Affecting everything, affected by everything

 kw: book reviews, nonfiction, neurology, medicine, memoirs

A medical student begins losing her sight, but at first cannot tell; eventually she realizes that her brain is filling in plausible details where her vision has stopped working. An older woman's leg makes running motions when she tries to sleep, sometimes kicking her husband; when it begins happening while she walks it gets very hard to walk reliably. A man wakes up in the morning, feeling fine; he talks with his doctor as usual—from the doctor's perspective—but his speech is mostly nonsensical and he doesn't realize he's beginning yet another day like the prior 7,600 or so because he has been in this hospital for 21 years.

I have heard it said that if there were only one human in the Universe, that more than half of the total complexity of the Universe would be found in that person's brain. When a functional object has not just billions but quadrillions or quintillions of moving parts, it is amazing that it functions at all, let alone with any reliability.

Neurologist Pria Anand, in The Mind Electric: A Neurologist on the Strangeness and Wonder of Our Brains, brings together more than a dozen stories, including a few of her own experiences, connecting them with history and mythology, to illuminate some of the things that do go wrong in the brain. Treating people (usually women) with migraine headaches is one thing. Experiencing them herself, complete with premonitory auras and even hallucinations, is quite another. For the sake of their sanity, doctors must learn to keep a certain distance from their patients. When a doctor is suffering the same symptoms, that distance is hard to maintain.

My mother died with Alzheimer's Dementia, as did her sister and their father before them. During her last year my mother was cared for by a wonderful nurse named Mary. But Mary, who also had relatives with similar dementia, eventually couldn't stand the strain and had a nervous breakdown. After Dad retained a new nurse, Mary would visit frequently, now as a friend rather than a caretaker. Mary recovered.

Many of the syndromes Dr. Anand discusses are found more in women than men, some are hard to diagnose, and in many cases a woman may be dismissed as "hysterical" by doctor after doctor before finding one with sufficient experience, and compassion, to ferret out the cause. Even something like Restless Leg may be dismissed as a hysterical manifestation, and since it has several possible causes, a doctor may be reluctant to order a whole bunch of tests to narrow the search for a cause.

I learned a few things. One that is important: the cerebellum is more than a control center for the body as I had thought. It mediates coordination, bringing together the will or desire, the evidence of the senses, and the knowledge of place and space, to weave the coordinated movements required to carry out the "orders" of the cerebrum. It can also briefly override the autonomic functions of the brain stem. We can briefly "take control" such as holding our breath when swimming underwater. But a disruption or injury to the breathing control circuit between the cerebellum and the brain stem, can produce a syndrome in which a person must breathe by an act of will, making it impossible to sleep. But being forced to stay awake has its own horrific result: in about two weeks without sleep, you just die. Diseases that damage the cerebellum produce any number of motion and coordination disorders.

Blindness is not just an eye problem. Several things can happen to or in the eye to affect our vision, such as damage to the cornea, the lens, or the retina. But between the eyes and the back of the brain where "vision happens", the optic nerves pass their signals through a few structures. A hiccup anywhere along the line can cause partial or total blindness. Damage at some junctures cause a person to be entirely sightless and yet not know it. Treating such a person cannot be aimed at restoring sight, but at setting up the support systems (relatives, spouse, friends, etc.) to keep the person oriented and safe. If such a one can't realize she's blind, she could walk into traffic or off a cliff with total confidence.

You may have heard of fever dreams. This has two meanings, one being the hallucinations that accompany malarial fevers. The other is more prosaic, something I experienced a few times as a child: when my fever due to a flu or cold rose about 102°F I would have what I called the Banging Dream. It would begin with a sound like a grain of sand ticking as it dropped from one side to the other of a small metal container that was being rocked back and forth; the container and the grain would enlarge slowly, and within a minute or two I would feel like my head was a huge steel drum in which a boulder was crashing back and forth. The basis was the sound of my own heartbeat, amplified monstrously as my overheated brain lost control of my senses. Other people experience moving colors, or "visits" from dead relatives…there is a panoply of odd things the brain under stress will do.

The author is such a good storyteller that I am at a loss how to proceed. Read for yourself and let her lead you on a guided tour of the world of a neurological resident and practicing neurologist.

Swapping out part after part

 kw: book reviews, nonfiction, medicine, prosthetics, transplanting

To start on a personal note: In these book reviews I typically relate the book's subject to my own experience. I started this blog when I was nearly sixty, and now, 21 years later, I'd say I have experienced a lot. In the light of the present book, however, I suppose I am fortunate that I have hardly anything personal to relate. Reading Replaceable You: Adventures in Human Anatomy by Mary Roach has been a fascinating adventure into realms unknown.

When I saw the title I wondered if the subject might be the various rates at which "we" are replaced, from daily for the lining of the stomach to never for the lens of the eye (unless we get cataracts removed and replaced with intra-ocular lenses–but that's a prosthesis). Perhaps you've heard that most of our substance is replaced every seven years. That's sorta so, and sorta not. But Ms Roach's subject is medical replacements, whether mechanical or transplanted. Plus an augmentation or two like breast and butt implants. 

This image was made using the Phoenix 1.0 engine in Leonardo AI.

The book starts with the nose. What do you do when it has been lopped off in a duel, as happened to Cyrano? A century or more ago, a strap-on or glue-on prosthesis of tin or leather was the best one could do. Later, various methods were developed of auto-transplantation (moving some "stuff" from elsewhere on your body to your nasal area). Get over your squeamishness if you want to read not just this chapter, but the book in general!

I must say, the author appears to have gotten entirely past any hints of squeamishness. She reports observing a variety of procedures in the operating room, including the careful disassembly of an organ donor, from whom the corneas are removed first, then almost everything but the head and bowels, even entire legs (stripped from inside the skin, which is repacked with filler materials for the funeral). A donor's parts can be enough to "edit" more than seventy other people.

Skin removed by catastrophic flensing or burning can't be attended to with any kind of prosthesis; the best solution is auto-transplants. It turns out that other kinds of skin can be used temporarily while your own body grows enough skin for repeated transplants. Frog skin isn't rejected too fast, plus it has antibacterial properties. If you don't mind being partly green for a few weeks!

Even intimate parts aren't exempt from needing repair, or reconstruction/construction. There are two ways to produce an artificial vagina for a trans woman. One is by turning the penis inside out, to be followed by a lifetime of "dilation" to keep this essentially permanent wound from sealing up. The other is by using other tissues of varying sensitivity to simulate vaginal mucosa, and sections of colon appear to work the best. And repairing (or constructing) male "equipment" can be equally cringe-inducing.

Are we still the sum of our parts, when more and more of those parts are "other"? In the chapter on xenotransplantation, using parts from pigs or other animals, the question is addressed: Is a genetically-modified pig heart OK to transplant into a Jew? With typically Talmudic wisdom, the consensus of the rabbis is, Yes, because the heart is not being eaten. At the moment, organs from pigs are a temporary measure, to stretch the life of a heart patient while waiting for a heart from a human donor.

We hope one day to be able to either grow an organ from someone's own stem cells, which becomes a homo-transplant. I have seen a few science fiction stories where rich persons (usually such persons are evil) have lab-grown bodies, self-clones, to be harvested as needed. If it can be thought of, someone will probably try to do it some day. A technology that is perhaps easier, and certainly can be faster, is to 3D print with special nozzles that spit out cells onto a framework, usually of collagen (which provides the structural framework of most organs). However, even a simple item like an earlobe has four or more cell types. It is like writing a multicolored letter using one of those special pens with four colors of ink you activate by pushing down one cartridge or the other. And for muscles in particular, the cells need to be in a certain orientation.

Thinking it over, I remembered that I have a few teeth with crowns. Dental crowns aren't mentioned in Replaceable, but they could have been. I wear glasses. I suppose those qualify as a supportive prosthetic. But other than that, I count myself lucky I've never needed to get a prosthetic hand, foot, leg, lung (Mary tried to sleep a night in an iron lung; she lasted two hours), or a transplanted finger, kidney or pancreas (a friend of mine was cured of diabetes...).

I've previously reviewed four of Mary Roach's books. She is becoming one of my favorite writers.

Dominance of the spineless

 kw: book reviews, nonfiction, science, oceanography, biology, invertebrates, medicine

Behold a gallery of sponge animals. They headline The Ocean's Menagerie: How Earth's Strangest Creatures Reshape the Rules of Life by Drew Harvell.

