Douglas Lea was born in Liverpool on 8 February 1910. From Liverpool
Collegiate School, he went with scholarships to Trinity College, Cambridge, in
1928. He gained firsts in Part I of the Mathematical Tripos in 1929, and in
Part II (physics) of the Natural Sciences Tripos in 1931... He started research in physics at the Cavendish laboratory at a time when Lord Rutherford’s genius pervaded the laboratory, though Lea’s discovery
in 1937 of the capture of a neutron by a proton to form deuterium, with
the emission of gamma rays, was associated more with Sir James Chadwick…
Lea was elected to a fellowship at Trinity College in 1934 and received his Ph.D. in 1935.
I’m always curious about why scientists decide to make the transition from physics to biology. In this case, Lea was worried that nuclear physics had become overcrowded, and there were more opportunities in the less-explored biological sciences.
What a galaxy of talent there was at the Cavendish at that time and what
halcyon days for physics; but Lea could already see the writing on the wall.
As Eileen Lea, his wife, put it in a letter to me recently, this turning to biology
was the result of a deliberate search for an important unexplored field.
Lea at once recognized that until survival curves could be generated with
good precision, it would not be possible to make any inferences regarding the
mode of action of the radiation. He wrote in the first paragraph of his first
paper in the field of biology (Lea, Haines and Coulson 1936):
‘The mechanism of disinfection, however, remains obscure. Theories have
been proposed, but little attempt seems to have been made to analyse the
implications of the various hypotheses and point by point to confirm or disprove
them. Moreover, some writers have ignored the fact that the physical
processes accompanying the passage of various radiations through matter are
fairly completely understood.’
Lea pioneered the “single-target single-hit” model to describe survival curves. This is essentially an mathematical application of the binomial distribution to deduce that the survival probability falls exponentially with the dose. The sixth edition of Intermediate Physics for Medicine and Biology will say more about Lea’s model, in part because my new coauthor, Gene Surdutovich, is an expert on the physics of radiobiology. We will be citing Lea’s influential book Actions of Radiations on Living Cells, published in 1947, the year Lea died at the tender age of 37.
Can we draw any conclusions about Lea’s transition from physics to biology, and his legacy as a scientist? Hall writes
We must view Douglas Lea, his experimental work as well as his attitude to
life, against the background of his times. He chose to stay in Cambridge, but
meanwhile, in the bigger population centres, events were moving rapidly in the
application of physics to radiobiology...
What has been the contribution of the physicist to radiobiology at every
stage? To be quantitative; to work with simple systems and to deduce basic
principles that have a general application. This is the legacy that we have
inherited from men like Douglas Lea. It is clearly difficult to follow in the
footsteps of one who walked with such majestic strides, but it is evidently our
duty to try.
Professor Katz... goes far beyond the first essentials to develop the subject in depth… What impresses me particularly is that each idea is pursued to the numerical level. Each theoretical development comes out in this form, in clearly stated problems worked through with the relevant numbers.
One theme of this blog is to explore the intersection of biology and medicine with physics. I often highlight physicists, like myself, who have made the transition from physics to biology. Katz is an example of a scientist who made the less common transition from physiology and medicine to physics.
To explore this topic in more detail, I examined his memoirs published in The History of Neuroscience in Autobiography. Katz was born in 1911 in Leipzig, Germany. That made him a 21 year old Jew when Hitler took power, which explains why he spent most of his career in England.
In elementary school, Katz obtained a classical education, with an emphasis on Latin and Greek. He wrote
During my last three school years, we had to choose between a continuation of the classical linguistic course, and a mathematically and scientifically oriented curriculum. I chose the former … It was not the lack of natural science training that I later came to regret. This deficiency was made up quite satisfactorily by excellent elementary science teaching in the preclinical university course. But the weakness of my grounding in mathematics was something for which I have never been able to compensate.
He went on to study medicine, getting his M.D. in 1934. In medical school, he studied physics with Peter Debye, mentioned several times in IPMB.
