Kenneth Stewart Cole

Kenneth Stewart Cole
Born	10 July 1900 Ithaca, New York
Died	18 April 1984 La Jolla
Fields	Biophysics
Alma mater	Oberlin College Cornell University
Notable awards	National Medal of Science (1967)

Kenneth Stewart Cole (July 10, 1900 – April 18, 1984) was an American biophysicist described by his peers as "a pioneer in the application of physical science to biology".^[1] Cole was awarded the National Medal of Science in 1967.^[2][3]

Biography

Kenneth Cole was known to his wife as Ken but to all his friends as Kacy. His father, Charles Nelson Cole, was an instructor in Latin at Cornell University, and two years later the family moved to Oberlin, Ohio, when his father took a post at Oberlin College. His father would later become the Dean. Kenneth's mother was Mabel Stewart, and he had a younger brother, Robert H., with whom he remained very close throughout his life despite a large difference in age; they were joint authors of four papers published between 1936 and 1942.^[4]

Cole graduated from Oberlin College in 1922 and received a Ph.D. in physics with Floyd K. Richtmyer from Cornell University in 1926. He spent summers working at the General Electric Laboratory in Schenectady, New York.

In 1932, Cole married Elizabeth Evans Roberts, an attorney. Later, her work was mostly concerned with civil rights and in 1956 she joined the staff of the new Civil Rights Commission ^[4]

Kenneth joined the staff of Columbia University in 1937 and remained there until 1946. He had also been associated with the Presbyterian Hospital, and the Guggenheim Foundation for Advanced Study at Princeton University and the University of Chicago. From 1949 to 1954 he was the technical director of the Naval Medicine Research Institute in Bethesda, Maryland. In 1954 he became chief of the laboratory of biophysics of the National Institute of Neurological Diseases and Blindness. He achieved advances that led to the "sodium theory" of nerve transmission that later won Nobel Prizes for Alan L. Hodgkin and Andrew F. Huxley in 1947. He was awarded the National Medal of Science in 1967, the award citation, read: "As a result, we know far more about how the nervous system functions." In 1972 he was made a member of the Royal Society of London. The Biophysical Society awards the Kenneth S. Cole medal to a scientist studying cell membranes. In 1980 he became an adjunct professor of the Department of Neurosciences at the Scripps Institute of Oceanography in San Diego. He had a son, Roger Braley Cole, and a daughter, Sarah Roberts Cole. He died on April 18, 1984.^[2]

Kenneth Cole Personal Biography

Kenneth Stewart Cole was born to Mabel Stewart Cole and Charles Nelson Cole in July 1900 in Ithaca, New York, where Dr. Cole was an instructor of Latin at Cornell University.^[5] In 1902 the family moved to Oberlin when Dr. Cole was appointed Assistant Professor of Classics, and for 25 years, Dean of Oberlin College. He got his nickname Kacy when he was ten. The song Casey Jones was popular and a girl he knew suggested the different spelling and it stuck. His memory of his childhood is that he was lonesome, but he was busy with a paper route. In high school he built a radio station and got approval for operation. He still had an operator’s license in the 1970's. He also worked in factories over the summer and became an Able Seaman. Otherwise, there is little known about his upbringing, but a couple of tales give some hints about the environment he grew up in.

         When the Charles Coles moved to Oberlin, the local chapter of the Daughters of the
    American Revolution came by and invited Mabel Cole to join on a provisional basis,
    pending her having suitable ancestors.  She agreed and got to work, discovering that the
    first ancestor to come to America was Roger Braley in 1680 and tracing ancestors back to
    Francis Brayton in England who was born in 1611.  When she had accumulated more
    ancestor points than anyone else in the Oberlin chapter, Mabel Cole told them what she
    thought of them and the whole idea of the D.A.R. and quit!  She discovered that while all
    of the ancestors she could identify came from Great Britain, most seem to have been
    French Huguenots who had emigrated after the revocation of the Edict of Nantes. 

         The other story is that when Kenneth Cole obtained his doctorate, his father told him that
    this was very nice, but all he had accomplished by getting it was not having to explain for
    the rest of his life why he didn’t have one.

