1958: Galveston physicians render infants Vitamin F deficient

There seems to be a dedicated readership numbering in the solid single digits who faithfully read each entry I post here. Those who would not be counted in such a group are encouraged to read my last post, Vitamin F, to obtain the relevant background that will give context to this one. It is very difficult to render human beings symptomatic with essential fatty acid deficiency, but nothing is impossible in the misguided hands of an unethical doctor. This post reveals doctors at a Texas hospital engaged in just such an experiment. The 1958 publication in Human Nutrition can be viewed here (PDF).

I wasn’t kind to physicians when I wrote the first post, and I’m even less so inclined to be now. I noted that in spite of clear evidence in 1930 that linoleate and docosahexaenoate are essential to human health and must be obtained from the diet, doctors administering total parenteral nutrition in the 1970s and 80s repeatedly made their patients ill by omitting these nutrients from their intravenous diets. But if you read Hansen et al. (PDF), something more sinister is afoot. This is a human nutritional intervention study. The patients were clearly not provided informed consent. Without any possible benefit, they were intentionally malnourished as infants in a way that was almost certain to cause them harm. The researcher’s objective for the study could be summarized like this: ‘What if we fed infants a diet intentionally devoid of essential fatty acids—what do you think would happen to them?’ With unbridled enthusiasm for this experimental test on human subjects—they found out.


Original caption: “Fig. 2 Appearance of skin of 6-week-old twins. A, Given a skim milk mixture lacking linoleic acid. B, Given a milk mixture containing linoleic acid.”

“The chief criteria of selection are that parents seem anxious to cooperate and their infants are normal neonates.” Translation: “We looked for parents who wouldn’t give us any shit about the fact that we were experimenting on their kids, and we wanted kids who were healthy so that if what we did made them sick, it would be easy to pick that out.”

The researchers proceeded to feed the kids a skim milk formula rendered nearly devoid of fat. The health consequences of such inadequate nutrition were soon obvious. Specifically, the infants had diarrhea in the form of “frequent, large, dark-brown, sirupy bowel movements.” They had perianal irritation. They had skin abnormalities, including thick, leathery, cracking dry skin; severe excoriation in the diaper region; fissures exuding plasma; and desquamation. According to Hansen et al., “This was particularly apparent in the colored infants where the fine, flaky, white scales stood in contrast to the dark background.” A female infant developed a severe staphylococcal infection of the thoracic cavity and was hospitalized.

At some point, someone had the common sense to call the game off. But tellingly, they often added back just saturated fat, betting again that the kids would remain sick until they supplied polyunsaturates as well. When normal milk was supplied to the experimental subjects, and they promptly recovered normal skin and bowel function. The more ominous symptoms of developmental delay and loss of sight associated with omega-3 fatty acid insufficiency were not reported. The perpetrators of this act of human experimentation are probably all dead. The test subjects themselves would now be about 60.

If there is a moral to this story it would be, “Always read your lagging references.” Those are the ones that you identified, but could not read in time to include them as citations because they were old, paywalled, or otherwise obstructed. Hansen et al. (PDF) was one of them, published as it was in 1958, and I didn’t read it until long after Vitamin F was written and posted. There is another moral to this story, and that one would be that the entitlement of the powerful knows no limits unless such limits are externally imposed upon them by other, equally powerful entities. In a democracy, all such power brokers must be fully transparent in their actions and answerable for their actions in a court of law. One hopes that the American era of uninformed human experimentation is over. I was personally quite shocked to see that in 1958, when I was a toddler, it was very much in business.

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Vitamin F


Sabine Rosenberger

Sabine Rosenberger

Sabine is a mouse midwife. She’s looking after about 20 expectant mouse moms, and the prognosis for the babies is not good. 3/4 of them will be born looking relatively normal, and no one is too concerned about these. The other 25% will be born with a severe, congenital defect of the skin and will be unable to seal up a water-tight barrier between themselves and the surrounding world. They will dry up like raisins and die of dehydration within 3 hours.

Sabine’s mouth is wide and full, with heavy lips that seem pushed forward in the early phase of giving someone a kiss. If you tease her, the lips will part showing big, healthy, white, German teeth. Her eyes are misty, gentle, and a bit sad, and without the watchful eyes of Sabine and her coworkers, no one would ever see these mice. They would be eaten by their own mothers and disappear from the litter, as if by magic. This is exactly what happened for the first 6 months as they tried to raise these special 12(R)LOX deficient mice. There just didn’t seem to be any. Then one night, by sheer random chance, she stumbled on a full litter minutes after they were born, and she saw the tiny, shriveling raisin babies.


12(R)LOX-/- knockout mouse pup

To understand why Sabine goes without sleep night after night, watching so that she can be a part of the brief, 3-hour lifetime of some tiny, sick, naked mice, it helps if you like chemistry. The popular journalist  @edyong209  likes to joke that he is a human-shaped bag full of microbes, but that’s not really correct. He’s a bag of salt water, with a long, smelly tunnel punched through it from one side to the other. Most of the microbes live in the tunnel, not in the water bag. The fact that all that salt water doesn’t just leak out of the bag is because of the remarkable, saran-wrap-tight seal that our dermal epithelial cells create as they finish their life cycle and cement themselves together just before they die. Mice and humans exist inside a smooth, elastic, water-impermeable skin with an outer layer that is made of senescent keratinocyte bricks mortared together with a cross-linked lipid and protein glue. For a cartoon of this, see Figure 1.

Figure 1

Each little zipper link connecting adjacent keratinocytes is composed of an omega-hydroxylated very long chain ceramide (30 to 36 carbons in length) covalently attached to glutamate. This cell-to-cell zipper only forms if the essential fatty acid linoleate is first attached to the end of the ceramide and then oxidized in-situ by the 12(R)LOX enzyme.

For almost my entire adult life, I have studied the catalytic biochemical reactions between oxygen atoms and the polyunsaturated fatty acids that reside in cell membranes. One of those reactions is catalyzed by the COX enzymes, and I wrote about it here. Another is catalyzed by the 12(S) LOX, and I wrote about it here. The making of skin glue is catalyzed by its close relative, 12(R)LOX.

It does not seem intuitively smart to set fire to the oils and lipids that make up the membranes of your skin cells, but as long as you do it in a slow, controlled way, adding exactly 2 molecules of dioxygen to each 18 and 20 carbon fatty acid, it’s not only a good idea, it’s essential to survival.

Polyunsaturated fatty acids are not formally called “vitamins” but they should be. Vitamins were named for the letters A through E, but then biochemistry seems to have gotten drunk or tired and lost its consistency. The use of Vitamin F for Fatty Acid was proposed, but because it was complicated, it fell into disuse. Some fatty acids cannot be made by humans, must be obtained in the diet, and if absent from the diet, cause a deficiency disease state that was first observed by George and Mildred Burr in 1930 in rats (PDF). Since doctors receive almost no training in nutrition, they rediscovered this disease in humans when they tried to feed patients entirely by vein in the 1970s (PDF). Very sick adults and neonates born with digestive system problems were fed intravenously, and the early TPN (Total Parenteral Nutrition) formulas contained no essential fats. Scaly red skin, kidney, neurologic, and immune system problems developed in these neonates, faithfully replicating the forty-year-old rat data. Today one cannot watch 30 minutes of television without being pitched several different brands of omega-3 fats, but unless one trusts an adman with science outreach, a refresher is always helpful.

Because the 12(R)LOX enzyme is missing from the little knockout mice that Sabine is caring for, the essential linoleate substrate waiting in their skin cells fails to react properly with oxygen. That is, they have their Vitamin F1, but they can’t metabolize it correctly. With no oxygenated epoxides present in the skin ceramides, no glue forms between the dead keratinocyte bricks. They stack loosely on each other, and water vapor escapes all around them. Essential fatty acid deficiency in rats and humans also includes notably dry, red, scaly skin.

