Costello, Leslie C. MS, PhD
In this discourse, I will express some critical views that have developed from personal experiences that span a period of 50 years as an academician-scientist and 60 years inclusive of my formal college and graduate education. During that period, major changes have occurred in the education and training of successive generations of young aspiring researchers. These changes have raised significant questions: Have today's biomedical scientists benefited from dramatically different education and training programs and requirements? Are today's scientists equal to, not as well prepared as, or better prepared than those of my generation and earlier? I do not believe that there is any statistical information to arrive at a definitive answer to this question. One can only relate experiences of the past in contrast to experiences of the present. Despite this limitation, a rationally supported and justifiable discourse can be presented, and that is my intent with this article. I would expect that some might agree with the issues and assessments that I offer. Most likely and expectedly, a greater number of individuals will disagree. A contributing factor to this expected outcome is the relatively small population of academician-scientists of my generation who are alive and/or still professionally active. The more contemporary population of researchers will have experienced firsthand neither the educational and training regimen nor the capabilities of their predecessors. The absence of such experiences leads to a natural bias in favor of the contemporary conditions.
The nature of the issues and criticisms I will present requires some disclaimers. First, I believe that there exist many excellent contemporary biomedical researchers. In fact, most biomedical researchers are extremely capable to perform their mission as they were trained to do. While I criticize the contemporary generation of researchers, my criticisms are not directed at their intellect and potential abilities. The criticisms are directed at those who have installed the educational and training programs to which today's student is exposed.
Broad Versus Specialized Graduate Biomedical Education and Training
I do not equate “researcher” with “scientist.” In my view, a researcher is one who can go into a laboratory environment, set up an experiment, perform certain technological procedures, and accumulate and analyze data. The researcher is either not required to or not capable of applying the experiment and results much beyond the limited scope of the immediate relevant area of interest. Much of the contemporary breed of biomedical researchers can be further characterized as “supertechnologists,” who specialize in and focus on technological approaches and procedures to develop the purpose or aim of an experiment. In contrast, in addition to the capabilities of a researcher, the scientist should have an understanding and knowledge of the origin and history of science and of the development and requirements of the scientific method. The scientist should be broadly trained beyond his or her specialty interest so as to possess a comprehensive appreciation of the integrative impact of the specialty. Indeed, that is or should be the intent of the PhD degree (or its equivalent) and of biomedical graduate education and training. I have also employed the category of “academician-scientists” merely to identify those who apply and integrate the role of the scientist in the academic environment and in academic programs.
So, with these definitions in mind, what type of graduates do contemporary biomedical graduate training programs produce? I am quite certain that most graduate and postgraduate training programs would describe themselves as programs that train scientists. However, I would argue (and will present supporting information) that most of today's programs train supertechnologists and researchers. Especially in health sciences programs (as contrasted with arts and sciences programs), few contemporary biomedical graduate programs provide the combined didactic, seminar, and laboratory experiences that are essential to the educational and training development of a true scientist.
If you doubt my assessment, do the following: In a graduate/postgraduate seminar class, ask the students to define the word “science.” I often pose this question, and I rarely obtain a correct response; in fact, I usually receive no response at all. Also ask them to describe the scientific method; describe empirical versus rational approaches; or contrast inductive versus deductive reasoning. In my experience, the responses are likely to be rambling, confused, shaky, or nonexistent.
Finally, ask some questions regarding giants in science or philosophy: “Who was Socrates and what is the Socratic method?” Perhaps this is a little too abstract. A more telling question to ask medical faculty members and graduate/postdoctoral trainees is, “Who is Claude Bernard?” I have asked this question on numerous occasions at various medical centers to audiences dominated by medical school faculty, postdocs, and graduate student trainees. Except for a few senior faculty members, the audience will not have heard of Claude Bernard. This is an astounding revelation. Can you imagine that students who have been exposed to human physiology courses have not heard of Claude Bernard in the context of his extensive research leading to the concept of “homeostasis; the milieu intérieur”? What does it reveal if those on the faculty and in the research and training programs in medical schools and allied medical sciences do not know who is considered to be the “Father of Physiology”?
