A "community" web site by and for developmental physiologists

and their students studying physiological ontogeny

at molecular through organismal levels.

"That's MY Opinion" is a Forum by which you can weigh in on issues relevant to developmental physiology, broadly defined.   Have you seen a paper or book review that has you flushed with excitement (or just flushed)?  Want to float an idea by a friendly, informed audience?  Express your opinion in approximately 500 words or less and send it to the Webmaster.  Have you read a "That's MY Opinion" that you just can't let go by without a comment or rebuttal?  Send it in, too!

(Posted to the DP Web Site November 26, 2007)

John S. Torday, MSc.,PhD.,  Professor, Department of Pediatrics and Obstetrics and Gynecology, Director, The Henry L. Guenther Laboratory for Cell/Molecular Research, Harbor-UCLA Medical Center, Phone: (310)222-8186 FAX: (310)222-3887

I found provocative Dr.Greenspan's essay on Bohr's concept of complementarity (The Scientist, October issue, entitled "Fascinating Bohr").. It is noteworthy that Dr.Greenspan is an immunologist, and that the immune system is one of the most complex, yet 'plastic' processes in all of biology. Paradoxically,it is also a biologic process which, if deciphered evolutionarily would provide great insight to our

origins and future as a species.  I would submit that if Einstein had achieved the Unified Field Theory there would be no duality of light, and that similarly, biology would not have to suffer the same duality of proximate and ultimate causation as suggested by Mayr if we understood evolutionary biology from its initial conditions and first principles. In Walter Isaacson's recently published biography of Einstein he commented that Einstein had an innate sense of the nature of light because he could actually visualize himself moving with the light beam....having viewed the American Museum of Natural History's Einstein exhibit a couple of years ago, I would submit that that same 'perspective' allowed Einstein to envisage the nature of Brownian Movement, the photoelectric effect and Relativity. We must gain the same insights for evolutionary biology in order to achieve A Periodic Table for Biology (Torday J.S., A Periodic Table for Biology. The Scientist 2004 Jun 18(12): 32-33). Complementarity is a metaphor for

 our lack of understanding of natural phenomena, and should be recognized as a 'work in progress' and not as an absolute truth.

A Periodic Table for Biology

(Posted to the DP Web Site June 16, 2004).

 

John S. Torday, MSc.,PhD.,  Professor, Department of Pediatrics and Obstetrics and Gynecology, Director, The Henry L. Guenther Laboratory for Cell/Molecular Research, Harbor-UCLA Medical Center, Phone: (310)222-8186 FAX: (310)222-3887

 

Like the Periodic Table, human genome data behooves biologists to systematize information and view it through a new lens. This is currently being done stochastically, inferring that genes are expressed randomly. The gene pools of contemporary species have evolved through natural selection. Therefore, we should be thinking about how to exploit this process in order to discern gene-selection patterns based on Developmental Physiology.

Our work has approached some of the intercellular signaling partners involved in lung development. Disrupting homeostasis in the lungs results in disease through those same signaling pathways. These pathways have played key roles in the evolution of lung structures beginning from the swim bladder in fish¹ ,  reflecting a continuum between ontogeny, phylogeny, physiology, and repair that may serve as a framework for integrating cell-cell signaling.

COOPERATION IS KEY.  The cooperativity that underlies endosymbiosis in the rise of eukaryotes has evolved from a metabolic form to a cellular form that has been recapitulated throughout the evolution of multicellular organisms as well as vertebrate phylogeny and ontogeny.

Interrupting cellular crosstalk causes cells to readapt in a process recognized as disease. Similar chains of events occur in all structures that ascribe to such developmental cell-cell interactions. The recognition that ontogeny, phylogeny, physiology and pathophysiology are a genetic continuum suggests that such motifs represent “rules” that could serve as construction guidelines for a biologic Periodic Table.

ELEMENTAL BIOLOGY.  The genius of the Periodic Table of elements lies in its hierarchical organization with atomic weight as its first principle. A comparable approach to the creation of a biologic Periodic Table would need t#515D2Co be based on specific functional principles of homeostasis, linked mechanistically through the genes that determine such processes.

