George Edward Billman (born July 23, 1954) is an American
physiologist
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical a ...
and professor at
Ohio State University
The Ohio State University, commonly called Ohio State or OSU, is a public land-grant research university in Columbus, Ohio. A member of the University System of Ohio, it has been ranked by major institutional rankings among the best publ ...
. After receiving a Ph.D from the
University of Kentucky
The University of Kentucky (UK, UKY, or U of K) is a Public University, public Land-grant University, land-grant research university in Lexington, Kentucky. Founded in 1865 by John Bryan Bowman as the Agricultural and Mechanical College of Kentu ...
in 1980, Billman began his professional career at the
University of Oklahoma
The University of Oklahoma (OU) is a Public university, public research university in Norman, Oklahoma. Founded in 1890, it had existed in Oklahoma Territory near Indian Territory for 17 years before the two Territories became the state of Oklahom ...
. In 1984, he joined the Ohio State staff, where he became an associate professor in 1990 and a full professor in 1996.
Billman's research has focused on
cardiovascular function, in particular its role in the induction of
ventricular fibrillation
Ventricular fibrillation (V-fib or VF) is an abnormal heart rhythm in which the ventricles of the heart quiver. It is due to disorganized electrical activity. Ventricular fibrillation results in cardiac arrest with loss of consciousness and no p ...
(VF). He developed non-invasive methods to study
autonomic neural regulation of the heart, using a canine model of
sudden cardiac death
Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
(SCD). These techniques have subsequently been used in human patients to identify people at high risk for VF. Billman has used his sudden cardiac death models to study the effects of exercise training on susceptibility to SCD and the effects of
omega-3 fatty acid
Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...
s, among other things. Due to his use of live animals in experiments, Billman has been criticized by
animal rights
Animal rights is the philosophy according to which many or all sentient animals have moral worth that is independent of their utility for humans, and that their most basic interests—such as avoiding suffering—should be afforded the sa ...
activists; however, a 2009 regulatory investigation found no evidence of wrongdoing.
Early life and education
George Edward Billman was born on July 23, 1954, in
Fort Worth
Fort Worth is the fifth-largest city in the U.S. state of Texas and the 13th-largest city in the United States. It is the county seat of Tarrant County, covering nearly into four other counties: Denton, Johnson, Parker, and Wise. According ...
, Texas.
He attended
Xavier University
Xavier University ( ) is a private Jesuit university in Cincinnati and Evanston (Cincinnati), Ohio. It is the sixth-oldest Catholic and fourth-oldest Jesuit university in the United States. Xavier has an undergraduate enrollment of 4,860 studen ...
, graduating ''
cum laude
Latin honors are a system of Latin phrases used in some colleges and universities to indicate the level of distinction with which an academic degree has been earned. The system is primarily used in the United States. It is also used in some Sou ...
'' in 1975 with a
bachelor's degree
A bachelor's degree (from Middle Latin ''baccalaureus'') or baccalaureate (from Modern Latin ''baccalaureatus'') is an undergraduate academic degree awarded by colleges and universities upon completion of a course of study lasting three to six ...
in
natural science
Natural science is one of the branches of science concerned with the description, understanding and prediction of natural phenomena, based on empirical evidence from observation and experimentation. Mechanisms such as peer review and repeatab ...
. He did his doctoral work at the
University of Kentucky
The University of Kentucky (UK, UKY, or U of K) is a Public University, public Land-grant University, land-grant research university in Lexington, Kentucky. Founded in 1865 by John Bryan Bowman as the Agricultural and Mechanical College of Kentu ...
, earning a
Ph.D
A Doctor of Philosophy (PhD, Ph.D., or DPhil; Latin: or ') is the most common Academic degree, degree at the highest academic level awarded following a course of study. PhDs are awarded for programs across the whole breadth of academic fields ...
in
physiology
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
and
biophysics
Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations. ...
in 1980.