During my first year I had to make up for my total lack of knowledge in the natural sciences. The medical students joined the scientists in their elementary courses in botany, chemistry, physics, and zoology, in addition to the preclinical subjects of anatomy, physiology, and biochemistry. I found
it an advantage not having taken science in high school. All the material I was presented with during my first year at the university was fresh and new, some of it taught by persons of the highest caliber, and there was a good deal that I found absolutely fascinating. I had the benefit of an outstanding physics teacher, the famous Peter Debye (who a few years later received a Nobel Prize in chemistry). He gave his lectures, accompanied by experimental demonstrations, every morning from 8 until 9. Debye was both a great scientist and a great showman who took visible pride in his lectures. He was a marvelous expositor of facts, ideas, and theories. Debye clearly enjoyed teaching as much as research, and he showed his delight in all the successful tricks that he demonstrated in class with a constant smile on his face.
I guess you don’t need a book like IPMB if you’ve got Peter Debey as your physics teacher.
I was influenced strongly by the superb collection of Helmholtz's public lectures. In these, Helmholtz--one of the greatest experimental scientists of all time--explained difficult subjects with exemplary clarity.
In medical school he became fascinated with electrophysiology, which at that time was one of biology’s more mathematical subjects.
I was attracted to neurophysiology at an early stage, from about 1930 onward. In those days, the establishment of the laws of electric excitation of nerve, and their precise mathematical formulation were regarded as a great thing… I felt it was fascinating that one could make accurate and repeatable measurements of electric excitability on living tissues and express the results by a simple mathematical equation. ..
Having myself been involved in the experimental tests, I can say that I found the work attractive and indeed fascinating for two quite different reasons. In the first place the work enabled one to make reproducible measurements of quite extraordinary accuracy with simple equipment. Secondly, although the verification of the theoretical equations was not by itself very fruitful, a number of discrepancies from the predictions of the simple theory gradually emerged which did have important consequences. Such discrepancies led to the recognition of the nonlinear characteristic of the nerve membrane, and of the occurrence of a regenerative voltage change even in the subthreshold range of membrane potentials (the local response), which in turn provided a clue to the mechanism whereby an impulse is initiated.
With Hitler’s rise, Katz emigrated to England and found a position in A. V. Hill’s laboratory.
I came to London to join A.V. Hill's laboratory to serve my apprenticeship with him. That time, 1935 to 1939, was the most inspiring period of my life. Hill's personality had a profound influence on me.
Hill is known for his contributions to muscle physiology, and his work had a strong mathematical component. As a student, Hill had attended Cambridge, where he studied mathematics and was Third Wrangler on the Mathematical Tripos exam.
Finally, during World War II Katz worked on radar, a physics and math heavy subject.
In 1941 I obtained my British naturalization papers in Sydney and shortly afterwards managed to enlist with the Royal Australian Air Force (RAAF), first as a rookie, then graduating as a radar officer. Otto Schmitt had taught me some fairly advanced tricks that one could play with thermionic valves, and that helped me a great deal during my period as a radar trainee. But my four years in the RAAF taught me a great many more useful things, about electronics as well as about human beings…. During the last year of the war I was posted back to Sydney as a liaison officer at the Radiophysics Laboratory. This was quite an interesting place, housed within the University of Sydney and harboring a number of young physicists who later became Fellows of the Royal Society.
Having become a naturalised British citizen in 1941, he was accepted to join the Royal Australian Air Force in 1942 and served as a flight lieutenant in charge of running a mobile radar unit in the south-west Pacific until 1943. This posting was followed by a job back in Sydney for two years, developing radar at Sydney University’s Radio-Physics Laboratory.
To summarize, I am not sure exactly how physics and mathematics became so important in Katz’s research, but given the scientists he trained under and worked with, it’s hardly a surprise. In any case, I still find Katz’s book Nerve, Muscle, and Synapse useful now, sixty years after its first publication. And I’m quite comfortable classifying Bernard Katz as a biological physicist.
One recurring theme in this blog is how scientists make the transition from working in the physical sciences to studying the biological sciences. Indeed, this theme is intimately related to Intermediate Physics for Medicine and Biology. Recently, I decided to consider a case study of how a prominent scientist straddled physics, biology, and medicine. So, I searched for someone famous who illustrates how one trained in physics can end up contributing to the life sciences. I selected Louis Pasteur.
