Untangling the March for Science

If there was a single cartoon that captured the essence of the “March for Science”, this was it.

Sciencemarch.PNG

The image of a sanctimonious Bill Nye grinning approvingly over some gender studies nonsense, while the true icons of science look down from heaven in horror and disbelief – that was priceless. I actually do make my living practicing science, but more important, I structure my life by practicing science. I know the difference between science and politics – and this march wasn’t about science.

 

Climate Etc.

by Judith Curry

Pondering some thorny issues regarding science, its place in society and its relationship to politics.

View original post 2,564 more words

Posted in Uncategorized | Leave a comment

Activism and the Academy

Is this really necessary?

Is this really necessary?

I am a member of a thing I call the Academy. It is a club, but without any roster, dues, or membership requirement – other than a preoccupation with science. It is non-exclusive, without judgment of any kind with respect to wealth, race, sex, creed, or place of origin. It owns no property, has no location, but it manifests itself continuously and repetitively in a thing called the scientific research conference. These meetings are something like the fruiting events of a slime mold, where thousands of fully separate and individual organisms (in this case humans, rather than amoeboids) come together and form a brief coalition with a specific goal, protocol, duration, and set of organizing principles.

The Academy convenes spontaneously whenever a topic within a discipline becomes of such current impact and importance that a critical mass of Academy members feels compelled to organize. In an ad hoc fashion, with funds begged and borrowed, a venue is located and a set of speakers selected and invited, and the Academy prepares to convene. While I have never witnessed a more tolerant and inclusive body, the Academy is still a meritocracy. No one travels thousands of miles to hear a bumbling fool who knows less than they do butcher a scientific subject. The speakers who are invited to present at a conference are typically and reliably the best in their field, irrespective of any other identifier. It’s like the NBA, only you substitute scientific mastery and communication for 3-pointer percentage and slam dunks. You go to a Cavs game to see Labron-caliber basketball, and you go to a Genomics meeting to hear Doudna-caliber science. Inclusion ratios are just an incidental finding.

Meetings of the Academy move forward under a strict but informal protocol that extends beyond the stipulation that you will not be invited to speak unless you are well established in your field and have clearly contributed novel discoveries to human knowledge. The academy will listen quietly and politely while you state your case and present your findings. They will openly challenge you and question you immediately thereafter but in an orderly fashion. Name calling and politics are considered gauche and are not tolerated, nor are personal, ad hominem, appeal to consensus, or all other manner of false reasoning attacks.

I value my membership in and the existence of the Academy more than any other single thing in my professional life. More than the diploma that I earned from the University of Michigan School of Medicine that hangs on my office wall; more than the small stack of peer reviewed, pre-printed articles with my name on them that I keep in my desk drawer. (Yes, I came of age in the time when articles were snail-mailed between colleagues because email had not yet been invented.) I value it because it just allowed me to be present last week in a beautiful setting in Lake Tahoe and to hear Robert Murphy from the University of Colorado describe the histologic visualization of brain tissue using laser desorption mass spec imaging of phospholipids.

From there, I flew to La Jolla where I learned from Dr. Razelle Kurzrock about precision cancer therapy and the genomic biopsy of breast cancer from human blood.

Kurzrock Presentation 1

I also listened to Carl Zimmer and Ed Yong, who like me are accepted and included in the Academy despite the fact that they have no new, original research to present when they arrive.

Yong 2

The Academy welcomes curiosity, a genuine interest in the truth, and a willingness to act as a conduit of that truth to the greater public. When I returned home, I added my participant’s badges from these meetings to a drawer containing literally hundreds of other icons of my past participation in a coming together of the members of the Academy in a civil and respectful fashion for the benefit of all of science. It is simply the best thing a civil society and a democracy can manifest, this utterly free and collegial exchange of knowledge and ideas, replete with remarks, retorts, and pointed questions that challenge the data, the models, and every other intellectual aspect of the topic up for discussion.

In spite of what I’ve just written, I absolutely dread what seems to be on the agenda for the next convention of the Academy, organized under the hashtag of #ScienceMarch. To begin with, there is something fundamentally wrong with the calling card for this convention. Conferences of scientists take place inauspiciously and quietly, in near seclusion, for a very good reason—because science is about thought, logic, and reason, and those activities tend to be degraded by noise, agitation, and political posturing. Rather than bringing together the best science has to offer, this conference seems to be dominated by those whose science is a bit dodgy. This convention has no coherent topic but seems to be simultaneously about dozens of purely political issues that science cannot un-complicate or reduce to some artificial policy-defined certainty.

The world does need to pay attention to scientists but not because we yell more loudly than some other special interest group—the world needs to value us because we invent things, correct things, and reveal past errors in our fundamental understanding. #ScienceMarch seems to be an immature, self-important shriek for attention. Scientists offer a way to a better tomorrow, as we have for centuries, bringing to humanity vaccines, antibiotics, computers, MRI scans, and millions of other clear advances in our well being. We inform the world when a species is suffering and in danger of disappearing from the earth as only those properly trained and practicing wildlife ecology are prepared and competent to do.

