Are Electromagnetic Fields Making Me Ill? How Electricity and Magnetism Affect Our Health

Are Electromagnetic Fields Making Me Ill?
How Electricity and Magnetism Affect Our Health,
by Brad Roth

Big News! This week Springer published my new book: Are Electromagnetic Fields Making Me Ill? How Electricity and Magnetism Affect Our Health. This book is different from Intermediate Physics for Medicine and Biology: it’s short (122 pages), uses no math, and is aimed at a general audience. Readers of this blog may find parts of the book familiar; over the last couple years I’ve written posts that served as first drafts of some sections. Below is an excerpt from the Introduction.

This book is about electric and magnetic fields, and their effect on your body. We will examine the use of magnets for pain relief, the risk of power line magnetic fields, the safety of cell phones, and the possibility that microwave weapons are responsible for the Havana syndrome. Many medical treatments are based on electromagnetism, including well established ones like heart pacemakers and neural prostheses, and more questionable ones such as bone healing, transcutaneous electrical nerve stimulation, and transcranial direct current stimulation. Innumerable books and articles have been written about each of these topics; my goal in this book is to examine them together, to get the big picture.

This book is not a research monograph. It presents no original discoveries and makes no attempt to be comprehensive. Moreover, it omits numerous details and technicalities that experts often argue about. It does, however, try to offer an overall view of the field that is accurate.

My target readers are nonscientists: journalists, politicians, teachers, students, and anyone who has heard about electric and magnetic fields interacting with biological tissue and wants to learn more. I use no mathematics, avoid jargon, and employ abbreviations only when repeating the same mouthful of words over and over again becomes tedious. I tried my best to make the book understandable to a wide audience….

Sometimes the effect of electric and magnetic fields is controversial. For any debate, I have tried to present both sides. Nevertheless, readers will soon catch on that I’m a skeptic. Each chapter title is a question, of which my answer is usually “probably not” or “no.”

Here is the Table of Contents.

1. Introduction 
2. Can Magnets Cure All Your Ills? 
3. Can a 9-Volt Battery Make You Smarter? 
4. Do Power Lines Cause Cancer? 
5. Will Electrical Stimulation Help Your Aching Back? 
6. Is Your Cell Phone Killing You? 
7. Did 5G Cell Phone Radiation Cause Covid-19? 
8. Did Cuba Attack America with Microwaves? 
9. Is That Airport Security Scanner Dangerous? 
10. Conclusion

Although Russ Hobbie is not a coauthor on my new book, readers familiar with IPMB will see his influence on each page. In one of our last email exchanges before he passed away, I sent Russ an early draft of the book and he claimed to love it (that may have been Russ being kind, as he always was).

Enjoy!

Listen to me read the final chapter of Are Electromagnetic Fields Making Me Ill?

https://www.youtube.com/watch?v=5jJLkBsU4V0

So Simple a Beginning

So Simple a Beginning,
by Raghuveer Parthasarathy.

My friend Raghuveer (Raghu) Parthasarathy (author of the blog The Eighteenth Elephant) recently published a biological physics book titled So Simple a Beginning: How Four Physical Principles Shape Our Living World. Here is an excerpt from his introduction.

I’ve already hinted at the view of nature… this book expands upon, which I identify as biophysical. The term implies a unification of biology and physics. It encapsulates the notion that the substances, shapes, and actions that constitute life are governed and constrained by the universal laws of physics, and that illuminating the connections between physical rules and biological manifestations reveals a framework upon which the dazzling variety of life is built. The notion of universality is central to the utility of physics, and to its appeal… Biophysics extends to the living world the quest for unity that lies at the heart of physics.

So, what are these four principles that Raghu says shape our living world?

• Self-Assembly: “the idea that the instructions for building with biological components—whether molecules, cells, or tissues—are encoded in the physical characteristics of the components themselves.”
• Regulatory Circuits: “The wet, squishy building blocks of life assemble into machines that can sense their environment, perform calculations, and make logical decisions.”
• Predictable Randomness: “The physical processes underlying the machinery of life are fundamentally random but, paradoxically, their average outcomes are reliably predictable.”
• Scaling: “Physical forces depend on the size and shape in ways that determine the forms accessible to living, growing, and evolving organisms.”

So Simple a Beginning is a very different book than Intermediate Physics for Medicine and Biology. SSaB is an introductory book for the general public; IPMB is an intermediate textbook for upper-level undergraduates in the sciences. SSaB examines life from the molecular scale to organs and organisms; IPMB focuses more on tissue-scale physiology and up, with only passing mention of molecular biology and biochemistry. SSaB has no math; IPMB has equations on nearly every page. SSaB has no end-of-chapter homework problems; one of IPMB’s strengths is its large collection of exercises for the reader. SSaB is elegantly and beautifully written; IPMB’s prose is workmanlike, nothing too graceful but adequate for the job. Finally, SSaB contains dozens of Raghu’s charming drawings and paintings; IPMB’s figures tend to be competent but not artistic. I’m gonna send out a strongly worded letter to whoever’s in charge of distributing talent. No one should have the ability to write well and draw skillfully. Raghu does both. That’s cheating.

I’ll end with the final paragraph of Raghu’s introduction. He quotes Darwin’s famous last paragraph of On the Origin of Species. He probably wanted to title his book This View of Life but Stephen Jay Gould already claimed that phrase for his series of essays about evolution. Instead, Raghu took So Simple a Beginning. Raghu’s writing reminds me of Gould, one of my favorite authors. He writes like Gould would have written had Gould been a physicist.

As interesting as these topics and examples may be, their cumulative effect is greater than the sum of their parts. Biophysics transforms the way we look at the world. At the end of On the Origin of Species, Darwin writes:

There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.

I hope to convince you that Nature has a grandeur even deeper than what Darwin discerned. Rather than a contrast between the fixed, clockwork laws of physics and the generation of endless and beautiful forms, the two are inextricably linked. We can identify the crucial “simple beginning” not as the origin of life, nor the formation of our planet, but as the primeval emergence of the physical laws that characterize our universe. The influence of these laws on life didn’t end billions of years ago, but rather shaped and continue to shape all the wonderful forms around us and within us. To discern simplicity amid complexity and to draw connections between life’s diverse phenomena and universal physical concepts gives us a deeper appreciation of ourselves, our fellow living creatures, and the natural world that we inhabit. I hope you’ll agree.

I agree. Read So Simple a Beginning. You’ll love it.

 

Raghuveer Parthasarathy describes So Simple a Beginning.

https://www.youtube.com/watch?v=fxnqq9Dv18o

Louis Harold Gray: A Founding Father of Radiobiology

Louis Harold Gray:
A Founding Father of Radiobiology,
by Sinclair Wynchank.

