Archibald V. Hill’s contribution to science and society

Abstract

A brief account of A.V. Hill's contribution to our understanding of muscle contraction is given. This includes an overview of discoveries that led to solving the problem how chemical events provide the energy for mechanical work. Hill helped to train and educate a generation of scientists to use concise mathematical treatment of biological phenomena. He also taught his students moral values important when pursuing research. Finally Hill's deep belief in the international nature of scientific work and his human qualities led him to join Lord Rutherford to become founder member of the Academic Assistance Council, an organization that rescued around 1500 academics from Nazi occupied Europe during the Second World War. With all these activities taken together Hill can be considered a person who made an exceptionally important contribution to the cultural and scientific life of the 20th and 21st century.

Full text

A.V. Hill’s contribution to science and society
European Journal Translational Myology - Basic Applied Myology 2013; 23 (3): 73-76
- 73 -
Archibald V. Hill’s contribution to science and society
Gerta Vrbová
Department of Cell and Developmental Biology, Faculty of Life Sciences, University
College London, UK
Abstract
A brief account of A.V. Hill’s contribution to our understanding of muscle contraction is
given. This includes an overview of discoveries that led to solving the problem how chemical
events provide the energy for mechanical work. Hill helped to train and educate a generation
of scientists to use concise mathematical treatment of biological phenomena. He also taught
his students moral values important when pursuing research. Finally Hill’s deep belief in the
international nature of scientific work and his human qualities led him to join Lord Rutherford
to become founder member of the Academic Assistance Council, an organization that rescued
around 1500 academics from Nazi occupied Europe during the Second World War. With all
these activities taken together Hill can be considered a person who made an exceptionally
important contribution to the cultural and scientific life of the 20th and 21st century.
Key Words: muscle contraction; energy for mechanical work; Academic Assistance Council
European Journal Translational Myology - Basic Applied Myology 2013; 23 (3): 73-76
On a Tuesday morning in March 2010 I was
walking along the corridor to the Medical Sciences
building at University College London (UCL), and a
young girl, probably a student asked me to point out
the way to the A.V. Hill Lecture Theatre. I stopped and
before giving her the instructions how to find it, I
asked her: ‘Do you know who A.V. Hill was?’ As
expected her answer was: ‘I have no idea, but I am in a
hurry, we have a lecture on muscle physiology there,
and I am late.’
I felt sad and disappointed by her lack of interest.
However her ignorance and probably that of other
students who attend lectures in the A.V. Hill lecture
theatre prompted me to write a brief account of the
significance of A.V. Hill for science and society.
In 1923 A.V. Hill succeeded Ernest Starling and was
appointed to the post of Jodrell Professor of
Physiology at UCL, a Department that already had an
outstanding reputation and tradition. At the time of his
appointment at UCL, Hill was a well-established
scientists who had won the Nobel Prize in physiology
in 1923 (as had Otto Meyerhoff).
He played a pivotal role in helping to bring
mathematical rigor into physiology, for example by
introducing the ‘Hill equation’ to explain the effects of
the aggregation of hemoglobin molecules on its
dissociation curves [5]. This equation is simple and
widely deployed in bioscience and later proved useful
in Hill’s work on muscle.
Hill’s arrival heralded new interesting developments at
UCL. The first was the emphasis on progress made in
the understanding of muscular contraction, and the
second was Hill’s dedication to establishing national
and international cooperation between scientists. This
included a commitment of actively helping scientists in
need.
In 1933 Hill was a founder member and vice chairman
of the Academic Assistance Council (AAC). This
organization was dedicated to assist academics who for
reasons including persecution and conflict were unable
to continue their work in their country of origin. In the
30s it included Jewish and other academics forced to
flee the emerging Nazi regimes in Europe. By actively
participating in the work of this organization Hill
continued the liberal tradition of UCL set out in1826
when the College was founded becoming the first
secular institution of higher education in the UK. UCL
then as now pledged that it would accept students of
any race or religious or political belief.
In this brief article three main features of A.V. Hill’s
contribution to science and society will be discussed:
1. His scientific work.
2. His influence and inspiration to scientific
colleagues internationally.
3. His contribution to assisting refugee academics.