There are humans born with the same genetic abnormality as these mice. That is, they also have a non-functional, null mutation of the 12(R)LOX enzyme and likewise cannot make peroxides and epoxides of linoleate. But human babies are quite a bit larger than mice, so the process of drying out takes much longer. Their parents care for them and add lotions to their skin instead of cannibalizing them, so these babies survive. Still, they have a nasty, scaly skin that reminded pathologists of carp scales, so their disease was named Autosomal Recessive Congenital Ichthyosis (ARCI). Any defect in this pathway, from the synthesis of the very long omega-hydroxyl ceramides to the final attachment to proteins by trans-glutamase, will manifest in some form of dehydration and scaly skin.


Collodian baby born with a mutation in the 12(R)LOX/eLOX-3 pathway

In theory, one could make a chemical replacement compound for the oxidized linoleate ceramides, and these people could rub it into their skin and become more like everyone else. In practice—this has been quite hard.

When the baby mice are born, researchers quickly euthanize them and remove as much of their skin as possible. Consider what skinning a neonatal mouse could be like, and you’ll realize that’s not very much skin. The cells are suspended in medium and grown in a special 3-D culture system that lets them orient in a natural plate-like manner and try to form a skin barrier, although a very leaky one. It does not matter that it’s leaky, because the cells are surrounded by liquid culture medium. Then a compound can be applied to them, and the barrier can be tested a few days later to see if it still leaks.

The lab in Heidelberg where these experiments are conducted estimates their overhead costs to test each new experimental fatty acid I supply them at about 50,000 Euros. It takes 12 months just to get permission from the government to mate the parent mice. Early in 2015, we made it all the way through this cycle: Ask for permission and fill out numerous forms (wait, wait, wait), mate, gestate, parturate, and euthanize in Germany. Meanwhile a single hopeful new compound gets prepared in America by our chemist Andrei, who came to us from Kiev, Ukraine. The compound we made worked… a little bit. The data look “promising.” Now we can make a slight change, and maybe this fall, try a new fatty acid. Two new compounds per year can still result in an important medical advance. But only if one is very, very patient, like Sabine.


The author with Dr. Peter Krieg of DKFZ in Heldelberg

There are hundreds of naturally occurring fatty acids, but they can be lumped in three main groups. The first, including Butyric (from butter) Palmitic (from palm oil) and Oleic (from olive oil) are non-essential, and can be built in 2-carbon steps by humans if needed. The second group is the omega-6 polyunsaturates. Of these, Linoleic is required in substantial amounts because of its structural role in the skin. Arachidonic is also essential, but less important because it can be made from Linoleic, and is needed in much smaller amounts to make potent lipid signalling molecules like Prostaglandins. The third group, the omega-3 fatty acids, are the ones most often pitched as supplements. Alpha-linolenic from flax seed oil is the poor man’s omega-3. It is cheap, can only be converted by the body into the crucial DHA omega-3 inefficiently, and is mostly burned off for energy. EPA has no specific role of its own, but it is almost always present in fish oils in amounts comparable to DHA and the two are readily interconverted. DHA has crucial structural roles like Linoleate, but the case for DHA being the parent of a potent lipid signalling cascade is much less firm than is the case for arachidonic acid.

There are hundreds of naturally occurring fatty acids, but they can be lumped in three main groups. The first, including Butyric (from butter) Palmitic (from palm oil) and Oleic (from olive oil) are non-essential, and can be built in 2-carbon steps by humans if needed. The second group is the omega-6 polyunsaturates. Of these, Linoleic is required in substantial amounts because of its structural role in the skin. Arachidonic is also essential, but less important because it can be made from Linoleic, and is needed in much smaller amounts to make potent lipid signalling molecules like Prostaglandins. The third group, the omega-3 fatty acids, are the ones most often pitched as supplements. Alpha-linolenic from flax seed oil is the poor man’s omega-3. It is cheap, can only be converted by the body into the crucial DHA omega-3 inefficiently, and is mostly burned off for energy. EPA has no specific role of its own, but it is almost always present in fish oils in amounts comparable to DHA and the two are readily interconverted. DHA has crucial structural roles like Linoleate, but the case for DHA being the parent of a potent lipid signalling cascade is much less firm than is the case for arachidonic acid. It is important to note that the omega-6 and omega-3 families cannot substitute for each other. A few grams of vegetable oil and a few grams of fish oil on a weekly basis will prevent EFA deficiency. Perhaps, on an appropriate day, a serving of fish and chips.


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Pig Blood

fishGirl_easelThere were two dead pigs dangling from the ceiling, spinning around together in a slow pirouette. Another was submerged in a vat of scalding water, and one more lay sprawled on the grate of a heavy iron rack. Kurt had been working since ten to six. There was a lot to do getting the slaughterhouse going in the morning. The boiler had to be fired, the knives sharpened – and lots more. The boss would be in by eight to start gutting, and would want things set to go. He glanced at his two guests standing awkwardly in the shadows. “Geeks,” he muttered under his breath.


“Ready?” Kurt asked. The girl, dressed in faded jeans, a white lab coat, and old Nike running shoes, nodded and held a bucket under the chin of one of the twirling bodies. Kurt stroked his hip with the palm of his hand and produced a thin metal blade from the knife scabbard he wore. The knife flashed silver and then disappeared. Blood, dark and gurgling, poured out into the bucket with a sudden spurt. A pink froth rose around the rim as the girl lugged the now heavy bucket a few steps to the 5-gallon bottle. It was made of heavy green-blue glass, a true water bottle from the days before plastic made glass obsolete. A man was holding a funnel in the mouth of the bottle, steadying it for her to pour. The blood gurgled and foamed some more as it flooded down the insides of the glass. The man, dressed as she was, straightened and said, “ I think we ought to put another 80 cc of buffer in the next time. I mean, we’ve got it – might as well use it.” They washed out the funnel and the bucket in the sink while he struggled to get the water temperature right. There were no handles for running the faucet. Instead, there were two metal pedals under the sink – one for hot and one for cold. The pedals were awfully close together and his feet couldn’t seem to distinguish one from the other, so the water see-sawed from steaming to ice cold and back again. They jerked their hands in and out of the stream each time it happened, exchanging startled expressions. When all the glassware was clean and ready, they waited.

There was a Red Devil kerosene space heater glowing orange next to the wall. They shuffled around it, holding up their cold feet and melting the rubber on the tips of their sneakers as they waited for the next set of pigs. A sharp crack made them both jump as Kurt shot the fifth pig of the day between the eyes. She took a small step toward the pen to watch. He measured out an extra dose of buffer from the brown glass container, added it to the bucket, then leaned back against the wall, studying her. Her hair was pulled back from her face and pinned neatly behind her head. A few stray wisps fell in front of her ear. It was red, but a very dark red. In the dim, misty light of the slaughterhouse it seemed dark brown, but it would shimmer with copper when they stepped outside into the bright January sunlight. She was small, and he noticed how tiny her white feet seemed as she stood next to Kurt in his big black rubber boots. Freckles were scattered from her forehead to her chin, thickest over her cheeks and her nose, but he got the impression that they didn’t stop at any particular place and probably continued down past her shirt collar in all directions. Her eyes were wide and pretty, but the color was hard to describe. Sometimes they seemed very green, but with a change of mood or light they might turn slate gray or even look dark and brownish. He liked them, but he found himself staring at them from time to time, trying to settle in his mind what color they really were. He scowled at himself and turned to stare at the heater, realizing that he’d been studying her.

