 |
|
Hannah V. Carey |
When I joined the American
Physiological Society nearly 22 years ago, I could not have envisioned that
one day I would become President of this Society. I am humbled and honored
to be asked to lead an organization that has always been at the core of my
academic life. My love of physiology and dedication to the APS is due in
large part to the influence of my postdoctoral advisor, Helen J. Cooke, who
has mentored me throughout my career. In addition to excellent scientific
guidance, Helen instilled in me the idea that participation in scientific
societies—and in particular the APS—should be an integral part of my
professional life. I have also been blessed with the guidance and
encouragement of a number of other colleagues who have helped shape my
career and my participation in the APS. To all of them, I extend my
heartfelt thanks.
Election to President of the APS is particularly special for me, because I
will be only the third woman to serve in this position. I am pleased to see
that the involvement of women as members and in the governance of the
Society has increased significantly since the time I joined as a trainee
member. Our Society is also becoming increasingly diverse as it embraces
members from minority groups, and I expect this to continue in the years
ahead, aided by programs like the Porter Physiology Development Program. I
believe that this diversity in APS contributes substantially to our strength
as a society. Equally powerful is another sense in which the APS is diverse:
in the nature of the science we do and the questions we ask. We hold a
variety of professional degrees including MD, PhD, DVM, DO; we utilize an
astounding variety of research tools, model systems and scientific
approaches. APS members engage in a wide range of professional activities
including research that is academic or industry-based, and that is focused
on basic, clinical or translational investigations. We are educators in the
academic and public arenas, and we advocate for science and for physiology
as a keystone discipline for the life sciences. Our health as a Society
depends on us capitalizing on these diverse backgrounds, interests and
scientific approaches, and working together when challenged with threats,
such as diminished research funding, public misperception of science, and
animal activism.
The diversity we display as physiologists also provides a rich resource base
for us to take a leadership role as society addresses the health challenges
we face as a global community. Global health is generally viewed as the
application of public health on a global scale, particularly as it pertains
to health concerns of human populations in developing regions of the world.
A broader and more inclusive view, however, encompasses the science and
practice of sustaining the health and well-being literally of our globe,
including human populations and the cultures associated with them, animal
populations, and the ecosystems within which we all live. These views of
global health—the human-centric and broader, ecosystem centric—are quite
complementary, and in fact inter-dependent: our health as a species is
intimately linked to the health and well-being of the animals (and other
living beings) around us. In the remainder of this essay, I’d like to
highlight three related themes that illustrate how I see our role and,
indeed, responsibility, as a discipline and as a Society to be leaders in
global health. These are: the contributions of physiology to human public
health, the physiological basis of ecosystem health, and the unique position
of physiology, as the integrative life science, to translate these two
interdependent, mutually beneficial areas into “One Physiology” that fosters
the global health of our planet.
Physiology and Global Health: Human Public Health
There is no doubt that physiological research has made substantial
contributions to the science that underlies public health. Probably the best
example of a resounding success story is the development of oral rehydration
therapy (ORT) to combat life-threatening diarrheal diseases, which still
kill nearly two million children worldwide each year, particularly in
developing countries. The discovery by epithelial transport physiologists
beginning in the 1950s, first of the mechanism of sodium-coupled glucose
absorption in the intestine, followed by the recognition that secretory
diarrheas (such as those induced by bacterial enterotoxins) do not impair
sodium-coupled absorptive mechanisms led to the development of ORT.
Continued research is leading to refinements in ORT formulations to help
meet this challenge and further reduce diarrhea-associated mortalities.
Advances in understanding the molecular physiology of epithelial chloride (CFTR)
channels that drive fluid secretion in the gut are leading the way in the
development of new therapies that will provide additional protection against
the massive fluid losses induced by diarrheal diseases. This is important,
because although use of traditional ORT has led to the yearly decline in
deaths from acute diarrhea worldwide from 12 million to less than two
million, it does little to decrease the duration of diarrheal episodes.