After high school he enrolled at Oberlin College and had an uneventful freshman year. He joined the Student Army Training Corps early into his sophomore year but the war ended before he was deployed, something which bothered him for the rest of his life. After his junior year he worked his way west, among other things fighting a forest fire. When he got to the coast he got a job on a merchant ship which went through the Panama Canal and on to the east coast. He applied to the Bureau of Standards but was rejected. Then a friend helped him get work at the GE Lab in Schnectedy as a physicist for 13 months, where he got his first taste of science. All in all, various happenings led to it taking six years for him to graduate from Oberlin College.

For graduate school he went to Cornell to study physics under F.K. Richtmyer with an instructorship. He recalled having a grim first year, but he developed an interest in biology. For work over the summer he responded to an advertisement for two biophysicists, but was again rejected. A friend referred him to the Cleveland Clinic where he spent the summer and learned of biological membranes while assisting a Dr. Fricke to calibrate his “bridge” for measuring their electrical differences. In his third year at Cornell he began his thesis, but ran into a problem. His topic was in biophysics but the Physics Department told him that they had no-one competent to supervise something so biological and that he should work with the Biology Department, which naturally had the reverse problem. Eventually things got worked out and Kacy obtained his “Phud” as he was wont to describe it. He spent the summer of 1926 at Woods Hole’s Marine Biological Laboratory where he got to know his lifelong friend, W.J.V. Osterhout.

Post-graduate life began with a joint National Research Council fellowship in physics and biology at Harvard. Life was full with symphonies, theater, and bridge. His landlady, widow of a professor, providentially mentioned the giant squid axion in conversation. Summers were spent in Woods Hole, measuring the electric potential across the membrane of sea urchin eggs and sailing. At Osterhoff’s suggestion he applied to Dr. Dubai’s lab in Germany. Initially his application was rejected, but friends again intervened and Dubai relented and accepted him for a postgraduate position in his laboratory in Leipzig in 1927 or 1928. He encountered the early stages of the Hitler movement but recalled not recognizing its significance. Another recollection was taking the Orient express to Istanbul, visiting Athens on the way back. The American community in Leipzig was small, so when an American engineer stopped there with his daughter when returning from advising Soviet Russia on their coal mines it was cause for an event to which Kacy Cole was naturally invited. The daughter was Elizabeth Roberts and she had just completed her Doctorate in Law from U. Cal, Berkley. In retrospect, she and Kacy must have gotten along well.

In 1929, he returned from Germany and took an Assistant Professor of Physiology position at Columbia and as Consultant Physicist at Presbyterian Hospital. He was the second PhD on the medical faculty and initially they had little idea what to do with him beyond teaching. That ended when they discovered that he could calibrate the new, and somewhat confusing, X-ray therapy equipment. He also worked out measures to prevent anesthesia explosions and developed methods of treating an aortic aneurism with a surgeon. Although there is very little mention of it, Elizabeth Roberts decided to work as an attorney in Manhattan about the same time. Summers were spent at Woods Hole and he and his much younger brother Robert Cole worked on their research at night and mornings while refurbishing an old sailboat and racing in afternoons. Then. in 1932, he married Elizabeth Roberts and brought her to Woods Hole. She found it difficult – “All you do is sail and I get seasick!” – but all that got worked out. The next few years were spent at Columbia, with summers in Woods Hole.

In April of 1937, Elizabeth Cole gave birth to a son and there was an issue of what the name should be. Finally the thought came to consult the genealogy which Mabel Cole had done so long ago. That gave them the name they needed, Roger Braley, but also gave them a bit of a shock. They discovered that Mabel’s grandmother was the sister of Elizabeth’s grandmother, but that water was well under the bridge. That a woman from California coming back from Russia and meeting a man from Ohio in Germany could possibly be closely related to him was absurd, but it happened. In the late 1930's, Kacy was in England at Oxford when he got a telegram which sent him off to Hungary to extract the mother of Elizabeth’s brother-in-law. He did manage this by waving around his American passport and not acknowledging that he knew any German, he just got excited in English.

During the later 1930's, Kacy worked on nerve membranes, much of it with A.J. (Bing) Curtis. By 1940 Columbia’s biophysics staff was up to six and he was tired of the hospital environment, so he took a fellowship at Princeton’s Institute for Advanced Study and the Coles had a happy year in a college town. A daughter, Sarah Roberts, came in the spring of 1941.

