Blood flows through
a branching network of vessels (Sect. 1.19), the smallest
of which are capillaries. Each capillary has a diameter of
about 8 μm, meaning that the red blood cells can barely pass
through it single-file.
Eight microns is pretty small; too small to see with your naked eye. So how did we learn about capillaries? The first person to observe capillaries was the Italian microbiologist Marcello Malpighi (1628–1694). He was one of the early users of a microscope.
Malpighi received a medical degree from the University of Bologna, and eventually became the private physician for Pope Innocent XII. He favored rational medicine, based on empirical evidence, during a time when much medicine was still based on ancient authorities with little experimental support.
English physician William Harvey had previously discovered the circulation of blood, showing that the heart pumped blood to the body through the arteries and then returned it to the heart through the veins. Harvey’s theory implied there must be some connection between the arteries and veins so blood could flow in a continuous circuit, but he never identified that connection. Even the great anatomist Andreas Vesalius had wrong ideas about this issue. Malpighi’s greatest discovery was using the microscope to observe capillaries, the tiny blood vessels joining an artery to a vein. He was one of the first scientists to observe red blood cells, and also studied the clotting of blood. He described this research in his book De Polypo Cordis, published in 1666.
In addition, he examined the structure of small insects, such as the silkworm, and discovered that they do not use lungs to breathe but instead small holes in their skin called tracheae (Homework Problem 42 in Chapter 4 of IPMB discusses this issue further). He also observed the microstructure of plants and the development of chick embryos.
Early microscopists like Malpighi, as well as Robert Hooke and Antonie van Leeuwenhoek, demonstrate why Russ and I encourage readers to think about distances and sizes in the very first section of IPMB. Having an intuitive feel for distance scales—what can be seen with the naked eye, what requires a light microscope, and what is too small to see even with a microscope—is so important for understanding biology as well as the history of biology. Early microscopists explored with world of life at a scale from one to one hundred microns; the realm of protozoans, cells, and bacteria. Below that scale, diffraction blurs images, and studies of viruses and macromolecules had to await more advanced technologies such as the electron microscope.
Malpighi died in 1694, at the age of 66, from a stroke. He is often considered the father of histology and embryology.
Recently several research groups have used sub-millimeter sized microcoils to perform magnetic stimulation of nerves. This review assesses the magnitude of the electric field induced by these microcoils. In some cases magnetic stimulation is a plausible mechanism for neural excitation, but in other cases the induced electric field is far too small to excite a neuron. These results indicate that microcoil magnetic stimulation may not occur via magnetic stimulation, but by some other mechanism. One alternative mechanism is capacitive coupling.
Basically, this paper reviews the entire field of microcoil stimulation, and finds that in some cases the idea is plausible, but in other cases it is not. One thing I like about the article is that I develop a toy model for calculating the electric field produced by the coil. While the model is an approximation, it should determine the electric field correct to at least an order of magnitude. The strengths of the model are that it provides great insight, it is so simple computationally that anyone can reproduce the calculation, and it supplies a common way to analyze a host of different publications. One goal of Intermediate Physics for Medicine and Biology is to train students in forming and analyzing such toy models. I think that the field of microcoil stimulation illustrates what happens when researchers skip the simple model and go straight to complicated numerical calculations using code that is treated as a black box. These computations often produce numbers but little intuition or understanding. The user cannot tell if something goes wrong. Back when I was teaching, I would urge my students to “think before you calculate!” This review shows why.
The conclusion of the review states
Magnetic stimulation by microcoils is an active and growing field in neural stimulation. It may have promise for the development of neural prostheses. This review, however, suggests there are many unanswered questions in this area of research… Frankly, the field appears prone to errors. One must analyze the articles carefully to separate the wheat from the chaff.
Transcranial magnetic stimulation works by magnetic induction. Stimulation using a millimeter-sized, multi-turn coil placed close to the target neuron and carrying several amps of current may work by magnetic induction, but the electric field it generates is sometimes slightly below the threshold value you expect is required to excite neurons. Nevertheless, magnetic induction in these cases seems plausible. On the other hand, when milliamps of current are passed through a single-turn wire, magnetic induction does not seem to be a plausible mechanism for excitation; the electric field appears to be too weak. One alternative mechanism is capacitive coupling. An important goal of future microcoil magnetic stimulation research is to resolve what exactly is the underlying mechanism.
The article is open access, so anyone can read it online without a subscription. Enjoy!
Micro-magnetic stimulation (μMS) through micro-scale coils is a rapidly
advancing form of neuromodulation that possesses qualities that give it the potential to be
used as an alternative to electrical stimulation in cases where it cannot be used. However,
reliability of the technique is inconsistent as reported in the peer reviewed literature,
suggesting that there is not a strong understanding of the basis of the technique. In this
thesis, we provide empirical evidence of the efficacy of μMS in dissociated cortical
cultures and a review of μMS’ consistency across early pioneering works. We then simulate
the electric fields generated by μMS using COMSOL and couple the fields to neuron
models in Python to study their response across a range of parameters in neural stimulation.
