Dr. Willows will give us a glimpse of some of the exciting uses of these organisms in behavioral research. Mr. BROWN. Dr. Willows, I would just like to ask you-in making your presentation, to put yourself in our position and try and communicate as effectively as possible to help meet our problems. Dr. WILLOWs. Mr. Chairman, I have seen the film from the floor debate of last spring; I think I understand the situation, and I will try to provide some of the material that you need. STATEMENT OF DR. DENNIS WILLOWS, DIRECTOR, NEUROBIOLOGY PROGRAM, NSF Dr. WILLOWS. Mr. Chairman, and members of the committee, neurobiology is a new science relative to many of the others that you are familiar with. It has undergone an extraordinary amount of growth over the past decade. The number of people who are practitioners of that science have roughly multiplied by 10. One of the reasons for that is that scientists have moved into the field from a variety of traditional disciplines: from medical sciences, from biological sciences, from physics, chemistry, and psychology. And you may wonder, why the influx? Why the growth? It is simple. It is because of success. There has been an extraordinary amount of success in determining basic relationships between nerve cells and the brain and between the brain and behavior during that period. I think there is the sense among the many people who work in the field that there are some dramatic findings on the very near horizon and they want to be part of them. The influx of scientists from different areas has brought with it also part of the strength of those fields; that is, these people who have moved in from biological and other sciences have brought with them a variety of techniques for tackling a very difficult problem of the brain. We are now free to approach the nervous system from a broad range of different techniques, including some which are model systems. That is to say some people have brought with them the idea that we can use simpler ways to solve hard problems rather than taking the brute force, the direct approach, to problems in the brain. I will elaborate, as we proceed. If I may, I would like to cite, for the record, a number of examples of particularly useful model systems in studying brain-behavior relationships but here, to save time, I will describe, in detail, just a couple of them. Had tax money in the 1930's been committed to supporting a study entitled, "How the Squid Controls Its Jet-Like Escape Behavior," I suspect that there might have been some questions raised, some curious questions raised about why the money was being spent. Indeed, there may have been even articles in the press suggesting, in an entertainment form, that the money might have been spent better other ways. But it is now perfectly clear to those of us in neurological research that that work has enabled the following critically important developments. First, the discovery that the squid has the largest nerve in the animal kingdom. The nerve which permits the jet-like escape response is about the size of a pencil lead in diameter and several inches long. Second, the fact of the existence of that big nerve means that neurobiologists have been permitted-indeed there has been some Nobel Prize winning research done to determine how nerve electricity comes about, how nerve impulses are transmitted along nerves. Where does that lead? That leads, first, to an understanding of a whole variety of central nervous system disorders which we otherwise wouldn't have and, in addition, understanding how anesthetics work, how to make better anesthetics, how nerve toxins work, and an understanding of the actions of the venoms from a variety of snakes and scorpions. They make their actions on the control of electrical activity in nerves. They are now fully understood and, in many cases, can be dealt with rationally. In part, due to that kind of work, but also to a lot of other publicly and privately supported work over the past 30 to 50 years, it has now become very clear-indeed, and this is very important-that the nerve cells of all animals from humans down to and including the lowest forms of life in the animal kingdom, are fundamentally identical in terms of their electrical, chemical, and membrane properties. They are similar enough that we can often solve very difficult human and mammalian nervous system problems by using model systems from these lower animals where the experiments are easier to do. Let me give you some numbers which will emphasize that point. The brain in the human being has on the order of 50 billion neurons, give or take a few depending upon age and other things. The brain of fish has several orders of magnitude fewer cells, around 100 million, and insects have even fewer a million or so. The lowly slug, the marine sea slug-and I will show you an example-has something like 10,000 neurons in its brain. We have come from 50 billion down to 10,000. If we compare cell size, the size of the neurons in the brain, in the human case, they are something of the order of 10 micrometers. That is very small, 20 wavelengths of visible light. It is too small to see. As we go down through the same series of animals, we end up with the slug that has nerve cells 1,000 micrometers in diameter. This is very large, and the message in those numbers is very clear. You can put a million human brain cells inside a single nerve cell of the brain of the slug. That suggests to neuroscientists that if there is a problem which requires studying cellular processes-electrical properties, chemical properties, the connections between cells that regulate behavior-it makes sense to go looking for an animal where those cells are accessible to electrode penetration, to chemical manipulations. Now, my second and last specific example is the unusual contribution to neuroscience made by the marine slug, the bottom animal on that list I mentioned a few moments ago. There are cells which are enormous in the brain of this animal. You can see them with the naked eye. With a low-powered microscope, you can see cells all over the surfaces of these brains, clearly set out from one another and reidentifiable as individuals from animal to animal. Let me show you an example, if