An argument has been put forward that this street protest is necessary, because those we have elected to political power do not properly respect us and our carefully accumulated evidence. This is an obvious reference to the Trump administration’s disdain for climate and immunization science. I have covered those two very different topics elsewhere, and they are important, but the hard truth is that simply by ignoring science, this administration has committed no crime. Nor have they discovered anything novel. Every president I can think of since Nixon, including Obama, viewed science cynically and manipulatively, to be supported, misquoted, and prostituted only when it helped their particular politics.

So how do I imagine the #ScienceMarch will go? In a word—badly. We are visually a very odd and identifiable group living in an age of unusual intolerance and bigotry. We have allowed a small clique of self-serving politically frenzied climatologists tarnish our scientific integrity with their outlandish claims of impending disaster and ecosystem collapse that never happens. This is the political faction who have been so rudely ejected from their positions of power by the election of Donald Trump, and this street protest seems primarily to be a knee jerk tantrum at this abrupt loss of status. Do scientists suppose that if we behave like a bunch of striking transit workers out to protect our cushy union jobs, we’re going to get more respect, not less? It seems more likely to me that those in power will notice how many of us seem to have gotten here on a VISA and will try to tighten that process beyond its current ridiculous restrictions. They will notice that we are well paid and generally live stimulating, comfortable lives and will lobby for cuts in government research spending, salaries, and graduate stipends. (Note the proposed $1.2 billion NIH budget cut.) In the worst case, there will be more violence against identifiable, highly-intelligent minority victims such as Srinivas Kuchibhotla in Kansas City.

It’s hard to deny that America is in a state of political turmoil. We have elected as president a stupid man who believes he is smart, and the reflections of his ignorance and mendacity are radiating out through the executive branch of our government. Truth, forever the domain and highest object of science, is in short supply in the age of alternative facts. It is not as if we have never had as president a dishonest, paranoid, and criminally inclined person, as we did with Richard Nixon. I remember well the night when Nixon fired Archibald Cox, the special prosecutor who was following his nose closer and closer to the White House as he investigated the Watergate break in. That was the night I took to the streets myself, not as a scientist with a lab coat on, demanding more attention for myself or my profession, but as an outraged student protester who was determined to end the corruption infecting the highest office in the land. The music of that earlier time was of the Byrds singing “To Everything There is a Season.” That night, it was time.

If this protest is really about impeaching the president, then let that legal process proceed according to the constitution. If Trump abrogates it in the manner that Nixon tried to do, then a protest march by all Americans may become justified.  America has a lot of special interest groups. Do we really need a new, political entity defined only by the generality of “We study things?” What we really need is the calm, measured, self-critical voice of real science. This is the science that lives in the Academy. I worry that it will suffer a gruesome death in the street protest environment.

I’m frankly very torn as to what to do on April 22. Many of my friends will be taking part in protests organized by #ScienceMarch. I may join them, for a time, strictly as a scientist, to observe what is happening and see whether we, as scientists, have any business out on the street.  I hope that what I will see is the Academy asserting its true principles, as I have tried to describe them so far. I hope that what I don’t see is that we are on the verge of abandoning them.

 

 

Posted in Science | Tagged | Leave a comment

Utah

start.jpg

Red dust from the desert filtered into the tent as the morning sun rose. At dawn the light was diffuse and the triangle of fabric enclosed space was peaceful. Then the first of the sun’s direct rays brushed the canvas with an incandescent glow. It lit up the dust particles as they drifted about on tiny currents of air. A boy of 19 crawled stiffly out from under the flap on his hands and knees. He stood up, stretched, and then drank long and sloppily from a plastic gallon water jug. Water streamed down his neck and dark stains spread down his T-shirt to his navel. He shuffled a few more steps from the tent, and urinated on a cactus, frowning at the paltry stream of salty orange liquid. Then he and went back for another long drink from the water jug.

He eyed the open tent flap and the form of his companion dozing under the bright red quilted down. There had been arguments yesterday, and he was both irritated that the guy was not waking up and glad not to have to put up with talking to him. Pulling a small notebook quietly from his side of the tent, he settled in the dry sand and opened it to read the last entry he had written. It was a self portrait from a day in August, the summer before, on the last day of his summer construction job.

Self Portrait (This part of the reading is best done while playing this Bob Seeger tune)

It was Friday afternoon. Sunlight filtered down through the aspen leaves, falling in soft patches on the grass. He lay back on the ground beside the trees with the tall grass swaying gently beside him, the pattern of sunlight and shadow flickering over his legs. His right hand rested easily on the handle of a battered chainsaw, its casing still hot to the touch, a fine blue tendril of smoke curling up from its oily muffler. The diesel engine of a backhoe throbbed in the distance. The aspen leaves trembled softly, whispering in quiet shock at the destruction that had stopped just short of their roots.

