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Updates found with 'basic mechanical processes'

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Updates found with 'basic mechanical processes'

Newswise — As a basic unit of life, the cell is one of the most carefully studied components of all living organisms. Yet details on basic processes such as how cells are shaped have remained a mystery. Working at the intersection of biology and physics, scientists at the University of California San Diego have made an unexpected discovery at the root of cell formation.As reported in the journal Cell on Feb. 8, 2018, biologists Javier Lopez-Garrido, Kit Pogliano and their colleagues at UC San Diego and Imperial College in London found that DNA executes an unexpected architectural role in shaping the cells of bacteria.Studying the bacterium Bacillus subtilis, the researchers used an array of experiments and technologies to reveal that DNA, beyond serving to encode genetic information, also “pumps up” bacterial cells.“Our study illustrates that DNA acts like air in a balloon, inflating the cell, ” said Lopez-Garrido, an assistant research scientist in UC San Diego’s Division of Biological Sciences and the study’s first author. “DNA is best known for being the molecule with genetic information but it’s becoming more and more obvious that it does other things that are not related to that.”The researchers say the results could have relevance in human cells in terms of how they are generated and shaped, as well as aid explanations of basic mechanical processes and the structure of the nucleus and mitochondria. The results could also allow scientists to have a glimpse into the origins of cellular life itself. Modern bacterial cells have evolved a variety of mechanisms to control their internal pressure, said Lopez-Garrido. However, those mechanisms were absent in primitive cells at the dawn of life on earth. The finding that DNA can inflate a cell might allow scientists to achieve a better understanding of the physiology of the first cells on the planet.“Biologists tend to think of cell growth as following normal, biosynthetic pathways, but we found a pathway that is not normal, as it does not depend on processes normally required for growth, ” said Pogliano, a professor in the Section of Molecular Biology and the paper’s senior author. “All you need for this cell to grow is to inflate it with DNA and its associated positively charged ions, and the ability to make more membrane so the cell can get bigger. Nothing else seems to be required.”The researchers employed time-lapse fluorescent microscopy to methodically track cell formation in Bacillus subtilis through a process known as sporulation. During this process cells split into a mother cell and a smaller cell, or forespore. Also using cryo-electron tomography to capture extreme close-ups of the process unfolding, the researchers witnessed the mother cells inflating the forespore with DNA in a stretching and swelling process, ultimately leading to a new, egg-shaped cell.“It’s amazing how we are just beginning to scratch the surface of how physics impacts living organisms, ” said Pogliano. “This is a unique example of a very simple biophysical property impacting cell shape and it illustrates the value of physicists working closely with biologists. Understanding how physics and biology intersect is a huge area for future growth.”Coauthors of the study include Nikola Ojkic and Robert Endres of Imperial College; and Kanika Khanna, Felix Wagner and Elizabeth Villa of UC San Diego.Funding was provided by the European Research Council (starting grant 280492-PPHPI), National Institutes of Health (grant R01-GM57045), NIH Director’s New Innovator Award (1DP2GM123494-01) and a European Molecular Biology Organization (EMBO) Long Term Fellowship (ALTF 1274-2011). The researchers used the UC San Diego Cryo-EM Facility (supported by NIH grant R01-GM33050) and the San Diego Nanotechnology Infrastructure of UC San Diego (supported by National Science Foundation grant ECCS-1542148).
