Photobiomodulation

Harvest with her copy of
Intermediate Physics for
Medicine and Biology.

My Treeing Walker Coonhound Harvest is getting older and having some trouble with arthritis. The vet says she’s showing signs of hip dysplasia, but it’s not too severe yet. I want to nip this problem in the bud, so we have started a treatment regime that includes oral supplements, pain medication, moderate exercise, weight control, and massage. We’re also trying photobiomodulation, sometimes called low-level laser therapy or cold laser therapy.

Russ Hobbie and I don’t mention photobiomodulation in Intermediate Physics for Medicine and Biology. Is it for real? That’s what I want to discuss in today’s blog post. I’ll give you a hint: my answer will be “maybe.”

Harvest getting
photobiomodulation treatment.

We bought a device called Lumasoothe 2 Light Therapy for Pets (lumasoothe.com). I use it in it’s IR Deep Treatment Mode, which shines three wavelengths of light—infrared (940 nm), red (650 nm) and green (520 nm)—from an array of light emitting diodes. I doubt the green light can penetrate to the hip, but red and especially infrared are not attenuated as much. In IPMB, Russ and I talk about how red light is highly scattered, and you can see that by noticing how the red spreads out to the sides of the applicator (kind of like when you hold a flashlight up to your mouth and your checks glow red). The light is delivered in pulses that come at a frequency of about 2.5 Hz (I used the metronome that sits atop my piano to estimate the frequency). I can’t imagine any advantage to pulsing the light, and suspect it’s done simply for the visual effect. I apply the light to Harvest’s hips, about 15 minutes each side.

Mechanisms and Applications
of the Anti-Inflammatory Effects
of Photobiomodulation.

When we first purchased the device, I assumed it worked by heating tissue. But researchers and device manufacturers insist the mechanism is not thermal. So how does it work? To explore that and other issues, I searched the literature, and found a particularly clear open-access review article by Michael Hamblin, then with the Harvard-MIT Division of Health Sciences and Technology: “Mechanisms and applications of the anti-inflammatory effects of photobiomodulation” (AIMS Biophysics, Volume 4, Pages 337–36, 2017). Hamblin has a long history of research on photodynamic therapy (analyzed in Chapter 14 of IPMB), and his more recent work has focused on photobiomodulation.

Hamblin begins (with references removed),

Photobiomodulation (PBM) was discovered almost 50 years ago by Endre Mester in Hungary. For most of this time PBM was known as “low-level laser therapy” as ruby laser (694 nm) and HeNe lasers (633 nm) were the first devices used. Recently a consensus decision was taken to use the terminology “PBM” since the term “low-level” was very subjective, and it is now known that actual lasers are not required, as non-coherent light-emitting diodes (LEDs) work equally well. For much of this time the mechanism of action of PBM was unclear, but in recent years much progress has been made in elucidating chromophores and signaling pathways.

Any time you are talking about a therapy, the dose is crucial. According to a study by medcovet, the output of Lumasoothe is 0.225 J/cm² per minute (it’s advertised at 6.4). I don’t know which of these values to use, so I’ll just pick something in the middle: 1 J/cm². If we divide by 60 seconds, this converts to about 0.017 W/cm². The intensity of sunlight that reaches the earth’s surface is about 0.1 W/cm², so the device puts out less than the intensity of sunlight (at noon, at the equator, with no clouds). The advertised intensity would be similar to the intensity of sunlight. Of course, sunlight includes a wide band of frequencies, while the Lumasoothe emits just three. 

There seems to be an optimum dose, as is often found in toxicology. Hamblin explains

The “biphasic dose response” describes a situation in which there is an optimum value of the “dose” of PBM most often defined by the energy density (J/cm²). It has been consistently found that when the dose of PBM is increased a maximum response is reached at some value, and if the dose in increased beyond that maximal value, the response diminishes, disappears and it is even possible that negative or inhibitory effects are produced at very high fluences.

Joules per square centimeter per minute may not be the best unit to assess heating effects of the Lumasoothe. Let’s assume that 0.017 W/cm² of light penetrates into the tissue about one centimeter (a guess). This means that the device dumps 0.017 watts into a cubic centimeter of tissue. That volume of tissue has a density of about that of water: 1 g/cm³. So the specific absorption rate should be about 0.017 W/g or 17 W/kg. That’s not negligible. A person’s metabolism generates only about 1.5 W/kg. Diathermy to heat tissues uses about 20 W/kg. I don’t think we can rule out some heating using this device. (However, I shined it on my forearm for about two minutes and didn’t feel any obvious warming.)

Hamblin believes there are non-thermal mechanisms involved.

Cytochrome c oxidase (CCO) is unit IV in the mitochondrial electron transport chain. It transfers one electron (from each of four cytochrome c molecules), to a single oxygen molecule, producing two molecules of water. At the same time the four protons required, are translocated across the mitochondrial membrane, producing a proton gradient that the ATP synthase enzyme needs to synthesize ATP. CCO has two heme centers (a and a3) and two copper centers (CuA and CuB). Each of these metal centers can exist in an oxidized or a reduced state, and these have different absorption spectra, meaning CCO can absorb light well into the NIR [near infrared] region (up to 950 nm). Tiina Karu from Russia was the first to suggest that the action spectrum of PBM effects matched the absorption spectrum of CCO, and this observation was confirmed by Wong-Riley et al in Wisconsin. The assumption that CCO is a main target of PBM also explains the wide use of red/NIR wavelengths as these longer wavelengths have much better tissue penetration than say blue or green light which are better absorbed by hemoglobin. The most popular theory to explain exactly why photon absorption by CCO could led [sic] to increase of the enzyme activity, increased oxygen consumption, and increased ATP production is based on photodissociation of inhibitory nitric oxide (NO). Since NO is non-covalently bound to the heme and Cu centers and competitively blocks oxygen at a ratio of 1:10, a relatively low energy photon can kick out the NO and allow a lot of respiration to take place.

