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MY Opinion" is a Forum by which you can weigh in on issues relevant to
developmental physiology, broadly defined. Have you
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
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
(Posted to the DP Web Site
November 26, 2007)
John S. Torday,
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
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
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.
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.
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.
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
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.
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.
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
to the DP Web Site March 7, 2003).
(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.
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
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
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
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.
"That's MY Opinion"......
The Power of Comparative
Physiology: Evolution, Integration and Application
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
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
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
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
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
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
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
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 21st
And "That's MY Opinion"......
Back to top
Physiology Welcomes (But Was Not Revived By) Gene Chip
to the DP Web Site October 23, 2002).
Warren Burggren, Professor of Biology, Department of
Biological Sciences, University of North Texas, Denton, Texas,
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!
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.
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
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.
really is wonderful to see comparative physiologists highly enthused by
gene chip technology being featured in a prestigious journal like
gene chips will be an important new arrow in an already well-stocked
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
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
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
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
And "That's MY