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Differentiation sensitizes stem-like glioblastoma tumor-initiating cells to mechanical inputsSPONSORED BY: Thermo Fisher Scientific/GibcoCONTINUING EDUCATION (CME/CE/CEU) CREDITS: P.A.C.E. CE | Florida CEMechanobiology of Glioblastoma-Initiating CellsGlioblastoma (GBM) is the most aggressive primary brain cancer, with nearly universal recurrence after treatment. GBMs are highly heterogeneous at the cellular level, and there is much evidence that recurrence, chemoresistance, and invasion are driven by a rare and specialized population of tumor initiating cells (TICs) within the tumor. These TICs are thought to share some similarities with stem cells in that they can both self-renew and differentiate to produce a range of cell types found in the bulk tumor. Because glioblastoma is above all a disease of tissue invasion and because invasion involves complex mechanical signaling between the microenvironment and the invading cells, we probed how TICs respond to mechanical cues. We found that in contrast to the majority of other cell types, TICs surprisingly showed very little stiffness-dependent change in cell shape and migration. Furthermore, we found that by increasing cellular force generation we could increase mechanosensitivity and extend survival in a mouse xenograft model. We next asked how the mechanosensitivity of these TICs changes as they are exposed to bone morphogenetic protein 4 (BMP4), which has been previously shown to elicit a differentiation-like effect on GBM TICs and extend survival in a xenograft model. We found that TICs treated with BMP4 showed increased stiffness-dependent changes in cell shape and reduced tissue invasion. We next performed RNA sequencing for a systems-level picture of how differentiation impacts mechanical signaling in TICs. We identified several pathways that showed mechanically-regulated changes impacted by differentiation, particularly those governing cell-extracellular matrix adhesions. These findings demonstrate that manipulation of mechanotransductive signaling can be leveraged to control tumor growth and invasion, and provide insight on alterations in mechanical signaling in stem-like and differentiated tumor initiating cells.
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Stem cell PortalMarch 21, 2018Mending broken hearts with cardiomyocyte moldsWhether caused by an undetected birth defect or by a heart attack (myocardial infarction), when a heart sustains damage it can be difficult to repair.If heart muscle cells — cardiomyocytes — could be repaired by cells taken from one’s own body, the patient's recovery improves. But manufacturing heart cells requires an exacting process tailored specifically to an individual.In a study published recently in Advanced Functional Materials, a team of researchers at Michigan Technological University in collaboration with Harvard Medical School shows how cardiomyocytes grown in a heart-like environment mature more quickly, have improved functionality and are less likely to be rejected by patients’ bodies.Many people with heart injuries from heart attacks or birth defects could benefit from the “self-therapeutic” process of injecting healthy cells into the damaged heart muscle. Labs use induced pluripotent stem cells (iPSCs), which using biochemical cues can be “programmed” to become any type of cell, whether for the heart muscle or otherwise. Yet current processes result in underdeveloped cells.To date, manufacturing cardiomyocytes has occurred in two-dimensional settings (essentially, petri dishes). But the growth environment plays a large role in the ways the cells develop. Thus, simulating the actual heart environment — with lots of pressure and specific forces acting on the growing cells — could lead to more robust cardiomyocytes.“Unfortunately stem cell therapeutics don’t have high success rates, partly because the cells are not mature and fully functional. The maturation and functionality are essential, ” said Parisa Pour Shahid Saeed Abadi, Ph.D., assistant professor of mechanical engineering, whose work in creating heart cell growth environments is detailed in the study.Mimicking the natural heart environmentDr. Abadi and her co-authors have created three-dimensional substrates — essentially, molds — that recreate the environment in which heart cells grow inside the human body. Biomechanical properties the substrates induce include pressure and stiffness.“The mechanical properties of substrates play an important role in the cell behavior because the mechanical cues that cells sense in the actual (heart) environment is unique, ” Dr. Abadi said. “We are using biochemical and biomechanical cues to enhance the differentiation and maturation. If we don’t take advantage of the physical cues and only rely on chemical cues, the process suffers from low efficiency and batch-to-batch inconsistency.”Using photolithography and reflow processing, Dr. Abadi’s substrates are patterned at the micron and submicron levels, approximating the natural physical forces cells experience. Photolithography uses ultraviolet light to remove portions of polydimethylsiloxane (PDMS) substrate to mold it into cylindrical shapes.Additional micro-patterning of the substrate changes the cytoskeleton in the cell and the shape of the nucleus, which cause the genes in the cell to change. As the cardiomyocytes mature, they beat stronger and resemble the cells found in natural, mature heart muscle.“On day one we start seeing the effect of the substrate on the morphology of the cells, ” Dr. Abadi said.Abadi’s lab continues to improve the substrate preparation methods. As cardiomyocytes need to communicate with each other during their growth, Dr. Abadi also plans to stimulate electrical conductivity between cells. Translational studies in animals are the next step for the research.These lab-fabricated, fluorescently stained cardiomyocytes — heart muscle cells — exhibit the maturation and functionality of heart cells grown within a heart.Induced pluripotent stem cell-derived cardiomyocytes beating in substrate.