Even more relevant to this discourse is the contribution of Bernard in pioneering the application of the scientific method (experimentalism) to the development and elucidation of principles to be applied to the understanding and practice of medicine. His book, An Introduction to the Study of Experimental Medicine,1 first published in 1865, revolutionized medicine (and medical/biomedical science). Bernard's book was the initiation of the transformation of medicine from an art to a science, from an empirical basis to a rational basis. As such, Bernard is also considered to be the “Father of Modern Medicine.” Every medical student, every graduate and postgraduate trainee in all of the biological and medical sciences should be required to read Bernard's book, which has long been available in English translation. In addition to its vivid, interesting, and significant descriptions of the application of the scientific approach to medicine, Bernard emphasizes the role, obligations, and responsibilities of the scientist. This alone would define and instill a code of conduct in biomedical graduate students that could lessen the occurrence of many of the contemporary issues of scientific misconduct. Such deficiencies of the graduate/postdoctoral training programs are exacerbated by the failure of contemporary undergraduate biomedical science programs to provide a reasonable meaningful biology background, especially for those aspiring young scientists and clinicians who proceed to a medical, graduate, or postdoctoral training program. (Indeed, this concern should be the subject of a separate in-depth discussion and assessment.)
The above examples represent the absence in contemporary programs of the historical and philosophical perspectives of science. Such deficiencies caused me to introduce a graduate/postgraduate-level course that includes discussions of the evolution and application of the scientific method in the biomedical sciences, as well as the responsibilities, obligations, and dedication of the researcher to the principles of the scientific method. You would be surprised to observe the positive reception and appreciation by the graduate and postgraduate students to the presentation and dialog of the historical and philosophical aspects of science and life. Through such discourse, their minds are opened to issues and questions that otherwise would remain unknown to and unappreciated by them. Is not this the most fundamental purpose of a program that desires to produce the next generation of thinkers and discoverers?
Regrettably, today's biomedical sciences education and training programs assume a different philosophy. Instead of, “The past is prolog from which we can learn,” the new philosophy (purposely or otherwise) is, “The past is irrelevant and teaches us nothing of importance.” Indeed, I submit that in this contemporary environment, the conferring of the doctor of philosophy degree (the leading degree conferred on scientists) borders on being a misrepresentation. The contemporary graduate programs in biomedical sciences are devoid of any meaningful incorporation of historical and philosophical background and of discussions that should be included in a doctor of philosophy degree. I further submit, for these reasons and additional reasons presented below, that a new degree should be considered for the contemporary biomedical science graduate and postgraduate education and training programs. I would suggest that a doctor of technology degree or a doctor of molecular biology degree would be more appropriate. In some cases, the degree would be more accurately provided at the master's rather than the doctorate level. Such would be more representative of the limited and specialized purpose and outcome of the current training programs.
I hasten to add that I do not believe in this type of training for true scientists and academician-scientists. To ensure that students obtain the proper historical and philosophical context and broader implications for their research training, it is more meaningful and preferable to modify the existing graduate training programs to incorporate the necessary didactic experiences that will fill this void. Doing so will require careful consideration in applying meaningful changes and possibly additional program requirements for the trainee.
I have noticed, during the period of 60 years in the realm of biomedical graduate education, another troublesome trend. Although not typical of all graduate/postgraduate trainees, it is evident that, too often, the trainee is engaged in a five-day-per-week, 8 am-5 pm program schedule, after which the labs and offices are vacated. During my PhD training, I and my fellow graduate students were in the laboratory or graduate student office suite or at the library until late evenings, on Saturdays, and even on Sundays when necessary. Moreover, before agreeing to mentor a graduate student, I would advise the candidate that his or her graduate program requirements had to be the highest personal commitment of time and effort, second only to urgent family matters. Is this the prevailing condition today? Consider also that before 1975 or so, the availability of personal computers, copy machines, and other such technological resources did not exist. Obtaining information, performing literature searches, and gaining access to published reports and reprints were tedious, time-consuming activities that required countless hours in the library. Today, a one-hour search of PubMed can provide a complete and comprehensive 50-year literature search of a subject along with the immediate download of relevant publications. To achieve this 40 years ago would have required more than two months of full-time searching at a medical library and would still have been incomplete. Under today's conditions and with dedicated time and effort of the trainee, it seems to me that graduate training programs could achieve the biomedical scientific training that I describe without prolonging the duration of the training program in years.