Louis Pasteur, by Patrice Debré.
I base this study on the biography Louis Pasteur by Patrice Debré (translated from French to English by Elborg Forster). As I read this book, I focused on the key events in Pasteur’s education and early research when he made this transition.
Pasteur began his career as a physical scientist studying at the École normale supérieure in Paris.
For his doctorate, Pasteur had to submit two theses, one in physics and one in chemistry. The physics thesis brought together several studies concerning the use of the polarimeter… Pasteur’s first studies showed, or rather confirmed, that two isomorphic substances rotate polarized light to the same degree.
Polarization was a new topic in physics at that time. Étienne-Louis Malus, a fellow Frenchman, discovered the Law of Malus, governing how much light passes through two polarizers, in 1808, just 14 years before Pasteur’s birth. Pasteur’s friend and mentor Jean-Baptiste Biot first showed that polarized light could be rotated when passed through certain crystals. Pasteur’s contribution was to prove that crystals formed from tartaric acid could rotate polarized light either clockwise or counterclockwise, depending on the chirality of the crystal (this acid is asymmetric, having two forms that are mirror images of each other, like the left hand and the right hand). In a famous experiment, he inspected the structure of each crystal under a microscope and determined if it was left or right handed. When he then separated the two types of crystals he could obtain rotation in either direction, although a mixture of the two crystals did not rotate light. This discovery, made in 1848, at first appears to arise from physics and chemistry alone, but its relation to biology is that most biological molecules exist in only one version. Handedness matters in biology. Debré writes
In discovering the principles of molecular asymmetry, Pasteur had done nothing less than to forge a key—and this key has unlocked the door to the whole of modern biology… When Pasteur considered asymmetry on a cosmic scale, he went beyond the confines of physics and chemistry to confront the fundamental questions about life.
Pasteur’s next step toward biology came when he was a young professor at the University of Lille.
At the beginning of the academic year 1856, an industrialist of Lille, M. Bigo, whose son Emile was taking Pasteur’s course at the Faculty of Sciences, came to see him. Many manufacturers of beet root alcohol, he said, were having problems with their production…
This led to Pasteur’s research on fermentation, when a microorganism such as yeast brings about a change to a food or beverage, such as producing alcohol. Fermentation and light polarization do not appear to have much in common, but they do.
The findings Pasteur presented to the Academy of Sciences of Lille, and subsequently that of Paris, seemed very different from the studies he had undertaken previously. He was known as a specialist on crystals, and now he had become a theoretician of fermentation. Ranging from polarized planes of light to culture media, his reagents had little in common. Yet the preoccupations that guided Pasteur’s thinking at that period were not really different from those that had haunted him for a long time: he wanted to understand the relationship between life and molecular asymmetry.
The idea that a living microscopic organism was responsible for fermentation was one of Pasteur’s key insights. In fact, there were two types of yeast involved in beet root fermentation. The desirable one produced alcohol. The undesirable one, that led to all the problems, produced lactic acid. Debré concludes
A few years after the request of industrialist Bigo, Pasteur had thus established beyond a doubt that the lactic acid in the vats in the rue d’Esquermes came from an unfortunate contamination with this yeast. He even suggested the means to get rid of this contamination… Pasteur’s research on fermentation created microbiology.
Pasteur’s work on fermentation led to the related question of spontaneous generation. Many scientists at the time thought that living organisms could spontaneously arise in dead and decaying tissue, but Pasteur showed that such decay was always due to germs that entered the tissue from the air.
Pasteur’s transition to biology became complete after Jean-Baptiste Dumas asked him to investigate a disease that was destroying the silkworm industry in France. To address this issue, he needed to learn more biology.
Pasteur came from crystals. Owing to his scant knowledge of animal biology, he was somewhat apprehensive about experiments on animals. As soon as he accepted Dumas’s assignment, he therefore went, along with his assistant Emile Duclaux, to the physiology course taught by Claude Bernard at the Sorbonne. There he took notes and humbly relived his years of training in the halls of the university. But he found it difficult to learn a whole new field; and indeed, since he had neither the time nor the patience to do this, he soon preferred to form his own ideas on the problem at hand.