PTHrP AS ARCHETYPE.  The recognition that development, phylogeny, homeostasis and pathophysiology represent a continuum of interrelated genes affords the opportunity to consider how these cell and molecular motifs have been retained through convergent evolution. I have previously hypothesized that the progressive complexity of the gas exchange unit has resulted from the phylogenetic amplification of the PTHrP signaling pathway.¹ During lung evolution from the swim bladder, the structure-function interrelationship between alveolar surface area and surfactant production has amplified. I have hypothesized that both of these properties of the lung are mechanistically linked through stretch regulation of PTHrP signaling.¹ Cyclic stretch enhances the expression of both PTHrP and its receptor on apposing epithelial type II cells and mesodermal fibroblasts.

As the metabolic demand on vertebrates drove their evolution, the lung surfactant system became more efficient through the process of natural selection as follows: PTHrP amplification of surfactant, along with PTHrP inhibition of fibroblast growth, may have promoted the thinning of the alveolar walls and allowed the progressive phylogenetic and developmental decreases in alveolar size.

EVOLUTION AS SOLUTION . We are beginning to recognize the convergent expression of genes that have given rise to the complexity of physiologic processes.  Lung evolution has been driven by the amplification of the PTHrP signaling pathway,¹ providing insights to the development, function, and dysfunction of the lung. Phylogeny, ontogeny, physiology and pathophysiology may be represented by a family of parallel lines, providing enough variables to solve for all of these equations as the aggregate process of evolution.

References

1. J.S. Torday, V.K. Rehan, “Deconvoluting lung evolution using functional/comparative genomics,” Am J Resp Cell Mol Biol, in press, July 2004.

Opting Out of Academic Science

Olivia Eyre 

(Olivia Eyre is a pseudonym for a doctoral student in the biological sciences at a leading research institution in the East. She is chronicling her search for an academic or nonacademic position this year.  From The Chronicle of Higher Education on line, March 6, 2003)

       The news is finally out. For months, I had been unable to tell my adviser that I was seriously considering something other than the postdoc position everyone expected me to pursue in academe. So I broke the news in a report to my thesis committee by tacking on a cryptic phrase: "It is with some disappointment that I realize that I am not willing to make the all-consuming personal commitment required to pursue a career in academic science. I am beginning to explore my options outside of academia, and hope to find an environment where I can utilize my skills."

        In the past, I had strongly suspected that none of my committee members read my thesis reports. Apparently, this was not the case. As a doctoral student in the biological sciences at a major research institution, I am supposed to want an academic career. The suggestion that I might break with expectations brought blizzards of advice crashing upon me from many sources.

First, my adviser. He alternated between assuring me that he didn't want to pressure me into any specific choice and insisting that I will live a life filled with sadness and regret if I don't do an academic postdoc. He assured me that I was slamming many doors of opportunity shut, never to be opened again. He waxed poetic about the beauty and joy of an academic life (shortly thereafter, he stormed through the lab complaining about a course he was teaching). He warned me that there was little chance for independent research in an industry position (I wasn't so impertinent as to point out that there is no time left over for independent investigation while working for him). He urged me to "take my time" and consider my options carefully because I shouldn't make "a big mistake" at this point in my career. I was ready to give in and do as I was told.

        Second to put in her opinion was one of the deans of my program. She suggested that I consider a postdoc in a well-established lab, set reasonable work hours, and try to have a normal life. The idea of a normal life that includes some amount of free time is appealing, although I'm not entirely sure that my next P.I. would be happy with a postdoc who worked half time (i.e., a 40-hour workweek). She assured me that she had decided to switch from an all-day, all-night schedule in graduate school to an 8-to-5 model as a postdoc. However, working that reduced schedule meant that she had never sought a position as a principal investigator on a grant or worked as a group leader of a project in the lab where she was a postdoc.

        Neither my adviser, my dean, my fellow students, nor various Web forums have managed to convince me that academic postdocs are anything more than graduate school without the courses. I would be working in a new lab, and would perhaps learn some new techniques, but no one was able to explain to me why taking a postdoc position in academe was a prerequisite for an industry position.