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HUMAN DEVELOPMENTHow to build a human brainSome steps for growing mini versions of human organs are easier than othersBY INGFEI CHEN 3:30PM, FEBRUARY 20, 2018SHARE ARTICLEorganoid brainBRAIN-MAKING 101 As blobs of two types of brainlike tissue fuse, interneurons (green) migrate from the left clump to the right, linking with neurons (not stained) in the right blob. On both sides, neural support cells called glia appear in purple.PAŞCA LAB/STANFORD UNIV.Magazine issue: Vol. 193, No. 4, March 3, 2018, p. 22SPONSOR MESSAGEIn a white lab coat and blue latex gloves, Neda Vishlaghi peers through a light microscope at six milky-white blobs. Each is about the size of a couscous grain, bathed in the pale orange broth of a petri dish. With tweezers in one hand and surgical scissors in the other, she deftly snips one tiny clump in half.When growing human brains, sometimes you need to do some pruning.The blobs are 8-week-old bits of brainlike tissue. While they wouldn’t be mistaken for Lilliputian-sized brains, some of their fine-grained features bear a remarkable resemblance to the human cerebral cortex, home to our memories, decision making and other high-level cognitive powers.Vishlaghi created these “minibrains” at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, where she’s a research assistant. First she immersed batches of human pluripotent stem cells — which can morph into any cell type in the body — in a special mix of chemicals.The free-floating cells multiplied and coalesced into itty-bitty balls of neural tissue. Nurtured with meticulously timed doses of growth-supporting ingredients, the cell clumps were eventually transferred to petri dishes of broth laced with Matrigel, a gelatin-like matrix of proteins.On day 56, the blobs display shadowy clusters of neural “rosettes.” Under a laser scanning microscope, razor-thin slices of those rosettes reveal loose-knit layers of a variety of dividing neural stem cells and the nerve cells, or neurons, they give rise to. The layered structures look similar to the architecture of a human fetal brain at 14 weeks of gestation.By eight weeks, brainlike clumps (top) show neural clusters called rosettes. Within one cluster (red box, expanded at bottom), stem cells (blue and teal) churn out layers of neural precursor cells (pink) and neurons (not stained).BOTH: M. WATANABE ET AL/CELL REPORTS 2017Across the globe, labs such as this one, led by UCLA developmental biologist and neuroscientist Bennett Novitch, are cultivating thousands of these brainy clumps for research. Less than five years ago, a team of biologists in Austria and the United Kingdom and one in Japan wowed the world when they announced they had made rudimentary bits of 3-D human cerebral cortex in a dish. Since then, researchers have been eagerly tinkering with techniques for producing these miniature brain models, like chefs obsessively refining their favorite recipes.“It’s like making a cake: You have many different ways in which you can do it, ” says Novitch, who prefers using the Japanese method with a few tweaks. “There are all sorts of little tricks that people have come up with to overcome some of the common challenges.”For instance, because the brain blobs lack a built-in blood supply, they must absorb enough oxygen and nutrients from the tissue-culture broth to remain healthy. To help, some labs circulate the broth around the tissue clumps. The UCLA researchers choose instead to grow theirs at higher oxygen levels and chop the blobs at the 35-day mark, when they are as wide as three millimeters, and then about every two weeks after. Sounds radical, but the slicing gives cells on the inside — some of which start dying — exposure to much-needed oxygen and nutrients. Those divided bits then continue growing separately. But cutting can be done only so many times before the expanding rosette structures inside are damaged.With all the experimenting, researchers have cooked up a lot of innovations, including some nifty progress reported in just the last year. Scientists have concocted tiny versions of several brain regions ranging from the hypothalamus, which regulates body temperature, thirst and hunger, to the movement-controlling basal ganglia. Electrical chatter among neurons, reflecting active brain circuits, has been detected. And research groups have recently begun linking bits of specific regions like Legos. Scientists have even observed some early developmental processes as they happen within the human brain blobs.Stem cell payoffThe work is part of a broader scientific bonanza that comes from coaxing human stem cells to self-assemble into balls of organlike tissue, known as organoids, that are usually no bigger than a lentil. Although the organoids don’t grow enough to replicate entire human organs, these mini-versions can mimic the 3-D cellular infrastructure of everything from our guts to our lungs. That’s something you can’t get from studies of rodents, which have different biology than humans do.Mini-organ models promise enormous advantages for understanding basic human biology, teasing apart human disease processes, and offering an accurate testing ground for finding or vetting drug therapies. And by creating personalized organoids from the reprogrammed cells of patients, scientists could study disease in a very individualized way — or maybe even use organoid structures to replace certain damaged tissues, such as in the liver or spinal cord.“Organoids offer an unprecedented level of access into the inner workings of the human brain, ” Novitch says, noting that our brains are largely off-limits to poking and cutting into for research. If scientists can study accurate models of working neural circuits in these brain bits, he and others say, researchers might finally get a handle on uniquely human neurological conditions. Such disorders, which include epilepsy and, experts theorize, schizophrenia and autism (SN Online: 7/17/15), can arise when the brain’s communication networks develop off-kilter.
