Louis Pasteur, Biological Physicist

Louis Pasteur (1822–1895)

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 rabies vaccine. 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. 

 

 

https://www.youtube.com/watch?v=OXdbQ1JkX7c
 

 https://www.youtube.com/watch?v=1lLNZQVPpQA

J. Robert Oppenheimer, Biological Physicist

J. Robert Oppenheimer.

Did you watch Oppenheimer in the theater this summer? I did. The movie told how J. Robert Oppenheimer led the Manhattan Project that built the first atomic bomb during World War II. But the movie skipped Oppenheimer’s research in biological physics related to photosynthesis.

Russ Hobbie and I only make a passing mention of photosynthesis in Chapter 3 of Intermediate Physics for Medicine and Biology.

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.

From Photon to Neuron,
by Philip Nelson.

To learn more about Oppie and photosynthesis, I turn to Philip Nelson’s wonderful textbook From Photon to Neuron: Light, Imaging, Vision. His discussion of photosynthesis begins

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.

So, what nuclear energy transfer process was Oppenheimer talking about? In Arnold and Oppenheimer’s paper, they wrote

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, E_γ, is transferred directly to a bound electron, which is then ejected.

Introductory Nuclear Physics,
by Kenneth Krane.

More detail can be found in Introductory Nuclear Physics by Kenneth Krane.

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.

Oppenheimer and General Groves
at the Trinity test site. I love
Oppie’s pork pie hat.

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. 

 

 

The official trailer to Oppenheimer.

https://www.youtube.com/watch?v=bK6ldnjE3Y0

 

 

Photosynthesis.

https://www.youtube.com/watch?v=jlO8NiPbgrk&t=14s

Philip Morse, Biological Physicist

This Sunday is the 120th anniversary of the birth of American physicist Philip Morse (1903–1985). Russ Hobbie and I mention Morse in Chapter 13 of our book Intermediate Physics for Medicine and Biology. We write

A classic textbook by Morse and Ingard (1968) provides a more thorough coverage of theoretical acoustics.

Theoretical Acoustics,
by Morse and Ingard.

The reference is to the book

Morse PM, Ingard KU (1968) Theoretical Acoustics. McGraw-Hill, New York.

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.

It was at Case [School of Applied Science, now Case Western Reserve University] that his lifelong interest in acoustics began. Morse received his BS in 1926, and pursued his graduate studies at Princeton University. It was a very exciting time, as the new quantum mechanics was the focus of attention.

Anyone who’s studied the vibrational states of molecules will probably have seen the Morse potential.

He wrote several papers alone and with Ernst Stueckelberg on molecular physics—in one of these he developed the “Morse potential.”

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.

Although Morse was not involved in the Manhattan Project, he did do applied physics research during World War II.

He and his colleagues played a decisive role in the defeat of the German submarine campaign. He gave a fascinating account of that effort in his autobiography, In At The Beginnings: A Physicist’s Life.

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 chaired the advisory committee that supervised the production of the Handbook of Mathematical Functions, with Formulas, Graphs, and Mathematical Tables.

Morse was the driving force behind the useful Handbook of Mathematical Functions, edited by Milton Abramovitz and Irene Stegun and produced by NBS [National Bureau of Standards] in 1964.

Feshbach concluded

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.

 

Happy birthday, Philip Morse!

Felix Savart, Biological Physicist

Bust of Félix Savart
in the Institut de France.
From Wikipedia.

 

 

I’m fascinated by scientists who make the transition from medicine to physics, which is the opposite of my own transition from physics to medicine. One example is Félix Savart. In this blog post, I provide several excerpts from a 1959 article by Victor McKusick and H. Kenneth Wiskind, titled Félix Savart (1791–1841), Physician-Physicist: Early Studies Pertinent to the Understanding of Murmurs (Journal of the History of Medicine and Allied Sciences, Volume 14, Pages 411–423).

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.

McKusick and Wiskind compare Savart to three other physicians who made the transition to physics: Hermann von Helmholtz, Thomas Young, and Jean Leonard Marie Poiseuille. When Savart was 28, he made a life-changing trip to Paris.

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.

Savart’s name appears in Intermediate Physics for Medicine and Biology only when paired with Biot for the Biot-Savart Law. Russ Hobbie and I write

8.2.3 The Biot-Savart Law

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.

Another unit for frequency interval, discussed previously in this blog, is the cent. A savart is about 4 cents.