The Dominance of Molecular Biology in the Contemporary Education and Training Programs
In addition to the historical and philosophical deficiencies in contemporary biomedical science graduate programs, the dominance of focus on molecular biology and molecular technology has created a myopic generation of researchers. This is a generation of supertechnologists whose knowledge runs deep in molecular biology and shallow in the integrated processes of normal bodily function and disease. Their didactic, technological, and experimental experiences are focused on molecular genetics, cell signaling, proteomics, microarrays, etc. Conversely, they gain a limited understanding—if any at all—of human physiology and pathophysiology, or in integrated organ systems function, biochemical principles and cell metabolism, or even physiology. In today's biomedical sciences graduate programs, there is little, if any, exposure to areas such as comparative morphology, comparative embryology, or physical and chemical composition of protoplasm. To illustrate these deficiencies, ask a group of trainees questions such as, What is the physical state of protoplasm? What are the colloidal properties that support living matter? What are the attributes of life? Or, at the organ level, ask questions such as, What are the definitions of analogous versus homologous relationships? What human structure is homologous to the sinus venosus of lower vertebrates? How and when are the endoderm, ectoderm, and mesoderm formed in embryogenesis? Perhaps more revealing would be to ask this group of molecular geneticists to describe Lamarckism versus Mendelism.
Unfortunately, it is the view of contemporary researchers and academicians that such knowledge is extraneous and not essential to address the contemporary biomedical scientific research issues and interests. After all, as the contemporary view promises, molecular genetics and molecular biology will unlock and resolve all of the contemporary biomedical issues and will provide the basis for eradication or treatment of medical diseases. Such a misguided view results from the prevalence of highly specialized researchers who have displaced the role of scientists and are now the directors and developers of biomedical graduate training and research programs.
Is it not telling when medical schools or health sciences campuses do not provide a PhD program in physiology but, as an alternative, offer a PhD degree in molecular medicine? It seems apparent to me that the products of these two programs will be significantly different. I happen to maintain the belief that human diseases collectively are manifestations of pathophysiological conditions. I happen to believe that pathophysiological conditions are disruptions of the normal integrated processes of the human body. These processes include integration of organ systems, cell physiology, molecular biology, and physical-chemical dynamics. I happen to believe that an understanding of these integrated structural, functional, metabolic processes is essential to all biomedical scientists, regardless of the specialty research track that one wishes to pursue.
If not included in the formal graduate training program, these integrated relationships will not be inculcated into the knowledge base and into the thought processes of the developing biomedical scientist. Indeed, the trainee will likely never have any thoughts of the existence and importance of such relationships. Here is where the specialized biomedical training program fails. The primary purpose, in my view, of a graduate program should be to seed the mind with these relationships and principles. The specialty interest should then be integrated into the issues of the nature of health and disease. However, it takes time and attention to provide and to incorporate the background and the discussions of these issues and ideas. Unfortunately, regardless of the proclamations of the aims of many biomedical graduate programs, the primary time, effort, and demands of the trainee too often are to pursue and to advance the research interests of the mentor. I believe that the graduate training of a biomedical scientist, especially the PhD graduate (or equivalent), requires the inculcation of these relationships into the mind, the intellect, and the thought processes of the individual. The trainee will have a lifetime beyond the formal graduate training program to develop further his or her specialty interest and expertise. Indeed, this is why PhD graduates of earlier generations were expected to enter into a postdoctorate program to obtain additional specialized research training to supplement their comprehensive doctorate education.