The grove where he lay stood at the edge of a wide swath of downed timber. A patchwork of stumps, broken branches, and bare logs stretched down one hundred yards to the wide brown expanse of bare earth that would soon be a dam. The backhoe was perched on the side of the mountain, preparing a trench for the placement of a pipeline. He watched through half-closed eyes as the silvery teeth of the shovel sliced into the earth, watched as the mechanical arm contracted, lifting a scoop of wet brown dirt up from the ground. Over and over the arm dipped and rose, slowly extending the trench that ran up the hillside to the aspen grove.

He was young and slender, with blue eyes that sparkled with a mixture of curiosity and confidence. His arms were smooth and brown, his hands hardened from a summer of labor. Pitch stains marred the battered yellow hardhat that was pushed forward to shield his eyes from the afternoon sun. A lock of dark brown hair tinted with gold pushed out from under its brim around his ear. A few stray chips of wood clung to the golden hair on the back of his arm. He brushed them away and sank deeper into the grass.

He was pleased with himself – pleased with life. Though his blue jeans were black with oil and his arms grimy with dust and sweat, there was no dirt in his soul. His smooth features and quiet smile betrayed wounds no deeper than the fine white lines from this summer’s scars etched on the back of his hand. His world was expanding, as was his own opinion of himself. This summer he had learned to cut a tree and make it fall where he wanted it. He had learned to work ten hours a day. He had learned that there wasn’t a lot that he couldn’t do. The weeks had passed and the trees had fallen, one after another, creaking and splintering in an explosion of dust and bark and flying branches. Through the felling of trees, he honed his skill with the saw, his judgment of their weight and balance. He had gotten good at something.

It was Friday, his work was done, and the world lay stretched out before him. He gazed over the gently nodding heads of grass at the mountains shimmering in the distance. He was unhurried, and looked with detached amusement at the dusty confusion of the construction site below him. He smiled softly and closed his eyes.

An ant ran quickly over his leg, as the backhoe droned on in the distance. He would lie here in the warm afternoon sun, do as he pleased, and think, among other things, that this would always be possible. When the backhoe stopped, it would be 5:00. Quitting time. Then he would get up, pick up his saw, and walk down the mountain for the last time. The aspen leaves rustled softly, and a patch of warm sunlight flickered over his face.

Utah, 7 Months later

On this morning, he slid the notebook back inside the tent flap. He put a full canteen of water and a candy bar inside a small day pack along with a camera and a flannel shirt. He glanced briefly at the smooth red sandstone formations of southeast Utah spread out around him, and at the white snowcaps of the Manti-La Salle Mountains far to the north.

1.jpg

Then he glanced back at the tent, and with an adolescent smile imagined his companion waking in a few hours to wonder where he had gone. Not telling him was the first of many mistakes. A disaster is not usually the result of one egregious error. More often, it is the sequential accumulation of 4 or 5 of them, culminating in one that builds on the earlier ones in an irreversible slide into really bad things. He was about to find that out.

He started walking purposefully across the flat desert, heading toward a break in the low sandstone cliffs. The smooth braided pattern in the sand told that when there was water, it flowed in this direction. There were track trails and small burrows of kangaroo rats, and from time to time the straight, purposeful trail of a coyote. Eventually banks of eroded sand rose up on each side, and his trail became the bottom of a wide, sandy ditch. He began to find stones washed into piles along the sandbars. Most of them were grainy black and red basalts that looked baked from their years in the desert sun, but there were also milky white quartz and pink shards of chert. He picked them up, turned them in his hand, and tried to knock a few sharp flakes from some of them like an Indian would do. He had the vague idea that he would follow this dry wash until it reached the Colorado River, then follow the riverbank down into the town of Moab and get a hamburger. It was barely 10:00 in the morning, and he was hungry already.

2

He ate half the candy bar, took a long drink of water, and climbed up the side of the wash onto hard red sandstone. On both sides, the rock rose up in banded layers of ginger, mustard, and cinnamon for more than three hundred feet. From here he could see how the water had sliced through the cliff wall a mile or more ahead, leaving a notch. Through this window he could see far to the east, where some bright green cottonwood trees hinted that there was much more water. That was probably the Colorado River. He dropped back down into the wash, where the walking was easy for a while on the hard packed sand. But eventually the sand disappeared and he was forced to hop from boulder to boulder between towering walls that squeezed in closer from each side. Sometimes he had to lower himself by hand over the lip of a narrow chute, or slide down where the water had flowed and drop into the sand where it had formed a pool.