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Patient Derived Xenograft/PDX Models Market by Type (Mouse & Rat), Tumor Type (Gastrointestinal, Gynecological, Respiratory), Application (Pre-Clinical Drug Development & Biomarker Analysis), End User (Pharma & Biotech, CRO) - Global Forecast to 2022The growth of the overall Patient Derived Xenograft Models Market can be attributed to the growing demand for personalized medicine, continuous support for cancer research from the public as well as private sectors, and growth in the number of R& D activities in the pharmaceutical industry.In addition, Growth in biomedical research in the US, rising preclinical activities by CROs and pharmaceutical companies, and growing stem cell research in Canada are the major factors expected to drive the growth of the market during the forecast period.The report analyzes the patient derived xenograft models market by type, tumor type, application, end user, and region.Based on application, the PDX models market has been broadly segmented into preclinical drug development & basic cancer research and biomarker analysis. In 2017, the preclinical drug development and basic cancer research segment is expected to account for the largest share of the global patient derived xenograft models market. Growth in this segment is mainly driven by the increasing number of research activities in the field of oncology drug research.The pharmaceutical and biotechnology companies segment is estimated to account for the largest share of the patient derived xenograft models market in 2017. The large share of this segment is due to the increasing expenditure on R& D by companies for drug development.
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In the future we won’t edit genomes—we’ll just print out new onesWhy redesigning the humble yeast could kick off the next industrial revolution.by Bryan Walsh February 16, 2018At least since thirsty Sumerians began brewing beer thousands of years ago, Homo sapiens has had a tight relationship with Saccharomyces cerevisiae, the unicellular fungus better known as brewer’s yeast. Through fermentation, humans were able to harness a microscopic species for our own ends. These days yeast cells produce ethanol and insulin and are the workhorse of science labs.That doesn’t mean S. cerevisiae can’t be further improved—at least not if Jef Boeke has his way. The director of the Institute for Systems Genetics at New York University’s Langone Health, Boeke is leading an international team of hundreds dedicated to synthesizing the 12.5 million genetic letters that make up a yeast’s cells genome.In practice, that means gradually replacing each yeast chromosome—there are 16 of them—with DNA fabricated on stove-size chemical synthesizers. As they go, Boeke and collaborators at nearly a dozen institutions are streamlining the yeast genome and putting in back doors to let researchers shuffle its genes at will. In the end, the synthetic yeast—called Sc2.0—will be fully customizable.“Over the next 10 years synthetic biology is going to be producing all kinds of compounds and materials with microorganisms, ” says Boeke. “We hope that our yeast is going to play a big role in that.”Think of the project as something like Henry Ford’s first automobile—hand built and, for now, one of a kind. One day, though, we may routinely design genomes on computer screens. Instead of engineering or even editing the DNA of an organism, it could become easier to just print out a fresh copy. Imagine designer algae that make fuel; disease-proof organs; even extinct species resurrected.Jef Boeke leads an effort to create yeast with a man-made genome.“I think this could be bigger than the space revolution or the computer revolution, ” says George Church, a genome scientist at Harvard Medical School.Researchers have previously synthesized the genetic instructions that operate viruses and bacteria. But yeast cells are eukaryotic—meaning they confine their genomes in a nucleus and bundle them in chromosomes, just as humans do. Their genomes are also much bigger.That’s a problem because synthesizing DNA is still nowhere near as cheap as reading it. A human genome can now be sequenced for $1, 000, with the cost still falling. By comparison, to replace every DNA letter in yeast, Boeke will have to buy $1.25 million worth of it. Add labor and computer power, and the total cost of the project, already under way for