From 1980–1982, Billman was a research associate under H. Lowell Stone at the
University of Oklahoma
The University of Oklahoma (OU) is a Public university, public research university in Norman, Oklahoma. Founded in 1890, it had existed in Oklahoma Territory near Indian Territory for 17 years before the two Territories became the state of Oklahom ...
.
Career
In 1982, Billman was promoted to Assistant Professor of Research at Oklahoma. In 1984, he accepted an assistant professor position at
Ohio State University
The Ohio State University, commonly called Ohio State or OSU, is a public land-grant research university in Columbus, Ohio. A member of the University System of Ohio, it has been ranked by major institutional rankings among the best publ ...
. He was promoted to associate professor in 1990 and made a full professor in 1996. Billman was elected a Fellow of the
American Heart Association
The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate cardiac care in an effort to reduce disability and death ...
in 2001.
In 2011, he was elected a Fellow of the
Heart Rhythm Society
The Heart Rhythm Society is an international non-profit organization that promotes education and advocacy for cardiac arrhythmia professionals and patients. The society was founded in 1979 and counted over 7,100 members from over 70 countries as o ...
.
He is also a member of
The Physiological Society
The Physiological Society, founded in 1876, is a learned society for physiologists
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organism ...
in London, the
American Physiological Society
The American Physiological Society is a non-profit professional society for physiologists. It has nearly 10,000 members, most of whom hold doctoral degrees in medicine, physiology or other health professions. Its mission is to support research and ...
, the International Society for the Study of Fatty Acids and Lipids (ISSFAL), and
Sigma Xi
Sigma Xi, The Scientific Research Honor Society () is a highly prestigious, non-profit honor society for scientists and engineers. Sigma Xi was founded at Cornell University by a junior faculty member and a small group of graduate students in 1886 ...
.
Billman has served on the editorial boards of the ''
American Journal of Physiology
The ''American Journal of Physiology'' is a peer-reviewed scientific journal on physiology published by the American Physiological Society.
Vols. for 1898–1941 and 1948-56 include the Society's proceedings, including abstracts of papers presente ...
: Regulatory, Integrative and Comparative Physiology'' (2004–2007), ''Current Cardiology Reviews'' (2004–), ''
Experimental Physiology
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when ...
'' (2006−2010), the ''
Journal of Cardiovascular Pharmacology and Therapeutics'' (2001–), and the ''
Journal of Applied Physiology
The ''Journal of Applied Physiology'' is a monthly peer-reviewed medical journal of physiology published by the American Physiological Society. The journal was established in 1948, and is currently edited by Sue Bodine. According to the ''Journal ...
'' (2007–). He was an associate editor of ''
Pharmacology & Therapeutics'' from 1999–2014.
In June 2014, he was selected as the editor-in-chief of the recently formed ''
Frontiers in Physiology
Frontiers Media SA is a publisher of peer-reviewed, open access, scientific journals currently active in science, technology, and medicine. It was founded in 2007 by Kamila and Henry Markram, and has since expanded to other academic fields. Fro ...
'', a position he continues to hold as of 2014.
Billman consulted for
Eli Lilly
Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and r ...
from 1987–1988,
Glaxo
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...
from 1989–1991,
Procter & Gamble
The Procter & Gamble Company (P&G) is an American multinational consumer goods corporation headquartered in Cincinnati, Ohio, founded in 1837 by William Procter and James Gamble. It specializes in a wide range of personal health/consumer hea ...
from 1995–99. He has been a consultant for
Sanofi Aventis
Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
since 1999.
Research
Billman's research has focused on
cardiovascular physiology Cardiovascular physiology is the study of the cardiovascular system, specifically addressing the physiology of the heart ("cardio") and blood vessels ("vascular").