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.

Bart Hopkin describes the Savart wheel.
https://www.youtube.com/watch?v=yhen0XGyheY

A Trapezoid violin, designed by Félix Savart.
https://www.youtube.com/watch?v=Q3npNDKkqsc

 

Jennifer Cash describes the Biot-Savart law.
https://www.youtube.com/watch?v=1BoIH6Quhiw

Thomas Young, Biological Physicist

The Last Man Who Knew Everything,
by Andrew Robinson.

Almost ten years ago in this blog, I speculated about who was the greatest biological physicist of all time, and suggested that it was the German scientist Hermann von Helmholtz. Today, I present another candidate for GOAT: the English physicist and physician Thomas Young. Young’s life is described in Andrew Robinson’s biography The Last Man Who Knew Everything.

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.

Young also studied color vision based on the idea that the retina can detect three primary colors. This work was rediscovered and further developed by Helmholtz fifty years later. Young was also one of the first to suggest that light is a transverse wave and therefore can be polarized.

In Chapter 1 of IPMB, Russ and I define the Young’s modulus, which relates stress to strain in elasticity and plays a key role in biomechanics. Young also studied capillary action and surface tension, two critical phenomena in biology.

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.

Roger Bacon, Biological Physicist

The Story of Civilization,
by Will and Ariel Durant.

About a year ago I began reading the eleven-volume series The Story of Civilization by Will and Ariel Durant. I just finished Volume 4, The Age of Faith. A History of Medieval Civilization—Christian, Islamic, and Judaic—from Constantine to Dante: A.D. 325–1300. Of course, I’m always on the lookout for how a book overlaps with Intermediate Physics for Medicine and Biology. In The Age of Faith I found a scholar from the Middle Ages who might qualify as a biological physicist: Roger Bacon. Durant writes (citations removed)

VII. ROGER BACON: c. 1214–92

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.

Now, on to The Renaissance. 

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.

 

In Our Time: Season 19/Episode 30, Roger Bacon (April 20, 2017)

https://www.youtube.com/watch?v=i3riF-F7hGY

 

The Durants—Will & Ariel Durant: The Story of Civilization Documentary.

https://www.youtube.com/watch?v=Jc8aFTuCAu0

Eric Betzig, Biological Physicist

Important advances in fluorescence microscopy highlight the interaction of physics and biology. This effort is led by Eric Betzig of Berkeley, winner of the 2014 Chemistry Nobel Prize. Betzig obtained his bachelor’s and doctorate degrees in physics, and only later began collaborating with biologists. He is a case-study for how physicists can contribute to the life sciences, a central theme of Intermediate Physics for Medicine and Biology.

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.

https://www.youtube.com/watch?v=2R2ll9SRCeo

“Your Textbooks Are Wrong, This Is What Cells Actually Look Like.” Produced by Seeker.

https://www.youtube.com/watch?v=9euW5iCjKDo

Carl Woese, Biological Physicist

The Tangled Tree,
by David Quammen.

Recently I listened to the audiobook The Tangled Tree: A Radical History of Life, by David Quammen. The book is a wide-ranging history of molecular phylogenetics and its central character is Carl Woese. His landmark discovery was the place of the archaea in the history of life.

The discovery and identification of the archaea, which had long been mistaken for subgroups of bacteria, revealed the present-day life at the microbial scale is very different from what science had previously depicted, and that the early history of life was very different too.

Quammen writes

Carl Woese was a complicated man—fiercely dedicated and very private—who seized upon deep questions, cobbled together ingenious techniques to pursue those questions, flouted some of the rules of scientific decorum, make enemies, ignored niceties, said what he thought, focused obsessively on his own research program to the exclusion of most other concerns, and turned up at least one or two discoveries that shook the pillars of biological thought.

How does Woese’s career intersect with Intermediate Physics for Medicine and Biology? As an undergraduate at Amherst College, Woese was a physics major. Therefore, he represents yet another example of a scientist who made the switch from physics to biology. Quammen doesn’t explore this aspect of Woese’s career much, so I searched for what motivated his change, what challenges he faced, and what advantages his physics background provided. An article in the Amherst Magazine provided some insight. While at Amherst, Woese

fell in love with physics while studying under William M. Fairbank, who would go on from Amherst to become “one of the great low-temperature physicists in the world.” Fairbank inspired Woese to go on for his physics Ph.D. at Yale, and it was there that Woese became fascinated with biophysics: the study of biological processes at the molecular level. After earning his doctorate in 1953, Woese took a brief fling at medical school (“I couldn’t bear to treat sick children, so I quit”), then studied at the famed Louis Pasteur Institute in Paris and worked for a while in an experimental biophysics lab operated by General Electric. By 1964 he had signed on at the University of Illinois where, ever since, he has taught microbiology and studied the molecular processes that go on inside single-celled creatures.