He tried not to say anything much to her for the rest of the morning. The pigs came to them in pairs every fifteen minutes, and they worked steadily until the five gallon bottle was full and foam poured out the top and ran down the side. As he was wiping it clean, she came to him carrying a heart that had been severed from its great vessels and flung into a barrel. It was in V-fib, shivering as if from the unaccustomed cold outside a living body. He ran warm water into it from the sink, and showed her where the valves were and how they controlled the flow of liquid. Suddenly there were four or five strong, coordinated beats as the heart shuddered back into a normal rhythm. Bloody water squirted out onto the wall. Then the heart went limp in his hands, and he turned to her in mock grief, saying, “I’m afraid that I have some terrible news.” She laughed and said, “Doctor, I think you’d have better luck if there was more of the patient left.” He smiled at her and felt his own heart suddenly racing.

The massive container of blood made them waddle like ducks as they staggered together through the door. But in all that gore there was only an ounce or two of the stuff they were seeking – the leukocytes. Pig leukocytes (white blood cells) contain an enzyme called 12-LOX, which is essentially the same as the 12-LOX enzyme in humans. Prostate cancers that grow increasingly invasive also seem to make a lot more 12-LOX than what might be considered normal. It was his interest in this enzyme that brought the two of them to the slaughterhouse. Over the few months of her internship, the girl became rather good at isolating 12-LOX from pig leukocytes. It would not be until some years and many pig blood failures later that he would truly appreciate her talent in this area. A pig blood prep takes at least 6 more hours after collecting the blood. Red blood cells are full of iron, so they are a bit heavier than the white cells. When you spin them in a centrifuge, they end up concentrated near the bottom while the white cells float toward the top. So they spun them, and then skimmed off the layer rich in leukocytes from the top. All cells have about the same amount of salt in them as sea water, so if you pour salt-less distilled water onto them, that water seeps across their membranes and causes them to swell up like a balloon and pop. The white cells resist this by pumping the excess water back out, so the red cells are the first to pop when stressed in this way. They alternately centrifuged and exploded the cells to get rid of all but the leukocytes. Over the course of the afternoon, the five gallons of blood was reduced to perhaps 3 tablespoons of pure white cells, looking something like wet baby’s oatmeal. When she brought it to him her face was bright and proud. Their eyes met in a brief exchange as they rolled the gelatinous mass into the ultrasonicator. She knew how pleased he was. The duet they were playing together was simple and beautiful, with competence and knowledge intertwined like fingers holding hands.

On Saturday morning she would follow him on his rounds at the hospital. His patients were old and dying, withering away, their tissues bathed from within by the malevolent secretions of their tumors. They looked forward to her visits more eagerly than his, because she brought only a fresh and compassionate face, some tender teasing, and no needles or devastating laboratory numbers. He could see a faint spark in their tired eyes. Reproduction was now out of the question for them – but some of the equipment needed for sex resides in the brain. Those parts were still working, and it was touching to see how happy it made them to have that mechanism stirred into wakefulness by the figure of a young girl.

He thought for a moment about the millions of dollars and countless hours being spent in pursuit of 12-LOX, an inscrutable little molecule whose allegiance in this battle was not even known. 12-LOX had a voracious appetite for polyunsaturates – the things that butter companies were so bursting with pride about. Polyunstaurates are just fats, and 12-LOX pulled them out of the membranes around it and burned them. Dozens of times each second, 12-LOX reached out its microscopic arms, plucked an unsaturated fat from the folds of the cell wall and slid the hapless molecule across the iron atom at the 12-LOX reactive core. Electrons flew like sparks from a flint, impaling the fatty acid with a molecule of oxygen. The resulting new compounds had such long names that no one ever wrote them. Five or six capital letters gave a name and muted the strangeness of something not at all well understood. If a person ate a lot of fish and their omega-3 fats, 12-LOX would ignite them and make something called 12-HpEPE. She wrinkled her nose and grinned the first time he said it, because it was pronounced “H-Pee-Pee.” 12-HpEPE made the leukocytes of his prostate cancer patients agitated and enraged. Sometimes. It was difficult to harvest the leukocytes of cancer patients, because his team was not permitted the same liberties with them that they took with the pigs. The blood samples were small, and the isolations irreproducible. On a few occasions, he had seen the leukocytes respond to the 12-HpEPE with a focused, lethal assault on the tumor cells. He sent the young girl to the library to look for studies of the cancer rates among the Inuit, who eat staggering amounts of omega-3 fats. He thought that cancer might be rare among people who eat whales and seals. She came back to inform him that most of the Inuit eat spam and pancakes now, and struggle with alcohol abuse. Those still eating a native diet are being pursued aggressively by outsiders who don’t approve of the mercury and PCB content of their fat. Thus, they tend not to allow doctors to cut open their deceased, but they seem to have the same amounts of cancer that everyone else has. His struggle to build a coherent design around his life and work seemed to be faltering.

Winter passed and the summer came, giving her the chance to work in the lab full time. At night they would sit together in his office, reviewing their data, reading science journals and quietly murmuring questions or comments to one another. There was a paper that said 12-LOX was present in fish gills, so they went off in search of a rainbow trout. They rented a canoe. His eyes kept returning to the sweet, seductive hourglass shape of her waist and hips as she sat upright in the seat ahead of him, dipping the paddle into the water. They talked about meteors. Something he said amused her and she laughed, half-turning her head. Her eyes were deep green and sparkling like the river water.

In biological terms, they began to establish a pair bond. It’s something quite central to reproduction, especially in mammals like humans, where both parents care for the young. Pair bonding happens all the time. But in cultural terms, they were just skating on thin ice. He was married, and although she was not, she was quite young. When they were together in public, they did nothing to try to attract attention, but they did so anyway. It was a particular group of fortyish, frumpy women who seemed to notice them most. Angry women, their brains addled by pair bonding failures of their own, they scowled at the couple, their eyes filled with exasperation. In the stilted jargon of the day, they would have called her a victim. The more calculating terminology from an earlier generation would have labeled her lucky. The reality was that pair bonds are the subject of much scrutiny, debate, and even intervention in the society in which they lived. When the end of the summer came, she went back east to the University and their slow dance ended abruptly. Some cards and letters were exchanged. He came up for a weekend visit and they took a hike in the mountains. It was one of those unaccountably warm late October days, when the leaves seemed to bake on the woodland forest floor. All sorts of odors, musty and inviting ones, sweet and seductive, were in the air. They lay back in the softly crackling carpet of leaves and exchanged smiles. The tree branches rose high above them. The silence around them was full and pregnant, and each small whisper seemed to roar. The privacy of being alone together in a vast expanse of forest was quite intoxicating, and they did not return from the woods until dark. Nothing actionable transpired. She began studying for an exam, and he drove the rental car to the airport at an unnecessary speed. He was heading west for a fly fishing trip.

In the northwest corner of Wyoming there is a narrow, rocky valley flanked by tall mountains, and the Yellowstone flows deep and emerald green through it. Smaller streams cascade down the steep ravines, through dense stands of ponderosa pine and black fir. He was fishing in one of these, a torrent called Hell Roaring Creek. After working his way upstream past miles of rapids and black boulders glistening with spray, he came to a deep pool. For a brief space of twenty feet, the river stopped its headlong plunge down the mountain to form a crystal alcove. It was so calm and clear that he could easily see small pebbles on the bottom more than ten feet below. He slowly tied on a fly, a tiny puff of brown deer hair and yellow silk with a fine black barb barely visible at the end. The fly fell gently onto the surface. Almost at once a smooth, dark shape rose from the depths. A splash of burgundy red ran up the center of its bronzed side. Black speckles the size of peppercorns stood out so clearly on its broad green back that he could have counted them. It was a cutthroat trout, bigger and more beautiful than any he had ever seen. With a calm, deliberate sweep of the tail, the fish rose to within inches of the fly quivering on the water. The man drew in a sharp breath and swallowed, blinking rapidly. His wrist was trembling as he held the fly rod steady in the air. The vibrant shape below him seemed to dissolve and reform slightly displaced as gentle ripples passed over it. He saw the mouth open slowly, saw the crimson slash of color along the gills and the pale white of its inner lip. Seconds passed. He could smell the pungent wild mint that he was crushing beneath his bent knee. Then it was over. The fish whirled and streaked for the bottom. The violent sweep of its tail submerged the fly and sent water spraying into the air. For many minutes, the man remained crouched, frozen. He slowly reeled in his line, changed to a different fly, and set the new offering out onto the water. But the stark terror of vulnerability was now clear to the fish. It never showed itself again. It seemed as if an hour passed before the man was able to lift himself from the bank and continue upstream.

