5 Kohout,J., Wicherski, M. and Pion, G. (1991) Characteristics of Graduate Departments of Psychology: 1988-89, Office of Demographic, Employment and Educational Research, American PsychologicalAssociation 6 National ScienceFoundation (1990) Women and Minorities in Science and Engineering, pp. 90-301, National Science Foundation 7 Marshall, L. H. (1979) Exp. Neurol. 64, 1-32 8 Breneman, H. R. and Youn, T. I. K. (1988) Academic Labor Markets and Careers, Falmer Press 9 Bowen,W. G. and Sosa,J. A. (1989) Prospects for Faculty in the Arts and Sciences, A Study of Factors Affecting Demand and Supply, 1987-2012, Princeton UniversityPress 10 Bowen,H. R. and Schuster,J. H. (1988)American Professors: A National Resource Imperiled, Oxford UniversityPress 11 Brush,S. G. (1991) Am. Sci. 79, 404-419 12 EI-Khawas,E. (1989) Campus Trends 1989 (Report No. 78), Higher EducationPanel, American Council on Education 13 Gomberg, I. L. and Atelsek, F. J. (1983) Neuroscience
Personnel and Training (Report No. 57), Higher Education
Panel, American Council on Education 14 Hall, R. M. (1982) The Classroom Climate: A Chilly One For Women? Project on the Status and Education of Women, Association of American Colleges 15 Hill, S. (1991) Science and Engineering Doctorates: 1960-1990, National ScienceFoundation 16 Lane, M. J. (1988) Eng. Educ. May, 750-755 17 Lewis,R. (1990) The Scientist4, 24-31 18 Thurgood, D. H. and Weinman, J. M. (1991) Summary Report 1990: Doctorate Recipients from the United States Universities, National Academy Press 19 Wilkinson,R. K. (1990)Scienceand Engineering Personnel: A National Overview, National ScienceFoundation 20 Widnall, S. E. (1988) Science 241, 1740-1745 21 Bloom,F. E.and Randolph, M. A., eds (1990) Funding Health Sciences Research; A Strategy to Restore Balance, National Academy Press 22 Bloom, F. E. (1992) Trends Neurosci. 15, 383-386
Acknowledgements We thankRose Sherickfor assistance with dataanalysisand Beth Vojta for assistancein the preparation of the manuscript.
Trainingneurosdentistsfor the 21st century Floyd E. Bloom Maintaining the highest possible level of talented researchers relies critically on the at~'lity to recruit, train and retain the best young students to the neurosciences. This arbde addresses the need for trainers to look beyond technical skills, on which research training convenOonally concentrates, to some para-scientific skills that may help assuresurvival during the apparently perennial periods of scarce resources.
The 21st century is less than a decade away, and the neuroscience doctorates to be awarded in the class of 2001 wilt be graduating from high school this June, assuming four years of college and five years of graduate training. Our first job is to convince them to go to college, a second to major in something that will be accepted as suitable preliminary education by departments and programs of neuroscience, and a third to recruit them to our particular field. I see the field of neurosciences as quite broad, including virtually any activity that contributes to an understanding of the biological basis of mental activity, regardless of species, in health or disease. In this article I will offer my views of the requirements we must face to recruit students and to nurture their growth into successful neuroscientists. The points I want to make will be limited to three: 'Why do we need to train more neuroscientists when grants are already so hard to get?', 'What do we need to teach them about neuroscience?' and 'What else do we need to teach them about doing science generally?' Why do we need to train more neuroscientists? I chaired a committee of the Institute of Medicine that worked between May 1988 and November 1990. This effort was commissioned to compile an analysis of funding sources for research projects, training, facilities and equipment by all federal and
Based on an address to the Association of Neuroscience Departments and Programs (ANDP), 15 April 1991, Arlington, VA, USA. TINS, VoI. 15, No. 10, 1992
non-federal research sponsors. The committee was directed to develop a coordinated set of funding policies to restore balance among these four components of the research enterprise in order to ensure optimal use of whatever the research budget may become, and to sustain the most vigorous health research enterprise possible. When that report 1 was released, one of its several conclusions for health-related research, generally, was recognition of the continual need for new scientists and for retaining those already trained in the research system. The committee viewed this need as so important that it recommended that even if there were no new funds for research, training, under existing and newly recommended mechanisms of training support, should be gradually expanded by re-allocating funds from research projects by 0.20% of the budget annually, to rise from the present 4.2% in the fiscal year (FY) 1991 to 5.75% in FY 1995 and eventually to 6.75% in FY 2000. Although this zero-based decision was never even remotely a matter of choice for implementation, many senior scientists disagreed, saying when grants were already scarce, increased training was foolish and unnecessary. However, the committee took the position that it was necessary to consider the longer view, namely the development of scientific personnel from now until the first quarter of the 21st century, and that unless some significant actions were taken immediately, there would be a serious shortage in US scientific personnel that would threaten our ability to prepare for the scientific challenges of the 21st century. According to data from several sources within the US, the personnel shortfall will arise for a number of reasons. In the next 15 years, many of the individuals who conceived the ideas that have revolutionized health sciences research will be retiring. Neglect in recruiting, training and retaining their replacements will inevitably lead to a decline in research capacity, not just for the US, but perhaps
© 1992, Elsev,erSciencePubhshers Ltd, (UK)
FloydE. Bloomis at the Deptof Neuropharmacology, TheScrippsResearch Institute, LaJolla, CA92037, USA.