Only great scientists have units named after them: the newton, the joule, the watt. An important unit in medical physics is the gray. Chapter 15 of Intermediate Physics for Medicine and Biology states

The absorbed dose is the expectation value of the energy imparted per unit mass:

D = dE/dm .            (15.68)

It is measured in joules per kilogram or gray (Gy).

Is the gray named after a scientist or does it have something to do with the color? And if a scientist, then just who is Dr. Gray? The answer can be found in Sinclair Wynchank’s scientific biography Louis Harold Gray: A Founding Father of Radiobiology (Springer, 2007). My summary of Gray’s life is taken from Wynchank’s excellent book.

Gray—known to his friends as “Hal”—was an English radiobiologist born in London in 1905. His parents were poor, and he attended high school at Christ’s Hospital, a British public boarding school established to help boys who could not afford other institutions. The school was noted for its excellent teaching of science. Gray thrived and performed well enough in the sciences that in 1924 he was awarded a scholarship to Trinity College, part of the University of Cambridge.

Cambridge was famous for being the home of the Cavendish Laboratory, headed by Ernest Rutherford. When Gray graduated with a bachelors degree in physics he joined the Cavendish as a graduate student. His thesis advisor was James Chadwick, who discovered the neutron and was Rutherford’s right-hand-man. As a graduate student, Gray derived the Bragg-Gray relationship (see Equation 16.35 in IPMB). Wynchank writes

Hal’s first scientific publication was in 1929 and it provided a method of calculating the dose of X-rays that were used to irradiate someone (the cavity ionisation principle). This was a most important piece of work, for it allows someone to have an X-ray picture taken and then for it to be known what X-ray dosage had been given. Excessive use of X-rays is very dangerous and in the early days of X-ray applications, some doctors and patients died because they had received excessive doses of this radiation… every reader of these words, who has had a chest, or any other X-ray, has benefited from this work of Hal. It is now known as the Bragg-Gray principle, since both Hal and Professor W. H. Bragg, a friend of Rutherford, a Nobelist, former exhibitioner of Trinity College and professor of physics at Leeds, had both independently described the principle. But Bragg had not realised its importance and its long range implications.

After obtaining his PhD in 1931, Gray remained at Cambridge but changed his research direction to study the interaction of radiation with biological materials. After Chadwick discovered the neutron in 1932, Gray became interested how neutrons interacted with tissue. In that same year, Gray married Frieda (Freye) Marjorie Picot, an English Literature major at Girton College, Cambridge.

Wynchank continues:

Hal’s work at Cambridge ended in 1933 when he took up a post of hospital physicist at the Mount Vernon Hospital in Northwood, on the northern edge of London... Hal’s principal reason for the move was to be able to do full time research in his newly chosen field, the study of ionising radiation to aid cancer treatment... [In February 1938, Hal built] the world’s first accelerator neutron source for biological research... Hal’s insight with regard to this crucial function of energy deposition in tissue irradiation led finally to the unit of absorbed dose of radiation being re-defined in terms of energy and being adopted internationally in 1953. Later the unit was posthumously named after him, being officially termed the “Gray”... In 2 years of slog and improvising most creatively, [Hal and his collaborator] built the neutron generator and then studied the relative effectiveness of various radiations: neutrons, alphas, X-rays and gammas, when they cause cellular damage... Hal found that his neutrons when irradiating mouse tumours were 17 times more effective than gammas.

Gray and Freye had two sons, born in 1939 and 1943. Gray was a firm pacifist. During World War II his work was considered so important that he was exempted from military duty.

At the start of 1946, Hal was appointed senior physicist in the Radiotherapy Research Unit (RRU) of the Medical Research Council (MRC), located at the large and very prestigious postgraduate Hammersmith Hospital in West London... Hal was the first to explain the oxygen enhancement effect, although others had previously suggested that some parts of a tumour might lack oxygen and so be able to resist destruction by ionising radiation... Radioactive atoms (radioisotopes) were also investigated at the RRU. Their valuable clinical applications resulted from collaborative studies at the Hammersmith Hospital and elsewhere. This was the beginning of a new medical speciality, nuclear medicine.

In 1953, after a dispute with his supervisor about the relative priority of clinical versus basic research, Gray abruptly left the RRU and accepted a new position in a London laboratory funded by the charity known as the British Empire Cancer Campaign (BECC).

Hal’s life work after Cambridge can be summed up as relating radiobiology to radiotherapy, so that more effective treatment of cancer would result. Almost single-handedly he was the initiator of the relevance of oxygen, stressing its potential importance to the treatment of patients. This oxygen effect (that is its presence) increased radiation’s destructive power. He made many radiotherapists appreciate the importance, where it was appropriate, of experimental results to the better understanding of how to manage their patients… Free radicals’ effects on the DNA molecule, a crucial component of life, were also studied by Hal and his colleagues… Ways of improving the action of radiation were studied and the findings allowed more effective treatment. One successful such approach was to find pharmaceuticals which, if located in the region to be irradiated, cause the radiation to kill more cancer cells. These pharmaceutical products are radiosensitisers and Hal was one of the first to investigate them.

Gray received many prestigious awards, including election as a Fellow of the Royal Society of London. He died in July 1965, at the age of 59, from a stroke. Had Gray not died so young, he might have eventually been awarded a Nobel Prize.

I’ll end with a tribute to Gray that readers of IPMB will appreciate. Gray was

“the first—and quite possibly the last—scientist to have had a thorough appreciation in all four sectors of radiation research: physics, chemistry, biology and medicine.”

 ____________________________________________

A personal note: Academically speaking I am descended from James Chadwick, so Louis Harold Gray is my academic great-great-great uncle. It’s good to know you better, Uncle Hal!

Numerical Recipes is Online

Numerical Recipes,
by Press, Teukolsky, Vetterling, and Flannery.

In Intermediate Physics for Medicine and Biology, Russ Hobbie and I often refer to Numerical Recipes: The Art of Scientific Computing, by William Press, Saul Teukolsky, William Vetterling, and Brian Flannery. We usually cite the second edition of the book with programs written in C (1995), but the copy on my bookshelf is the second edition using Fortran 77 (1992). For those of you who don’t own a copy of this wonderful book, did you know you can read it online?

The address of the Numerical Recipes website is easy to remember: numerical.recipes. There you will find free copies of the second editions of Numerical Recipes for Fortran 77, Fortran 90, C, and C++ (2002). If you want easy, quick access to the third edition (2007), you will have to pay a fee. But if you are willing to put up with brief delays and annoying messages (which the authors call “nags”), you also can read the third edition for free.

The text below is from the Preface to the third edition.