The work physiologists do is closely tied to other areas of public health,
such as elucidating mechanisms of obesity, type 2 diabetes, cardiovascular
disease and metabolic syndrome. These are health issues recognized as
nearing epidemic levels in some parts of the developed world, but are
becoming increasingly recognized as public health issues for developing
countries as well. This paradox of public health crises in human populations
where malnutrition and related diseases are common, in close proximity to
populations suffering from consequences of excess food and reduced activity
levels is particularly prevalent in “transition” countries like Vietnam and
China, in which there is great disparity between people living at very low
and very high income levels. Other areas in which physiological research
interfaces with public health include respiratory biology (e.g.,
asthma/allergy, influenza outbreaks and resulting complications from acute
respiratory distress syndrome), reproductive physiology, the physiology and
pathophysiology of aging, exercise and environmental physiology, and many
others.
These examples illustrate the stellar manner in which physiology facilitates
translational research from the bench to the global community. How might we
as a Society strengthen this relationship? One way is to help spark the
passion among our trainees to pursue a career in basic or translational
research that encompasses a public health perspective. We could, for
example, assist the development of programs that expose young physiologists
in their training to real-world experiences that demonstrate directly the
benefits their research can have on the global community. An ideal candidate
might be a postdoctoral fellow who has already identified for their research
focus a particular area of physiology that has applications to global
health. With stipend support, the fellow would step out of the laboratory
environment for a limited period (e.g., two to four months) and step in to
the world of global health in practice. Shadowing and rounding with
physicians and other experts in a clinical area related to their research
interests could help shape the goals and approaches of their future research
programs, or simply provide the passion that is so needed for a fulfilling
and productive research career. The ability to implement new programs like
this when funding levels are stagnant is, of course, the challenge. Along
with our sister societies in FASEB, APS continues to be a strong advocate
for more federal support of basic and translational research. As President I
will work hard to assist that effort that is so essential for
investigator-initiated research, but is increasingly important for
interdisciplinary/multidisciplinary approaches that bring the achievement of
basic scientists to the clinical setting. The physiology/global health
“externship” program described here is of a more modest scale; one route
that could be explored for funding is a partnership between APS and
government agencies or nonprofit foundations that focus on global health and
translational biomedicine.
Physiology and Global Health: Ecosystem Health
In our discussion of the role physiology plays in global health, we must not
lose sight of the fact that discoveries made by physiologists benefit not
only human life, but also the health and well-being of the animals whose
planet we share. Discoveries made in the quest to improve human health
become part of the arsenal used to treat our companion animals, our domestic
animal populations, and wild species. Similarly, animal models of disease
from the veterinary world can be translated to human medicine, and indeed
most therapies used for humans have been discovered and evaluated through
the use of animal models. But the interplay between the two is broader than
that: our ability to achieve healthy and fulfilling lives absolutely depends
on the health of the organisms around us, and their existence depends on
ours. As we know all too well from data accumulating on the impacts of human
populations on other species, we have the potential to influence species
survival on our planet, and for existing species, to influence what the
quality of their lives can be. In turn, our actions that may have adverse
effects on the survival of other species can alter the healthy balance of
coexistence that benefits us all. This interdependence of human-animal
interactions on the earth is illustrated by the growing recognition that
maintenance of biodiversity influences the spread of pathogens, and, thus,
our ability to control the spread of infectious diseases. West Nile virus,
for example, is spread from wild birds to people via mosquitoes. Because
some birds are poor hosts for the virus, maintaining their population
numbers within avian communities helps reduce the incidence of the disease
in humans. Another example is the decline in some of our major fish
populations. Not only does this represent a crisis in ecosystem management
and the potential for collapse of oceanic food chains, it also jeopardizes
our access to nutrients that can provide significant health benefits, such
as fish oils that contain high levels of cardioprotective omega-3 fatty
acids. These sorts of relationships underscore the important linkages
between animal population biology, biodiversity and human health. Because
the maintenance of biodiversity, particularly in our changing global
environment, starts with understanding how animals adapt physiologically to
changes in their biotic and abiotic environments, we play crucial roles in
global health—for us as humans, and for the health of the complex ecosystems
around us. Although physiological investigations with non-laboratory animals
has traditionally been considered the realm of comparative and ecological
physiology, it’s important to keep in mind that all of us contribute to the
collective understanding of how life works, and the science that each of us
does builds on the work of others.