Considering the matter for a moment, I concluded that the word "reshape" in the title ought to be "reveal." I suppose the publisher thought the title as it is makes better clickbait.

The thousands (almost 10,000 so far) species of sponge comprise the phylum Porifera. Their shapes and sizes are so variable, that pores are the only consistent feature. Brainless, apparently without nervous systems, they are remarkably successful predators. Most consume plankton (little floating things), but some grow over and consume coral animals, and some have inner chambers with other critters such as shrimp living inside. The shrimp gets a safe home, and the sponge eats the leftovers the shrimp drops. Being stationary, sponges need good defenses against predation and against diseases caused by bacteria, fungi and viruses. Dr. Harvell tells us that they have the most multifarious immune system of all animals. Her particular interest is figuring out how their various chemical defenses work, and which ones might lead to medical advances for humans. She writes, "…I call the capability to produce potent biologically active chemicals a sponge superpower." Sponge research is likely to lead to either better antibiotics, or to new alternatives to antibiotics, for example.

This image shows several corals along with a variety of sea anemones, which are related to corals. Both are members of the phylum Cnidaria, which also includes jellyfish (called "jellies" by scientists because they most definitely aren't fish). The phylum contains more than 11,000 species. Though they are  brainless, they have simple nervous systems that coordinate their movements.

The basic body plan is a radially-symmetric, columnar tube with only one opening (a combined mouth-anus) surrounded by stinging tentacles. Sea anemones are larger and solitary, while corals are colonial and build skeletons; the stony corals build mineral skeletons that form the backbones of reefs.

Stony corals are the subject of the second chapter (of 8). They are considered a "canary in the coal mine" related to ocean acidification. Later in the book we find that the pH of the ocean is presently very near 8.0; elsewhere I read values ranging to 8.05. A century ago ocean pH was about 8.15

Sidebar on pH: It is a logarithm, the negative logarithm of hydrogen ion concentration in water. Pure, distilled water has pH of 7, which means that the concentration is 10^-7, or one ten-millionth, or one hydrogen ion per ten million molecules of water (pH=7 is called "Neutral"). Thus a pH of 8 means one hundred-millionth. Putting these on a linear scale, adjusted with 1 meaning one per billion (pH=9) and 10 meaning pH=8, pH=8.05 converts to 8.9 and pH=8.15 converts to 7.08. Dividing the linear values, 8.15/7.08 = 1.15, which means that "acidity" is 15% greater at pH=8.05. Both these values are slightly alkaline, one more than the other.

What does 15% extra acidity mean to a coral (or any other ocean creature that uses calcite for its skeleton or shell)? Acid dissolves calcite, which doesn't dissolve when pH is 7 or larger. Acids have lower pH. For example, the pH of orange juice is about 4, and lemon juice pH is less than 3 (sour! You can taste pH). In sum, getting calcite to precipitate out of sea water is easier, and takes less chemical energy, when the water is a little alkaline. It takes a coral more energy to form its calcite skeleton at pH=8.05, compared to 8.15. Do note that fears of "shells dissolving" in the oceans any time in the near future are groundless. However, corals and shelled animals are having a little harder time forming their skeletons and shells.

On to Chapter 3, about sea fans and other gorgonians. These are also in the phylum Cnidaria, and are often called "soft corals" because they don't form rocky skeletons, using chiton or similar biopolymers instead. The word "gorgonian" refers to the Gorgon of mythology, who had snakes instead of hair on her head. An early biologist thought that these animals looked a little like that.

Collecting part of one of these is easier than collecting a stony coral: you don't need a hammer and chisel! And collecting is what the author did, of many of these creatures. Soft corals have immune defenses nearly as potent and various as sponges do, plus stinging cells like other cnidarians. Usually, the stinging cells, or nematocysts, not only immobilize prey, they also fend off most predators. Most. That word introduces the fourth chapter.

The term "sea slug" is rather ugly, because most of us know slugs in the garden as voracious pests, with slippery grayish bodies that offend most folks. I like the term "Nudibranch" better; it means "naked gills". As this illustration shows, these oceangoing mollusks are often beautiful. Being mollusks, they are members of the second largest phylum, Mollusca, with at least 100,000 species, and perhaps a million or more—we know so little about the ocean… Mollusks have a pass-through body, with both mouth and anus, plus a brain and nervous system. 

Nudibranchs' bright colors warn of a darker side to them. Many are venomous, but not in the way a snake or spider is. Many nudibranchs eat corals and other cnidarians, and they have an astounding biochemical trick: they can capture the nematocysts of their prey without setting them off and incorporate them into their own frilly tissues. Brushing up against one is like encountering a jellyfish and can sometimes be life-threatening.

The giant clam, subject of Chapter 5, is a quite different kind of mollusk, with a different superpower. They channel light and even shift its color, to "feed" symbiotic algae that provide much of the clam's nourishment.

The bright colors of their mantles are a combination of filtered light and fluorescence. Ultraviolet and violet-blue light in particular are useless for inducing photosynthesis. Fluorescent chemicals convert some of these "blue and ultra-blue" colors to colors the algae can use. In addition, the algae are arranged in small physical structures that stack them in ways that increase their overall efficiency. We have a lot to learn from clams! On a side note, we learn that these big clams cannot close their shell all the way. Old rumors about divers being trapped by giant clams are bunk.

One more group of mollusks fills Chapter 6. The skin of an octopus is possibly the most complex organ in the animal kingdom. This image shows an octopus most of the way through a rapid transition into looking like a lumpy rock. A careful look will reveal an eye, and further down, a few of the suckers that haven't yet been tucked under.

Octopuses, cuttlefish, and squids can change color, not just wholesale, but in patterns. The first two can also raise lumps, bumps and spikes in their skin to produce all kinds of shapes. A moment before this photo was taken, the octopus had smooth orange-red skin. It changed so fast that it seemed to vanish before the diver's eyes. Single frames from the video showed that the entire transformation took about a quarter second (7 or 8 frames in a 30-fps video). Great numbers of tiny muscles surround chromatocytes (color organs the size of a poppy seed) and sections of skin (to shift from flat to bumpy or spiky), under direct nerve control. Perhaps that is why an octopus or cuttlefish has nine brains. Lots of logistics going on!

Back to Cnidaria for Chapter 7: Jellies and their light shows. I have only seen these animals at the surface. On a couple of occasions my friends and I pulled dozens of 2-foot-wide jellies out of the surf at Huntington Beach in California, to make swimming safer. If you dive at night, you are more likely to see the light show. Not only jellies, but many other soft-bodies sea critters make their own light, or have captured special bacteria that do it for them. This amazing medusa has several colors of bioluminescence. It was photographed by its own light.

How poor is our land-borne experience! We have only fireflies and glowworms (certain female fireflies) and a number of other beetles to light up an evening, and a few species of glowing mushrooms. In the ocean, 90% of species produce light. Naturally, scientists are scurrying to learn their secrets. One is very useful already: green fluorescent protein (GFP), derived from a jelly. DNA to produce it is easy to splice into various parts of other animals' genomes, producing mice that glow green, or small fish with certain organs that glow with varying brightness as metabolism waxes and wanes.

Another phylum shows up in the last chapter, Echinodermata, the "spiny skins". Sea stars (colloquially, starfish) are not quite radially symmetric, as the Cnidaria are. There is a respiratory port off-center on top, making them bilaterally symmetrical, just barely.

This gallery shows 13 species of sea star, and three related echinoderms. The phylum contains more than 7,500 species so far known, while we have fossils of 13,000 extinct species. All are predatory.

This chapter focuses first on an experiment in removing sea stars from a section of seacoast. The area became overrun by mussels, which grew to the size of footballs. Where sea stars were present, there were still lots of mussels, but also areas where many other animals could settle, which greatly increased biodiversity.

More recently, there was a "starfish pandemic", and nearly all the common ochre stars along the west coast of the US and into Canada died, plus just as many "sun stars", a deep-water species with 24 arms. Over time, natural selection did its work and the numbers of ochre stars began to recover, but not, at the date of writing, the sun stars. The author and others are doing captive breeding to develop a resistant variety of sun star, in hopes of repopulating the deep coastal plain. Why, you might ask? Sun stars prey on sea urchins. If unchecked, sea urchins eat all the kelp. Kelp forests protect many species of fish and other pelagic (midwater) animals, including commercial species. Sun stars in deeper water and ochre stars in tidal areas are keystone predators: their presence controls the biodiversity of entire areas.