“I was just going to say, when I was interrupted...” begins Oliver Wendell Holmes in the second series of his famous essays, The Autocrat of the Breakfast Table. The interruption referred to was a gap of 25 years. In our case, as the autocrats of Numerical Recipes, the gap between our second and third editions has been “only” 15 years. Scientific computing has changed enormously in that time.

The first edition of Numerical Recipes was roughly coincident with the first commercial success of the personal computer. The second edition came at about the time that the Internet, as we know it today, was created. Now, as we launch the third edition, the practice of science and engineering, and thus scientific computing, has been profoundly altered by the mature Internet and Web. It is no longer difficult to find somebody’s algorithm, and usually free code, for almost any conceivable scientific application. The critical questions have instead become, “How does it work?” and “Is it any good?” Correspondingly, the second edition of Numerical Recipes has come to be valued more and more for its text explanations, concise mathematical derivations, critical judgments, and advice, and less for its code implementations per se.

Recognizing the change, we have expanded and improved the text in many places in this edition and added many completely new sections. We seriously considered leaving the code out entirely, or making it available only on the Web. However, in the end, we decided that without code, it wouldn’t be Numerical Recipes. That is, without code you, the reader, could never know whether our advice was in fact honest, implementable, and practical. Many discussions of algorithms in the literature and on the Web omit crucial details that can only be uncovered by actually coding (our job) or reading compilable code (your job). Also, we needed actual code to teach and illustrate the large number of lessons about object-oriented programming that are implicit and explicit in this edition.

Russ and I cited Numerical Recipes in IPMB when we discussed integration, least squares fitting, random number generators, partial differential equations, the fast Fourier transform, aliasing, the correlation function, the power spectral density, and bilinear interpolation. Over the years, in my own research I have consulted the book about other topics, including solving systems of linear equations, evaluation of special functions, and computational analysis of eigensystems.

I highly recommend Numerical Recipes to anyone doing numerical computing. I found the book to be indispensable.

The Annotated Hodgkin & Huxley: A Readers Guide

The Annotated Hodgkin & Huxley,
by Indira Raman and David Ferster.

I have always loved the classic set of five papers published by Hodgkin and Huxley in the Journal of Physiology. I often assigned the best of these, the fifth paper, when I taught my Biological Physics class. But reading the original papers can be a challenge. I was therefore delighted to discover The Annotated Hodgkin & Huxley: A Readers Guide, by Indira Raman and David Ferster. In their introduction, they write

After nearly seventy years, Alan Hodgkin and Andrew Huxley’s 1952 papers on the mechanisms underlying the action potential seem more and more like the Shakespeare plays of neurophysiology, works of astounding beauty that become less accessible to each successive generation of scientists. Everyone knows the basic plot (the squid dies at the beginning), but with their upside-down and backwards graphs and records, unfamiliar terminology and techniques, now arcane scientific asides, and complex mathematical underpinnings, the papers become a major effort to read closely without guidance. It is our goal to provide such guidance, by translating graphs and terminology into the modern idiom, explaining the methods and underlying theory, and providing historical perspective on the events that led up to the experiments described. By doing so, we hope to bring the pleasure of reading these extraordinary papers to any physiologist inclined to read them.

Raman and Ferster then give seven reasons to be so inclined.

• “The sheer pleasure of an exciting scientific saga...” 
• “Coming to know the electrical principles that govern the operation of neurons...” 
• “To see firsthand what it is like to be at a scientific frontier...” 
• “The series of papers provide an exemplary…illustration of the scientific method at its best...” 
• “To understand the purpose and power of quantification and computation in science...” 
• “The papers teach us that rigorous science does not require the elimination of error and artifact,”
• “To develop a sense of one’s place in history.”

After a brief chapter about the historical background, the fun really begins. Each of the five papers is presented verbatim on even-numbered pages, with annotations (notes, redrawn figures, explanations, comments) on facing odd-numbered pages. 

One annoying problem with the original papers is that Hodgkin and Huxley defined the transmembrane potential differently than everyone else; they took resting potential to be zero and denote depolarization as negative. Raman and Ferster have redrawn all the figures using the modern definition; rest is −65 mV and depolarization is positive. With this change, the plots of the m, h, and n gates (which control the opening and closing of the sodium and potassium channels) versus transmembrane potential look the same as they do in Fig. 6.37 of Intermediate Physics for Medicine and Biology. I sometimes wish I could take a time machine, go back to 1952, and say “Hey Al! Hey Andy! Don’t use that silly convention for specifying the transmembrane potential. It will be a blemish your otherwise flawless series of papers.”

One of my favorite annotations is in response to Hodgkin and Huxley’s sentence “the equations derived in Part II of this paper [the fifth article in the series] predict with fair accuracy many of the electrical properties of the squid giant axon.” Raman and Ferster write “This may be the greatest understatement of the entire series of five papers.” I would say it’s one of the greatest understatements in all of science.

The final annotation follows Hodgkin and Huxley’s final sentence of their fifth paper: “it is concluded that the responses of an isolated giant axon of Loligo to electrical stimuli are due to reversible alterations in sodium and potassium permeability arising from changes in membrane potential.” Raman and Ferster add “H&H end their tour de force with a mild but precise statement that electrical excitability in the squid giant axon results from voltage-gated conductances. The discoveries that underlie this simple conclusion, however, completely transformed the understanding of cellular excitability in particular and bioelectricity in general. As John W. Moore—a postdoc with Kenneth Cole in 1952—once quipped, it took the rest of the field about a decade to catch up.”

The appendices at the end of The Annotated Hodgkin & Huxley are useful, particularly Appendix Five about numerical methods for solving the Hodgkin & Huxley equations. Huxley performed his calculations on a mechanical calculator. Raman and Ferster write

The mechanical calculator Huxley used was a pre-war era Brunsviga Model 20… which is an adding machine with a few features that streamline the calculations. To multiply 1234 by 5678, for example, one must follow these steps:

• Enter 1234 on the sliding levers (on the machine’s curved face), one digit at a time. 
• Position the carriage (at the front of the machine) in the ones position. 
• Turn the crank eight (at the far right) times. 
• Slide the carriage to the tens position 
• Turn the crank seven times. 
• Slide the carriage to the hundreds position. 
• Turn the crank six times. 
• Slide the carriage to the thousands position. 
• Turn the crank five times.
  

Thus, 30 individual operations are required to multiply two four-digit numbers.

Andrew Huxley, you are my hero.

Happy 70th anniversary of the publication of these landmark papers. I’ll end with a quote about them from Raman and Ferster’s epilogue

The following decades saw tremendous advances in physiology that built directly on the discoveries of H&H. Ultimately, what began as a basic scientific inquiry in a fragile invertebrate with a fortuitously oversized axon would provide the basis for the development of a vast array of biomedical research fields. The studies that the H&H papers made possible would not only yield immeasurable insights into brain and muscle function but also identify, explain, and alleviate medical conditions as diverse as epilepsies, ataxias, myotonias, arrhythmias, and pain.

