Category Archives: Human Genetic Engineering

She just wanted to be somewhere safe, somewhere familiar, where people looked and spoke like her and she could stand to eat the food. Midnight Robber by Nalo Hopkinson

Midnight Robber (2000) is about a woman, divided. Raised on the high-tech utopian planet of Touissant, Tan-Tan grows up on a planet populated by the descendants of a Caribbean diaspora, where all labor is performed by an all-seeing AI. But when she is exiled to Touissants parallel universe twin planet, the no-tech New Half-Way Tree, with her sexually abusive father, she becomes divided between good and evil Tan-Tans. To make herself and New Half-Way Tree whole, she adopts the persona of the legendary Robber Queen and becomes a legend herself. It is a wondrous blend of science fictional tropes and Caribbean mythology written in a Caribbean vernacular which vividly recalls the history of slavery and imperialism that shaped Touissant and its people, published at a time when diverse voices and perspectives within science fiction were blossoming.

Science fiction has long been dominated by white, Western perspectives. Vernes tech-forward adventures and Wells sociological allegories established two distinctive styles, but still centered on white imperialism and class struggle. Subsequent futures depicted in Verne-like pulp and Golden Age stories, where lone white heroes conquered evil powers or alien planets, mirrored colonialist history and the subjugation of non-white races. The civil rights era saw the incorporation of more Wellsian sociological concerns, and an increase in the number of non-white faces in the future, but they were often tokensparts of a dominant white monoculture. Important figures that presaged modern diversity included Star Treks Lieutenant Uhura, played by Nichelle Nichols. Nichols was the first black woman to play a non-servant character on TV; though her glorified secretary role frustrated Nichols, her presence was a political act, showing there was space for black people in the future.

Another key figure was the musician and poet Sun Ra, who laid the aesthetic foundation for what would become known as the Afrofuturist movement (the term coined by Mark Dery in a 1994 essay), which showed pride in black history and imagined the future through a black cultural lens. Within science fiction, the foundational work of Samuel Delany and Octavia Butler painted realistic futures in which the histories and cultural differences of people of color had a place. Finally, an important modern figure in the decentralization of the dominant Western perspective is Nalo Hopkinson.

A similarly long-standing paradigm lies at the heart of biology, extending back to Darwins theoretical and Mendels practical frameworks for the evolution of genetic traits via natural selection. Our natures werent determined by experience, as Lamarck posited, but by genes. Therefore, genes determine our reproductive fitness, and if we can understand genes, we might take our futures into our own hands to better treat disease and ease human suffering. This theory was tragically over-applied, even by Darwin, who in Descent of Man (1871) conflated culture with biology, assuming the Wests conquest of indigenous cultures meant white people were genetically superior. After the Nazis committed genocide in the name of an all-white future, ideas and practices based in eugenics declined, as biological understanding of genes matured. The Central Dogma of the 60s maintained the idea of a mechanistic meaning of life, as advances in genetic engineering and the age of genomics enabled our greatest understanding yet of how genes and disease work. The last major barrier between us and our transhumanist future therefore involved understanding how genes determine cellular identity, and as well see, key figures in answering that question are stem cells.

***

Hopkinson was born December 20, 1960 in Kingston, Jamaica. Her mother was a library technician and her father wrote, taught, and acted. Growing up, Hopkinson was immersed in the Caribbean literary scene, fed on a steady diet of theater, dance, readings, and visual arts exhibitions. She loved to readfrom folklore, to classical literature, to Kurt Vonnegutand loved science fiction, from Spock and Uhura on Star Trek, to Le Guin, James Tiptree Jr., and Delany. Despite being surrounded by a vibrant writing community, it didnt occur to her to become a writer herself. What they were writing was poetry and mimetic fiction, Hopkinson said, whereas I was reading science fiction and fantasy. It wasnt until I was 16 and stumbled upon an anthology of stories written at the Clarion Science Fiction Workshop that I realized there were places where you could be taught how to write fiction. Growing up, her family moved often, from Jamaica to Guyana to Trinidad and back, but in 1977, they moved to Toronto to get treatment for her fathers chronic kidney disease, and Hopkinson suddenly became a minority, thousands of miles from home.

Development can be described as an orderly alienation. In mammals, zygotes divide and subsets of cells become functionally specialized into, say, neurons or liver cells. Following the discovery of DNA as the genetic material in the 1950s, a question arose: did dividing cells retain all genes from the zygote, or were genes lost as it specialized? British embryologist John Gurdon addressed this question in a series of experiments in the 60s using frogs. Gurdon transplanted nuclei from varyingly differentiated cells into oocytes stripped of their genetic material to see if a new frog was made. He found the more differentiated a cell was, the lower the chance of success, but the successes confirmed that no genetic material was lost. Meanwhile, Canadian biologists Ernest McCulloch and James Till were transplanting bone marrow to treat irradiated mice when they noticed it caused lumps in the mices spleens, and the number of lumps correlated with the cellular dosage. Their lab subsequently demonstrated that each lump was a clonal colony from a single donor cell, and a subset of those cells was self-renewing and could form further colonies of any blood cell type. They had discovered hematopoietic stem cells. In 1981 the first embryonic stem cells (ESCs) from mice were successfully propagated in culture by British biologist Martin Evans, winning him the Nobel Prize in 2007. This breakthrough allowed biologists to alter genes in ESCs, then use Gurdons technique to create transgenic mice with that alteration in every cellcreating the first animal models of disease.

