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Category Archives: Human Genetic Engineering

MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer – Science Magazine

How cancer cells adapt to stress

Bacteria adapt to harsh conditions such as antibiotic exposure by acquiring new mutations, a process called stress-induced mutagenesis. Cipponi et al. investigated whether similar programs of mutagenesis play a role in the response of cancer cells to targeted therapies. Using in vitro models of intense drug selection and genome-wide functional screens, the authors found evidence for an analogous process in cancer and showed that it is regulated by the mammalian target of rapamycin (mTOR) signaling pathway. This pathway appears to mediate a stress-related switch to error-prone DNA repair, resulting in the generation of mutations that facilitate the emergence of drug resistance.

Science, this issue p. 1127

In microorganisms, evolutionarily conserved mechanisms facilitate adaptation to harsh conditions through stress-induced mutagenesis (SIM). Analogous processes may underpin progression and therapeutic failure in human cancer. We describe SIM in multiple in vitro and in vivo models of human cancers under nongenotoxic drug selection, paradoxically enhancing adaptation at a competing intrinsic fitness cost. A genome-wide approach identified the mechanistic target of rapamycin (MTOR) as a stress-sensing rheostat mediating SIM across multiple cancer types and conditions. These observations are consistent with a two-phase model for drug resistance, in which an initially rapid expansion of genetic diversity is counterbalanced by an intrinsic fitness penalty, subsequently normalizing to complete adaptation under the new conditions. This model suggests synthetic lethal strategies to minimize resistance to anticancer therapy.

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Antibiotic-destroying genes widespread in bacteria in soil and on people | The Source | Washington University in St. Louis – Washington University in…

Shown above are two different 3D views of TetX7 (green), a tetracycline-destroying enzyme that causes resistance to all tetracycline antibiotics (the small multicolored molecule in the center). Researchers at Washington University in St. Louis and the National Institutes of Health (NIH) have found that genes that confer the power to destroy tetracyclines are widespread in bacteria that live in the soil and on people. (Video: Timothy Wencewicz)

The latest generation of tetracyclines a class of powerful, first-line antibiotics was designed to thwart the two most common ways bacteria resist such drugs. But a new study from researchers at Washington University in St. Louis and the National Institutes of Health (NIH) has found that genes representing yet another method of resistance are widespread in bacteria that live in the soil and on people. Some of these genes confer the power to destroy all tetracyclines, including the latest generation of these antibiotics.

However, the researchers have created a chemical compound that shields tetracyclines from destruction. When the chemical compound was given in combination with tetracyclines as part of the new study, the antibiotics lethal effects were restored.

The findings, available online in Communications Biology, indicate an emerging threat to one of the most widely used classes of antibiotics but also a promising way to protect against that threat.

We first found tetracycline-destroying genes five years ago in harmless environmental bacteria, and we said at the time that there was a risk the genes could get into bacteria that cause disease, leading to infections that would be very difficult to treat, said co-senior authorGautam Dantas, professor of pathology and immunology and of molecular microbiology at Washington University School of Medicine in St. Louis. Once we started looking for these genes in clinical samples, we found them immediately. The fact that we were able to find them so rapidly tells me that these genes are more widespread than we thought. Its no longer a theoretical risk that this will be a problem in the clinic. Its already a problem.

In 2015, Dantas, also a professor of biomedical engineering, andTimothy Wencewicz, associate professor of chemistry in Arts & Sciences at Washington University, discovered 10 different genes that each gave bacteria the ability to dice up the toxic part of the tetracycline molecule, thereby inactivating the drug. These genes code for proteins the researchers dubbed tetracycline destructases.

But they didnt know how widespread such genes were. To find out, Dantas and first author Andrew Gasparrini then a graduate student in Dantas lab screened 53 soil, 176 human stool, two animal feces, and 13 latrine samples for genes similar to the 10 theyd already found. The survey yielded 69 additional possible tetracycline-destructase genes.

Then they cloned some of the genes intoE. colibacteria that had no resistance to tetracyclines and tested whether the genetically modified bacteria survived exposure to the drugs.E. colithat had received supposed destructase genes from soil bacteria inactivated some of the tetracyclines.E. colithat had received genes from bacteria associated with people destroyed all 11 tetracyclines.