Cells, Gels and the Engines of Life

Cells, Gels and the Engines of Life,
by Gerald Pollack.

I recently read Gerald Pollack’s book Cells, Gels and the Engines of Life: A New, Unifying Approach to Cell Function. I’ve always taken a simple, physicist’s view of a cell: salt water inside, salt water outside, with a membrane between; the membrane being where all the action is. Pollack’s perspective is entirely different, and challenges the standard dogma in cell biology. He focuses on the how the inside of a cell resembles a gel.

The gel-like nature of the cytoplasm forms the foundation of this book. Biologists acknowledge the cytoplasm’s gel-like character, but textbooks nevertheless build on aqueous solution behavior. A gel is quite different from an aqueous solution—it is a matrix of polymers to which water and ions cling. That’s why gelatin desserts retain water, and why a cracked egg feels gooey.

The concept of a gel-like cytoplasm turns out to be replete with power. It accounts for the characteristic partitioning of ions between the inside and outside of the cell... It also explains the cell’s electrical potential: potentials of substantial magnitude can be measured in gels as well as in demembranated cells... Thus, the gel-like character of the cytoplasm accounts for the basic features of cell biophysics.

What do I think of Pollack’s radical attitude toward biology? I’m not sold on his ideas, but his book certainly made me rethink my fundamental assumptions about biology in general, and electrophysiology in particular.

Pumps and Channels

In Intermediate Physics for Medicine and Biology, Russ Hobbie and I describe the standard view of how ion gradients across the cell membrane are created by a pump (page 155).

To maintain the ion concentrations a membrane protein called the sodium-potassium pump uses metabolic energy to pump potassium into the cell and sodium out.

On page 193, we discuss ion channels.

Selective ion channels are responsible for the initiation and propagation of the action potentials.

Pollack doesn’t believe pumps and channels are important. How can this be? What about patch clamping? Section 9.7 of IPMB talks this revolutionary technique (page 251).

The next big advance was patch-clamp recording (Neher and Sakmann 1976). Micropipettes were sealed against a cell membrane that had been cleaned of connective tissue by treatment with enzymes. A very-high-resistance seal resulted [(2–3)×10⁷ Ω] that allowed one to see the opening and closing of individual channels.

Pollack says

The existence of single ion channels appeared to be confirmed by ground-breaking experiments using the patch-clamp technique… This dazzling result has so revolutionized the field of membrane electrophysiology that the originators of this technique, Erwin Neher and Bert Sakmann, were awarded the Nobel Prize. The observation of discrete events would seem to confirm beyond doubt that the ions flow through discrete channels.

Results from the laboratory of Fred Sachs, on the other hand, make one wonder. Sachs found that when the patch of membrane was replaced by a patch of silicon rubber, the discrete currents did not disappear… they remained essentially indistinguishable from those measured when the membrane was present.

Yikes! Pollack’s arguments against pumps don’t terrify me quite as much.

Pumping faces obstacles of space and energy. The membrane’s size is fixed but the number of pumps will inevitably continue to grow. At some stage the demand for space could exceed the supply, and what then? Pumping also requires energy. The Na/K pump alone is estimated to consume an appreciable fraction of the cell’s energy supply, and that pump is one of very many, including those in internal membranes. How is the cell to cope with the associated energy requirement?

 

 Membranes

Pollack goes on to renounce the importance of the cell membrane.

Continuing to move boldly, we took it upon ourselves in this chapter to reconsider the notion of the continuous ion barrier [the membrane]. If the barrier were continuous, we reasoned, violating its continuity by tearing large holes should allow ions to surge across the cell boundary and solutes to leak out, dramatically altering the cell’s makeup, shutting down cell function, and eventually killing the cell.

But that did not happen. Whether created by shoving a micropipette into the cell, plucking a patch from the membrane, riddling the membrane with an electrical barrage [electroporation], or slicing the cell into two, the wounds seemed to matter little; the cell could often continue to function as though there had been no violation. It was as though function could be sustained by the cytoplasm alone.

 

The Resting Transmembrane Potential

Russ and I explain the resting potential of a cell in the conventional way: the membrane is selectively permeable to potassium, and the potassium ion concentration is higher inside the cell than outside. The concentrations will be in equilibrium when the resting potential is negative, with a magnitude given by the Nernst equation. Pollack’s explanation is completely different, and focuses on the structuring of water near the hydrophilic surface of proteins.

Cell water excludes ions because it is structured. Exclusion is more pronounced for sodium than for potassium because sodium’s hydration shell is larger and hence more difficult to accommodate in the structured water lattice. Thus, intracellular sodium concentration remains low, whereas potassium can partition more easily into the cytoplasm.

No pumps, no channels, no membranes, no Nernst equation, and no metabolic ATP. Just water.

 

 The Action Potential

Pollack’s story may sound plausible, if not convincing, so far, but what about the action potential? This is where gels come in the forefront of the story. According to Pollack, the cytoplasm is like a gel that can undergo a polymer-gel phase transition. Normally the cytoplasmic polymers are cross linked by calcium, allowing in little water. If the calcium is not there to do the cross-linking, water gets sucked in, loosening the structure.

A plausible way in which the action potential could be initiated, then, is by replacing calcium with a monovalent [singly charged ion such as sodium or potassium]. Classically, sodium is thought to enter the cytoplasm through a localized, receptor-mediated permeability increase. In the proposed [Pollack’s] model, sodium ions flow into the peripheral cytoskeleton and begin displacing calcium. Replacement loosens the network, enabling it to adsorb water and expand. As it expands, permeability is increased, allowing for more sodium entry, further Ca displacement, additional expansion, etc.—like ripping open a zipper.

It sure doesn’t sound much like Hodgkin and Huxley.

Internal Perfusion

For a moment, I thought I had a devastating counter-example that would demolish Pollack’s theory. As mentioned before in this blog, you can squeeze the cytoplasm out of a squid giant axon and replace it by salt water, and the axon still works. But Pollack must have seen me coming; he shot down my counter-example in advance.

Lying just inside the cell membrane is a dense polymer-gel matrix known as the peripheral cytoskeleton… The presence of such a matrix had been unknown during the Hodgkin-Huxley era when experimental axons were routinely “rolled” to extrude the cytoplasm and presumably leave only the membrane. What in fact remains is the combination of membrane plus contiguous cytoskeleton.