That’s a considerable amount of biochemistry, which I’m not an expert in. I’ll assume Hamblin knows a lot more about it than I do. I worry, however, when he writes “the assumption that…” and “the most popular theory…” It makes me wonder how well this mechanism is established. He goes on to suggest other mechanisms, such as the production of reactive oxygen species and a reduction in inflammation.

Hamblin concludes

The clinical applications of PBM have been increasing apace in recent years. The recent adoption of inexpensive large area LED arrays, that have replaced costly, small area laser beams with a risk of eye damage, has accelerated this increase in popularity. Advances in understanding of PBM mechanisms of action at a molecular and cellular level, have provided a scientific rationale for its use for multiple diseases. Many patients have become disillusioned with traditional pharmaceutical approaches to a range of chronic conditions, with their accompanying distressing side-effects and have turned to complementary and alternative medicine for more natural remedies. PBM has an almost complete lack of reported adverse effects, provided the parameters are understood at least at a basic level. The remarkable range of medical benefits provided by PBM, has led some to suggest that it may be “too good to be true”. However one of the most general benefits of PBM that has recently emerged, is its pronounced anti-inflammatory effects. While the exact cellular signaling pathways responsible for this anti-inflammatory action are not yet completely understood, it is becoming clear that both local and systemic mechanisms are operating. The local reduction of edema, and reductions in markers of oxidative stress and pro-inflammatory cytokines are well established. However there also appears to be a systemic effect whereby light delivered to the body, can positively benefit distant tissues and organs.

I have to admit that Hamblin makes a strong case. But there is another side to the question. Hamblin himself uses that worrisome phrase “complementary and alternative medicine.” I have to wonder about thermal effects. We know that temperature can influence healing (that’s why people often use a heating pad). If photobiomodulation causes even a little heating, this might explain some of its effect.

I’ve talked a lot in this blog about websites or groups that debunk alternative medicine. Stephen Barrett of quackwatch looked at Low Level Laser Therapy in 2018, and concluded that “At this writing, the bottom line appears to be that LLLT devices may bring about temporary relief of some types of pain, but there’s no reason to believe that they will influence the course of any ailment or are more effective than standard forms of heat delivery.” Mark Crislip writing for Science Based Medicine in 2012 concluded “I suspect that time and careful studies on the efficacy of low level laser will have the same results as the last decade of acupuncture studies: there is no there there.” Jonathan Jarry wrote about “The Hype Around Photobiomodulation,” saying “That is not to say that all of PBM’s applications are hogwash or that future research will never produce more effective applications of it. But given biomedical research’s modest success rate these days and the ease of coming up with a molecular pathway that fits our wishes, we’re going to need more than mice studies and a plausible mechanism of action to see photobiomodulation in a more favourable light. A healthy skepticism is needed here, especially when it comes to claims of red light improving dementia.” 

What about clinical trials? An interesting one titled “Photobiomodulation Therapy is Not Better Than Placebo in Patients with Chronic Nonspecific Low Back Pain: A Randomised Placebo-Controlled Trial” was published in the journal PAIN in 2021 (Volume 162, Pages 1612–1620). It concluded “Photobiomodulation therapy was not better than placebo to reduce pain and disability in patients with chronic nonspecific LBP [low back pain].” The importance of a randomized, controlled study with an effective placebo is crucial. We need more of these types of studies.

Are Electromagnetic Fields
Making Me Ill?

So, what’s the bottom line? In my book Are Electromagnetic Fields Making Me Ill?, I divided different medical devices, procedures, and hypotheses into three categories: Firmly Established, Questionable, and Improbable (basically: yes, maybe, and no). I would put photobiomodulation therapy in the maybe category, along with transcutaneous electrical nerve stimulation, bone healing using electromagnetic fields, and transcranial direct current stimulation. As a scientist, I’m skeptical about photobiomodulation therapy. But as dog lover, I’m using it every day to try and help Harvest’s hip dysplasia. This probably says more about how much I love Harvest than about my confidence in the technique. My advice is to not get your hopes up, and to follow your vet’s advice about traditional and better-established treatments. The good news: I don’t see much potential for side effects. Is it worth the money to purchase the device? My wife and I were willing to take a moderately expensive bet on a low probability outcome for Harvest’s sake. because she’s the goodest gurl. 

Mechanisms & History of Photobiomodulation with Dr. Michael Hamblin

https://www.youtube.com/watch?v=udnRpZ8l1_0

The Age of Reason Begins

The Age of Reason Begins,
by Will and Ariel Durant.

The title of this week’s post is ironic, because with all the events of the last few months I often suspect that the Age of Reason is coming to a close. The title comes from volume seven of Will and Ariel Durant’s The Story of Civilization. After I retired from Oakland University, I set about reading the entire eleven-volume series. The subtitle of The Age of Reason Begins is: A History of European Civilization in the Period of Shakespeare, Bacon, Montaigne, Rembrandt, Galileo, and Descartes: 1558–1648.

Today I want to focus on Francis Bacon, who is probably the central figure in the Durants’ book (his picture was their choice for gracing the book’s cover). They introduce him this way.

Francis Bacon, who was destined to have more influence on European thought than any other Elizabethan, had been born (1561) in the very aura of the court, at York House, official residence of the Lord Keeper of the Great Seal, who was his father, Sir Nicholas; Elizabeth called the boy ‘the young Lord Keeper.’ His frail constitution drove him from sports to studies; his agile intellect grasped knowledge hungrily; soon his erudition was among the wonders of those ‘spacious times.’

Why bring up Bacon now? Well, the last few months have seen unprecedented attacks on science and scientists: Budget cuts to the National Institutes of Health and the National Science Foundation, climate change denial and vaccine hesitancy, conspiracy theories, political requirements for government funding, the demonization of scientists such an Anthony Fauci, and more. It seems like something horrible happens every day. This makes me wonder: what is the key feature of science that must be preserved above all else? What one thing must we save? I can think of many possibilities. Science drives our economy and prosperity. Scientific discoveries have led to amazing advances in human health. Educating and providing opportunities for our young scientists is a critical investment in our future. Yet, as important as these things are, they aren’t the central issue. They aren’t what we must save lest all be lost. It’s this key element of science, its essence, that brings me to Francis Bacon.

