The facility lies midway between Munichs city center and its international airport, roughly 23 miles to the north. From the outside, it still looks like the state-run farm it once was, but peer through the windows of the old farmhouse and youll see rooms stuffed with cutting-edge laboratory equipment.

In a newer building at the back of the farm, Barbara Kessler pulls off her sneakers and sprays her bare feet and hands with antiseptic. The wiry veterinarian steps over a taped line in the shower room, leaving behind everything she can from the outside world: clothes, watch, earrings. She scrubs her body and haira buzz cut, so its easier to manage these frequent washings.

After the shower, she finds her size among the neat stacks of supplied clothes and pulls on a pair of black pants, a red shirt, and black Crocs. Outside the dressing room, she adds a black knit cap to keep even her short-cropped hair from passing on germs, and then strides down the hall to the boot room, where she carefully steps into knee-high rubber boots that are power-washed after each wearing.

LAETITIA VANCON

All these precautions are to protect animals not known for their cleanliness: pigs. And once Kessler opens the door to the indoor pens, the smell is unmistakable. Its a pigsty, after all.

When Kessler unlocks one pen to show off its resident, a young sow wanders out and starts exploring. Like other pigs here, the sow is left nameless, so her caregivers wont get too attached. She has to be coaxed back behind a metal gate. To the untrained eye, she acts and looks like pretty much any other pig, but smaller.

Its whats inside this animal that matters. Her body has been made a little less pig-like, with four genetic modifications that make her organs more likely to be accepted when transplanted into a human. If all goes according to plan, the heart busily pumping inside a pig like this might one day beat instead inside a person.

Different types of tissues from genetically engineered pigs are already being tested in humans. In China, researchers have transplanted insulin-producing pancreatic islet cells from gene-edited pigs into people with diabetes. A team in South Korea says its ready to try transplanting pig corneas into people, once it gets government approval. And at Massachusetts General Hospital, researchers announced in October that they had used gene-edited pig skin as a temporary wound covering for a person with severe burns. The skin patch, they say, worked as effectively as human skin, which is much harder to obtain.

But when it comes to life-or-death organs, like hearts and livers, transplant surgeons still must rely on human parts. One day, the dream goes, genetically modified pigs like this sow will be sliced open, their hearts, kidneys, lungs and livers sped to transplant centers to save desperately sick patients from death.

Laetitia Vancon

The death of Baby Fae

Today in the United States, 7,300 people die each year because they cant find an organ donortwo-thirds of them for want of a kidney. In many cases, the only hope is someone elses tragedy: an accident that kills someone whose organs can be harvested.

Surgeons looking for another source of organs at first looked to monkeys, because theyre the animals most similar to us. In 1984, a little girl known as Baby Fae received a baboon heart but died 20 days later, after her immune system attacked it. Baby Faes short life and quick death received global attention; many condemned the idea of killing our closest animal relatives to save ourselves. An opinion piece by a cardiologist in the Washington Post described the procedure as medical adventurism. Another, in the Journal of Medical Ethics, was headlined Baby Fae: A beastly business.

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Then, in the 1990s, researchers and biotech companies turned to pigs as the donor of choice. Since we eat pigs (120 million of them a year in the US alone), taking their organs seemed less morally fraught to many. Scientifically, their organs are roughly the right size, with similar anatomy, and pigs reach adulthood in about six monthsmuch faster than primates. But a problem arose: pigs harbor viruses that might make the jump to people. Whats more, with the simple genetic engineering available at the time, the transplanted organs didnt last long when they were tested in monkeys. They were simply, genetically speaking, too foreign.

When it comes to life-or-death organs, like hearts and livers, transplant surgeons still must rely on human parts.

More than two decades later, advances in genetic engineering have revived the prospect of so-called xenotransplants. The hottest source of debate in the field: exactly how many gene edits are needed in pigs like these to overcome the species barrier. A well-funded US company, eGenesis, which leads the more-is-better-camp, says it has made a double-digit number of changes to the pigs it raises with a sister company in China.

The Germans at the Munich facility are in the less-is-more camp. The pigs they work with have three key genetic modifications originally made more than a decade agoall designed to keep baboons and humans from rejecting their organs. Knocking out a gene that produces a sugar called galactosyltransferase prevented the recipients immune system from immediately rejecting an organ from a different species. The second change added a gene expressing human CD46, a protein that helps the immune system attack foreign invaders without overreacting and causing autoimmune disease; the third introduced a gene for a protein called thrombomodulin, which prevents the blood clots that would otherwise destroy the transplanted organ.

A smaller number of edits can be better controlled and measured, and their effects are easier to document, says Eckhard Wolf, who runs this former state farm on the outskirts of Munich, now called the Center for Innovative Medical Models. If something goes wrong, as often happens in xenotransplantation, it will be clear where the issue lies. With more edits come more potential problems. At some point, you are in a situation that you have no idea what an additional genetic modification does, he says.