Kacy had been at the math conference in August, 1939 where Leo Szilard recruited Albert Einstein to write a letter to President Roosevelt, telling him of the weapons potential of a uranium chain reaction.^[6] Then in late 1941 the war came. Kenneth Cole volunteered for the army, feeling that he had not done his part a generation before. He was not accepted, but Arthur Compton asked him to come to Chicago to “consult” in the Metallurgical Lab. He was asked to head a small division of the Manhattan Project which dealt with the biological aspects of the bomb they were attempting to build. A new chapter had begun.

The environment of the Metallurgical Lab was strange to scientists. With tight security they felt quite isolated and they were not at all sure of the success of the effort. Kacy later recalled “the desperation of my friend Szilard that was in the air when I joined the Met Lab in 1942.”

In the early months the odds of success in time to help the war were thought to

be poor. Some thought of their being as poor as one in a million. Then there was the constant drain of recruitment, training, and administration efforts to distract from research on the problems in the massive effort. The small section on biological impact grew from a few men to over 350, with a third in Tennessee.^[7] And DuPont, the Army, the academic “longhairs” (as Kacy called them), and the administrators were forever in squabbles over something or other. Still, thirty-odd years later Kacy recalled, “It was a terribly exciting thing, a million times bigger, faster, and worse than anything done before.”

Libby, as Kacy called his wife, looked for a home fruitlessly. She finally bought an apartment house where the top floor could all be merged into a large apartment for the family. She also worked at improving things and escaping rent-control. Later she joined a law firm in Chicago’s Loop, spending much of her time easing some who were profiting greatly from the war out of clearly illegal schemes to evade the excess profits tax. Sometimes no-one had the energy to make dinner and the kids hardly saw their father. Child care was mostly in the capable hands of Edna Dobson, a rather round black woman who stayed with the family until her demise in the late 1980's.

         After some animal experiments, Kacy felt he had to have some verification that the data
    had some relevance to humans.  Needing a volunteer he attached some radium to his
    wristwatch band and in due time came down with the moderate case of radiation
    poisoning he expected.  He was pleased that his estimates had been borne out.  General
    Leslie Grove was less pleased.  He had a senior scientist working on a super-secret
    project involving uranium showing radiation poisoning.  In about a day Kacy was on his
    way down to Brazil to help them organize their scientific efforts until his hair grew back
    and other symptoms disappeared.

         Kacy was friends with the other senior scientists.  Something that is hard to realize now is
    that the scientific community was relatively small and largely knew each other worldwide
    and where they did not have personal contact they always had friends in common.  He
    was particularly close to the brilliant Leo Szilard.  At one point Leo gave him a book and
    several weeks later started a discussion of it.  This repeated a couple of times, when Kacy
    realized that Leo hadn’t read the book they were discussing – he was having him pre-read
    books of interest to find out which were actually worth his time.  Kacy was furious for
    about a week until the thought struck him that Leo didn’t trust many people to do his pre-
    reading, which bemused him to the point he was no longer mad.

After the atomic pile had its chain reaction the Metallurgical Lab staff mostly relaxed and went back to theory as the real effort moved to Tennessee, New Mexico, and Washington. Kacy’s work intensified as knowing the impact of The Bomb became more critical. He did get to be one of the observers at the activation of the atomic pile and the test explosion. Shortly after becoming president, Truman had the senior scientists surveyed on whether The Bomb should be dropped on Japan. This caused considerable agonizing but in the end everyone agreed that it should be used except for two – Leo Szilard and Kenneth Cole. After the horror of Nagasaki Kacy was even more upset that our supposed civilization had done this. Leo Szilard, of course, went on to organize anti-nuclear efforts. Kacy’s view was that, [the Manhattan Project] took four years out of my life that I might not have chosen with my eyes open – but I cannot regret them.” Another view was that, “During the war [Kacy and his team] produced much of the foundation of what is now known of the biomedical effects of radiation.”

For a short while after the war Kacy was at the University of Chicago, establishing their biophysics graduate course and spending summers in Woods Hole where major progress was made on measuring impedance through inserting a wire into the giant squid axion. Hodgkin and Huxley visited Chicago in 1947 to observe the new work.