Bacon was an early promoter of the scientific method. The Durants write

Bacon felt that the old Organon [of Aristotle] had kept science stagnant by its stress on theoretical thought rather than practical observation. His Novum Organum proposed a new organ and system of thought—the inductive study of nature itself through experience and experiment. Though this book too was left incomplete, it is, with all its imperfections, the most brilliant production in English philosophy, the first clear call for an Age of Reason.

Let me explain (and perhaps expand on) Bacon’s idea in my own words. How do we know what is true and what is not? By evidence. By experiment. By data. By comparing our ideas to what we can measure happening in the world. By accepting as true only those hypotheses that survive our best efforts to disprove them. By submitting our conclusions to rigorous peer review from our fellow scientists. Yet the current Republican administration seems to have its own ideas of what is true, regardless of the evidence. This is the very opposite of science. It is anti-science.

For example, the reality of climate change and humanity’s impact on global warming is backed by an enormous body of data. We have records of temperature, carbon dioxide concentration, and increasingly violent storms. We have sophisticated mathematical models with which we can conduct numerical experiments to predict what will happen in the future. The evidence is truly overwhelming. Yet, many—including President Trump—don’t care about the evidence. They claim climate change is a “hoax.” They don’t back these claims with facts. They don’t approach the topic as an inductive study based on experience and experiment. They believe things for their own reasons that have nothing to do with evidence or science.

Another example is vaccines. There are so many clinical studies showing that vaccines don’t cause autism. Again, the evidence is overwhelming. Yet people like Health and Human Services Secretary Robert F. Kennedy, Jr. believe just the opposite: that autism is caused by vaccines. They don’t support such claims by presenting new evidence. While they occasionally drag up discredited studies or cherry-pick data, they don’t systematically examine all the evidence and weigh both sides. They don’t try to falsify their hypotheses. They don’t subject their ideas to peer-review. 

Still another example is the source of covid. The evidence is uncertain enough that we cannot say definitively how the covid pandemic arose. Yet, the data points strongly in one direction: Spillover from an animal to a human. Nevertheless, the government’s covid.gov website now claims that the “lab leak” hypothesis has been proven, and asserts that covid arose from sinister events in a lab in China. No, we don’t know that. While we can’t yet be certain, the evidence suggests that the cause was not a lab leak. Just because some politicians want the source of covid to be a lab leak doesn’t make it so.

One more example, of particular relevance to Intermediate Physics for Medicine and Biology, is cell phone safety. Although again there are uncertainties in the data (especially in laboratory experiments), the evidence suggests that radiofrequency electromagnetic radiation from cell phones does not cause cancer. I think that to say “suggests” is an understatement. The evidence is compelling that cell phones are safe. Yet RFK Jr. and others continue to argue otherwise, as if evidence doesn’t matter.

I would love to be proved wrong, and shown that, say, climate change is actually not happening. That would truly be wonderful, and millions of lives would be saved. But you have to prove that using evidence. You can’t just declare it. My dad was born in Kansas City and he used to say “I’m from Missouri and you have to show me!” That’s the gist of what it means to be a scientist. You have to show me, not tell me. Convince me with the data.

So, what is the feature of science that is essential? What aspect, if we lose it, means we no longer have science at all. I would say the belief that evidence matters. That experiments are how we determine what is true and what is not. If we give that up, all is lost and we’re back to the age of faith. Not religious faith necessarily, but an age where truth is determined not by evidence but by what is consistent with your personal beliefs, your friends and family, your wishful thinking, your fears, or your politics. The supremacy of evidence is where we must focus our resistance. That must be our line in the sand that we will not cross. That must be the hill from which we defend against the onslaught of the Republican War on Science, so that the Age of Reason can resume.

Francis Bacon,
From the cover of
The Age of Reason Begins.

The Durants conclude

Because he [Bacon] expressed the noblest passion of his age—for the betterment of life through the extension of knowledge—posterity raised to his memory a living monument of influence. Scientists were stirred and invigorated not by his method but by his spirit. How refreshing, after centuries of minds imprisoned in their roots or caught in webs of their own wistful weaving, to come upon a man who loved the sharp tang of fact, the vitalizing air of seeking and finding, the zest of casting lines of doubt into the deepest pools of ignorance, superstition, and fear!...

…[Bacon] repudiated the reliance upon traditions and authorities; he required rational and natural explanations instead of emotional presumptions, supernatural interventions, and popular mythology. He raised a banner for all the sciences, and drew to it the most eager minds of the succeeding centuries.

The Philosophy of Sir Francis Bacon, from Let’s Talk Philosophy.

https://www.youtube.com/watch?v=Mj4N0O7QnPY

Where Have You Gone, Physicist Bob Park? Our Nation Turns Its Lonely Eyes to You. Woo, Woo, Woo.

Voodoo Science, by Bob Park, superimposed on
Intermediate Physics for Medicine and Biology.

Bob Park died five years ago this week. He had been in poor health since suffering a stroke in 2013. Park was a physicist and the director of public information at the Washington office of the American Physical Society. He was a leading voice against pseudoscience, both in his weekly column What’s New (which, when in graduate school, I used to look forward to seeing in my email every Friday) and in his books such as Voodoo Science.

I wonder what Park would say if he were alive today? I suspect he would be horrified. But I doubt he would have said that. He was not a whine-and-fuss sort of guy. His tools were humor, irony, and sarcasm. Here is what I imagine What’s New would have looked like this week.