This is followed by an aim to measure the electric fields of these micro-scale coils to
determine whether they surpass stimulus thresholds reported in literature. Our key findings
suggest that μMS should not be feasible. Finally, we investigate confounding factors during
μMS stimulation that may have effects being mis-attributed to μMS.
I’m delighted that it’s not just my former graduate student Mohammed Alzahrani and me who are skeptical of microcoil magnetic stimulation. We are no longer alone!
Russ Hobbie wrote a review of a revised edition of Physics with Illustrative Examples from Medicine and Biology for the magazine Physics Today (July, 2001). Here are some excerpts.
The Physics Department of the Massachusetts Institute of Technology began about 30 years ago to offer a special calculus-based introductory course for freshmen and sophomores interested in biology. This led to the first edition of George B. Benedek and Felix M. H. Villars’s Physics with Illustrative Examples from Medicine and Biology. The book was issued by Addison-Wesley in 1979 as three paperback typescript volumes. The book fascinated many physicists with the applications of physics in biochemistry and physiology, but they have been out of print since 1990. Now that the AIP Press and Springer-Verlag have issued a second edition, as printed volumes, a new generation of physicists can learn from them…
These are classic books, and anyone planning to include biophysical examples in a calculus-level course should study them carefully. The authors are to be congratulated for their work, and I commend AIP Press and Springer-Verlag for making the books available again.
In his review, Russ lists the book as published in 1979, but I think there must have been earlier editions, because the first edition of Intermediate Physics for Medicine and Biology, published in 1978, cites Physics with Illustrative Examples from Medicine and Biology several times, and lists the publication date as 1973 (Volume 1) and 1974 (Volume 2). Clearly Benedek and Villars influenced the first edition of IPMB and all subsequent editions. You can learn more about Physics with Illustrative Examples from Medicine and Biologyhere, here, and here.
Benedek wasn’t just a textbook author. He invented quasi-elastic light scattering spectroscopy and became a fellow of the American Physical Society in 1962. He received the Association for Research in Vision and Ophthalmology’s Proctor Medal in 1997 for “outstanding research in basic or clinical sciences as applied to ophthalmology.” He was a true biological physicist. He’ll be missed.
MKUltra (pronouced M-K-ultra) was a covert Central Intelligence Agency research program carried out between 1953 and 1973 to investigate mind control. It used techniques such as high doses of the psychedelic drug LSD, hypnosis, sensory isolation, and electroshock therapy to influence a subject’s brain, and in particular to obtain secrets from unwilling people. This program is notorious for torturing studying subjects without their consent, which is considered a grave sin in research today.
One subproject of MKUltra (#119) was to use very low frequencyelectromagnetic fields to influence the brain. This project comes disturbingly close to techniques I’ve worked on over the years, such as transcranial magnetic stimulation. It got me to wondering: is mind control using electromagnetic fields possible?
I guess I have thought about this before, because in the August 14, 2015 post in this blog I suggested that the “psychic probe” described in Isaac Asimov’s famous Foundation Trilogy might be made by combining transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), which are both described in Chapter 8 of Intermediate Physics for Medicine and Biology. In that post I wrote “a combo TMS/MEG unit could therefore both detect and alter brain function.” Of course, I was writing tongue-in-cheek, joking about how a science fiction device might have worked within the constraints of real science. On the other hand, perhaps I was actually an MKUltra agent sending a secret message to my underground accomplices?
That last sentence mocks the recent conspiracy theories surrounding MKUltra. Last week the House Task Force on the Declassification of Federal Secrets held a hearing about the research program. It didn’t focus on the historical record (which is sparse because most of the MKUltra documents were destroyed) but instead went off on weird tangents, talking about things like mind control related to the assassination of President Kennedy. The purpose of this hearing seemed to be aimed primarily at blaming science in general for past errors. Some issues that were brought up, like MKUltra itself, were serious mistakes that should be, and have been, investigated. Others, like bogus lab leak theories related to the origin of Covid, were just crazy talk with no scientific justification. One researcher, Elizabeth Ginexi, a respected former program official at the National Institutes of Health, was invited by the Democrats to talk about the horrendous anti-science policies currently imposed on NIH by anti-vax zealot Robert F. Kennedy, Jr. Ginexi (a hero in my view) tried to discuss these vital issues, but was constantly cut off by Republican members of the committee who were focused on the bizarre and engaged in an attempt to demonize scientists and public health workers.
But back to my question: could electromagnetic fields be used for brain control? Well, transcranial magnetic stimulation is currently used to treat depression, so you can’t rule out the possibility. However, the technique is very nonspecific. I spent seven years at NIH trying to improve the focality and spatial resolution of transcranial magnetic stimulation. Generating a localized stimulus is extraordinarily difficult, especially for activating deep brain structures. You can use transcranial magnetic stimulation to make individual fingers move, but only because the hand has a widespread representation in the motor cortex. The idea that transcranial magnetic stimulation could control individual thoughts or suggest specific actions seems like science fiction to me. Other techniques that have been suggested as potentially useful for mind control are brain-computer interfaces and deep brain stimulation. Both of these have important medical uses. For example, deep brain stimulation can help reduce or control tremors caused by Parkinson’s disease. Perhaps these techniques could potentially be used for controlling behavior, but they are highly invasive (requiring surgery to implant electrodes in the brain).