Once again, Pasteur was successful in addressing a biological problem; this time bacteria infecting silkworms (they are not really a worm, but a caterpillar).
The caterpillar of Alés led Pasteur from microbiology to veterinary science to medicine… When Pasteur revolutionized the science of his era by discovering the germs and their role, it was only natural that he should become interested in medicine and hygiene.
At this point, Pasteur had essentially completed his transition from physics to biology and medicine. I won’t discuss his later work on the use of antiseptics in surgery, pasteurization, anthrax infection in sheep, or the development of a rabiesvaccine.
Debré summarizes,
In his last studies, Pasteur recalled that he had started out as a chemist. First in the laboratory of the rue d’Ulm and then in his Institute, his ultimate experiments indicate that he was trying to understand how the same microbe can either kill a person or stimulate his or her resistance. This is where bacteriology merged into immunology. Pasteur brought these neighboring disciplines together. Understanding the role of the molecules, the toxins, and the antitoxins involved both chemistry and biology.
So what do I conclude about Pasteur’s transition from the physical to the biological sciences? It wasn’t part of a long-range plan. Nor was it primarily motivated by the desire to help the sick, at least initially. I see two key points. First, the rotation of polarized light when passed through an organic substance led him naturally from physics to biology; scientific problems don’t always respect academic boundaries. Second, requests to address industrial problems further accelerated this transition, and those problems happened to be biological in nature. There seems to be a lot of chance involved in this transition (I think there often is for many scientists). But, as Pasteur famously said, chance favors the prepared mind.
The creation of glucose or other sugars is the reverse of the respiration
process and is called photosynthesis. The free energy
required to run the reaction the other direction is supplied by
light energy.
Photosynthetic organisms convert around 1014 kg of carbon from carbon dioxide into biomass each year. In addition to generating the food that we enjoy eating, photosynthetic organisms emit a waste product, free oxygen, that we enjoy breathing. They also stabilize Earth’s climate by removing atmospheric CO2.
Nelson begins the story by introducing William Arnold, Oppenheimer’s future collaborator.
W. Arnold was an undergraduate student interested in a career in astronomy. In 1930, he was finding it difficult to schedule all the required courses he needed for graduation. His advisor proposed that, in place of Elementary Biology, he could substitute a course on Plant Physiology organized by [Robert] Emerson. Arnold enjoyed the class, though he still preferred astronomy. But unable to find a place to continue his studies in that field after graduation, he accepted an offer from Emerson to stay on as his assistant.
Emerson and Arnold went on to perform critical experiments on photosynthesis. Then Emerson performed another experiment with [Charlton] Lewis, in which they found that chlorophyll does not absorb light with a wavelength of 480 nm (blue), but an accessory pigment called phycocyanin does. Emerson and Lewis concluded that “the energy absorbed by phycocyanin must be available for photosynthesis.”
Here is where Oppenheimer comes into the story. I will let Nelson tell it.
Could phycocyanin absorb light energy and somehow transfer it to the chlorophyll system?...
Arnold eventually left Emerson’s lab to study elsewhere, but they stayed in contact. Emerson told him about the results with Lewis, and suggested that he think about the energy-transfer problem. Arnold had once audited a course on quantum physics, so he visited the professor for that course to pose the puzzle. The professor was J. R. Oppenheimer, and he did have an idea. Oppenheimer realized that a similar energy transfer process was known in nuclear physics; from this he created a complete theory of fluorescence resonance energy transfer. Oppenheimer and Arnold also made quantitative estimates indicating that phycocyanin and chlorophyll could play the roles of donor and acceptor, and that this mechanism could give the high transfer efficiency needed to explain the data.
It is the purpose of the present paper to point out a mechanism
of energy transfer from phycocyanin to chlorophyll, the efficiency of
which seems to be high enough to account for the results of Emerson and
Lewis. This new process is, except for the scale, identical with the process of
internal conversion that we have in the study of radioactivity.
