John A. Williams

76th President of APS

We live in exciting but challenging times. Never before have we had the spectrum of tools and techniques now available to delve deeply into the mysteries of complex organisms. We can relate specific processes to molecular structure through recombinant DNA technology and expression of proteins in model cells used as physiological test tubes. Moreover, physiology is becoming central to understanding the function of genes and gene products in the setting of the organ or organism and how this is impacted by the environment. This general area, often termed “Functional,” “Physiological,” or “Integrative” Genomics has become a major focus for modern physiology.

Unfortunately, these opportunities are set against a possible impending shortage of resources. While all biomedical science has benefited enormously from the just completed 5 year doubling of the NIH budget, the Bush Administration's requested 2% increase for next year, which is less than the Biomedical Inflation Index, has NIH officials planning for a reduction in the number of new grants and possibly reducing grant length from 5 to 4 years. While we need to advocate for a more consistent increase in the NIH budget and hope that Congress will be as responsive as they have been in the recent past, the current political climate and the state of the economy may make it difficult. Other economic challenges also threaten our growth. With widespread deficits at the state level, public universities are undergoing significant budget cuts. Private universities are seeing their endowments shrink and often delaying implementation of new plans. Similarly, the APS investment portfolio has decreased somewhat due to the fall in the stock market. Thus, both as individual scientists and collectively as part of APS we will need to choose wisely how to allocate our resources to maximize our results.

The Discipline of Physiology

“Integrating the Life Sciences from Molecule to Organism” applies to APS and to the discipline of physiology. Much of physiology in the last two decades of the 20th century was reductionistic and with the tools of molecular biology led to the identification of specific molecules such as transporters, channels, receptors, and contractile proteins that underlie specific functions. Today, the biggest challenge is to explain how all these component molecules work together. While integrative physiology used to refer to how different organ systems worked together to maintain homeostasis, the current definition also focuses on how molecules function together to generate the properties of a cell or organelle and how cells function together in a tissue or organ. Often this higher-level function cannot be predicted solely by the properties of the component molecules, a phenomenon sometimes referred to as emergent properties. We physiologists strive to use both molecular and integrative approaches to illuminate function. Much of this work is now carried out in genetically modified animals, most often mice. A gene can be added, removed, or modified either in the whole animal or in a tissue specific or temporally controlled manner. This has worked well to explain the function of single genes but is less well suited for polygenic traits or where the animal adapts to maintain normal function.

We are seeing the rebirth of “Systems Biology” (4) which emphasizes the simultaneous determination of all or at least a large number of components in the living system under study rather than focusing on a single gene or protein. Moreover, it investigates the behavior and relationships of these elements of a biological system as it is functioning or being perturbed and subjects the data to computational analysis. At the same time there has also been a proliferation of “Omics” which began with the genome and the transcriptome, the collection of all mRNA transcripts. This was followed by the proteome, the collection of all the proteins in an organelle, cell, or organ, which can be resolved by two-dimensional gels or multi-dimensional liquid chromatography, and identified by mass spectrometry. In its infancy is the study of the metabalome, the large-scale collection of metabolic intermediates that can reveal information about the activity of specific metabolic pathways. These components, genes, proteins, and metabolites, can be put together with mathematical models, which is another hallmark of Systems Biology. In its handling of large data sets this approach overlaps with some areas of Bioinformatics. New organizations are springing up in these areas such as HUPO, the Human Proteome Organiza-tion, and the International Society for Computational Biology. We physiologists should embrace these new approaches to the study of functional biology because of the obvious relevance to our individual work and because of the opportunity to participate in collaborations with groups of investigators. Not all of this work is hypothesis driven and much at present is either methods development or “discovery science.” However, it will lead to testable hypotheses and also to potential therapeutic targets. While much of this research has begun in yeast or bacteria, it is being applied to specific cell types, namely B lymphocytes and cardiac myocytes by the “Alliance for Cellular Signaling,” a large consortium initiated by Al Gilman (5). The approach will ultimately reach the whole animal level and physiologists are just beginning to use it for studying processes such as blood pressure, the circadian clock, and exercise. In the IUPS this has been recognized as “The Physiome” a project led by Peter Hunter of New Zealand (www.physiome.org).

Departments of Physiology

While physiologists work in many types of universities, hospitals and research institutes, the central home for physiology in most American medical schools is the Department of Physiology. Physiology departments are usually charged with organizing the teaching of physiology to professional students and offer PhD education in physiology. In the not so distant past there was concern that physiology departments were being closed or merged. My perception is that this movement has subsided. However, we still need to be proactive in maintaining strong Departments of Physiology. In many Medical Schools and Universities the current emphasis is on developing interdisciplinary programs, institutes or centers, and new research space is programmed to bring investigators with a common research interest together. It is important for Physiology Departments to initiate or participate in programmatic centers. This will allow departments to grow and embrace new research areas that will be denied us if we strive to maintain an outdated ideal of the purity of our discipline. Expanding into interdisciplinary programs brings obvious problems, the main one being decentralization. We must not succumb to centripetal forces and departments need to maintain a strong central core to which outlying faculty will return for intellectual nourishment.