        In fact, I located an industrial scientist who had never done an academic postdoc and called him for an informational interview. Dr. Happily Employed (at a product-development company) buoyed my hopes. As a graduate student he had posted his CV with a placement service and landed a first job at a small biotech company. He had since worked his way through a series of other smaller and larger biotechs to his current position directing product development. He encouraged me to get out in the business world where I could play a role in making real products. This sounded exciting!

        Next, I indulged in a bit of nepotism. One of my uncles is a chemist-turned-middle-manager at Big Pharma. He offered to pass my résumé around, and initially seemed pretty upbeat. My hopes were dampened, however, when he shared the news that he had just survived the most recent round of musical-chair layoffs at his company. Apparently, it has become a trend for companies to announce that everyone is laid off; a number of positions are removed, and all employees have a chance to reapply for the remaining jobs. If your previous position is gone, you look for others within the company -- along with everyone else whose job was eliminated. I'm sure that this is someone's idea of maintaining a competitive environment. However, if positions are being cut, I'm not sure there is much slack to take on a new Ph.D.

        My Big Pharma uncle also gave me the name of a recruiter who had successfully placed him and a number of other people he knew. Ms. Recruiter was kind enough to talk with me on the phone, but she immediately began lamenting the state of the economy, describing hiring freezes (in addition to musical-chair layoffs) at big companies and cash shortages at small biotechs. I sent her my résumé, but I haven't heard a thing. I'm not holding my breath -- after all, many people have told me that companies are reluctant to pay headhunting fees in a market where there are so many job seekers.

        After talking to my uncle and his recruiter, I lost the hope gained from my conversation with Dr. Happily Employed. However, my mood was significantly improved by a meeting with the members of my thesis committee. They had decided that I should defend my thesis this March and then continue as a postdoc (with a 50-percent raise!) until I lined up my next position. Happily, my committee members invited me to speak with them individually about my career plans rather than ganging up on me.

        Getting the green light for graduation was a good thing, because my husband had gotten a big red light a few days later. We knew that his employer was in a downward spiral, but the company president announced that the doors would close in May. Suddenly, my husband and I had a lot more motivation to decide on our next move.

        We had already decided that we were through with expensive East Coast living, and my programmer husband was leery of joining the unemployed hordes on the West Coast. We quickly narrowed our list of acceptable locations to two -- the Research Triangle in North Carolina and a midsize Midwestern city, home of our alma mater.

        North Carolina has lots of big pharmaceutical companies and some small biotechs; Midwestern City doesn't. What Midwestern City does have is a good research university, a few companies, and the things in life that really matter: family close by, friends even closer, good job opportunities for my husband, high quality of living, and the feeling of being at home. Still, I lobbied for North Carolina. But my husband argued (rightfully) that I had promised that he would decide our next destination, since he was the trailing spouse in our current location. I will be able to find some sort of position there, although there are fewer options.

        The same day that we received the news of impending unemployment, one of my committee members asked to meet with me. I'll call him Zeus, which encompasses his high position of leadership, imposing stature, and the potent mixture of fear and respect he commands from everyone at my institution.

I wasn't sure what Zeus was going to say about my resistance to academe. Rather than thunderbolts, he cast rainbows. Zeus acknowledged the oversupply problems in the academic job market, but he encouraged me not to give up on myself. Of his own accord, Zeus suggested that my husband should select our next destination, and then Zeus would help me to find an appropriate position. Unlike the others who had advocated academic postdocs, Zeus was able to cite a number of specific examples of how postdoc experience led to good positions in industry. Zeus has a great deal of experience on scientific advisory boards of small and large companies, and was able to describe the career trajectories of a number of scientists.

        I hadn't thought that I was much more to Zeus than an obligation to attend thesis-committee meetings. I feel deeply fortunate that he has taken an interest in my fate, and that he can provide savvy advice on choosing a position (postdoc or otherwise) that will open a path for me in industry. I'm not sure why Zeus has decided to step down from the clouds and become Mentor to me (a mere mortal), but I am glad.

        The excitement of a new destination has begun to seep in. We spent a snowy Saturday goggling at real estate on the Internet. In Midwestern City, we probably will be able to buy an actual house. I have a date on Zeus's calendar to discuss the options that I've found in Midwestern City, and I'm excited about the next step.