Internal conversion is a topic Russ and I address in IPMB. We said
Whenever a nucleus loses energy by γ decay, there is a
competing process called internal conversion. The energy to
be lost in the transition, Eγ, is transferred directly to a bound
electron, which is then ejected.
Internal conversion is an electromagnetic process that competes with γ emission. In this case the electromagnetic multipole fields of the nucleus do not result in the emission of a photon; instead, the fields interact with the atomic electrons and cause one of the electrons to be emitted from the atom. In contrast to β decay, the electron is not created in the decay process but rather is a previously existing electron in an atomic orbit. For this reason internal conversion decay rates can be altered slightly by changing the chemical environment of the atom, thus changing somewhat the atomic orbits. Keep in mind, however, that this is not a two-step process in which a photon is first emitted by the nucleus and then knocks loose an orbiting electron by a process analogous to the photoelectric effect; such a process would have a negligibly small probability to occur.
Nelson compares the photosynthesis process to another process widely used in biological imaging: Fluorescence resonance energy transfer (FRET). He describes FRET this way.
We can find pairs of molecular species, called donor/acceptor pairs, with the property that physical proximity abolishes fluorescence from the donor. When such a pair are close, the acceptor nearly always pulls the excitation energy off the donor, before the donor has a chance to fluoresce. The acceptor may either emit a photon, or lose its excitation without fluorescence (“nonradiative” energy loss).
Let’s put this all together. The donor in FRET is like the phycocyanin molecule in photosynthesis is like the nucleus in internal conversion. The acceptor in FRET is like the chlorophyll molecule in photosynthesis is like the electron cloud in internal conversion. The fluorescence of the donor/phycocyanin/nucleus is suppressed (in the nuclear case, fluorescence would be gamma decay). Instead, the electromagnetic field of the donor/phycocyanin/nucleus interacts with, and transfers energy to, the acceptor/chlorophyll/electron cloud. In the case of FRET, the acceptor then fluoresces (which is what is detected when doing FRET imaging). The chlorophyll/electron cloud does not fluoresce, but instead ejects an electron in the case of internal conversion, or energizes an electron that can ultimately perform chemical reactions in the case of photosynthesis. All three processes are exquisitely sensitive to physical proximity. For FRET imaging, this sensitivity allows one to say if two molecules are close to each other. In photosynthesis, it means the chlorophyll and phycocyanin must be near one another. In internal conversion, it means the electrode cloud must overlap the nucleus, which implies that the process usually results in emission of a K-shell electron since those innermost electrons have the highest probability of being near the nucleus.
There’s lots of interesting stuff here: How working at the border between disciplines can result in breakthroughs; how physics concepts can contribute to biology; how addressing oddball questions arising from data can lead to new breakthroughs; how quantum mechanics can influence biological processes (Newton rules biology, except when he doesn’t); how seemingly different phenomena—such as FRET imaging, photosynthesis, and nuclear internal conversion—can have underlying similarities.
I wish my command of quantum mechanics was strong enough that I could explain all these resonance effects to you in more detail, but alas it is not.
If you haven’t seen Oppenheimer yet, I recommend you do. Go see Barbie too. Make it a full Barbenheimer. But if you want to learn about the father of the atomic bomb’s contributions to biology, you’d better stick with From Photon to Neuron or this blog.
In order to describe Morse’s life, I’ll quote excerpts from his obituary in the February, 1986 issue of Physics Today, written by his coauthor Herman Feshbach.
The Morse potential looks like the function plotted in Fig. 14.8 of IPMB, although we didn’t mention Morse by name in that chapter.
Morse joined MIT on the faculty. There he taught acoustics and quantum mechanics.
He gave advanced instruction to the brighter undergraduate students. One such undergraduate was Richard Feynman
and the subject was quantum mechanics. At this time he renewed his interest in acoustics. A consequence
was his book Vibration and Sound (1936), which he revised and expanded with Uno Ingard in 1968. Of equal importance to his book was his impact on the field: He brought up to date the methods employed by Lord Rayleigh and applied the results to practical problems of, for example, architectural acoustics.