These subjects are sometimes addressed separately, under the names cardiac physiolog ...
with an emphasis on
ventricular fibrillation
Ventricular fibrillation (V-fib or VF) is an abnormal heart rhythm in which the ventricles of the heart quiver. It is due to disorganized electrical activity. Ventricular fibrillation results in cardiac arrest with loss of consciousness and no p ...
(VF) and the
cardiovascular system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
's response to
stress
Stress may refer to:
Science and medicine
* Stress (biology), an organism's response to a stressor such as an environmental condition
* Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
.
His work has led to non-invasive (
electrocardiograph) techniques to detect susceptibility to
sudden cardiac death
Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
(SCD) in dogs. These electrocardiographic markers have subsequently been used clinically on humans.
Billman has studied the effects of
omega-3 fatty acid
Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...
s on the heart and circulatory system.
He has also studied the effects of exercise training and novel pharmaceutics on the test subject's susceptibility to fatal
cardiac arrhythmia
Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
s. He has performed experiments on live research dogs and using isolated ventricular
myocyte
A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
s.
Model of sudden cardiac death
Billman developed a technique of inducing fatal ventricular fibrillation in dogs in the lab of H. Lowell Stone starting in 1980, and used and refined it over the next 25 years.
The model subsequently has been described as "an elegant in vivo model of sudden cardiac death" by cardiologist Michel de Lorgeril ''et al.''
and "a highly reliable canine model of sudden cardiac death" by physiologist Alexander Leaf ''et al.''
The model is described in
Springer
Springer or springers may refer to:
Publishers
* Springer Science+Business Media, aka Springer International Publishing, a worldwide publishing group founded in 1842 in Germany formerly known as Springer-Verlag.
** Springer Nature, a multinationa ...
's handbook of reliable procedures for testing the potential effects of new drug candidates in the antiarrhythmic section.
In the procedure, the left main anterior
coronary artery
The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ of ...
is surgically blocked and a hydraulic cuff is placed around the left circumflex coronary artery, allowing the artery to be blocked on demand. Experiments proceed after a month of recovery and treadmill training.
Under stress from exercise combined with the blocking of the arteries, 50–60% of dogs enter fatal ventricular fibrillation within 2 minutes.
These dogs are labeled susceptible, while the other 40–50% are labeled resistant.
Dogs that enter VF are
defibrillate
Defibrillation is a treatment for life-threatening cardiac arrhythmias, specifically ventricular fibrillation (V-Fib) and ventricular tachycardia, non-perfusing ventricular tachycardia (V-Tach). A defibrillator delivers a dose of electric curren ...
d, allowing for repeated study of the same animals. Over time, initial results (fibrillation or no fibrillation) have proven to be 92% reproducible, allowing for precise testing of potential antiarrhythmic agents.
This model of sudden cardiac death has "yielded important insights" into
ischaemic
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
heart disease.
The initial study using the technique, published in 1982, found that decreased
baroreflex
The baroreflex or
baroreceptor reflex is one of the body's homeostatic mechanisms that helps to maintain blood pressure at nearly constant levels. The baroreflex provides a rapid negative feedback loop in which an elevated blood pressure causes the ...
sensitivity was associated with increased risk for ventricular fibrillation. This marked the first time an
autonomic response was seen as having prognostic value. The same association was demonstrated in humans by Kleiger ''et al.'' in 1987 and "definitively" demonstrated in dogs in 1988 by Schwartz, Billman, ''et al.''
On the basis of these findings, a large clinical study (Autonomic Tone and Reflexes After MI), was conducted. The 1,284 patient study "fully confirmed" baroreflex sensitivity as a valid predictor of sudden and non-sudden death after
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
(MI).
Billman's model of SCD has also shown that sudden death is not a direct function of the degree of a myocardial infarction and that baroreflex gain declines during MI. Resistant dogs show a reduced heart rate during ischemia, while susceptible dogs show increased heart rate (beyond that induced by the exercise). Reviewing the findings, physiologist
Dwain L. Eckberg wrote that the model "seems to be extremely relevant" to human patients at risk for sudden cardiac death.
