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Category Archives: Genetic Medicine

Large International Study Pinpoints Impact of TP53 Mutations on Blood Cancer Severity – PR Newswire India

Having two mutated copies of the TP53 gene - as opposed to a single mutated copy - is associated with worse outcomes in myelodysplastic syndrome and acute myeloid leukemia.

YARDVILLE, New Jersey, Aug. 25, 2020 /PRNewswire/ --The MDS Foundation announces that a large international study led by researchers at Memorial Sloan Kettering finds that having two mutated copies of theTP53gene, as opposed to a single mutated copy, is associated with worse outcomes in myelodysplastic syndrome and acute myeloid leukemia. The findings have immediate clinical relevance for risk assessment and treatment of people with myelodysplastic syndrome.

Considered the "guardian of the genome,"TP53is the most commonly mutated gene in cancer.TP53's normal function is to detect DNA damage and prevent cells from passing this damage on to daughter cells. WhenTP53is mutated, the protein made from this gene (called p53) can no longer perform this protective function, which can result in cancer. Across many cancer types, mutations inTP53are associated with much worse outcomes, like disease recurrence and shorter survival.

As with all genes, there are two copies ofTP53in our cells. One copy we get from our mothers, the other we get from our fathers. Until now, it was unclear whether a mutation in one copy of TP53 TP53was enough to cause worse outcomes, or if mutations in both copies were necessary. A new study led by researchers at Memorial Sloan Kettering definitively answers this question for a blood cancer calledmyelodysplastic syndrome (MDS), a precursor toacute myeloid leukemia.

"Our study is the first to assess the impact of having one versus two dysfunctional copies ofTP53on cancer outcomes," says molecular geneticist Dr.Elli Papaemmanuil, a member of the Epidemiology and Biostatistics Department at MSK and the lead scientist on the study, whose results were published August 3 in the journalNature Medicine. "From our results, it's clear that you need to lose function of both copies to see evidence of genome instability and a high-risk clinical phenotype in MDS."

"The consequences for cancer diagnosis and treatment are immediate and profound," she says.

A LARGE, MULTICENTER STUDY

The study analyzed genetic and clinical data from 4,444 patients with MDS who were being treated at hospitals all over the world. Researchers from 25 centers in 12 countries were involved in the study, which was conducted under the aegis in collaboration with investigators in the International Working Group for Prognosis in MDS(IWG-PM)whose goal is to develop new international guidelines for the treatment of this disease. Findings were independently validated using data from the Japanese MDS working group led by Dr.SeishiOgawa'sgroup at Kyoto University.

"Currently, the existing guidelines do not consider genomic data, likeTP53and other acquired mutations, when assessing a person's prognosis or determining appropriate treatment for this disease," says Dr.Peter Greenberg, Director of Stanford University's MDS Center, Chair of the National Comprehensive Cancer Network Practice Guidelines Panel for MDS, and a participant in the study. "Studies are ongoing reflecting this need for change."

Tracey Iraca, MDS Foundation Executive Director stated, "This study is important in updating the IPSS-R to include molecule information in light of the more personalized treatments now being explored for MDS patients."

Using new computational methods and the database and collaborative input of the IWG-PM, the investigators found that about one-third of MDS patients had only one mutated copy ofTP53.These patients had similar outcomes as patients who did not have aTP53mutation that is, good response to treatment, low rates of disease progression, and better survival. Two-thirds of patients, on the other hand, had two mutated copies of TP53. These patients had much worse outcomes including treatment-resistant disease, rapid disease progression, and low overall survival. In fact, the researchers found thatTP53mutation status either 0/1 or 2 mutated copies of the gene was the most important variable when predicting outcomes.

"Our findings are of immediate clinical relevance to MDS patients," Dr. Papaemmanuil says. "Going forward, all MDS patients should have theirTP53status assessed at diagnosis."

As for why it takes two "hits" toTP53to see an effect on cancer outcomes, Dr.Elsa Bernard, a postdoctoral scientist in the Papaemmanuil lab and the study's first author, speculates that having one normal copy is enough to provide adequate protection against DNA damage. This would explain why having only one mutated copy was not associated with genome instability or any worse survival over having two normal copies.

Given the frequency ofTP53mutations in cancer, these results argue for examining the impact of one versus two mutations in other cancers as well. They also reveal the need for clinical trials designed specifically with these molecular differences in mind.

"With the increasing adoption of molecular profiling at the time of cancer diagnosis, we need large evidence-based studies to inform how to translate these molecular findings into optimal treatment strategies," Dr. Papaemmanuil says.

PARTICIPATING MDS FOUNDATION CENTERS OF EXCELLENCE:Karolinska Institute (Sweden), University of Pavia (Italy), La Fe University Hospital (Spain), Radboudumc Medical Center Nijmegen (The Netherlands), Amsterdam UMC (The Netherlands), Cochin Hospital (France), Chang Gung Memorial Hospital (Taiwan), Medical University of Vienna (Austria), Hannover Medical School (Germany), University Hospital Dresden (Germany), Federal University of Ceara (Brazil), University of Oxford (United Kingdom), Institute of Hematology and Blood Transfusion (Czech Republic), University Medicine Gttingen (Germany), Saint-Louis Hospital (France), Saint James's University Hospital (United Kingdom), Chulalongkorn University (Thailand), Nagasaki University (Japan), Kyoto University (Japan), Chugoku Central Hospital (Japan), Tokyo Medical University (Japan), Massachusetts General Hospital, Vanderbilt-Ingram Cancer Center,University of Rochester Medical Center, Dana-Farber Cancer Institute, UC San Diego Moores Cancer Center, Stanford University Cancer Institute,Memorial Sloan Kettering Cancer Center(United States).