As influential as Morse’s book on acoustics is, his best-known book is probably the two-volume Methods of Theoretical Physics with Feshbach. That book is a little too advanced to be cited in IPMB, but I remember consulting it often during graduate school.
Handbook of Mathematical Functions, with Formulas, Graphs, and Mathematical Tables.
Morse’s was truly a distinguished career, characterized by a unique breadth and fostered by his wide range of interests and his ability to initiate and develop new ventures. He was a dedicated scientist, or better, natural philosopher. As he wrote: “For those of us who like exploration, immersion in scientific research is not dehumanizing; in fact it is a lot of fun. And in the end, if one is willing to grasp the opportunities it can enable one to contribute something to human welfare.”
Would Morse have considered himself a biological physicist? Probably not. But his main interest was acoustics, and sound perception is inherently biological. In a few places Theoretical Acoustics deals with the physics of hearing. I’m comfortable declaring him an honorary biological physicist.
Savart was born in Meziere, France on June 30, 1791. His family had a long history of excelling in engineering, but Savart chose a different path.
Savart decided on a medical career and about 1808 entered
the hospital in Metz. From 1810 to 1814 he served as a regimental
surgeon in Napoleon’s armies… After discharge from the army, he completed his medical
training in Strasbourg, where he received his doctor’s degree in
October 1816. The title of his doctorate thesis was "Du cirsocele."
The mundane topic of varicocele [enlarged veins in the scrotum] must have had little intrinsic appeal for him, and it is perhaps slight wonder he did not stay in medicine.
I can understand how that topic might drive a person away from the medical profession. For whatever reason, Savart spent little time practicing medicine. Instead, he was interested in physics, and particularly in sound.
In 1817 Savart returned to Metz with the intention of establishing
a medical practice… He
spent his time “more in fitting out a laboratory and building instruments
than in seeing sick people and perusing Hippocrates…” It
was during this period that he… began to devote himself specifically to
the study of acoustics, a subject which engaged his attention almost
exclusively for the remainder of his life.
In 1819 Savart went to Paris… to consult Jean-Baptiste Biot (1774–1862) in connection with his study of the acoustics of musical instruments.
This was undoubtedly a turning point in Savart’s career.
Biot encouraged and aided Savart in many ways and took him into
collaboration in a study of electricity.
In situations where the symmetry of the problem does not allow the [magnetic] field to be calculated from Ampere’s law, it is possible to find the field due to a steady current in a closed circuit using the Biot-Savart law.
Ironically, Savart is remembered among physicists for this one investigation into magnetism rather than a lifetime studying acoustics.
Savart was an excellent experimentalist and instrument builder. He made careful measurements of the frequencies produced by a trapezoid violin, which a French commission found to be as good as the violins of Stradivarius. McKusick and Wiskind describe one of his more significant inventions: the Savart wheel.
About 1830 Savart invented a toothed wheel for determining
the number of vibrations in a given musical tone. He attached
tongues of pasteboard to the hoop of the wheel and arranged for
these to strike a projecting object as the wheel was turned… [With this invention]
Savart [determined] the frequency
limits of audibility of sounds for the human ear [see Section 13.4 in IPMB]. He set the
low and high values at 8 and 24,000 cycles per second, respectively... The values he determined are of the same order of
magnitude as the 16 to 16,000 cycles per second one usually hears
quoted now.
Savart also has a unit named for him.
The savart is a unit related to the perceptible
change in frequency; 300 savarts are approximately equal to one
octave. However, this unit has not enjoyed general acceptance and
usage.
Savart became of member of the French Academie des Sciences in 1827, a position he held
“until his untimely death on 16 March 1841 at the age of fifty years.”
Félix Savart is a biological physicist in the mold of Helmholtz, Young, and Poiseuille. He’s just the sort of interdisciplinary scientist that Russ and I had in mind when writing Intermediate Physics for Medicine and Biology.