In 1982, one year after Evans discovery, Hopkinson graduated with honors from York University. She worked in the arts, as a library clerk, government culture research officer, and grants officer for the Toronto Arts Council, but wouldnt begin publishing her own fiction until she was 34. [I had been] politicized by feminist and Caribbean literature into valuing writing that spoke of particular cultural experiences of living under colonialism/patriarchy, and also of writing in ones own vernacular speech, Hopkinson said. In other words, I had models for strong fiction, and I knew intimately the body of work to which I would be responding. Then I discovered that Delany was a black man, which opened up a space for me in SF/F that I hadnt known I needed. She sought out more science fiction by black authors and found Butler, Charles Saunders, and Steven Barnes. Then the famous feminist science fiction author and editor Judy Merril offered an evening course in writing science fiction through a Toronto college, Hopkinson said. The course never ran, but it prompted me to write my first adult attempt at a science fiction story. Judy met once with the handful of us she would have accepted into the course and showed us how to run our own writing workshop without her. Hopkinsons dream of attending Clarion came true in 1995, with Delany as an instructor. Her early short stories channeled her love of myth and folklore, and her first book, written in Caribbean dialect, married Caribbean myth to the science fictional trappings of black market organ harvesting. Brown Girl in the Ring (1998) follows a young single mother as shes torn between her ancestral culture and modern life in a post-economic collapse Toronto. It won the Aspect and Locus Awards for Best First Novel, and Hopkinson was awarded the John W. Campbell Award for Best New Writer.

In 1996, Dolly the Sheep was created using Gurdons technique to determine if mammalian cells also could revert to more a more primitive, pluripotent state. Widespread animal cloning attempts soon followed, (something Hopkinson used as a science fictional element in Brown Girl) but it was inefficient, and often produced abnormal animals. Ideas of human cloning captured the public imagination as stem cell research exploded onto the scene. One ready source for human ESC (hESC) materials was from embryos which would otherwise be destroyed following in vitro fertilization (IVF) but the U.S. passed the Dickey-Wicker Amendment prohibited federal funding of research that destroyed such embryos. Nevertheless, in 1998 Wisconsin researcher James Thomson, using private funding, successfully isolated and cultured hESCs. Soon after, researchers around the world figured out how to nudge cells down different lineages, with ideas that transplant rejection and genetic disease would soon become things of the past, sliding neatly into the hole that the failure of genetic engineering techniques had left behind. But another blow to the stem cell research community came in 2001, when President Bushs stem cell ban limited research in the U.S. to nineteen existing cell lines.

In the late 1990s, another piece of technology capturing the public imagination was the internet, which promised to bring the world together in unprecedented ways. One such way was through private listservs, the kind used by writer and academic Alondra Nelson to create a space for students and artists to explore Afrofuturist ideas about technology, space, freedom, culture and art with science fiction at the center. It was wonderful, Hopkinson said. It gave me a place to talk and debate with like-minded people about the conjunction of blackness and science fiction without being shouted down by white men or having to teach Racism 101. Connections create communities, which in turn create movements, and in 1999, Delanys essay, Racism and Science Fiction, prompted a call for more meaningful discussions around race in the SF community. In response, Hopkinson became a co-founder of the Carl Brandon society, which works to increase awareness and representation of people of color in the community.

Hopkinsons second novel, Robber, was a breakthrough success and was nominated for Hugo, Nebula, and Tiptree Awards. She would also release Skin Folk (2001), a collection of stories in which mythical figures of West African and Afro-Caribbean culture walk among us, which would win the World Fantasy Award and was selected as one ofThe New York Times Best Books of the Year. Hopkinson also obtained masters degree in fiction writing (which helped alleviate U.S. border hassles when traveling for speaking engagements) during which she wrote The Salt Roads (2003). I knew it would take a level of research, focus and concentration I was struggling to maintain, Hopkinson said. I figured it would help to have a mentor to coach me through it. That turned out to be James Morrow, and he did so admirably. Roads is a masterful work of slipstream literary fantasy that follows the lives of women scattered through time, bound together by the salt uniting all black life. It was nominated for a Nebula and won the Gaylactic Spectrum Award. Hopkinson also edited anthologies centering around different cultures and perspectives, including Whispers from the Cotton Tree Root: Caribbean Fabulist Fiction (2000), Mojo: Conjure Stories (2003), and So Long, Been Dreaming: Postcolonial Science Fiction & Fantasy (2004). She also came out with the award-winning novelThe New Moons Arms in 2007, in which a peri-menopausal woman in a fictional Caribbean town is confronted by her past and the changes she must make to keep her family in her life.

While the stem cell ban hamstrung hESC work, Gurdons research facilitated yet another scientific breakthrough. Researchers began untangling how gene expression changed as stem cells differentiated, and in 2006, Shinya Yamanaka of Kyoto University reported the successful creation of mouse stem cells from differentiated cells. Using a list of 24 pluripotency-associated genes, Yamanaka systematically tested different gene combinations on terminally differentiated cells. He found four genesthereafter known as Yamanaka factorsthat could turn them into induced-pluripotent stem cells (iPSCs), and he and Gurdon would share a 2012 Nobel prize. In 2009, President Obama lifted restrictions on hESC research, and the first clinical trial involving products made using stem cells happened that year. The first human trials using hESCs to treat spinal injuries happened in 2014, and the first iPSC clinical trials for blindness began this past December.