383
more globally, although no good personnel estimates exist for other countries. Accurately assessing the magnitude and timing of an impending personnel shortage depends upon a variety of factors. Growth of scientific employment in academia, government and the private sector is tied closely to the economic health of the nation. As the post World War II 'baby boomers' grow older, their retirement rate will be compounded by an expected higher death rate among the more elderly scientist population. The composition of the future health scientist workforce will also be affected by changing demographics in age, gender, ethnicity and immigration patterns, as well as by the quality and career attraction of scientific training. As mentors we cannot also be economic tyrants, nor assure a continuous equilibrium between job opportunity and scientific qualifications. Nevertheless, some data are pretty solid in the US picture. The current national data indicate that the number of high school graduates is expected to decline by 12% between 1988 and 1992, and to remain low until at least 1994, when the grandchildren of the baby boomers will complete their secondary education. The consequences of this demographic shift for the US are that there will be declining numbers of undergraduate students in US colleges at least until 1998, at exactly the time when the increasing retirement rates will deplete the ranks of the university faculty. Given these trends, what are the chances for recruiting students to scientific research careers? Unfortunately not good, at least for science generally*. A recent study by the US Congressional Office of Technology Assessment indicated that if one took an average 4000 students in the ninth grade (aged 14-16 years) today, only 500 would have adequate math and science training to consider admission to a science or engineering college curriculum. While women were equal in number to men at this point, of the 500 entering college, only 40 of the 250 women and 140 of the 250 men would actually select a science or engineering major, and only 66 of the 500 would actually complete that science major and become eligible for admission to graduate or medical school. These trends for health sciences research and education are ominous, but not the whole story in this dynamic issue, as our report tried to document. Given these general personnel trends, and the current intensive competition for recruitment of the outstanding graduate students by your neuroscience departments, the future is hard to predict without frequent samplings of the field and its personnel. Solid current data are required to define current academic talent needs and employment opportunities. What is the age spectrum of our membership and faculties? How many will be retiring, and when? How many are in training? How long do our neuroscientists last in the grant game?
What are the prospects for neuroscience employment in undergraduate teaching, in biotechnology, or in a long-term clinical research enterprise? How many ways are there to stay active and contribute without an investigator-initiated research grant? Can we predict what we need to teach them about neuroscience? In 1970, the year in which the Society for Neuroscience completed its organization and began to plan for its first annual meeting, Francis O. Schmitt, then Director of the Neurosciences Research Program, which he himself described as 'an international inter-university organization for the stimulation of advance in neuroscience', wrote an article for Nature 2 entitled 'Promising trends in neuroscience'. Among the five main trends he called to the reader's attention were these three:
(1) The properties of membranes: the biophysical properties of the lipids, and their surface glycoproteins; the molecular basis for selective permeability to Na ÷ and K+. (2) Neuroplasmic dynamics and synapses: the properties of axoplasmic transport and the chemicomechanical basis for this transportation; the possibility that the six then likely neurotransmitters might grow to as many as twelve; the idea that drugs such as tranquilizers, antidepressants and psychotomimetics may interact at particular synaptic sites and thus represent solid tools for analysis of synaptic function; the importance of the first intravesicular protein, chromogranin A; the importance of the (then the only) intracellular second messenger cAMP; the possibility that dynamic responses to synaptic activity were likely to lead to changes in turnover of important synthetic enzymes and even to the regulation of selective RNAs as a permanent response to the activity. (3) Neurogenetics and neurogenesis: the then initial work by Seymour Benzer, Sydney Brenner and Sy Levinthal to capitalize on the study of neuronal systems of very small organisms to link genes and neuronal function; the use of mutant mice, like reeler, to link abnormalities in genes to abnormalities in neuronal development and brain function; the use of neuronal tissue culture; the possibility that cloned cell lines could be derived from neuroblastoma cells.