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1. A.V. Hill Scientific Work
When A.V. Hill arrived to UCL in 1923 the question as
to how muscle uses energy from chemical reactions in
order to do mechanical work was still obscure. At the
beginning of the 20th century it was universally
accepted that the primary biochemical reaction
associated with providing energy for muscle
contraction was lactic acid, released from a
hypothetical large molecule called ‘lactacidogen’. The
hydrogen ions liberated were supposed to neutralize
negative charges on the contractile protein filaments
allowing them to fold and shorten. However there were
several findings that were inconsistent with this idea,
including measurements of heat production during
muscle contraction made by Hill. It was therefore not
surprising that this hypothesis was overthrown in what
Hill called ‘a revolution in muscle research’, and can
be considered the first of several such revolutions [7].
Hill dates the outbreak of this revolution to the end of
1926 when Philip and Grace Eggleton, research
fellows in the Physiology and Biochemistry
Department at UCL submitted a paper to the
Biochemical Journal reporting that the amount of an
unidentified organic phosphate compound present in
muscle decreased during contraction with a
corresponding increase in inorganic phosphate [3].
Although this weakened ‘the lactic acid hypothesis’,
supporters of the lactic acid theory did not give up
immediately. It was not until 1930 when Lundsgaard
observed that a muscle that is poisoned with
iodoacetatic acid and therefore cannot use oxygen to
break down glycogen to form lactic acid is
nevertheless able to perform several contractions [9].
Thus the energy required for this mechanical work has
to be provided by reactions that did not require the
production of lactic acid and the breakdown of organic
phosphate molecules might be the source of this
energy.
The position of organic phosphate in providing energy
for mechanical work started the second revolution in
muscle research. This was supported by evidence that
suggested that the only pathway for the utilization of
the phosphate from phosphorylcreatine was to re-
phosphorylate adenosine-diphosphate (ADP) to
adenosine triphosphate (ATP), and it was soon
accepted that the primary reaction providing energy for
muscle contraction was the conversion of ATP to ADP
plus inorganic phosphate. Conclusive proof for this
idea was difficult to obtain because the re-
phosphorylation of ATP from ADP was extremely
rapid and therefore no decrease in ATP could be
detected during muscle contraction. However, in 1962
Cain, Infante and Davies demonstrated that a muscle
poisoned with fluorodinitrobenzene could perform
several contractions with the utilization of ATP but not
of phosphorylcreatine [2].
An important discovery based on measurements of heat
production during contraction by Hill and colleagues
showed an increase in heat production and therefore of
the amount of chemical change when the muscle was
allowed to shorten [7]. This finding highlighted the
importance of the relationship between the metabolic
and mechanical conditions during contraction.
Measurement of heat production during muscle
contraction, the method favored in Hills department
also revealed some other fundamental processes of
muscle physiology. Hill’s mathematical treatment of
muscle dynamics based on a biophysical model of
muscle mechanics was the starting point of AF
Huxley’s model of muscle contraction [8], which
remains the valid paradigm of the behavior of all motor
protein and cell mobility systems.
The observation that oxygen is not needed during
contraction but is necessary during recovery inspired
the term ‘oxygen debt’ a useful concept in exercise
physiology even today [7]. These were original and
revolutionary discoveries that brought our
understanding as to how chemical energy is converted
to mechanical work, to a new level.
Hill considered measurement of physiological events
using physical and electrical methods to be an
important counterpart to other methods used in
biology, partly because of the speed at which they can
be recorded. His appreciation of the use of these
techniques to examine biological processes inspired
him to help to establish the first Department of
Biophysics at UCL. After being awarded by the Royal
Society the Foulerton Professorship in 1926 A.V. Hill
became the first head of the Department of Biophysics
and had been succeeded in 1952 by his pupil Bernard
Katz, one of the scientists that were helped to leave
Nazi Germany in 1935.
2. A.V. Hill influence and inspiration to scientific
colleagues internationally
A.V. Hill had several PhD students. He is remembered
by them with great affection, not only because of his
scientific influence but also because of the way he
treated them as human beings and colleagues. This is
perhaps best described by his Chinese student TP Feng,
who came to UCL in 1930 and stayed for 3 years.
After returning to China Feng became the director of
the Shanghai Institute of Physiology. In his memoirs
TP Feng writes: ‘The way Hill dealt with the first
paper I wrote, entitled “The Heat-Tension Ratio in
Prolonged Tetanic Contractions “is worth mentioning.
The problem had been suggested by him and was
carried out under his direction with much assistance
from Mr. Parkinson, A.V. Hills’ much appreciated and
gifted technician. I naturally put Hill’s name as a co-
author. He promptly took his name off the paper
saying: “If this is the only paper you write while you
are here it will not make much difference whether my
name is on it or not, and it will not mean much to you”.