 

Conclusion

I have only begun to cover the ideas discussed in Cells, Gels and the Engines of Life. Pollack provides us with a wonderfully written, beautifully illustrated, carefully argued, and well cited alternative view of biology. It was a joy to read, but I remain skeptical. I can think of many arguments in support of the “standard model” of cell physiology that Pollack doesn’t address. My “salt water inside, salt water outside” assumption may be too simplistic, and Pollack’s book is useful for pointing out its many limitations, but Pollack’s ideas have limitations too. Cells, Gels and the Engines of Life is an interesting read, but think long and hard before you start believing it.

Physical Models of Living Systems, Second Edition

Physical Models of Living Systems, 2nd Edition,
by Philip Nelson.

In a 2015 blog post, I discussed Philip Nelson’s then-new book Physical Models of Living Systems. I wrote that “It’s an excellent book, well written and beautifully illustrated.” Recently, Nelson published a second edition of Physical Models of Living Systems. All the nice things I wrote about the first edition remain true in the second, but now there are four new chapters to increase your fun. In this post, I’ll focus on the new chapters.

Chapter 6: Random Walks on an Energy Landscape

I like how Nelson organizes each chapter around a biological question and a physical idea.

Biological question: How can pulling two things apart strengthen their bond?

Physical idea: Bond breaking is a first passage process, controlled by the lowest activation barrier, and that barrier can increase upon moderate loading.

The chapter describes slip bonds and catch bonds. A slip bond is the normal case when the bond’s strength decreases as you pull on it, and a catch bond is the unusual case when its strength increases as you pull. Wikipedia compares a catch bond to one of those Chinese finger traps.

Photograph by Carol Spears on Wikipedia. 

https://commons.wikimedia.org/wiki/File:Finger_trap_toys.jpg

 

Nelson explains catch bonds using random walk simulations; first a free random walk, then one with an applied force, next one in a harmonic oscillator potential, and finally one with a oscillator potential plus a barrier, where if you reach the top of the barrier the bond breaks. The “strength” of the bond then becomes the walking time before reaching the barrier (a “first passage process”). By manipulating the potential shape, he finds clutch bond behavior. He then relates these simple simulations (which the reader can easily perform on their own computer) to T cell activation and leukocyte rolling. In each chapter, he sums up the analysis with a section he calls “The Big Picture.” For this chapter, he writes

Our physical model… was absurdly simple, but it nevertheless contained a lot of buried treasure: the basic facts about free Brownian motion, drift under constant force, equilibration in a trapping potential field, the Boltzmann distribution in equilibrium, the Arrhenius rule for escape in quasiequilibrium, and the entire surprising phenomenon of catch bonding. The key step was to understand bond breaking as a first passage problem.

Chapter 8: Single Particle Reconstruction in Cryo-electron Microscopy

Biological question: How can we combine many noisy images of a viral protein to get one clean image?

Physical idea: We must first align the images, but our best estimate of the required alignment is actually a probability distribution.

In this chapter, Nelson examines how to take noisy electron microscope images of an object that are each rotated or shifted relative to each other, and align them to get a clear picture. He warns us “You can’t win by averaging noisy signals unless you know the proper alignment.” What biological example does he look at? The coronavirus spike protein! Apparently the procedure described in this chapter played a big role in the development of the covid-19 vaccine. The story makes me want to seek out the scientists who developed this method and give them a big hug. 

Chapter 14: Demographic Variation in Epidemic Spread

Biological question: Why do some outbreaks of a communicable illness spread explosively, whereas others, in similar communities, fizzle after the first few cases?

Physical idea: A tiny subpopulation of superspreader individuals can have a huge effect on the course of an epidemic.

This chapter starts with the SIR model of an epidemic (S = susceptible, I = infected, and R = recovered) that I’ve discussed before in this blog. Nelson tweaked it to examine what happens just as the epidemic begins if you have a handful of superspreaders. Once again, the model is applied to understanding covid. In the big picture Nelson writes

We have found that because outbreaks always begin with just one or a few infective individuals, the discrete, stochastic character of transmission has a large effect on outbreak dynamics. Thus, a community that is lucky to get only a mild outbreak in the first instance must not become complacent, imagining themselves to be somehow protected: Always some outbreaks fizzle, but any such instance is just as likely to be followed by a severe outbreak on a later introduction as in any other community. 

There are many ways to improve the realism of the SIR model, but we focused on just one: the well documented fact that some illnesses have superspreader individuals. The implications are profound. Although Figure 14.5a is frightening, such time courses can be replaced by the milder ones in Figure 14.3 by promptly identifying and quarantining just a few percent of the infected population. For example, backward contact tracing seeks to identify contacts of each sick individual who may have been the source of that person’s infection. When multiple backward trails point to the same person, that person may be a superspreader.

Chapter 15: Bet-Hedging Via Stochastic, Excitable Dynamics

Biological question: How can a pathogen hide from the immune system?

Physical idea: Positive feedback with small copy numbers can lead to a stochastic toggle that transiently changes state after a long, random delay.

I like this chapter because it makes good use of phase portrait plots. The pathogen behaves almost like a nerve, which can either sit at rest or fire an action potential, with the all-or-none response relying on a positive feedback loop. 

What bet is being hedged? If you’re in a situation where normally one type of behavior is favored, but on rare occasions the environment changes and an unusual behavior may be needed to save the species, then sometimes organisms will keep most individuals in the normal state but will have a few random individuals in the unusual state just in case.

The second edition of Physical Models of Living Systems still has all the good stuff from the first edition: lovely color figures (including some by David Goodsell), lots of homework problems, comparisons to real data, and a winning combination of words, pictures, equations, and computer code. Add in the four new chapters—and a kindle price under ten dollars!—and you have a masterpiece.

My favorite part of the second edition: Like in the first edition, Nelson cites Intermediate Physics in Medicine and Biology. And, he remembers to update the citation to IPMB's 5th edition!

When Death Becomes Life

When Death Becomes Life,
by Joshua Mezrich.

In last week’s post, I told you about a book I didn’t like. This week, I’ll tell you about one I liked. About a year ago, Russ Hobbie suggested I read When Death Becomes Life: Notes From a Transplant Surgeon, by Joshua Mezrich. Mezrich is a transplant surgeon at the Wisconsin School of Medicine and Public Health. The book starts

The following book is neither a memoir nor a complete history of transplantation. I am not old enough to write a memoir, and a few excellent complete histories of transplantation exist already (and are listed in the bibliography). My goal is not to provide a chronological depiction of my coming-of-age as a surgeon, but rather, to use my experiences and those of my patients to give context for the story of the modern pioneers who made transplantation a reality.

Russ and I discuss transplants briefly in Chapter 5 of Intermediate Physics for Medicine and Biology, when describing the artificial kidney.