Hopkinson, too, encountered complications and delays at points in her career. For years, Hopkinson suffered escalating symptoms from fibromyalgia, a chronic disease that runs in her family, which interfered with her writing, causing Hopkinson and her partner to struggle with poverty and homelessness. But in 2011, Hopkinson applied to become a professor of Creative Writing at the University of California, Riverside. It seemed in many ways tailor-made for me, Hopkinson said. They specifically wanted a science fiction writer (unheard of in North American Creative Writing departments); they wanted someone with expertise working with a diverse range of people; they were willing to hire someone without a PhD, if their publications were sufficient; they were offering the security of tenure. She got the job, and thanks to a steady paycheck and the benefits of the mild California climate, she got back to writing. Her YA novel, The Chaos (2012), coming-of-age novelSister Mine (2013), and another short story collection, Falling in Love with Hominids (2015) soon followed. Her recent work includes House of Whispers (2018-present), a series in DC Comics Sandman Universe, the final collected volume of which is due out this June. Hopkinson also received an honorary doctorate in 2016 from Anglia Ruskin University in the U.K., and was Guest of Honor at 2017 Worldcon, a year in which women and people of color dominated the historically white, male ballot.

While the Yamanaka factors meant that iPSCs became a standard lab technique, iPSCs are not identical to hESCs. Fascinatingly, two of these factors act together to maintain the silencing of large swaths of DNA. Back in the 1980s, researchers discovered that some regions of DNA are modified by small methyl groups, which can be passed down through cell division. Different cell types have different DNA methylation patterns, and their distribution is far from random; they accumulate in the promoter regions just upstream of genes where their on/off switches are, and the greater the number of methyl groups, the lesser the genes expression. Furthermore, epigenetic modifications, like methylation, can be laid down by our environments (via diet, or stress) which can also be passed down through generations. Even some diseases, like fibromyalgia, have recently been implicated as such an epigenetic disease. Turns out that the long-standing biological paradigm that rejected Lamarck also missed the bigger picture: Nature is, in fact, intimately informed by nurture and environment.

In the past 150 years, we have seen ideas of community grow and expand as the world became more connected, so that they now encompass the globe. The histories of science fiction and biology are full of stories of pioneers opening new doorsbe they doors of greater representation or greater understanding, or bothand others following. If evolution has taught us anything, its that nature abhors a monoculture, and the universe tends towards diversification; healthy communities are ones which understand that we are not apart from the world, but of it, and that diversity of types, be they cells or perspectives, is a strength.

Kelly Lagor is a scientist by day and a science fiction writer by night. Her work has appeared at Tor.com and other places, and you can find her tweeting about all kinds of nonsense @klagor

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On the Origins of Modern Biology and the Fantastic: Part 19 Nalo Hopkinson and Stem Cell Research - tor.com

Drawing by Nathaniel St. Clair

Growing up in a village

I was born in a Greek village where land and food self-sufficiency were everything. My father had a few strips of land where he raised enough food for his family and the family of his brother who lost his life during the war years of the 1940s. My father cultivated wheat, barley, lentils, vine grapes for wine, and olive trees for oil.

Animals made our lives possible and easier. We had a mule, a donkey, goats, sheep, chickens, dogs and cats.

I learned to respect and love these animals. I could not conceive life without them.

My most interesting agrarian memory comes from our harvesting of grapes during the heat of Summer in late August. My sisters and cousins would fill wicker baskets with ripe bunches of white, blue and red grapes, load them on the donkey, and my younger cousin, George, and I would take them home. We would unload the baskets and pour the grapes into the linos, a rectangular stone and cement enclosure a meter high with a cement bottom. One of the stone walls of the linos had a hole that allowed the liquid wine to drain to a small cement pit below.

After filling the linos with the ripe and tasty fruits of Dionysos, George and I washed our legs and entered the soft hills of grapes, which we treaded to pulp while laughing and having fun.

In America

At age eighteen I left the village for America where I discovered the beauty and pleasures of Greek civilization and much, much more. This happened slowly.

Like other young Greeks and most foreign students from many countries, I saw America as a land of opportunity for those with technical knowledge and skills. This pushed my love for the Greek classics to the back recesses of my mind. In 1961, when I arrived in America, I simply wanted some education that would enable me to earn a good living. I had a vague notion of a good life.

However, my education in zoology and Greek history and the history of science and my work on Capitol Hill and the US Environmental Protection Agency brought me face to face with modernity and I did not like it. I could not stand looking at skyscrapers and cringed at seeing gigantic tractors crushing the land. I had the feeling I had to turn to classical thought. If I were to survive the hubris and crimes of technicians armed to the teeth, I would have to have the support of my ancestors.

I read Pythagorean writings with great interest. Pythagoras was a sixth century BCE philosopher of heavens and Earth. He said number was the constituent of everything in the cosmos. He thought music and songs had a healing and educational effect, invigorating humans with inner harmony. He even said he heard the music of the spherical planets moving around the Sun, which he equated to a large fire at the center of the cosmos. He called that firethe House of Zeus. He was in love with animals and life. He was against destroying or eating any living thing, animals in particular. He was certain there was a brotherhood between humans and animals. He urged the Greeks to stop eating meat and never sacrifice animals to the gods.

I read Xenophon, an Athenian military man and historian who flourished in the first half of fourth century BCE. I agreed with his theory and conviction that agriculture was a school for courage, freedom, military training, and the raising of food and civilization.

Then the fourth century BCE philosopher Aristotle came into my life like a breath of fresh air. In contrast to the dry and uninspiring classes I took while studying zoology at the University of Illinois, the writings of Aristotle brought me in touch with the roots of zoology. His works on animals, especially hisHistory of Animals,lifted me to heavens. They were insightful, riveting, enormously important, and pioneering. They explained to me the origins, complexity, and beauty of the animal kingdom, the perfection of nature, and the meaning and importance of the science of zoology, which Aristotle invented.

At work

I cannot say these Hellenic scientific and philosophical insights blended nicely with my life. After a couple of years on Capitol Hill, in 1979, I started working for the US Environmental Protection Agency. For the first time, I began to grasp what America was all about.