The Consequences of the Contemporary Biomedical Research Training Programs
The preceding shortcomings, while important, are representations of intellectual issues of the biomedical scientist. More significant is their impact on the health issues and welfare of the medical community and the public-at-large. The nearly singular focus on the molecular biology and molecular genetics approach to health and disease issues, in my view, poses a serious problem. It is not that I do not believe and recognize the enormous value and contributions that molecular biology advances have contributed during the past three decades. Indeed, I have incorporated these very tools and concepts in my own work. Advances in molecular biology have given insight into and have identified many important biomedical issues that need to be investigated. Advances in molecular technology have provided tools, methods, and approaches to investigate biomedical issues that heretofore could not be addressed or resolved. What is troubling is that, by and large, molecular biology/molecular technology has become the raison d'etre. It has evolved into a more dominant determinant of contemporary science than warranted and has done so at the expense of other important research directions that need to be applied to the same contemporary biomedical issues. Other important approaches, directions, and ideas have been squeezed out of the mainstream of today's directed biomedical research and funding.
We have a situation of “the tail wagging the dog”! In the real world of obtaining funding for research and of obtaining standing in the scientific community, contemporary standards dictate the “acceptable” biomedical issues and approaches. One can no longer look at an unresolved biomedical question, integrate the existing information, apply a rational assessment, set forth a concept to pursue, formulate the hypothesis, and then design and conduct the appropriate experiments with the appropriate experimental methods and tools. Today, one must begin by looking at the molecular biology issue and the molecular technology approach and then ask the question, “How can I use these to formulate the research into a specific biomedical question?” In the absence of this focus, a research proposal will have a greatly reduced likelihood of acceptance and funding.
The Effect on the Direction and Funding of Biomedical Research
The direction, focus, and funding of biomedical research areas are established by public and private granting agencies and foundations; of these, the National Institutes of Health (NIH) is the dominant player. NIH and others rely on the contemporary scientific/medical community to provide the medical/scientific input that establishes the focus and direction of biomedical research and to provide the expertise involved in the review and approval or rejection of the research projects to be funded. It is noteworthy that the recent director of NIH, Dr. Elias Zerhouni, focused on the need to integrate and apply molecular biology research into the understanding of physiological and pathophysiological implications of body function and disease. This objective is exemplified in statements such as “What new areas of science do we need to focus on that have a lot of promise to them, but may need NIH encouragement? Systems biology is one” and “Solving the puzzle of complex diseases … will require a holistic understanding of the interplay between factors such as genetics, diet, infectious agents.”2
Unfortunately, a tremendous pragmatic gap exists between these stated goals and aspirations and what is actually reflected in the focus of the programs arising from the NIH Office of Extramural Research and in the focus and composition of the study sections as determined by the NIH Center for Scientific Review. A glaring example of this gap is demonstrated in cancer research programs. For example, there currently exists a renewed interest in and focus on the importance of metabolic alterations in the development of cancer (and other diseases), which has led to an NIH focus on metabolomics and metabolic biomarkers. Yet, among the myriad NIH cancer study sections, not a single cancer study section exists that has a focus or expertise in tumor cell metabolism. A grant proposal that focuses on the use of a metabolic biomarker for the detection/screening of cancer will most likely be assigned to the Cancer Biomarker Study Section, which has no focus, interest, or expertise in intermediary metabolism. The same applies to proposed studies of alterations in tumor cell intermediary metabolism. A reading of the descriptions of the many cancer study sections available on the NIH Web site (http://www.csr.nih.gov/Roster_proto/sectionI.asp) vividly reveals the overwhelming repetition and redundancy of focus on molecular genetics, molecular biology, and signaling pathways. Metabolic studies are out of the mainstream interest of the cancer study sections. Thus, there exists a disconnect among NIH aspirations for metabolomics in cancer, support for research regarding the understanding of altered tumor cell metabolism, and the study section review process.
Such conditions are a result of the contemporary direction and focus of biomedical research, which is established by the myopic, highly specialized molecular biology interests of today's biomedical community. Research proposals that do not share that narrow focus are not reviewed by receptive, open-minded, and knowledgeable reviewers. When the review of a grant program is dependent on the consensus of two, three, or four reviewers, the possibility for funding outside of this mainstream is further reduced.