The size of a heart

In 2018, the hearts of pigs from the Munich center were transplanted into 14 baboons. Two of the monkeys survived for six months, the longest any animal has lived with a heart from another species. In a report in Nature last December, the German researchers described their achievement as a milestone on the way to clinical cardiac xenotransplantation.

Laetitia Vancon

Of the first five baboons to get a pig heart, four died within a day or two, and when the fifth died after a month, its heart was diseased. In the next batch of baboons, Wolfs collaborator Bruno Reichart, a retired heart transplant surgeon, flooded the organ with nutrients, hormones, and red blood cells from the time it was removed from the pig until it was fully functional in the recipient animal. Three baboons treated with this approach lived for 18, 27, and 40days.

The last five baboons had the same procedure but were also kept on an immunosuppressant drug. Two lived for 182 and 195 days, but they had to be euthanized last year when still in good health, because it was so challenging to continue the anti-rejection therapy.It isnt practical to leave an intravenous line in a baboon for longer than six months. But neither is it a simple thing to convince a baboon to take drugs. Like young children, they resist drinking anything that smells like medication.

Reichart says he is working on a better delivery system that will enable the baboons to stay on the anti-rejection drugs for at least a yearthe amount of time he says is needed to prove that xenotransplantation is ready to be tested in people.

Midway through their baboon study, however, Wolf and Reichart noticed an unanticipated problem: the hearts, harvested from juvenile pigs to make sure they were small enough for
baboons, kept on growing as if they were still destined to keep alive a 600-pound (270-kilogram) pig. The transplanted heart weighed 62% more than a typical baboon heart: massive cardiac overgrowth, as their paper described it. In the baboons, the new hearts crowded out other essential organs and, in a few cases, caused the animals death.

Laetitia Vancon

At the pig facility, Kessler showed me Wolfs solution to this problem: two sister sows, created with one more CRISPR gene edit. Researchers have turned off the animals growth hormone receptor(GHR) gene, leaving them roughly half the weight of a typical pig. Both tip the scales at about 175 pounds (79 kg),compared with nearly 400 pounds for a normal sow. The pregnant sister stood across the hall, alone in a pen facing the wall. Metal bars kept her from lying down against the wallsa precaution to protect the piglet litter. Though she was bred with a full-sized male pig, roughly half of her offspring should be missing their GHR gene.

The cost of saving a life

It isnt cheap to create a gene-edited pig and then raise it to the standard required by the US Food and Drug Administration and other agencies that would regulate pig-to-human transplants around the world. Kessler and her colleagues clone pig embryos by putting the desired genetic material into eggs collected Mondays and Tuesdays from a local slaughterhouse. To minimize germs, every new line of pigs must start by conceiving the animal in a lab dish, delivering it by Caesarean section, and separating it from its mother at birth. Later germ-free generations dont require as many precautions and cost only about 10 times the price of raising a pig for bacon and pork, Kessler says.

About 120 gene-edited adult pigs and 150 piglets live on this pig farm (one of only a handful worldwide), but even it cant afford to raise pigs to the standard that will be needed before an organ is transplanted into a person. Wolfs government grant wont cover the cost of HEPA filters to clean the air in every room of the pig facility, or to irradiate the special vegetarian feed pellets that are trucked in. The researchers lobbied for years for funding to build a perimeter fence to keep wild boarsand their germsoff the property.

LAETITIA VANCON

Reichart says he just needs funding to complete one more trial, keeping baboons alive for a full year with the pigs hearts, before hell be ready to test them in people. Other groups are also getting close. In Florida, transplant surgeon Joseph Tector, newly relocated to the University of Miami, says he just needs time to build a pig facility like Wolfs only stricter, and then hell be ready to test pig kidneys in people. The University of Alabama-Birmingham has a pig facility to support clinical transplants, with experts looking at both hearts and kidneys. Their first clinical trial of xenotransplantation might be in babies born with congenital heart malformations. A pig heart could serveas was hoped for Baby Faea bridge until they can receive a human heart.

Reichart says he doesnt need to be the first to successfully do a xenotransplant. But he believes hes likely to be among the first, since hes so close. After decades of research, the pigs in the Munich lab just might be the ones that allow surgeons to break the species barrier.

Read more here:
Meet the pigs that could solve the human organ transplant crisis - MIT Technology Review

October 31stwill mark the 37th anniversary of one of biotechnologys most significant milestones -- the approval by the FDA of human insulin synthesized in genetically engineered bacteria.It launched a revolutionary new era in pharmaceutical development, and as the FDA medical reviewer of the product and the head of the evaluation team, I had a front-row seat.

The saga is remarkable in several ways, not least of which is that although both the drugmakers and regulators were exploring unknown territory, the development of the drug and its regulatory review progressed smoothly and rapidly.