Maintaining a strong department is also important to counteract the fact that teaching is often now being organized in an integrative curriculum at the expense of departmental courses. This is especially true in the first years of Medical School where the current fashion is the integrated curriculum. Departments of Physiology need to maintain a strong presence in organizing and presenting material so that they will remain valued by clinicians and administrators in their institution. Graduate teaching is now often organized with an integrated first year to allow students to shop for mentors and switch disciplines. Overall, I believe these gateway programs will allow physiologists to attract more PhD students if we design our teaching to emphasize the relevance of what we do to the state of modern biology in the post-genomic era.

Another movement affecting Departments of Physiology, which I believe will have a positive affect, is the changing of some departmental names to more closely reflect their mission. Newer names include Cellular and Molecular Physiology, Molecular and Integrative Physiology and even Physiology and Functional Genomics. Although somewhat cosmetic, I think these newer names may help dissolve any image of physiology as “stodgy.” I am personally pleased to see physiology remain in the new departmental names. These names may also help us in convincing our Deans that the various disciplines and departments are different and that both intellectual diversity and the ability to have successful interdisciplinary programs depends on maintaining strong departments.

The American Physiological Society

Our Society has grown in complexity since the adoption of the strategic plan of 2000 (6). The essential core of APS continues to be its meetings and publications. In the area of meetings, Experimental Biology (EB) has flourished, especially in the years when all of our sister societies participate. It is, of course, quite different from the FASEB Meetings I first attended on the Atlantic City Boardwalk. Both Physiology InFocus as a “meeting within a meeting” and the Section's Named Lectureships are well attended. One positive recent feature has been the addition of the American Federation for Medical Research as a participating organization. Their participation as well as the presence of APS translational symposiums has added venues for us to learn more about how our work can impact on medicine. The Microcirculatory Society also now meets as part of EB. There has also been an expansion of activities at EB directed toward young scientists including symposia on careers, teaching and mentoring. We need, if anything, to do more to encourage students and fellows to attend and to establish this meeting as an integral part of their careers. Travel grants, inexpensive registration, student awards and having a fun time all help augment the scientific benefits of attending for young scientists. We also need to incorporate the “Omic” disciplines into EB and explore the possibility that new societies in systems or computational biology might affiliate with EB in a mutually beneficial manner. Both EB and the topical APS conferences have continued to be ably organized or overseen by the hardworking members of our Joint Program Committee.

Our publishing program remains sound and is continuing to make a smooth transition incorporating electronic publishing. We now have a very efficient web based system, APS Central, for submitting manuscripts and organizing the peer review process. For those concerned about impact factors, our numbers are up. As both a reader and an author, I appreciate the increased use of color and the member benefit of free color in my articles. The legacy project to make all our back journal issues available in electronic format is underway and will be completed in the next few years. All issues, including the legacy issues, are available online free to all members. This valuable member benefit was adopted by Council in 2002. The proposal to establish new BioMed Central journals by the Public Library of Science which would be purely electronic journals supported by user fees estimated at up to $1500 per article is a continuing threat to the well being of academic publishing. The added quality and the work put in to publish journals by academic societies such as ours should not be undervalued. Even though free access for all is appealing I am not convinced that we would be well served by a single central repository such as the Public Library of Science, which publishes and maintains electronic journals. A major concern for all of us is the high subscription prices of the for profit companies in the publishing industry which has now coalesced into a very few large companies. Further challenges we share with other academic publishers include development of a tiered price structure for electronic access based on the size of the institution and whether to bundle our subscriptions. It appears that the existence of paper copies will not go away rapidly although I realize that in my departmental library the paper journals serve more for ambiance than anything else. In the eventual future, all paper copies will be printed on demand by the user. While our sectionalized journals in the near future will stay much as they are, the new Editors of Physiological Genomics and NIPS have ideas to give them a new look.

In the educational arena much of APS effort has been on K-12 education either in preparing material for students, or through educating teachers through the Frontiers in Physiology Program to help them absorb and transmit the excitement of science to their students. It is unfortunately hard to quantitatively document the effectiveness of such efforts but we hope it will yield more students considering Physiology as a career and a more informed public. These and other APS educational programs are funded both by external grants and by APS funds drawn from our investment income. APS has also recently begun to put more emphasis on physiology education of the type many of us are carrying out in both undergraduate and graduate education and an additional staff member has been added. I would encourage you all to look at and consider contributing to the APS “Archives of Teaching Resources” which is designed to include material for undergraduate, graduate, and medical student teaching.