3.jpg

He was mesmerized by the beauty of the sculpted and braided rock all around him. He stopped and took several pictures of the walls, the sky, and of his own footprints. He even took off his shoes, and made a purposeful track of human prints across a small basin of damp sand, and then photographed them.

footprints

The air was dry, juniper scented and warm at midday, and his T-shirt once again was spotted with dampness – this time his own sweat. It was mid afternoon when the narrow gorge suddenly opened up and he found himself on a gentle sagebrush slope a few hundred yards from the river. It was March, and the snowmelt was starting in earnest hundreds of miles upstream in Colorado. The river was dark, murky and pressing ominously at its banks.

5

There was an old pinion pine there on the hillside, so he sat down in its shade and had the last half of the candy bar and most of the rest of the water. The last few swallows were left in the bottom of the aluminum container, just in case. As he surveyed up and down the river, he began to feel slightly worried. The sun was already low, sending long shadows from the cliffs on his right out across the rolling whitecaps. He could see cars, like small dots on the highway on the other side. But the town he was hoping to walk down to was nowhere in sight. He pulled on his pack, found a game trail that roughly ran parallel to the river, and began to walk rapidly. He amazed himself at how much distance he had covered. He quickly added several more miles, winding in and out with the course of the river. Glancing at his watch, he guessed that he had already traveled about twelve miles since he set off that morning. Suddenly he rounded another bend in the canyon and his spirits sank.

6

As the river meandered back and forth between the tall cliffs that contained it, periodically it would sweep right up to the base of the sandstone and there would be no room for a trail or path of any kind between the cliff and the river. Such a place confronted him now. His shoulder brushed against the canyon wall as he stood on the last narrow ledge of rock. Ahead of him, the river hissed and whispered as it undercut the cliff. Behind him, a few willows poked up out of the thin strip of sandbar that ended at his feet. He looked carefully at the water, trying to imagine how deep it was, and how fast it would carry him if he tried to swim. It was cold in the shadow of the canyon towering above him, and he shivered. He retreated a few feet, scanning the sandstone wall that was pinning him against the river. For a brief moment, he considered backtracking all of the way up the river and into the gorge he had descended in the morning. But as he looked at his watch, he abandoned that idea. There wasn’t nearly enough time.

Almost without thinking about it, he started to climb. There were handholds, and then a small crack. Maybe he was telling himself that he needed to get a bit higher in order to see further downstream. There was something exhilarating about grasping a small handhold far above your head, and then hoisting your body up into space. He quickly ascended about thirty-five feet, and then came to a decision point. He was directly above the water. Any slip now and he would probably strike a glancing blow on the cliff, and then drown in the Colorado River. But to advance, he needed to surmount a small overhang. It extended out over his head about eighteen inches, making it hard to see what was above it. There was a good jam crack for one hand. He decided. He tightened his daypack on his shoulders, reached up with his fist and clenched it inside the narrow crack. Fear was gnawing at his stomach. He pulled himself slowly up, bumping his head against the overhang. His head was pushed sideways by the rock, his ear resting flat on his right shoulder. The rock bit into his knuckles. With his free hand, he reached out and above the overhang, grappling for a handhold. He found one. One more breath, and he released the fist from the jam crack. His body swung gently, sickeningly away from the cliff, and he pulled down with all his adolescent strength on the ledge above. His head rose up over the lip, and the aching hand that had been jammed into the crack below shot out to grip the easy corner of stone, waiting just where he needed it to be. With a quick heave he scraped his belly up over the edge and pulled himself away from the tug of the empty space and the river below.

He licked the blood off the back of his hand and fingers. The wrist quivered slightly as he held it against his mouth. A warm glow spread across his shoulders – partly the adrenaline of cheating death – but it was also the sun. What had not been visible from below was a wide defect in the canyon wall, a series of bowls and stair steps, and the setting sun was shining brightly above its edge. Turning to see it, he felt triumphant. With one final look at the blackness of the river swirling forty feet below, he turned and bounded up into the sunlight.

7

Where he thought he would go now, and what exactly the plan was to get to Moab, was never clear. The brain of a nineteen year old male lives in a stiff brew of hormonal substances, especially during physical exertion. He went mostly without having the sensation of thinking. It felt as if he floated by magic up to the canyon rim. Great circular bowls of sandstone were crossed, ledges scaled. Sheer cliffs, taller but less difficult than the first overhang by the river, fell behind him. The twilight sun made the canyon walls wild with colors, vivid crimson blending in with purples and cinnamon and pools of black shade. Flaming clouds reached out from the sky. Just as the sun was setting, he topped out and could see for miles in all directions. Including south, downriver, where the twinkling lights of Moab accented the canyon shadows – much farther away than he would have liked. There was no chance of continuing to follow the river. The jumble of ravines and cliff walls facing him from that direction was impenetrable. But there was one wide canyon, he would later know that it was called Courthouse Wash, and he could see it leading away from the city and back into the desert just to the west of him, where it dwindled into the slick-rock scrub. His plan, had there been enough daylight to execute it, might have worked. He struck out at a brisk walk, determined to find and drop down into the shallow headwaters of the canyon, much like he had followed a different canyon earlier in the day. He would simply follow the path of the water back down to the town.

