not his fault. But what's the difference between a Chris Reeve, who is doing remarkable things with his life, and some quadriplegic that is sitting in the back ward of a VA hospital feeling sorry for himself for the rest of his life. That's not the quadraplegia that's different. It's something about that person's character, and it's something about all be like every other illness I don't agree with. Brain illnesses that affect complex behaviors are as complex as the behaviors are, and our ethics, our sense of morality about them and the issue of where does free will and responsibility reside, and in fact responsibility and free will we would be in really judging examples where determinism gets away with things and takes over, then of course organized social behaviors, which are dependent upon people assuming responsibility, regardless of their Now one of the things that's most exciting to me as somebody who has studied manic depressive illness is this, that we have noticed that manic depressive illness, which is clearly a genetic illness, as genetic as anything in psychiatry and more genetic than many things in medicine, nevertheless requires activation. It requires psychosocial stress in the beginning of the illness, but once several episodes have been activated, then it goes on automatic pilot and it doesn't require any My colleague, Bob Post, reasoned a number of years ago that this may be analogous to the process of kindling, where if you give a complex system that has many regulatory groups in it, like the brain and particularly the limbic area of the brain, the emotional brain, if you give it repeated stimulation with rest periods in between you can get a larger and larger response each time even though the stimulation doesn't get any larger. It's like the reverse of tolerance. And then eventually you'll get seizures. The critical thing is you can take the stimulation away at a certain point and the brain will have a seizure at the time it remembered and You heard the reference to post-traumatic stress disorder, and this is cellular memory, and now how that cellular memory is being established is being uncovered. The same thing can happen with cocaine, which was mentioned. If you repeatedly take cocaine, and people don't take cocaine continuously, they take it at episodically, and you get a larger and larger response each time, and then you get what John Belushi found, where a dose that you previously cocaine craving one only has to look at a videotape that Chuck O'Brian in Pennsylvania has made. He took an addict who was a cocaine addict, brought him into his research lab and hooked him up. He took a bunch of them, but this was just one example, and he hooked them up to a PET scanner, had them self-administer cocaine, and it got through the ethics committee because they were actively doing it anyway, and then he saw the brain dopamine tree light up, the limbic dopamine cells light up like a Christmas tree. urines and was definitely sure for a whole year they were drug free. He brought them back in, and these were cured, he put them in the lab, hooked them up with the PET scanner, had them open a box and there was a needle and a syringe, the works, and just looking at the works caused the limbic dopamine cells to fire, and it was hard to tell between the real dopamine and the remembered dopamine, the real cocaine and the remembered cocaine. That's the power environmental event working through the transmitters you heard about, through very specific receptors, through G proteins, into cyclinic AMP, and the phosphorylation of various proteins, particularly the phosphorylation of proteins that are involved in early genes that regulate the expression of other genes, and what you have here is a system that can go from the environment through things that take microseconds, milliseconds, seconds and minutes here, things that take hours, and then finally as these converted into growth factors, for example, you get into effects that can take days, months and years.
that goes through the outside of the cell, the cytoplasm, the nucleus and then back into the cytoplasm and to other cells which allows these environmental psychosocial stresses to be translated into real and often permanent changes in protein.
we're very interested in this because we've found now that kindling is age dependent, that is the brain's ability to be kindled diminishes dramatically after the animal, and monkeys and rats have been studied, individual that normal life stresses can trigger this illness and that once triggered goes on for the rest of your life and requires life-long medication, if you in fact block that before it can even happen in a child let's say who never had had the illness yet, but who was generically vulnerable to it, you might prevent the illness from ever developing, and then by the time they grew out of the vulnerability of kindling you take them off the medication and they can spend the rest of their life never having had the illness and never needing life-long medication.
genetic markers because you couldn't ethically do that with what we know now. You wouldn't be able to pick the kids out that accurately. For every child who has a bi-polar parent there is only one out of five chances that that kid will have it himself.
generic markers in particularly the recent replication of the chromosome 18 work, which is a large area and it's going to require a lot of narrowing down, but I would predict, as has been predicted more generically, I would predict that by the end of this decade we will have generic markers for manic depressive illness, and we will be able to try then the experiment of preventive treatment.