Over the last 5 years APS has worked synergistically with the Association of Chairs of Departments of Physiology (ACDP) in several arenas. We participated in a joint project, initiated by Gabriel Navar as President of ACDP, to develop a detailed list of learning objectives for Medical Physiology. This has recently been published as “Medical Physiology Core Curriculum Objectives Project” and is also available on the APS website. It should help document the need for adequate time on physiology in the Medical School curriculum based on the extent of information to be learned and promote the central role of Physiology in medical education. More recently, the APS Education Committee has begun developing a list of “Core Competencies” at different educational levels from undergraduate through graduate student and postdoctoral fellows. We have invited the participation of ACDP and will work together to generate this set of skills and experiences that our students should obtain at different educational levels.

One group of trainees that neither individual investigators, the universities, nor APS have paid enough attention to is Postdoctoral Fellows. Usually, as investigators, we consider the main challenge to be finding the funds to support the fellow or just finding a fellow and expect that they will learn to run a laboratory through osmosis in what is essentially an apprentice program. Postdocs tend to be more associated with a lab then a department and are often the forgotten group. Recently we have seen two forces working to improve the postdoctoral environment. First, NIH has steadily increased the amount of their postdoctoral stipend that serves as a de facto benchmark to approach a livable wage commensurate with their level of education. Second, there have been a number of local postdoctoral organizations formed to lobby their cause, especially for better salaries and benefits. As physiologists we need to consider what we are doing to promote the career development of our fellows. The aforementioned Core Competencies project should help us collectively define our responsibilities and help develop techniques to aid their professional development. In my opinion, every fellow should learn to write and review papers, write a grant, present a seminar, and oversee a technician or student. They should hear about recruiting and training laboratory workers, funding sources, as well as career options. This training may be best done at the School, the Department, and the laboratory level and APS should also play an important role. In the coming year, the APS will be creating a Trainee Advisory Committee to help define the role APS will play in these efforts.

A final area in which APS has recently expanded its efforts is Public Affairs. This involves our Public Affairs Staff, the Executive Office, and our Public Affairs and Animal Care Experiment-ation Committees. Most of our effort is in lobbying for adequate federal research funding for our science to realize its potential and maintaining a climate in which animals, under appropriate care and supervision, are available for research. In lobbying for research funding we usually work with our sister organizations or disciplines as the life science community is well served by speaking with a loud and combined voice. FASEB has taken this on as one of its main reasons for being and APS participates in generating their annual consensus report. It is also important for each of us as individuals to both contact our legislators and build support for research in the community. To assist members in this area the APS Office of Public Affairs has developed a new staffed Legislative Action Center and a website accessible under Public Affairs on the APS home page.

In the area of appropriate use of animals in research, APS is a lead organization. Whether they come officially from APS or from our individual experts, our opinions are respected “on the Hill.” We need to also continue to work with local organizations at the state level and support the patient advocacy groups that stress that “Animal Research Saves Lives.” For those of us who attended the IUPS congress in New Zealand, one of the highlights was Marty Frank confronting and dialoging with the demonstrators on the street in front of the convention center. In another venue, this February APS developed a letter sent by President Barbara Horwitz to the San Diego newspaper supporting the right of educators to appropriately use animals in the teaching of medical students and resist the pressure from a minority group of faculty who are advocating stopping animal use as immoral. As individuals we need to both support appropriate advocacy groups and also be prepared to jump into action.

Finally, in closing, I will return to the important subject of strategic planning. Much of APS's current effort is being guided by the 2000 Strategic Plan. We need to realize, however, that strategic plans are not immutable but evolving documents. Some programs we start will serve a useful period and then may need attention or ending. Just as with Biomedical Research, APS clearly has more opportunities than resources and it is often harder to end than to start programs. Secondly, we need to continue strategic planning on an ongoing basis and involve as many individuals as possible. In the current year this will primarily involve Council and the Sections through the Section Advisory Committee (SAC). It is my intent to begin planning for an APS retreat in 2005 to generate a new Strategic Plan. I would also encourage any of you with ideas to improve APS to contact me. I am looking forward to serving you in the coming year.

References

1. Horwitz, B.A. “75th President of the APS.” The Physiologist 45:87, 96-99, 2002.
2. Hall, J.E. “74th President of APS.” 44:65, 74-79, 2002.
3. DiBona, G.F. “73rd President of APS.” The Physiologist 43:57, 66-70, 2000.
4. Kitano, H. “System Biology: A Brief Overview.” Science 295:1662-1664, 2002.
5. Participating Investigators, “Over-view of the Alliance for Cellular Signaling.” Nature 420:703-706, 2002
6. Boron, W.F. “The APS Strategic Plan - A vision for the New Millennium.” The Physiologist 43:71-74, 2000.

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