         Oscar Meyer (advertised in Chicago as the “finest hotdog in town”), the family
    dachshund, accompanied everyone from Chicago but developed a spinal problem which
    paralyzed his hind quarters.  Kacy put together a tether from aluminum wire covered with
    rubber tubing attached to clothesline and a handle.  He and Oscar went for regular walks,
    Oscar managing the front and Kacy the back.  Once the two came back puffing and Kacy
    proudly announced that he and Oscar “had treed a cat.”

In 1947 Kacy took leave from the Univ. of Chicago to return to Brazil as Visiting Professor at their new Instito do Biofisica.

In 1949, Kacy accepted a position as the Naval Medical Research center’s Technical Director. He was hesitant but still had the nagging feeling that he owed his country something. Libby sold the apartment building for a good profit because rents were higher and was delighted with her new home in Chevy Chase. Edna Dobson came to Washington with the family. Unfortunately, life at the Naval Medical Research Institute was difficult as this was the time when Senator McCarthy did his thing. Kacy managed to defend his research staff but it seemed like there was barely time for anything else. Still, he stayed with the job for a decade, until late in 1959 when he took a position across the road to set up a Laboratory of Biophysics at NIH’s National Institute of Neurological Diseases and Blindness. Research continued at MBL in Woods Hole over the summers during the Naval Medical period. The apparatus later termed the “Voltage Clamp” by Hodgkin and Huxley which had been begun in 1947 was fully refined by 1954 and it was finally possible, as Kacy put it, to “ask a nerve a civil question and get a civil answer.” Hodgkin and Huxley went on to do some impressive work with the Voltage Clamp and they received the 1963 Nobel Prize in Physiology for it, shared with J.C. Eccles for his unrelated work. At the time the origin of the Voltage Clamp was not widely known, but the University of Upsala awarded Kacy an honorary medical degree in 1967, which some saw as a subtle raspberry aimed at the Nobel Committee. In any case, the ceremony was most impressive, with the hat, the ring, and such.

Kacy received many other awards in this period. In 1966, Brazil awarded him their highest civilian award, the National Order of the Southern Cross. Back in 1954, Oberlin awarded him an honorary doctorate along with one to Edward R. Morrow, which particularly pleased him because he had listened to Edward R. Morrow’s nightly news broadcast every night since they started in London early in World War Two and he had an opportunity to personally express his appreciation. In 1968, Kacy was one of the recipients of the National Medal of Science along with the inventor of the Polaroid camera and developer of the helicopter. In 1972, he was named a Foreign Member of the Royal Society – “Only a few Americans have received this honor.’

During the 1963-4 school year Kacy was Regents’ Professor at the University of California, Berkley, giving a series of lectures which he later turned into his book, “Membranes, Ions, and Impulses.” It received lengthy and favorable reviews in Nature, and Science, among others. The Nature review does caution that while the dust jacket claims that elementary calculus is adequate, the first 20 pages included Poisson’s equations, Laplace’s equations in vector form, and Kramers-Kronig integrals. In 1966, Kacy removed himself as director of the Laboratory because, as he put it, he didn’t feel that he should continue to make decisions which affected the lives of others. He also moved to part-time employment and finally retired from NIH around 1980.

Two efforts marked Kacy’s later years. One was a long-term effort to find a home for Biophysics in the organizational world. It was the usual problem of the physicists having problems with the biology and the biologists having problems with the physics. He talked about the problem with Leo Szilard but finally concluded that Leo’s opinion was that Biophysics was “what Leo Szilard chooses to do.” Ultimately the choice was to go it alone with a separate Biophysics Society and Kacy was an acknowledged “prime mover” in the process. The other effort was to visit friends active in research throughout the world, facilitating the movement of ideas – as he put it, he was a bee moving pollen from flower to flower.

In his early 80's, Kacy moved to San Diego where he could visit friends in Scripts Institute to somewhat keep up. He also flew large radio-controlled model planes. In 1982 he was diagnosed with an aortic aneurism. Since he was using a portable oxygen tank because of severe emphysema from smoking for a good 60 years, he was a poor operative risk. He decided that he would rather have however long he got rather than undergoing surgery and, as he put it, “being in and out of hospitals for the rest of my life.” He died two years later at an age of 84. In his will he established a self-liquidating fund for an award to young biophysicists who had not yet been recognized. He felt strongly that the tendency to give awards mostly to those already awarded was wrong. It was self-liquidating because he felt that the dead hand of the past should not influence events indefinitely.