Throughout the book the author complains of the effects of climatic warming and ocean acidification that are based on increasing carbon dioxide in the atmosphere. In the ocean areas she frequents, the effects are visible. She calls it a Gut Punch. Her Epilogue is a long plea for more rational approaches to management of the ocean. While I agree with her on one level, I find it sad that we, as a species, find the need to "manage" 3/4 of the planet's surface. What we really need is to manage ourselves, but the lesson of the Bible, along with most other religious texts, is that humans excel at mismanagement, and any god you may imagine has a hard time keeping us in check. 

For context: The God of the Bible spent two millennia dealing with one family, the descendants of Abraham, to finally rid them of their tendency toward idolatry. He has spent the two millennia since then dealing with the spiritual descendants of Abraham, that is, the Christians, and has yet to rid them (us) of their (our) tendency to divide (there are more than 40,000 "denominations"), primarily over opinions, which are our modern idols. Mismanagement of the human soul is the source of mismanagement of planet Earth. This is why we need a Savior.

Freakonomics with a stethoscope

 kw: book reviews, nonfiction, medicine, economics, motivation, biases

You're 48 years old. You have a pain in your gut. Over the next few days it gets worse, and you begin to have diarrhea. You see a doctor, who says it might be an ulcer and suggests an OTC antacid. That seems to help, but not 100%. Being an agreeable sort, and in the midst of a demanding career, you carry on for several months. The diarrhea and pain come and go, come and go. Then the pain gets worse, and the diarrhea gets worse, and gets darker, even tarlike. What now?

This happened to a young friend's mother, and "What Now? meant seeing her doctor quickly, getting a colonoscopy at age 49, and dying of colon cancer a month later.

Now suppose the age above was not 48 but 52. The fourth sentence and what follows is likely to read, "You see a doctor, who orders a colonoscopy. Cancer is confirmed, and removed in an operation. Several months of chemotherapy follow, and you live many more years."

When I had gut pain at age 53, the doctor should have ordered a colonoscopy, but didn't. Why? The insurance industry scores doctors badly who order too many of the more costly tests! I eventually did have a colonoscopy, but I had to order it myself! I soon had a serious operation, half a year of chemotherapy, and now I am 78. Had I waited for this rather passive doctor to get around to ordering the test, I'd have died 25 years ago. I didn't go back to that doctor. There's a further wrinkle in this, which I'll return to.

What's the difference between age 48 and age 52? I could have used 49 and 51. The cutoff for "elevated risk of colon cancer" is age 50. Not only is it hard to get the insurance company to pay for a colonoscopy if you are "too young", the guidelined cutoff is a mental barrier for your doctor, who probably just won't think of investigating more deeply.

Such cognitive biases and blind spots are the subject of Random Acts of Medicine: The Hidden Forces that Sway Doctors, Impact Patients, and Shape Our Health, by doctors Anupam B. Jena and Christopher Worsham. Dr. Jena is host of the podcast Freakonomics, M.D., and the book takes an approach similar to that in Freakonomics and Superfreakonomics by Steven Leavitt and Stephen J. Dubner, two books I have close at hand. Together, these three books emphasize that at its root, economics is the study of motivation, of why people do things.

In the dozens of cases reported in the book, the doctors and their associates plumbed the databases of Medicare and the CDC for information that allows them to winkle out the little anomalies that reveal biases such as the "first digit bias" that puts age 48 or 49 into the "forties" bin and 51 or 52 with the "fifties". Untimely deaths can and do result form such biases.

If these two doctors stepped into the waiting room and you had the chance to choose one of them to perform your yearly physical, which would you choose? (The image was generated using Leonardo AI)

Granted, neither you nor I will be offered the chance to choose a doctor "on the spot," but if you were…? Here's the wrinkle from above: Fifty years ago I would have been more inclined to choose the man, not because of race but because he's male. Since then I've had to change doctors a number of times because of my moving or doctors moving elsewhere or retiring (or the passive doctor I "fired"). I've had both male and female doctors. By age forty, a man starts getting the "digital prostate exam", sometimes called the "golden finger". Having been probed by both male and female doctors, I found that I really prefer a doctor with long, slender fingers! A female musician who happens to be a doctor fits the bill perfectly. I've also learned that women are more willing to take an extra few minutes, and more likely to think sideways in case there is a second factor, not just "the diagnosis". My current doctor is female, and is tied for best doctor I've ever had.

What do doctors Jena and Worsham have to say about that? They studied Medicare records of 1.5 million hospitalizations, and gathered information about the outcome of care by 58,000 doctors, of which 32.1% were women. The criteria were thirty-day survival and rate of readmission. After the data were normalized to eliminate confounding things, here are the key facts:

• 11.3% of the patients died within 30 days of being hospitalized.
• For women internists, mortality was 11.1% and readmission rate was 15.0%.
• For men internists, mortality was 11.5% and readmission rate was 15.6%.

Are these differences small enough to be negligible? No. More than 10 million seniors are hospitalized for medical conditions (excluding accidents) yearly. The doctors conclude, "…if male internists were performing at the level of women, there would be thirty-two thousand fewer deaths…each year." 32,000. That's 80% of the death toll from highway accidents.

Earlier in the book, we find that the month a child is born influences the likelihood of getting a flu shot during yearly pediatric exams. That influences the number of kids that get the flu. Why? The new flu shots become available in autumn, preparing to deal with the surge of influenza in the wintertime. A parent of a youngster whose checkup is in May or June is told to return to the doctor in October for a flu shot. Less than half do so. Some may take the child to a drug store clinic or instant clinic, but that is a small percentage. So kids with birthdays in the spring or fall, or even late winter, are less likely to be vaccinated, and more likely to get the flu, or to get a bad case.

The last chapter of the book dwells on the COVID-19 pandemic, and the role of politics in medicine. Humans have been called "the political animal"; politics gets into everything! The struggle for power is the source of the world's greatest evils. I'll leave it up to you to read their insipid take on the matter (sorry, docs!). Instead I'll riff on the experiences of myself and my wife.

We were reluctant to get the mRNA agent that was being called a vaccine. We learned some stories of people who survived the disease well enough, but had "Long Covid" and in some cases were debilitated for months. That tipped the scales; we decided to get the shots, which we did in April 2020. We were generally compliant with things like masking and "social distancing". By the time various "boosters" were announced, we'd done sufficient research to realize that the "vaccine" was usually useless and often harmful. Here is a point I wish the doctors had put in the book: The yearly number of serious adverse reactions to the mRNA agent is just a little greater than the sum total of serious adverse reactions to all other vaccines combined!

How many remember in the middle of the controversy, Dr. Anthony Fauci saying, "I AM Science!" He had already admitted to lying a couple of times, and had been caught in a few other lies. Here he lost all remaining credibility. He doesn't understand science, not even a little bit!

Here is what the mRNA agent does: It induces your body to create a particular protein found on the spike of the SARS-Cov-2 virus. That protein triggers the immune system to create antibodies to that single protein. It is a two step process. By contrast, a vaccine consists of broken-up viruses or proteins extracted from them, which triggers the immune system to create antibodies to most or all of the proteins in the vaccine. The extra step that came before increases the variability:

• Different people have different levels of response to a "foreign" protein. One person's immune system may produce ten or one hundred times as many antibodies as another's. This is why vaccines aren't 100% effective. Flu vaccines in particular show this effect.
• Different people have different levels of response to the mRNA agent. One person may wind up with ten or one hundred times the level of "spike protein", which in turn is subject to the range of variable response noted above.

A good portion of my career I used the statistics of distributions. I'll save you the agony of figuring out any equations. Rather, let me just say that when you have two distributions, the mathematical tool used is called convolution. The final, overall distribution is very wide indeed. In this case, a range of a few thousand to one. Also, you may have heard of the "Gaussian distribution", also called the "Normal curve", a smooth curve with a symmetrical hump in the middle. That's not what we have here. The response distributions here are more likely Lognormal distributions, which have a small number of large values and a much larger number of small values. Convolving two of these yields an extra-wide distribution, but heavily weighted toward very few powerful responses, a large-ish number of "middling" ones (centered on the "target" response the pharma company aimed for), and an overwhelming number of small to almost nonexistent responses. These small responses led to the "breakthrough" cases of COVID-19 disease among those who took the shots. For some people, the shot may as well have been distilled water.