What’s New, by Bob Park

Friday, April 25, 2025

1. VITAMIN A FOR THE MEASLES

The Texas measles outbreak continues. Over 600 cases have now been reported, which is more than for the entire year in 2024. Health and Human Services Secretary Robert F. Kennedy, Jr. encouraged parents to treat their children suffering from measles with vitamin A, and now children are suffering from liver disease because of vitamin A overdosing. Why don’t parents simply ask their pediatrician what to do? Because pediatricians are part of the conspiracy, of course!

2. IF WE IGNORE IT, IT WILL GO AWAY

The Trump administration is trying to undo all the progress fighting climate change that has accumulated over the last few decades. His thinking is: if you ignore climate change, the problem goes away. Besides, it’s all a HOAX! King Canute tried this. He commanded the tide to stop coming in. How do you think that turned out? Physics has a way of winning in the end, whether or not it’s politically popular.  

3. LAB LEAK

The Trump administration has rewritten the covid.gov website to advocate for the lab leak hypothesis for the source of covid-19. Don't worry that the evidence is flimsy! If covid resulted from a lab leak, then it’s the scientists fault. Blame those arrogant liberal elitists like Fauci. But watch out for the next spillover event! (Can I interest anyone in some bird flu?)

4. LYSENKO

Back in the USSR, when Stalin was in charge, a crackpot named Lysenko took control of Russian science. He didn’t believe in modern genetics, regardless of the evidence. Russian agriculture collapsed and millions died. Here in the United States, we have our own version of the Lysenko affair. Trump is Stalin, RFK Jr is Lysenko, and vaccine hesitancy and climate change are genetics. I fear the outcome will be the same, which is bad for science and worse for humanity.

5. HOORAY FOR HARVARD

The NIH (remember that place that used to be the greatest biomedical research institution anywhere, ever?) has stopped funding grants to several universities, including Harvard. HARVARD! Apparently these universities will not cave in to Trump's ideological agenda. What will happen next? Who knows. Maybe Trump will be stopped by the Supreme Court. Maybe the House and Senate will decide they’ve had enough. And maybe, just maybe, it will be the end of American science.

Asimov’s Corollary

Regular readers of this blog know that I am a huge fan of Isaac Asimov. I decided on a career in science in large part from reading Asimov’s books. As a teenager I particularly enjoyed his collections of essays from The Magazine of Fantasy and Science Fiction. He wrote an essay there each month about science: astronomy, physics, chemistry, biology, geology, medicine, and even mathematics. Every time he collected seventeen essays, he would publish them in a book. It would not be an exaggeration to say that I came to be a coauthor on Intermediate Physics for Medicine and Biology largely because of the influence those essay collections had on me when I was young.

Quasar, Quasar, Burning Bright,
by Isaac Asimov.

This week I want to look at one of those essays that is especially germane today. It appears as the final chapter in the book Quasar, Quasar, Burning Bright. The essay is titled “Asimov’s Corollary,” and was first published in the February, 1977 issue of The Magazine of Fantasy and Science Fiction. Now, almost fifty years later, it seems more relevant than ever.  I urge you to get a copy and read it in its entirety. I will quote parts that I think are especially important. 

To help set the stage, let me note a few things.

• When Asimov mentions “Arthur” he is talking about Arthur C. Clarke, his fellow science fiction writer and good buddy. Along with Robert Heinlein, Asimov and Clarke are considered the “Big Three” in science fiction.
• Asimov loved to talk about himself. You might at first think he’s egotistical, but once you’ve read enough of his works you will realize it’s all a big act…sort of. It is one of the reasons I loved to read his essays.
• By today’s standards Asimov and Clarke sound a bit sexist, assuming all scientists are men. This is, in part, a sign of the times when they lived. I won’t defend their sexism, but I’ll forgive them because of all the good they did and all they taught me.

Asimov writes:

In Arthur’s book Profiles of the Future (Harper & Row, 1962) he advances what he himself calls “Clarke’s Law.” It goes as follows:

When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong…

…Naturally when I read a paragraph like that, knowing Arthur as I do, I begin to wonder if, among all the others, he is thinking of me…

Asimov was an elderly scientist at that time, and was fond of making all sorts of predictions, many of which claimed something was impossible.

Doesn’t Clarke’s Law make me uneasy, then? Don’t I feel as though I am sure to be quoted extensively, and with derision, in some book written a century hence by some successor to Arthur?

No, I don’t. Although I accept Clarke’s Law and think Arthur is right in his suspicion that the forward-looking pioneers of today are the backward-yearning conservatives of tomorrow, I have no worries about myself. I am very selective about the scientific heresies I denounce, for I am guided by what I call Asimov’s Corollary to Clarke’s Law. Here is Asimov’s Corollary:

When, however, the lay public rallies around an idea that is denounced by elderly but distinguished scientists and supports that idea with great fervor and emotion—the distinguished but elderly scientists are then, after all, probably right.

But why should this be?… Human beings have the habit (a bad one, perhaps, but an unavoidable one) of being human; which is to say that they believe in that which comforts them…

Asimov then examines a few cases of people believing things without evidence. He concludes

Then why do people believe? Because they want to. Because the mass desire to believe creates a social pressure that is difficult (and, in most times and places, dangerous) to face down. Because few people have had the chance of being educated into the understanding of what is meant by evidence or into the techniques of arguing rationally.

But mostly because they want to...

When I read this, I think of people claiming (falsely, we know from the evidence) that vaccines cause autism; I think of people claiming (again, falsely) that cell phone radiation causes cancer; and I think of people claiming (still again, falsely) that climate change is a hoax. When I hear these assertions, made passionately and vehemently but with no evidence provided, I think that the elderly scientists (what I would call “the scientific consensus”) is right after all. And while Asimov writes “probably,” I would write “almost certainly.”

I miss you, Isaac Asimov. We need you now more than ever.