November came and a soft orange moon hung low in the sky. He left and traveled to Australia and Japan, disorienting his biological clock. He began to wake regularly at 1:00 a.m., when there was little to do except watch the moon moving slowly through the tree branches. He thought of her often, and when he did the image of the fish in Hell Roaring Creek kept pushing into his thoughts as well. At night it seemed that memories that had nothing really to do with each other got jumbled together, and then night after night they would come back again in the same order. The fish suspended in the crystal water became so blended with the memory of the color of her hair and the shape of her smile that he couldn’t think of one without seeing the other. It was months before he had a normal night’s sleep. He couldn’t escape the sadness that came over him when he thought of her, because he knew that if the fish had taken the fly, he surely would have killed and eaten it.

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Who were the Denisovans anyway?

The authors are actually quite deferential to the older physical paleoanthropologists. Spoken more bluntly, archaic genomic DNA analysis has supplanted these disciplines and is now the authoritative voice. Physical tools, bones and other specimens fill in the details of a picture painted by genetics.


Human evolution used to be the preserve of two groups of academics: the ones who liked fossils and the ones who liked stone tools. Both regarded the other as peculiar for being obsessed with the wrong part of a massive jigsaw puzzle. Then in 1987 the geneticists arrived and they’ve been making things much more untidy ever since…

As recently as 40,000 years ago there were at least four species of hominin living in Eurasia. While we know of three from fossils and archaeological material. The fourth, however, is known almost purely from ancient DNA. ‘Species X’, or more commonly the Denisovans, are helping to re-write our understanding of human evolution during the later Pleistocene. But who were they and were did they go?

Turist_den-peschera_cut Denisova cave, image by Nerika via Wikimedia Commons

The Denisovans are a species of hominin that occupy a very peculiar place in the human…

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Sympathy for the Devil

Tim Hunt is a 72-year old British Nobel laureate who was forced to resign from his position at the University College of London this week because of things he said at a press conference. Those sentences have been reproduced widely in both the social and conventional media. Sir Hunt has (or perhaps, once had) a remarkable mental acuity that enabled him to discover and describe the cyclin-dependent kinases that control the progression of cells through the processes of growth and division. His antagonists, judging from the creatively framed opprobrium of their social media posts, are no less well endowed. Paleoanthropologists have long pondered how evolution could have selected for an ability such as this, when it is clear that throughout our most recent and formative evolutionary years it was unnecessary to comprehend cell biology. The answer to that paradox lies starkly exposed in the rise and fall of Tim Hunt.

In his comments, Hunt describes the workplace environment of a scientific laboratory. This is a social setting where a dozen or more humans work together while solving a multitude of puzzles. In a very culturally-loaded context, they work to solve the puzzle of career advancement within the written and unwritten parameters of their particular institution and job title. In a different context where culture is essentially irrelevant, they seek to solve scientific enigmas that reveal themselves only grudgingly through imagination, experiment, observation, and data analysis. And at a third level, following imperatives that are at once obvious and at the same time utterly inscrutable, they attempt to seek and attract mates, form pair bonds, and carry forward the fundamental biology of life. A large brain and acute intellect isn’t necessary if this third mission is the only task an organism faces and it can do so in a largely asocial context. But to be human, and to have some degree of success working to solve all three of these dilemmas simultaneously, requires a supercomputer.

A glance at human physiology is enough to inform us that we expect to be born into a warm environment where cooling will be a bigger challenge than heating ourselves. We expect freely available fresh water, intermittent and unreliable food, to be assaulted by worms and other parasites, and to risk stepping on venomous snakes. Our physical environment changed over tens of thousands of years, so even these pre-adaptations are no longer ideal. There has never been any such certainty as to culture. The first dozen years or so of life is spent assiduously acquiring and integrating ones current culture in all its myriad details, from language and vocal fry to Radical Face to gender equity or the nuanced lack thereof. What’s permitted and what isn’t, what’s heroic and what is gauche must not only be learned once, but must be re-learned and edited over and over again. Thus the need for an unlimited surplus of both storage capacity and processor power in the human brain. And this brings us also to the sad fall of Tim Hunt.

Tim Hunt committed a social faux pas within the context of being embedded in the current largely English speaking, western industrialized democratic scientific culture. The consequence for this, as we have seen, is to be ridiculed and humiliated and to lose rank. It could have been worse—archaeology seems constantly to find yet another bound and ritually murdered human corpse lodged in a forgotten peat bog or buried in desert sands. Who is to say what offense of chauvinism they committed. Witches and heretics have been burned at the stake within our written history. Such inquisitions need not be ancient. Bodies by the hundreds of thousands are accumulating today in the deserts of Iraq and Syria, and failure to adhere to and be recognized as legitimate in the eyes of the culture and regime enjoying present power is the most proximate reason that those bones are there.

Tim Hunt will not be murdered for his statements, and although his cultural indoctrination was not so precisely hewn as to prevent him from making them in the first place, his general understanding that he was not risking his life was probably part of the underlying hubris of his incaution. But consider also his age. No brain is immune to the insults of time, no matter how flawlessly and incredibly it performed in the prime of youth.  Nobel laureates as a class seem prone to remaining in the limelight, and to making poorly worded statements that enrage the present politics, long after their magnificent scientific and cultural processor is winking out. We all comprehend that in a real sense, the greatest threats we face in everyday life come from our fellow man. We have evolved this uncommonly large brain as our one defense against that, and when its power begins to wane, so do our defenses. So pity Tim Hunt.

I myself was once moved to write an essay about girls in the lab. I will reproduce it here, although I’d be pleased if the charitable reader would buy it in book form, and in so doing contribute to a worthy cause.


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Teddy Wayne recently wrote a piece for the Sunday New York Times called “The Childless Life” (the digital version is titled “No Kids for Me, Thanks”) which at face value was a discussion of the individual choice to go vocally, self-righteously extinct. In it, he reviewed a recent collection of essays written by persons who will leave behind no descendants, on purpose. “Selfish, Shallow, and Self-Absorbed” is an anthology, the collected expressions of a group of 16 authors, all of whom have chosen both to remain childless and to write about that fact. The Venn diagram of scientists and writers should have some modest overlap, but apparently not in the case of these Lineage-Enders.

In fairness, it was @HollyDunsworth who first suggested the title “Lineage-Enders” in a tweet that anticipated someone might be reading the NYT article and wonder why it seemed so utterly uninformed by Darwinian thought. We complain a lot in America because numerous opinion surveys show a majority of us do not believe or understand the theory of evolution. Responsibility for that seems to extend to the literati, as it’s basically nonsense to write about the self-selected infertility of the educated elite without gazing through evolution’s eyepiece. So with your indulgence, I will discuss the evolutionary implications of Lineage-Enders (LE).


One need not read every word of the childless to come to an overarching theme: Children bother these people. They resent that children are loud with unstructured lives that interrupt what adults would be doing if left alone. Lineage-Enders as a group resent sharing of space, patience, silence, and resources with small and uncivilized toddlers. They complain loudly that, when burdened by childcare responsibility, they as adults are not as completely happy and fulfilled as they imagine they otherwise might be. They are basically bad parents, and many admit as much. There have always been “bad parents,” but it is important to separate the pejorative from the shrewd life strategy trajectory.