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Another remark in a similar vein at the end of my stay
in London should also be retold. “You have done good
work here and you have done most of the work
independently. But people will still think that you are
under my direction. You must go back and continue to
do good work all by yourself, then you will be
recognized as a fully independent worker.” I don’t
know whether A.V. Hill talked to other students like
this, but his words left a deep impression on me’ [4].
Another of his students who wrote about him with
much affection was his successor as head of the
Department of Biophysics, Bernard Katz. After Katz
fled Germany in 1935 he was accepted as a PhD
student by A.V. Hill at UCL London, where he stayed
until 1939. He referred to A.V. Hill as his greatest
scientific influence and described this period as ‘the
most inspiring period of my life’.
Hill’s influence on his pupils and colleagues was
probably inspired by his strong sense of responsibility
that scientists have in society and particularly the
international nature of science. In an article in Science
written during the Second World War he writes: ’It is
nevertheless a fact that the nature of our occupation
makes scientific men particular international in their
outlook. In its judgment on facts science claims to be
independent of political opinion, of nationality, of
material profit. It believes that nature will give a single
answer to any questions properly framed and that only
one picture can ultimately be put together from the
very complex jigsaw puzzle which the world presents.
Individual and national bias, fashion, material
advantage, a temporary emergency, may determine
which part of the puzzle at any moment is subject to
the greatest activity. For its final judgment however,
for its estimates of scientific validity, there is a single
court of appeal in nature itself, and nobody disputes its
jurisdiction. Those who talk, for example of Aryan and
non-Aryan physics or of proletarian and capitalist
genetics, as though they were different simply make
themselves ridiculous. For such reasons the community
of scientific people throughout the world is convinced
of international collaboration.’ And later: ’In no other
form of human activity, therefore, has so complete an
internationalism spread throughout the national
structure of society: in no other profession or craft is
there so general an understanding or appreciation of
fellow workers in other parts of the world. This implies
no special merit or broadmindedness on the part of
scientific men; it is their very good fortune, a good
fortune which involves obligations as well as
privileges. For example when the Nazis in 1933 began
their persecution of Jews and liberals in Germany it
was the scientific community in many other countries
which came most quickly to the rescue of their
colleagues; not out of any special generosity but
because firstly they had personal knowledge of those
who were being persecuted, and secondly they realized
that such persecution struck at the basis of the position
of science and scientific workers in society’ and later :
‘It may be then that through this by-product of
international cooperation science may do as great a
service to society (just as learning did in the Middle
ages) as by any direct results in improving knowledge
and controlling natural forces: not- as I would
emphasize again- from any special virtue which we
scientists have, but because in science world society
can see a model of international cooperation carried on
not merely for idealistic reasons but because it is the
obvious and necessary basis of any system that is to
work’ [6].
These views and ideas motivated Hill to become a
founder member of the Academic Assistance Council
(AAC) an organization that offered help to Jewish and
other liberal scientists persecuted in Nazi Germany and
other fascist countries
3. A.V. Hill and the Council for Assisting Refugee
Academics
In 1933 whilst studying in Vienna, William Beveridge
the director of the London School of Economics
learned that academics deemed ‘undesirable’ by the
Nazi government either because they were Jews or of a
different political opinion than the Nazis were
dismissed from their position and unable to work.
Dismayed by this, Beveridge returned to England keen
to help these scholars [1]. He established the Academic
Assistance Council (AAC) which later became Council
for Assisting Refugee Academics (CARA) and finally
The Society for Protection of Science and Learning
(SPSL). This organization assisted academics forced to
flee Nazi Germany, and later other countries ruled by
Nazi Germany. He persuaded the prominent physicist
Ernest Rutherford to become the first President and
Hill Vice President of AAC.
In May 1933 Beveridge distributed a letter signed by
many distinguished academics amongst them 5 Nobel
laureates to publicize the new organization. The letter
was published in major British newspapers. In June,
Rutherford identified the charity’s aims as twofold: 1.
to create a fund for academic assistance of displaced
scholars, and 2. to act as a center of information, i.e.
putting academics in touch with organizations that can
best help them [11]. By the outbreak of the war the
S.P.S.L. had aided at least 1500 scholars. A.V. Hill’s
commitment to the organization that enabled scientists
to continue scientific work was expressed in his letter
to Beveridge on New Year’s Day 1934: ‘It is not that
these people will perish as human beings, but that as
scholars and scientists they will have to take up
something else in order to live.’ With hindsight and our
present knowledge of the Holocaust this statement
seems to have greatly underestimated the dangers and
perils faced by these scientists, who would have
perished had they not got out of the countries ruled by
Nazi Germany. Thus by helping their colleagues,