The scary thing is that one of the tetracycline destructases we found in human-associated bacteria Tet(X7) may have evolved from an ancestral destructase in soil bacteria, but it has a broader range and enhanced efficiency, said Wencewicz, who is a co-senior author on the new study. Usually theres a trade-off between how broad an enzyme is and how efficient it is. But Tet(X7) manages to be broad and efficient, and thats a potentially deadly combination.

In the first screen, the researchers had found tetracycline-destructase genes only in bacteria not known to cause disease in people. To find out whether disease-causing species also carried such genes, the scientists scanned the genetic sequences of clinical samples Dantas had collected over the years. They found Tet(X7) in a bacterium that had caused a lung infection and sent a man to intensive care in Pakistan in 2016.

Tetracyclines have been around since the 1940s. They are one of the most widely used classes of antibiotics, used for diseases ranging from pneumonia, to skin or urinary tract infections, to stomach ulcers, as well as in agriculture and aquaculture. In recent decades, mounting antibiotic resistance has driven pharmaceutical companies to spend hundreds of millions of dollars developing a new generation of tetracyclines that is impervious to the two most common resistance strategies: expelling drugs from the bacterial cell before they can do harm, and fortifying vulnerable parts of the bacterial cell.

The emergence of a third method of antibiotic resistance in disease-causing bacteria could be disastrous for public health. To better understand how Tet(X7) works, co-senior author Niraj Tolia, a senior investigator at the National Institute of Allergy and Infectious Diseases at the NIH, and co-author Hirdesh Kumar, a postdoctoral researcher in Tolias lab, solved the structure of the protein.

I established that Tet(X7) is very similar to known structures but way more active, and we dont really know why because the part that interacts with the tetracycline rings is the same, Kumar said. Im now taking a molecular dynamics approach so we can see the protein in action. If we can understand why it is so efficient, we can design even better inhibitors.

Wencewicz and colleagues previouslydesigned a chemical compoundthat preserves the potency of tetracyclines by preventing destructases from chewing up the antibiotics. In the most recent study, co-author Jana L. Markley, a postdoctoral researcher in Wencewiczs lab, evaluated that inhibitor against the bacterium from the patient in Pakistan and its powerful Tet(X7) destructase. Adding the compound made the bacteria two to four times more sensitive to all three of the latest generation of tetracyclines.

Our team has a motto extending the wise words of Benjamin Franklin: In this world nothing can be said to be certain, except death, taxes and antibiotic resistance, Wencewicz said. Antibiotic resistance is going to happen. We need to get ahead of it and design inhibitors now to protect our antibiotics, because if we wait until it becomes a crisis, its too late.

Originally published by the School of Medicine

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Antibiotic-destroying genes widespread in bacteria in soil and on people | The Source | Washington University in St. Louis - Washington University in...

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Can Operation Warp Speed have a COVID-19 vaccine this year? – Los Angeles Times

To capture the speed and audacity of its plan to field a coronavirus vaccine, the Trump administration reached into science fictions vault for an inspiring moniker: Operation Warp Speed.

The vaccine initiatives name challenges a mantra penned by an actual science fiction writer, Arthur C. Clarke: Science demands patience.

Patience is essential for those who ply the science of vaccines. But in that field, challenging economic conditions and a forbidding regulatory system converge with the immune systems complexity and the resilience of microscopic pathogens. Add in drug companies preference for big profits and the result is a trash heap of failed and abandoned efforts.

In the last 25 years, the U.S. Food and Drug Administration has approved new vaccines for only seven diseases. A vaccine to protect against the Ebola virus won approval just last year, three years after the epidemic in West Africa ended.

But in the midst of a COVID-19 pandemic that has killed more than 100,000 Americans and cratered the U.S. economy, Trump has shown little tolerance for sciences deliberate pace. And scientists, with fingers crossed, are falling in line.

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The president declared that he wants 300 million doses enough to protect as many as 90% of Americans developed, manufactured and delivered by January 2021. He has ordered academics, government officials, private companies and the U.S. military to work together to make it so.

That means big and it means fast, Trump said. A massive scientific, industrial and logistical endeavor unlike anything our country has seen since the Manhattan Project.