Some of these ideas were crystallized by presentations made during the APS-sponsored
Intersociety Conference, “Comparative Physiology: Integrating Diversity,”
which was held in Virginia Beach in October of last year. In particular,
presentations by the conference’s plenary speakers illustrated each in their
own way, that physiology is crucial to our understanding of species
adaptation to change, and, thus, our ability to predict survival of species
in a changing world. Of particular note, Terrie Williams of UC-Santa Cruz
ended her presentation with a challenge to the audience (and larger
scientific community) that called for the development of a national center
network to enhance physiological research and the organization of
physiological data on wild species, and particularly those endangered or
vulnerable to changing environmental conditions.
I am pleased to report that further discussions on this concept have been
taking place subsequent to the Virginia Beach Conference, facilitated by our
Executive Director, Martin Frank, and a small advisory group. The APS is now
poised to move to the forefront this critical role that physiology plays in
the global health of animal life on our planet. On March 18-19 of this year
a workshop, supported by the National Science Foundation, is being held to
discuss the feasibility of developing a National Center Network for
Physiological Research, Integration, Synthesis and Modeling (PRISM). PRISM
proposes a comprehensive approach to cataloging physiological diversity and
applying research findings in a broader, more global perspective, thus
enhancing their impact. One of the core goals of the PRISM network would be
to improve the ability of physiologists, working collaboratively with other
environmental scientists, to identify the potential for adaptation (or loss)
when species are challenged by environmental perturbations. Many of these
challenges, including climate change, introduction of environmental toxins
and changes in complex food chains, ultimately impact humans and are of
increasing concern to the public. The proposed network would, thus, serve as
a resource for physiologists and other scientists searching for new ways to
mitigate species loss in a changing world. This in turn will help guide
management decisions that impact the interrelationships between humans,
animals and the environment.
Developing a resource whose mission is the synthesis and integration of
research efforts in comparative and ecological physiology also benefits
human and animal biomedicine. Detailed understanding of how animals adapt
physiologically to their specific ecological niches, particularly those that
involve adaptations to environmental extremes, can provide insight into the
capacity of physiological systems to respond to perturbations (1). Such
species could be used in a data mining approach to identify mechanisms for
translation into new therapeutic targets in the clinical arena. Indeed, the
NIH has recognized the valuable resource provided by species uniquely
adapted to environmental extremes, as illustrated by the recent Program
Announcement “Elucidating Nature’s Solutions to Heart, Lung, and Blood
Diseases and Sleep Disorder Processes” (3). As mentioned earlier, building
an infrastructure to promote physiological synthesis and integration would
also benefit human-animal interactions from the perspective of managing food
animal resources for maximum sustainability. Ideally, the PRISM project
would promote a culture of collaboration among biomedical and comparative
physiologists, scientists in other relevant disciplines, and environmental
managers to address global issues and foster the health of humans and
animals on our planet. Because of the highly multidisciplinary nature of
PRISM, it is expected that the funding required to develop and sustain the
program would derive from multiple sources, such as the National Science
Foundation, National Institutes of Health, private nonprofit agencies and
even industry.
A key aspect of the PRISM program would be integrating the expertise of
established investigators with the enthusiasm of young scientists, which is
essential for training the next generation of whole animal physiologists.