Cocaine and heart function
According to a 1990
review article
A review article is an article that summarizes the current state of understanding on a topic within a certain discipline. A review article is generally considered a secondary source since it may analyze and discuss the method and conclusions i ...
by Billman, cocaine has two primary circulatory effects – increased
sympathetic stimulation and cardiac
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
inhibition – that lead to a variety of heart problems. The drug also causes increased heart rate and blood pressure. In a 1995 review article, he said resulting secondary effects include arrhythmia,
coronary vasospasm Coronary vasospasm refers to when a coronary artery suddenly undergoes either complete or sub-total temporary occlusion.
In 1959, Variant angina, Prinzmetal et al. described a type of chest pain resulting from coronary vasospasm, referring to it as ...
, myocardial infarction, and ventricular fibrillation.
Omega-3 fatty acids
In 1994, Billman used his model of SCD to test the ability of omega-3 polyunsaturated fatty acids to prevent fatal arrhythmias. In the test, eight dogs otherwise susceptible to ventricular fibrillation were given a direct infusion of
fish oil
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), precursors of certain eicosanoids that are known to reduce inflammation in the body a ...
. Seven of the eight did not have VF during the test. Five of five animals re-tested in a follow-up control test (i.e. without treatment) had VF. The observed effect most likely resulted from a combination of direct chemical interaction on the cardiac cell membrane and a reduced heart rate caused by the omega-3s.
The study was picked up by a nationally syndicated columnist, and thus reported in various popular media outlets.
Follow-up studies in 1997 and 1999 confirmed the results (
P<0.005) and found both
eicosapentaenoic acid
Eicosapentaenoic acid (EPA; also icosapentaenoic acid) is an omega-3 fatty acid. In physiological literature, it is given the name 20:5(n-3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid with a 20-c ...
and
docosahexaenoic acid
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-lino ...
(found in fish oil), as well as
α-Linolenic acid
''alpha''-Linolenic acid (ALA), also known as α-Linolenic acid (from Greek ''alpha'' meaning "first" and ''linon'' meaning flax), is an ''n''−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, waln ...
(found in vegetable oil) to have antiarrhythmic effects.
The same effect has been shown to occur in humans by other researchers. Billman's more recent work has focused on discovering the biochemical mechanisms of the antiarrhythmic effects omega-3 fatty acids, and on whether the same protection can be gained through dietary omega-3 fatty acids.
A 2003 review of the research suggested the effect was due to electrophysiological properties of free omega-3s in
sarcolemma
The sarcolemma (''sarco'' (from ''sarx'') from Greek; flesh, and ''lemma'' from Greek; sheath) also called the myolemma, is the cell membrane surrounding a skeletal muscle fiber or a cardiomyocyte.
It consists of a lipid bilayer and a thin oute ...
. Dietary fatty acids are incorporated into membrane
phospholipids
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
and are then released during
ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
, suggesting a possible mechanism whereby the cardiac muscle is more resistant to entering arrhythmia under stress.
However, large-scale clinical trials of dietary omega-3s have been inconclusive, with some studies finding significant reduction in sudden cardiac death and others finding no effect.
Meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
performed in 2014, found statistically significant reduction in sudden cardiac death (
odds ratio
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
(OR) 0.86;
confidence interval
In frequentist statistics, a confidence interval (CI) is a range of estimates for an unknown parameter. A confidence interval is computed at a designated ''confidence level''; the 95% confidence level is most common, but other levels, such as 9 ...
(CI) 0.76 to 0.98), while 2013 meta-analysis using a different data set found a non-statistically significant reduction (OR 0.82; CI 0.60 to 1.21).
Response to research
Billman's experiments have been protested by animal rights activists.
In 2007, a local group known as Protect Our Earth's Treasures, spurred by Ohio State approving the use of up to 120 additional dogs, protested Billman's research. Specifically, they were against the surgical blocking of arteries in Billman's model of sudden cardiac death and the subsequent euthanizing of surviving animals for future study.