I may have the lights off for just a second. This animal is a tropical marine slug. It is about a foot long. It has some interesting behavior, believe it or not. It is capable of swimming, and carrying out a variety of simple acts, but some complex ones as well. It is probably capable of learning simple tasks. But the important thing about it is that if we look at its nervous system and that is what you are seeing now-this is its living nervous system-the nervous system extends from here, over to here, and it is covered with readily visible nerve cells. The brain is all of the orange material and the nerves carrying information out to the periphery of the animal are here, here and other places. But look here at this large globular structure. Each of those spheres is about 1,000 micrometers in diameter, about the size of a dot at the end of a sentence in a typed paragraph. Each of those is a single neuron and fortunately, if you go from animal to animal in that species, you can find those same cells in the same places. What's more, you can record from them, stimulate them. You can dissect them one at a time; that is, reach in with tiny forceps and pick them off the brain, put them into test-tubes, study their chemistry, to learn what they are producing and what they are doing. Needless to say, those same tasks would be very difficult to perform in most other animals. This shows you a recording situation where, in fact, I had the brain immobilized on a platform, in a living animal and was recording, through the black-colored electrodes there are six of them distributed around it. Here, here and here. And each of them is penetrating and recording from a single identified cell, in the brain. Again, that is the kind of opportunity that model systems provide for the study of the wiring, and the chemistry of single brain cells. The results of these kinds of studies have been reported in several published forms, but you may have heard and may have noticed them in the popular press lately. For instance, in the Washington Post in early January, there was a front-page article entitled "Dramatic Strides Being Made in Brain Chemistry." That article pointed out how some new protein materials called "enkephalins" have been found in the mammalian nervous system and are almost certainly going to revolutionize medical treatment and understanding of the human brain because they are thought to control pain and depression, schizophrenia, drug addiction and a variety of derangements of the nervous system. What has been found is where these substances are being produced in the brain. We also know where they act, but we do not know how they act. That is the crux of the matter, and I would suggest to you that given large cells and brains like the models I have just shown you, we have an ideal opportunity to go to look. Scientists in these fields know now that they can explore tough questions about membrane action of the enkephalins using a number of model systems. Finally, let me say that, in the fascinating area of how does the brain learn, there are some extraordinary opportunities for simple system use. You can, in a system like the one I have just described involving the marine slug, record and stimulate from brain cells while an animal is learning a task and find out what changes, in the chemistry, and in the electrical activity of the cells, are going on. It is an unheard of opportunity, at least in these simple terms, and it is likely to make a big difference as to what happens to neuroscience over the next 5 to 10 years. The key role for the NSF, in neuroscience support, has to be to search out and support the development of new materials for research of this kind. It is not good enough to support "more of the same" indefinitely, that is, the same kind of research that has been going on in the field, indefinitely. NSF's particular specialty has been in being free, scientifically free, to find new and better ways to solve difficult problems. We anticipate this extraordinary progresss to continue and with very significant consequences for scientists and non-scientists alike. Thank you. [The prepared statement of Dr. Willows follows:] STATEMENT OF DR. A.O. DENNIS WILLOWS DIRECTOR NEUROBIOLOGY PROGRAM NATIONAL SCIENCE FOUNDATION BEFORE THE SUBCOMMITTEE ON SCIENCE AND TECHNOLOGY Mr. Chairman and Members of the Committee: Neurobiology, the study of the brain mechanisms of behavior is a relatively new science. It has undergone an extraordinary amount of growth in the last ten years with an influx of scientists from physics, chemistry, psychology, biology and medicine. The primary reason for the growth however, is the success that has already been achieved in understanding the relationship between brain and behavior, and further the sense in the minds of many scientists, that there are a number of very important developments on the near horizon. The influx of scientists from diverse scientific fields inco neurobiology has been a major source of strength. It has meant that work has progressed on a very broad front and a variety of techniques and approaches have been used. In particular, it has resulted in the development of a number of simple model systems which have facilitated the study of difficult brain-behavior problems but in experimental circumstances which are very favorable to progress. Let me cite a number of examples for the record and mention two in particular in a little detail: Had tax money been used to support work on "How the squid controls its jet-like escape behavior" by a biologist in the 1930's, it is likely that indignant protest might have resulted, and the matter might well have been reported as a form of entertainment in some of the press. Fortunately, the work was accomplished. Yet it is absolutely clear now, that had this attitude prevailed, and the work been discouraged, the following would not have occurred: (1)The discovery that the squid has the largest nerve in the animal kingdom. (ii)Nobel Prize winning research showing the squid nerve is an ideal model for studies of how nerve electricity and transmission comes about. (111) Development of an understanding of the basis for many nervous system disorders in all animals, humans included. |