Woese’s education parallels my own: a physics major in college, followed a physics PhD but an increasing emphasis on applying physics to biology, then post doctoral study at a leading research center: the Pasteur Institute for Woese and the National Institutes of Health for me. William Fairbank plays a role in both of our careers, as undergraduate mentor to Woese and as academic grandfather to me; my PhD advisor, John Wikswo, had Fairbank as his PhD advisor. You could say that Woese was my academic uncle.

The article continues

Soon after arriving in Urbana-Champaign, Woese dared to tackle a fundamental problem in microbiology—a key problem that had stumped both Stanford's C.B. van Niel and Roger Stanier of Cal-Berkeley, the leading microbiologists of the generation preceding Woese’s. The problem, in a phrase: How could you classify—or “phylogenetically order”—the vast ranks of bacterial and other one-celled organisms, given the fact that their small size and vast complexity made it extremely difficult to study and identify their anatomical and physiological features?

Years later, after gaining a worldwide reputation for solving the problem by making the key identifications at the molecular level by sequencing genetic macromolecules and then comparing one organism’s genetic inheritance to another’s, Woese realized that his training in physics at Amherst had played a major role in his discoveries. As he later told reporters: “I hadn’t been trained as a microbiologist, so I didn’t have their bias [against classifying micro-organic species]. And my physics background had taught me the vital importance of using ‘Occam’s Razor’ whenever I could, because it had taught me that most questions—no matter how seemingly complex—usually turn out to have rather simple, straightforward answers.”

Woese returned to his physics roots later in his career. In The Tangled Tree, Quammen writes

One day in September 2002 [Woese] reached out by email to a theoretical physicist in another corner of the University of Illinois campus. Nigel Goldenfeld was an Englishman, almost thirty years younger, who had arrived in Urbana as an assistant professor, risen to full professor, and spent his middle career studying the dynamics of complex interactive systems. That included topics such as crystal growth, the turbulent flow of fluids, structural transitions in materials, and how snowflakes take shape. The common element was patterns evolving over time. Goldenfeld had never met Woese but knew him by reputation. Later, he called that first ping “the most important email of my life”… In the email, Woese now explained that he wanted to discuss—with someone—the subject of complex dynamic systems. He felt that molecular biology had exhausted its vision, he wrote, and that it needed refocusing around drastic new insights…Woese wanted a partner who understood complex interactive systems and could quantify their dynamics with brilliant math. Whether that partner knew a bacterium from an archaeon, or Darwin from Dawkins, mattered less to him.

Goldenfeld and Woese wrote several papers together, including “Life is Physics: Evolution as a Collective Phenomenon Far From Equilibrium” (Annual Review of Condensed Matter Physics, Volume 2, Pages 375-399, 2011), in which they

discuss how condensed matter physics concepts might provide a useful perspective in evolutionary biology, the conceptual failings of the modern evolutionary synthesis, the open-ended growth of complexity, and the quintessentially self-referential nature of evolutionary dynamics.

In another paper about “Biology’s Next Revolution” (Nature, Volume 445, Page 369, 2007)  they begin

One of the most fundamental patterns of scientific discovery is the revolution in thought that accompanies the acquisition of an entirely new body of data. The new window on the Universe opened up by satellite-based astronomy has in the last decade overthrown our most cherished notions of Cosmology, especially related to the size, dynamics and composition of the Universe. Similarly, the convergence of new theoretical ideas in evolution together with the coming avalanche of environmental genomic data, especially from marine microbes and viruses, will fundamentally alter our understanding of the global biosphere, and is likely to cause a revision of such basic and widely-held notions as species, organism and evolution. Here’s why we foresee such a dramatic transformation on the horizon, and how biologists will need to join forces with quantitative scientists, such as physicists, to create a biology that embraces collective phenomena and supersedes the molecular reductionism of the twentieth century.

Woese and Goldenfeld are IPMB type of people.