Insulin in crude form was first produced in 1922 by Canadian researchers Frederick Banting and Charles Best, which lifted the death sentence that had previously been imposed on diabetics. By the end of that year drug company, Eli Lilly and Company had devised a method for much higher purification. Over the next half-century or so, the purified insulins obtained from pig or cow pancreases, which differ slightly in chemical composition from human insulin, were constantly improved in purity and formulated in ways that refined their performance.

During the early 1970s, as the supply of animal pancreases declined and the prevalence of insulin-requiring diabetes grew, there were widespread fears of possible future shortages of insulin.Fortuitously, around the same time, a new and powerful tool recombinant DNA technology, also known as genetic modification, genetic engineering, or gene-splicing became available and offered the promise of unlimited amounts of insulin that was identical to the molecule produced by humans.

The seminal molecular genetic engineering experiment wasreported in a 1973 research articleby academic scientists Stanley Cohen, Herbert Boyer and their collaborators. They isolated a ringlet of DNA called a plasmid from a bacterium, used certain enzymes to splice a gene from another bacterium into that plasmid, and then introduced the resulting recombinant, or chimeric, DNA intoE. colibacteria.

When these now recombinant bacteria reproduced, the plasmids containing the foreign DNA were likewise propagated and produced amplified amounts of the functional recombinant DNA. And because DNA contains the genetic code that directs the synthesis of proteins, this new methodology promised the ability to induce genetically modified bacteria (or other cells) to synthesize desired proteins in large amounts.

The scientists at Lilly immediately saw the promise of this technology for the production of unlimited quantities of human insulin in bacteria. After obtaining from startup Genentech, Inc., the recombinantE. colibacteria that contained the genetic blueprint for and that synthesized human insulin, they developed processes for the large-scale cultivation of the organism (in huge fermenters similar to those that make wine or beer) and for the purification and formulation of the insulin.

Insulins had long been Lillys flagship products, and the companys expertise was evident in the purification, laboratory testing and clinical trials of human insulin. The companys scientists painstakingly verified that their product was extremely pure and identical to pancreatic human insulin (which differs slightly in chemical composition from beef and pork insulin).

Lilly began clinical trials of its human insulin in July 1980. The product performed superbly. There were no systematic problems with treating naive patients (who had never before received injections of insulin) or those switched from animal to human insulin. A small number of patients who had had adverse reactions of some kind to the animal insulins tolerated the human insulin well.

The dossier that provided evidence of safety and efficacy was submitted in May 1982 to the FDA, where I was the medical reviewer and head of the evaluation team. Over many years the FDA had had prodigious experience with insulins and also with drugs derived from various microorganisms, so it was decided that no fundamentally new regulatory paradigms were necessary to evaluate the recombinant human insulin.

In other words, recombinant DNA techniques were viewed as an extension, or refinement, of long-used and familiar methods for making drugs. That proved to be a historic, precedent-setting decision.

Based on my teams exhaustive review of Lillys data, which were obtained from pre-clinical testing in animals and clinical trials in thousands of diabetics, FDA granted marketing approval for human insulin in October 1982. The review and approval took only five months when the agencys average approval time for new drugs was 30.5 months.

In retrospect, that rapid approval was particularly remarkable for a drug that was produced with a revolutionary new technology, and that after approval would be available in pharmacies nationwide to millions of American diabetics.

The back story, however, is revealing. My team and I were ready to recommend approvalafterfour months review. But when I took the packet to my supervisor, he said, Four months? No way! If anything goes wrong with this product down the road, people will say we rushed it, and well be toast. Thats the bureaucratic mind-set. I dont know how long he would have delayed it, but when he went on vacation a month later, I took the packet to his boss, the division director, and he signed off.

That anecdote illustrates Milton Friedmans observation that to understand the motivation of an individual or organization, you need to follow the self-interest. A large part of regulators self-interest lies in staying out of trouble. One way to do that, my supervisor understood, is not to approve in record time products that might experience unanticipated problems, even if it is the right thing to do.

The Humulin approval had significant effects. A New York Timesarticlementioned my prediction that the speedy approval was a major step forward in the scientific and commercial viability of recombinant DNA technology. We have now come of age, I said, and potential investors and entrepreneurs agreed. Seeing that biopharmaceuticals would compete with other medicines on a level playing field, the biotechnology industry was on the fast track.

Scores of genetically engineered drugs have been approved over the years, but the rapidity of the human insulin approval proved to be an anomaly. Even with a toolbox of improved technologies available to both the FDA and industry, bringing a new drug to market on average now takes 10-12 years and costs, on average, over$2.5 billion.Regulators are highly risk-averse, few new drugs are approved without convening extramural advisory committees, and decisions are sometimes hijacked by political forces exerted on the FDA.