I was so embarrassed the United States had fallen so low: pretending its scientists at the EPA and other agencies like the US Department of Agriculture could employ science in the regulation of the abominable chemical weapons it called pesticides. Those deleterious chemicals kill more than unwanted insects and weeds. They kill all life. They should have never reached agriculture, a political, cultural and scientific process of raising food and civilization.

I was confused, and not a little concerned about this gigantic country I had chosen as my second home.

Decoding scientific research

Unable to influence or change policy, I turned to research and writing. Scientists often publish important work. But to protect themselves, they garble their stories and publish them in obscure journals read by few people.

I tracked down dozens of those stories, which I decoded and merged with the highlights of the stories I heard from my EPA colleagues, who also gave me their memos and briefings. In addition, I met a few outstanding scientists who answered my questions: about pesticides, agriculture, animal farms, water, endangered species, biodiversity, politics. They worked for universities or the federal departments of the Interior and Agriculture.

Out of this chronic investigation, the picture that emerged was disturbing and just as deleterious as that about pesticides.

The plight of animals

The industrialization of agriculture started in late nineteenth century. Machines replaced animals in the cultivation of the land and the irrigation and harvesting of crops. The size of the farms expanded without limits. Stone and wooden fences between farms became obsolete. The new mechanized farm surpassed the slave-run plantation. Almost nothing could stand on its way, least of all animals.

The factory farm, sometimes described as meat processing operation, put domesticated animals in the maws of machine feeding, slaughter, and sales to the insatiable appetites of meat-eating humans the industry calls consumers. Armies of academic and for profit corporate scientists issue false claims that confuse the public by legitimizing the inhuman treatment of animals.

Most of these agribusiness scientists teach and do research and extension at land-grant universities funded by the federal and state governments and industry. They are a parody of the original agricultural colleges founded by theMorrill Act of 1862.

Congressman Justin Smith Morrill of Vermont introduced the land grant college bill and President Abraham Lincoln signed it. Morrill and Lincoln inspired that great innovation to help family farmers. Now these 76 schools have become thebrains of agribusiness, thinking and inventing all the gadgetry and machinery and chemicals fueling Americas gigantic farms and agribusiness.

Land-grant universities designed animal farms. It does not bother them that it is wrong treating animals like inanimate things good only for eating.

Animals are living beings. They have feelings of enjoyment and fear. Those who have pet dogs and cats see their pets like their children. I have had dogs all my life. They are my best friends. I speak to them in Greek and English. They look at me straight in the eyes and shake their tales. I saw once a few days old calf in a farm at the Central Valley of California. It had tags on both ears. It turned and looked at me, his big eyes telling me of its horrible fate, taken away from its mother and expecting slaughter soon, so the farmer might sell veal.

At another time, in a visit to China, I saw a white bull in absolute terror written all over its eyes.

Animals probably coevolved with humans and, for millennia, were indispensable to human survival and civilization.

With some exceptions, most people have been eating domesticated and wild animals for millennia. However, the difference between traditional people and modern people eating animals is fundamental.

Traditional people ate animals because they often had to. Those living in mountainous regions with limited access to fishing or growing fruits and vegetables, relied on sheep and goats. Ancient Greeks, for example, ate primarily wheat and barley bread, cheese, olive oil, fruits and vegetables, and every so often they ate the meat of sheep and goats and even sacrificed them to their gods.

In contrast, modern animal farms completely dissolve any contacts people have had with animals or the natural world. They make animals dead meat through mechanical slaughter. Ordering a hamburger is no different from ordering French fries. Both have been made commodities of a cruel factory.

Mechanizing the slaughter of animals is the last straw of human violence against animals. It dehumanizes the relationship of people with animals. It undermines the philosophical and biological connections humans have had with the natural world.

Gaming the system

In practical political terms, the brutal treatment of animals has been increasing corruption among farmers, ranchers, butchers, and consumers. Large farmers / ranchers game the system. Their money power trumps our meager protection of human health and that of the natural world: laws defining and protecting organic food, meaning food raised without synthetic chemicals and without the genetic engineering of crops; laws designed to prevent pollution of the water we drink and laws protecting endanger species.

Large ranchers / meat companies are monopolizing the slaughtering of animals, forcing out of business smaller companies competing with them. In 1986, thelargest 4 poultry processing companiescontrolled 35 percent of the market. In 2015, they slaughtered 51 percent of the countryspoultry.

With the virus plague all over the country and in the slaughtering plants, and with the non-existent regulatory regime of the Trump administration,meat monopoliesendanger workers, farmers and those eating meat.

Meat monopolies are also taking over a large part of the slaughter of grass-fed animals. Which is to say, they occupy a significant niche in organic food production, pretending their organic brand shows a concern for human health and the environment.

The risks and effects of animal farms

Large farmers /ranchers, and slaughter companies put cattle, pigs, and chickens and turkeys by the hundreds and thousands next to each other in confined spaces. According to PETA, an animal welfare organization, factory farm animals are flooding the country with huge amounts of toxic and pathogenicwaste:

Animals on factory farms generate many times the amount of excrement produced by the entire U.S. population, and this waste pollutes the air we breathe and the water we drink. Every second, our nations factory farms create roughly 89,000 pounds of waste, which contains highly concentrated chemical and bacterial toxinsall without the benefit of waste-treatment systems.

At about 2010, theCenters for Disease Control and Preventionissued a study that justifies the concerns of PETA. The study concluded: Concentrated animal feeding operations [CAFOs] or large industrial animal farms can cause a myriad of environmental and public health problems.