My wife and I count ourselves lucky. We had mild reactions to the mRNA shots, a little stronger than the "sore arm" we get from a flu shot, but not too bad. The same-day response was to the mRNA itself, and the next day's soreness was in reaction to the protein thus created. We learned later that some people dropped dead on the spot! These must have been those with a super-strong response in both steps of the process. Their immune responses overwhelmed the body.

I have several friends who are doctors. One of them, because of his work, was doubly treated; he received both the Pfizer and the Moderna mRNA agents. He has since had COVID twice. But before that, he and I worked out a strategy to deal with the infection: Stop eating for a couple of days. Those who died from the infection actually died from pneumonia, which was caused by the body's overreaction to the virus. The ones with the strongest immune systems died first! What is the gooey junk that fills the lungs during pneumonia made from? Sugar. This is why diabetics have the highest risk. What happens when we skip meals? Blood sugar is reduced. It drops a lot. This hinders pneumonia.

Secondly, the two "Democrat-hated" drugs, Hydroxychloroquine and Ivermectin, are useful not because they are anti-viral. They aren't. It is because they tamp down the cytokine reactions that lead to pneumonia. HCQ works in the first day or two, and Ivermectin later on. My doctor friend obtained supplies of both medications for himself and for my wife and me.

At the end of August, 2022, I caught COVID. Here I found out that the joke was on me. The primary symptom I had was powerful nausea. I threw up everything, and I couldn't even drink water! So I couldn't take HCQ!! I went to the one clinic in the area with antivirals on hand, and was given those plus anti-nausea pills so I could swallow the meds and keep them down. Although I'd moved to the spare bedroom the day I woke up sick, my wife got sick a week after I did. She had a very sore throat, making it painful to take any pills. She went to the clinic and also got the antiviral. Both of us recovered quickly. By the way, I had lingering low appetite, my kind of "long Covid", and I took advantage of it to lose some weight, around 30#.

A year and a half later, the above scenario was repeated. Same symptoms, same need to get the antivirals, same quick recovery. I was able to lose another 15#, and I learned what it takes to hold my weight. So I count SARS-Cov-2 my friend!

Another year or so has passed. My family doctor is in agreement with what we've done and with my determination never to get a "booster." They're too dangerous.

That is a long digression from a wonderful book. Doctors Jena and Worsham show how and why doctors make certain kinds of errors, and discuss ways these errors are being mitigated. Reading this book is useful to all of us as patients, so we have the mental tools to work with our doctor(s). We can't replace them, but we can either help or hinder their work. We all know that something will get us sooner or later. Together we can make "later" be even later, and thrive in the meantime.

When viruses help us

 kw: book reviews, nonfiction, science, virology, bacteriophages, antibiotic resistance, medicine

These barely-living creatures look to me like a balloon attached to a hypodermic syringe. They are T2 bacteriophages injecting DNA into E. coli bacteria. The common term for a bacteriophage, a virus that infects bacteria, is "phage", which means "eater". They eat bacteria.

The phage's DNA is packed into the "balloon", a protein capsule, so tightly that the pressure inside is more than 300 psi. No wonder that, once the "syringe" pierces the cell wall of the bacterium, the DNA erupts into the cellular interior. There, "shepherd" proteins that accompany it help it integrate with the cell's DNA and begin to make great numbers of copies of the phage. Once all supplies within the cell are exhausted, lytic enzymes cause the cell to rupture, releasing thousands of new phages.

To learn of phages and the breadth of their usefulness, I read The Good Virus: The Amazing Story and Forgotten Promise of the Phage by Tom Ireland. The book has two strong themes: that phages save lives in an almost miraculous way; and that political and scientific blindness have hindered the study of phages in the "free world", primarily because they were primarily developed as a therapeutic tool in the Georgian SSR and Soviet Russia. By the time scientists in the West learned of their antibacterial use, the cultural trend was "Better dead than Red."

The first viruses discovered were phages. Doctors noticed that sometimes the bacterial "lawn" growing in a Petri dish would develop "plaques"—clear, circular holes—but that nothing could be seen under the microscope, just bits of broken bacteria. Later, by filtering the liquid mix from the clear spots through a very fine porcelain filter, a "something" could be produced that killed bacteria. The term "filterable virus" was coined. Only later, when the electron microscope was invented, were phages seen and given their name.

Bacterial cells are so different from the cells of animals that phages cannot infect us. While there are 600 or so human pathogenic viruses, there are tens to hundreds of thousands of known phages (so far), many millions of phages known only from DNA screening of water and soil, and from billions to perhaps more than a trillion varieties of phages in existence worldwide. I way "varieties" because the biological understanding of "species" doesn't really fit the way viruses, and phages in particular, evolve and reproduce.

Step a little closer to home. It is rather tricky to count the cells in a human body. About 80% of "our" cells are red blood cells, so when you hear a number like 30 trillion, realize that about 24 trillion are RBC's, and the other six trillion are nucleated cells (RBC's don't have a nucleus). We have a microbiome, mainly in our gut but also across our skin, that numbers 60-100 trillion bacterial cells. Bacteria are so small that this amazing number of cells weighs, in total, a few pounds, or a kilogram or two. How about viruses? They are in the air we breathe so of course we contain some. Just counting the phages that have been found preying on bacteria within and on us, the number is about ten phage particles per bacterial cell, or roughly a quadrillion. Phages are so tiny that a quadrillion of them totals about 1/30th of a gram.

After phages were discovered more than a century ago, they were found to have antibacterial properties that could be used to cure infections. Before the discovery of effective and economical antibiotics such as Penicillin, phages were the only cure.

Side note: no medicine is perfect. Whether antibiotic or phage therapy, the dose doesn't destroy 100% of the invading bacteria. Rather, bacterial numbers are reduced to the point that our immune system has time to kill every single bacterium that remains, and then we are fully well. We need at least a minimally functioning immune system to overcome an infection, no matter what medicines we may use.

An early practitioner and proponent of phage therapy, Felix D'Herelle, called phages a "third arm of the immune system". The classical arms of the immune system ("arm" in this case meaning "weapon system") are innate immunity and adaptive immunity. The first is immediate, the second requires cellular learning, but also confers longer-lasting immunity. More recently I have read that our microbiome can be considered a preventive arm of immunity, because the good bacteria in us prevent pathogens from getting a foothold and causing disease. Thus I would call phages either a part of this third arm, or a fourth arm, destroying many pathogens once they "land".

A long section of the book tells of the Eliava Institute in Georgia (European Georgia), in Tblisi, a focus of "medical vacations" by people with multi-drug-resistant bacterial infections. For decades Eliava was the only place where a patient could have a sample taken, a phage therapy either found in the "archives" at Eliava or developed from searching in dirty water (!), and, hopefully before dying, being treated and their life saved.

Later chapters tell us of an increasing number of phage therapy centers arising. Parallel to them, recent excitement about the possibilities of phages has led to some businesses developing ways to create custom phages from scratch. This is based on work done with the ΦX174 phage: This virus was the first organism to have its DNA completely sequenced, in 1977; and a slightly simplified phage based upon it was synthesized in 2012. It was first isolated in 1935 from sewer water in Paris. That makes sense, because it infects E. coli, the famous "poop germ".

ΦX174 is one of the smallest viruses. It doesn't have the syringe like the "T" phages and some others. It is just a tiny balloon containing the DNA for 11 genes. The capsule has 12 spikes that allow it to attach to a bacterial cell.

Phages, with their simplified genomes, were first-line tools in the early days of the genetic revolution, even before the structure of DNA was discovered in 1951 by Crick and Watson. They remain useful for genetic studies.

One reason for producing synthetic phages is that the capsules of certain ones, without the DNA content, can penetrate the brain-blood barrier. If the content of such a capsule is a chemotherapy drug, and the spikes are created to attach to cancer cells, extremely targeted therapy becomes possible, in the brain or elsewhere.

That is just one use for phages that we find in the last couple of chapters of The Good Virus. The author also discusses fears of "gray goo", because viruses are actually nanotechnological machines. If a nanotech machine has the directive, "reproduce at all costs", can it spread throughout the biosphere, turning all plants, animals, and everything into a mass of nothing but themselves? Considering that nature has already developed exactly such machines, but that they are engaged in an eternal "arms race" with bacteria—which quickly learn to fight back—we realize that no gray goo scenario is imminent.

One more note: not all phages are wholly beneficial to us. This lovely image from Science Photo Library shows A45 phages attacking Streptococcus pyogenes cells. These phages carry genes that induce the cells to release fever-inducing chemicals, which cause strep throat. If the Strep that naturally exists in you is healthy, there's no problem. When the bacteria get sick, though, so do you!

