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The Changing Face of Cutaneous Biology as Seen from the National Institutes of Health

      Over the past 50 y, research in skin biology and diseases has changed dramatically. These changes include (i) who is doing the research, from M.D. clinician dermatologists to predominantly Ph.D. research scientists and full-time or nearly full-time M.D. and M.D.–Ph.D. scientists, (ii) where, from small laboratories in the U.S.A. to large laboratories and multiinvestigator collaborations worldwide, (iii) what, from a focus on common skin diseases to an emphasis on understanding basic processes in skin, both in normal and disease states, and (iv) how, from patient observations, histology, and clinical immunology to cell and tissue culture, molecular biology and genetics, genomics and proteomics. Financing of this research has also changed, from the use of clinical surplus funds supplemented by U.S. government (National Institutes of Health, Veterans Administration, and other) monies to a greater dependence on government and private (pharmaceutical industry and philanthropy) funding. The future, funding issues aside, promises great advances with translation of basic knowledge to the diagnosis, prevention, and treatment of skin diseases.

      Keywords

      In the last 50 y, research in cutaneous biology and diseases of the skin has changed significantly and is continuing to change. In this review, I will use the reporter's approach by looking at a modification of the five Ws – who, what, when, where, and why. The why is clear-cut for all of those interested in cutaneous biology and I will not discuss that any further. The when has been defined as the last 50 y but I will make some comments concerning future directions as well. I will add an additional category of how.

      Who

      In the 1950s, most research in the area of cutaneous biology was, in fact, dermatology research. It was done by dermatologist physicians who were primarily clinicians. These individuals spent much of their time seeing patients with the diseases in which they were interested and training resident physicians but then went to the laboratory to do research that was often disease oriented. The other members of the research team sometimes included Ph.D. trained scientists but in only a small number of cases were Ph.D. scientists the heads of the laboratories or research teams. There were very few, if any, physicians who spent the overwhelming majority of their time doing research. In the 1960s and the 1970s, a greater number of physicians who spent most of their time doing research, many of whom held the combined M.D. and Ph.D. degrees, began to appear in the field. During this time, also, more Ph.D. trained scientists became involved in research and more of them became heads of the projects and heads of laboratories. In the 1980s and in the last decade, this trend has accelerated. We now see, at least in terms of National Institutes of Health (NIH) supported cutaneous biology research, that the majority of projects and the majority of laboratories are headed by Ph.D. scientists. M.D. Ph.D. scientists remain a significant component and have maintained a steady influence over the last 20 y. Clinicians now rarely head more basic projects but are often collaborators, particularly when disease pathogenesis is being investigated. In the last decade and more specifically in the last 2 or 3 y, there has been an increasing emphasis on translational research as well as epidemiology and outcomes research. This field is still relatively small and is predominantly an area of M.D. investigators with public health credentials, either an M.P.H. or Ph.D. in epidemiology and related fields. In the future, it is likely that this last area will grow the most, at least in proportion to its modest beginnings, but that the overall cutaneous biology enterprise will continue to be driven by Ph.D. and M.D.-Ph.D. scientists looking at basic cutaneous biology processes and disease pathogenesis. There will always be a place for the clinician scientist who is necessary in order for an appropriate understanding of how the cutaneous biology findings relate to the disease process in the patient and to the potential for the development of therapeutic and/or preventive interventions.
      In the 1950s, most cutaneous biology research took place in small laboratories. These usually consisted of the principal investigator, one or two additional scientists, and one or two technicians or fewer individuals. This slowly gave way over the next 20 to 30 y to the development of larger laboratories where the principal investigator, now more often a Ph.D. scientist or an M.D. or M.D.–Ph.D. scientist spending essentially full time in research, would head a larger laboratory pursuing several lines of research simultaneously and supported by a number of other scientists both fully trained and undergoing postdoctoral training. These individuals would also be supported by several technicians. As techniques became more sophisticated and specialized, collaborations between laboratories in order to do certain components of the research also became much more common. In the last 10 y, we are seeing the development of what can be termed mega science, a good example of which is the human genome project. This type of approach is likely to continue to address specific large questions that cannot readily be approached in any other way, but the results of the mega science may actually make it more feasible for individuals in smaller laboratories to apply these results to their own specific questions without the necessity for developing the infrastructure themselves. Thus, developments such as the human and mouse genomes available on the Internet and the development of chip technologies commercially available to pursue genomic and proteomic type studies may, in the future, facilitate the return to individual small to medium size laboratories focusing on specific questions but able to tap into these commercially and government supported general resources to provide the wherewithal to pursue the studies.