The study reported that even the air close to CAFOs is unhealthy:

The most typical pollutants found in air surrounding CAFOs are ammonia, hydrogen sulfide, methane, and particulate matter, all of which have varying human health risks.

These risks are serious. The CDC study summarized the health effects of ammonia, hydrogen sulfide, methane, and particulate matter in the air:

The CDC report also listed some of the pathogens found in the enormous amounts of manure in the CAFOs:

Sources of infection from pathogens include fecal-oral transmission, inhalation, drinking water, or incidental water consumption during recreational water activities.The potential for transfer of pathogens among animals is higher in confinement, as there are more animals in a smaller amount of space.Healthy or asymptomatic animals may carry microbial agents that can infect humans, who can then spread that infection throughout a community, before the infection is discovered among animals. (emphasis mine)

For us, in 2020, living through the corona virus plague, these results are terrifying. The sources for the pandemic are all over the United States, in thousands upon thousands of CAFOs. Yet, the US government has been turning a blind eye, allowing these festering disease factories to go on.

Despite the grave risks to both animals and people, the owners of these large animal feeding operations refuse to shut them down, much less face the responsibility for the colossal and toxic and pathogenic wastes of their factories. They pour all those rivers of filth and plague into lagoons.

The stench from those wastes is powerful enough to make life unbearable to powerless and, usually, minority communities neighboring animal farms. This is especially blatant in east North Carolina where blacks live not far from millions of pigs confined for feeding and slaughter in giantindustrial hog farms.

CAFOs are equally dangerous to wildlife. Their waste lagoons become death lakes for flying and migrating birds. In addition, during storms, waste lagoons overflow into creeks, rivers and ground water aquifers harming both wildlife and humans.

To prevent plagues among thousands of caged animals and plagues from escaping animal farms, agribusiness workers add antibiotics and hormones to the pesticide-rich and genetically engineered feed animals eat. This guarantees the consumers of those animals also eat meat rich in antibiotics, pesticides, hormones and genetically engineered crops and potentially pathogenic diseases.

The other significant consequences of mass slaughter of animals is water pollution and the gases these animals emit into the atmosphere.

Manure gives off methane and nitrous oxide, which, respectively, are 23 and 300 times more potent greenhouse gases than carbon dioxide. These emissions from manure have been affecting climate change in a significant degree.

According to theHumane Society, the countrys largest animal protection organization, There is no question that the meat, egg, and dairy industries contribute significantly to greenhouse gas emissions. Thesociety encourages each individual to take important, daily steps to mitigate the devastating effects of climate change:

Stop eating meat

For these reasons (ethical, political, environmental and existential), vegetarianism is more timely and important now than ever before.

Stop eating meat. Stop being a consumer cannibalizing other living creatures. That way, you send an unmistakable message to careless administrations, like the hazardous administration of Trump, corporate exploiters, meat monopolists and profiteers and eaters of animals. You tell those unethical and violent business and political guys that you are not going to continue supporting their hazardous business.

Second, abandoning meat means you help our chances of surviving the colossal climate change around the corner.

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The Virtues of Not Eating Animals - CounterPunch

An international research team has identified a candidate thinness gene that could help to explain why some people can seemingly stay slim no matter what they eat. A genetic association study that analyzed data from more than 47,000 people in an Estonian biobank implicated ALK as a key gene that may regulate thinness and play a role in resisting weight gain in metabolically healthy thin people. Further studies in animal models showed that deleting ALK resulted in thinner flies and thinner mice, and demonstrated that ALK expression in the brain may be involved in regulating energy expenditure.

ALK is already a recognized anticancer target, and the researchers suggest that targeting the gene may represent a future therapeutic strategy against obesity. If you think about it, its realistic that we could shut down ALK and reduce ALK function to see if we did stay skinny, said Josef Penninger, PhD, director of the Life Sciences Institute and professor of the department of medical genetics at the University of British Columbia. ALK inhibitors are used in cancer treatments already. Its targetable. We could possibly inhibit ALK, and we actually will try to do this in the future. Penninger is senior author of the teams published paper in Cell, which is titled, Identification of ALK in Thinness. The reported studies involved a multidisciplinary team of researchers in Austria, Switzerland, Estonia, China, Australia, Canada, and Sweden, and the U.S.

Theres considerable variability in how susceptible different people are to putting on weight. We all know these people: its around one percent of the population, said Penninger. They can eat whatever they want and be metabolically healthy. They eat a lot, they dont do squats all the time, but they just dont gain weight.

Body mass index (BMI), which is commonly used to classify weight categories, is a highly complex trait that is impacted by genes and environmental cues, the researchers wrote. And while more than 700 common single nucleotide polymorphisms (SNPs) have been linked with BMI, only a limited number of genes involved in regulating human body weight have been identified and validated. To date, most studies have focused on susceptibility to obesity, and only a few have looked at the genetic basis of thinness in humans or animal models. Everybody studies obesity and the genetics of obesity, Penninger pointed out. We thought, Lets just turn it around and start a new research field. Lets study thinness.

To do this Penningers team analyzed data from the Estonian Biobank, which includes 47,102 people aged 2044 years. The investigators carried out a genome-wide association study (GWAS) to compare the DNA samples and clinical data of healthy thin individualswho were in the lowest 6th percentilewith normal-weight individuals, in the search for genetic variants linked with thinness. Their results highlighted genetic variants in the ALK gene that were specific to the thin individuals.

Scientists have known that the ALK gene frequently mutates in various types of cancer, and while it is viewed as an oncogene that can drive the development of tumors, the role of ALK outside of cancer isnt understood. ALK has been extensively studied in cancer, but little is known about the biological role of ALK outside the context of cancer, they wrote. The new finding suggested that the ALK gene might play a role as a thinness gene involved in weight-gain resistance.