a decade, is considerably more.Along with Church, among others, Boeke is a leader of GP-write, an organization advocating for international research to reduce the cost of designing, engineering, and testing genomes by a factor of a thousand over the next decade. “We have all kinds of challenges facing ourselves as a species on this planet, and biology could have a huge impact on them, ” he says. “But only if we can drive down costs.”Bottom upA scientist named Ronald Davis at Stanford first suggested the possibility of synthesizing the yeast genome at a conference in 2004—though initially, Boeke didn’t see the point. “Why would anyone want to do this?” he recalls thinking.But Boeke came around to the idea that manufacturing a yeast genome might be the best way to comprehend the organism. By replacing each part, you might learn which genes are necessary and which the organism can live without. Some team members call the idea “build to understand.”“It’s a different take on trying to understand how living things work, ” says Leslie Mitchell, a postdoctoral fellow in the NYU lab and one of the main designers of the synthetic yeast. “We learn what gaps in our knowledge exist in a bottom-up genetic approach.”Joel Bader, a computer scientist at Johns Hopkins, signed on to develop software that let scientists see the yeast chromosomes on a screen and keep track of versions as they changed, like a Google Docs for biology. And in 2008, to make the DNA, Boeke launched an undergraduate course at Hopkins called “Build a Genome.” Students would learn basic molecular biology as each one assembled a continuous stretch of 10, 000 DNA letters that would go toward the synthetic-yeast project. Later, several institutions in China joined to share the workload, along with collaborators in Britain, Australia, and Japan.“We assign chromosomes to individual teams, like assigning a chapter of a book, and they have the freedom to decide how to do it, as long as it’s based 100 percent on what we design, ” says Patrick Cai, a synthetic biologist at the University of Manchester and the yeast project’s international coordinator.Next stepsIt took Boeke and his team eight years before they were able to publish their first fully artificial yeast chromosome. The project has since accelerated. Last March, the next five synthetic yeast chromosomes were described in a suite of papers in Science, and Boeke says that all 16 chromosomes are now at least 80 percent done. These efforts represent the largest amount of genetic material ever synthesized and then joined together.It helps that the yeast genome has proved remarkably resilient to the team’s visions and revisions. “Probably the biggest headline here is that you can torture the genome in a multitude of different ways, and the yeast just laughs, ” says Boeke.
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Harvard Men's Health WatchHearing loss a possible risk factor for dementiaIn the journalsPublished: March, 2018Older adults who develop hearing loss are more likely to experience greater cognitive decline and develop dementia than their counterparts without hearing problems, according to a meta-analysis published online Dec. 7, 2017, by JAMA Otolaryngology — Head and Neck Surgery. Researchers examined data from 36 studies including more than 20, 000 people who underwent both cognitive evaluations and hearing tests. Those with age-related hearing loss were more likely to have cognitive impairment or a diagnosis of dementia.The study found a small but statistically meaningful association between hearing loss and a variety of specific cognitive abilities, including executive function, memory, processing speed, and visuospatial ability (how you recognize shapes and sizes and estimate the distance between two objects). The association between hearing loss and weaker cognitive skills was still strong even after accounting for risk factors like high blood pressure and smoking.It is not yet known how hearing loss may be related to cognitive decline and dementia. The researchers speculated that these abilities may share a common neural pathway. For instance, hearing loss may require increased mental energy to perceive speech, which leaves fewer mental resources available for other cognitive processes like memory. There also may be an indirect link. For example, hearing loss can lead to greater social isolation, which can increase the risk of cognitive problems.