An even worse case of "sick bacteria causing sick people" results when this filamentous phage known as CTXφ infects Vibrio cholerae: the deadly waterborne disease cholera. No doubt, other such cases abound.

Nonetheless, the usefulness of the great majority of bacteriophages is so great that the author optimistically hopes that they will provide a very beneficial path toward treating infections that our antibiotics are increasingly unable to cope with.

By the way, images and articles regarding phages and E. coli seem to outnumber the rest, not because that's the most common, but because E. coli are used for so many kinds of genetic studies that they dominate the literature.

The dark side of genetic medicine

 kw: book reviews, partial reviews, nonfiction, medicine, genetics, corruption

I began to read The Tyrrany of the Gene: Personalized Medicine and its Threat to Public Health, and soon realized that I could see where the author was going. The Introduction and first chapter lay out his thesis. I read the last chapter, titled The "Gleevec Scenario", and for me, the picture was complete.

Genetic Medicine, AKA Personalized Medicine and Precision Medicine, is the current fad in medical and pharmaceutical circles. However, it is miraculous for a few, useless to most, and incredibly expensive: even the few who can benefit from a precision therapy cannot afford it; without a very robust insurance plan (hard to find or afford), they often cannot even afford the copay.

The Introduction features the sad story of the author's father, who died of lung cancer thirteen months after trying to get out of bed one day and finding that his legs were paralyzed. A metastatic cancer had damaged the nerve trunk to his legs. He had fourth stage lung cancer. When one of the bits of cancer was surgically removed and tested genetically, it was found to be susceptible to a new medication that helps a few percent of lung cancer patients. The cost was a few thousand dollars per month. What kept this from becoming a million-dollar story? The father's life was extended by only a few months. At first, the tumors receded and his body began to heal. He was able to wiggle his toes. Then the tumors became resistant to the medication and resumed growing. Whether his life was extended by two months or ten, from his original situation, is not known. What is known is that the "miracle" was temporary. The author cherishes the memory of those few extra months. Fortunately, his family could afford the medication over that period of time.

Why are such treatments so costly? The author tells of medications that can cost tens to hundreds of thousands of dollars monthly. The reason, we are told, is that it costs millions or tens (or hundreds) of millions of dollars for a pharma company to research and test a drug, and to comply with all the regulations to bring it to market. If the number of people who can be helped is only a few thousand, or perhaps a million, the sunk cost has to be recouped by high prices. This is true, but the last chapter focuses on another factor.

When Gleevec was developed it was miraculous, for a small number of patients. Here, "small" is in proportion to the millions of people who have a certain kind of leukemia that Gleevec can't help. The number of people that could be helped was still large enough that the original developer and manufacturer, Novartis, made billions of dollars in profit. Right away I smell a rat: Gleevec did not cost billions to discover and bring to market. Its cost could have been reduced by a factor of ten and Novartis would still have made tens of millions in profit.

The second factor is "Because We Can". The last chapter shows that over time several medications similar to Gleevec were developed, and then put on the market at even higher prices. So much so, that when generic Gleevec appeared (after a few years of legal delays of the end of patent protection), the generic cost more than the original had at the beginning!

The pharmaceutical industry is an astonishing mixture of blessing and curse. Let us not forget that "big pharma" is the largest lobbyist in Washington (and other national capitols in which lobbying, AKA bribery, is permitted). Yet many, but probably not most, of the industry's products are lifesavers, or at least life-enhancers.

From time to time there is a flurry of interest in radical life extension, and a certain debate arises: If it becomes possible to extend almost anyone's life to 150 or 200 years, but it costs a few million dollars for each extra year, is it ethical to develop it? If only the super rich can afford it, won't they become an oligarchy? Of course, America and other Western nations are already de facto oligarchies, and many of the super rich are already taking advantage of better medical treatment, and frequently have longer lives than most of us. Precision/Personalized Medicine fits right into this scenario.

We have to think this through…except most people are unwilling to think, living on autopilot. 

The author's second theme is public health. There is less emphasis on public health measures as more and more funding and interest are focused on genetic medicine. This is a mistake. Public health advances such as separating sewage from drinking water sources and promoting hand washing have been responsible for most of the increase in average life span and general health since the middle-to-late 1800's. We still have more to do, but now it is being done more slowly or is neglected.

I read an article or book by Lewis Thomas years ago, about the three kinds of medicine:

1. Medical repair, as exemplified by surgery and cancer chemotherapy. This is the most intrusive and costly.
2. Maintenance medicine, ranging from analgesics such as aspirin and ibuprofen to symptomatic relief such as cough medicines and to antibiotics. Such remedies are mostly in the form of pills or injections and are usually inexpensive.
3. Preventive medicine, not only vaccines and antitoxins but also vitamins and other supplements that improve our health or prevent disease. These are usually the least costly (but not always!).

Public health measures could be considered meta-preventive medicine. They remove causes of disease and damage. The author's father had been a smoker for part of his life. Very, very few lifelong nonsmokers get lung cancer. He also had a couple of other "risk factors", secondhand smoke as a child, and a period of time exposed to asbestos. Had his history been different, all three factors would not have occurred. Yet, the two most prevalent addicting drugs, alcohol and nicotine, still plague a large proportion of the population, causing great amounts of premature death. Further, overuse of sugar is behind "metabolic syndrome", which includes Type II Diabetes and, as in the case of my uncle, frequent amputation of toes or feet, and reduction of life span by ten to thirty years (my uncle died in his early 70's; his widow lived more than 100 years. Based on family history, he could have lived to age 85 or 90).

Public health is not "sexy"; genetics is. But it's more effective for more people.

I decided not to read the whole book because it is suffused with the author's pain, and he had made his points well enough in the parts I read, that I get the picture. It's worth reading at least a few chapters of this book; it may induce you to help with the tough Thinking part.

Monkeypox and STDs - it isn't just sex, it's promiscuity

 kw: medicine, medical musings, disease, monkeypox, std's, sti's

At one time diseases such as syphilis and gonorrhea were called Venereal Diseases, or VD's. "Venereal" refers to Venus, the Roman goddess of "love", actually, "lust." A generation or two later the preferred term vacillated between Sexually Transmitted Diseases (STD's) and Sexually Transmitted Infections (STI's). These days the political correctness police don't know quite what to call these "social diseases." Also, in the past generation more diseases have attained this status, including Chlamydia, venereal warts, genital herpes, and, of course, HIV/AIDS.

The most recent disease to be tentatively added to the list is Monkeypox. It has mainly afflicted those in central Africa, particularly Nigeria. In those areas, it afflicts people of all ages, including children, and while more men than women are afflicted, the difference is not huge. In the rest of the world, now that it is spreading everywhere, the picture is different. Particularly in the West, most victims, 90% or more, are gay men. Thus there is a huge outcry in some quarters against those who would call Monkeypox a STD or STI, calling them "homophobic". What is Monkeypox, really?

The virus that causes Monkeypox is related to the Smallpox virus. Smallpox was very transmissible, but usually required contact. However, even the briefest contact, such as brushing by someone in a crowd, was often sufficient. Monkeypox is apparently not nearly that transmissible.

There used to be fears that one could catch syphilis from a solid handshake. That turns out to be slightly true, but only if both persons have very sweaty hands, and the person originally infected has been touching disease lesions (they do itch). It is actually quite hard to catch syphilis. It is easier to catch Monkeypox.

Let's step back a moment to consider a point nearly always missed: EVERY infectious disease can be transmitted by sexual contact. The small list of "STD" infections consists of those diseases that are so hard to catch, sex is required for transmission. 

Is Monkeypox such an infection? It is probably almost that hard to catch. It may inhabit a borderland, a near-STD-but-not-quite. That is, while it's safe to say that anyone who has syphilis caught is sexually, there are apparently a small percentage of cases of Monkeypox that were caught by less intimate contact. But the number is small.

The fact remains that in Western countries, more than 90% of those who have caught Monkeypox are gay men. The very few women who have caught it all seem to have a bisexual boyfriend.

What is it about gay men that has made them so susceptible? I point out the "Gay culture", characterized in the 1980's by the "San Francisco bathhouse" phenomenon, where a designated "receiver" (I don't know the real term, and I don't care what it is) would be sodomized by 30-60 men, one after another. One can imagine that any diseases found in that crowd would spread and spread and spread, week after week. Such practices fueled the early spread of AIDS. That culture may have died down somewhat since, but it is not extinct, and it is fueling the spread of Monkeypox.

