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It’s Just ATP

Published on August 16, 2023

1956 views

A while back, I wrote an article called ‘Just a Vitamin Deficiency‘ in an effort to dispel the notion that vitamin deficiencies are inconsequential to health. Truth be told, I have written dozens of similar articles hoping to change the tide of disregard. A few weeks after publishing the vitamin article I began this one. I wanted to address the growing body of research suggesting that ATP production is somehow immaterial to health and healing. The two ideas are connected, of course, because without vitamins and minerals we cannot produce ATP and without ATP we cannot catabolize nutrients from the foods we consume into more ATP. In health, medicine, and research, we seemed to have lost sight of these connections in favor of ever more complicated, and indeed, bifurcated explanations of our ill health.

I decided not to publish this article originally. It seemed redundant. Then, lo and behold, another article hit social media once again bemoaning how energy production was unimportant relative to all of the other cool functions overseen by the mitochondria.

The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information.

To be fair, the article is exceptionally detailed and very well done and I agree with the authors overall. They clearly demonstrate the complexity of mitochondrial function. Where I have a problem though, is in the failure to recognize the primacy of ATP over all other functions. This is among my top pet peeves in the world of mitochondrial research and medicine. It is as if the simple act of making energy is not sexy enough to consider in health or disease. While I understand that the mitochondria are central regulators of just about everything and I understand that there are dozens or more cool pathways that are managed directly by the mitochondria and their various signaling proteins, what I do not understand is how we seem to miss the fact that all of these functions, and I mean all of them, require ATP. Indeed, decrements in ATP capacity often initiate, and certainly sustain, many of the negative reactions we see outlined in the annals of mitochondrial research.

In this particular article, the authors concede that defects in oxidative phosphorylation (OXPHOS) impact all of the functions they so eloquently describe.

Because most biochemical reactions taking place within mitochondria are directly or indirectly linked to OxPhos and Δψm [mitochondrial membrane potential], including substrate and ion uptake, mtDNA perturbations have widespread consequences for several metabolic pathways.

For the uninitiated, OXPHOS is the process by which the metabolized products of the foods we consume are shuttled through various enzymatic reactions within the mitochondria to ultimately produce ATP. Defects in OXPHOS not only imperil energy production but also set into motion a cascades of negative reactions. From an article published earlier this year:

OxPhos defects trigger mtDNA instability and cell-autonomous stress responses associated with the hypersecretory phenotype, recapitulating findings in plasma of patients with elevated metabokine and cell-free mitochondrial DNA (cf-mtDNA) levels. These responses are linked to the upregulation of multiple energy-dependent transcriptional programs, including the integrated stress response (ISR).

OXPHOS is clearly important to mitochondrial function, and why wouldn’t it be? The synthesis of energy, of ATP, is the foundation of life. Think about it for a moment. Energy is fundamental to survival, not incidental, but fundamental. So, if energy wanes all of the functions dependent upon said energy become disturbed. Sure, there are other mechanisms by which a particular pathway may become unfavorably altered, and sure, delineating those mechanisms is important, but each and every one of those patterns requires energy to execute. The degree to which energy metabolism is inadequate to the task will influence, if not determine, the pattern of response, irrespective of the other variables that may be at play.

Breathing, for example, requires energy and not just the mechanical act of inhalation and exhalation, but the absorption, trafficking and metabolism of oxygen (O2). Of course there are a lot of factors that can impede breathing and oxygen management that seem outside of the purview of mitochondrial influence, but in reality, they are not. Energy or ATP is required at every step, including arguably the most important step – the utilization of O2 to create more ATP.

For O2 to be used, we need ATP.

For ATP, we need functional mitochondria.

For functional mitochondria, we need macro- and micronutrients.

Food provides the substrates that allow the mitochondria to produce ATP. It provides macronutrients like protein, fats, and carbohydrates, and perhaps most importantly, food provides the micronutrients to utilize that fuel. It’s that simple, or at least it used to be, before industrial food manufacturing so thoroughly decimated the food supply leaving vast swaths of the population starved for vitamins and minerals.