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Use of Genomics in specialised/personalised medicine is a mayor opportunity in the marketSujith Sharma sr.corporate communicator in healthcare domain in MarketsandMarketsThe global market for genomics has seen umpteen changes and developments over the years, thanks to the ever-growing technology. Moreover, government initiatives and funding and active investments from the market players towards genetic research on personalized medicines, increasing demand for personalized medicines, innovations and developments in technology, lower costs and time-saving techniques in DNA sequencing are expected to further trigger the growth of this market.Genomics, as the name suggests, is basically the study and analysis of the functioning and structure of genomes i.e., the complete set of DNA in a single cell of an individual. It is said to be transforming the medicine sector, especially since it can help in identifying a person’s health problems, diseases he/she may be prone to, and what medications will better suit the person. While the concept of genomics has been around for the past decades, it has only recently become a buzzword worldwide, and will continue to gain popularity in the near future as well.North America accounted for the largest share of the Genomics market in 2017, followed by Europe. The large share of the North American Genomics market can be attributed to the growth in biotechnology and genomics research grants and funds in the US, focus on precision medicine and pan-Canadian program.The various players in the Genomics market include F. Hoffmann-La Roche (Switzerland), Thermo Fisher Scientific (US), BGI (China), Illumina (US), QIAGEN (Netherlands), GE Healthcare (UK), Bio-Rad Laboratories (US), Eurofins Scientific (Germany), Agilent Technologies, (US), Oxford Nanopore Technologies (UK), Pacific Biosciences of California (US), and Eppendorf (Germany) among others.
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Gene Editing for GoodHow CRISPR Could Transform Global DevelopmentBy Bill GatesToday, more people are living healthy, productive lives than ever before. This good news may come as a surprise, but there is plenty of evidence for it. Since the early 1990s, global child mortality has been cut in half. There have been massive reductions in cases of tuberculosis, malaria, and HIV/AIDS. The incidence of polio has decreased by 99 percent, bringing the world to the verge of eradicating a major infectious disease, a feat humanity has accomplished only once before, with smallpox. The proportion of the world’s population in extreme poverty, defined by the World Bank as living on less than $1.90 per day, has fallen from 35 percent to about 11 percent.Continued progress is not inevitable, however, and a great deal of unnecessary suffering and inequity remains. By the end of this year, five million children under the age of five will have died—mostly in poor countries and mostly from preventable causes. Hundreds of millions of other children will continue to suffer needlessly from diseases and malnutrition that can cause lifelong cognitive and physical disabilities. And more than 750 million people—mostly rural farm families in sub-Saharan Africa and South Asia—still live in extreme poverty, according to World Bank estimates. The women and girls among them, in particular, are denied economic opportunity.Some of the remaining suffering can be eased by continuing to fund the development assistance programs and multilateral partnerships that are known to work. These efforts can help sustain progress, especially as the world gets better at using data to help guide the allocation of resources. But ultimately, eliminating the most persistent diseases and causes of poverty will require scientific discovery and technological innovations.That includes CRISPR and other technologies for targeted gene editing. Over the next decade, gene editing could help humanity overcome some of the biggest and most persistent challenges in global health and development. The technology is making it much easier for scientists to discover better diagnostics, treatments, and other tools to fight diseases that still kill and disable millions of people every year, primarily the poor. It is also accelerating research that could help end extreme poverty by enabling millions of farmers in the developing world to grow crops and raise livestock that are more productive, more nutritious, and hardier. New technologies are often met with skepticism. But if the world is to continue the remarkable progress of the past few decades, it is vital that scientists, subject to safety and ethics guidelines, be encouraged to continue taking advantage of such promising tools as CRISPR.FEEDING THE WORLDEarlier this year, I traveled to Scotland, where I met with some extraordinary scientists associated with the Centre for Tropical Livestock Genetics and Health at the University of Edinburgh. I learned about advanced genomic research to help farmers in Africa breed more productive chickens and cows. As the scientists explained, the breeds of dairy cows that can survive in hot, tropical environments tend to produce far less milk than do Holsteins—which fare poorly in hot places but are extremely productive in more moderate climates, thanks in part to naturally occurring mutations that breeders have selected for generations. The scientists in Scotland are collaborating with counterparts in Ethiopia, Kenya, Nigeria, Tanzania, and