Other FDA-regulated biotech sectors have fared worse.Incomprehensibly, the FDAdeclined to grant Generally Recognized As Safe (GRAS) statusto two proteins that would be life-saving as additives to oral rehydration solution administered to children with diarrhea.

In addition, FDA officials have made a horrendousmessof the regulation of genetically engineered animals, which FDA chose to regulate as new animal drugs, including a grotesquely prolonged, 20-plus year review of a faster-growing Atlantic salmon, and genetically engineered mosquitoes to control mosquitoes that carry viral diseases.(It took FDA more than five years to realize that the latter were actually pesticides which are outside the Agencys purview -- and that jurisdiction should, therefore, be turfed to EPA.)As a result, the entire biotech sector of genetically engineered animals is moribund.

Its too bad that government regulation hasnt aged as gracefully as genetic engineering technology itself.

Original post:
Record-Time FDA Approval of Human Insulin In 1982: When Genetic Engineering Came of Age - American Council on Science and Health

When I started with Yuval Noah Hararis Homo Deus,I expected to jog along with a fun and clever assessment of human history and its near future as a cyborg-like merger of human and computer.

But I had trouble early on.

Dr. Harari repeatedly throws out a flurry of proclamations, often sweeping claims as arguments, then follows them with his intended conclusion, sometimes sweeping, head scratching and not always adding up. Then there are terms about which he seems to have a slightly skewed understanding.

I collided with his usage of Cognitive Revolution almost from the start. According to Harari, the "Cognitive Revolution" occurred 70,000 years ago causing the homo sapiens mind to shift, turning the species from an insignificant African ape into modern humans as ruler of the world. I looked for supportive context or attribution in the text, but it wasnt there. Nor was there any footnote for the claim.

I knew the term from a different context entirely. I Googled to be sure. "Cognitive Revolution" was the name of a 1950's multidisciplinary movement (now cognitive science) studying the mind and its workings. Noam Chomsky was one of the pioneers of the field.

I could find no reference about Hararis usage until I added Harari or Homo Deus to the search terms. Then I got hits on Homo Deus and "Sapiens" (his previous book, where The Cognitive Revolution is the title of the very first section of Sapiens). This is where Harari sets out his theory of sapiens cognition as a basis for the next brain change.

In Homo DeusHarari states, this revolution resulted from a few small changes in the Sapiens DNA and a slight rewiring of the Sapiens brains. another rewiring of our brain will suffice to launch a second cognitive revolution. Using, he continues, genetic engineering, nanotechnology and brain-computer interfaces.

I looked for further source information on Hararis claim. The best I came up with was an arguable theory about a population bottleneck some 70,000 to 60,000 years ago caused by an extinction when a volcano in Indonesia, Toba, erupted 74,000 years ago.

The theory, now mostly refuted, was that Tobas eruption lowered temperatures around the world wiping out many species, dropping the human population drastically.

Recent studies looking at sediment cores around the world for 100 years before and 200 years after Toba erupted, showed no signs of species die offs. Any effect was mild enough that it did not show up in the sediment layers.

Depending on the source, Homo Sapiens is believed to have emerged about 300,000 years ago (or even 400,000 years ago) and was in Europe at least by 200,000 years ago. A skull found in Greece was just dated to 210,000 years ago. Throw in speculation about big chills at 195,000 and 150,000 years ago and a possibility that humans dropped to as little as 40 people, or 600 people or a few thousand people or were always not that plentiful or came from a small group which left Africa at some time or other.

In East Asia, human remains in China have been dated to 100,000 years ago. In Japan, there is evidence of watercraft 84,000 years ago, in Honshu. Those early East-Asia dates argue against Hararis theory.

Harari doesnt tell us where he got the term. Did he hear it somewhere and misunderstand it, making assumptions? Could he have stumbled on Cognitive Revolution on his own? Fact checking at the publisher should have revealed this term in prior use. Nor could I find any reference by Harari referencing the 1950s movement of that name in either Sapiens or Homo Deus or elsewhere, including numerous videos.

The same doubt goes for assumptions about brain changes 70,000 years ago. What we have of skulls doesnt show a change in brain dimensions. Harari uses the brain-change at 70,000 years ago version of pre-history to bolster the viability of humans making the next change in our species.

There is very little we can say with certainty about our origins. That makes doubtful Hararis prediction that we are about to re-design our own species by attaching computing devices to our brains.

The real Cognitive Revolution:https://courses.lumenlearning.com/waymaker-psychology/chapter/reading-the-cognitive-revolution-and-multicultural-psychology/

A nice, brief synopsis of Homo Sapiens:https://australianmuseum.net.au/learn/science/human-evolution/homo-sapiens-modern-humans/

Revisiting and refuting a theory about an extinction at 74,000 years ago:https://www.smithsonianmag.com/smart-news/ancient-humans-weathered-toba-supervolcano-just-fine-180968479/

Concept of Behavioral Modernityhttps://en.wikipedia.org/wiki/Behavioral_modernity

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Radio Readers BookByte: Cognitive Revolution - HPPR

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Imagine designing the perfect device for the internet of things. What functions must it have? For a start, it must be able to communicate, both with other devices and with its human overlords. It must be able to store and process information. And it must monitor its environment with a range of sensors. Finally, it will need some kind of built-in motor.