The researchers investigated the association between ALK and thinness through a series of studies in Drosophila fruit flies, and in mice. Their experiments demonstrated that mice in which the ALK gene was knocked out remained thin and were resistant to diet-induced obesity. Intriguingly, Alk knockout mice were significantly protected against HFD-induced obesity, the researchers wrote. ALK deficiency was also linked with reduced weight gain in a genetic obesity mouse model. Even when the ALK knockout mice had the same diet and activity levels as normal mice, they still demonstrated lower body weight and body fat from an early age, which persisted into adulthood.

Further studies in mice suggested that ALK, which is highly expressed in the brain, plays a role in instructing the fat tissues to burn more fat from food. Expression analysis revealed high Alk mRNA levels in the hypothalamus, especially in the PVN, which is also true for humans, the investigators wrote. Mechanistically, we found that ALK expression in hypothalamic neurons controls energy expenditure via sympathetic control of adipose tissue lipolysis Our genetic and mechanistic experiments identify ALK as a thinness gene, which is involved in the resistance to weight gain.

The findings could help scientists develop therapeutics against ALK as a future strategy against obesity. The team also plans to further study how neurons that express ALK regulate the brain at a molecular level to balance metabolism and promote thinness.

The Estonian Biobank that the team studied was ideal because of its wide age range and its strong phenotype data. We took advantage of the wide age range of the unique Estonian biobank recruitment as well as its strong phenotypic datasets, making ECGUT [Estonian Genome Center of the University of Tartu] an ideal starting point to identify potential variants and genes playing a role in thinness, the scientists noted. Even so, one limitation for replicating these findings is that biobanks that collect biological or medical data and tissue samples dont have a universal standard in data collection, which makes comparability a challenge. The researchers say they will need to confirm their findings with other data banks through meta-analyses. You learn a lot from biobanks, said Penninger. But, like everything, its not the ultimate answer to life, but theyre the starting points and very good points for confirmation, very important links and associations to human health.

The team suggests its work is unique in its combination of populationand genome-wide-scale analyses into the genetic basis of thinness, with in vivo analyses of gene function in mice and flies. Its great to bring together different groups, from nutrition to biobanking, to hardcore mouse and fly genetics, stated Penninger. Together, this is one story including evolutionary trees in metabolism, the evolutionary role of ALK, human evidence, and hardcore biochemistry and genetics to provide causal evidence.

Read more here:
Gene for "Thinness" Identified that May Help to Resist Weight Gain - Genetic Engineering & Biotechnology News

No one likes getting a shot at the doctors office. As kids, we werent used to having a sharp needle prick our skin, let alone by someone doing it on purpose. An estimated 10% of the population is affected by trypanophobia the fear of needles or injections. Luckily, for most, shots are an infrequent occurrence often limited to vaccinations. However, for millions of others, injections are a more frequent fact of life required in dealing with disease. The need for these injections and their associated doctor visits mean the physical discomfort of the treatment is often compounded by a financial burden.

Fortunately, plant biotechnology is poised to drastically improve how we consume medication. Using the modern tools of genetic engineering, researchers are developing plant-based drugs that are cheaper, easier to take and even more effective than their existing counterparts.

Cant more medicines be reformulated for oral delivery?

While many diseases can be treated with orally administered medications, other drugs such as biologics or biopharmaceuticals, medicines derived from living organisms, must be delivered using other strategies. Conventional drugs like aspirin are chemically synthesized and can survive digestion, whereas biologics like hormones, antibodies, enzymes, and other complex organic molecules are vulnerable to degradation by enzymes in our saliva and stomach, as well as environmental conditions like pH and heat. This makes biologics in pill form unlikely to survive the harsh environment of the digestive tract.

Pricey biologics

In addition to the unpleasant nature of biologic injections is their associated costs. Biologics are made by taking the DNA blueprint for the molecule and expressing it in bacterial, yeast, or mammalian cells. Once these cells, typically grown in large vats filled with nutrient media, produce the molecule of interest, it must be isolated and purified. Each step of this process must be exact and carefully maintained as small variations may change the structure and identity of the drug, potentially altering its behavior. This complex manufacturing process in addition to more rigorous FDA regulations mean higher drug prices for consumers. Combined with the price of doctor visits to get these frequent injections or infusions, the annual cost of some biologics can reach hundreds of thousands of dollars.

There are more than 200 FDA-approved biologic drugs. While less than two percent of people in the US rely on biologics, they make up 40 percent of prescription drug spending. Identifying a better way to produce and administer biologics has the potential to ease the physical and financial burden associated with these drugs. For this reason, researchers are turning to the original inspiration for medications: plants.

Turning plants into pharmaceutical factories

Evidence for plant use in medicine dates back all the way to the Palaeolithic Age. But instead of trying to find new plants that produce medically relevant compounds, researchers are turning to genetic engineering to express the same biologics currently grown in bacterial, yeast, or mammalian cells.

Producing biologics in plants has a number of advantages. Plants are potentially less costly to grow, requiring inexpensive fertilizers instead of specialized cell culture growth media. Plants can also be grown in fields or greenhouses without requiring sterile environments, meaning that scaling up production would just require more growing area as opposed to additional expensive bioreactors. An added benefit is that plants do not serve as hosts for human pathogens, reducing the likelihood of harm from contaminants that bacterial or mammalian cells may house.