8

The sun set, and a sudden chill came to the desert. He pulled his flannel shirt on and rolled up the sleeves. The canteen rattled – it was long since empty. With a growing sense of urgency he pushed past the clumps of brush. It began to be difficult to see the landscape in the distance, and then it was hard just to make out where to put his feet. The stars came out in a glorious sweep across the sky. A dome shaped mound of rock rose up in his path, and as he skirted around it to the left, he suddenly stopped short. In front of him, spread out on the ground, was the same sparkling display of stars. Against an inky purple backdrop, stars were glittering up at him from his feet. Hesitantly, he reached down, almost as if he feared that he might drop off into this space. And he touched – water. As soon as he saw the ripple spreading away from his hand, his brain knew once again where he was. Quickly dropping to his belly, he drank long and deep. He filled the canteen. And he realized that it was now completely, totally dark. He sat on the edge of an enormous sandstone bowl, with a calm reflecting pool of water in it, and wondered what he should do. From the feel of his legs, he had walked more than eighteen miles. His focus on getting to Moab was now blurred by fatigue.

The moon rose, not full but a solid quarter of bright white shining on the horizon. He could see his feet well, and began once again to walk through the night. The problem with night-walking is depth perception, and distance. Almost anything a few feet away gives off enough reflected light to discern where and what it is. But the amount of reflected light drops away with the cube of the distance. Very quickly, even things in full view but far enough away melt into the darkness. Objects in the shadows cannot be seen at all. As an area of darkness appeared in front of him, he could not tell at all if it might be a shallow depression or a gaping canyon.

His solution was to throw objects. Very soon after he left the reflecting pool of water, he came to what he guessed to be the dry wash he was seeking. Nearing the edge, he threw a fist-sized rock out into the night. It never landed. He found a foot long dead branch, and hurled that. Seconds later, he heard it clattering far below him. His hair bristled with cold fear. He was on the edge of a chasm several hundred feet deep. Edging back from the rim, he turned to the right and circled wide around it, coming back at least half a mile further upstream. When a dark abyss blocked his path, he stopped short and threw test objects. Several times his small missiles impacted immediately, and he skidded down into a shallow dip and continued along his way. The moon rose higher, and he imagined that he could see further.

On his next approach to the canyon, he passed through a small V and saw a pair of rock towers, silvery in the night, flanking him on both sides. He was tired, frustrated and hungry. He sat down on his heels and edged much further toward the black nothing facing him before launching a test rock. For two, three seconds – nothing – and then a hollow boom as the rock splintered in the depths. He gasped and clenched his teeth, because his feet were slipping down on the steeply curved rock. For a few seconds, he hung in pure equilibrium with friction and gravity – then a few inches at a time, he scraped his way up and away from the brink.

By this time he was muttering to himself. He was shivering with cold. His legs ached. He turned one more time to the right and circled away and then back toward the canyon. On this last approach, he was encouraged to see the unmistakable branches of a cottonwood tree piercing up from the dark. What he did then – how close he edged out into the night – what objects he threw – no one knows, because he cannot remember. There was an ominous, slow slide that accelerated past the point of stopping. He flipped from his back to his front, raking the cliff with his hands, and the flesh was rasped away from his fingertips, the nails splintering into the night. A long and silent drop through space ended with a crushing impact and a flash of pain through his left leg. There were more thuds as he cartwheeled away from the rock, and a sudden stop as his body wedged on an outcrop. Thinking it all over, he lifted his head slightly and felt his body wrenched sideways. Now he was falling horizontally, and that is how he landed. His head plowed into the ground with an audible splat. He had landed in shallow water. In shock, he leaped up and was suddenly hobbling as he began to see that his left leg did not work at all. Soaking wet, he staggered perhaps fifteen feet through slithering bulrushes and collapsed on his back. There he lay for the rest of the night.

There were only two things he could do. Hold his leg up, his knee curled over his stomach, to find some position where it caused him less pain. And shiver. Still wet in the thirty-degree desert night, he was wracked at once with shivering so violent that he could scarcely draw a breath. He pulled bullrushes from both sides and tucked them under his back to lift it off the damp sand. The moon crossed the narrow slot of night sky above the canyon walls. Coyotes howled straight above him, where his trail ended at the rim. His teeth rattled in their sockets. For hours, he shook like an epileptic, hissing for breath, unable to move. His eyes were clinched tight. There was no need to open them for the same view of black stone walls and a narrow strip of starry sky. His mouth gaped open in shock and exhaustion when finally he saw dusky red stone and a pearl grey sky. He had survived the night.