the United States. They are studying ways to edit the genes of tropical breeds of cattle to give them the same favorable genetic traits that make Holsteins so productive, potentially boosting the tropical breeds’ milk and protein production by as much as 50 percent. Conversely, scientists are also considering editing the genes of Holsteins to produce a sub-breed with a short, sleek coat of hair, which would allow the cattle to tolerate heat.This sort of research is vital, because a cow or a few chickens, goats, or sheep can make a big difference in the lives of the world’s poorest people, three-quarters of whom get their food and income by farming small plots of land. Farmers with livestock can sell eggs or milk to pay for day-to-day expenses. Chickens, in particular, tend to be raised by women, who are more likely than men to use the proceeds to buy household necessities. Livestock help farmers’ families get the nutrition they need, setting children up for healthy growth and success in school.Similarly, improving the productivity of crops is fundamental to ending extreme poverty. Sixty percent of people in sub-Saharan Africa earn their living by working the land. But given the region’s generally low agricultural productivity—yields of basic cereals are five times higher in North America—Africa remains a net importer of food. This gap between supply and demand will only grow as the number of mouths to feed increases. Africa’s population is expected to more than double by 2050, reaching 2.5 billion, and its food production will need to match that growth to feed everyone on the continent. The challenge will become even more difficult as climate change threatens the livelihoods of smallholder farmers in Africa and South Asia.Gene editing to make crops more abundant and resilient could be a lifesaver on a massive scale. The technology is already beginning to show results, attracting public and private investment, and for good reason. Scientists are developing crops with traits that enhance their growth, reduce the need for fertilizers and pesticides, boost their nutritional value, and make the plants hardier during droughts and hot spells. Already, many crops that have been improved by gene editing are being developed and tested in the field, including mushrooms with longer shelf lives, potatoes low in acrylamide (a potential carcinogen), and soybeans that produce healthier oil.Improving the productivity of crops is fundamental to ending extreme poverty.For a decade, the Bill & Melinda Gates Foundation has been backing research into the use of gene editing in agriculture. In one of the first projects we funded, scientists from the University of Oxford are developing improved varieties of rice, including one called C4 rice. Using gene editing and other tools, the Oxford scientists were able to rearrange the cellular structures in rice plant leaves, making C4 rice a remarkable 20 percent more efficient at photosynthesis, the process by which plants convert sunlight into food. The result is a crop that not only produces higher yields but also needs less water. That’s good for food security, farmers’ livelihoods, and the environment, and it will also help smallholder farmers adapt to climate change.Such alterations of the genomes of plants and even animals are not new. Humans have been doing this for thousands of years through selective breeding. Scientists began recombining DNA molecules in the early 1970s, and today, genetic engineering is widely used in agriculture and in medicine, the latter to mass-produce human insulin, hormones, vaccines, and many drugs. Gene editing is different in that it does not produce transgenic plants or animals—meaning it does not involve combining DNA from different organisms. With CRISPR, enzymes are used to target and delete a section of DNA or alter it in other ways that result in favorable or useful traits. Most important, it makes the discovery and development of innovations much faster and more precise.ENDING MALARIA In global health, one of the most promising near-term uses of gene editing involves research on malaria. Although insecticide-treated bed nets and more effective drugs have cut malaria deaths dramatically in recent decades, the parasitic disease still takes a terrible toll. Every year, about 200 million cases of malaria are recorded, and some 450, 000 people die from it, about 70 percent of them children under five. Children who survive often suffer lasting mental and physical impairments. In adults, the high fever, chills, and anemia caused by malaria can keep people from working and trap families in a cycle of illness and poverty. Beyond the human suffering, the economic costs are staggering. In sub-Saharan Africa, which is home to 90 percent of all malaria cases, the direct and indirect costs associated with the disease add up to an estimated 1.3 percent of GDP—a significant drag on countries working to lift themselves out of poverty.With sufficient funding and smart interventions using existing approaches, malaria is largely preventable and treatable—but not completely. Current tools for prevention, such as spraying for insects and their larvae, have only a temporary effect. The standard treatment for malaria today—medicine derived from artemisinin, a compound isolated from an herb used in traditional Chinese medicine—may relieve symptoms, but it may also leave behind in the human body a form of the malaria parasite that can still be spread by mosquitoes. To