Now let me close with a couple of comments about genes, and I'm very glad that both Dr. Levitt and Dr. Zillmer mentioned the complexity of this and the way the public often dichotomizes this into a zero sum gain, you know, the more genetic the explanation the less environmental. That's In fact, if you really want to understand the power of the environment you want to do it in a generically vulnerable population, somebody vulnerable to that environment, because if you look at the effect of the environment on any large group of people the individual generically related differences in those people are so large that it usually washes out the environmental effect. It's very hard to see because there is so much genetic Take, for example, the childhood issue of childhood aggression. If you look at the measurement of adverse adopted home environment, and these are kids who are adopted away so you separate the genetic from the environment, and if you look at the predicted number of the childhood aggressive symptoms, if they have a biological parent with antisocial personality, which has been shown in other studies to have about 67 percent of the variance explained by genetics, if you have a biological parent with antisocial personality what you see is the more adverse the environment the more likely that kid is going to grow up in trouble. Whereas if you don't have a biological parent with antisocial personality the environment doesn't make any difference with respect to this behavior.
important it is to correct an adverse environment you would want to look at the kids who were genetically vulnerable to it and not pretend that there was no such thing or to say that looking at generic differences there was some way to lessen the consequences of the environment. It's exactly the Then my final slide is based on some work that David Reese is doing at GW, who is one of our most gifted psychosocial researchers, and what he's looking at is large cohorts of people where they have identical twins, plain siblings, half siblings and blended families. That's the only benefit I think of with our very high divorce rate is you have a lot of half siblings to study for genetics.
variability coverage, 100 shared genes, 50 percent shared genes in siblings, 25 percent shared genes in half sibs, and no shared in blended families. So he has a tremendous ability to measure what's happening notion we had of you have parents' genes that influenced a particular parenting behavior, and let's say introversion and extroversion, which has been shown to be about 50 percent genetic, that since a child shares about 50 percent of his genes with each parent, and if the child is just like daddy that's because of this. But in fact that's not what happens, and the reason is that behavioral things that you inherit affect other people through the So it's really more like this. A parent's genes influence a parent's behavior, which in turn influences how the child is parented. We know, for example, that children who are born that are very underresponsive and very quiet, laid-back children, and you can pick them out very early in infancy, and any mother who has had several children can tell you these differences, versus a very active, exploratory child, and this has nothing to do with IQ, the child who is very quiet is much more likely to be given books to read at a very early age, whereas the child who is very active will be more likely to be encouraged to do very active things, like sports.
So then somebody comes along who says well the reason this kid is a scholar is because his parents gave him books at an early age, but his parents gave him books at an early age because of the child's temperament that encourage that. So people's genetics has a lot to do with the environment we get, which makes it further complicated to try to separate these two, and there is no way you can separate genes and environment by studying parents and children who forward is to do these studies in so-called generically informative samples where you can eliminate the genetic component, and then you can really see how powerful the environment is.
particularly interested in relating to generic factors in aggression. There are biological factors in aggression and genetic factors in aggression and it became a big, huge controversy, some of which was the way it was handled by the government and by the example, who inherits the tendency to be impulsive and aggressive from a father, and this clearly seems to be a male inheritance pattern, and that kid comes up at the age of two and he kicks his father in the shins, something most kids don't do necessarily, but genetically related and himself have an impulse control problem, an aggression problem, he is much more likely to hit that kid back. That hitting of the child we now know doubles the likelihood that that kid is going to become violent himself. getting the father's genes twice. He's getting it through the DNA, half of which he gets from his father, and he's getting it through the environment because his father is expressing his genetic kid's genetic vulnerability is being massively amplified by the environment, and if you wanted to choose who to intervene with, you wouldn't intervene with every child who is in a bad environment or who has a bad father, you would intervene with those who you could find some clues might be the ones who are thinking, but we have to remember that there is something about the common sense of the public that senses that biological determinism in the case of complex moral human behaviors is a slippery slope MR. SHOSTAK: Thank you, Dr. Goodwin.
question and go directly to Dr. Whitehouse to finish I'm going to also make a prediction to add to Pat's. In exactly that same week several thousand gerontologists will also be coming to Washington, and probably there are about 10 of them that know that the Society for Neuroscientists is meeting at the same time, but they'll find it when they're looking However, that is a bridge to a topic which I think bridges between gerontology and neuroscience, Alzheimer's disease, and I want to talk to you about diagnosis and treatment in the context of just where Fred left us, science and society, exciting science and challenging complex applicable issues.