There is no shortage of devices that have many of these features. Most are based on widely available, low-cost devices such as Raspberry Pis, Arduino boards, and the like.

But another set of machines with similar functions is much more plentiful, say Raphael Kim and Stefan Poslad at Queen Mary University of London in the UK. They point out that bacteria communicate effectively and have built-in engines and sensors, as well as powerful information storage and processing architecture.

And that raises an interesting possibility, they say. Why not use bacteria to create a biological version of the internet of things? Today, in a call to action, they lay out some of the thinking and the technologies that could make this possible.

The way bacteria store and process information is an emerging area of research, much of it focused on the bacterial workhorse Escherichia coli. These (and other) bacteria store information in ring-shaped DNA structures called plasmids, which they transmit from one organism to the next in a process called conjugation.

Last year, Federico Tavella at the University of Padua in Italy and colleagues built a circuit in which one strain of immotile E. coli transmitted a simple Hello world message to a motile strain, which carried the information to another location.

This kind of information transmission occurs all the time in the bacterial world, creating a fantastically complex network. But Tavella and cos proof-of-principle experiment shows how it can be exploited to create a kind of bio-internet, say Kim and Poslad.

E. coli make a perfect medium for this network. They are motilethey have a built-in engine in the form of waving, thread-like appendages called flagella, which generate thrust. They have receptors in their cell walls that sense aspects of their environmenttemperature, light, chemicals, etc. They store information in DNA and process it using ribosomes. And they are tiny, allowing them to exist in environments that human-made technologies have trouble accessing.

E. coli are relatively easy to manipulate and engineer as well. The grassroots movement of DIY biology is making biotechnology tools cheaper and more easily available. The Amino Lab, for example, is a genetic engineering kit for schoolchildren, allowing them to reprogram E. coli to glow in the dark, among other things.

This kind of biohacking is becoming relatively common and shows the remarkable potential of a bio-internet of things. Kim and Poslad talk about a wide range of possibilities. Bacteria could be programmed and deployed in different surroundings, such as the sea and smart cities, to sense for toxins and pollutants, gather data, and undertake bioremediation processes, they say.

Bacteria could even be reprogrammed to treat diseases. Harbouring DNA that encode useful hormones, for instance, the bacteria can swim to a chosen destination within the human body, [and] produce and release the hormones when triggered by the microbes internal sensor, they suggest.

Of course, there are various downsides. While genetic engineering makes possible all kinds of amusing experiments, darker possibilities give biosecurity experts sleepless nights. Its not hard to imagine bacteria acting as vectors for various nasty diseases, for example.

Its also easy to lose bacteria. One thing they do not have is the equivalent of GPS. So tracking them is hard. Indeed, it can be almost impossible to track the information they transmit once it is released into the wild.

And therein lies one of the problems with a biological internet of things. The conventional internet is a way of starting with a message at one point in space and re-creating it at another point chosen by the sender. It allows humans, and increasingly devices, to communicate with each other across the planet.

Kim and Poslads bio-internet, on the other hand, offers a way of creating and releasing a message but little in the way of controlling where it ends up. The bionetwork created by bacterial conjugation is so mind-bogglingly vast that information can spread more or less anywhere. Biologists have observed the process of conjugation transferring genetic material from bacteria to yeast, to plants, and even to mammalian cells.

Evolution plays a role too. All living things are subject to its forces. No matter how benign a bacterium might seem, the process of evolution can wreak havoc via mutation and selection, with outcomes that are impossible to predict.

Then there is the problem of bad actors influencing this network. The conventional internet has attracted more than its fair share of individuals who release malware for nefarious purposes. The interest they might have in a biological internet of things is the stuff of nightmares.

Kim and Poslad acknowledge some of these issues, saying that creating a bacteria-based network presents fresh ethical issues. Such challenges offer a rich area for discussion on the wider implication of bacteria driven Internet of Things systems, they conclude with some understatement.

Thats a discussion worth having sooner rather than later.

Ref: arxiv.org/abs/1910.01974 : The Thing with E. coli: Highlighting Opportunities and Challenges of Integrating Bacteria in IoT and HCI

The rest is here:
The scientists who are creating a bio-internet of things - MIT Technology Review

The human body is more than flesh and blood it bears cultural values and tales of morality. Swirling around todays bodies are important discussions about transgender rights, ableism, genetic engineering and body positivity. We can trace how ideal and atypical bodies are shown in advertising, movies and art, helping us understand shifting norms and persistent biases.