The artificial kidney provides an example of the use of the transport equations to solve an engineering problem. The problem has been extensively considered by chemical engineers, and we will give only a simple description here… The reader should also be aware that this “high-technology” solution to the problem of chronic renal disease is not entirely satisfactory… The alternative treatment, a transplant, has its own problems, related primarily to the immunosuppressive therapy.

Mezrich describes the kidney in this way.

The kidney is an exquisite organ. I like to tell my residents that “the dumbest kidney is smarter than the smartest doctor.” In a healthy person with a working organ, blood flows into the kidney and goes through an ingenious system of glomeruli—that is, circular tufts of thin blood vessels surrounding the tubules of the kidney. Across the kidney’s membranes and structures, toxins, wastes, and electrolytes are filtered out into the tubules to be secreted as urine. Kidneys are also involved in controlling blood pressure and stimulating the production of red blood cells. It’s amazing how a working kidney seems to know exactly what to do with fluids and reabsorption, whereas we doctors have so much trouble regulating fluid in patients, no matter how many labs and vitals we check.

After Mezrich told of the challenges he faced in his first kidney transplant, he wrote

Since then, I have done hundreds of kidney transplants, and I promise much more smoothly than that first one. To this day, though, I experience the same feeling of amazement when the organ pinks up and urine squirts out. To this day, I still can’t believe it works—and not just for a few days or a few months. With a little luck, the little beans I successfully transplant into patients should keep pumping out urine for years.

Mezrich tells the story of Willem Kolff’s invention of the dialysis machine (the artificial kidney) in Nazi-occupied Holland. There’s a lot of physics in dialysis, but even more in Jack Gibbon’s development of the first heart-lung machine. Mezrich also reviews the discovery of the immunosuppressive drug cyclosporine (he calls it the penicillin of transplantation), which made long-term kidney, liver, pancreas, and heart transplants possible.

By juxtaposing the history of transplantation with his own career as a transplant surgeon, Mezrich makes clear both the historical development and the special challenges of his field. Anyone applying physics or engineering to medicine would benefit from his unique insights. His look at the human side of medicine contrasts with the more technical information found in Intermediate Physics for Medicine and Biology.

Somehow, Thanksgiving seems like the appropriate time to write about When Death Becomes Life. Certainly, we all owe a great debt to the doctors, nurses, support staff, researchers, organ donors, and their families for this lifesaving surgery. I urge you to sign up to be an organ donor at https://www.organdonor.gov/sign-up. 

I’ll give Mezrich the final word.

By illustrating what it took for me to practice transplantation, and by painting a picture, with the stories of my patients, of how the discipline has touched so many, I hope to highlight the incredible gift transplantation is to all involved, from the doctors to the recipients to those of us lucky enough to be the stewards of the organs. I also will show the true courage of the pioneers in transplant, those who had the courage to fail but also the courage to succeed.

How Death Becomes Life, by Joshua Mezrich. Talks at Google. 

https://www.youtube.com/watch?v=oA-EZ2Tsv1I

The Body Electric

The Body Electric,
By Robert Becker and Gary Selden

Go to www.amazon.com and look up the best selling book in the category “biophysics.” You’ll often find #1 is The Body Electric: Electromagnetism and the Foundation of Life, by Robert Becker and Gary Selden. (Selden helped with the writing, but the book tells Becker’s story.) The purpose of today’s post is to explain why this book is awful.

1. Let’s begin with Becker’s views on nerve conduction (page 86).

“According to the theory, an impulse should travel with equal ease in either direction along the nerve fiber. If the nerve is stimulated in the middle, an impulse should travel in both directions to opposite ends. Instead, impulses travel only in one direction; in experiments they can be made to travel ‘upstream,’ but only with great difficulty. This may not seem like such a big deal, but it is very significant. Something seems to polarize the nerve.”

I stimulated many nerves as a graduate student, back in the days when I did experiments. Action potentials propagate just fine in either direction. I had no difficulty making one travel upstream.

2. Becker didn’t understand why nerves, which fire all-or-none action potentials, can produce smooth, coordinated muscle movements (page 87).

“In addition, impulses always have the same magnitude and speed. This may not seem like such a big thing either, but think about it. It means the nerve can carry only one message, like the digital computer’s 1 or 0… The motor activities we take for granted—getting out of a chair and walking across the room, picking up a cup and drinking coffee, and so on—require integration of all the muscles and sensory organs working smoothly together to produce coordinated movements that we don’t even have to think about. No one has ever explained how the simple code of impulses can do all that.”

A muscle contains many motor units. Each motor unit is controlled by a single motor neuron. If you want a muscle to contract with a small force, you activate one motor unit. If you want a muscle to contract more forcefully, you activate many motor units. Motor unit recruitment, plus changes in nerve firing rate, explains the smooth operation of muscles. 

3. Becker didn’t believe that nerves worked using ionic currents, meaning the movement of ions like sodium, potassium, and chloride dissolved in the salt water that makes up our tissues (page 92).

“At that earlier time, there had been only two known modes of current conduction, ionic and metallic. Metallic conduction can be visualized as a cloud of electrons moving along the surface of metal, usually a wire. It can be automatically excluded from living creatures because no one has ever found any wires in them. Ionic current is conducted in solutions by the movement of ions—atoms or molecules charged by having more or fewer than the number of electrons needed to balance their protons’ positive charges. Since ions are much bigger than electrons, they move more laboriously through the conducting medium, and ionic currents die out after short distances. They work fine across the thin membrane of the nerve fiber, but it would be impossible to sustain an ionic current down the length of even the shortest nerve.”

Regular readers of this blog will recall my post about Baker, Hodgkin and Shaw’s experiment in which they squeezed the axoplasm out of a squid nerve axon and replaced it with salt water. The nerve worked just fine. 

Some individual molecules work by transfer of electrons (for instance, the electron transport chain in mitochondria), but currents flowing through tissue are produced by ions. Ionic currents don’t “die out” after short distances.
 

4. Instead of ionic conduction, Becker believed that nerves conducted electricity by semiconduction (page 94).

“I postulated a primitive, analog-coded information system that was closely related to the nerves but not necessarily located in the nerve fibers themselves. I theorized that this system used semiconducting direct currents and that, either alone or in concert with the nerve impulse system, it regulated growth, healing, and perhaps other basic processes.”

Later, he performed measurements of the Hall effect (a voltage induced by current flowing in a magnetic field) and wrote (page 102):

“The experiment demonstrated unequivocally that there was a real electric current flowing along the salamander’s foreleg, and it virtually proved that the current was semiconducting. In fact, the half-dozen tests I’d performed supported every point of my hypothesis.”

Scientists have made semiconductors based on biological ideas: organic semiconductors and semiconductors based on synthetic biology. But there’s no evidence that semiconductors play a role in our normal physiology. Our bodies are basically all salt water. Ionic conduction is the way currents flow through our tissue.
 