      What

      In the 1950s, most cutaneous biology research was focused on common dermatologic diseases. This paralleled the interests of the primarily M.D. dermatologist investigators. Mechanisms of disease and mechanisms of treatment in patients and in specimens derived from patients were the primary focus. This gave way in the 1960s, 1970s, and 1980s to investigations of the molecular basis of structure, function, and diseases of the skin. In the 1980s and 1990s, molecular genetics culminating with the human genome project became the major thrust of many of these projects. With the imminent completion of the human and mouse genomes and with the emphasis on understanding how genes are translated into structure and function, research is now shifting to genomics and proteomics. This will be the major thrust for a period of time, but as information develops the data will need to be integrated into what is now being termed integrative biology, i.e., the ability to assemble all of these many bits of information into an understanding of how the cells and the organism function as a whole. Another outgrowth of the genomics, prodeomics, and integrative biology approaches will be a more rational approach to the translation of this information into interventions in the treatment of disease as well as diagnosis and prevention.

      Where

      In the 1950s, with Europe economically recovering from the Second World War, as was Japan, most cutaneous biology research took place in North America, the U.S.A. and Canada. In the 1960s, 1970s, and 1980s, European investigators and Japanese investigators progressively swelled the ranks of cutaneous biology and continued to do so. Now with the globalization of trade and science, research is worldwide but still is predominantly in the technologically advanced societies. The worldwide expansion of cutaneous biology research is likely to continue. There is some concern that particularly interventional trials and research involving human subjects may tend to migrate to Third World countries with less strict controls over the welfare of human subjects and where such expensive human subject research can be done more cheaply. This aspect of globalization may be viewed as a danger or as a benefit assuming sufficient human subject safety can be assured as it maximizes the ability to get certain studies done.

      How

      In the 1950s and 1960s, most cutaneous biology/dermatology research was based on patient observation and the techniques of light microscopy, biochemistry, and earlier immunologic approaches. This gave way to cell and tissue culture, which in the last 20 or 30 y has progressively given way to the tools of molecular biology, molecular genetics, and now chip technology as applied to genetics, genomics, and prodeomics. The amount of data being generated by these techniques is growing exponentially and will require advances in bio-informatics in order to be able to make sense of all the data and apply them to an integrated knowledge of the function of the cell and the organism in health and disease. Another future development will be the reemphasis on clinical research, clinical trials, and outcome research, with the application of new techniques and technology both in terms of trial design and based on molecular and genetic knowledge, resulting in the development of new interventions and diagnostic and preventive procedures. In a sense, this will be coming full circle going back to patient observation of the 1950s but with the tools of the twenty-first century.
      In the 1950s, much of the cutaneous biology research was supported with clinical revenues within the departments of dermatology in which it was taking place. The NIH began supporting such research in the 1950s and such research support was based as much on the idea and the qualifications of the principal investigator as on the specific detailed approaches being employed. As technology advanced and training became necessary in the use of these technologies, NIH expanded its mechanisms for the support of the training of younger investigators as well as the support of newly trained investigators. This took the form of both specialized project support mechanisms and career support mechanisms as well. These have been continuously refined and expanded as the enterprise has grown and the variety of approaches has multiplied. In addition, NIH is making more and more use of mechanisms to support larger science collaborations including program project support, center support grants, and contracts for the support of clinical trials, registries, and specific reagent development. Much of NIH's support for the human genome project has been through the contract mechanism. Nevertheless, particularly in cutaneous biology, the bulk of NIH support for research has been individual project grants and that is likely to be the case for the foreseeable future. Other mechanisms will be applied as appropriate in particular cases and when stimulation of certain areas of the science is needed, such as support for registries and support for training of individuals in epidemiology, health sciences research, and outcomes research, but at least for cutaneous biology NIH support is likely to remain individual project based along with support for postdoctoral training and early career support.
      The last 50 y have shown dramatic changes in cutaneous biology research, in terms of who does the research, how the research is done, and how the research is supported. Changes will continue into the twenty-first century but we can all look forward to continued government support of high level research in cutaneous biology and the translation of findings to the care of patients with skin diseases.