I also want to thank the Institute, by the way, for allowing me to play with power point in a computer demonstration for the very first time. So we'll see how our exciting science and complex susceptibility. There is a test that is available now called Apolipoprotein E. This test would identify everybody in this room as either being a 2, a 3 or a 4 type, or actually you would be a 2/2 or a 4/4 because you have a gene from each parent, and we audience that are Apolipoprotein E-4 are more at risk for Alzheimer's disease. The questions we'll address in a minute include would you like to know. So we'll talk about the diagnosis of Alzheimer's disease in the context of molecular biological descriptions of outcomes. Are there new therapeutic outcomes in Alzheimer's disease? Absolutely, and in a few weeks you will hear here in Washington that there is a new medicine that is going to be approved for the treatment of Alzheimer's disease. Aricept or E2020 is co-developed by Azi, a Japanese company, and symptoms of Alzheimer's disease, to improve the memory and the attention. You will also be hearing more about attempts to slow the progression of the disease in Alzheimer's disease based on this work that Pat talked about of neuroplasticity. Can we slow the death of nerve cells and actually make a more fundamental impact on this disease than just a symptomatic treatment, not that the news of a better symptomatic treatment will become available is not develop with you both from a scientific and a policy perspective, Apolipoprotein E genetic susceptibility testing and new therapeutic advances.
By the way, those of you who can't see or don't like color, just pull out the single page sheet in your handout which has all these slides on it.
Apolipoprotein E susceptibility, a simple blood test can provide information concerning an increased or a decreased risk of getting Alzheimer's disease, that's to say the use in a pre-symptomatic fashion, or having Alzheimer's disease, that's to say if you walk in the doctor's office, you have a memory problem and you want to know what's causing that memory problem, and of course Alzheimer's disease is So this is available now, and I put quotes around that word because of the question that follows: How much predictive value would you want that to have? Does it increase your risk one percent, a hundred percent, two hundred percent? quite variable, five to ten-fold, and certainly a significant increase in risk, but does it vary depending upon the population you come from, Japanese, African-American or wherever. We don't This test is being marketed in my opinion prematurely because we don't understand what the predictive values are for different populations. For what purposes? There is some evidence that Apolipoprotein E subtyping predicts whether you will respond to a medication. So it might be useful if it were to be used for that purpose. But if it were used by an insurance company to prevent you from having long-term care insurance, you might think that's not a particularly good purpose.
Apolipoprotein E-4, would cost you $195, and most of you perhaps aren't old enough and don't want this information because Medicare currently doesn't cover Would you want to know? Would you want to know what your Apolipoprotein E type was or whether you were a 4 or not? I might mention that if you're an E-2 you might actually have a slightly lower risk of getting Alzheimer's disease than if you were an E-3. So it's not only a question of one being a susceptibility factor, but the other E-2 being a protective factor, and of course companies are trying to develop an understanding of why these different Apolipoprotein Es affect your risk because we would love to develop a medication that would make individuals who are E-4 less at risk by virtue of whatever biology E-2 gives you to protect you.
what transition, oh, that's the gene, it slips in --- to therapies for Alzheimer's disease.
And, as I said, we conceptualize these in two categories. Symptomatic, and this is based on the understanding that you heard from Pat and Eric as well, and in fact everybody had to show their neurotransmitter slide. This neurotransmitter that these medications affect in Alzheimer's disease is called acetylcholine. Tacrine or Cognex has been approved for a number of years. It is marginally effective in a modest number of people, and I switch my adjectives there depending on how I feel about the It's certainly a first drug, and actually this morning in Cleveland I was part of a lecture on the history of Alzheimer's disease and we were talking about the first therapies for syphilis, which included giving patients malaria. Well you have to remember that the first interventions that we develop for the treatment of diseases are often not ideal, and certainly Cognex is a first step.
risky projection and forecast than the scientists emerging in Washington, but I think it will be approved. It has already had an approvable letter, and I think the formal approval will be announced in a matter of several weeks. This will be an incremental improvement for reasons that I don't have time to go into, and it actually will I think dramatically change the care of patients with Alzheimer's disease, at least in the sense that everybody will be scrounging to get on this medication more than they scrounged to get on Cognex.