 

There is a cult of ignorance. 

https://www.youtube.com/watch?v=oTV1iQyjFFU

 

 Isaac Asimov predicts the future.

https://www.youtube.com/watch?v=cIB1b_8hqB0

Quackwatch

One goal of Intermediate Physics for Medicine and Biology is to provide readers with an understanding of the physics underlying biomedicine, so they can recognize and refute pseudoscientific ideas. For instance, in Chapter 9 of IPMB Russ Hobbie and I discuss the physics behind the discredited claim that weak, low frequency electromagnetic fields (ranging in frequency from 60 Hz powerline fields to cell phone radiowaves) are dangerous.

These days, with so much pseudoscience parading as fact, and with the United State’s Secretary of the Department of Health and Human Services being a leading proponent of anti-science nonsense, what we need is something to point out and refute all this quackery. What we need is Quackwatch.org. According Quackwatch’s mission statement, 

Quackwatch is a network of Web sites and mailing lists developed by Stephen Barrett, M.D. and maintained by the Center for Inquiry (CFI). Their primary focus is on quackery-related information that is difficult or impossible to get elsewhere. Dr. Barrett’s activities include:

• Investigating questionable claims

• Answering inquiries about products and services

• Advising quackery victims

• Distributing reliable publications

• Debunking pseudoscientific claims

• Reporting illegal marketing

• Improving the quality of health information on the Internet

• Attacking misleading advertising on the Internet 

For those of you who prefer social media, you can follow Quackwatch on Facebook and Twitter.

Quackwatch was established by Stephen Barrett, a retired medical doctor. These days he’s in his 90’s and deserves a rest after a lifetime of defending science. Unfortunately, there’s no rest for the weary; we need him now more than ever.

Five years ago, Quackwatch become part of the Center for Inquiry, another group that opposes pseudoscience malarkey and that publishes the Skeptical Inquirer magazine. I mention both Quackwatch and the Center for Inquiry in my book Are Electromagnetic Fields Making Me Ill?

Thank you Stephen Barrett for giving the world your wonderful website Quackwatch.org. I wish we all deserved it. 

 

Quackery: A History of Fake Medicine and Cure-alls. CBS Sunday Morning.

https://www.youtube.com/watch?v=G_3K0lFuvHQ

My 50+ Years of Antiquackery Activity with Stephen Barrett and William M. London. Center for Inquiry.

https://www.youtube.com/watch?v=EjYIjBae0wM

Vaccines Did Not Cause Rachel's Autism

Vaccines Did Not
Cause Rachel’s Autism,
by Peter Hotez.

I recently listened to an audio recording of Peter Hotez’s book Vaccines Did Not Cause Rachel’s Autism: My Journey as a Vaccine Scientist, Pediatrician, and Autism Dad. Hotez is the same author who wrote The Deadly Rise of Anti-Science, which I reviewed previously in this blog. I’m troubled by the current anti-vaccine sentiment, which is foolish and dangerous. Along with climate change denial, vaccine hesitancy is a worrisome example of an alarming anti-science movement in the United States.

Hotez’s book provides insight into the challenges faced by parents with autistic children (by the way, Peter Hotez is not the hero of this book; the hero is his wife Ann). Moreover, the book makes a compelling argument that vaccines do not cause autism. Hotez reviews much of the scientific literature relevant to the relationship of vaccines to autism. In particular, he mentions a meta-analysis of clinical studies published by a group from Australia. As much as I enjoyed and admired Hotez’s book, I probably would have led off by discussing that publication, rather than waiting until late in the book to bring it up.

“Vaccines are Not Associated With Autism:
An Evidence-Based Meta-Analysis of
Case-Control and Cohort Studies”
by Taylor, Swerdfeger, and Eslick,
Vaccine, 32:3623–3629, 2014.

Today I’ll discuss that article, titled “Vaccines are Not Associated With Autism: An Evidence-Based Meta-Analysis of Case-Control and Cohort Studies” by Luke Taylor, Amy Swerdfeger, and Guy Eslick. This paper appeared in 2014 in the journal Vaccine (Volume 32, Pages 3623–3629). The abstract appears below.

There has been enormous debate regarding the possibility of a link between childhood vaccinations and the subsequent development of autism. This has in recent times become a major public health issue with vaccine preventable diseases increasing in the community due to the fear of a ‘link’ between vaccinations and autism. We performed a meta-analysis to summarise available evidence from case-control and cohort studies on this topic (MEDLINE, PubMed, EMBASE, Google Scholar up to April, 2014). Eligible studies assessed the relationship between vaccine administration and the subsequent development of autism or autism spectrum disorders (ASD). Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus with another author. Five cohort studies involving 1,256,407 children, and five case-control studies involving 9,920 children were included in this analysis. The cohort data revealed no relationship between vaccination and autism (OR: 0.99; 95% CI: 0.92 to 1.06) or ASD (OR: 0.91; 95% CI: 0.68 to 1.20), nor was there a relationship between autism and MMR (OR: 0.84; 95% CI: 0.70 to 1.01), or thimerosal (OR: 1.00; 95% CI: 0.77 to 1.31), or mercury (Hg) (OR: 1.00; 95% CI: 0.93 to 1.07). Similarly the case-control data found no evidence for increased risk of developing autism or ASD following MMR, Hg, or thimersal exposure when grouped by condition (OR: 0.90, 95% CI: 0.83 to 0.98; p = 0.02) or grouped by exposure type (OR: 0.85, 95% CI: 0.76 to 0.95; p = 0.01). Findings of this meta-analysis suggest that vaccinations are not associated with the development of autism or autism spectrum disorder. Furthermore, the components of the vaccines (thimersal or mercury) or multiple vaccines (MMR) are not associated with the development of autism or autism spectrum disorder.

Some of the terms and concepts mentioned in the abstract may be unfamiliar, so let me explain them.