Quammen concludes

In later years, as he grew more widely acclaimed, receiving honors of all kinds short of the Nobel Prize, Woese seems also to have grown bitter. He considered himself an outsider. He was elected to the National Academy of Sciences, an august body, but tardily, at age sixty, and the delay annoyed him…He was a brilliant crank, and his work triggered a drastic revision of one of the most basic concepts in biology: the idea of the tree of life, the great arboreal image of relatedness and diversification.

The Place of Carl Woese in Evolutionary Biology

https://www.youtube.com/watch?v=dnnYy8QlQy8 

 Listen to David Quammen discuss The Tangled Tree.

https://www.youtube.com/watch?v=3fjJLKKJPEg

Leonardo Da Vinci, Biological Physicist

Leonardo da Vinci,
by Walter Isaacson.

Leonardo da Vinci (1452 – 1519) is never mentioned in Intermediate Physics for Medicine and Biology, but his presence can be felt throughout. Over the Christmas break I listened to Walter Isaacson’s biography of da Vinci. He’s best known for his famous paintings such as The Last Supper and Mona Lisa. Yet, his accomplishments as a scientist are what tie him to IPMB.

I’m a big fan of Isaacson, and I enjoyed his biographies of Einstein and Jobs (his book about Franklin is on my to-read list). In his introduction, Isaacson describes why he chose to write about da Vinci.

I embarked on this book because Leonardo da Vinci is the ultimate example of the main theme of my previous biographies: how the ability to make connections across disciplines—arts and sciences, humanities and technology—is a key to innovation, imagination, and genius. Benjamin Franklin, a previous subject of mine, was a Leonardo of his era: with no formal education, he taught himself to become an imaginative polymath who was Enlightenment America’s best scientist, inventor, diplomat, writer, and business strategist… Albert Einstein, when he was stymied in his pursuit of his theory of relativity, would pull out his violin and play Mozart… Ada Lovelace, whom I profiled in a book on innovators, combined the poetic sensibility of her father, Lord Byron, with her mother’s love of the beauty of math to envision a general-purpose computer. And Steve Jobs climaxed his product launches with an image of street signs showing the intersection of the liberal arts and technology. Leonardo was his hero.

Drawings of blood vessels,
by Leonardo da Vinci.
Credit: Wellcome Collection,
CC BY.

In Chapter 14 of IPMB, Russ Hobbie and I describe the many different medical imaging techniques used to study atherosclerosis: the narrowing of an artery. I learned from Isaacson that da Vinci was the first to understand this deadly disease. He figured it out during his autopsy of a man who claimed, just before died, that he was over one hundred years old.

In his quest to figure out how the centenarian died, Leonardo made a significant scientific discovery: he documented the process that leads to arteriosclerosis, in which the walls of arteries are thickened and stiffened by the accumulation of plaque-like substances. “I made an autopsy in order to ascertain the cause of so peaceful a death, and found that it proceeded from weakness through the failure of blood and of the artery that feeds the heart and the other lower members, which I found to be very dry, shrunken, and withered,” he wrote. Next to a drawing of the veins in the right arm, he compared the centenarian’s blood vessels to those of a two-year-old boy who also died at the hospital. He found those of the boy to be supple and unconstricted, “contrary to what I found in the old man.” Using his skill of thinking and describing through analogies, he concluded, “The network of vessels behaves in man as in oranges, in which the peel becomes tougher and the pulp diminishes the older they become.”

I’m standing in front of The American Horse,
inspired by da Vinci’s unfinished Horse sculpture,
at Meijer Gardens in Grand Rapids, Michigan.

One aspect of da Vinci’s career that I hadn’t appreciated before was how many of his projects were unfinished, including paintings such as the Adoration of the Magi and the Battle of Anghiari, as well as his Horse sculpture. Much of his scientific work was incomplete, or at least unpublished. An example was his collaborative research with Marcantonio della Torre, an anatomy professor at the University of Pavia.

Marcantonio died in 1511 of the plague that was devastating Italy that year. It is enticing to imagine what he and Leonardo could have accomplished. One of the things that could have most benefited Leonardo in his career was a partner who would help him follow through and publish his brilliant work. Together he and Marcantonio could have produced a groundbreaking illustrated treatise on anatomy that would have transformed a field still dominated by scholars who mainly regurgitated the notions of the second-century Greek physician Galen. Instead, Leonardo’s anatomy studies became another example of how he was disadvantaged by having few rigorous and disciplined collaborators along the lines of Luca Pacioli, whose text on geometric proportions Leonardo had illustrated. With Marcantonio dead, Leonardo retreated to the country villa of Francesco Melzi’s family to ride out the plague.