Are Electromagnetic Fields Making Me Ill?
What about techniques growing out of subproject 119? That work was led by W. Ross Adey and Mary (“Mollie”) Brazier, two leading scientists studying how electromagnetic fields interact with, and are produced by, the brain. I mentioned Adey in my book Are Electromagnetic Fields Making Me Ill?. He claimed to find “window” effects, for which one particular applied field strength resulted in an observable effect, but stronger or weaker fields did not. Similarly, he found that certain frequencies had marked responses (“resonances”) but both higher and lower frequencies did not. These window effects are not very reproducible and are not widely accepted today. Generally, resonant effects are claimed at very low frequencies (say, 20 Hz). Ultimately subproject 119 ended in failure because no mind control methods were found. Some say that a modern offshoot of this research is microwave weapons responsible for the Havana syndrome. Again, in Are Electromagnetic Fields Making Me Ill? I discuss why electromagnetic fields are almost certainly not responsible for the Havana syndrome. My opinion is that this is another anti-science conspiracy theory.
The final question I address is: could something like MKUltra happen today? The ethics rules governing research are far more stringent now than several decades ago. About 15 years ago, I served for one year in an interim role as Oakland University’s Vice Provost for Research, which is the chief research officer at the institution. Among other things, I was in charge of overseeing research misconduct issues at OU. Any human subjects research had to go through our Institutional Review Board. If a faculty member merely wanted to give a simple survey to students, that survey had to be assessed by this board and a detailed consent form was required. Any potentially dangerous human studies were monitored particularly closely, and informed consent was essential. It’s the same at all academic institutions. MKUltra would be virtually impossible in today’s academic research environment. Could it happen in the CIA or another research center associated with the military? I don’t know. Perhaps. But the CIA and other intelligence agencies can’t compete with academia and scientific institutions like the NIH and NSF when it comes to scientific advances. (Take, for example, the recent brouhaha over the military’s claims about “ghost murmur” which are almost certainly bogus.) I don’t believe MKUltra or anything related to it is going on today, especially involving electromagnetic fields to control the brain. I believe that such a suggestion is a conspiracy theory, advanced to discredit scientists and scientific institutions. It’s part of the Republican War on Science. Please, don’t believe the anti-science crackpots. At the very least, insist that they support their claims with evidence. They rarely can.
Angela Rasmussen and Liz Ginexi discuss MKUltra and What Really Happened in the Wuhan Lab
I’m old enough to remember the bicentennial. In 1976 the USA reached the age of 200. I was 15 years old, about to start my junior year in high school, and living in Ashland, Ohio. I recall the bicentennial being a much bigger event than what we are experiencing this year. Perhaps I was simply younger and more easily impressed. Or, perhaps, Chuck Todd’s explanation is correct; I’ve always liked Chuck. Or, perhaps, the problem is that semiquincentennial is so @#%& hard to pronounce!
What was the status of Intermediate Physics for Medicine and Biology back in the summer of 1976? Russ Hobbie, then the sole author, was 43 years old. Just three years before he finished auditing all the courses medical students take in the first two years at the University of Minnesota and must have been hard at work on the first edition of IPMB, published two years later, in 1978, the year I graduated from high school. I didn’t become aware of the book until I reached graduate school at Vanderbilt University. I probably saw it first in 1982 or 1983.
Move forward 50 years and the 6th edition of IPMB should appear (assuming all goes well) just a couple months after the semiquincentennial celebration. Russ Hobbie passed away in 2021, but Gene Surdutovich will join as an author of this new edition.
I expect that during the tricentennial celebration in 2076 people will look back at 2026 as a dark and dangerous time for science, when anti-science forces came to dominate the federal government, promoting vaccine hesitancy, climate change denial, and other nonsense. I hope that by 2076 this era will have passed, and science will have become respectable again, but I’m not certain that will be the case. Will IPMB still be read and used in college courses? Who knows? I’ll be gone by then, and most likely Gene will too. But perhaps new coauthors will come along, and the tricentennial will coincide with the 11th edition of Intermediate Physics for Medicine and Biology!
For you scientists and science-lovers celebrating the 4th of July, I recommend a series of events sponsored by the American Philosophical Society about science during the founding of the United States, called America’s Scientific Revolutionaries. I particularly like the lecture in the video below, about Benjamin Rush—an American Founding Father who was also a medical doctor—and his role in early American medicine. The video is also about the war on vaccines today, and features vaccine scientist Paul Offit. It’s an interesting analysis of how much progress medicine has been made in the last 250 years, how much ground we have lost recently, and the work ahead of us during the next half century.
Communicating Disease: Assessing Benjamin Rush's Public Health Legacies at America's 250th.
I am an emeritus professor of physics at Oakland University, and coauthor of the textbook Intermediate Physics for Medicine and Biology. The purpose of this blog is specifically to support and promote my textbook, and in general to illustrate applications of physics to medicine and biology.