Cognex and Aricept on the basis of essentially two criteria. They would improve performance on a paper and pencil test of memory and attention and language, and somebody thought the patient was better, either the doctor or the caregiver, and in the case of Aricept there were statistically significant differences in both what we call clinical globe impression of changes and caregiving ratings.
that's exciting, is slowing the progression of the disease by preventing the death of nerve cells. That's what actually happen in Alzheimer's brains that we want to stop, the death of nerve cells, and there are many ideas about how to do that.
particularly germane for approximately half the audience is estrogen. Estrogen both from a basic biological perspective and from epidemiological studies actually has been shown, or there is evidence to suggest that if you take estrogen it slows the onset of the disease or perhaps slows the disease middle of a major study which includes a study of whether estrogen will in fact slow the development of Alzheimer's disease in healthy women who are not yet laboratory and clinically to consider interventions that actually might prevent the death of nerve cells and slow the progression of disease.
questions, social issues and ethical and policy issues relating to genetic diagnostic tests.
this in his talk, is that people are generally very bad at using genetic information. In genetic counseling circumstances you can give people very complex genetic information about whether their child will be affected by a disease, and they basically will round that up to either zero or one, the doctor said my child is going to get it or and the doctor said my child is not going to get it. So there is evidence that not only patients and families, but doctors deal with risk information with great difficulty and differently, too. So we've got to appreciate when we get these numbers that affect our risk for various diseases that we're not rational creatures in dealing with the information and neither susceptibility for Alzheimer's disease is? We already alluded to the insurance company issue, and you know there has been legislation in Washington around this issue and there are recommendations in Europe about preventing insurance companies from getting access to genetic information. This is a very complex topic. Sure we would like to protect ourselves from genetic discrimination. On the other hand, insurance is a vehicle for social policy that allows us to understand risks to a population level and try to plan for them. So it's not to me clear that simply preventing insurance companies from having this information is necessarily the right course of action, although individual discrimination various ages for very important offices. Should we have known Ronald Reagan's Apolipoprotein E type when he was a candidate for office? We know that President Reagan developed Alzheimer's disease at some point during his life and we can speculate in relationship to his tenure in office.
How much is it worth to know this genetic susceptibility information, and I mean that in terms of economics, but also in how much is it worth to society to have this kind of information. It's going to cost us to get this information, it's going to cost to develop this genetic information and just how much is it worth in a rather broad kind of justice sense is how I'm asking the question there.
Finally, social issues and therapeutics. This is the question doctors get: Okay, Aricept, it's a new medication, doctor, how good is it, and would you want your mother to take this drug? they have positive effects, statistically significant effects, but the effects are in terms of quality of life and in terms of daily living rather modest. We set a threshold in this country with the approval of Cognex, and that actually was a fairly healthy, rational, participatory, democratic process of sorts where guidelines were developed and people spoke on behalf of certain criteria, the criteria I already mentioned, objective psychometric tests and some kind said well that wasn't good enough, and in fact the market has determined that Cognex is not very good. It hasn't sold very well. But our expectations about therapies and how we set standards are very improvement from slowing progression of disease? This is a very complex issue. I said to you there are two classes of drugs, one to provide symptomatic benefit and the other to slow progression of disease.