The heterosexual spread of AIDS in Africa in the 1980's was fueled by both men and women having numerous partners, just not as intensely as in the bathhouses. Monkeypox in Africa is following a similar course.

The obvious conclusion is that we need a new term. Monkeypox and the other "social diseases" that came before are actually diseases of promiscuity. Someone who has either zero or one sexual partner for one's whole life will never catch any of such diseases (Rape counts as adding one more sexual partner, however unwilling the victim).

I tentatively propose the term Promiscuity Diseases, PD's, to give the medical establishment and society in general time to mull over what we have here, and possibly coin a better term.

Been Shrunk?

kw: book reviews, nonfiction, science, medicine, psychology, psychiatry, psychiatrists

I am pretty sure the number of psychiatrists I have engaged approaches ten. Only two were "normal", whatever that might mean. I have also had talk therapy with several other psychologists, and I remember only one who was someone I'd be willing to befriend.

Over the years I did, finally, come to understand that a psychologist or therapist is empowered only to offer talk therapy, while a psychiatrist, who may also conduct talk therapy, is an MD who can prescribe medication if needed, or prescribe visits to a therapist. I was rather slow on the uptake. I thought of them all under the derogatory heading "head shrinkers."

Up front disclaimer: I am considered "crazy" by many, and looked at askance by many more. The label I've earned is Bipolar 2: I am a middle-of-the-road mood cycler. Bipolar 1 is the more extreme version and shades into what I call Bipolar Zero: someone with maniacal energy for a few weeks at a time, followed by months of melancholy and reclusiveness, culminating in deep depression and perhaps a suicide attempt (or several); only to pop back into mania almost overnight. That is one pattern of the classic Manic-Depressive syndrome. My "mania" is called "hypomania", meaning sorta-kinda-manic, and my depressive periods are more a kind of introversion and withdrawal. I also cycle rapidly, with several cycles yearly rather than one or at most two, the more usual pattern. I suspected this about myself beginning about age 30, but it was more of an "I wonder" sort of idea for a long time.

At about age 55 I saw a psychiatrist and it was confirmed. This was the wise and lovely Dr. Valentine (I don't mind using her name; I'll defer for the others). She confirmed that I was Bipolar 2, and discussed several courses of action with me. I had gone to her when a short stint using Zoloft had the unexpected (to me) result of triggering full-blown mania. My GP, who had suggested trying Zoloft because I felt very depressed (more than my usual month-or-two-of moodiness), saw that I was manic when I saw him after taking Zoloft for two weeks. I was interrupting him—heck, I was interrupting myself!—and making all sorts of grandiose statements. At my most effusive, I had not been so grandiose before. Dr. Valentine prescribed a mild mood stabilizer. I don't remember which one (this was almost 20 years ago).

The drug eventually had side effects I didn't want to cope with, including the need for a daily nap. However, when I called for an appointment I found Dr. Valentine had moved her practice to another state. The mental health appointments were being paid for through a program at DuPont called Employee Assistance Program (EAP), which contracted work through ComPsych. I had to go through them to find an in-network doctor. No doctor I saw after this came even close to the combination of caring and expertise. Though they were competent, they were all rather off-center, and some were downright looney. I realized that ComPsych draws mostly from the bottom of the barrel: doctors who need the referrals because they couldn't stay in business otherwise. I could seldom stay with a doctor for more than a year or two, sometimes because I wanted someone less crazy than myself, and sometimes because they left the business or moved elsewhere. I live in an area that is poorly served because state laws are not very doctor-friendly. That means, whether a family doctor, a psychiatrist, or any specialist, about half the doctors around here are really altruists, serving where they know they are needed, and the rest are here because they couldn't make it in a more competitive environment. I have had some of both, in all areas (Luckily for me, when I needed cancer surgery, I got a true expert! But that's a story for another day).

I have to mention one example of "barrel bottom" psychiatry. I was sent to a psychiatrist because I had a suicidal episode. I was stopping a drug that made me gain weight and didn't help with depression all that much anyway. After a short, almost cursory interview, the doctor prescribed Depakote and gave me a bag with some samples. I was shocked. A friend of mine, who has more severe Bipolar than I, had been on Depakote and gained 90 pounds. I already weighed about 30 pounds more than I liked. I started to leave, and then I put the bag back on the desk and said, "You must be insane. This medication will make me even fatter than I am already. How will that improve my depression?" I walked out and I didn't pay the copay.

With many decades of experience with psychiatrists and psychologists under my belt (starting at age 12, but with significant gaps before middle age), I was quite interested to see Shrink Rap: Three Psychiatrists Explain Their Work, by Drs. Dinah Miller, Annette Hanson, and Steven Ray Daviss. The book is based upon the blog Shrink Wrap and the podcast My Three Shrinks, but it is much more than a simple compilation.

Each chapter uses one or two example "patients" to illustrate various facets of the work of the three doctors. Each "patient" is a composite, so as not to expose too much about any one person, who might be harmed by public exposure. Considering that some of the "cases" are mild, while others are quite severe, this is a valid concern. Consider "Josh", who is mostly pretty ordinary but has had some reverses. It is quite usual these days for an extended period of depression to prompt a doctor to prescribe Zoloft. "Josh" and his doctor found out what I and my doctor did: hidden Bipolar gets manifested by the general mood-lifting action of Zoloft. Josh's experience was more extreme than mine. And then, when he had a medical condition that was treated with steroids, he went full-blown manic, and needed to be hospitalized for a while. He missed a semester of college. The doctors who treated him had quite a job on their hands. It is kind of like accidentally starting a raging fire, and then trying to put it out without drowning everybody. And this was one of the milder cases.

I've had experience with clinical and therapeutic psychiatry. I was most interested in the discussions around forensic psychiatry. Previously I knew nothing about it. The word "forensic" conjures up doctors sifting for clues to a crime, or using DNA to confirm an identity, or not. "Forensic" is derived from an old word for "legal", so forensic psychiatry is its practice related to legal matters, such as determining the competence of a defendant whose lawyer is claiming an insanity defense, or judging the fitness of a parent in a divorce case who is accused of criminal abuse (if there is no criminal complaint, a different psychiatric specialist is consulted). A forensic psychiatrist will also interview a newly-arrested suspect who exhibits abnormal behavior.

There are a couple of chapters that weigh the relative merits of talk therapy versus medications. Both have their uses, but it is often quite a puzzle to determine which might be more effective. It has been said that the human brain is so complex that if there were only one human brain in the universe, it would contain within itself more than half the total complexity of the universe. Dealing with brain malfunction is thus the most difficult task of all. For many decades people have been studying human personality and its ills (actually, many millennia, though we usually set the starting point "only" two millennia ago with Aristotle). The study intensified in the past two centuries, beginning with Freud and Jung. Now in the early 21st Century, we are about an inch beyond the starting line in a "race" to figure out how to help people with emotional, personality, and brain malfunctions.

There is a lot more I could go into, and it is all very interesting, but I will bow out here. The book is like a textbook in some ways, though it is mercifully brief by comparison, and yet comprehensive. I came away with a better appreciation for the complex decisions that these doctors must make, and the great gulfs of unknown they must navigate. Heart surgery has been likened to doing an engine overhaul while the engine is running. Psychiatry is similar, except you can't even lift the hood to get at the engine. That limits things. I am glad that not every psychiatrist I dealt with was a bottom feeder; at least two or three were very helpful to me, in different ways and quite different times. The three authors of the book are based in the Baltimore area. If I need a shrink again (I hope I don't; I manage well without medication now), I might contact one of them!

It keeps you alive … until it doesn't

kw: book reviews, nonfiction, medicine, immune system

Once we didn't know anything about immunity. People died in droves from simple infections and diseases. Plague could ravage the earth, and nobody knew why. Then, no more than a couple of centuries ago, doctors began to recognize something in our bodies that fought invasions, infections, and diseases. By the Twentieth Century a number of special kinds of cells were known, and their role in destroying bacteria and viruses was being studied. When I was young, they were just called "white blood cells" and the main difference between a small number of known cell types was the number of nuclei and their size. That soon began to change.