The ills of modern food production notwithstanding, without sufficient micronutrients to metabolize food into fuel and ultimately into ATP, alternate processing pathways are used; pathways that consume more ATP than they produce, and pathways that burn dirtier and emit more toxins than the body has the energy/ATP to deal with. This is the root of all metabolic disorders and more often than not, most modern illness, regardless of diagnosis.

So, while detailing all of the cool things that mitochondria are responsible for is important to understand, especially if we are ever to move medicine away from the compartmentalized model that it has so fixated on, let us not forget ATP is the basis of life.

Perhaps, in our investigations mitochondrial function, we ought to examine ATP capacity, not just output but capacity, and the pathways therein used to produce this ATP and manage the metabolism of foods. Perhaps then we will finally understand how critical the right nutrients are to mitochondrial health. Perhaps we also ought to look at how to support native mitochondrial function, not by blocking aberrantly altered pathways, but by providing the mitochondria with the most basic building blocks for optimal ATP production – nutrition. If we can get the mitochondria to more efficiently produce ATP, would that not then favorably influence everything else?

From that perspective, it seems obvious that ATP, the energy cells consume to do all of the things that cells do, would be fundamental to health, and to life itself, but like things that should be obvious to modern medicine, it is not. Sadly, it does not appear to be obvious even to those who research and treat mitochondrial illness. ATP capacity is not something we can ignore, but we do, and this, I believe, is one of the biggest failings of modern medicine and modern mitochondrial research.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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The Exquisite Simplicity of Health and Illness: Mitochondria and Energy

by Derrick Lonsdale MD, FACN, CNS

Published on May 9, 2023

10659 views

For years I have struggled to get people to understand the relative simplicity of what causes us to get sick. Our medical model implies that each disease has a specific cause, and therefore, has a specific treatment. If you look seriously at what makes us tick, there are several obvious factors involved. Yes, we are provided with a “blueprint”, given in code called DNA, by our parents. Since the discovery of DNA, medical research has emphasized almost to exclusion of other factors, that genetics is the primary research area. The most amazing recent finding is that our cellular genes (the blueprint) can be manipulated by our diet and lifestyle.

Diet and Stress

Even though the great Hans Selye studied the effects of physical stress on animals, we have neglected it in relationship to human health. He said that humans were suffering from what he called the diseases of adaptation. What he meant by that was that any form of “stress” has to be met by an adaptation that requires a huge amount of energy. The brain causes the body to go into a defensive mode when we are attacked by a microorganism and it should not be surprising that it requires energy. Sometimes a severe form of stress is associated with fever that should be regarded as an automated defensive action. In fact, I knew of a patient in whom the cause of her persistent fever could not be determined by standard laboratory methods. It was written off as “psychosomatic”, because of personality factors.

The idea, however, seems to me to be a reduction to absurdity based on collective ignorance of the underlying mechanism. The symptoms that we develop are caused by all the actions that make up the defensive mode and we call that the disease. For example, fever is part of the defense because it renders the attacking organism less efficient. Hence, the attacking organism is a “stressor”. Perhaps prolonged mental stress can produce fever in a metabolically abnormal brain because of causative misinterpretation by the brain.

It has long been time-honored that we bring the temperature down artificially as part of the treatment for infection, thus losing an important part of the defense. It wasn’t the flu virus that caused Reye’s syndrome, a disease that caused the death of many children. It was the aspirin given by the mothers to bring their child’s temperature down.

Energy Deficiency and Mitochondria

When you read a telegram giving you bad news, when you ride a bicycle, when you run cross country or shovel snow, we take it for granted that the energy will be forthcoming, that is if we think about it at all. Energy deficiency in the heart muscle could easily explain the “drop-dead” phenomenon occasionally experienced by elderly people in the winter when shoveling snow, usually written off as a heart attack from coronary disease that could easily be part of the event. Could that death have been prevented by analyzing the state of nutrition for that individual?