But if we can't measure nerve cells, and maybe we will with some of these powerful imaging techniques in the future, and we can't actually see the nerve cells, how do we know the difference between a drug that provides prolonged symptomatic benefit that extends into the future from one that actually slows the progression of disease in terms of having an effect on the more basic biology, namely, the prevention of death itself. That is actually a big international regulatory issue in not only Alzheimer's disease but other diseases because drug companies would love you to believe that taking their pill will slow the disease rather than just providing around the world there are now pharmaco-economic considerations of a magnitude that governments are concerned about. In other words, you get the drug approved on the basis of the criteria that I've mentioned, and it's demonstrated they have some efficacy, but what about its social value at the Australia was the first country to require companies to not only do scientific studies, the kinds that we're used to doing, but also doing pharmaco-economic studies to demonstrate cost benefit and it's also an issue in Alzheimer's disease because Cognex was on the formulary of some HMOs but not others. So the decision about whether to include it on the formulary or whether to pay for it is actually a much more complicated decision in many ways than just determining whether the FDA should approve the particularly when we talk about slowing the progression of disease. That seems like such a wonderful goal, but is there a point in the illness where we would no longer want to slow the progression major discussions going on in many parts of our society, not the least of which are two Federal Courts, I think the Second and Ninth District, around the issue of the right to die, and is there a point in dementia where somebody is severely demented, cannot feed themselves and cannot recognize their wife of 50 years, where in fact we should be talking not about slowing the progression of disease, but perhaps even accelerating disease or at least considering Alzheimer's disease as a terminal disease in which palliative care approaches would be more It's hard to do this in seven minutes, and particularly the Institute for Alternative Futures This is probably the hardest Foresight Seminar to put together every year, our scientific one. We're futurists and not scientists. So we have to find something we can understand and then we have to find speakers who can communicate to a non-scientific audience as well, and I want to thank our panel for To say that in last day or two as we were pulling this seminar together our minds were blown by all the information would be an understatement. I only wish I could share with you some of the discussions we had in the last two days about the implications of all this, that maybe neuroscientists should be the educators of tomorrow because they're going to understand we're we going to learn, that maybe neuroscientists should be the futurists because they're going to understand how the brain evolves, and that maybe neuroscientists should run the telephone system because they're finally going to Some of the implications are just big. So why don't we just open up the discussion now to you all so that you can engage us or yourselves around other questions around the future of neuroscience and time, but in the far back and work this way.
Pelegrini, and I work for Congresswoman Louise Slaughter, who has been very interested and concerned with genetic testing and the potential for discrimination. I would like to know if any of the panelists see the scientific community developing a stronger advocacy and education role because to some extent you are going to be the ones who have to interpret this information for us and tell us where this information is, unfortunately, that it kind of comes out of a scientific establishment and then the researchers say well there it is and do what you want with it. I think we're going to need a lot more direction, and we're going to end up going through a lot of possibly difficult social upheaval as we deal Human Gene Project as part of the ELSI Program, which I really would speak on behalf of, the Ethical, Legal and Social Issues, and the Human Gene Project is I think mandated to provide a certain amount of grants in this area. Our grant is on the ethics of genetic testing, and we're doing a book and looking at new the scientists to agree that there is information that is valuable for society to consider in the area of Alzheimer's genetics. Molecular biologists, the people who discover these genes and these susceptibilities, don't in general understand population genetics, and there are great dangers of doing a study on a small number of people who happen to come to one center and generalizing to having that be valuable to society as a whole. That's why I said the commercialization of this particular test I think So one is making sure we have something to contribute to society for society to consider in a rational fashion. Then it's to engage society through a process of education, and I think we have to recognize that educational technologies have changed dramatically. We're working on a worldwide web page in a process to educate people through that means because interactive CD/ROMs will offer a tremendous opportunity for people to learn this kind of material. But that is a big challenge, and I would encourage you to support efforts to let scientists, once they have something to say, say it.
that, and I think that's where science is at its best. I don't agree though with some scientists who step out and make kind of value judgments and moral judgments. It's like asking movie stars what politician they support, you know, and that's supposed to mean something. We don't want to get into the philosopher king notion that because somebody is a scientist they have a better sense of what's right and wrong for society than anyone else That's a very tricky area, and we've seen other cultures where scientists have gone over the edge in doing that with some of the early things that were happening in Germany in the '30s where scientists were sort of tempted to be philosopher kings, and they don't have any better moral wisdom than anyone else. Some of them have none at all, and some of them have as much as you would want, but there has been a change in the sense that at least scientific societies are encouraging their members to bear the responsibility of being part of the educational process much more now than it was even 10 years ago. So irrespective of scientists being placed in a position of producing opinion about policy, there is a baseline responsibility that we all feel, and more and more scientists are feeling that and are participating in programs through organized societies that are educating our future generations or current generations. It's not easy to do it with current generations to be honest.