Still shivering violently, he began to slide backwards on his tailbone away from the wash. An hour and perhaps twenty feet later, he came upon his backpack. He strapped it on backwards, covering his stomach, and it was then that he noticed his arms. His flannel shirt sleeves had nearly been severed at the elbows from impacts with the rock. Black rivulets of dried blood showed through the tears. He ripped the sleeves free, and then slid his raw palms into them, clenching his fists to make them stay. Blood soaked out into the cloth, and they were soon glued into place by a crude cement of dried plasma and sand. With better protection on his hands, he could push down harder with them, still backing away from the puddle of water in the bottom of Courthouse Wash, now crusted with a thin film of ice. He began to bump up over hard sandstone. His neck, wrenched by the impact, ached and burned as he tried to look behind him to pick a path up the smooth rock and toward a juniper tree sprouting above on a small rise. The sun was sliding down the far canyon wall, glowing orange in the midst of the cool morning shadows. He could see that eventually, it would reach the flat rock and the tree just above him. All his energy was focused into dragging himself into the warmth of that yellow glow. And every few feet, despite all his skill, his swollen left leg would impact something with a few ounces of force. He would collapse and groan, grasping his thigh above the knee with both hands as if to choke the nerves that were feeding him this agony. Slowly the throbbing would subside, and his head would clear enough to consider moving on. This went on for hours, and the rock was well warmed by the time he slid fitfully out of the shadows and collapsed near the tree.

9

After thirty minutes in the morning sun, his body finally relaxed. He peeled away his flannel shirt and stretched it out flat on the rock to dry. It was now a short-sleeved flannel shirt, with a rip from the armpit to the hip, but it was the only warm clothing he had. His left foot was screaming from the constriction of his shoe, so many painful minutes where devoted to loosening the laces and pulling them out. Weakness overcame him frequently, and he would simply lie back on the ground for five or ten minutes before rousing himself and continuing with these small tasks. The shoe was finally loose, and he let it drop to the ground. He began to roll the sock down toward his ankle, but could not finish. The sock was imbedded in the flesh of his leg, which was swollen at the ankle to the size of his thigh. Where he could unroll the sock, it left a crisscross pattern of cotton in purple green skin that immediately oozed a yellow sticky fluid. Any slight torque or pressure on it sent bolts of pain shooting up into his brain.

He could not see it, but the smaller bone in his leg, the fibula, was just a chain of fragments, none of them more than an inch or two long. The tibia, the large bone, was shattered at the end and one of the pieces was protruding inward where the knobby ball of his old ankle had once been. Over time, a purple stain began to form there that soaked through his tightly stretched sock.

Film.jpg

He took the camera from the pack, rewound and removed the film, and unscrewed the lens. It was his brother’s camera. For a few moments he felt badly about damaging it. He set the film out on a small sandstone table. He was already beginning to think that he might die, and he felt good to have left his own footprints on the last frame of film that he had taken. He built a small wall of rocks around the bright yellow and black cylinder, and scratched an arrow in the rock, pointing down the wash, where he had already determined that he must go. Canyon wrens called from the cliffs, with a slow, descending song that sounded like a windup toy running out of energy. It was a parody of his own actions, stirring into life and then slumping over, stilled by exhaustion.

Pulling together some withered weeds and scraps of twig and bark from the juniper, he focused the camera lens on them. Gradually they heated, then smoked, and he had a small yellow flame. The smoke was acrid in his nostrils, and he panicked as he realized he had no more wood. He flailed about on his back, scraping at anything flammable within reach. But he could not find enough wood. His little fire burned, ate through the small sticks that he had managed, and died. He slumped back, disappointed but secure in the knowledge that he could do this, and would not be cold another night.

By now the sun was high overhead, and he began to need shade more than warmth. The skin was wearing away from his back and hips, but this was still the only way he could move without jarring his leg unbearably. So he skidded along on his tailbone until he was under the shadow of the tree. Leaning against it, cushioned by his daypack, he fell asleep for the first time. When he awoke, the canyon was in shadow, and the edge of the sunlight was twenty feet above him, on the ledge where he had lodged briefly before the last part of the fall. He realized that he could only start fire for those few hours each day when the sun was directly overhead, shining on the floor of the wash. The prospect of another cold night in the bulrushes drove him to move now.

He stuffed the camera and its components back into the backpack. Scuttling back into the wash, he dragged himself to the puddle and drank from it. It was easy to lay the canteen on its side, let it fill, and then drink without getting wet again. It was surprisingly cold and clean tasting water. For the first time since he had defiled the cactus more than a day ago, he needed to pee. But in the only position his leg could tolerate, it would go all over his stomach. With an infinite amount of care, he tilted himself to one side, and made a round, foaming puddle in the sand right next to his hip. It was so salty it burned, and seemed to be the color of root beer. But something in this simple act confirmed for him that he was gaining strength. His body was functioning, adjusting. Even his swollen leg seemed to be forming itself into a sort of turgid, sturdy cast.