It was quite impressive to read this list some 20 years later and to see how well Schmitt had read the road ahead. And yet, there was nothing there about the use of axoplasmic transport to determine intricate neuronal circuitry, the development of tools to define new transmitters, the possibility of other second messengers, the multiplicity of ionic channels, the multifarious roles of Caz÷, the development of the in vitro brain slice, or the explosion of molecular biology methods, to mention just a few items that were then just around the corner. I mention the good hits and the few misses simply to *A recent study of the ANDP, 1991, suggests that neuroscience emphasize that it will almost certainly be impossible may still be drawing a good share of the needed new blood despite the general personnel trends. Spear, L. (1992) 1990- to form a fixed base of promising trends. To me, this means that we should view any predictions with 1991 Survey of Neuroscience Training Programs, ANDP.
384
TINS, VoL 15, No. 10, 1992
caution, and let the data and the flow of science refine them, and that we do our monitoring and refining of the teaching content often. If we are successful in problem solving today, there will only be better problems to solve tomorrow. Let's look at training needs from the interdisciplinary perspective mentioned earlier. If I were to try to define for you the minimum skills I would like to see in your students when they come to me for postdoctoral collaboration, I would ask only that they have a basic understanding - that is, an understanding of the advantages, disadvantages and inherent limitations - of the eight classic strategies of modern neuroscience. To lighten our intellectual load for a moment, let me quickly define them lightheartedly before going on to conclude. The first three 'classic' techniques were the methods exploited by our neuroscience pioneers: 'wire and fire' (electrophysiologists who stimulated and recorded the activity of single or groups of neurons); 'cook and look' (histochemical methods that revealed the cytological and ultrastructural elements of the nervous system); 'age and gauge' (development and aging as natural perturbations that refined measurements of choice). My entry into CNS research in the mid-1960s saw two more methods added to the mainstream: 'sap and map' (the biochemical documentation of cellular microheterogeneity) and 'spritz and bitch' (a means to simulate the release of putative neurotransmitters and drugs, which could then act at their receptors, by local microadministration methods; 'bitch' implies the contentious and disputative interpretation of the data acquired and often the personalities of those who selected the method). In our modern era, three complementary strategies hold sway: 'grind and bind' (ligand displacement methods to define receptors and their subtypes on brain membrane fragments or sections of tissues); 'burn and turn' (the combining of brain lesions, drug injections and behavioral methods to assess the dynamic up-and-down regulation of receptors in the intact animal); 'clone and moan' (the application of recombinant DNA technologies to identify and sequence brain genes, prepare transgenic animals or gene knockouts as disease models; 'moan' implies the frequency with which genes isolated from one region for one reason turn out to have similarity to genes already identified from other cells for other reasons). In my humble opinion, two new strategies are surely ready to be added to the list: 'patch and match' ('patching', or patch clamping, whole cells or isolated membranes, to match the properties of their responses with known ion channels and transductive mechanisms); 'do and view' (non-invasive imaging methods like positron emission tomography, single positron emission computed tomography and magnetic source imaging to reveal the brain engaged in cognitive tasks). Can we teach them to survive as scientists? The term 'mentor' is used quite a lot by trainers, but I did not understand its origins fully until they TINS, Vol. 15, No. 10, 1992
were explained to me by Bob Levine of Yale University: the first Mentor, or at least the one for whom the term was coined, was the friend to whom Odysseus entrusted the education of his son Telemachus and the keeping of his household during his 20-year journey to Troy - with an emphasis in this case of the long-term responsibility of the mentor to the 'mentee'. More than 50 years ago, the educatorphilosopher Laszlo Moholy-Nagy 3 made this point the greatest problem in education today is to teach students to think in terms of our own time and to give them a comprehensive picture of the world around us. According to the views of another respected thinker, Ortega y Gassett4, life consists of giving up the state of availability (by which the writer meant available options). Availability is the characteristic of youth facing maturity: in youth nothing is determined and nothing is irrevocable. Feelingthat one is everything potentially, one can easily assume that one is everything actually. The growing insecurity of existence proceeds to eliminate possibilities and leads to maturity. But try to picture a youth with conditions of extreme security - what will happen? Probably the youth will remain a youth, his tendency to remain available will be flattered, encouraged and finally fixed. In the remainder of life will not be found a moment of painful effort. What could have been destiny may degenerate into a series of hobbies. Effort is only effort when it begins to hurt. Between these two extremes of high security and gain with pain lies a middle ground we may find more fruitful for our younger colleagues' development. We must give them a realistic perception of the world in which they will have to exist, and be certain that they are aware of the risks that lie ahead. We must also be sure that our students understand how governmental and foundation research budgets come to be, how scientific policies are developed, and what the role and responsibilities of scientists in that process are, as well as what they might be. This basic set of skills I am talking about here could be termed 'Survival Skills'. In starkest overview it means understanding what the public wishes to support and finding ways to ask your questions within a suitable context of that opportunity. For many years there has been strong public interest in health, nutrition and environment. Currently, we have gained public awareness of the brain and behavior thanks in large measure to the enactment of the resolution creating the 'Decade of the Brain'. However, according to some observers, the public's understanding of science is for the most part too limited to justify firm answers to questions about public appreciation of science - especially the kind of appreciation we will require if we are to draw from the public the augmented budgets we will need to bring off the new programs prompted by the Decade of the Brain. The ambivalent attitude of the public to science is extremely fragile. Our 385