Fred's dogma of the genetics of the parent impacting upon the genetics of the child. So getting beyond the genetics of our generation that in general find it very difficult to synthesize scientific information and get to the future generation is really a critical issue of how do you do that well because there is this prefilter, and I've tried to do this and it's difficult to go through my generation to youngsters who are really excited about hearing So I think that is very important to focus on and figure out ways of doing that much, much better, and scientists now are much more willing to stand up and do those sorts of things.
and I'm very concerned about genetic testing. There is a lesson that we learned, like Fred talked about in the '30s. I wrote a book on sort of the psychological processes of the physicians who made those decisions about people who had mental illness and who were retarded. You probably know this already, but they thought they made the right decision. They had new technologies where they could define mental illness in different ways and identify it better, and they made decisions that were what we consider amoral and the wrong decision. That's why we had the Nuremberg laws and consent forms and all those things that should help us not do the same mistake again, except with genetic testing who is going to be the keeper of that information, and how wrote a book about how the public perceives numbers.
It's very complicated and they don't understand probabilities. It doesn't have to do with intelligence, but it's just that people are not used to understanding randomness and probabilities, and who is going to communicate this to the patient. Maybe the scientists may be the worst person to do So really our technology is on a run-away train, and the information that we're getting from this technology has to be formatted in the right way.
I'm concerned about that, and I don't know the remember, too, that the T-4 program that you just defined that happened in Nazi Germany was very strongly influenced by an eugenics movement that was occurring in this country, and that in fact the eugenics movement has had a lot to do to color the way people do genetic counseling even today, which is on a very non-directive fashion. So there are consequences of this kind of attitude even in our The comment I was going to make was it is great and I celebrate with Pat that scientists are now willing to go out there and participate in the educational process. However, the educational process and philosophies are changing. We can't have scientists just going out and wanting to teach the public as if, and I was guilty of this myself, we have this valuable information that we need to share.
Education is about learning, too. So the scientists have to listen before the lecture to what the public is perceiving and what they need to know and not just assume that, gee, I'm now out in the public educating people and isn't this great that I've got all this knowledge that you guys have got to pay attention to.
feeling that you're just simply transferring information, which is not the right process, versus being part of the educational process.
way, and that's really key because the public really doesn't need any more transfer of information. They can do it, I mean it's available, but it's interactive process that's really key. You know, 10 years ago literally those sorts of things were not of value judgment where scientists would be united in their position, and that is when some voices will encourage us not to get certain kinds of knowledge. They simply prefer ignorance to knowledge because of the potential misuse of knowledge. I don't know any serious scientist who could agree with that, and I think attempts to stifle knowledge because of legitimate concerns about misuse have been destructive, and in looking at history that has been destructive to civilizations who have tried that.
something last week about Alzheimer's disease and nicotine, that actually those who smoke are less susceptible to getting Alzheimer's disease. Is it Morris Tobacco Company and, believe me, we went through a lot of ethical discussions about that. But having accepted the funds with essentially no restrictions, we have been exploring that for two One is that in the brains of patients with Alzheimer's disease the acetylcholine is missing. Nicotinic receptors are stimulated by acetylcholine and nicotinic receptors are reduced in the brains of patients with Alzheimer's disease. Smoking increases receptors and epidemiological studies suggest the possibility, just as with estrogen, that smokers may get less Alzheimer's disease and not just because So there is scientific rationale for it. So you a shot to put nicotine in a test tube and say that nicotine affects amyloy, which it did in this work, which I think is good work, and to jump from that to well, you know, we should all be smoking or taking nicotine patches or chewing nicorette chewing gum of course is not the right interpretation. But there is science to that, and of course we've got to be a little careful because when people read a study and they say it's supported by the Phillip Morris Company they tend to discount that, but I mean there is something in cigarette smoking that's a clue. So we've got to try to maintain a certain sense of equilibrium about that kind of stuff, or why schizophrenics smoke. I mean 90 percent of Online. The first question is very near and dear to my heart. We have a huge megasite on natural medicine and health, and we're not interested in just education, but we're interested in behavior change, and that's where it ultimately, you know, results in positive directions, because many times education as the government delivers it is just more shovelware, as we call it. So there needs to be some coolness about the delivery of what you come up with in terms and what I'm striving for is maybe there is an organization that doesn't exist now that needs to be, you know, a organizer and deliverer of the go-between science and maybe what affects behavior change.