Young (1773–1829) went to medical school and was a practicing physician. How did he learn enough math and physics to become a biological physicist? In Young’s case, it was easy. He was a child prodigy and a polymath who learned more through private study than in a classroom. As an adolescent he was studying optics and building telescopes and microscopes. As a teenager he taught himself calculus. By the age of 17 was reading Newton’s Principia. By 21 he was a Fellow of the Royal Society.
Some of his most significant contributions to biological physics were his investigations into physiological optics, including accommodation and astigmatism. In Intermediate Physics for Medicine and Biology, Russ Hobbie and I state that the “ability of the lens to change shape and provide additional converging power is called accommodation.” Robinson describes Young’s experiments that proved the changing shape of the lens of the eye is the mechanism for accommodation. For instance, he was able to rule out a mechanism based on changes in the length of the eyeball by making careful and somewhat gruesome measurements on his own eye as he changed his focus. He showed that patients whose lens had been removed, perhaps because of a cataract, could no longer adjust their focus. He also was one of the first to identify astigmatism, which Russ and I describe as “images of objects oriented at different angles… form at different distances from the lens.”
Young’s name is mentioned in IPMB once, when analyzing the wave nature of light: “Thomas Young performed some interference experiments that could be explained only by assuming that light is a wave.” The Last Man Who Knew Everything describes Young’s initial experiment, where he split a beam of light by letting it pass on each side of a thin card, with the beams recombining to form an interference pattern on a screen. Young presents his famous double-slit experiment in his book A Course of Lectures on Natural Philosophy and the Mechanical Arts. Robinson debates if Young actually performed the double-slit experiment or if for him it was just a thought experiment. In any case, Young’s hypothesis about interference fringes was correct. I’ve performed Young’s double-slit experiment many times in front of introductory physics classes. It establishes that light is a wave and allows students to measure its wavelength. Interference underlies an important technique in medical and biological physics described in IPMB: Optical Coherence Tomography.
A green laser passing through two slits 0.1 mm apart produces an interference pattern. Photo by Graham Beards, published in Wikipedia.
Was Young a better biological physicist than Helmholtz? Probably not. Was Young a better scientist? It’s a close call, but I would say yes (Helmholtz had nothing as influential as the double slit experiment). Was Young a better scholar? Almost certainly. In addition to his scientific contributions, he had an extensive knowledge of languages and helped decipher the Rosetta Stone that allowed us to understand Egyptian hieroglyphics. He really was a man who knew everything.
The most famous of medieval scientists was born in Somerset about 1214. We know that he lived till 1292, and that in 1267 he called himself an old man. He studied at Oxford under Grosseteste, and caught from the great polymath a fascination for science; already in that circle of Oxford Franciscans the English spirit of empiricism and utilitarianism was taking form. He went to Paris about 1240, but did not find there the stimulation that Oxford had given him…
Bacon is known for his support of the role of experiment in science. So much of medieval thought was based on religion and mysticism, and an emphasis on science and experiment is refreshing.
We must not think of him [Bacon] as a lone originator, a scientific voice crying out in the scholastic wilderness. In every field he was indebted to his predecessors, and his originality was the forceful summation of a long development. Alexander Neckham, Bartholomew the Englishman, Robert Grosseteste, and Adam Marsh had established a scientific tradition at Oxford; Bacon inherited it, and proclaimed it to the world. He acknowledged his indebtedness, and gave his predecessors unmeasured praise. He recognized also his debt—and the debt of Christendom—to Islamic science and philosophy, and through these to the Greeks…
Like Russ Hobbie and I, Bacon appreciated the role of math in science. Durant summarized Bacon’s view as “though science must use experiment as its method, it does not become fully scientific until it can reduce its conclusions to mathematical form.”
Bacon’s work on optics and vision overlaps with topics in IPMB. Durant notes that “one result of these studies in optics [performed by Bacon and others] was the invention of spectacles.” I can hardly think of a better example of physics interacting with physiology than eyeglasses. Durant concludes:
Experimenting with lenses and mirrors, Bacon sought to formulate the laws of refraction, reflection, magnification, and microscopy. Recalling the power of a convex lens to concentrate many rays of the sun at one burning point, and to spread the rays beyond that point to form a magnified image, he wrote:
We can so shape transparent bodies [lenses], and arrange them in such a way with respect to our sight and the objects of vision, that the rays will be refracted and bent in any direction we desire; and under any angle we wish we shall see the object near or at a distance. Thus from an incredible distance we might read the smallest letters…
These are brilliant passages. Almost every element in their theory can be found before Bacon, and above all in al-Haitham [an Arab scientist also known as Alhazen]; but the material was brought together in a practical and revolutionary vision that in time transformed the world. It was these passages that led Leonard Digges (d. c. 1571) to formulate the theory of which the telescope was invented.