make matters worse, the malaria parasite has begun to develop resistance to drugs, and mosquitoes are developing resistance to insecticides.Efforts against malaria must continue to make use of existing tools, but moving toward eradication will require scientific and technological advances in multiple areas. For instance, sophisticated geospatial surveillance systems, combined with computational modeling and simulation, will make it possible to tailor antimalarial efforts to unique local conditions. Gene editing can play a big role, too. There are more than 3, 500 known mosquito species worldwide, but just a handful of them are any good at transmitting malaria parasites between people. Only female mosquitoes can spread malaria, and so researchers have used CRISPR to successfully create gene drives—making inheritable edits to their genes—that cause females to become sterile or skew them toward producing mostly male offspring. Scientists are also exploring other ways to use CRISPR to inhibit mosquitoes’ ability to transmit malaria—for example, by introducing genes that could eliminate the parasites as they pass through a mosquito’s gut on their way to its salivary glands, the main path through which infections are transmitted to humans. In comparable ways, the tool also holds promise for fighting other diseases carried by mosquitoes, such as dengue fever and the Zika virus.It will be several years, however, before any genetically edited mosquitoes are released into the wild for field trials. Although many questions about safety and efficacy will have to be answered first, there is reason to be optimistic that creating gene drives in malaria-spreading mosquitoes will not do much, if any, harm to the environment. That’s because the edits would target only the few species that tend to transmit the disease. And although natural selection will eventually produce mosquitoes that are resistant to any gene drives released into the wild, part of the value of CRISPR is that it expedites the development of new approaches—meaning that scientists can stay one step ahead.THE PATH FORWARDLike other new and potentially powerful technologies, gene editing raises legitimate questions and understandable concerns about possible risks and misuse. How, then, should the technology be regulated? Rules developed decades ago for other forms of genetic engineering do not necessarily fit. Noting that gene-edited organisms are not transgenic, the U.S. Department of Agriculture has reasonably concluded that genetically edited plants are like plants with naturally occurring mutations and thus are not subject to special regulations and raise no special safety concerns.The benefits of emerging technologies should not be reserved only for people in developed countries.Gene editing in animals or even humans raises more complicated questions of safety and ethics. In 2014, the World Health Organization issued guidelines for testing genetically modified mosquitoes, including standards for efficacy, biosafety, bioethics, and public participation. In 2016, the National Academy of Sciences built on the WHO’s guidelines with recommendations for responsible conduct in gene-drive research on animals. (The Gates Foundation co-funded this work with the National Institutes of Health, the Foundation for the National Institutes of Health, and the Defense Advanced Research Projects Agency.) These recommendations emphasized the need for thorough research in the lab, including interim evaluations at set points, before scientists move to field trials. They also urged scientists to assess any ecological risks and to actively involve the public, especially in the communities and countries directly affected by the research. Wherever gene-editing research takes place, it should involve all the key stakeholders—scientists, civil society, government leaders, and local communities—from wherever it is likely to be deployed.Part of the challenge in regulating gene editing is that the rules and practices in different countries may differ widely. A more harmonized policy environment would prove more efficient, and it would probably also raise overall standards. International organizations, especially of scientists, could help establish global norms. Meanwhile, funders of gene-editing research must ensure that it is conducted in compliance with standards such as those advanced by the WHO and the National Academy of Sciences, no matter where the research takes place.When it comes to gene-editing research on malaria, the Gates Foundation has joined with others to help universities and other institutions in the regions affected by the disease to conduct risk assessments and advise regional bodies on experiments and future field tests. The goal is to empower affected countries and communities to take the lead in the research, evaluate its costs and benefits, and make informed decisions about whether and when to apply the resulting technology.Finally, it’s important to recognize the costs and risks of failing to explore the use of new tools such as CRISPR for global health and development. The benefits of emerging technologies should not be reserved only for people in developed countries. Nor should decisions about whether to take advantage of them. Used responsibly, gene editing holds the potential to save millions of lives and empower millions of people to lift themselves out of poverty. It would be a tragedy to pass up the opportunity.
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