Technology moves out exponentially, and the public is way the hell back here, you know, wondering what in the hell they're going to do. They're caught up in a cacophony of noise every which way and they're scrambling for natural medicines, alternative medicines because they're losing faith in say the just from the Select Committee on Nutrition and Mental Illnesses, and it was McGovern and it was done years back and there was Abram Hoffer and a lot of these people there, and this was a quote from scientific evidence it is sufficiently strong that this nutritional information should be put immediately before the American people. To do otherwise would be irresponsible. The public is then in a position to make informed individual judgments." one-and-a half-inch thick. We've taken those findings and we've republished them. They're out-of- print classics, and we have them in a section on our web site addressing some of those nutritional issues.
their own decisions, and I fear for that direction. I see a big need for a behavior change and conversion of the technology that is way out here and the public that is utilizing it, and not just in America, but fund a lot of this research, but they don't fund natural medicine research because it's not of sort, and maybe it's private, I don't know if it's government, but that there would be a place to do this conversion process? There is dire need for that part of the private sector that you define as perhaps not having an interest in that area, but there are other segments of the private sector that do. There are good companies, there are companies throughout the world that fund research on the value of nutrition in affecting brain growth and development.
In fact, I was at a meeting two weeks ago sponsored by the American Health Foundation in which there were scientists, nutritionists, members of Headstart programs, educators, linguists, economists, et cetera. Studies have been published for 20 or 30 years or 40 years about the benefits of early intervention of nutrition, of safe environments and of positive experiences during critical periods of That information is there, and if you sit down with a person one on one I don't think anyone would deny the fact that good nutrition and a good positive environment for a child two years old is going to have a positive impact on how their brain develops and how they'll end up as adults.
What you're asking for is translating that into policy. That's the difficult part. We're still debating about whether Headstart is good or not, and they can lay out 40, 50 or 100 studies, and there is no doubt about it, and nutrition, the same thing.
what you're talking about is somewhat lip service. There is a huge segment of society that's going out there and playing with acetylcarnatine and cysteine.
The health food stores, they taking it in their own hands. They're looking at the neurotransmitter applications of these, they know about the serotonin and they read about it in Time Magazine, and they're asking their doctors who don't know about the to your question is it's not likely, and particularly in our society, that there is room for one organization or one locus, particularly given so many organizations involved. In fact, I misspoke. I should of course told you that our study was supported by Kraft and not Phillip Morris. Of course country did have a problem when these things slipped between food and drugs because a few years ago when the Congress tried to regulate these products, and this is a $6 billion industry in this country and it is a multi-billion dollar industry around the world.
People takes lots of products to improve their memories and improve their sexual function. Those are the two big topics, and there is a lot of waste of money because there is not a lot of science there.
alternative medicines which is speaking to western medicine and scientific medicine that is missing in what we offer people because people are taking these things for a reason, but they're not taking them with good reason, not that there may not be something in some these traditional Chinese approaches, but they haven't been evaluated, and I think it's very difficult for people to make those decisions on their medicine. Niacin is not. Abram Hoffer did hundreds of studies to indicate the effects of schizophrenia and niacin, you know, and it has been around for years. But that isn't alternative medicine. That's nutrition, and you guy it at a health store.
MR. SHOSTAK: Dave, I'm going to let Dr.
Goodwin respond, and then take the last question.
complicated issues interfacing here. One is the subtlety of a lot of these effects, and Hoffer's work wasn't replicated under more stringent conditions, but that doesn't mean it didn't happen because of maybe hope and expectancy. Sometimes double blind studies miss the expectancy component of it.
One of the arguments that I think we have to be careful about that was argued up here on the Hill about these things that fall between foods and drugs was well let's just turn it all over to the FDA. I think there is a lot of legitimate reason to One, we're dealing with a range of things in which, as you point out, they're not patentable and so nobody has an incentive to spend the average of $360 million per compound to get it through FDA.
areas over the years, and it has usually been a disaster. They, for example, pulled tryptophan from the market quite legitimately 10 years ago. They found out what was wrong with it, and it was a contaminant from the company in Japan that made it. This was research going on in my institute and we're the ones that found it within two years.