And "That's MY Opinion"......

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The Power of Comparative Physiology: Evolution, Integration and Application

(Posted to the DP Web Site March 7, 2003).

James W. Hicks, Editor in Chief, Physiological and Biochemical Zoology, 321 Steinhaus Hall, University of California, Irvine, Irvine, CA 92697-2525

        In August of 2002, a scientific conference entitled “The Power of Comparative Physiology: Evolution, Integration and Application” took place in San Diego, California.  This meeting, sponsored by The American Physiological Society, The National Science Foundation and the U.S. Army, brought together comparative physiologists from around the world and was subsequently reported on in Science (Recharged Field’s Rallying Cry: Gene Chips for All Organisms, 297:1985-1987 20 September 2002).  The article in Science highlighted the enthusiasm with which the comparative physiological community regards the exciting promises of genomics on a large comparative scale.  Unfortunately, the Science article utterly failed to emphasize and convey to its readership one crucial element of the meeting—the power of comparative physiology.  As Chair of the organizing committee for the San Diego conference, I found this elision particularly disheartening.  The power of comparative physiology, quite simply, is its broad, far-reaching, and integrative nature.  The questions investigated by comparative physiologists incorporate a range of biological levels of organization, from the molecular to the organismal, while simultaneously analyzing and interpreting the findings within an evolutionary and environmental context.  This level of integration is, quite frankly, not reached in any other area of physiological research.

        In contrast to areas of biological investigation that focus on human health issues, comparative physiology does not often lend itself to such simplistic questions as “what is the big discovery?” or “how will this research benefit humans?”  Subsequently, it can be difficult for scientific writers and reporters to summarize the results of comparative physiological research in a succinct soundbyte of the kind welcomed by and expected from the popular media. In the end, the popular media often presents the relevance of comparative physiology in terms of potential medical advancement or to highlight some “odd” or “unique” animal that the reporter thinks will capture the public’s attention.

        The more important question might be what motivates comparative physiologists.  To put it quite simply, comparative physiologists are driven by two basic questions: how animals work, and why animals work the way they do.  These two seemingly straightforward questions have far-reaching implications and require a variety of investigative approaches.  The comparative physiologist is challenged to determine the details of physiological mechanisms while simultaneously gaining insights into ultimate causation, i.e. the evolutionary or adaptive significance of a physiological process or trait.  This manifold focus on proximal mechanism and ultimate causality requires that comparative physiologists bring to their investigations a diversity of analytical approaches often absent in the more narrowly defined fields of medical physiology, biochemistry and molecular biology.  To successfully address their investigations comparative physiologists must effectively integrate molecular, cellular, organismal, morphological, biomechanical, biophysical, ecological and evolutionary information.   The laboratory of Dr. Barbara Block (Hopkins Marine Station, and Stanford University) exemplifies this integrative method. Her research program investigates questions related to the physiology of large pelagic fish or more simply “how do tuna work?”  Her pursuit of answers to this seemingly uncomplicated question has revealed insights into the molecular mechanisms of Ca²⁺ cycling in skeletal muscle, uncovered novel aspects of cardiovascular physiology, and has provided new information about the ecology, natural history, and evolutionary biology of these animals.

         Dr. Block is an exceptional scientist, but her approach is not exceptional within the traditions of comparative physiology.  A review of the scientific program presented at the San Diego meeting will convince most readers that large-scale integrative approaches typify comparative physiology. Symposia presented at this meeting reflected a range of topics from comparative genomics to the physiology of marine mammals to biological inspirations for robotic design.  The results presented at this gathering of international scientists were relevant to many areas of biology including molecular biology, cellular biology, developmental biology, evolutionary biology, paleobiology, bioengineering, ecology, conservation biology, and medical physiology.  What other area of physiological research can claim that within a single conference, the research presented will have such far-reaching and diverse applications?  It is this diversity of approaches and this level of integration that makes comparative physiology such powerful science.