5. Becker declared he had discovered the mechanism of acupuncture (page 234).

“The acupuncture meridians, I suggested, were electrical conductors that carried an injury message to the brain, which responded by sending back the appropriate level of direct current to stimulate healing in the troubled area…. If the lines and points [corresponding to acupuncture meridians] really were conductors and amplifiers, the skin above them would show specific electrical differences compared to the surrounding skin.”

Acupuncture is based on pseudoscience; No anatomical structures such as “meridians” exist, and the vital force “qi” has never been observed. Listen to Harriet Hall describe acupuncture. Read what Edzard Ernst says.

6. Becker asserted that static magnetic fields could act as an anesthetic (page 238).

“A strong enough magnetic field oriented at right angles to a current magnetically ‘clamped it’, stopping the flow [of current]. By placing frogs and salamanders between the poles of an electromagnet so that the back-to-front current in their heads was perpendicular to the magnetic lines of force, we could anesthetize the animals just as well as we could with chemicals.”

Such neurological effects are not caused by static magnetic fields. Patients have undergone magnetic resonance imaging in static magnetic fields far larger than what Becker used, and no one has been anesthetized, regardless of the orientation of their head. Using magnets for pain has been discredited.

7. Becker thought that the cells forming the myelin sheaths surrounding myelinated nerve axons carried their own electric current that could have biological effects (page 239).

“Electron microscope work has shown that the cytoplasm of all Schwann cells is linked together through holes in the adjacent membranes, forming a syncytium that could provide the uninterrupted pathway needed by the current.”

The Schwann cells make up the myelin sheath. Myelin consists of layers of fat with little cytoplasm between the layers. Its purpose is to insulate a nerve between openings called nodes of Ranvier. There is no evidence myelin carries significant current, but even if it did carry current along a nerve through the myelin, it would be interrupted ever millimeter or so by a node. 
 

8. Becker believed that magnetoencephalography confirmed his claim that DC current existed in the brain (page 241)

“The MEG research so far seems to be establishing that every electrical evoked potential is accompanied by a magnetic evoked potential. This would mean that the evoked potentials and the EEG of which they’re a part reflect true electrical activity, not some artifact of nerve impulses being discharged in unison, as was earlier theorized. Some of the MEG’s components could come from such additive nerve impulses, but other aspects of it clearly indicate direct currents in the brain.”

DC currents in the brain are uncommon, and primarily associated with brain injury or migraines. Researchers in biomagnetism interpret their results as arising from additive nerve impulses, discharged in unison.

9. Becker promoted the idea that extrasensory perception was a result of DC or extremely low frequency (ELF) electromagnetic fields (page 267).

“At this time the DC perineural system [myelin sheaths around nerves] and its electromagnetic fields provide the only theory of parapsychology that’s amenable to direct experiment. And it yields hypotheses for almost all such phenomena except precognition. Telepathy may be transmission and reception via a biologically programmed channel of ELF vibrations in the perineural system’s electromagnetic field.”

What can I say? I don’t believe in extrasensory perception.
 

10. Becker suggested electromagnetic effects could explain psychokinesis, such as spoon-bending by pure thought (page 269).

“Once we admit the idea of this kind of influence, then the same kind of willed action of biofields on the electromagnetic structure of inanimate matter becomes a possibility. This encompasses all forms of psychokinesis, from metal-bending experiments in which trickery has been excluded to more rigidly controlled tests with interferometers, strain gauges, and random number generators.”

I don’t believe in psychokinesis either.  Neither did James Randi, who died just a year ago.

11. Becker claimed that weak magnetic fields could affect cognitive ability in humans (page 276).

“We exposed volunteers to magnetic fields placed so the lines of force passed through the brain from ear to ear, cutting across the brainstem-frontal current. The fields were 5 to 11 gauss [0.0005 to 0.0011 tesla], not much compared with the 3,000 gauss needed to put a salamander to sleep, but ten to twenty times earth’s background and well above the level of most magnetic storms. We measured their influence on a standard test of reaction time—having subjects press a button as fast as possible in response to a red light. Steady fields produced no effect, but when we modulated the field with a slow pulse of a cycle every five seconds (one of the delta-wave frequencies we’d observed in salamander brains during a change from one level of consciousness to another), people’s reaction slowed down.”

Many reviews of the biological effects of magnetic fields conclude there are no such effects.
 

12. Becker championed the idea that 60-Hz, power line magnetic fields could cause cancer. But he went even further, saying the such “electropollution” could threaten human existence (page 327).

“Everyone worries about nuclear weapons as the most serious threat to our survival. Their danger is indeed immediate and overwhelming. In the long run, however, I believe the ultimate weapon is manipulation of our electromagnetic environment, because it’s imperceptibility subtle and strikes at the core of life itself. We’re dealing here with the most important scientific discovery ever—the nature of life. Even if we survive the chemical and atomic threats to our existence, there’s a strong possibility that increasing electropollution could set in motion irreversible changes leading to our extinction before we’re even aware of them.” 

The “electropollution” Becker speaks of is weak electric and magnetic fields, such as produced by power lines. Power line magnetic fields are safe, and earlier claims that they are not have been shown to be false (see my previous post). “Electropollution” is closer to an imaginary threat than an existential one.

What do I make of all this? Becker’s book is full of nonsense. Moreover, I know little about some of the topics in the book, such as regeneration, bone growth, and injury currents. There could well be more mistakes than just those I’ve caught.

Becker died almost twelve years ago. Am I beating a dead horse? No. According to Google Scholar, The Body Electric has been cited more than 1000 times in the scientific literature (twice as many times as Intermediate Physics for Medicine and Biology), including over 25 times in 2021 already. It’s cited by the supporters of the worst kind of alternative medicine foolishness. The 5G opponents quote him. The power lines and cancer folks quote him. The magnets for pain promoters quote him.

You might wonder: am I upset just because The Body Electric gets more sales and citations than IPMB? Well, maybe that’s part of it. But I believe debunking Becker’s book is a public service. People need to learn real science.

My favorite story in The Body Electric is the time a bigwig physiologist visited Becker’s lab, and told him outright that his results were “artifact, all artifact” (page 106). Thereafter, Becker and his colleagues referred to this fellow derisively as “Artifact Man” and held him up as a symbol for dogmatism. I love Artifact Man.

Chapter 1 sums up Becker’s view of medicine with a defense of “faith healing, magic healing, psychic healing, and spontaneous healing” (page 25). He goes on to say (page 29) 

“The more I consider the origins of medicine, the more I’m convinced that all true physicians seek the same thing. The gulf between folk therapy and our own stainless-steel version is illusory. Western medicine springs from the same roots and, in the final analysis, acts through the same little-understood forces as its country cousins. Our doctors ignore this kinship at their—and worse, their patients’—peril. All worthwhile medical research and every medicine man’s intuition is part of the same quest for knowledge of the same elusive healing energy.”