The new effort will demand the support, development, testing and assessment of several promising vaccine candidates by scientists at the National Institutes of Health, the FDA and companies and academic institutions across the world.

It will require the manufacture, procurement and storage of complex biologic medicines, as well as the vials, needles, syringes and storage equipment needed to deliver them. All will be needed on a massive scale.

And all that materiel will need to be transported, distributed and possibly administered by an army of logistics specialists.

Wherever possible, Operation Warp Speed envisions that many steps that have always followed each other in strict sequence clinical trials and production, for instance, or government approval and supply-chain development be done in parallel.

The program has already awarded a total of $2.16 billion to five companies with vaccine candidates at different stages of development.

To lead the effort, Trump tapped immunologist Moncef Slaoui, a pharmaceutical venture capitalist and former chairman of vaccines at the drug giant GlaxoSmithKline. The U.S. Armys most senior logistics and procurement specialist, Gen. Gustave Perna, will be the operations chief operating officer. Both expressed confidence in the operations success.

Perna called the project herculean. Slaoui, who has been criticized for holding a major stake in at least one of the vaccine makers that stands to benefit from Operation Warp Speed, told Trump we will do the best we can.

The time is short and the stakes are high. Just over four months after the coronavirus announced its presence inside the United States, President Trump is determined to send the country back to work.

With no effective treatment in sight, and no indication that the coronavirus would magically disappear, as Trump has frequently predicted, a vaccine will be the ultimate game changer in the pandemic, according Dr. Anthony Fauci, the nations leading expert on the outbreak.

Theres never a guarantee of success, Fauci said. But he added that he was cautiously optimistic that by winter, at least one of nearly a dozen promising vaccine candidates would have shown itself to be safe and effective in inducing immunity in humans.

Vaccine scientists are similarly cautious, especially of a testing schedule that will compress both the size and duration of safety and effectiveness trials and even overlap them in a bid to save time.

Its fine for politicians to say were going to have a vaccine next month, said Mayo Clinic immunologist Dr. Gregory Poland. But the literature is littered with false starts and unanticipated safety effects in vaccines.

Poland noted that a vaccines rarer side effects are often not recognized until its put into broad use. To ferret out an adverse outcome that only occurs in one person in 100,000, for instance, a company would need to test it in 384,250 people from broad backgrounds and with a variety of medical conditions, he said.

Such large trials are unlikely in the rush to field a vaccine, Poland said, and he fears the result could be a dangerous erosion of public trust. The yearly flu shot carries a risk of less than 1 in 1 million cases of the neurological complication Guillain-Barre syndrome, he said. And even with that low a risk, close to half of Americans refuse to get it.

You have a whole spectrum of people out there who wont be reassured by any amount of information, Poland said. If we dont pay strict attention to safety, this is going to backfire.

Money may help. Congress approved $8.3 billion in early March to fund federal agencies pandemic response. And scientists across the world have been scrambling to design vaccines to protect a population with no immunity to the deadly new pathogen.

Scientists in China, Kazakhstan, India, Russia, Germany, Sweden and the United States have brought 10 potential COVID-19 vaccines to the point where they are being evaluated in humans in some form. Another 115 are considered by the World Health Organization to be in the preclinical stage of development.

In some cases, these preclinical vaccine candidates are scarcely off the drawing board. In others, they are still being tweaked or tested in cells. Some are being tried in lab animals.

The prospective vaccines range widely in their design and novelty. There are those that challenge a persons immune system with a killed or attenuated virus, the traditional approach used by the polio vaccine and other immunizations. Others are products of genetic engineering and have never been tried in a vaccine before.

The vaccine candidates also vary in their ease of manufacture, the number of doses a patient needs to gain lasting immunity, and the way they are administered.

FDA Commissioner Dr. Stephen Hahn has said his agency evaluated about 10 vaccine candidates in early studies. By late May, it had narrowed its focus to five candidates that will begin a rapid and sometimes overlapping progression through human studies of safety and effectiveness.

Meanwhile, the groundwork for large-scale production is already being laid. Trump has said that the U.S. military may aid in the manufacture, and companies with the capability to produce vaccines will be recruited to do so.