Hands_Plant        womanwithgoat

Just for argument’s sake, let’s propose that two distinct parenting behavioral strategies resting on separately heritable genetic foundations arose in early hominids. The first we will call Ultra-Nurtures (UN) and although the genetics of this condition are not certain, the phenotype is well understood. Everyone knows a UN human being, and it might be argued that this behavior is the more prevalent human pattern. Being UN allowed us to be farmers and to treat all manner of non-human things as we would treat our own children. Thus, helpless wolf cubs were coddled and fed, turning them into dogs instead of small bite-sized breakfasts. Tiny sprigs of green were watered, sheltered, and turned into wheat and corn. The same for small, orphaned foals, who most likely would have required the milk of a human female to survive long enough to begin to eat grass and start the long journey to domestic horses. Ultra-Nurture humans are both male and female, but the endlessly cheerful daycare lady sitting on the floor with kids piled around her lap is a good icon.


(There exist already long and contentious threads of discussion about behaviors and their heritability as well as their teachability. There isn’t any question that there are environmental inputs that act on underlying, genetic predispositions to act out behavioral programs of activity. Those include reproductive life strategy activities. For the rest of this essay, I will refer to the LE and the UN behaviors as being enabled by a small number of discrete and identifiable genetic elements, full stop. This is not a nature/nurture debate.)

The second group is the one we are now calling Lineage-Enders (LE), but for millions of years they were anything but—it is more accurate to call them parental resource hoarders and to recognize that they had a robust reproductive strategy that exploited the weaknesses of their UN relatives. As soon as early hominids were living in cohesive, complex social groups of cousins, grandparents, and other close relatives, abandonment of one’s own toddler at an early age into the arms of a more devoted aunt, sister, or other relative would have enabled the child-intolerant (LE) female to engage again in sex and speed her own re-entry into the reproductive cycle. On the other hand, the indulgent, patient, Ultra-Nurturing adoptive parents of these abandoned infants probably shared many genes in common with them and so continued to enhance their own Darwinian fitness through proxy reproduction of close kin. Aggressive, child-intolerant males could devote themselves to building alliances of dominance instead of building toys and teaching life skills to children. That works especially well if they are able to mate with a number of females, preferably from both LE and UN backgrounds. With the right fractional survival of each type of offspring, the coexistence of LE and UN fractions within human society is evolutionarily stable. It does give rise to the occasional pejorative, as earlier noted, and so we have “bad parent,” “loose woman,” “ladie’s man,” and a host of others, as each judgmentally examines the behaviors of the other and looks for exploitation.

Prior to the transition to eusociality, LE genes would have been catastrophically disadvantaged. But I would argue that cognitive patterns that typify LE parenting styles are also fundamental to our explosion of intellect. It’s not hard to conceptualize that the urge to study intently, to concentrate, and to think carefully and methodically might have some conflicts with the typical modern parenting experience. Still, the genes underlying LE behavior have probably been under positive selection for millions of years.

This equilibrium was demolished by the molecule norethynyl estradiol, invented in 1951 by Carl Djerassi and now universally known and understood as The Pill.

ThePill     Carl_Djerassi

This earthshaking chemical advance enabled women for the first time to be absolutely in control of their fertility, while simultaneously opening the door of extinction to the Lineage-Enders. Prior to effective, cheap birth control, the LE fraction of humanity was reproducing fitfully, if distastefully. Their lack of interest in caring for children did not preclude an avid interest in the activity, sex, that produces them, and so were born countless under-parented, neglected, and sometimes abandoned small people who made their own selfish way in the world the best they could. Most of them who survived and even thrived did so because the other important group of humans, the Ultra-Nurtures, took pity on these children and made sure they were fed and well cared for. But for the last several generations of man, the desire not to reproduce could be acted upon in an executive manner by any woman with LE inclinations. Those unwanted children would no longer be born—but why?

The widespread human predilection to adopt and care for unrelated children is anticipated by sporadic cases of infant adoption in social, non-human primates. There is no such biological precedent for the Lineage-Enders, so their motivations must be taken at face value. An attenuated gag reflex can be helpful here. Much has been written, in addition to the above mentioned anthology. Sezin Koehler is a Lineage-Ender, and she writes about that here. So pleasant to know that all this hyperbole is just a few decades from dying out.

The poster child for LE humans is probably @Ericholthaus, the “sniveling beta-male” ridiculed by Fox News for his labored public weeping over the multiple challenges of humanity and the gratuitously self-indulgent idea that his own personal vasectomy might have such an impact as to represent a turning point for mankind. Even more hilariously, he then squelched, backed out of the sterilization, and got his partner pregnant—the rationalization being that this made him feel “hopeful.” Never has there been a person more in need of a gentle reminder of his own inconsequentiality. And although he has blurred the line demarcating his own extinction by a generation, he does bring to mind a salient point: If Mr. Holthaus had the intellectual capacity of a fig tree, he would recognize that he is currently living in a period of rich and plentiful food and resources. If the dreaded future that he envisions is really just a generation to come, then his most viable and Darwinian reproductive strategy would be to produce as many babies with as many women as physically possible and distribute them far and wide, the better to insure that some fraction of them actually pull through his imaginary, upcoming human population bottleneck. That is—he would be masting.

Neuroscience has discovered interesting discontinuities between what we actually do and how we describe why we took these actions once we become aware that they have happened. The rationalizations of LE humans ramble with hand wringing piousness over carbon footprints, disease, malnutrition, and the peculiarities of their personal psychoanalysis with repetition of terms like fulfillment, actualization, achievement, and etc. (gag). I would argue instead that they are LE because this is their genetically predisposed reproductive strategy, and their verbalizations are all just window dressing to try to spin up their self-induced extinction to a crowd of inquisitive onlookers.

I am not a Lineage-Ender. In typical UN fashion, I have raised to maturity 3 unrelated stepdaughters who share no immediate genetic relationship to me, although they now share 25% of their genes with four of my children. I have raised two millennial males to adulthood (well, not quite, but to that amorphous near-adult state that is specific to this generation), and I have three more kids not yet out of high school. As a semen donor when a younger man, I donated my genes and any inclusive parenting predisposition to many dozens of women who lacked only male gametes in their profound desire to reproduce and have a baby for themselves. My kind will go forth and multiply, exponentially.

In closing, I have only some final thoughts for the Lineage-Enders. The first is that no one will notice. The freeways will be just as jammed in 2040 despite the absence of your un-offspring and their un-purchased automobiles. Other campers will still beat me to the signup counter in Yellowstone Park, making me wait an additional day to go with my grandkids to my favorite campsite at Black Tail Deer Creek. Airlines will still manage to cram 300 people onto an airplane when tickets have been sold to 320 and the plane was designed for 288. Atmospheric carbon dioxide concentration will still march forward in its inexorable grandeur, and will not twitch in the slightest 0.0000000001 ppmv due to anything either of us has done.

But what will change is something called the allele frequency, ƒ, for any unique genes that you may be carrying on your chromosomes, versus the ones on my chromosomes. For your genes, you are placing an a=0 value in the equation ƒ=a/n*N. For myself, I am placing a large integer value in the place of a, probably about 400. There is no implication that those particular genes unique to me, or to you, are also advantageous. Sometimes I think some of mine may be detrimental, or in the case of my null mutant KCNQ3 ion channel, perhaps responsible for some really intractable insomnia. But this is not for me to judge—it is for the viability of future generations to establish by that most Darwinian process called survival of the fittest. For you, the process is done. You are completely unfit. Oral contraceptives have been the undoing of your reproductive strategy. And do you remember that annoying woman stuck in the elevator with Tom Hanks in “You’ve Got Mail,” so anxious to get out so she could have her eyes lasered?  Future humans may notice a few less of those.

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Of Mice and Men, and Cats and Women

 Wookie Bear


Wookie Bear is a facultative guest parasite of humans. She receives grooming, medical care, treatment for her own parasites (mostly worms and arthropods), shelter, heat, and all her food requirements from her host. She uses large, expressive eyes and a cry that mimics a human infant in order to insinuate herself into the host living space. Her host also disposes of her fecal waste and urine.