chances for success are likely to be improved by connecting the research efforts to health and society, and by more effective communication of our science through the media. An essential element of such efforts is the need to interact effectively with elected officials, as well as with others in the government and in other agencies that support neuroscience research, such as corporate and private sources, and to help them understand the opportunities of science and the need for effective scientific evaluation of proposals for their sponsorship. These are our responsibilities as mentors, and definitely deserve an explicit place in the curriculum of the 21st century. Five other para-scientific activities, 'advanced survival skills', if you like, should in my view also be explicitly included in the educational agenda for the decade ahead. Problem selection. One of the least discussed and most essential traits to be learned by the young scientist is the ability to define what is important to do among all of the things that are do-able today, and what is so important to be done that even if the methods to do so do not yet exist, we should try to devise them. We who are fortunate enough to be actively engaged today are blessed with an unequalled technological arsenal to ask good scientific questions with rigorous methods, and to acquire reproducible data in abundance. But picking the questions to be asked, developing a sense of how long to persist in a line of attack before acknowledging futility, and how to move from one level of problem solving to another are probably skills that can be learned with practice. Perhaps as a start, formats can be found to make explicit the operational strategies that we erstwhile mentors have implicitly acquired. Time management. As a young faculty appointee or even as a postdoctoral fellow, it is easy to be overwhelmed by the amount of information that flows before you. One could fruitfully spend all day, everyday, in the library, analysing the literature or reading reviews, or preparing lectures and laboratory demonstrations. Time flows very quickly when you are on a limited period of guaranteed support; planning for two years of work means planning by months, and by weeks, and within days. In a field where we can't make money, the only way to show a profit is to use time efficiently. This basic skill of the business world is no less important to the starting scientist. Funds management. The young faculty member successful at grant getting is likely to become responsible for annual budgets worth hundreds of thousands of dollars and several people's careers. Nothing in my research training ever prepared me for this eventuality. The skills to develop budgets for projects you want to begin, and how to live within budgets for projects you have already begun, are definitely teachable, and better done sooner than later. Literature management. The relentless growth of the scientific literature is both a burden and a blessing. It is estimated that if a person reads two 386
papers every day, that at the end of a year they will only be 800 years behind. The .number of new journals and new electronic data surveys make just keeping up with new developments, even in your own sub-field, seem unreasonable. The trend magazines and fax digests that reduce the primary data to someone's synthetic view of a small field may or may not be a satisfactory alternative to your own indepth examination of the literature, depending upon the views of the article's author. In an era when it is deemed irresponsible not to cite others' prior contributions to the field in which you have chosen to work, you are obliged to read, and doomed to lose time if you do. Methods must be found to gain control over the literature and capture the information it contains. The discovery of how to do this will be an essential tool, and not just for neuroscientists. Data management. Two critical issues for our future, already federally mandated for the current US training curriculum, are the need to promote the ethical conduct of science and the obligation to use animals responsibly in our experiments. Both issues remain central activities for all trainers and trainees. Although the term 'data integrity' has ominous connotations, it seems inescapable that certifying the validity of your observations and avoiding selfdelusion are absolute essentials of everyday life in the science of today and from now on. Compared to the rigorous record-keeping instructions given to our colleagues in corporate research, who must follow the 'good lab practice' research methods, scientists in academic research laboratories are given precious little direct instruction in data-keeping, depending on the background, experiences and scrutiny of the laboratory personnel. Development of standards for record-keeping, especially of data that are now primarily collected as electronically stored computer outputs, for record security, and for data interpretation are urgently needed. One final thought: when I was in high school, the thought of becoming a scientist never occurred to me, while obviously it did to many of you. Mentoring is a responsibility, but enthusiasm and the love of discovery can get anyone excited. Let's share what we've experienced.
