Page images

much smaller numbers of relatively enormous cells many of which are individually re-identifiable to researchers. And yet these extraordinary cells function electrically and chemically in ways that are very similar to those of mammals. Neural circuit design principles, and mechanisms by which properly co-ordinated impulse patterns can be generated in nerve networks have come from studies of such systems. These studies suggest simplified and efficient ways to get the needed answers from mammalian nervous systems.


The problem: When a nerve has been cut, what clues guide regrowth? Why does the cut off portion die and fail to reconnect? Why do damaged parts of the brain and spinal cord in higher animals and human beings repair themselves so rarely, if at all.

Developing neurons in many of the model systems can be traced individually, and clues gained about the physical guideposts, and chemical factors that influence proper growth. Many such clues have been gained from studies of simpler animals such as insects, crustaceans, mollusks, amphibia (such as frogs), reptiles and fish. These animals seem to have retained the ability to reconnect damaged nerves and to repair or even replace destroyed nervous system components. Amongst the lower vertebrates, the goldfish has retained the capacity to regenerate its spinal cord, and replace lost nerve cells. The differences in these capabilities between mammals and the simpler animals likely holds keys to understanding why human repair/replacement is so limited, and what might be done about it.


The problem: How do brains learn? What happens in nerve cells when an animal learns to ignore a monotonous stimulus, to associate different stimuli, to "remember"?

It is now very clear that many animals can learn in ways that are similar or identical to man. It is also clear that for simple kinds of learning at least, the brain cell changes that come about because of learning take place at the site where nerve cells communicate with one another. The problem for scientists therefore becomes one of finding the most efficient experimental situation in which to study these nerve cell changes. There are many examples of simple animals with extraordinarily large and identifiable nerve cells including fishes, insects and mollusks. In these cases it has proven possible to probe the site and mechanisms of these changes.


The questions: What nerve cell or nerve membrane defects cause epileptic seizures in brain? Why do certain substances and stimuli initiate nervous system convulsions? What properties must drugs have to prevent the development of uncontrolled nervous system seizures?

Often seizure like activity can be developed in a controlled way in isolated nervous systems or nerve cells of very simple animals such as crustaceans (e.8. crabs) and mollusks (e.8. snails and slugs) by exposing them to convulsive drugs or reagents. Then the electrical and chemical causes of the disturbances can be sought directly. Clues about the action of convulsive drugs upon the excitability and stability of nerve cell membranes can and have been helpful in interpreting the similar effects seen in the nerve cells of mammals.

(A human disease that results in severe muscle weakness)

The questions: Why do the nerves and muscles of affected individuals function abnormally? What can be done about it?

The basic cause of the problem has now been worked out. The disease is caused by antibody destruction of the receptor molecules that serve as the chemical link from nerve to muscle. The explanation of the disease rests squarely upon (1) the basic understanding of nerve to muscle transmission derived from studies of frog material, and (11) the discovery and extensive use of the special receptor molecules on electric ray tissue that contain the same substances found in humans but occur on the elctric organ of rays in concentrations that are thousands of times greater than found in any mammal.

The eventual cure will almost certainly depend upon similar model systems for knowledge of how to use specific molecules to repair or block the damage.


The problem: Why do defects of genetic and developmental origin occur? What are the steps that link genes on chromosomes to the development of normal or abnormal nervous system structures?

It is often possible in simple systems having smaller numbers of large, re-identifiable nerve cells, to trace the growth of specific brain cells as they develop from their origin in the embryo into the juvenile and adult animal. For instance, lately

it has been found possible to put a distinctive, colored label into a particular cell in an insect embryo and then observe the subsequent locations of the chain of labelled nerve cells as they "bud off" from the "parent cell". This reveals a surprising amount about the series of events that control proper nervous system growth. Should a defect occur under these circumstances, it may be possible to determine where and why it happened. Since it is clear that cell growth and early developmental events follow similar rules, and depend upon genes in the same way in all animals, man can learn much from such studies.

Mr. Brown. All right, Dr. Willows. I find this extremely stimulating and exciting. It certainly is ammunition to provide a defense for research in biological science, but you need to go one step further, so I am going to ask you a couple of questions here.

The bulk of research in all the biological sciences, up to at least today, I presume, has gone on at universities and has been supported as part of the educational process of universities; is that correct?

Dr. Willows. That is correct.