Around fifty years ago our image of immune cells was like Rambo: Find enemy, blow enemy to bits. Over time, and with huge amounts of research, nuances were discovered. Chemical probing became more sophisticated, and dozens of cell types could be discerned; at first just macrophages ("big eaters") and the B and T "killer cells" were known, but later many more. Now some cells are known that slow down the killers, so the whole system can strike a balance between "scorched earth" and "admit all comers".

An Elegant Defense: The Extraordinary New Science of The Immune System – A Tale in Four Lives, by Matt Richtel, presents the history and development of immune system science in a comprehensive way, and that's just his introduction (about 35% of the book). Then he tells four life stories, one of his boyhood friend Jason Greenstein and his dramatic battle with Hodgkin's lymphoma; another of Bob Hoff, the poster child of "elite controllers", whose immune system keeps AIDS at bay; and two women, Linda Bowman and Merredith (last name withheld), whose immune systems—not so much like Rambo but more like the bodyguards of Indian Prime Minister Indira Ghandi, who assassinated her—turned against them.

We think of organs as rather solid things, like stomach and heart, made of cells that cling to one another as definite tissues. It is amazing to realize that a few pounds of our substance consists of free-roaming cells, that can look a lot like amoebae, and which move freely between our blood and any tissue in the body. However, the brain has its own immune system; the blood-brain barrier is too tight for the immune cells from the rest of the body to penetrate.

Twenty years ago, after I was operated on for colon cancer, I asked my oncologist how chemotherapy would affect my immune system. He said, "The cancer itself is evidence that your immune system wasn't quite up to the task. It will be weakened some more by the chemo, but will recover. Later on we'll instruct you how to keep it healthy." His advice must have worked; I'm still here.

A few years later a pre-teen girl in our church developed juvenile Lupus. Her immune system was overdoing things and attacking her body, not continually but in periodic episodes. With some reading and asking questions of doctors we found that the main trigger of her attacks was UV light in sunlight. Then I remembered a portion of Brave New World by Aldous Huxley: certain people were given jobs underground or in the dark, because they suffered from Lupus if they were exposed to the sun. We put special UV-blocking film on the windows of the church's meeting place, her family had their cars' windows tinted, and she got special UV-blocking clothing. Within about ten years she recovered from it, as often happens with juvenile Lupus. She needs less vitamin D now. Her skin, which was once the whitest I've ever seen, can tan a little, but she's still careful not to get too much sun.

I don't think it wise to summarize the sturm und drang of the ordeals endured by the four persons. There is just too much detail. The key message for me is that the immune system isn't just a killer organ. It is a balance organ.

Imagine that our immune system were infallible in determining what is Self and what is Other, and totally effective in eliminating Other. We would certainly be germ-free. However, the expense would likely be more than the body could afford, keeping a horde of hunter-killer entities supplied. One doctor described such an outcome as a "ten-foot pimple". Perhaps one could get used to it, but I'd rather not try!

In such a case, we would have no microbiota. But we do have our "internal flora" and I am not sure we could live without them. Some of the bacteria in our gut produce vitamin B-12. Others produce other nutrients and life-support chemicals. It is like the animal body (not just human!) is evolved to "steal" a lot of capabilities so it doesn't need to develop them itself. It is an advanced version of my practice of hiring contractors (like some concrete workers who are outside repairing my sidewalk as I write). There are lots of things I don't know how to do; I could learn, but it saves time when I can afford to hire work done.

Thus, the immune system has reached accommodation with thousands of species of bacteria and other microbes (I'm not sure what-all) to run our bodies more efficiently. Many of those species guard against pathogens and effectively form an extended part of our immune system.

There is a sad note at the end of the book when the author discusses death. Medicine isn't really about life-saving so much as life-extending and health-extending. We would like to live forever. Before there was modern medicine, or even Herodotus-level medicine, a few people would live more than 100 years, sometimes approaching 120 years. In fact, someone who is more than 100 years old today lived a number of years in a world without antibiotics or the public health measures that keep cholera and other scourges at bay. The only person in the modern era who lived 120 years or more was Jeanne Louise Calment, who lived just about 122½ years. She flirted with Van Gogh as a teen!

To put it bluntly, our amazing immune system, honed by four billion years of natural selection, usually does an excellent job keeping us alive and usually healthy until we have had time to reproduce and raise our children. Then it backs off, and backs off… For some, their natural life span is 60-70 years. For others it can be decades longer. The limit seems to be 120-ish, with no more than one or two persons per generation exceeding 110 years. Medical science has increased the average life span without making a dent in the limiting life span. Along the way, for most of us, our health span has increased dramatically compared to our grandparents and before. A great deal more must be learned if we are to modify our immune system's "program of senescence".

This book deserves a permanent place on our shelves. The author's summary of immune system science quite amazes me. I'll have to re-read some parts to get comfortable with the details. Keeping a body alive is no single-shot task; it demands an army that has dozens of specialized functions, including negotiators. Amazing!

Coronavirus and Sunlight

kw: medicine, viruses, coronavirus, ultraviolet, inactivation

I contend that the safest place to see others face-to-face is outside on a sunny, breezy day. Masks are not needed outdoors, only indoors. Here is why.

If someone is ill with the novel coronavirus SARS-Cov-2, the cause of Covid-19 disease, any droplets that leave their body with their breath will contain virus particles, called virions on medical literature. The virions are rather large, some 125 nm in diameter. That's about four times the size of rhinoviruses, the most common cause of the common cold, and a it's a little larger than influenza viruses. However, 125 nm is 1/8,000th of a millimeter. No mask you can afford will capture them, but that is not the point.

Indoors among "the public", the threat is not isolated virions but the droplets released in small amounts by speaking or heavy breathing, in larger amounts by a cough, and in very great amounts by a sneeze. The droplets are mostly between 1,000 and 10,000 times the size of the virions they might contain. Nearly any such droplets that encounter your face covering or mask will be caught in it. So when you wear a mask to the store, when you get home wash it with hand soap and let it dry, or replace it if you have a lot of the disposable kind.

What happens outside? Unless the humidity is very high, the droplets evaporate in a few minutes, or even a few seconds. The virions are now "free". Even before the droplets evaporate, however, if the sun is up, something wonderful happens! Ultraviolet light from the sun destroys the virus genome. The question is, how soon?

I found and downloaded an article, "Predicted Inactivation of Viruses of Relevance to Biodefense by Solar Radiation", by C. David Lytle and Jose-Luis Sagripanti, in Journal of Virology, v79, No. 22, Nov. 2005, p. 14244–14252. The work was supported by DoD and relates to defense against biowarfare agents.

The authors gathered data on solar UV and Hg-vapor UV (such as that used in hospital disinfection lamps), and how quickly different kinds of viruses are destroyed. There are a lot of details, but the relevant conclusions related to coronaviruses are these:

• Sensitivity units are reported two ways, as D37 and as 1-log.
• D37 is the dose of UV needed to destroy all but 37% of the particles. 0.37 is 1/e, and is related to natural logarithms.
• 1-log is the dose of UV needed to destroy 90% (all but 10%) of the particles. It is related to common logarithms, of base 10. This is more understandable and relevant to us.
• The viruses of greatest interest in the article are filoviruses such as Ebola or Marburg. D37 for these is about 7.4 and 1-log is 17. (These data are from Tables 2 and 4)
• The virus of interest today is a coronavirus; the family Coronaviridae has D37 in the range 2.5-3.9 (Table 2), for which I calculate 1-log of 5.7-9.0. Thus SARS-Cov-2 is about twice as sensitive to UV light as the Ebola virus. That's good news.
• The effectiveness of solar radiation depends on the angle of the sun. A specific datum relevant to the DE-PA border area where I live is for Davis, CA, on a typical, sunny July 15. The 1-log level of deactivation for a filovirus occurs in 55 minutes. (If you're lucky enough to live in Hawaii, the sun's UV is twice as strong there, and the relevant time is 21 minutes.)

From these data I calculate that 1-log deactivation (10% remaining viable) takes between 19 and 29 minutes. Let's round these to 20 and 30 minutes. Deactivation is a stochastic matter. If a UV photon passes through the right part of a coronavirus virion, it will damage the RNA. Most of them miss. So let's look at the 20-minute level for a theoretical virus. In 20 minutes, 10% are still viable. In 40 minutes, only 1% are still viable. In an hour, 0.1% are still viable, and so it goes. That is one in a thousand after an hour, and one in a million after two hours, and one in a billion after three hours. For a "tougher" coronavirus, at the 30-minute end of that range, viability after an hour is about 1%, and after three hours it is about one in a million.