Selected references 1 Bloom,F. E. and Randolph,M. A., eds (1990) FundingHealth Sciences Research: A Strategy to Restore Balance, National Academy Press 2 Schmitt, F. O. (1970) Nature 227, 1006-1008 3 Moholy-Nagy, L. (1947) Vision in Motion, P. Theobald 4 Ortega y Gassett,J. (1968) The Dehumanization of Art and Notes on the Novel, Princeton University Press
Writing for TINS Most of the articles published in Trends in Neurosciences are
specially invited by the editor.
However, unsolicited articles will also be considered for publication. If you wish to write for TINS, please contact the editor, or a member of the Editorial Advisory Board first, with an outline of your intended article. TINS, Vol. 15, No. 10, 1992
Personnel and Training (Report No. 57), Higher Education
Panel, American Council on Education 14 Hall, R. M. (1982) The Classroom Climate: A Chilly One For Women? Project on the Status and Education of Women, Association of American Colleges 15 Hill, S. (1991) Science and Engineering Doctorates: 1960-1990, National ScienceFoundation 16 Lane, M. J. (1988) Eng. Educ. May, 750-755 17 Lewis,R. (1990) The Scientist4, 24-31 18 Thurgood, D. H. and Weinman, J. M. (1991) Summary Report 1990: Doctorate Recipients from the United States Universities, National Academy Press 19 Wilkinson,R. K. (1990)Scienceand Engineering Personnel: A National Overview, National ScienceFoundation 20 Widnall, S. E. (1988) Science 241, 1740-1745 21 Bloom,F. E.and Randolph, M. A., eds (1990) Funding Health Sciences Research; A Strategy to Restore Balance, National Academy Press 22 Bloom, F. E. (1992) Trends Neurosci. 15, 383-386
Acknowledgements We thankRose Sherickfor assistance with dataanalysisand Beth Vojta for assistancein the preparation of the manuscript.
Trainingneurosdentistsfor the 21st century Floyd E. Bloom Maintaining the highest possible level of talented researchers relies critically on the at~'lity to recruit, train and retain the best young students to the neurosciences. This arbde addresses the need for trainers to look beyond technical skills, on which research training convenOonally concentrates, to some para-scientific skills that may help assuresurvival during the apparently perennial periods of scarce resources.
The 21st century is less than a decade away, and the neuroscience doctorates to be awarded in the class of 2001 wilt be graduating from high school this June, assuming four years of college and five years of graduate training. Our first job is to convince them to go to college, a second to major in something that will be accepted as suitable preliminary education by departments and programs of neuroscience, and a third to recruit them to our particular field. I see the field of neurosciences as quite broad, including virtually any activity that contributes to an understanding of the biological basis of mental activity, regardless of species, in health or disease. In this article I will offer my views of the requirements we must face to recruit students and to nurture their growth into successful neuroscientists. The points I want to make will be limited to three: 'Why do we need to train more neuroscientists when grants are already so hard to get?', 'What do we need to teach them about neuroscience?' and 'What else do we need to teach them about doing science generally?' Why do we need to train more neuroscientists? I chaired a committee of the Institute of Medicine that worked between May 1988 and November 1990. This effort was commissioned to compile an analysis of funding sources for research projects, training, facilities and equipment by all federal and
Based on an address to the Association of Neuroscience Departments and Programs (ANDP), 15 April 1991, Arlington, VA, USA. TINS, VoI. 15, No. 10, 1992
non-federal research sponsors. The committee was directed to develop a coordinated set of funding policies to restore balance among these four components of the research enterprise in order to ensure optimal use of whatever the research budget may become, and to sustain the most vigorous health research enterprise possible. When that report 1 was released, one of its several conclusions for health-related research, generally, was recognition of the continual need for new scientists and for retaining those already trained in the research system. The committee viewed this need as so important that it recommended that even if there were no new funds for research, training, under existing and newly recommended mechanisms of training support, should be gradually expanded by re-allocating funds from research projects by 0.20% of the budget annually, to rise from the present 4.2% in the fiscal year (FY) 1991 to 5.75% in FY 1995 and eventually to 6.75% in FY 2000. Although this zero-based decision was never even remotely a matter of choice for implementation, many senior scientists disagreed, saying when grants were already scarce, increased training was foolish and unnecessary. However, the committee took the position that it was necessary to consider the longer view, namely the development of scientific personnel from now until the first quarter of the 21st century, and that unless some significant actions were taken immediately, there would be a serious shortage in US scientific personnel that would threaten our ability to prepare for the scientific challenges of the 21st century. According to data from several sources within the US, the personnel shortfall will arise for a number of reasons. In the next 15 years, many of the individuals who conceived the ideas that have revolutionized health sciences research will be retiring. Neglect in recruiting, training and retaining their replacements will inevitably lead to a decline in research capacity, not just for the US, but perhaps
© 1992, Elsev,erSciencePubhshers Ltd, (UK)
FloydE. Bloomis at the Deptof Neuropharmacology, TheScrippsResearch Institute, LaJolla, CA92037, USA.