Another great discovery is that we have a separate set of genes that preside over the functions of our mitochondria. These are the organelles within each of our cells that produce the energy that enables us to function. Sick mitochondria produce sick people, because energy consumed must be met by energy synthesized. We now know that mitochondria have their own genes completely separate from the “blueprint” genes. Mitochondrial genes are passed to the children by the mother. When damaged mitochondrial genes are passed on to children, it becomes a form of maternal inheritance. An obvious question is whether the damage to genes can be caused in adult life from malnutrition or whether the damaged genes passed on to the children are invariably inherited from grandma.

Energy synthesis depends upon an exquisitely complicated set of nutrients that are derived from what we eat, so nutrition becomes the third factor. It is therefore very likely that an element of each of these factors is always involved. Yes, it is true that a genetic mistake may be the primary cause, but a lot of genetic mistakes are really risk factors that begin to produce a given disease in relationship to “stress” and “nutrition”, both of which always play a part.

We now know that the induction of the first symptoms of beriberi, a well-known vitamin deficiency disease that has dogged mankind for centuries, can be fully initiated by sunlight exposure in a person with marginal deficiency. There may be mild symptoms attributed to other “more acceptable” causes or even no symptoms of vitamin deficiency prior to sunlight exposure. In the early investigation of beriberi, the appearance of symptoms in many individuals at the same time misled the investigators who concluded that it was due to a mysterious infection. We now have reason to believe that ultraviolet light imposes a “stress” in an individual whose metabolism is marginal, thus initiating the true underlying cause.

Healing Comes Naturally If We Let It

The human body, as we all recognize, is beautifully designed and healing is a natural phenomenon built into our system. The body knows exactly what to do, but like stress factors, healing requires energy. So, it seems to make absolute sense that we cannot possibly produce healing by the use of compounds that are completely foreign to our cellular system. Shouldn’t we be using methods that assist the healing process by stimulating mitochondria to produce the necessary energy? Surely, the only possible assistance must be through the use of nutrients. At present, we know that there are well over 40 separate non-caloric nutrients that we must get from our food to maintain health and this may not be a full complement.

Feeding the Body Fuel to Heal: Of Vitamins and Minerals

I give this as a forerunner to news that I came across quite recently. I am reasonably sure that it will be known by people who love American sports. Everyone knows the name of Bernie Kosar, the great quarterback of the Cleveland Browns back in the good old days. Bernie understood the highs and lows of football. He had hundreds of concussions, broken bones and torn ligaments over 8 ½ seasons. In retirement he suffered pounding headaches, sleepless nights, anxiety and increased weight. Speech slurring made people think that he was drunk. Amazingly, his family didn’t believe that he had genuine symptoms and thought that he was merely trying to gain attention. The slurred speech was thought to be due to alcohol, the weight gain from overeating. After his retirement, apparently he spent some time in Florida and he learned there of a physician who was using intravenous vitamins to treat the kind of symptoms of which he complained. He tried it and immediately began to feel better. In fact he was so impressed that when he came north to live in Ohio he looked for a physician who could continue this treatment. He was directed to a doctor Pesek, founding holistic physician and CEO of Vital Health in Cleveland, Ohio. Dr.Pesek uses holistic superfoods and megadose vitamins to treat his patients. Kosar gets two or three intravenous infusions of vitamins a month. His headaches have decreased, his sleep is improved and he has lost 60 pounds in weight. This is loss of accumulated water in the tissues, a signature of mitochondrial disease, not loss of fat. In fact he is so impressed that he is going to bring it to the notice of the NFL concussion settlement. He wishes that he had started it earlier. He says that “he knows of guys who are older and some who are younger than me and it goes south quickly”.