I am infested with parasites. My entire house is lousy with them—the word lousy is derived from the singular form for lice, a particular small mammalian ectoparasite. We categorize our parasites by where they live—the endoparasites like ascarid worms and nematodes,  giardia, and strange things ingested in bad sushi live in our bowels. The ectoparasites (fleas, ticks, bedbugs, lice, etc.) expose themselves on our surface. They crawl in our pubic hair. They get us sent home from school with red faced parents who stop at the pharmacy for foul smelling shampoos and fine-toothed egg combs. 100% of humans tested at age 18 by Dr. Michelle Trautwein carry the ectoparasitic facial skin mite Demodex folliculorum or its close relative Demodex brevis. These mildly disgusting little arachnids live inside your hair follicles and sebaceous glands, respectively, and cause very little harm because this living space provides room for only a few milligrams of total parasitic load per human.

Demodex folliculorum

An example of a human ectoparasite. The facial mite (Demodex folliculorum) at high magnification.

The hookworm is a good example of the typical endoparasite. Hookworms such as Necator americanus attach to the epithelial lining of the small intestine where they munch on the intestinal villae, cause bleeding, and then drink the leaking blood.

Hookwormshookworms08 An 8 ounce load of intestinal hookworms is a severe infestation and will result in weight loss, anemia, malabsorption, and other overt symptoms of chronic illness. An amount of hookworms equal to the weight of a single house cat, perhaps 10 pounds, would eventually prove fatal. A link to a nice review of these conventional parasites (PDF) in human evolution was recently posted on Twitter by Jennifer Wagner @DNAlawyer. Like most modestly hygienic Americans, I have very small whole-body burdens of both exoparasites and endoparasites. But when it comes to social guest parasites, I’m suffering from an acute infestation.

Social parasitism is a unique parasitic niche, inhabited by creatures specifically adapted to exploit the complex living spaces, communication channels, and behaviors of social animals. While many species of animals form groups and have some social structure, highly social (eusocial) species are restricted to humans, ants, bees, termites, and wasps. (See E.O Wilson, The Insect Societies for many hours of reading about the latter four of those.) Entomologists have long studied the parasitic insects that live in close relationships with the social insects, as I will expand on below, and often give them the euphemistic name of guest. On further reading, one sees that they behave very badly as guests, if that is their status. Almost all of them end up consuming the eggs and young of their social insect host, which is fairly rude. I think “social guest parasite” is a more fitting term. Hosts usually mount some sort of immune or behavioral defense against their conventional parasites. The distinguishing feature of a social guest parasite is that the host actively coddles and protects it, most often mistaking it for its own kind.

The two main human social parasites are Felis silvestris catus the house cat, and Canis Canis the dog. I have the former. I am supporting at least 10 cats or about 120 pounds of parasites. This is not a survivable parasite load for any of the common intestinal worm infestations that I’ve taken care to avoid. Fortunately for me, my social guest parasites live on the couch, not in my bowels.

Three young adult Felis silvestris catus parasites occupy a living space within the home.

Three young adult Felis silvestris catus parasites occupy a living space within the home.

There is considerable argument whether the dog should be considered a human social symbiont or commensual and not a parasite, as the cat clearly is. Dogs work for humans and shoulder large labor burdens for them, as can be seen by Googling “Inuit sled dog” or “Irish border collie.” Cats, on the other hand, do not even listen to their human hosts, much less perform any chores for them. Dogs also are eaten as food in many cultures, making them livestock, while cats are not.* When humans keep, feed, and shelter a dog, the dog thinks the human is God and serves him faithfully. When humans keep, feed, and shelter a cat, the cat understands that it is God and expects the human to serve him faithfully. So we will leave dogs out of the current discussion as possibly still man’s best friend, and concentrate on cats, who are not.

Assisted by the spread of mankind, cats have extended their population from a small area of North Africa and the Middle East to the entire habitable area of the world. There are about 200 million of them in the US alone, evenly split between the parasitic niche (domesticated) and the feral state (in between hosts). An estimated $30 billion is spent each year by American hosts sustaining this parasite load of about 3 cat pounds per person. Even with the ever increasing cost of raising children, the amount of resources  currently diverted to pet cats would raise an additional 3 million Americans to adulthood every year.

Our human social history is very short, but exactly how short is hard to say, as behaviors leave no fossils. Our entire genus goes back no more than 2.5 million years, and it is reasonable to think that when the human lineage split from that of chimps and bonobos, we had a rudimentary social system similar to theirs today. Chimps do not have pets; they do not have any affinity for cats or dogs, and so they have no guest parasites that exploit their sociality. Homo sapiens has been attended by guest parasites that exploit our unique and robust sociality for a very brief evolutionary interval, perhaps between 10,000 and 20,000 years. In that perspective, we are just seeing the nascent glimmerings (as in oncoming headlights) of the possible exploitation that is yet to come.

To get a better view of what can happen to hosts and guests locked in social parasitism, it is informative to look first at ants and termites. Their own sociality both predates ours by many tens of millions of years, and their social guest parasites are much more refined than our own. There are many forms of social parasitism in insects we can look at, including an advanced social parasite of ants, the Large Blue butterfly Phengaris arion. Life Cycle A


After hatching from its egg and feeding for a time on plant material, the caterpillar of P. arion drops to the ground and wanders aimlessly until approached by an ant.

The caterpillar hunches into a contorted posture while releasing pheromones. Together, the behavioral cue and chemical message informs the ant that it has found one of its own larvae, and it gently picks up the guest parasite and carries it back to the brood chamber of the ant colony. Here the butterfly larva slaughters and eats the ant brood while soliciting tropholaxis (demanding vomited food) from the nurse ants until it matures and undergoes pupation. Hatching of the adult butterfly completes the cycle.

The extremes to which evolution has selected features of guest parasite anatomy is exemplified by the termitophilous staphylinid beetles, guest parasites of African termites, shown below. The abdomen of the beetle has been distended and projected back over the dorsum of the insect, so that its anus sits directly above the head. Curious worker termites who approach the beetle actually interact with the anus and false appendages, rather than the actual head of the beetle hidden below. Pheromones secreted by perianal glands mimic those of worker termites. Exudatoria, or fake legs, dangle from the sides, making this a termite version of a human adult blow up doll. Following the lead of the Great Blue, staphylinid larvae become large consumers of termite eggs and larvae.


C. ovambolandicus shows an extreme level of physogastry (abdominal hypertrophy) believed to enable it to represent its distal abdomen and anus to worker termites as a false surrogate for its actual head.

Back to the Future…

It is interesting to speculate as to how evolution will shape this emerging guest parasitism by cats of humans. If we learn anything from the study of insects, it should teach us that social guest parasites gravitate towards exploitation of the brood. House cats have eaten the fingers of babies in the past, but this isn’t a behavior that is likely to be widely tolerated. Instead, just as the staphylinid beetle A. Pubicollis induces regurgitation by its Myrmica hosts, it is possible that cats will learn to accost babies in their cribs, licking and pawing the oropharynx in a surreptitious manner to induce vomiting, then quickly consuming the regurgitated milk before a defensive response can be mounted by the human host parent.


A. Pubicollis, above right, uses its antennae and front legs to tap, stroke, and induce the regurgitation of food from its host ant. A human infant host could be relieved of its stomach contents by similar feline behaviors, leading to the nutritional disparity seen at left.