He strapped the pack onto his belly, and set off down the wash like a crab. His injured leg was held high, his one good foot thrusting forward alone. He would lift his butt until it came up against the back of his ankle, shoving with both palms pointed backward. Each repetition of the motion gained him about eighteen inches…and so he continued, collapsing briefly from time to time to rest. The leg was quite hard now, and the color of ripe plums. It did not hurt as much anymore.

The sunlight rose up the wall nearly to the canyon rim and became fiery red, although the sky in the slot above him was just a cool blue. The floor of the wash was now solid, sculpted sandstone. It curved into bowls and half circles, dropped over brief sills and waterfalls that made his insect-like crawl difficult. A clump of cottonwoods sprouted from one wall. There in front of them, a bathtub-sized depression had been carved by the running water. It was half filled with sand and wind drifted leaves. With darkness coming swiftly, he realized that this was his best chance to survive the night. Between the trees and the base of the cliff were more dry leaves. He scooped them with his hands, kicking them with his good foot, and shuffled them one small bunch at a time into the bathtub. Within an hour, he had a blanket of leaves almost a foot deep.

As he dropped into the leaf pile and covered himself, it was instantly clear that this would be a better night. He was already warm from the last few hours’ exertion. Under the leaves, he could not believe the warmth that his body seemed to be generating. Sweat ran down the back of his neck. He moved the backpack around and made a small pillow of it, and sat waiting for the darkness. It came quickly. A few hours after sunset, he could tell that the moon had risen because the turrets and rim rocks of the canyon above him seemed to be lit with a pale white spotlight. He suddenly noticed twin rock domes high above him, with a narrow V-shaped groove between them. They perched on the canyon rim, and there was a wide circular undercut that reached up from hundreds of feet below. Its top curved like an arch, creating a mantle perhaps thirty feet tall and ten feet thick for the towers to stand on. His spit turned dry in his mouth as he recognized, from the floor of the wash, a place he had been early the night before. It was the place where he had almost been unable to pull himself back; where he had hung in the balance with gravity, straining with his clenched fingers to get a grip on the smooth, curved sandstone and get away from the edge. He imagined how tiny he must have looked from here, perched on the rim. His eyes followed the smooth, sweeping path his body would have taken, arcing out from the undercut edge of the cliff, and finally impacting after 250 feet on a jumble of sandstone blocks the size of washing machines just a few yards away. He felt sick. Long gone was the euphoria of the climb out of the Colorado River. Forgotten was the magic scene of stars dancing on the floor of the desert. His stomach was a clinched knot. His mind was now much more focused, clear and rational. His liver was furiously making glucose from the amino acids streaming back from his wasting muscles and his injuries. His brain helped conserve this energy by thinking slowly, and only about immediate survival. He piled the leaves more closely around him, and watched the moonlight inch its way down the canyon wall. He slept as well as anyone with a broken leg does. It was scarcely cold at all.

In the morning he waited in the leaf bed until the sun was almost down to the floor of the wash. Twice, he heard the sound of an airplane. The aircraft and its buzzing drone grew louder, then faded, without anything ever coming into sight in the narrow slot of sky between the canyon walls. It was clear that he was almost hidden in the bottom of the wash. No one would find him unless they walked up the canyon on foot. He had to get moving.

He crawled to a pool where the water emerged from the sand to flow freely down the canyon. Once again, it had crusted with ice. He pulled out his pack and took stock of himself. He had one shoe, a camera, and a canteen. He soaked each of his stinging hands in the pool until the sandy shirtsleeve bandages came loose. There was no skin on the ends of his fingers, but dark scabs had begun to form. He rinsed the blood and dirt from the damp cloth, squeezed it dry and clasped the makeshift bandages again in his clenched fists. Gingerly, he lowered his left leg into the freezing water and let the cold dull the pain. It suddenly seemed important to get off the tightly stretched sock and get a better look at his ankle. Tugging at the toes and rolling down from the top, he was able to loosen the fabric slightly. There was a sharp sting as the last resistance gave way. He could see that most of the skin on the inside of the ankle had peeled away with the fabric. What remained was a tightly swollen mass of purple tissue, senseless to the touch, and glistening like plastic except where the skin was broken and honey colored liquid was oozing quietly into droplets.

He moved up to a flat ledge above the pool, rolled onto his side, and let the ankle bake in the sun. A thin high overcast had developed, and he could no longer focus enough heat from the camera lens to burn anything. A few brown charred spots were made on a couple of leaves – but no fire. Again he slept, but was awakened by the whump-whump of a helicopter coming in very close to him. He jumped up, struck the broken leg on the ground, screamed, and collapsed. Turning his head, he saw the machine for a brief second as it crossed the canyon several hundred yards above him. The sound echoed for a minute off the canyon walls, faded, and the silence returned.