383
more globally, although no good personnel estimates exist for other countries. Accurately assessing the magnitude and timing of an impending personnel shortage depends upon a variety of factors. Growth of scientific employment in academia, government and the private sector is tied closely to the economic health of the nation. As the post World War II 'baby boomers' grow older, their retirement rate will be compounded by an expected higher death rate among the more elderly scientist population. The composition of the future health scientist workforce will also be affected by changing demographics in age, gender, ethnicity and immigration patterns, as well as by the quality and career attraction of scientific training. As mentors we cannot also be economic tyrants, nor assure a continuous equilibrium between job opportunity and scientific qualifications. Nevertheless, some data are pretty solid in the US picture. The current national data indicate that the number of high school graduates is expected to decline by 12% between 1988 and 1992, and to remain low until at least 1994, when the grandchildren of the baby boomers will complete their secondary education. The consequences of this demographic shift for the US are that there will be declining numbers of undergraduate students in US colleges at least until 1998, at exactly the time when the increasing retirement rates will deplete the ranks of the university faculty. Given these trends, what are the chances for recruiting students to scientific research careers? Unfortunately not good, at least for science generally*. A recent study by the US Congressional Office of Technology Assessment indicated that if one took an average 4000 students in the ninth grade (aged 14-16 years) today, only 500 would have adequate math and science training to consider admission to a science or engineering college curriculum. While women were equal in number to men at this point, of the 500 entering college, only 40 of the 250 women and 140 of the 250 men would actually select a science or engineering major, and only 66 of the 500 would actually complete that science major and become eligible for admission to graduate or medical school. These trends for health sciences research and education are ominous, but not the whole story in this dynamic issue, as our report tried to document. Given these general personnel trends, and the current intensive competition for recruitment of the outstanding graduate students by your neuroscience departments, the future is hard to predict without frequent samplings of the field and its personnel. Solid current data are required to define current academic talent needs and employment opportunities. What is the age spectrum of our membership and faculties? How many will be retiring, and when? How many are in training? How long do our neuroscientists last in the grant game?
What are the prospects for neuroscience employment in undergraduate teaching, in biotechnology, or in a long-term clinical research enterprise? How many ways are there to stay active and contribute without an investigator-initiated research grant? Can we predict what we need to teach them about neuroscience? In 1970, the year in which the Society for Neuroscience completed its organization and began to plan for its first annual meeting, Francis O. Schmitt, then Director of the Neurosciences Research Program, which he himself described as 'an international inter-university organization for the stimulation of advance in neuroscience', wrote an article for Nature 2 entitled 'Promising trends in neuroscience'. Among the five main trends he called to the reader's attention were these three:
(1) The properties of membranes: the biophysical properties of the lipids, and their surface glycoproteins; the molecular basis for selective permeability to Na ÷ and K+. (2) Neuroplasmic dynamics and synapses: the properties of axoplasmic transport and the chemicomechanical basis for this transportation; the possibility that the six then likely neurotransmitters might grow to as many as twelve; the idea that drugs such as tranquilizers, antidepressants and psychotomimetics may interact at particular synaptic sites and thus represent solid tools for analysis of synaptic function; the importance of the first intravesicular protein, chromogranin A; the importance of the (then the only) intracellular second messenger cAMP; the possibility that dynamic responses to synaptic activity were likely to lead to changes in turnover of important synthetic enzymes and even to the regulation of selective RNAs as a permanent response to the activity. (3) Neurogenetics and neurogenesis: the then initial work by Seymour Benzer, Sydney Brenner and Sy Levinthal to capitalize on the study of neuronal systems of very small organisms to link genes and neuronal function; the use of mutant mice, like reeler, to link abnormalities in genes to abnormalities in neuronal development and brain function; the use of neuronal tissue culture; the possibility that cloned cell lines could be derived from neuroblastoma cells.