The passing of human breast milk from the mother to the guest parasite cat via an infant intermediary could be exactly the break another emerging parasite has been waiting for. Toxoplasma Gondii is a protozoan obligate intracellular parasite with a variety of intermediate hosts, such as mice, rats, swine, cattle, and (yes) humans, but only one definitive host: the domestic house cat. T. gondii and F. sylvestris have accommodated well to each other, in that the parasite inflicts no apparent harm or damage to the cat, and the cat in turn provides ample resources in its intestine for the production of millions of parasite oocysts, which are shed in cat feces. Sporulation of the oocysts a few days or as much as a year after defecation produces the virulent form of the parasite, which can be ingested by any of the intermediate hosts. The state of diplomacy between T. gondii and the intermediate hosts, particularly mice and humans, resembles more of a smoldering insurgency. Unable to form its egg stage in these hosts, the parasite instead forms dormant cysts or bradyzoites in the host brain and muscle tissue. Famously, it alters the behaviors of the parasitized mice, causing them to lose their instinctive fear of cats and to expose themselves to easy predation. Consumption of the deranged mouse allows ingestion of the cysts and completion of the T. gondii life cycle.  More controversially, latent cerebral T. gondii infection in humans has also been linked to an increase in suicidal and high-risk behaviors. But the suicide of the human fails to close the life cycle loop of the parasite since cats are generally prevented from consuming the brain or muscle of deceased persons. Meanwhile, toxoplasmosis exacts a small but continuous health toll on the  human host, causing a low grade, flu-like illness in many and catastrophic birth defects when an active maternal infection is transmitted to the growing human fetus.

The next emerging zoonosis might not be an offshoot of ebola or malaria, but simply a small redirection of the human T. gondii tropism from muscle and placenta to breast tissue, where the active tachyzoite stage of the parasite would be secreted directly into human breast milk. Toxoplasmosis transmitted via breast milk has been documented in mice in controlled experiments**, but such data in humans is absent. Transfer of the partially digested milk from the infant stomach to the social guest parasitic house cat would complete the protozoal life cycle with some enormous new advantages. First, the cat would not have to kill and eat the intermediate host, but simply rob it of its stomach contents. Rather than a single transfer of protozoan back to cat, there could be hundreds of transfers over many months, with the human breast recruited as a factory for the production of T. gondii parasites. T. gondii could also use its well documented ability to influence host brain function by inducing pregnant human females to desire and to tolerate cats, especially around their nursery room. In this way, the protozoan would suddenly have full access to exploit the human as a definitive host, rather than as a biological dead end.

Humans will play more than a passive role in the evolution of this relationship. Cats currently face an exceptional negative selection pressure from their human hosts, who tend to restrain, sedate, and sterilize their guest parasites. Pet sterilization increases with household income, rising to 93% of all cats in homes with more than $35,000 in annual income. Only those individual cats who can somehow evade this ongoing mass culling will provide the genes and characteristics that typify the cat species of the future. For a cat in a wealthy American household, the best choice may be simply to get out—to flee the initial host and join the 100 million feral cats, only 3% of whom have been neutered. In this scenario, parasitism of a human household would be a transitional step in the development of cats, employed by kittens that gain an advantage over feral-raised kittens by way of the food and vaccinations they obtain from the humans. Those prompted to escape before neutering would become the dominant individuals in the feral population that breeds relatively freely. A queen cat would be a female who insinuates herself into the household just around the time the woman is pregnant, in order to establish the lucrative co-parasitism of the expected infant. By timing her own pregnancy to coincide with that of her human host, the cat could take advantage of the general chaos that surrounds the human neonatal period, increasing the odds that she would not be spayed because the overwhelmed hosts simply forgot to do it.

Cats living in the developing world and in the poorer households of wealthy countries still face a 50/50 chance of being neutered before they can reproduce. Accelerated sexual maturation and precocious mating has been observed in many species, including overexploited populations of fish, in response to this sort of inescapable early mortality.***

Kirk M Maxey with a juvenile social guest parasite who is soliciting grooming, heat transfer, and protection from the host.

* Yes, they do eat cats in parts of China, but they eat everything in China, including the civet cats that first introduced the SARS virus into the world. As noted above, eating cats is probably a very bad idea in the first place, considering their close affiliation with toxoplasmosis.

** Am.J.Dis.Chld. Eichenwald, H. p307, 1948 (I was unable to read this 1948 reference without feeding money to the JAMA Paywall, which you, kind reader, will not have to do. The full PDF is available in the Reference section of my blog. After 67 years, it’s about time it became public knowledge.

*** Spayed and neutered cats do not actually die, but live on for as long as 20 years in the host living space, consuming host resources. Since these individuals are already dead in a Darwinian sense, it would be highly adaptive for the cat to develop mutations that actually kill it during or immediately after such a surgical operation. That would free the host living space for another cat, which would likely be sourced from the same breeding population as the original, now deceased neutered one. The host human would be less likely to insist on sterilizing each subsequent pet, as humans tend to grieve the loss of their guest parasites in the same manner as the actual human offspring that the cats are replacing.

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This post was inspired by Michael Eisen (@mbeisen), who innocently asked about the DNA content of various foods on Twitter a few days ago. As expected, the responses were mostly the rantings of idiots, all sound and fury, signifying nothing. Michael Eisen also brought my attention to a recent Oklahoma State University survey that returned the surprising result that 80% of Americans don’t understand the difference between DNA itself and genetically engineered DNA. Although, there’s some debate about the veracity of the survey, as Ben Lillie (@BenLillie) points out that previous research doesn’t back the claim that Americans are so dense, but I’ve shown before that survey design can alter the outcome.

Due to this cacophony, I remembered an old post I’d abandoned about eggs, or yeitse. (Yeitse is the Russian word for egg. It helps if there is one cool fact that you can take home from any blog post. 🙂 In it, I noted that eggs are virtually DNA-free. So I spruced up the old text and hope that Michael will find it more informative than the usual 140 character Twitter snark.

An egg weighs about 57 grams and contains 213 milligrams of cholesterol. It is about 80% water, and the rest of the weight is evenly split between protein and fat. Eggs have been appreciated as a great source of concentrated nutrients for thousands of years, except for perhaps the last 50. It has been proposed that the building of the pyramids was enabled by the prior domestication of the chicken. Chickens permitted the pharaohs to set up massive, mobile protein manufacturing plants (chicken coops) in any area, immediately adjacent to new construction sites, and thus feed the manual laborers that were their primary source of motive power.

Eggs, as I mentioned, are a rich source of cholesterol. Humans first began to badly misunderstand the egg at the same time that they began to associate, but not fully comprehend, cholesterol and atherosclerosis. When they examined the diseased blood vessels of well fed men suffering from heart attacks, they found disgusting, yellowish gobs of material distorting the walls of these vessels. The material was mostly cholesterol. Not recognizing (or perhaps forgetting) that cholesterol makes up about 35% of every membrane in every cell in the body, and that most of the cholesterol in the human is made especially for this purpose by the liver—they decided that eating cholesterol caused heart disease.

So they took an animal that does not normally eat eggs, and they fed them eggs anyway. They also picked an animal that does not make cholesterol in its liver, like people, but gets it by eating plants. This animal, the white rabbit, developed really bad atherosclerosis when overfed with eggs. So forgetting that people are not rabbits, it was announced that atherosclerosis is caused by the eating of eggs. And most people believed it, and tried to stop eating them.


An egg is just a single cell. You tend to forget that, holding one in your hand and tossing it up into the air. If you were holding an onion of about the same size, you would be holding several million cells. There are other differences between an egg and an onion, but one that really stands out is the amount of DNA. It takes about 30 times more DNA to make an onion than a chicken. That is, the chicken genome contains about 1.8 billion bases, but the onion genome contains more than 70 billion. It’s not entirely clear why an onion takes such a detailed instruction manual, while a chicken can be made using an IKEA version. An egg that you buy in the store usually isn’t fertilized, so it contains only one single copy of the chicken genome. Even if the chicken had sex and the egg was fertilized, there would be only two copies. In an onion, you get millions of copies of the onion genome. None of this would really matter, except that about the same time humans began to misunderstand eggs, they also began to get some funny ideas about DNA.