I enjoy reading the Durants’ books. They contain not only the usual political and military history of the world, but also the history of science, art history, music history, comparative religion, linguistics, the history of medicine, philosophy, and literature. While The Story of Civilization may not be the definitive source on any of these topics, it is the best integration of all of them into one work that I am aware of. Had the Durants lived longer, future volumes (which they tentatively titled The Age of Darwin and The Age of Einstein) might have focused even more on the role of science in civilization.
I won’t finish The Story of Civilization anytime soon; I still have seven volumes to go. The series runs to over ten thousand pages, single-spaced, small font (I had to buy more powerful reading glasses for this project). I’ll continue to search for discussions of medical physics and biological physics throughout.
The Story of Civilization. 1. Our Oriental Heritage, 2. The Life of Greece, 3. Caesar and Christ, 4. The Age of Faith, 5. The Renaissance, 6. The Reformation, 7. The Age of Reason Begins, 8. The Age of Louis XIV, 9. The Age of Voltaire, 10. Rousseau and Revolution, and 11. The Age of Napoleon.
If you want to learn about Betzig’s career and work, watch the video at the bottom of this post. In it, he explains how designing a new microscope requires trade-offs between spatial resolution, temporal resolution, imaging depth, and phototoxicity. Many super-resolution fluorescence microscopes (having extraordinarily high spatial resolution, well beyond the diffraction limit) require intense light sources, which cause bleaching or even destruction of the fluorophore. This phototoxicity arises because the excitation light illuminates the entire sample, although much of it doesn’t contribute to the image (as in a confocal microscope). Moreover, microscopes with high spatial resolution must acquire a huge amount of data to form an image, which makes them too slow to follow the rapid dynamics of a living cell.
Eric Betzig’s explanation of the trade-offs between spatial resolution, temporal resolution, imaging depth, and phototoxicity.
Betzig’s key idea is to trade lower spatial resolution for improved temporal resolution and less phototoxicity, creating an unprecedented tool for imaging structure and function in living cells. The figure below illustrates his light-sheet fluorescence microscope.
A light-sheet fluorescence microscope.
The sample (red) is illuminated by a thin sheet of short-wavelength excitation light (blue). This light excites fluorescent molecules in a thin layer of the sample; the position of the sheet can be varied in the z direction, like in MRI. For each slice, the long-wavelength fluorescent light (green) is imaged in the x and y directions by the microscope with its objective lens.
The advantage of this method is that only those parts of the sample to be imaged are exposed to excitation light, reducing the total exposure and therefore the phototoxicity. The thickness of the light sheet can be adjusted to set the depth resolution. The imaging by the microscope can be done quickly, increasing its temporal resolution.
A disadvantage of this microscope is that the fluorescent light is scattered as it passes through the tissue between the light sheet and the objective. However, the degradation of the image can be reduced with adaptive optics, a technique used by astronomers to compensate for scattering caused by turbulence in the atmosphere.
Listen to Betzig describe his career and research in the hour-and-a-half video below. If you don’t have that much time, or you are more interested in the microscope than in Betzig himself, watch the eight-minute video about recent developments in the Advanced Bioimaging Center at Berkeley. It was produced by Seeker, a media company that makes award-winning videos to explain scientific innovations.
Enjoy!
A 2015 talk by Eric Betzig about imaging life at high spatiotemporal resolution.
I am an emeritus professor of physics at Oakland University, and coauthor of the textbook Intermediate Physics for Medicine and Biology. The purpose of this blog is specifically to support and promote my textbook, and in general to illustrate applications of physics to medicine and biology.