Once the drug-producing plants are grown, the medically relevant proteins may be extracted and purified. But plants allow for this platform to be taken one step further: by turning the biologic- expressing plants into a freeze-dried (lyophilized) powder and placing it into a capsule, the drugs can be delivered orally. Plant cell walls contain cellulose which cannot be digested by enzymes in the stomach but can be broken down by the commensal bacteria living in our intestines. Plant-encapsulated drugs are then released in the blood-rich absorptive environment of the small intestine, where they become bioavailable and distributed to target tissues. By producing these drugs in a lyophilized form, manufacturers can cut out the expensive purification process and the need for cold transport and storage.

Current research efforts

Theres been some reported success using this method, including a March 2020 paper from a team at the University of Pennsylvania describing a lettuce expressing a novel human insulin-like growth factor-1 (IGF-1). IGF-1 helps promote skeletal muscle and bone development. For this reason, IGF-1 injections have been used in the treatment of several muscle disorders and have the potential for therapeutic benefit in healing bone fractures.

To study if plant-grown IGF-1 might be an effective replacement for traditional IGF injections, the team modified human IGF-1 to allow for uptake through the gut. They found that their modified version not only stimulated proliferation of several cell types better than current commercial IGF-1, but also that the plant-encapsulated drug could be administered orally to mice and would effectively be delivered to blood serum. The team also found that this administration of the drug significantly increased bone density in diabetic mice as compared to a control group.

In addition to medication production, companies are also looking to utilize some of the benefits of plant-based production for vaccines. Medicago, a Canada-based company seeking approval for their plant-produced flu vaccine, has announced that using this same technology, they have produced a candidate vaccine for COVID-19 in twenty days. By growing the protein for the vaccine in plants, as opposed to using eggs to propagate the virus, Medicago has been able to cut the cost and time required to produce a new vaccine. The vaccine is now awaiting clinical testing and FDA approval.

Similar to the work on orally administered IGF-1, theres also a lot of interest in making edible vaccines. In the future, you may no longer need to go to a clinic to get a seasonal flu vaccine, but instead eat a salad made with vaccine-containing lettuce or tomatoes. This could potentially reduce patient discomfort and increase vaccine compliance, minimizing everybodys risk of contracting infectious diseases. Edible vaccines would also help expand access to immunization in parts of the world were delivering vaccines may be difficult.

Plant-produced pharmaceuticals have the potential to improve the quality of life for millions of people by reducing the physical and financial burden of relying on biologics to stay healthy. There may even come a day when getting a shot at the doctors office is a thing of the past replaced by a quick trip to the grocery store.

Tautvydas Shuipys is a PhD candidate in the Genetics and Genomics Graduate Program at the University of Florida. Follow him on Twitter @tshuipys

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Drug factories: GMOs and gene editing are poised to transform medicine. Here's how. - Genetic Literacy Project

If humanity is ever going to settle down on Mars, we may need to become a little less human.

Crewed missions to Mars, which NASA wants to start flying in the 2030s, will be tough on astronauts, exposing them to high radiation loads, bone-wasting microgravity and other hazards for several years at a time. But these pioneers should still be able to make it back to Earth in relatively good nick, agency officials have said.

It might be a different story for those who choose not to come home, however. If we want to stay safe and healthy while living permanently on Mars, or any other world beyond our home planet, we may need to make some tweaks to our species' basic blueprint, experts say.

Related: Space radiation threat to astronauts explained (infographic)

Genetic engineering and other advanced technologies "may need to come into play if people want to live and work and thrive, and establish their family, and stay on Mars," Kennda Lynch, an astrobiologist and geomicrobiologist at the Lunar and Planetary Institute in Houston, said on May 12 during a webinar hosted by the New York Academy of Sciences called "Alienating Mars: Challenges of Space Colonization."

"That's when these kinds of technologies might be critical or necessary," she said.

Genetic enhancement may not be restricted to the pages of sci-fi novels for much longer. For example, scientists have already inserted genes from tardigrades tiny, adorable and famously tough animals that can survive the vacuum of space into human cells in the laboratory. The engineered cells exhibited a greater resistance to radiation than their normal counterparts, said fellow webinar participant Christopher Mason, a geneticist at Weill Cornell Medicine, the medical school of Cornell University in New York City.

NASA and other space agencies already take measures to protect their astronauts physically, via spacecraft shielding, and pharmacologically via a variety of medicines. So, it's not a huge conceptual leap to consider protecting them genetically as well, provided that these measures are proven to be safe, Mason said.

"And are we maybe ethically bound to do so?" he said during the webinar. "I think if it's a long enough mission, you might have to do something, assuming it's safe, which we can't say yet."

Tardigrades and "extremophile" microbes, such as the radiation-resistant bacterium Deinococcus radiodurans, "are a great, basically natural reservoir of amazing traits and talents in biology," added Mason, who has been studying the effects of long-term spaceflight on NASA astronaut Scott Kelly. (Kelly spent nearly a year aboard the International Space Station in 2015 and 2016.) "Maybe we use some of them."

Harnessing these traits might also someday allow astronauts to journey farther than Mars, out to some even more exotic and dangerous cosmic locales. For instance, a crewed journey to the Jupiter moon Europa, which harbors a huge ocean beneath its icy shell, is out of the question at the moment. In addition to being very cold, Europa lies in the heart of Jupiter's powerful radiation belts.

"If we ever get there, those are the cases where the human body would be almost completely fried by the amount of radiation," Mason said. "There, it would be certain death unless you did something, including every kind of shielding you could possibly provide."

Genetic engineering at least lets us consider the possibility of sending astronauts to Europa, which is widely regarded as one of the solar system's best bets to harbor alien life. (The Jovian satellite is a high priority for NASA's robotic program of planetary exploration. In the mid-2020s, the agency will launch a mission called Europa Clipper, which will assess the moon's habitability during dozens of flybys. And Congress has ordered NASA to develop a robotic Europa lander as well, though this remains a concept mission at the moment.)