So if you're worried that someone emitting viruses is outside, and they blow downwind, two things work in your favor. Firstly, the swirling wind will spread them out so only a few have the chance to reach you, and secondly, if the person is some distance "upwind" from you, sunlight will zap the virions at a steady rate.

There are two further matters I am still researching. 

• How many virions need to enter the body to cause infection? A very infectious virus such as influenza can stably cause infection if around 100 virions are breathed in. This is because many of them are "beaten" by the innate immune system. For more susceptible people, not as many are needed, but I don't know what the normal range of natural resistance is, for people who are not vaccinated. It may not yet be known what the "average infectious load" (my term) is for coronavirus.
• Whether it is sunny or not, oxygen also deactivates virions. How quickly? Whatever I can find out, I'll report.

Medicine is becoming chemistry

kw: book reviews, nonfiction, medicine, drugs, biotechnology

When I was taking a specialized Geochemistry course, "Crystal Chemistry", I realized that chemistry is mostly geometry. From a geochemical point of view, most of the crust of the earth is a gigantic oxygen crystal, with the oxygen atoms in or near a closest-packing arrangement, held together by covalent bonds with various metal ions.

In biology, the geometric view is even more relevant. For example, enzymes work either by making a lock-and-key attachment, or by making two or more such attachments and then shifting or bending the resulting complex so a different lock-and-key is facilitated. Most drugs that have been discovered, or engineered, are actually little geometric items that either promote or block a biochemical pathway in the body. A few are replacements for necessary molecules that are sometimes present in insufficient amounts, such as insulin, to treat Type I Diabetes.

Side effects of drugs result when the lock-and-key match is not perfect, and the matching part on the drug is also a partial match to a critical component of a different biochemical pathway. Side effects also occur when the waste-disposal systems of the body break down a drug molecule: some breakdown products have geometrical properties that interfere with other biochemical pathways.

In Ten Drugs: How Plants, Powders, and Pills have Shaped the History of Medicine, Thomas Hager discusses the discovery and development of ten families of medical molecules. The subtitle tells of three that could stand in for them all:

• Plants – The first chapter tells us the history of Opium, derived from the sap of a particular species of poppy. It also discusses how researchers learned to refine opium to extract morphine, the primary molecule in the mix. Morphine was the first opiate to be discovered; opiates are derived from opium.
• Powders – Heroin, prepared by chemically altering morphine, and opioids (not derived directly from opium or its components, but entirely synthetic) such as Fentanyl, bookend the discovery of painkilling medicines. Heroin came very early (1897), leading to many products, with varying amounts of pain-relieving properties, and all of them very addictive. Fentanyl came later (1959), and led to exceedingly powerful pain medications, which are also powerfully addictive.
• Pills – "The Pill" refers to birth control medication, which changed sexual politics in America and much of the world, and upended social systems in its wake. It also may have triggered the "Feel bad? There's a pill for that" ethos we live in.

In the ninth chapter we find the convoluted story of Statins, the drugs that lower blood cholesterol, which are taken in an attempt to reduce fatalities from heart attack and stroke. For the worst cases of extra-high cholesterol, lowering it does indeed help. But it is still now known if taking statin drugs will actually save (that is, lengthen) the life of the vast majority of those who take them because their blood cholesterol is slightly higher than a threshold such as 200 mg/dl. That value is a nice, round number that is near the center of a broad distribution: Some people with low or even very low cholesterol get heart attacks, and most people with moderately high cholesterol live long, healthy lives. 200 is a kind of break-over point, "because you have to draw the line somewhere."

Let's look for a moment at breakdown products. Morphine, its derivatives, and related opioids, work by stimulating the endorphin system, which blocks pain. This system works naturally to reduce pain, but goes into hyperdrive when opiates and opioids are present. These chemicals also produce a high, the "endorphin rush". Opiates and opioids are broken down to release a small molecule called THIQ. Some of the THIQ avoids further breakdown to re-attach to the endorphin receptors, but then it never is removed. This is at least part of the mechanism of opiate tolerance. It takes a larger dose of the drug to get results. Eventually, the brain can become saturated, and no amount of drug will have a sufficient effect. At this point, some drug addicts die from overdose, and the rest stop using it because they aren't getting a high any more. If someone claims to have used heroin heavily for more than twenty years, they are probably lying. By 20 years, saturation has occurred.

The last chapter of the book discusses monoclonal antibodies, which are a recent innovation (1986). They are as close to a "magic bullet" as we have so far been able to produce. I learned that medicines with names ending in "-mab" are produced this way. These are large molecules, so none of them yet work on problems in the brain or central nervous system, because they are too big to pass the blood-brain barrier. Perhaps that will change, maybe by a means of removing most of the molecule and purifying the "bullet" part.

Where can medicine go from here? Most modern drugs are produced for chronic problems. The low-hanging fruit exemplified by antibiotics seem to be mostly exhausted. The Baby Boom generation now in their 60's and 70's have lots of chronic issues, and drug companies love finding drugs for those. For a strep throat, you take a ten-day course of antibiotics, and you're done. For high blood pressure, you're on a lifelong prescription plan. Pay, pay, pay all the way to the grave. So most of what "Big Pharma" produces is to feed the Boomers' need for more comfort in their dotage. Will this change; will some remaining big problems (malaria, Ebola) be effectively dealt with? The author is guardedly hopeful. But if vaccination for malaria winds up costing $100,000, how much help can that be, when billions of people need the vaccine?

Are there larger and larger numbers of pills and potions in our future? Or will better preventive medicine arrive? I guess we need to stay tuned.

And you thought your doctor was bad

kw: book reviews, nonfiction, medicine, podcasting, humor

When we need an operation, it helps to know a surgeon's success rate, not that you can easily find that out! Perhaps more importantly, for serious work, what is the surgeon's death rate (or survival rate)? Just to show how low the bar can be set, consider Dr. Robert Liston, who performed the first surgical operation under anesthesia in England in 1846. This was shortly after the miracle of ether was first demonstrated in the U.S. It was also just a year before he died. But prior to that, what was his death rate?

According to biographer Richard Gordon, quoted by Dr. Sydnee McElroy and her husband Justin McElroy in The Sawbones Book, in one case, that rate was 300%! To quote (from p. 101 in Sawbones):

"…Liston amputated a leg in two-and-a-half minutes. The patient died in the hospital from gangrene, but that happened a lot in the days before antibiotics. …[during the operation] Liston also amputated four fingers of an assistant… [and] managed to nick a doctor observing the surgery…"

The observing doctor, fearing a mortal wound (some nick!), died of fright on the spot. The assistant caught gangrene from his wounds and also died. One surgical operation, three deaths. Has anybody else you know of had a bad day that bad? Not even your doctor, right?

The book's full title is The Sawbones Book: The Horrifying, Hilarious Road to Modern Medicine. It is based on material from the podcast Sawbones. Having listened to an episode, I find that the book's portions (hard to call them chapters) follow the style of the podcasts: Sydnee tells a story while Justin interjects humor, and draws some from her also. Five of the items are biographical vignettes in the "Misguided Medicine Hall of Fame"; witness a blurb from Pliny the Elder: treat bloodshot eyes with a woman's milk in combination with honey and a bit of daffodil or powdered frankincense. Yowza!

Even though most of the stories range from tragicomic to entirely tragic, there are a few bright spots. While surgeons such as Dr. Liston had to learn to operate very fast to minimize a patient's agony, they learned a lot of practical anatomy. And in fairness, most were more careful than Liston and had a death rate well below 100%. Rampant experimentation did turn up things that could help: honey was prescribed for just about everything you can imagine (and a few you'd do better not to imagine!), but is usually ineffective. However, it is effective as a drying agent and germ barrier for open wounds. Another supposed universal cure: Urine. It doesn't cure anything. But if you are healthy, it is a sterile fluid, and if you get a cut and have no other source of sterile water, you can safely pee on the wound to wash it out. It'll sting, of course; there's a little salt! (and if you're not healthy, you could make things worse…) Finally, the last item is about the development of polio vaccine, which was actually a competition between Dr's Salk and Sabin, and their different approaches. Both succeeded, and both vaccines are still in use and almost 100% effective. That's a good story.

Sawbones is good reading and great fun, if a bit gross at times (for instance, you learn how to quickly exhume that corpse Dr. Frankenstein needs for his experiments). So don't read it while having breakfast. Any other time ought to be fine.