Healing the Brain

Because the methodology is “out of the box”, it is likely that a common explanation would be the so-called placebo effect. But that effect has to have a mechanism and perhaps the approach with nutrients actually stimulates this effect. What we know about brain injury is that the damage upsets the normal balance of metabolism. It causes a release of oxygen radicals, a phenomenon that can be likened to the production of sparks in a fire. The damage is cumulative, eventually giving rise to the kind of symptoms experienced by Kosar and also by Mohammed Ali, who went on to suffer from Parkinson’s disease. Neglect the early symptoms, almost always mistaken for psychosomatic disease, and the damage slowly accumulates, eventually becoming irreversible and untreatable. I suggest that this is represented as one of the many neurodegenerative diseases such as Alzheimer’s or Parkinson’s. Under the present medical model, it might easily be assumed that intravenous vitamins are a specific treatment for the effects of concussion and should be reserved for that. The point is that there are many avenues to metabolic imbalance. For example, if type I diabetes was determined by a genetic effect, why do the symptoms not appear for many years? If genes are solely responsible, diabetes should be present at birth. The answer is that other factors come into play including malnutrition and aging. In fact, in the state of genius, it might be that even the best possible diet does not provide sufficient energy, perhaps explaining the long-term illnesses of the historical figures, Mozart and Charles Darwin, both of whom suffered lifelong from symptoms that have often been regarded by historians mostly as psychosomatic.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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Image by PDPics from Pixabay.

This article was first published on July 31, 2017.

The Winnowing of the Western Diet: Reconsidering Food Sensitivities

by Chandler Marrs, PhD

Published on May 3, 2022

6174 views

A few weeks ago, I posted some articles on Facebook regarding the need for protein in one’s diet (here, here). I believe that the lack of protein in the modern diet and the subsequent substitution with processed carbohydrates is one of the leading contributors to metabolic disease. Over the last 50 years or so, we have become increasingly afraid of eating protein and fat. Convinced by industry-sponsored advertising and ill-conceived medical science postulating that only calories matter and that eating fat makes one fat, we avoided the higher calorie foods like meat and shifted our diets towards lab manipulated but lower calorie and lower fat, ultra-processed carbohydrates. This has left much of the population starved for both macro (protein, fats, and plant-based carbohydrates) and micro (vitamins and minerals) nutrients. Ironically, the push to avoid high-calorie foods has resulted in higher calorie intakes in those who regularly consume ‘low-calorie’ foods than those who consume the higher calorie whole foods.

Similarly ironic, a corresponding form of malnutrition develops as a result of the low nutrient content in these industrial foods – this despite nutrient fortification. We have labeled this type of malnutrition as high calorie malnutrition. It is a metabolic starvation of sorts that develops concurrently with obesity, but also, with many disease processes including, I would suspect, food sensitivities. With the choice of highly processed foods, excessive calories must be consumed to meet the minimum nutrient requirements. Sugar is metabolically easy energy. So too is fat. Protein, by comparison, is not. Unfortunately, sugar, though technically energy-rich, is nutrition poor, and therein lies much of the problem. Worse yet, the fats used in most processed foods are hydrogenated, and thus, provide few health benefits but carry many risks.

When I bring up the notion of eating more protein, fat, or simply eating more nutrient-dense foods in general, I am met with resistance, sometimes philosophical, but oftentimes, based upon long-entrenched food sensitivities that develop over time, eventually winnowing the number of non-triggering foods down to almost nothing. Over the last several years, the breadth and depth of individual food sensitivities has exploded. Sensitivities to protein and fats, in particular, seem to be growing, but also to fruits and vegetables and, of course, grains. These are not allergies in the traditional sense, though there may be an altered histamine response involved. Rather, they may represent a complicated response to a lack of particular nutrients that results in the inability to digest or metabolize certain foods.

In response to the aforementioned posts on protein, a reader asked:

Chandler Marrs, what about the inability to absorb protein? …About 17 years prior to my husband’s death, he started eating all kinds of junk food (carbs). Every piece of crap he could pick up at Dollar General…he had never had a sweet tooth or liked junk food till then. Visiting with his neurosurgeon after my husband’s death…on diet and progression of his issues, he told me that when [my husband] went to junk food it was for energy, that he was no longer able to absorb protein. He told me that my husband was doing what his body dictated he do, the only thing he could do for energy…

I don’t know the history behind this gentleman’s illness, nor any of the details beyond what was posted above, but I would not be surprised if cancer were involved, perhaps in the brain, either originally or one that metastasized. The reason behind my suspicions is that cancer involves a switch in energy metabolism, wherein sugars are no longer used effectively in the manufacture of ATP – cellular energy – creating a sense of starvation, particularly when other fuels are absent and/or the machinery used to convert the other fuels to energy is deranged. Even if cancer was not part of this gentleman’s illness, the craving for sugars and the suspected inability to absorb or utilize proteins and fats for energy production points to a common metabolic adaptation to a longstanding nutrient-poor diet. It is a chemical conditioning of sorts, much like a drug addiction, that nets cravings for the foods/fuels that maintain the new normal, whatever that state may be.