• Autism and Autism Spectrum Disorders. Autism is a disorder of the nervous system that begins during the development of a fetus. An autistic person may engage in repetitive, inflexible behaviors or have problems interacting with people. The disorder can vary in its severity and symptoms, so people with different degrees of severity are said to be on the autism spectrum.
• Vaccine. A vaccine is a biological agent that stimulates a person’s immune system to recognize and destroy a microorganism causing an infectious disease. Vaccines are often made from a weakened form of the microbe.
• The MMR Vaccine. The MMR vaccine protects children against three diseases: measles, mumps, and rubella (German measles). An initial dose of the MMR vaccine is typically given around a child’s first birthday and a second dose before entering school. It’s usually given by injection.
• Thimersal-Containing Vaccine. Thimersal is a molecule containing mercury. The element mercury, whose chemical symbol is Hg, is a known toxin. However, not all molecules containing mercury are as toxic as is mercury metal itself. Mercury compounds like thimersal are used in low doses as a preservative in some vaccines. Before 1991, thimersal was included in the childhood vaccine DPT which protects against diphtheria, tetanus (lockjaw), and pertussis (whopping cough). Now no childhood vaccines contain thimersal, although it’s still used in some flu vaccines.
• Meta-Analysis. Meta-analysis is a statistical method of analyzing and summarizing several clinical trials. A meta-analysis can increase the number of patients being analyzed, resulting a more statistical power. It can also help in resolving studies with inconsistent results.
• Case-Control Study. A case-control study is a clinical study that compares two groups: one having a disease and one not (the control). It is often retrospective, meaning it uses existing data from people known to have a disease, and therefore can be conducted quickly.
• Cohort Study. A cohort study is a clinical trial that takes a group of people and follows them through time to determine what fraction develop some disease. It is prospective, collecting data on exposure to some suspected cause. A cohort study can take a long time to complete and, for a rare disease, requires studying a large population, but it’s less susceptible to bias than a case-control study.
• Odds Ratio. The odds ratio (OR) is a statistical measure to determine if some factor has an effect. For example, suppose in a case-control study you examined the medical records of 600 people who had the MMR vaccine; 570 were healthy but 30 had autism (the odds of being healthy are 570:30, or 19:1). As a control, you examined the medical records of 400 people who did not have the MMR vaccine; 380 were healthy but 20 had autism (the odds of being healthy are 380:20, or 19:1). In that case, the odds ratio would be
  
  When the odds ratio is one, you conclude the MMR vaccine had no effect (the odds of having autism are the same whether or not you had the vaccine). If, however, among the 600 people who had the MMR vaccine 510 were healthy and 90 had autism (with the control group being unchanged from that given above) then the odds ratio would be
  
  In this case, the MMR vaccine would have a clear effect. For smoking and lung cancer, the odds ratio is quite large, about 10.
• 95% Confidence Interval. How large must the odds ratio be in order to conclude there is some effect? That depends on how much uncertainty there is. For instance, if you flip a coin four times, the most likely result is two heads and two tails. However, there is still one chance out of sixteen, about 6%, that you’ll get four heads. If you want to be more certain that a coin is fair and not biased, you would need to flip the coin more than four times. In the same spirit, to completely characterize how much confidence you have in the result of a clinical trial, you must indicate how large the uncertainty is in the result. Most clinical studies will give the odds ratio and a range of values for which—based on a statistical analysis—there is a 95% chance that the odds ratio is within that interval. The convention is that if the 95% confidence interval does not contain the value of one, then there is a statistically significant effect. If it does contain one, any effect is not statistically significant. Using a value of 95%, rather than say 98%, is arbitrary, but you have to draw the line somewhere, and 95% confidence is the usual medical criteria for significance. For example, if in one of these autism studies the odds ratio was 1.05 and the 95% confidence interval was 0.8 to 1.3, you would conclude that there is not a statistically significant effect of the vaccine. If, on the other hand, the odds ratio were 1.05 and the 95% confidence interval was 1.02 to 1.08, you would conclude there is a small but statistically significant effect of the vaccine on autism. Note that in statistics the word “significance” does not mean “important.” It means “unlikely to be due to chance.” One virtue of a meta-analysis is that by combining several studies the number of people analyzed increases, which can shrink the 95% confidence range, which provides better statistical power to say if the odds ratio is significantly different than one. 
• p-value. Whenever you have an arbitrary threshold, like saying a result is or is not statistically significant, you worry about cases that are near the threshold. To provide additional information, researchers sometimes give the p-value. It is the probability that a result at least this extreme could happen by chance. In medicine, usually p = 0.05 is the cutoff between a result being considered significant or not significant. But if the result has p = 0.03, you might say it is significant (less than 0.05) but you might think that it is still questionable and maybe you should repeat that study with a larger number of people. On the other hand, if p = 0.0002 you would say that the result almost certainly didn’t happen by chance and you would therefore have a lot of confidence in it. In this meta-analysis, the p-value is sometimes given, especially for borderline cases, to help the reader estimate the true significance of the result.
• MEDLINE, PubMed, EMBASE, Google Scholar. These databases contain information about scientific publications, including articles describing clinical trials. They can be searched using various keywords to find publications about a particular subject. MEDLINE is a database compiled by the National Library of Medicine, and covers all biomedical research. It can be searched online using a tool called PubMed, which includes MEDLINE plus a few other databases. EMBASE is an international database that focuses on the pharmaceutical industry. Google Scholar is a free web search engine that covers all scholarly publications.

Now that we understand the vocabulary, what does this meta-analysis show? It indicates that there is no evidence supporting a connection between vaccines and the development of autism. It also shows there is no risk that thimersal or mercury causes autism. In fact, some of the results suggest a weak protective effect caused by thimersal. For example, an odds ratio of 0.85 with a 95% confidence interval of 0.76 to 0.95 suggests that the odds ratio may be slightly less than one, which means the vaccine prevents people from getting autism. However, the p-value for this result was 0.01 which is small but not that small, and I wouldn’t put too much confidence in the claim that the vaccine is protective. But the results sure don’t suggest there is a health risk.