Related: The 6 most likely places to find alien life

Genetic engineering almost certainly won't be restricted to pioneering astronauts and colonists. Recent advances in synthetic biology herald a future in which "designer microbes" help colonists establish a foothold on the Red Planet, Lynch said.

"These are some of the things that we can actually do to help us make things we need, help us make materials to build our habitats," she said. "And these are a lot of things that scientists are researching right now to create these kinds of things for our trip to Mars."

Some researchers and exploration advocates have even suggested using designer microbes to terraform Mars, turning it into a world much more comfortable for humans. This possibility obviously raises big ethical questions, especially considering that Mars may have hosted life in the ancient past and might still host it today, in subsurface lakes or aquifers. (Permanently changing our own genomes for radiation protection or any other reason may also strike some folks as ethically dubious, of course.)

Most astrobiologists argue against terraforming Mars, stressing that we don't want to snuff out or fundamentally alter a native ecosystem that may have arisen on the Red Planet. That would be both unethical and unscientific, Lynch said.

After all, she said, one of the main reasons we're exploring Mars is to determine if Earth is the only world to host life.

"And how can we do that if we go and change the planet before we go and find out if life actually was living there?" Lynch said.

Mike Wall is the author of "Out There" (Grand Central Publishing, 2018; illustrated by Karl Tate), a book about the search for alien life. Follow him on Twitter @michaeldwall. Follow us on Twitter @Spacedotcom or Facebook.

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Colonizing Mars may require humanity to tweak its DNA - Space.com

Octant, a company backed by Andreessen Horowitz just now unveiling itself publicly to the world, is using the tools of synthetic biology to buck the latest trends in drug discovery.

As the pharmaceuticals industry turns its attention to precision medicine the search for ever more tailored treatments for specific diseases using genetic engineering Octant is using the same technologies to engage in drug discovery and diagnostics on a mass scale.

The companys technology genetically engineers DNA to act as an identifier for the most common drug receptors inside the human genome. Basically, its creating QR codes that can flag and identify how different protein receptors in cells respond to chemicals. These are the biological sensors which help control everything from immune responses to the senses of sight and smell, the firing of neurons; even the release of hormones and communications between cells in the body are regulated.

Our discovery platform was designed to map and measure the interconnected relationships between chemicals, multiple drug receptor pathways and diseases, enabling us to engineer multi-targeted drugs in a more rational way, across a wide spectrum of targets, said Sri Kosuri, Octants co-founder and chief executive officer, in a statement.

Octants work is based on a technology first developed at the University of California Los Angeles by Kosuri and a team of researchers, which slashed the cost of making genetic sequences to $2 per gene from $50 to $100 per gene.

Our method gives any lab that wants the power to build its own DNA sequences, Kosuri said in a 2018 statement. This is the first time that, without a million dollars, an average lab can make 10,000 genes from scratch.

Joining Kosuri in launching Octant is Ramsey Homsany, a longtime friend of Kosuris, and a former executive at Google and Dropbox . Homsany happened to have a background in molecular biology from school, and when Kosuri would talk about the implications of the technology he developed, the two men knew they needed to for a company.

We use these new tools to know which bar code is going with which construct or genetic variant or pathway that were working with [and] all of that fits into a single well, said Kosuri. What you can do on top of that is small molecule screening we can do that with thousands of different wells at a time. So we can build these maps between chemicals and targets and pathways that are essential to drug development.

Before coming to UCLA, Kosuri had a long history with companies developing products based on synthetic biology on both the coasts. Through some initial work that hed done in the early days of the biofuel boom in 2007, Kosuri was connected with Flagship Ventures, and the imminent Harvard-based synthetic biologist George Church . He also served as a scientific advisor to Gen9, a company acquired by the multi-billion dollar synthetic biology powerhouse, Ginkgo Bioworks.

Some of the most valuable drugs in history work on complex sets of drug targets, which is why Octants focus on polypharmacology is so compelling, said Jason Kelly, the co-founder and CEO of Gingko Bioworks, and a member of the Octant board, in a statement. Octant is engineering a lot of luck and cost out of the drug discovery equation with its novel platform and unique big data biology insights, which will drive the companys internal development programs as well as potential partnerships.

The new technology arrives at a unique moment in the industry where pharmaceutical companies are moving to target treatments for diseases that are tied to specific mutations, rather than look at treatments for more common disease problems, said Homsany.

People are dropping common disease problems, he said. The biggest players are dropping these cases and it seems like that just didnt make sense to us. So we thought about how would a company take these new technologies and apply them in a way that could solve some of this.

One reason for the industrys turn away from the big diseases that affect large swaths of the population is that new therapies are emerging to treat these conditions which dont rely on drugs. While they wouldnt get into specifics, Octant co-founders are pursuing treatments for what Kosuri said were conditions in the metabolic space and in the neuropsychiatric space.

Helping them pursue those targets, since Octant is very much a drug development company, is $30 million in financing from investors led by Andreessen Horowitz .

Drug discovery remains a process of trial and error. Using its deep expertise in synthetic biology, the Octant team has engineered human cells that provide real-time, precise and complete readouts of the complex interactions and effects that drug molecules have within living cells, said Jorge Conde, general partner at Andreessen Horowitz, and member of the Octant board of directors. By querying biology at this unprecedented scale, Octant has the potential to systematically create exhaustive maps of drug targets and corresponding, novel treatments for our most intractable diseases.

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Emerging from stealth, Octant is bringing the tools of synthetic biology to large scale drug discovery - TechCrunch