Trainees would be exposed to a parallel form of translational physiology,
one that starts with the best physiological training that incorporates
modern tools like genomics, proteomics, metabolomics and other technologies
commonly used in the human research toolbox, along with others required to
obtain accurate physiological data from free ranging animals such as
biologging and stable isotope analysis. In this way, trainees get exposure
to techniques used at the lab bench all the way to the “bedside” of the real
environment, so that they are best prepared to translate physiological
knowledge to management and policy decisions that will keep our earth’s
living resources in optimal health. This kind of expertise will help prepare
future investigators who will work in the area of “conservation physiology,”
a nascent sub-discipline of our field that is being increasingly recognized
as an essential component of conservation biology (2).
The Physiologist: Integrating and Translating Basic Research to Global
Health
The natural linkages between physiology and global health underscore the
reality that our discipline is a critical component of a true systems
biology approach to health. As molecular biology has moved into the
post-genomic era, systems biology has come to be regarded by many as
beginning at the molecule, working within the complexity of the cell and
ending at the plasma membrane. Complexity beyond the cell is often thought
of as too emergent a property to be currently amenable to a systems
approach. Yet, exploration from the genome to the outer reaches of a cell is
just the beginning of a systems approach to biology. Physiologists view a
living organism as much, much more than the network of signaling pathways
within a cell or a series of intercellular communication pathways between
similar or diverse cell types. Rather, higher-level emergent properties are
the essence of organismal function, and must be incorporated into
physiological modeling approaches to fully understand and predict responses
of the whole organism. A true systems biology approach to health thus
integrates molecular and cellular function with that of tissues, organs and
large scale, whole body signaling networks, and finally with an organism’s
interaction with its environment.
Research and practice in global health (as well as personalized medicine) is
becoming increasingly aided by modern tools that facilitate the molecular
assessment of health and disease status – that is, biomarkers. New
technologies are coming online that provide biomarker monitoring, and here
again physiology plays a crucial role. “Omic” tools like genomics,
proteomics, metabolomics and other related technologies all contribute to a
systems approach to health. However, integration and interpretation of the
output of these tools is essential for these technologies to be utilized to
their best advantage. Through their ability to carry out sophisticated
studies at the organ and whole animal levels, physiologists provide that
integration, and, therefore, should be key members of teams that practice a
systems approach to health. The development of high throughput
identification and quantitation strategies for biomarkers and their
application to health and disease—for humans as well as animals—is still in
its infancy, and physiologists should be active participants in the early
stages of translating these technologies to whole organ and organism
function for both research purposes and for individual and population health
assessment.
The Way Forward
As a Society we have the diversity, breadth, and depth to tackle problems
literally of a global scale that will make a difference. These skills enable
us to capitalize on our diversity – as human beings and as scientists – and
effectively utilize the integrative and translational components of the work
all of us do as physiologists. A slogan often heard in my institution, the
University of Wisconsin School of Veterinary Medicine, is “One Medicine.”
This reflects our mission that as a collection of bioscience researchers and
veterinary practitioners, the discoveries we make and our efforts to
translate them to the clinic are done to improve the health of humans and
animals alike. I would hold that as physiologists, our commitment and
passion for understanding how living organisms function also goes beyond
translating our work to the clinic. There is a pressing need for
physiologists to expand the traditional application of our work and be
active participants in the increasingly important decisions that affect how
we manage the biotic resources on our planet, and how we can best promote
healthy and sustaining relationships between human and animal life.
Expanding our view of the role we play in the health of our globe is good
for the APS, good for science and good for our world. This can happen if we
work together, as “One Physiology.”
I am grateful to a diverse set of colleagues who have shared ideas that
contributed to those expressed here, and provided comments on earlier drafts
of this article, including Terrie Williams, Martin Frank, Kent Sanders,
Allen Cowley, Helen Raybould, Christopher Olsen, Helen Cooke and Murray
Clayton.
References
1. Ramirez JM, Folkow LP and Blix AS. Hypoxia tolerance in mammals and
birds: from the wilderness to the clinic. Annu Rev Physiol 69:
113-143, 2007.
2. Wikelski M and Cooke SJ. Conservation physiology. Trends Ecol Evol
21: 38-46, 2006.
3.
http://www.grants.nih.gov/grants/guide/pa-files/PAR-06-382.html. |