It was quite impressive to read this list some 20 years later and to see how well Schmitt had read the road ahead. And yet, there was nothing there about the use of axoplasmic transport to determine intricate neuronal circuitry, the development of tools to define new transmitters, the possibility of other second messengers, the multiplicity of ionic channels, the multifarious roles of Caz÷, the development of the in vitro brain slice, or the explosion of molecular biology methods, to mention just a few items that were then just around the corner. I mention the good hits and the few misses simply to *A recent study of the ANDP, 1991, suggests that neuroscience emphasize that it will almost certainly be impossible may still be drawing a good share of the needed new blood despite the general personnel trends. Spear, L. (1992) 1990- to form a fixed base of promising trends. To me, this means that we should view any predictions with 1991 Survey of Neuroscience Training Programs, ANDP.
384
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caution, and let the data and the flow of science refine them, and that we do our monitoring and refining of the teaching content often. If we are successful in problem solving today, there will only be better problems to solve tomorrow. Let's look at training needs from the interdisciplinary perspective mentioned earlier. If I were to try to define for you the minimum skills I would like to see in your students when they come to me for postdoctoral collaboration, I would ask only that they have a basic understanding - that is, an understanding of the advantages, disadvantages and inherent limitations - of the eight classic strategies of modern neuroscience. To lighten our intellectual load for a moment, let me quickly define them lightheartedly before going on to conclude. The first three 'classic' techniques were the methods exploited by our neuroscience pioneers: 'wire and fire' (electrophysiologists who stimulated and recorded the activity of single or groups of neurons); 'cook and look' (histochemical methods that revealed the cytological and ultrastructural elements of the nervous system); 'age and gauge' (development and aging as natural perturbations that refined measurements of choice). My entry into CNS research in the mid-1960s saw two more methods added to the mainstream: 'sap and map' (the biochemical documentation of cellular microheterogeneity) and 'spritz and bitch' (a means to simulate the release of putative neurotransmitters and drugs, which could then act at their receptors, by local microadministration methods; 'bitch' implies the contentious and disputative interpretation of the data acquired and often the personalities of those who selected the method). In our modern era, three complementary strategies hold sway: 'grind and bind' (ligand displacement methods to define receptors and their subtypes on brain membrane fragments or sections of tissues); 'burn and turn' (the combining of brain lesions, drug injections and behavioral methods to assess the dynamic up-and-down regulation of receptors in the intact animal); 'clone and moan' (the application of recombinant DNA technologies to identify and sequence brain genes, prepare transgenic animals or gene knockouts as disease models; 'moan' implies the frequency with which genes isolated from one region for one reason turn out to have similarity to genes already identified from other cells for other reasons). In my humble opinion, two new strategies are surely ready to be added to the list: 'patch and match' ('patching', or patch clamping, whole cells or isolated membranes, to match the properties of their responses with known ion channels and transductive mechanisms); 'do and view' (non-invasive imaging methods like positron emission tomography, single positron emission computed tomography and magnetic source imaging to reveal the brain engaged in cognitive tasks). Can we teach them to survive as scientists? The term 'mentor' is used quite a lot by trainers, but I did not understand its origins fully until they TINS, Vol. 15, No. 10, 1992
were explained to me by Bob Levine of Yale University: the first Mentor, or at least the one for whom the term was coined, was the friend to whom Odysseus entrusted the education of his son Telemachus and the keeping of his household during his 20-year journey to Troy - with an emphasis in this case of the long-term responsibility of the mentor to the 'mentee'. More than 50 years ago, the educatorphilosopher Laszlo Moholy-Nagy 3 made this point the greatest problem in education today is to teach students to think in terms of our own time and to give them a comprehensive picture of the world around us. According to the views of another respected thinker, Ortega y Gassett4, life consists of giving up the state of availability (by which the writer meant available options). Availability is the characteristic of youth facing maturity: in youth nothing is determined and nothing is irrevocable. Feelingthat one is everything potentially, one can easily assume that one is everything actually. The growing insecurity of existence proceeds to eliminate possibilities and leads to maturity. But try to picture a youth with conditions of extreme security - what will happen? Probably the youth will remain a youth, his tendency to remain available will be flattered, encouraged and finally fixed. In the remainder of life will not be found a moment of painful effort. What could have been destiny may degenerate into a series of hobbies. Effort is only effort when it begins to hurt. Between these two extremes of high security and gain with pain lies a middle ground we may find more fruitful for our younger colleagues' development. We must give them a realistic perception of the world in which they will have to exist, and be certain that they are aware of the risks that lie ahead. We must also be sure that our students understand how governmental and foundation research budgets come to be, how scientific policies are developed, and what the role and responsibilities of scientists in that process are, as well as what they might be. This basic set of skills I am talking about here could be termed 'Survival Skills'. In starkest overview it means understanding what the public wishes to support and finding ways to ask your questions within a suitable context of that opportunity. For many years there has been strong public interest in health, nutrition and environment. Currently, we have gained public awareness of the brain and behavior thanks in large measure to the enactment of the resolution creating the 'Decade of the Brain'. However, according to some observers, the public's understanding of science is for the most part too limited to justify firm answers to questions about public appreciation of science - especially the kind of appreciation we will require if we are to draw from the public the augmented budgets we will need to bring off the new programs prompted by the Decade of the Brain. The ambivalent attitude of the public to science is extremely fragile. Our 385