         It has become trendy in recent years to increasingly focus on molecular aspects of biological systems, a focus that has driven the development of many new and exciting technologies. It is the fascination with this trend, in part, that drove the tenor and tone of the Science article.  Although molecular approaches have resulted in an explosion of information at the gene level, it is becoming increasingly clear that narrowly trained molecular biologist are often left struggling to integrate their findings into higher levels of organization and into broader physiological schemes.  In contrast the comparative approach, by its very nature, brings an almost philosophical approach to physiology, making broad integration the rule rather than the exception, and providing a framework within which its students can integrate a variety of levels of biological organization, think in terms of genetic and biological diversity, evaluate and consider environmental influences, and place research results within developmental and/or evolutionary trajectories.  Consequently, more so than the more specialized areas of physiological research, comparative physiology is ideally suited to discover not only differences among organisms, but also the unifying principles shared by diverse organisms.

        Although some might argue that comparative physiology has “lost its shine of first discovery,” or that the field is searching for something to “reinvigorate itself,” I am convinced that the broad, integrative nature of comparative physiology makes it critically important to the health and strength of physiological sciences— health and strength that will be required to insure significant advances during the 21^st century.

        And "That's MY Opinion"......

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"Comparative Physiology Welcomes (But  Was Not Revived By) Gene Chip Technology"

(Posted to the DP Web Site October 23, 2002).

Warren Burggren, Professor of Biology, Department of Biological Sciences, University of North Texas, Denton, Texas, U.S.A.  

 Like other comparative physiologists, I welcomed coverage in Science Magazine of the San Diego Fall Comparative APS Meeting (Recharged Field’s Rallying Cry: Gene Chips for All Organisms, 297:1985-1987 20 September 2002).   The correspondent (Elizabeth Pennisi) got many things just right – e.g. comparative physiologists’ excitement about gene chips – but she also seriously misrepresented the state of our field, erroneously describing a moribund field apparently rescued by a new technology!  

Ms. Pennisi’s article accurately captures the enthusiasm many comparative physiologists have for gene chip technology, especially as now being applied to animals other than the usual suspects.  Unfortunately, I found it difficult to focus on the article after reading Ms. Pennisi’s opening statements that comparative physiology, which allegedly had been in the doldrums, was now “recharged” and ready to “bloom again” explicitly because of gene chip technology.  

Sorry, Ms. Pennisi, but like many other comparative physiologists, I must have been too busy during the last several years training junior colleagues who were quickly snapped up for great jobs in their field to have noticed we were actually at a nadir!  Should  the NSF, which has awarded millions of $US to comparative physiologists in recent years, also be re-educated? 

To support her contention of a previously waning field, Ms. Pennisi states authoritatively that comparative physiologists had not met for eight years prior to the San Diego meeting.  Unfortunately, she was unaware of the multiple comparative physiology meetings held annually around the world (we luuuuuv to travel!).   Granted, the American Physiological Society had not had a dedicated comparative physiology meeting in eight years, though many of us attend and participate in the excellent comparative symposia sponsored by the APS at each one of its annual meetings.   I’m told that the Comparative APS meeting was not scheduled in 1998 because of an administrative snafu within the Society, which of course comprises many additional branches of physiology.   A bureaucratic error shouldn’t be interpreted as morbidity within a discipline, however good a story it makes.       

It really is wonderful to see comparative physiologists highly enthused by gene chip technology being featured in a prestigious journal like Science.  Clearly, gene chips will be an important new arrow in an already well-stocked quiver.   I can even overlook Ms. Pennisi’s portrayal of comparative physiologists involved in a “…micro-array stampede…” (we are talking about gene chips, not cow chips, right?)   However, to read that comparative physiology is “..coming out of its slump…” is just plain annoying to me, and does a disservice to an active, energetic field and particularly to our many new students. 

 For our field to remain vibrant we must aggressively integrate new approaches with proven ones.  However, we must also challenge science writers who imply that only those wielding emerging technologies are relevant and who dismiss the remainder as irregularly-meeting Luddites.   Comparative physiologists form an increasingly important bridge between those who have focused extensively on a few highly studied (if not ultimately representative) animal models, and those who wonder how the vast majority of unstudied animals actually work. 

As for me, I’ve found the last eight years in comparative to have been truly exhilarating, and I fully anticipate the next eight to be even more so.  See you at our next meeting!

And "That's MY Opinion"......