A bounteous art exhibition on display through Jan. 26 at the Seattle Art Museum offers powerful visions of how the body was represented and what it conveyed centuries ago in Italy. Flesh and Blood: Italian Masterpieces from the Capodimonte Museum really does boast masterpieces 39 beautifully crafted Renaissance and Baroque paintings (and one sculpture) by artists who were acknowledged masters in their time: Titian, Raphael, El Greco and many others. Not all of the artists were Italian but they all created work for Italian patrons. SAM curator Chiyo Ishikawa and her collaborators selected these works from the Capodimonte in Naples, the second-largest museum in Italy.

There is one female artist in the show: the incomparable Artemisia Gentileschi, who defied the customs of her day to become a professional artist. She painted several versions of Judith, a Jewish widow, in the act of killing Holofernes, an Assyrian general who besieged Judiths town. This early version is gorgeous and gruesome. Judiths strong arms cut across the canvas much like the sword she works against the generals throat. Someone long ago trimmed the canvas, leaving us with a tightly cropped revelation of female fortitude and righteousness. Gentileschis approach may have been shaped by her own experience the young artist painted this work just a few years after she was raped, in her home, by her art teacher.

Another painting hints at the relationship between gender and power, but with more mystery. Parmigianinos intriguing painting of an unknown woman includes the hallmarks of a marriageable young woman: She is elegantly dressed, revealing a tasteful amount of unblemished skin. This kind of portrait often signaled the acceptance of a suitors gifts (see: the jewelry and textiles shown in the painting), thereby entering a betrothal. But Ishikawa states that this was likely not a specific portrait and, instead, more of a symbolic representation of an ideal woman. I wonder how more typical signs of femininity would have been reconciled with the controlled forcefulness of her look, the bulk of her garments and the fierce teeth of the weasel-like marten, whose fur she wears.

Most of the other female-focused paintings in the exhibition are more conventional for their time, providing visions of maternal or spiritual devotion, sexual availability, chaste beauty or some odd combination thereof.

In Titians Dana, the title figure a mythological Greek princess lies naked on a bed, fully displayed for the viewers pleasure, while the god Zeus visits (in order to impregnate her), disguised as a shower of gold coins. The man who commissioned the work, Cardinal Alessandro Farnese, kept the large painting hidden behind a curtain, underscoring the works erotic intentions.

Male bodies, both dressed and naked, are exhibited as well, carrying connotations that range from divinity to gluttony. An altarpiece entitled Piet by Annibale Carracci shows the corpse of Jesus on his mothers lap. The thin, contorted torso, which has clearly suffered, and the lifeless hand, rendered in greenish grays, expose the mortal humanity of this divine figure.

Two stunning works by Jusepe de Ribera also use the male physique strategically. In a huge altarpiece, dramatic lighting calls attention to the sagging, wrinkled skin of St. Jerome, an early Christian ascetic who practiced penitential acts of self-deprivation and self-harm. The artist used feathery brush strokes on top of thicker layers of paint, hinting at how paint covers a canvas like skin, and reminding the faithful of the impermanence of an earthly body.

Riberas Drunken Silenus, on the other hand, is all about excess. Silenus, a companion of Dionysus, the Greek god of wine, sprawls across the canvas with a brightly lit, barrel-like belly and a cup raised for a refill. His corpulent body is painted with ruddy and dingy highlights, linking unethical (or at least undisciplined) behavior with an unkempt body. His pose deliberately refers to the reclining-female-nude motif, suggesting his state of unmasculinity or impotence.

A standout painting by Agostino Carracci underscores old biases against bodies that would have been considered atypical. This commissioned portrait depicts members of a sort of entertainment troupe employed by Cardinal Odoardo Farnese. A dwarf named Tiny Amon looks toward Hairy Harry, a man with a condition that causes excessive hair growth. Its an almost unthinkable outlook today, but these men were seen as curiosities, collected for the amusement of the court. Their role is accentuated by the loyal dogs, exotic bird and monkeys that surround them.

After gorging on all this bodily symbolism, its a relief to enter the last gallery of the exhibition, with its wonderful still-life paintings. Ishikawa posits that, unlike the still lifes of Northern Europe, which often used food and flowers to hint at the transience of earthly pleasures, these are simply about the abundance of the region. It is true that the bouquets are not wilting and that there arent human skulls or hourglasses inserted into the compositions. And yet, the slashing blood on a goats head and the sharp knife balanced precariously on the edge of a table seem to warn of the vulnerability of the flesh.

Throughout the exhibition, we are reminded of how art much like a pitcher of wine or a human body within the paintings is a vessel for meaning and message. Gender, race, class, age, ability and size play roles in communicating these meanings, in ways that feel historically remote, intimately resonant or disappointingly familiar.