What is often missed in the discussions of food sensitivities is that to digest and metabolize foods and convert them into usable and beneficial substrates for health, the machinery responsible requires nutrient co-factors e.g. vitamins and minerals. Absent those co-factors, food cannot be processed into ATP in the mitochondria. And absent ATP, none of the other processes in the body work. Since those co-factors come from the foods themselves, it is a reciprocating process. Nutrient dense foods provide the cofactors to process more micro-and macronutrients while effectively producing the requisite ATP. In contrast, nutrient poor foods provide an excess of sugars – potential energy – that can never fully be converted to actual energy or ATP because the machinery responsible for processing those foods is starving for nutrients, and thus, does not work very well. When one is not able to convert the food to energy nor to derive what few nutrients may come with these foods, cascades of ill-health begin. One of those cascades involves storing the excess as fat. To the extent one is able to store this fat, though unsightly, I imagine is a highly adaptive response, as individuals with similarly poor diets who do not or cannot store fat, risk a comparatively higher rate of all-cause mortality.

Returning to the question of food sensitivities, or more appropriately, the inability to digest and metabolize particular foods, I suspect that longstanding dietary factors, along with genetic and/or environmentally induced epigenetic variables, create and then maintain nutrient deficiencies that inhibit one’s ability to ‘eat’ certain foods. Across time and as those foods are avoided, nutrient availability continues to decline. Mitochondrial function is perturbed but adapts to the new environment, resulting in chemical reactions that induce inflammation and the other patterns so common with metabolic disturbances. This may include intense cravings for certain foods that are metabolically more accessible, like sugars. Admittedly, sugars are exactly what a body in this state does not need, but much like the cravings for drugs in an addiction model, I suspect the body has adapted to having this substance present in high concentrations. It has re-regulated itself accordingly, and because of this, both the absence of the substance and the addition of other, metabolically less well-adapted substances, cause great distress chemically. These changes are then experienced symptomatically.

We know from addiction models, that when a substance is present continuously and in high concentrations, the body adapts so that it can maintain some sort of homeostasis and survive. Receptors, transporters, enzymes, and the like, are reregulated. Some upregulate, others downregulate. As this reregulation occurs, the body becomes chemically conditioned to its new state, seeking to maintain it at whatever cost. When what is in excess carries no nutritional value, as it so often does, we have the bonus of starving the enzymes that make metabolism possible, further imperiling health. At the root of much of this reregulation is nutrition or lack thereof. Every enzyme in the body requires nutrient co-factors to function. Absent these nutrients, metabolism falters; not just the metabolism of foods to energy but the metabolism of drugs, the metabolism of neurotransmitters, hormones, and the like. Absent nutrients, we have widespread changes in the totality of our biochemistry. How those changes manifest is dependent upon the individual’s genetic makeup and environment, but make no mistake, they are occurring.

While it is clear that one can avoid many of these problems by eating a nutrient-dense diet, it is not as clear how one recovers these functions once they are lost. Do we simply feed the offending substance until tolerance develops? Or do we tackle the enzyme issues first, supplying the requisite nutrients in the form of supplements so that they function more effectively and then re-introduce the offending foods? I don’t know the answer, but my instincts tell me that enzyme issues have to be addressed first and the vitamin and mineral deficiencies corrected before the offending foods can be reintroduced. What I do know, however, is that something must be done. Human beings cannot live well or for very long without protein and fat. Those are requisite substrates for health.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

Image credit: Free public domain CC0 photo.
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This article was first published on June 20, 2019.