In April 2009,
PETA
Peta or PETA may refer to:
Acronym
* Pembela Tanah Air, a militia established by the occupying Japanese in Indonesia in 1943
* People for the Ethical Treatment of Animals, an American animal rights organization
* People Eating Tasty Animals, an ...
, which had long questioned Billman's techniques, filed formal complaints with the
U.S. Department of Agriculture
The United States Department of Agriculture (USDA) is the federal executive department responsible for developing and executing federal laws related to farming, forestry, rural economic development, and food. It aims to meet the needs of com ...
and the NIH's Office of Laboratory Animal Welfare. They alleged he was conducting redundant experiments and using unnecessarily cruel techniques.
Ohio State said PETA's claims "grossly misrepresented and severely discounted the scientific merit and potential public health benefit of this work."
Two federal investigations found no evidence of wrongdoing,
but PETA continued to campaign against the experiments.
In 2010, Ohio State issued an open letter in response to continued protest letters. In the statement, OSU said PETA was misleading the public by saying Billman's research was investigating the "obvious" fact that "exercise strengthens the heart" when the research was actually attempting to understand the biochemical and cellular mechanisms which lead to sudden cardiac death.
Billman received a new investigator award from National Institutes of Health (
NIH
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
) from 1983−1986.
He was the principal investigator on NIH R01 grants starting in 1986, 1995, 2002, and 2007, and on a
National Institute on Drug Abuse
The National Institute on Drug Abuse (NIDA) is a United States federal government research institute whose mission is to "advance science on the causes and consequences of drug use and addiction and to apply that knowledge to improve individual a ...
R01 grant starting in 1990.
He has also led studies paid for by
Hoffmann-La Roche
F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...
,
Merck
Merck refers primarily to the German Merck family and three companies founded by the family, including:
* the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668
** Merck Serono (known as EMD Serono in the Unite ...
, and Sanofi-Aventis.
Personal life
George Billman and his wife, Rosemary, have been married since 1975. The couple have two children – George T. and Elyse T.
Billman. He is an avid amateur
genealogist
Genealogy () is the study of families, family history, and the tracing of their lineages. Genealogists use oral interviews, historical records, genetic analysis, and other records to obtain information about a family and to demonstrate kinsh ...
, and has determined that his own ancestor, Hans Theobald Billmann, who emigrated to the United States in 1752, was not in turn descended from ancestors previously identified by other amateur researchers.
Publications
Billman has authored or co-authored more than 150 scientific papers, which have been cited more than 5000 times in
peer-review
Peer review is the evaluation of work by one or more people with similar competencies as the producers of the work (peers). It functions as a form of self-regulation by qualified members of a profession within the relevant field. Peer review ...
ed research. According to
Web of Science, he has an
h-index
The ''h''-index is an author-level metric that measures both the productivity and citation impact of the publications, initially used for an individual scientist or scholar. The ''h''-index correlates with obvious success indicators such as winn ...
of 38, with 11 papers receiving more than 100 citations. Billman was the editor of the 2010 book ''
Novel Therapeutic Targets for Antiarrhythmic Drugs'' published by
John Wiley and Sons
John Wiley & Sons, Inc., commonly known as Wiley (), is an American multinational publishing company founded in 1807 that focuses on academic publishing and instructional materials. The company produces books, journals, and encyclopedias, in p ...
, and contributed three chapters to it. According to the publisher, the book describes the state of cardiac arrhythmia treatment, and future directions the research may take.
In a review of the book,
Peter R. Kowey praised Billman for "
ncouragingblue sky thinking" in his contributions.
Books
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Selected journal articles
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References
{{DEFAULTSORT:Billman, George
1954 births
Living people
American physiologists
Ohio State University faculty
Xavier University alumni
University of Kentucky alumni