What I’ve analyzed today is one paper, albeit a meta-analysis. It’s over ten years old. There are lots of other data out there now, and Hotez describes some of it in Vaccines Did Not Cause Rachel’s Autism. He also emphasizes that autism is thought to arise from problems during the development of a fetus, long before the child receives any vaccines, so there’s no reason to suspect vaccines as a cause of autism. All this evidence, taken together, implies the probability of vaccines causing autism is extremely low.

Why do people still claim vaccines cause autism? There will certainly be cases where a child will receive a vaccine and then start showing symptoms of being on the autism spectrum. Some might point to such cases and say “see, I told you so!” The question is, how many of those children would have started showing symptoms of autism even if they didn’t get the vaccine? Homework problem 9 in Chapter 3 of Intermediate Physics for Medicine and Biology explores this type of question quantitatively. The reason you need a large, controlled statistical study is so you’re not fooled by a few such coincidences.

One thing clinical studies, such as the one that I discussed today, cannot give you is certainty. You can’t say with absolute certainty (p = 0) that vaccines don’t cause autism. Science doesn’t deal in certainties, just probabilities. All you can say is that the evidence suggests there is no connection between vaccines and autism. The best you can do is to collect enough evidence so that the probability of a relationship is very small. That is where we are today. The probability of vaccines causing autism is extremely low. That’s the best conclusion science can offer. And when the probability is vanishingly small, we often feel confident in summarizing the situation with a simple (if somewhat too simple) declarative sentence, such as Vaccines Did Not Cause Rachel’s Autism.

Outbreak News TV: Vaccines Did Not Cause Rachel's Autism.

https://www.youtube.com/watch?v=xDh3QZPx2ns&t=461s

Peter Hotez wins award for Scientific Freedom and Responsibility.

https://www.youtube.com/watch?v=WHtWmSz4cXE

Dr. Peter Hotez's mission to make a difference.

https://www.youtube.com/watch?v=xC-3ofA1hIE

The Cyclotron Resonance Hypothesis

Want a sneak peek at one of the new homework problems tentatively included in the 6th edition of Intermediate Physics for Medicine and Biology? Today I present a problem related to the flawed “cyclotron resonance hypothesis.” A lot of nonsense has been written about the idea of extremely low frequency electromagnetic fields influencing biology and medicine, and one of the proposed mechanisms for such effects is cyclotron resonance. 

In Section 8.1 of the 5th edition of IPMB, Russ Hobbie and I discuss the cyclotron.

One important application of magnetic forces in medicine is the cyclotron. Many hospitals have a cyclotron for the production of radiopharmaceuticals, especially for generating positron-emitting nuclei for use in Positron EmissionTomography (PET) imaging (see Chap. 17).

Consider a particle of charge q and mass m, moving with speed v in a direction perpendicular to a magnetic field B. The magnetic force will bend the path of the particle into a circle. Newton’s second law states that the mass times the centripetal acceleration, v²/r, is equal to the magnetic force

      mv²/r = qvB.      (8.5)

The speed is equal to [the] circumference of the circle, 2πr, divided by the period of the orbit, T. Substituting this expression for v into Eq. (8.5) and simplifying, we find

       T = 2π m/(qB).   (8.6)

In a cyclotron particles orbit at the cyclotron frequency, f = 1/T. Because the magnetic force is perpendicular to the motion, it does not increase the particles’ speed or energy. To do that, the particles are subjected periodically to an electric field that changes direction with the cyclotron frequency so that it is always accelerating, not decelerating, the particles. This would be difficult if not for the fortuitous disappearance of both v and r from Eq. (8.6), so that the cyclotron frequency only depends on the charge-to-mass ratio of the particles and the magnetic field, but not on their energy.

This analysis of cyclotron motion works great in a vacuum. The trouble begins when you apply the cyclotron concept to ions in the conducting fluids of the body. The proposed hypothesis says that when an ion is moving about in the presence of the earth’s magnetic field, the resulting magnetic force causes it to orbit about the magnetic field lines, with an orbital period equal to the reciprocal of the cyclotron frequency. If any electric field is present at that same frequency, it could interact with the ion, increasing its energy or causing it to cross the cell membrane.

Below is a draft of the new homework problem, which I hope debunks this erroneous hypothesis.

Section 9.1

Problem 7. One mechanism for how organisms are influenced by extremely low frequency electric fields is the cyclotron resonance hypothesis. 

(a) The strength of the earth's magnetic field is about 5 × 10^–5 T. A calcium ion has a mass of 6.7 × 10^–26 kg and a charge of 3.2 × 10^–19 C. Calculate the cyclotron frequency of the calcium ion. If an electric field exists in the tissue at that frequency, the calcium ion will be in resonance with the cyclotron frequency, which could magnify any biological effect. 

(b) This mechanism seems to provide a way for an extremely low frequency electric field to interact with calcium ions, and calcium influences many cellular processes. But consider this hypothesis in more detail. Use Eq. 4.12 to calculate the root-mean-square speed of a calcium ion at body temperature. Use this speed in Eq. 8.5 to calculate the radius of the orbit. Compare this to the size of a typical cell. 

(c) Now make a similar analysis, but assume the radius of the calcium ion orbit is about the size of a cell (since it would have difficulty crossing the cell membrane). Then use this radius in Eq. 8.5 to determine the speed of the calcium ion. If this is the root-mean-square speed, what is the body temperature? 

(d) Finally, compare the period of the orbit to the time between collisions of the calcium ion with a water molecule. What does this imply for the orbit?

This analysis should convince you that the cyclotron resonance hypothesis is unlikely to be correct. Although the frequency is reasonable, the orbital radius will be huge unless the ions are traveling extraordinarily slowly. Collisions with water molecules will completely disrupt the orbit.

For those who don't have the 5th edition of IPMB handy, Eq. 4.12 says the root-mean-square speed is equal to the square root of 3 times Boltzmann's constant times the absolute temperature divided by the mass of the particle. 