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scientists more than any other intellectual group helped
to defy the program to exterminate European Jews.
This is in marked contrast to other professional
organizations such as the medical or legal who for fear
of competition did not offer help to their colleagues.
Above all, as emphasized by Canadian historian David
Zimmerman the role of the S.P.S.L. in the history of
academic freedom has not been adequately recognized,
and Zimmerman seeks to redress this. He writes that
the S.P.S.L. became a quasi-government agent and
helped to rescue a generation of European scholars
[13]. Historian Gary Werskey emphasized the speed
and efficiency with which the A.A.C. was established.
He wrote, 'within a matter of weeks after the first
expulsions of Jewish scholars from Germany,
researchers like Hill and Lord Rutherford were able to
set up an Academic Assistance Council’. The
exceptional number of scientists rescued by this group
who achieved ground breaking discoveries during their
career is remarkable [12]. Scientific achievements are
difficult to measure, but the number of Nobel prizes
gives some indication. Before 1933 German scientists
had won 33 prizes in science since 1900, the highest
number of any nation, Britain won 18 and the USA 6.
After Hitler’s rise to power 7 Nobel Prize winners left
Germany and 20 of the refugees subsequently obtained
the Nobel Prize [10].
It is likely that by rescuing a generation of scholars
from Nazi ruled Europe A.V. Hill and other members
of the S.P.S.L. contributed more to scientific
development in the West then any single individual
could achieve. Therefore AV.Hills views that
international cooperation of scientists plays an
important role for scientific achievement have been
confirmed. His contribution to bring about this
cooperation while at UCL gives the college a special
place in helping to initiate outstanding scientific
developments in science and is consistent with UCL’s
liberal and secular values.
Conclusions
Although A.V. Hill’s contribution to the understanding
of the problem of how chemical processes provide the
energy to perform mechanical work in skeletal muscle
was outstanding his equally important achievement
was the realization that collaboration between
scientists at national and international level can
advance our understanding of the world around us
more than the work of any single individual. Hill
viewed the scientific community as a ‘family’ who’s
members strive to enhance our understanding of the
world. By providing active help to individuals within
this family Hill and others who assisted his efforts
contributed more to advancing science then any single
individual.
Acknowledgements
I am grateful to D. Miller who helped to add new
information about AV Hill’s work, and improved my
spelling.
Corresponding Author
G. Vrbová, Dept. of Cell and Dev. Biology, Faculty of
Life Sciences, University College London, WC1E
6BT, UK. As from: 25, Ellington Rd. London N10
3DD, UK. E-mail: g.vrbova@ucl.ac.uk
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[4] Feng Tei Pei. Muscle Nerve and Synapse, ed.
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