Mr. Brown. The obvious question that a Congressman is going to ask is why can't we continue that route and confine the role of the Federal Government to general support for university education instead of finding additional ways of pumping money into this particular field of admittedly exciting and useful research?

What is there about the Foundation that says that it has to be the vehicle by which we support this research?

Dr. WILLOWS. My first suggestion is that it is the best possible investment of public money that one can imagine.

Mr. Brown. How about this question.

Assuming that this the best possible investment of Federal money, we have many agencies distributing Federal money, including a very large one in the Department of Health, Education, and Welfare, called the National Institutes of Health.

Is there a peculiar role which distinguishes the NSF from what is to the lay person a more obvious role for the National Institutes of Health in the research work that they are doing?

Dr. Willows. Yes, indeed there is.

Mr. Brown. You understand, I know the answers to all these questions.

Dr. WILLOWS. I do, too.

At the end of my presentation, I mentioned the feeling that the Foundation's special role, in all of this, is to develop new tools and better ways of tackling basic research problems. This is something which is special to the Foundation. That is something that the NIH does less of, far less of.

You may be aware that many programs in the NIH are specifically targeted, and, in many cases, research which cannot be supported under the program guidelines that they are left to live with, come to the NSF. There have been a number of examples lately, individual sciences such as the visual sensory sciences field, which are worthy of research but which could not be supported at NIH because of their particular model system approach. They were subsequently given to the NSF for consideration because of its role in being responsible for generating new tools and better ways of tackling problems which are a little further down the line from direct medical application. That is one suggestion.

Mr. Brown. If you wish to comment, feel free to, Dr. Atkinson.

Dr. ATKINSON. Mr. Brown, I want to comment on Dr. Willows' presentation. He is a first-rate scientist, one of the rotators who come to work for NSF for a year or two, who are clearly involved in their science, and who are also still involved in the bureaucratic process of funding grants. The rotators are among the great assets of the Foundation, and I think his testimony demonstrates their valuable contribution.


Mr. Brown. Dr. Ritter, do you want to ask a question ?
Dr. RITTER. Yes.

You know, one of the conclusions you can draw from Dr. Willow's testimony is that that squid has a lot of nerve.

I guess I am fascinated and very very much interested in the use of language to communicate scientific and technological merit, purpose, achievement and I find it is a difficult arena.

I am personally very interested in the idea of comparing risk and trying to get it down to common terminology that all people can understand and I find that is my most difficult point. I am not interested in assessing risks, the absolute value of which is such and such times 10 to the minus 6, but just presenting information to people who are concerned, sometimes afraid.

I think this is where we are at and this has a real counterpart in the funding of the social sciences. I have tried to go through the GAO report while listening to your most fascinating presentation, and, you know, that title is part of the problem. If that title could have been, for example, “Better Understanding of Central Nervous System Functions in Humans by Studying the Main Nerve of a,” whatever a squid is. What is it? It is a cephalopod. First of all, no one is going to know what a cephalopod is. It is going to sound like some of these terms in the physical sciences which people let drop because they can't understand it. But also, it is an effort made to get at the basic reason that the project was done.

The basic reason the project is done is to understand more about our own human behavior and our own central nervous system. Now, as I go through the GAO report, there is a very marked problem with that, in that NSF has project summaries and titles which are really trying to serve two purposes. One is to communicate to the scientific community, and I don't think we can avoid that. I think that is very important and that is really NSF's basic role, to develop the science. But it is also now being increasingly used by the general public and different institutions within the general public who are more interested in the whys and wherefores of their tax money being spent than they are in communicating the hard-nose scientific data and information to be gleaned from a project.

I think until that dicotomy is dealt with effectively, we are going to run into continued problems. Social sciences, as opposed to some of these more physical activities will always, as the GÃO report has it, bring some difficulties because of the nature of the people's views, in social sciences. But in these situations we shouldn't have any problem at all and I think the chairman pointed this out with his concerns about the particular title. I think there are a lot of problems here, including better attention to what nonscientists are going to do with information and how it is communicated to your taxpaying public, which is supporting every single program. NSF has got to do a better job in that regard.

Dr. Willows. I didn't hear a question in this but I think what you said is a clear suggestion of directions we ought to be going.

Mr. RITTER. This information that you are giving us here is essentially, after the fact—and you are talking to, basically the convinced. You are now on the defensive and justifying why we picked up the

« PreviousContinue »