chances for success are likely to be improved by connecting the research efforts to health and society, and by more effective communication of our science through the media. An essential element of such efforts is the need to interact effectively with elected officials, as well as with others in the government and in other agencies that support neuroscience research, such as corporate and private sources, and to help them understand the opportunities of science and the need for effective scientific evaluation of proposals for their sponsorship. These are our responsibilities as mentors, and definitely deserve an explicit place in the curriculum of the 21st century. Five other para-scientific activities, 'advanced survival skills', if you like, should in my view also be explicitly included in the educational agenda for the decade ahead. Problem selection. One of the least discussed and most essential traits to be learned by the young scientist is the ability to define what is important to do among all of the things that are do-able today, and what is so important to be done that even if the methods to do so do not yet exist, we should try to devise them. We who are fortunate enough to be actively engaged today are blessed with an unequalled technological arsenal to ask good scientific questions with rigorous methods, and to acquire reproducible data in abundance. But picking the questions to be asked, developing a sense of how long to persist in a line of attack before acknowledging futility, and how to move from one level of problem solving to another are probably skills that can be learned with practice. Perhaps as a start, formats can be found to make explicit the operational strategies that we erstwhile mentors have implicitly acquired. Time management. As a young faculty appointee or even as a postdoctoral fellow, it is easy to be overwhelmed by the amount of information that flows before you. One could fruitfully spend all day, everyday, in the library, analysing the literature or reading reviews, or preparing lectures and laboratory demonstrations. Time flows very quickly when you are on a limited period of guaranteed support; planning for two years of work means planning by months, and by weeks, and within days. In a field where we can't make money, the only way to show a profit is to use time efficiently. This basic skill of the business world is no less important to the starting scientist. Funds management. The young faculty member successful at grant getting is likely to become responsible for annual budgets worth hundreds of thousands of dollars and several people's careers. Nothing in my research training ever prepared me for this eventuality. The skills to develop budgets for projects you want to begin, and how to live within budgets for projects you have already begun, are definitely teachable, and better done sooner than later. Literature management. The relentless growth of the scientific literature is both a burden and a blessing. It is estimated that if a person reads two 386
papers every day, that at the end of a year they will only be 800 years behind. The .number of new journals and new electronic data surveys make just keeping up with new developments, even in your own sub-field, seem unreasonable. The trend magazines and fax digests that reduce the primary data to someone's synthetic view of a small field may or may not be a satisfactory alternative to your own indepth examination of the literature, depending upon the views of the article's author. In an era when it is deemed irresponsible not to cite others' prior contributions to the field in which you have chosen to work, you are obliged to read, and doomed to lose time if you do. Methods must be found to gain control over the literature and capture the information it contains. The discovery of how to do this will be an essential tool, and not just for neuroscientists. Data management. Two critical issues for our future, already federally mandated for the current US training curriculum, are the need to promote the ethical conduct of science and the obligation to use animals responsibly in our experiments. Both issues remain central activities for all trainers and trainees. Although the term 'data integrity' has ominous connotations, it seems inescapable that certifying the validity of your observations and avoiding selfdelusion are absolute essentials of everyday life in the science of today and from now on. Compared to the rigorous record-keeping instructions given to our colleagues in corporate research, who must follow the 'good lab practice' research methods, scientists in academic research laboratories are given precious little direct instruction in data-keeping, depending on the background, experiences and scrutiny of the laboratory personnel. Development of standards for record-keeping, especially of data that are now primarily collected as electronically stored computer outputs, for record security, and for data interpretation are urgently needed. One final thought: when I was in high school, the thought of becoming a scientist never occurred to me, while obviously it did to many of you. Mentoring is a responsibility, but enthusiasm and the love of discovery can get anyone excited. Let's share what we've experienced.
Selected references 1 Bloom,F. E. and Randolph,M. A., eds (1990) FundingHealth Sciences Research: A Strategy to Restore Balance, National Academy Press 2 Schmitt, F. O. (1970) Nature 227, 1006-1008 3 Moholy-Nagy, L. (1947) Vision in Motion, P. Theobald 4 Ortega y Gassett,J. (1968) The Dehumanization of Art and Notes on the Novel, Princeton University Press
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