Emotion is an expensive thing when you have not eaten for several days. He only let the despair of having missed the helicopter sink down into his mind for a short time – then he pushed it away in favor of the optimism that people were actively looking for him. Darkness was coming, so he scooted back to the pool for more water. Both days since the fall he had spent several hours sleeping on the flat sandstone in full sunlight. It kept him warm, but was severely dehydrating. As he backed away from the pond, a small toad blundered out of the dry grass in front of him and he stamped on it with his good foot. He held the limp body in his fingers for a few moments, thinking he should eat it. It did not look remotely appetizing. He sniffed it, then threw it into the sagebrush. Later as he shivered under the blanket of leaves in the stone hollow, he wondered if it had been smart. He could lie on his right side now, just resting his left leg on a cushion of leaves piled over the right leg. It took the weight off his tailbone, and let him take short naps. In between, he listened to the pack rats rustling under the ledge above him, and stared up at the place where the two towers stood like grave markers in the moonlight. His body felt cold to him on this night, not warm like the night before. He noticed that his fingers were quivering as he held them clasped under his armpits. It was not explosive shivering like the night he had been wet. It was more like a gentle seizure that would not go away. He rocked his lower jaw back and forth, clicking his molars to the rhythm of “American Tune”, a song by Paul Simon. He ran over and over the verse that said, “And I dreamed I was dying. I dreamed that my soul rose unexpectedly, and looking back down at me, smiled reassuringly…” Then his perspective changed, and he was sitting back up between the twin towers, he had both of his shoes on, his left leg was fine, and he was watching the small lump of leaves far below him, shaking gently in the moonlight. He stayed there for the rest of the night, without pain, and without hunger. Only when he awoke did he find himself once again in a bowl in the rock filled with crumpled dry leaves.

As a thin grey light came back to the canyon next morning, a grim determination came over his mind. He climbed up out of the depression and rose up on his one good foot. Searching out a path, he hopped on one leg, and very quickly covered forty yards. Sinking to the ground, he traversed some broken boulders with his slower crab walk. As soon as he reached flat ground, he rose up again and hopped one-legged. Relentlessly, he drove himself down the canyon. It was more than a mile. Maybe it was 10:00 am when he rounded a curve in the wash and the right hand wall melted away, opening up into a wide, sand covered valley. He was crab walking around some sage clumps, heading for the center of the open space when he heard the helicopter. It was coming directly up the wash from the Colorado. In seconds it thundered into sight directly in front of him, and settled immediately down onto the dusty bank a few hundred feet away. He covered the intervening space so quickly on one foot that he was banging on the clear plastic door even before the pilot could open it.

All he could remember of the helicopter ride was how short it was, and how the pilot offered him a cigarette. He did not want a cigarette. But it made him angry that he had to be picked up by a helicopter when he was only half a mile from the town. He wanted to have made it there on his own.  At the hospital, he listened in disbelief as the doctor informed the staff and his family that his stomach would not be able to eat food, and that he could only be given coffee to drink. He did not want coffee. A hamburger and coke found their way into the room under a jacket within an hour, and as he ate this first meal, he rejoined the rest of the world.

But the person who came back into the world was not the same one that had picked up a chainsaw and started to cut trees ten months before. Some of the same Indians who inhabited this desert before the white man had a tradition of sending their young males off alone, intentionally, to discover for themselves what they could be. Over a time of 3 or 4 days without food, a vision called the Weyekin (from the native language of the Nez Perce) would reveal itself. The Weyekin helps to center the young male into his world and lets him understand the correct position for him within the tribe and the environment around him. This tradition must have had a high level of mortality, but perhaps there is also some benefit to this culling and seasoning of young men.

Posted in Short Stories | Tagged | Leave a comment

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.

babies

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.

Posted in Science | Tagged , , | Leave a comment

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.

mouse

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.

baby

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.

kirk

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.

 

Posted in Drug Development, Genetics, Medicine, R&D, Science | Leave a comment

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.

Posted in Uncategorized | Leave a comment

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.

TwilightBeasts

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…

View original post 1,820 more words

Posted in Uncategorized | Leave a comment

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.

 

Posted in CaBRI, Science, Short Stories | Tagged | Leave a comment

Lineage-Enders

WaterMother

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).

BadParents

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.

ultra_nurturing

(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.

Posted in Environment, Genetics, Natural History, Science, Sperm donation | Tagged , , , , | Leave a comment

Of Mice and Men, and Cats and Women

 Wookie Bear

WookieeBeah

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

ant1

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.

ant6

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.

baby_cat_bugs

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.

Posted in Genetics, Natural History, Science | Leave a comment