Given the pressing urgency of the administrations deadline, vaccine candidates that can be produced fastest, transported most easily and administered to patients most efficiently will likely win the most and earliest support, experts said.

The redundancy built into Operation Warp Speed may also prove a vital safeguard against failure.

If the coronavirus shows signs that it is mutating in ways that could make one vaccine candidate ineffective, the scientific judges could swiftly shift their preferences toward a competitor that can be adapted more readily to changes in the virus. If rare but untoward effects show up with broader use, back-up vaccines could be brought on line. Some vaccines will be found to work better or worse in specific populations, and can be used accordingly.

The result will be an evolving panoply of vaccine choices, not only because some will be ready earlier than others, but because some will be more effective than others in certain populations.

There will be of necessity multiple types of vaccines, Poland said.

Michael S. Kinch, who directs the Center for Drug Discovery at Washington University in St. Louis, said that while there are pitfalls inherent to Operation Warp Speed, another pandemic offers comforting reassurance that in fielding the right drug, patience is an essential virtue.

In the early days of the HIV/AIDS epidemic, the first generation of drugs was mediocre at best, he said. As scientists learned more about the virus and the disease it causes, the medicines became more effective.

That may be a model for what were going to have here, Kinch said. We may not get the best vaccine up front. But hopefully it will be good enough and will be replaced later by better vaccines. We have may just have to live with that until we get a better one.

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Genetic Engineering Market 2020 Reflect Impressive Expansion by Integrated DNA Technologies, Thermo Fisher Scientific, Merck KGaA, Horizon Discovery…

Genetic Engineering Market research added by the insight partners, offers a comprehensive analysis of growth trends prevailing in the global business domain. This report also provides definitive data concerning market, size, commercialization aspects and revenue forecast of the Genetic Engineering industry. In addition, the study explicitly highlights the competitive status of key players within the projection timeline while focusing on their portfolio and regional expansion endeavours.

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A gene is the basic physical and function unity of heredity. Genetic engineering is the changing the structure of the genes of a living things in order to make it healthier, stronger and more useful to human. Changing DNA in cell is to understand their biology. Genetic engineering are currently used in both animal and plant cells this modifications are helps to improve performance of cell.

MARKET DYNAMICS

The genetic engineering market is expected to grow during the forecast period due to rising use of genetic engineering in the field of medical as well as in agriculture, high prevalence of infectious disease and awareness of steam cell therapy, and increasing no of genomics project due to government raising funds in genetic engineering field and more R&D. Thus, various governments are taking initiatives to create awareness amongst people about genetic engineering.

The report also includes the profiles of key Genetic Engineering Market companies along with their SWOT analysis and market strategies. In addition, the report focuses on leading industry players with information such as company profiles, components and services offered, financial information of last 3 years, key development in past five years.

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Integrated DNA Technologies, Thermo Fisher Scientific, Merck KGaA, Horizon Discovery Group, Transposagen Biopharmaceuticals, New England Biolabs, Genscript Biotech Corporation, Lonza Group, Origene Technologies, Sangamo Therapeutics

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Market segmentation:

Genetic Engineering Market to 2027 Global Analysis and Forecasts by Technology (CRISPR, TALEN, ZFN, Antisense, Other Technologies); By Application (Cell line Engineering, Genetic Engineering, Diagnostics & Therapeutics); By End User (Pharmaceutical and Biotechnology Companies, Academic and Research Institutes, Contract Research Organizations) and Geography

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How big will the market for Genetic Engineering be in 2027? What is the current CAGR of the Genetic Engineering Market? Which product is expected to have the highest market growth? Which application should be used to win a large part of the market for Genetic Engineering ? Which region is likely to offer the most opportunities on the Genetic Engineering Market? Will the market competition change in the forecast period? Who are the main players currently active in the global Genetic Engineering Market? How will the market situation change within the coming years? What are the usual commercial tactics for players? What is the growth perspective of the global Genetic Engineering Market?

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Ethicists: We need more flexible tools for evaluating gene-edited food – The Conversation US

Is there now a way to genetically engineer crops to create food that people can confidently consider natural?