Electrical Model of Tissue

Tissue can be modeled as an electrical circuit with resistive and capacitive properties:

Equivalent Electrical Circuit

Its dispersion and absorption are represented by the empirical formula:

$\epsilon^* - \epsilon_\infty = \dfrac{\epsilon_0 - \epsilon_\infty}{1 + (i\omega\tau_0)^{1-\alpha}}$

In this equation $\epsilon^*$ is the complex dielectric constant, ${\epsilon_0 }$ and $\epsilon_\infty$ are the "static" and "infinite frequency" dielectric constants, $\omega = 2\pi$ times the frequency, and $\tau_0$ is a generalized relaxation time. The parameter $\alpha$ can assume values between 0 and 1, the former value giving the result of Debye for polar dielectrics. This expression requires that the locus of the dielectric constant in the complex plane be a circular arc with end points on the axis of reals and center below the axis.

It is worth emphasizing that the Cole–Cole model is an empirical model of the measured data. It has been successfully applied to a wide variety of tissues over the past 60 years, but it does not give any information about the underlying causes of the phenomena being measured.

Several references in the literature use a form of the Cole equation written in terms of impedance instead of a complex permittivity.^[8] The impedance $Z$ is given by:

$Z = R_\infty\frac{R_0-R_\infty}{1+(\tfrac{jf}{f_c})^{1-\alpha}}$

Where $R_0$ and $R_\infty$ are the resistances at zero frequency (i.e. DC) and infinity, respectively. $f_c$ is often referred to as the characteristic frequency. It should be emphasized that the characteristic frequency is not the same when the analysis is carried out in terms of the complex permittivity. A simple interpretation of the above equation is in terms of a circuit where a resistance $S$ is in series with a capacitor $C$ and this combination is placed in parallel with a resistance $R$. In this case $R_0 = R$ and $R_\infty\ = \tfrac{RS}{R+S}$. It can be shown that $f_c$ is given by $f_c=\tfrac{1}{2\pi C(R+S)}$

References

1. Goldman, D.E. 1985. Kenneth S. Cole 1900-1984. Biophysical Journal 47:859-860
2. "Kenneth Cole, 83, Scientist, is Dead". New York Times. April 20, 1984. Kenneth S. Cole, winner of the National Medal of Science and a pioneer in the study of the electrical properties of nerves and other living cells, died Wednesday at the Wesley Palms Retirement Home in La Jolla, California He was 83 years old. Dr. Cole, known as the father of biophysics, was one of the first scientists to apply the concepts and techniques of physics to the study of the excitation and response of living cells. His studies of electrical resistance in nerve cells, especially those of squid, laid the foundation for the rapid advance of neurophysiology in the 1930s and 1940s.
3. Schwan HP. 2001. The concept of bioimpedance from the start: evolution and personal historical reminiscences. Proc. IX Bioimpedance Conf., Oslo, Norway
4. Huxley, Andrew. "Kenneth Stewart Cole". Retrieved 2007-06-14.
5. Goldman, D.E. 1985. Kenneth S. Cole 1900-1984. Biophysical Journal 47:859-860
6. Schwan HP. 2001. The concept of bioimpedance from the start: evolution and personal historical reminiscences. Proc. IX Bioimpedance Conf., Oslo, Norway
7. Brown, B H; Smallwood, R H; Barber, D C; Lawford, P V; Hose, D R (1999). Medical Physics And Biomedical Engineering. Turtleback Books. p. 736. ISBN 9780613919692.
8. Brown, B H; Smallwood, R H; Barber, D C; Lawford, P V; Hose, D R (1999). Medical Physics And Biomedical Engineering. Turtleback Books. p. 736. ISBN 9780613919692.

Publications

• Cole, K.S. 1979. Mostly membranes. Annual Review of Physiology 41:1-23 PMID 373584
• Cole, K. S., and R. H. Cole. 1941. Dispersion and absorption in dielectrics. J. Chem. Phys. 9:341-351
• Cole, K.S., and Baker, R.F. 1941. Longitudial Impedance of the Squid Giant Axon. J. Gen. Physiol. 24:771-788 (Inductance of membrane)

External links

• National Academy of Sciences Biographical Memoir