I won’t give away the solution to this problem (once the 6th edition of IPMB is out, instructors can get the solution manual for free by emailing me at roth@oakland.edu). But here are some order-of-magnitude results. The cyclotron frequency is tens of hertz. The root-mean-square (thermal) speed of calcium at body temperature is hundreds of meters per second. The resulting orbital radius is about a meter. That is bigger than the body, and vastly bigger than a cell. To fit the orbit inside a cell, the speed would have to be much slower, on the order of a thousandth of a meter per second, which corresponds to a temperature of about a few nanokelvins. The orbital period is a couple hundredths of a second, but the time between collisions of the ion with a water molecule is one the order of 10^–13 seconds, so there are many billions of collisions per orbit. Any circular motion will be destroyed by collisions long before anything like an orbit is established. I’m sorry, but the hypothesis is rubbish.

Are Electromagnetic Fields
Making Me Ill?

If you want to learn more about how extremely low frequency electric fields interact with tissue, see my book Are Electromagnetic Fields Making Me Ill?

Finally, for you folks who are really on the ball, you may be wondering why this homework problem is listed as being in Chapter 9 when the discussion of the cyclotron is in Chapter 8 of the 5th edition of IPMB. (In this post I changed the equation numbers in the homework problem to match the 5th edition, so you would have them.) Hmm.. is there a new chapter in the 6th edition? More on that later…

 To be fair, I should let my late friend Abraham Liboff tell you his side of the story. In this video, Abe explains how he proposed the cyclotron resonance hypothesis. I liked Abe, but I didn’t like his hypothesis.

https://www.youtube.com/watch?v=YL-wqJ-PMAQ&list=PLCO-VktC6wofkMeEeZknT9Y4WhMnP76Ee&index=6

Electromagnetic Hypersensitivity

What is electromagnetic hypersensitivity? It’s an alleged condition in which a person is especially sensitive to weak radiofrequency electromagnetic fields, such as those emitted by a cell phone or other wireless technology. All sorts of symptoms are claimed to be associated with electromagnetic hypersensitivity, such as headaches, fatigue, anxiety, and sleep disturbances. An example of a person who says he has electromagnetic hypersensitivity is Arthur Firstenberg, author of The Invisible Rainbow, a book about his trials and tribulations. Many people purportedly suffering from electromagnetic hypersensitivity flock to Green Bank, West Virginia, because a radiotelescope there requires that the surrounding area being a “radio quiet zone.”

Is electromagnetic hypersensitivity real? Answering this question should be easy. Take people who claim such hypersensitivity, sit them down in a lab, turn a radiofrequency device on (or just pretend to), and ask them if they can sense it. Ask them about their symptoms. Of course, you must do this carefully, avoiding any subtle cues that might signal if the radiation is present. (For a cautionary tale about why such care is important, read this post.) You should do the study double blind (neither the patient nor the doctor who asks the questions should be told if the radiation is or is not on) and compare the patients to control subjects.

The effects of
radiofrequency
electromagnetic fields
exposure on human
self-reported symptoms.

Many such experiments have been done, and recently a systematic review of the results was published.

Xavier Bosch-Caplanch, Ekpereonne Esu, Chioma Moses Oringanje, Stefan Dongus, Hamed Jalilian, John Eyers, Christian Auer, Martin Meremikwu, and Martin Röösli (2024) The effects of radiofrequency electromagnetic fields exposure on human self-reported symptoms: A systematic review of human experimental studies. Environment International, Volume 187, Article number 108612.

This review is part of an ongoing project by the World Health Organization to assess potential health effects from exposure to radiofrequency electromagnetic fields. The authors come from a variety of countries, but several work at the respected Swiss Tropical and Public Health Institute. I’m particularly familiar with the fine research of Martin Röösli, a renowned leader in this field.

The authors surveyed all publications on this topic and established stringent eligibility criteria so only the highest quality papers were included in their review. A total of 41 studies met the criteria. What did they find? Here’s the key conclusion from the author’s abstract.

The available evidence suggested that study volunteers could not perceive the EMF [electromagnetic field] exposure status better than what is expected by chance and that IEI-EMF [Idiopathic environmental intolerance attributed to electromagnetic fields, their fancy name for electromagnetic hypersensitivity] individuals could not determine EMF conditions better than the general population.

The patients couldn’t determine if the fields were on or off better than chance. In other words, they were right about the field being on or off about as often as if they had decided the question by flipping a coin. The authors added

Available evidence suggests that [an] acute RF-EMF [radiofrequency electromagnetic field] below regulatory limits does not cause symptoms and corresponding claims in... everyday life are related to perceived and not to real EMF exposure status.

Let me repeat, the claims are related “to perceived and not to real EMF exposure.” This means that electromagnetic hypersensitivity is not caused by an electromagnetic field being present, but is caused by thinking that an electromagnetic field is present.

Yes, there are some limitations to this study, which are discussed and analyzed by the authors. The experimental conditions might differ from real-life exposures in the duration, frequency, and location of the field source. Most of the subjects were young, healthy volunteers, so the authors could not make conclusions about the elderly or chronically ill. The authors could not rule out the possibility that a few super-sensitive people are mixed in with a vast majority who can’t sense the fields (although they do offer some evidence suggesting that this is not the case).

Are Electromagnetic Fields
Making Me Ill?

Their results do not prove that a condition like electromagnetic hypersensitivity is impossible. Impossibility proofs are always difficult in science, and especially in medicine and biology. But the evidence suggests that the patients’ symptoms are related “to perceived and not to real EMF exposure.” While I don’t doubt that these patients are suffering, I’m skeptical that their distress is caused by electromagnetic fields. 

To learn more about potential health effects of electromagnetic fields, I refer you to Intermediate Physics for Medicine and Biology (especially Chapter 9) or Are Electromagnetic Fields Making Me Ill?

Martin Röösli - Electromagnetic Hypersensitivity and Vulnerable Populations

https://www.youtube.com/watch?v=UPXY0WQJ37Q

Is Electromagnetic Hypersensitivity Real?

https://www.youtube.com/watch?v=IrkL1Hm5myE