For as long as humans have been eating, they have been eating DNA. Whether from chickens, or onions, or goose liver—if you eat a cell, you eat DNA. Eating the DNA of another organism isn’t dangerous. Since it occurred commonly prior to January 1, 1958, the government considers it to be GRAS—or Generally Recognized As Safe. GRAS is a technical term used by health regulatory officials. It means, literally, that if a substance has been consumed by people for as long as anyone can remember, then it can’t hurt you. Seems like an odd concept, when you think about alcohol, which has a long history of human consumption and isn’t very good for you… but anyway, DNA falls into this category.

Very soon after people began to be fearful that their heart disease was being caused by eggs, they also began to be fearful of eating DNA, but not all DNA, or at least not most of it. They were specifically worried about recombinant DNA. Now, every time an organism reproduces, the DNA recombines, so all DNA is recombinant, by definition. But still, there was DNA out and about starting in the later part of the twentieth century that had been helped to recombine just the way some human scientists wanted it to. This came to be known as genetically modified, or GM. Again, that’s bad terminology, because DNA is constantly being modified. As stable as it is, DNA is continually damaged, cut, and locally annihilated by reactive chemicals and radiation. So all DNA is GM. Some very special DNA is GM at the behest of humans, and the rest is randomly and senselessly GM at the behest of entropy. So the intelligently modified DNA could be called genetically engineered, or GE.

Someone mentioned to me that it might be particularly risky to eat human genes. Jeffrey Dahmer did it. Not to say that makes what he did OK, but I think something altogether different was responsible for his lack of health and sanity. Likewise, there was the Argentine soccer team who got stranded in the Andes and had to eat each other to stay alive. Then again, there are certain sexual practices that culminate in one or the other of the participants getting a mouth full of semen. I think this was already happening in 1958, so it just might be GRAS. Some people swallow, and some don’t. As far as I know, there is no alleged health difference between these groups. What I do know for sure—one swallow like that contains more human DNA and protein than… well, that’s probably enough said about that.

Admittedly, people who eat human genes sometimes die, but I don’t think it is a causal relationship. It seems to me that eating human DNA can be associated with a risk of infectious disease, and a risk of incarceration, depending on how exactly it is done. In talking with people who fear recombinant DNA, it dawned on me that they were not well informed. They do not realize that when they catch a virus, it inserts copies of its own DNA right into theirs. Often, the genes the virus inserts are clever and malevolent, capable of deprogramming their cells and forcing them to make cloned copies of the virus. That’s quite scary, compared to just making a healthy nutrient as in golden rice or other GM,GE improved foods. It turns out that the genes of biotechnology critics are themselves genetically modified and perverted in ways that ought to induce an acute self-loathing. Perhaps it’s not possible to be virulently opposed to molecular biotechnology and still fully educated about the types of DNA modification and gene swapping routinely indulged in by bacteria and viruses, inside your own body, 24/7.


I notice the government has chimed in, and they are almost certainly wrong, because plant genomes run 3-50 times bigger than most animal genomes. That is because plants bear a heavy load of parasitic retrotransposons—bits of old jumping DNA, like the ones that make corn colorful.

Posted in Environment, Genetics, Science | Tagged , , | 4 Comments

When is a Survey not a Survey?

One of the great things about Twitter is that it alerts you to new papers and discussions of those papers that you’d otherwise not be privy to. Sadly, the 140 character limit badly stunts those discussions just when they are really warming to a good topic, as happened here:


Since I found this paper very interesting and applicable to my professional experience and personal experience as a participant in the Personal Genome Project, I read it—and then I personally took the survey on which it was based.

Unfortunately, about 5 minutes into the exercise, I was surprised when the “survey” actively challenged one of my answers. That is, it attempted to caution me that what I was in favor of, and I quote, “…is likely to be very expensive and time consuming. This may mean that the research is compromised.”

Maybe I have some assumptions with respect to the use of scientific surveys that form the basis of publications in peer reviewed journals that are a bit old-fashioned, but it seems obvious to me that this survey instrument is not really a survey at all if it seeks to guide the responder’s choices by 1) supplying added information that may change a response and 2) making claims that suggest there will be negative consequences because of a response.

Imagine for a moment that this survey was about diet and not about the incidental findings of genomics research. And suppose it asked the respondent how many servings of “crisps” (I just love sticking with the very British tone of this thing) they ate? Imagine, if after admitting to eating 8 servings of crisps each day, the survey instrument then prompted, “Eating that amount of crisps is unhealthy and is likely to make you very obese. Are you sure that you really eat that much?” The psychology of this situation is very well understood—a substantial percentage of people will slant their responses in order to seem to be good, normal persons as opposed to bad, unhealthy persons. Or in the case of genomics research, one certainly would try to avoid having an opinion that causes things to become very costly and time consuming, compromising genomics research.

Not only does this survey seek to instruct and then query, but I question very much the accuracy of the information it provides. There is free software available on the internet that can easily be used to call every SNP in the human genome. Or more to the point, to identify every known disease-associated mutation in the Online Mendelian Inheritance in Man (OMIM) which will supply more than 10,000 possible incidental findings. It is actually NOT very costly or time consuming to supply this information to each participant in a genomics research study, and a system could be established to automatically deliver boilerplate explanations and followup recommendations for these disease associated mutations, which brings us to the really relevant point of this all.

Any participant, in almost any medical research study of any kind, is going to receive a hands-on physical examination by a physician. This exercise is as old and stereotypical of anything in medicine today. Such an examination certainly has costs, but we recognize those as essential costs of conducting proper medicine and patient care. Further, we would never have a discussion as to whether any abnormalities that were unexpectedly observed during that exam should be shared with the patient—of course they should be shared. Those that seem to have some risk should be actively followed up.

Examining a patient’s genome is not really any different—it is simply a matter of volume. While a physical exam could return perhaps 100 findings, a genomic exam will return tens of thousands. By quickly sieving those through the available software mentioned earlier, it is not costly or burdensome to supply the patient with a brief written summary of what is known about the genetic findings that have been made, ranked in their order of importance or actionability. The idea that a genomics researcher could just decide not to do that is very irresponsible. But then, so is constructing a survey that seems to actively go fishing for a set of opinions that will justify this lazy attitude that there is no expectation on the part of the patient to ever be told this information either.

It is my experience that patients want to be told every important medical observation that could have an impact on their health and well being. The fact that this may need to be presented on a CD—that’s just how it is with genomic medicine.

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Re: Will a return of rising temperatures validate the climate models?

Instability is the first thing that one will notice if presented with climate data, on almost any scale. That is why the flat-line in global surface air temperature that began in 1998 is so unexpected. The debate over climate change is largely partisan, unscientific, acrimonious, and unyielding to moderation. But both sides in this political trench warfare seem to quietly admit that this stability cannot last, and that they’d better be prepared with spin pre-packaged when it comes undone.

From the perspective of alarmists, the longer we go without managing even 0.01 °C of warming, the further off their “drop dead limit” of 2° C gets. So predictably, a comment recently appeared in Nature written by David Victor and Charles Kennel (PDF) urging everyone to just forget about that 2° C thing. Like hurricanes that fail to appear and sea levels that don’t rise, surface air temperature is losing favor as a motivational factor. Climate alarmists are now searching for a “thing” to keep fighting, even if their main thing, which is warming, drops out on them.

In the other camp, climate realists are also taken somewhat aback by the duration of this stability, and readily admit that surface air temperature can’t be predicted in advance and may go in any direction, up or down. The problem for them comes if it starts back up. Does that mean that all of the failed climate models that blundered so badly for the last 20 years will be rehabilitated? Again, to get in ahead of the data, a recent post on the blog Climate etc. throws a preemptive strike at the possibility that the next flip of the global climate coin comes up heads – for Hotter:

The coincidence of the current plateau in global surface temperatures with the continuing rise in the atmospheric concentration of carbon dioxide has raised many questions about the climate models and their forecasts of serious anthropogenic global warming.

Or as Clint Eastwood said, “A man’s got to know his limitations.”

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