A personal experience from one of my grants (which was funded, so the funding decision does not affect my selection of these examples) clearly demonstrates the disconnect between contemporary molecular biology specialists and the application (to paraphrase Dr. Zerhouni's comments) to systems biology and holistic understanding required to solve the puzzle of complex diseases. With regard to prolactin regulation of metabolic genes in the prostate gland, numerous reported studies during 40 years with rats, pigs, and baboons have established that prolactin is involved in the regulation of prostate growth, function, and metabolism. Those studies employed the application of endocrinological principles and approaches which, briefly, are (1) in vivo study to remove hormone source and determine effect, (2) in vivo study to replace the hormone and determine effect, and (3) in vitro study to determine the direct effect of hormone on the target tissue. Despite this evidence, a reviewer contested the validity of prolactin regulation of prostate. The reviewer asserted that a reported prolactin-receptor-deficient transgenic mouse model exhibits prostate gland development and, thereby, demonstrates that prolactin is not involved in prostate development and function. I will not take time to identify the myriad issues and misinformation inherent in and imposed by the transgenic model. What is more relevant is that the reviewer had little, if any, understanding or knowledge of physiological and endocrinological principles. The reviewer should have raised the important question of why the transgenic model exhibits conditions that do not reflect the physiological and endocrinologic effects of the hormone.
A second reviewer raised concern that prolactin-stimulated expression of the metabolic genes exhibits only a two- to threefold increase. The fact that the increase is consistent and statistically significant and that the corresponding cellular metabolic reaction is increased were irrelevant to the reviewer. The reviewer employed the microarray criteria which dictate that >twofold changes in expression are required for statistical stringency to separate noise from signal. The reviewer had no comprehension that regulatory metabolic enzymes are not abundant proteins and that small changes in the enzyme abundance can have significant kinetic and metabolic effects at the cellular level. Such ignorance dominates the entire realm of microarray studies. As I have discussed,3 one must recognize the axiom, “Genetic and proteomic changes have no relevancy if the changes are not manifested in cellular function and metabolic alterations.” Microarray and proteomic approaches cannot define cellular metabolic alterations. This can only be accomplished by cellular metabolic studies. These examples characterize a lack of integrative capability that exists in the contemporary and dominant group of “gene specialists.” This does a great disservice to the development and advances of important and viable ideas. Additionally, it leads to a significant contribution of misinformation and disinformation regarding the viability of important concepts. This generation of researchers now dictates and will dictate the future direction and funding of basic and clinical research.
Every generation of biomedical graduate students has been and will be exposed to new advances and new technologies that are incorporated into the conduct of research among contemporary issues of the time. Every generation contributes new and important knowledge. The past generations absorbed and integrated the new advances into the mosaic of existing scientific/medical information and technology. In so doing, the earlier generations broadened their scope. I know this to be so because I, as others of my generation, am a beneficiary of this amalgamation. This is not happening today. For the most part, the molecular advances have amplified the molecular approach and have discarded and displaced the integrated principles, ideas, and approaches that accumulated over preceding generations. The broad, comprehensive background and understanding of science and the application of science to contemporary biomedical issues are not alive and well. The highly specialized, myopic contemporary approach reigns.
Where Do We Go From Here?
In this discourse, I have touched on my perception of an important contemporary biomedical issue. There is much more that could be added in support of this perception and its unfortunate consequences. I do not view this as a “right or wrong” issue or as an “appropriate or inappropriate” issue. I view it as an “outcome” issue. What educational and training practices are best to address the issues of health and disease? What kind of scientist, researcher, or supertechnologist is needed to solve the contemporary and future health problems of society? In all likelihood, a combination of these is required. The issue that I bring to the table is the importance of understanding what the biomedical education and training programs are producing—in terms of the strengths and the deficiencies, in terms of the capabilities and the shortcomings, in terms of the advantages and the disadvantages. Only by gaining this understanding can we be assured that the public welfare and the scientific/medical community will be best served with the best approaches, the best investments, and the best-qualified individuals in addressing and solving contemporary health issues.