Gene-editing technology sounds like it might offer this possibility. By altering an organisms genetic material, or genome, without introducing genes from other species, advocates of genome editing argue the technique can sidestep most of the difficult ethical and regulatory challenges plaguing organisms with added transgenes, which are genes from other species. Some even argue these cisgenic products are natural enough to count as organic.

As ethicists specializing in how technology alters human-nature relations, we can understand why advocates see the ethics this way. If crossing species lines is the measure of whether a technique counts as natural or not, then genome editing appears to have the potential to pass a naturalness test.

Genome editing, its boosters say, can make changes that look almost evolutionary. Arguably, these changes could have happened by themselves through the natural course of events, if anyone had the patience to wait for them. Conventional breeding for potatoes resistant to late blight is theoretically possible, for example, but it would take a lot of time.

Although we understand the potential advantages of speed, we dont think an ethics hinging on the idea of cisgenesis is adequate. We propose a better ethical lens to use in its place.

Our work is part of a four-year projectfunded by the Norwegian Research Council scrutinizing how gene editing could change how we think about food. The work brings together researchers from universities and scientific institutes in Norway, the U.K. and the U.S. to compare a range of techniques for producing useful new crops.

Our project is not focused on the safety of the crops under development, something that obviously requires concerted scientific investigation of its own. Although the safety of humans and the health of the environment is ethically crucial when developing new foods, other ethical issues must also be considered.

To see this, consider how objections against genetically modified organisms go far beyond safety. Ethical issues around food sovereignty range broadly across farmer choice, excess corporate power, economic security and other concerns. Ethical acceptability requires a much higher bar than safety alone.

Although we believe gene editing may have promise for addressing the agricultural challenges caused by rising global populations, climate change and the overuse of chemical pesticides, we dont think an ethical analysis based entirely on crossing species lines and naturalness is adequate.

It is already clear that arguing gene-edited food is ethical based on species lines has not satisfied all of gene editings critics. As Ricarda Steinbrecher, a molecular biologist cautious about gene editing, has said, Whether or not the DNA sequences come from closely related species is irrelevant, the process of genetic engineering is the same, involving the same risks and unpredictabilities, as with transgenesis.

Comments of this kind suggest talking about species lines is an unreliable guide. Species and subspecies boundaries are notoriously infirm. Charles Darwin himself conceded in Origin of Species, I look at the term species, as one arbitrarily given for the sake of convenience to a set of individuals closely resembling each other.

The 2005 edition of the Mammal Species of the World demonstrated this arbitrariness by collapsing all 12 subspecies of American cougars down to one Puma concolor cougar overnight. In 2017, the Cat Classification Task Force revised the Felidae family again.

If species lines are not clear, claiming naturalness based on not crossing species lines is, in our view, a shaky guide. The lack of clarity matters because a premature ethical green light could mean a premature regulatory green light, with broad implications for both agricultural producers and consumers.

We think a more reliable ethical measure is to ask about how a technique for crop breeding interferes with the integrity of the organism being altered.

The term integrity already has application in environmental ethics, ecology, cell biology, interhuman ethics, organic agriculture and genetics.

A unifying theme in all these domains is that integrity points toward some kind of functional wholeness of an organism, a cell, a genome or an ecological system. The idea of maintaining integrity tracks a central intuition about being cautious before interfering too much with living systems and their components.

The integrity lens makes it clear why the ethics of gene editing may not be radically different from the ethics of genetic modification using transgenes. The cell wall is still penetrated by the gene-editing components. The genome of the organism is cut at a site chosen by the scientist, and a repair is initiated which (it is hoped) will result in a desired change to the organism. When it comes to the techniques involved with gene editing a crop or other food for a desired trait, integrity is compromised at several levels and none has anything to do with crossing species lines. The integrity lens makes it clear the ethics is not resolved by debating naturalness or species boundaries.

Negotiation of each others integrity is a necessary part of human-to-human relations. Adopted as an ethical practice in the field of biotechnology, it might provide a better guide in attempts to accommodate different ethical, ecological and cultural priorities in policymaking. An ethic with a central place for discussion of integrity promises a framework that is both more flexible and discerning.

As new breeding techniques create new ethical debates over food, we think the ethical toolbox needs updating. Talking about crossing species lines simply isnt enough. If Darwin had known about gene editing, we think he would have agreed.

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

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

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