Old tropes continue today. The 2016 Report on the Status of Women and Girls inCaliforniastated that women appear nude (or partially nude) in films three times more frequently than men do. Standards of female beauty and sizing are still mostly based on young, tall and thinner-than-average bodies.

But there is an increasing spectrum of body types and messages in various images these days, mirroring slow shifts in attitudes toward gender, sex and beauty. Change will persevere as the producers of culture artists, actors, directors, writers increasingly emerge from within the diversity of the population. In fits and spurts, in art, entertainment and social media, we may see new forms of how the body is represented, and what it conveys.

_____

Flesh and Blood: Italian Masterpieces from the Capodimonte Museum, through Jan. 26, 2020; Seattle Art Museum, 1300 First Ave; $29.99 adult, $27.99 senior, $19.99 student, free for SAM members and children 14 and under; first Thursday reduced-ticket prices;seattleartmuseum.org

Gayle Clemans is an art critic, art historian and novelist; connect with her on Twitter and Instagram @gayleclemans.

See the rest here:
SAMs Flesh and Blood exhibit depicts desire, violence and more using the artistic vessel of the human body - Seattle Times

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New Clues as to Why Mutations in the MYH9 Gene Cause Broad Spectrum of Disorders in Humans

Researchers use in vivo imaging to watch how cells move and generate forces inside living tissues, study sheds new light on how motor proteins generate forces inside living tissues and how genetic factors alter these forces to result in disease

Newswise New York, NYOctober 28, 2019Myosins are motor proteins that convert chemical energy into mechanical work, generating force and movement. Myosin II generates forces that are essential to drive cell movements and cell shape changes that generate tissue structure. While researchers know that mutations in the genes that encode nonmuscle myosin II lead to diseases, including severe congenital defects as well as blood platelet dysfunction, nephritis, and deafness in adults, they do not fully understand the mechanisms that translate altered myosin activity into specific changes in tissue organization and physiology.

A team of researchers led by Karen Kasza, Clare Boothe Luce Assistant Professor of Mechanical Engineering, used the Drosophila embryo to model human disease mutations that affect myosin motor activity. Through in vivo imaging and biophysical analysis, they demonstrated that engineering human MYH9-related disease mutations into Drosophila myosin II produces motors with altered organization and dynamics that fail to drive rapid cell movements, resulting in defects in epithelial morphogenesis. The studythe first to demonstrate that these mutations result in slower cell movements in vivowas published October 15, 2019, by PNAS.

Its not currently possible to watch what happens at the cell level when these genes are mutated in humans, and its still really difficult to do this in mammalian model organisms like mice, says Kasza, the studys lead author who began the research as a postdoctoral fellow at the Sloan Kettering Institute and continued it when she joined Columbia Engineering in 2016.

Because there are so many similarities between the myosin II protein in humans and in fruit flies, Kaszas approach was to start by tackling how to watch the effects of myosin II mutations in fruit flies. Her group engineered the human disease mutations into fruit fly myosin and then observed how this affected the behaviors of the proteins, cells, and tissues in the organism.

They used high-resolution confocal fluorescence imaging to take movies of the process, together with biophysical approaches such as laser ablation, or laser nano-dissection, to measure the forces generated by the mutated myosin II motor proteins in vivo.

Kasza found that, while the mutated myosin II motor proteins actually went to the proper places inside cells and were able to generate force, the fine-scale organization of the myosin proteins and the speed of their movement inside cells were different than for the normal wild-type myosin protein. The team saw slower movements of cells within tissues that brought about abnormalities in embryo shape during development.

By watching how cells move and generate forces inside living tissues, weve uncovered new clues as to why mutations in theMYH9gene cause a broad spectrum of disorders in humans. Kasza observes. Our work sheds new light on how motor proteins generate forces inside living tissues and on how genetic factors alterthese forces to result in disease. This mechanistic understanding will help us better understand these diseases and could lead to new diagnostic or therapeutic strategies down the road.

The researchers are now working on new approaches to very precisely manipulate the forces generated by myosin motors inside living cells and tissues. These new tools will help the team to uncover how mechanical forces influence biochemical processes that control cell movements and cell fate. These studies will be essential to better understanding how dysregulation of mechanical forces contributes to disease.

About the Study

The study is titled Cellular defects resulting from disease-related myosin II mutations in Drosophila.

Authors are: Karen E. Kasza1,2,; Sara Supriyatno1; and Jennifer A. Zallen1.1Howard Hughes Medical Institute and Developmental Biology Program, Sloan Kettering Institute;2Department of Mechanical Engineering, Columbia Engineering.

The study was supported by NIH/NIGMS R01 grant GM102803 to JAZ. KEK holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, a Clare Boothe Luce Professorship, and a Packard Fellowship.JAZ is an investigator of the HowardHughes Medical Institute.

The authors declare no financial or other conflicts of interest.