Semmelweiss Syndrome: Ignoring the Obvious to Save Face

by Derrick Lonsdale MD, FACN, CNS

Published on February 5, 2018

2906 views

Who was Semmelweiss? Please read the post below to find out. We have an urgent message for both patient and physician. It isn’t really new because it started with Hippocrates in 400 BC “when he said ”let food be your medicine and medicine be your food”. He also said that no kind of treatment should ever be used that may do harm. All you have to do is to read the Physicians’ Desk Reference and read about almost any drug. It begins with a short sentence about what it must be used for. Then it very often states that nobody knows why the drug works. What follows is a lengthy discussion of side effects, pure evidence of its toxicity. The potential for harm is implicit. Hippocrates realized that healing was a natural process within the body itself and that any treatment method should assist this process. Today, we are well aware that this healing process requires a huge amount of energy that must be conserved and focused by resting body and mind. Modern biochemistry provides us with facts that show the wisdom of Hippocrates when he said “let food be your medicine”!

An Obvious Fallacy in Modern Medicine

Healing is a natural process from within the body that operates best when it is focused. The modern hospital, with its constant clatter and its complete failure to give the patient the rest and tranquility required for energy conservation, works against the healing process. The question that we must ask, is how we should proceed in order to assist healing. The answer must be obvious: help to supply the means by which energy is produced and conserved in the body. Health is a balance between the attack of environment (the enemy) and the constant mobilization of adaptive function that requires energy to maintain functional efficiency (the defense)

Alternative Medicine

This is the philosophy that has given rise to the development of a small group of physicians that use nutrient-based medicine. The point is this: modern medicine attempts always to kill the enemy. Kill the bacteria, the virus, the cancer cell, without killing the patient. Alternative medicine respects this only if it does no harm to the patient. The main approach of these physicians is to anticipate the body’s requirements in all its different ways in attempting to heal itself, the philosophy that was put forward by Hippocrates. These physicians often find that they are excluded from the conventional medical hierarchy, spurned by their former colleagues and despised. When they have a brilliant success with a patient, it is invariably labeled as “spontaneous remission” and we have wondered why this seems to be so inevitable in human affairs.

The Story of Semmelweis

The apocryphal story is that of Ignaz Semmelweiss who was a European physician who practiced before microorganisms had been discovered. He observed that doctors came in from the morgue and delivered their patients without washing their hands or changing clothes. The puerperal fever (childbed fever) rate was excessively high, of course. Semmelweiss concluded that the doctors must be bringing something in on their hands. He divided the ward into two sections and directed that doctors attending patients on one side should wash their hands in chlorinated lime before they performed a delivery, whereas the doctors on the other side should continue in the same old way. It did not need a statistician to see the difference in the incidence of infection. But what happened to Semmelweiss was just as predictable. He had done something new that disagreed with the medical establishment of the day. He was accused of being unscientific by suggesting that an unknown substance on the hands of the doctors was the cause of the problem. He was fired from the hospital and eventually died in a mental institution. He was right and they were wrong. The truly amazing thing is that the medical establishment never bothered to look at the results and times have not changed.

Nutrients Matter: It’s That Simple

People who have to admit their loved ones to hospital as an emergency, knowing and understanding the dramatic effect of nutrient-based treatment, are almost always completely powerless to get the attending physician even to listen to them. A physician of my acquaintance had a patient in hospital with pneumonia due to a resistant bacterial organism. He gave the patient nutritional IVs with water soluble vitamins. The patient recovered. In the next bed was a patient with exactly the same pneumonia who was under the care of another physician. My acquaintance approached what should have been his colleague and suggested that he do the same treatment, using the vitamin therapy. He was told flatly to mind his own business. The patient died. You would think that the second physician would want to discuss the reasoning and the scientific evidence to support the action. Was the belief in his own competence (ego) more important than the life of his patient? This is happening today in the world of medicine. We have come to accept it as the great “Bonanza” of scientific advance. Readers should be aware that the leadership for change will not come from the medical profession. It will come from those most interested in solving those personal health problems that have defied solution, sometimes for years. This website can spread the good news that there are often alternatives to be sought.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

Image: An injection against croup at the Hôpital Trousseau, Paris. Photogravure by Bruun Clement, 1899, after P.A.A. Brouillet, 1893. Wellcome Collection. Public Domain Mark. Source: Wellcome Collection.

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