Eight years have passed and tryptophan is not back on the market. So it's like once the FDA takes that action and then to get them to untake it.
I rode in an airplane with David Kessler the other day, and I said, David, why is tryptophan still off the market, and he said well the science isn't it.
under a prescription drug, and now it's $40.
MR. ROBERTS: So it is back on the market.
the last year. For a long time it wasn't even available in prescription when the scientific case had already been settled. So regulatory machinery is very sticky and what is done very difficult to get undone. FDA has its plate more than full with drugs where you have huge companies and huge budgets that can allow them to go through that, but all these little things I just don't know where they go. vitamins, like some people want to do, it would simply close down the vitamin industry altogether because there is no vitamin company that has the wherewithal to get double blind control studies. It's not the safety issue, but it's the efficacy thing that hangs it up. It's easier to demonstrate safety or lack of it than it is to demonstrate fundamental. I'm Ebrahim Mayat from NIH. fundamental. First of all, there is a problem with neuroscientific education today, and I'm a neuroscientist myself, in that our education is highly specialized. So when we go to graduate school all we are taught to do is bring our papers, bring our papers, bring our papers. So 99 percent of our energy is spent on churning out those papers. As a result, we are basically ignorant of social issues of knowledge, and I think that neuroscientists, the way they are trained today, will not exactly be in a good position to advise society of future issues of, and First, there must be a good interface between the medical and legal professions, and maybe even between philosophers and scientists, and, secondly, I think neuroscientists should have some idea about social issues, and I think if neuroscientists want to influence education in some way they should think about improving their own education first.
are faculty members. So who wants to start? science education when I was in government, and one of the things we found is that there are no rewards in the scientific establishment for getting outside of that narrow focus of publishing data and writing grants. Even the prizes that are out there are prizes for science and not for science citizenship. So even scientific societies could begin to change that. They could start giving awards for scientific citizenship that would match their awards they give for the actual science itself. Government could do that with science education grants that are a little more imaginative than what is coming out of NSF today, which are mostly more curricula development by people in the education establishment and not by It's a very huge problem. Most scientists are not equipped even to play their legitimate scientific role in the interface between science and policy. We are in an ivory tower, and part of it is of our own construction, and I think your point is scientists are willing to change their environment, and there are some examples of that. When scientists within a discipline, and neuroscience is a very broad discipline when you consider it ranges from understanding genes and genetics to understanding network and chaos theory. There is not quite any other biologically linked discipline that spans that place across that whole spectrum naturally between scientists that's how they educate each other. So when you have a center that contains cognitive biologists, psychologists, psychiatrists, neurologists, developmental biologists and molecular and cellular biologists and they see each other and they talk to each other and they think about things in a much more integrated way, that will I think eventually evolve into something that you're hoping to see because they become part of the education process. They themselves now have to learn about to educate and how to become educated in a much broader think we're moving ahead on this issue, and I think it's true for every discipline, whether you're a physicist or a neuroscientist or a psychologist. You see that information of schools where we've moved multidisciplinary approaches to transdisciplinary approaches where different disciplines are learning from each other. You see that information of schools, like schools of engineering that physicists, sociologists, anthropologists and psychologists. I just came back from the Max Paunk(?) Institute in Munich for Psychiatry, and they have a whole hospital that is totally integrated with neurologists, psychiatrists, psychologists and neuropsychologists.
It's completely integrated and not just pro forma.
that the important questions that are going to be asked in the future are going to come out of that kind of environment. That's really the entry to making anything significant. So the old people who are just going to sit in one office and come up with ideas that are not related to anything else, those ideas won't be funded, they won't be published and people won't care about them any more.
So you're absolutely right, and that's why I came here actually, to hear other speakers and your questions so I could be in touch maybe with the bigger picture of what's going on out there.
The next seminar is tentatively scheduled for December 4th hopefully right back in here, and it listening, thank you to our speakers, and we'll see Innovations in Pharmaceutical Science: Breakthroughs in Neuroscience concluded at 2:07 p.m. . . .

Source: http://www.altfutures.org/pubs/ForesightSeminars/1996InnovationsPharmaceuticalSciencetranscript.pdf