No, No, No. The origins of medicine should be science. The gulf between folk therapy and modern medicine is wide and must get wider. Our doctors ignore science at their—and worse, their patients’—peril.

Okay, I’m done now. I realize this post is more of a rant than is usual for me. Sorry about that, but there’s something about The Body Electric that really gets my goat.

The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

The Code Breaker,
by Walter Isaacson

My favorite authors are Simon Winchester, David Quammen, and Walter Isaacson. This week I read Isaacson’s latest book: The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race. I would place it alongside The Eighth Day of Creation and The Making of the Atomic Bomb as one of the best books about the history of science. 

In his introduction, Isaacson writes

The invention of CRISPR and the plague of COVID will hasten our transition to the third great revolution of modern times. These revolutions arose from the discovery, beginning just over a century ago, of the three fundamental kernels of our existence: the atom, the bit, and the gene.

The first half of the twentieth century, beginning with Albert Einstein’s 1905 papers on relativity and quantum theory, featured a revolution driven by physics. In the five decades following his miracle year, his theories led to atom bombs and nuclear power, transistors and spaceships, lasers and radar.

The second half of the twentieth century was an information-technology era, based on the idea that all information could be encoded by binary digits—known as bits—and all logical processes could be performed by circuits with on-off switches. In the 1950s, this led to the development of the microchip, the computer, and the internet. When these three innovations were combined, the digital revolution was born.

Now we have entered a third and even more momentous era, a life-science revolution. Children who study digital coding will be joined by those who study genetic code.

Early in the book, Isaacson describes Francisco Mojica’s discovery that bacteria have “CRISPR spacer sequences”: strands of DNA that serve as an immune system protecting them from viruses.

As we humans struggle to fight off novel strains of viruses, it’s useful to note that bacteria have been doing this for about three billion years, give or take a few million centuries. Almost from the beginning of life on this planet, there’s been an intense arms race between bacteria, which developed elaborate methods of defending against viruses, and the ever-evolving viruses, which sought ways to thwart those defenses.

Mojica found that bacteria with CRISPR space sequences seems to be immune from infection by a virus that had the same sequence. But bacteria without the spacer did get infected. It was a pretty ingenious defense system, but there was something even cooler: it appeared to adapt to new threats. When new viruses came along, the bacteria that survived were able to incorporate some of that virus’s DNA and thus create, in its progeny, an acquired immunity to that new virus. Mojica recalls being so overcome by emotion at this realization that he got tears in his eyes. The beauty of nature can sometimes do that to you.

The Code Breaker focuses on the life and work of Jennifer Doudna, who won the 2020 Nobel Prize in Chemistry. However, the star of the book is not Doudna, nor Emmanuelle Charpentier (who shared the prize with Doudna), nor Mojica, nor any of the other scientific heroes. The star is RNA, the molecule that carries genetic information from DNA in the nucleus to the cytoplasm where proteins are produced.

By 2008, scientists had discovered a handful of enzymes produced by genes that are adjacent to the CRISPR sequences in a bacteria’s DNA. These CRISPR-associated (Cas) enzymes enable the system to cut and paste new memories of viruses that attack the bacteria. They also create short segments of RNA, known as CRISPR RNA (crRNA), that can guide a scissors-like enzyme to a dangerous virus and cut up its genetic material. Presto! That’s how the wily bacteria create an adaptive immune system!

Doudna and Charpentier’s Nobel Prize resulted from their developing the CRISPR-Cas9 system into a powerful technique for gene editing.

The study of CRISPR would become a vivid example of the call-and-response duet between basic science and translational medicine. At the beginning it was driven by the pure curiosity of microbe-hunters who wanted to explain an oddity they had stumbled upon when sequencing the DNA of offbeat bacteria. Then it was studied in an effort to protect the bacteria in yogurt cultures from attacking viruses. That led to a basic discovery about the fundamental workings of biology. Now a biochemical analysis was pointing the way to the invention of a tool with potential practical uses. “Once we figured out the components of the CRISPR-Cas9 assembly, we realized that we could program it on our own,” Doudna says. “In other words, we could add a different crRNA and get it to cut any different DNA sequence we chose.”

Several other themes appear throughout The Code Breaker: 

• The role of competition and collaboration in science, 
• How industry partnerships and intellectual property affect scientific discovery, 
• The ethics of gene editing, and
• The epic scientific response to the COVID-19 pandemic. 

I’m amazed that Isaacson’s book is so up-to-date. I received my second dose of the Pfizer-BioNTech vaccine last Saturday and then read The Code Breaker in a three-day marathon. My arm was still sore while reading the chapter near the end of the book about RNA Covid vaccines like Pfizer’s.

There’s a lot of biology and medicine in The Code Breaker, but not much physics. Yet, some of the topics discussed in Intermediate Physics for Medicine and Biology appear briefly. Doudna uses x-ray diffraction to decipher the structure of RNA. Electroporation helps get vaccines and drugs into cells. Electrophoresis, microfluidics, and electron microscopy are mentioned. I wonder if injecting more physics and math into this field would supercharge its progress. 

CRISPR isn’t the first gene-editing tool, but it increases the precision of the technique. As Winchester noted in The Perfectionists, precision is a hallmark of technology in the modern world. Quammen’s book Spillover suggests that humanity may be doomed by an endless flood of viral pandemics, but The Code Breaker offers hope that science will provide the tools needed to prevail over the viruses.

I will close with my favorite passage from The Code Breaker: Isaacson’s paean to curiosity-driven scientific research.

The invention of easily reprogrammable RNA vaccines was a lightning-fast triumph of human ingenuity, but it was based on decades of curiosity-driven research into one of the most fundamental aspects of life on planet earth: how genes encoded by DNA are transcribed into snippets of RNA that tell cells what proteins to assemble. Likewise, CRISPR gene-editing technology came from understanding the way that bacteria use snippets of RNA to guide enzymes to chop up dangerous viruses. Great inventions come from understanding basic science. Nature is beautiful that way.

 

.

“How CRISPR lets us edit our DNA,” a TED talk by Jennifer Doudna. 

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

Nobel Lecture, Jennifer Doudna, 2020 Nobel Prize in Chemistry.

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

Walter Isaacson, The Code Breaker, Talks at Google.

https://www.youtube.com/watch?v=-LuAuZ09uSs

 

CRISPR-Cas9 (“Mr. Sandman” Parody), by Tim Blais at A Capella Science.

https://www.youtube.com/watch?v=k99bMtg4zRk