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LINKS:

Paper: https://doi.org/10.1073/pnas.1909227116 DOI: 10.1073/pnas.1909227116https://www.pnas.org/http://engineering.columbia.edu/https://engineering.columbia.edu/faculty/karen-kaszahttps://me.columbia.edu/

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Columbia EngineeringColumbia Engineering, based in New York City, is one of the top engineering schools in the U.S. and one of the oldest in the nation. Also known as The Fu Foundation School of Engineering and Applied Science, the School expands knowledge and advances technology through the pioneering research of its more than 220 faculty, while educating undergraduate and graduate students in a collaborative environment to become leaders informed by a firm foundation in engineering. The Schools faculty are at the center of the Universitys cross-disciplinary research, contributing to the Data Science Institute, Earth Institute, Zuckerman Mind Brain Behavior Institute, Precision Medicine Initiative, and the Columbia Nano Initiative. Guided by its strategic vision, Columbia Engineering for Humanity, the School aims to translate ideas into innovations that foster a sustainable, healthy, secure, connected, and creative humanity.

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New Clues as to Why Mutations in the MYH9 Gene Cause a Broad Spectrum of Disorders in Humans - Newswise

The Shed explores the impact of technology on our lives in Manual Override, a group exhibition that will include six works, four of which are newly commissioned. On view in The Shed's Griffin Theater from November 13, 2019 through January 12, 2020, the exhibition features work by Morehshin Allahyari, Simon Fujiwara, Lynn Hershman Leeson, Sondra Perry, and Martine Syms. Manual Override is organized by critic Nora N. Khan, The Shed's first guest curator, with Alessandra Gomez, curatorial assistant.

Manual Override features artists who critique the social, cultural, and ethical issues embedded in emerging technological systems and infrastructures ranging from mass surveillance to predictive policing. Central to the exhibition is the idea of a manual override, or human interference in an automated system, a gesture in response to an error in programming, or poor judgment in design. "How do you pause a system you can't see, touch, or access? As these systems become increasingly oppressive and beyond our understanding, and management, what options do we have?" asks Nora Khan. In response, each artist posits new forms of "overriding" to subvert the values of invasive technological systems. They do so through building networks of artistic collaboration across scientific and technological fields, including genetic engineering, simulation design, machine learning, and experimental computation.

For decades, pioneering artist and filmmaker Lynn Hershman Leeson has been working with scientists, geneticists, and engineers to explore the impact of technological progress on our understanding of the self. Hershman Leeson premieres the final episode in her seminal video series, The Electronic Diaries (1984-2019), and the new Shed commission, Shadow Stalker (2019). A new generation of artists-Morehshin Allahyari, Sondra Perry, Simon Fujiwara, and Martine Syms-have developed research practices that echo Hershman Leeson's hybrid collaborative model, which serves as the conceptual foundation for Manual Override.

"Manual Override challenges us to think in new ways about the ever-growing role and effect of technology in our lives," said Alex Poots, Artistic Director and CEO of The Shed. "Inspired by the groundbreaking work of Lynn Hershman Leeson, whose vision continues to influence generations of artists, our guest curator Nora Khan's exhibition explores the intersection between art, science, technology, psychology, and sociology in contemporary life. An important part of Manual Override is the range of new commissions that enable featured artists to realize their ambitious vision."

For more information visit: https://theshed.org/program/63-manual-override?sourceNumber=&utm_campaign=PressRelease%3AManualOverride&utm_content=version_A&utm_medium=email&utm_source=wordfly

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The Shed Will Present New Exhibition 'Manual Override' - Broadway World

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The next generation of wireless cellular, called 5G, has started to roll out across the US, delivering speeds orders of magnitude faster than the 4G networks in use today.

For consumers, that means better video playback on mobile devices, but for businesses, 5G is expected to enable all manner of connected devices to work together more efficiently from connected cars to factory automation to smart buildings.

Joseph Cortese, associate director at the cybersecurity firm A-LIGN, said that will be a good thing.

"We will see a rush of businesses attempting to be the first-to-market with 5G enabled devices," Cortese said. "This will lead to an enormous swell in the size of the Internet of Things, with thousands of new devices joining the network." The Internet of Things is the name given to networks of connected devices in homes, business, and across cities.

But Cortese also said we need to be prepared for cyberattacks, which reliance on 5G could make unimaginably worse.

"Distributed denial of service attacks have the potential to quickly overload 5G networks and impact critical services. In the past, DDoS attacks have troubled services like Netflix and Airbnb, but in the future, the Internet of Things will be used for things like directing traffic patterns and providing emergency services workers with critical information."

In such an attack, large parts of a city's infrastructure will be rendered useless. In a smart city that depends on the Internet of Things, operations would be brought to a halt.

Cortese said, "Even a simple attack has the potential to cripple a smart city that relies on 5G networks to function."

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Scientists reveal the 13 dark technology scenarios that keep them up at night - Business Insider