I think Isaacson lets da Vinci off the hook too easily. Leonardo needed some of Michael Faraday’s discipline to “Work, Finish, Publish.”

A drawing of the heart, by
Leonardo da Vinci.

Much of Chapter 7 in IPMB is about the heart. da Vinci contributed much to our understanding the heart’s anatomy.

Leonardo’s studies of the human heart, conducted as part of his overall anatomical and dissection work, were the most sustained and successful of his scientific endeavors. Informed by his love of hydraulic engineering and his fascination with the flow of liquids, he made discoveries that were not fully appreciated for centuries…

Leonardo was among the first to fully appreciate that the heart, not the liver, was the center of the blood system. “All the veins and arteries arise from the heart,” he wrote on the page that includes the drawings comparing the branches and roots of a seed with the veins and arteries emanating from the heart. He proved this by showing, in both words and a detailed drawing, “that the largest veins and arteries are found where they join with the heart, and the further they are removed from the heart, the finer they become, dividing into very small branches.” He became the first to analyze how the size of the branches diminish with each split, and he traced them down to tiny capillaries that were almost invisible. To those who would respond that the veins are rooted in the liver the way a plant is rooted in the soil, he pointed out that a plant’s roots and branches emanate from a central seed, which is analogous to the heart.

Leonardo was also able to show, contrary to Galen, that the heart is simply a muscle rather than some form of special vital tissue. Like all the muscles, the heart has its own blood supply and nerves. “It is nourished by an artery and veins, as are other muscles,” he found.

Self portrait,
by Leonardo da Vinci.

One of the greatest contributions of physics and engineering to medicine is artificial heart valves. Again, this work builds on da Vinci’s discoveries, including his research on biomechanics and hydrodynamics.

Leonardo’s greatest achievement in his heart studies, and indeed in all of his anatomical work, was his discovery of the way the aortic valve works, a triumph that was confirmed only in modern times. It was birthed by his understanding, indeed love, of spiral flows. For his entire career, Leonardo was fascinated by the swirls of water eddies, wind currents, and hair curls cascading down a neck. He applied this knowledge to determining how the spiral flow of blood through a part of the aorta known as the sinus of Valsalva creates eddies and swirls that serve to close the valve of a beating heart…

Leonardo’s breakthroughs on heart valves were followed, however, by a failure: not discovering that the blood in the body circulates. His understanding of one-way valves should have made him realize the flaw in the Galenic theory, universally accepted during his time, that the blood is pulsed back and forth by the heart, moving to-and-fro. But Leonardo, somewhat unusually, was blinded by book learning. The “unlettered” man who disdained those who relied on received wisdom and vowed to make experiment his mistress failed to do so in this case. His genius and creativity had always come from proceeding without preconceptions. His study of blood flow, however, was one of the rare cases where he had acquired enough textbooks and expert tutors that he failed to think differently. A full explanation of blood circulation in the human body would have to wait for William Harvey a century later.

Vitruvian Man,
by Leonardo da Vinci.

I’ll let Isaacson sum up the moral of his story. It’s a lesson that is relevant for interdisciplinary scientists working at the intersection between physics and physiology, who draw connections between mathematics and medicine.

The fifteenth century of Leonardo and Columbus and Gutenberg was a time of inventions, exploration, and the spread of knowledge by new technologies. In short, it was a time like our own. That is why we have much to learn from Leonardo. His ability to combine art, science, technology, the humanities, and the imagination remains an enduring recipe for creativity. So, too, was his ease at being a bit of a misfit: illegitimate, gay, vegetarian, left-handed, easily distracted, and at times heretical. Florence flourished in the fifteenth century because it was comfortable with such people. Above all, Leonardo’s relentless curiosity and experimentation should remind us of the importance of instilling, in both ourselves and our children, not just received knowledge but a willingness to question it—to be imaginative and, like talented misfits and rebels in any era, to think different.

The Last Supper, by Leonardo da Vinci.

Mona Lisa, by Leonardo da Vinci.

Listen to Walter Isaacson talk about Leonardo da Vinci on Sunday Morning.
https://www.youtube.com/embed/KJboCFa4iVQ?feature=player_embedded%22%20width=%22320