ADDITIONAL PARTICIPATING CENTERS:Dsseldorf MDS Registry (Germany), Gruppo Romano Laziale MDS (Italy), University of Bologna (Italy), Institut Josep Carreras (Spain), Aou Careggi Hospital (Italy), Democritus University of Thrace (Greece), Hospital Israelita Albert Einstein (Brazil), Rete Ematologica Lombarda (Italy), Japanese Data Center for Hematopoietic Cell Transplantation (Japan), Tsukuba University (Japan), Gifu Municipal Hospital (Japan), Kobe City Medical Center General Hospital (Japan), Gifu University (Japan), NTT Medical Center Tokyo (Japan), Osaka Red Cross Hospital (Japan), Kurashiki Central Hospital (Japan), Sasebo City General Hospital (Japan)

FUNDING: This study was supported in part by the Celgene Corporation, the MDS Foundation, Inc., Bloodwise, Austrian Science Fund, Italian MIUR-PRIN grants, Associazione Italiana per la Ricerca sul Cancro, 51000 project, the Francois Wallace Monahan Fellowship, the Josie Robertson Foundation, the European Hematology Association, American Society of Hematology, Gabrielle's Angels Foundation, V Foundation, Damon Runyon-Rachleff, the Geoffrey Beene Foundation, the Japan Agency for Medical Research and Development, Japan Society for the Promotion of Science, and the Japanese Ministry of Education, Culture, Sports, Science and Technology. Dr. Papaemmanuil is a Josie Robertson-funded investigator at MSK. Drs. Papaemmanuil and Bernard have received research funding from Celgene.

The MDS Foundation, Inc.is an international non-profit advocacy organization whose mission is to support and educate patients and healthcare providers with innovative research into the fields of MDS, Acute Myeloid Leukemia (AML) and related myeloid neoplasms in order to accelerate progress leading to the diagnosis, control and cure of these diseases.

Media Contact:TraceyIraca, Executive Director, MDS Foundation, Inc.Phone: (609)298-1600 x 211Mobile: (609)647-2080Email: [emailprotected]

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Large International Study Pinpoints Impact of TP53 Mutations on Blood Cancer Severity - PR Newswire India

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We can programme plants to grow biomolecules. Is farming the future of vaccines? – Horizon magazine

The basic idea of molecular farming is to genetically modify plants so that, alongside all their usual biochemicals, their cells produce biomolecules that are useful to us. Its not a new idea.

The field was kicked off in 1989, when researchers fixed tobacco plants so that they produced a proof of concept antibody protein. Plenty of hype ensued in the following decade or so. One of the early ideas was that this could produce edible medicines bananas, for instance, that expressed vaccines in their cells. Molecular farming seemed like a world changing idea, capable of providing medicine easily and cheaply to billions of people.

One reason it didnt take off, says Professor Julian Ma at St Georges, University of London, UK, is that it can be difficult to control dosage with edible vaccines: How do you stop somebody eating 20 bananas because they think its good for them? There was a moment where everybody got seriously excited. And then realised oh no, its actually not going to be quite so straightforward.

Living things have biomachinery that uses a nucleic acid code as an instruction manual for building proteins. Molecular farming hijacks this machinery and gets it to use synthetic instructions to produce new proteins. But bacteria and other mammalian cells, such as the Chinese hamster ovary (CHO) cell, can do this too. Indeed, CHO cells are the most common way of culturing proteins. Cultured proteins are mostly used as drugs, for treating conditions like diabetes and problems with blood clotting. Culturing methods are more expensive and time consuming than molecular farming but the processes involved are well established and validated for safety molecular farming hasnt got there yet. But it is beginning to catch up.

Plants

A few years ago, Prof. Ma conducted a proof of concept study to show that an antibody could be produced in plants and isolated from them using simple separation techniques and that the resulting proteins could be just as pure and thus safe for medical use.

Another helpful factor is the rise of a genetic modification technology called transient expression. This is a technique that involves having cells express some DNA temporarily. Crucially, it is easy in plants. It involves dipping them in a special solution and then allowing them to grow. This means that in some cases plant scientists can go from genetically modifying plants to having them express new proteins in two weeks or less.

Molecular farming facilities are getting more common. That farm in Owensboro belongs to Kentucky BioProcessing, a long-established firm that helped produce the ZMapp antibodies to help treat Ebola during the 2015 outbreak. Another large facility is being built in Quebec, Canada. And Brazil has also announced it intends to build one, says Prof. Ma. I see that as a bit of a breakthough. Its the first one in the southern hemisphere.

It is in this context that Dr Diego Orzez at the Institute for Plant Molecular and Cellular Biology in Valencia, Spain, is running the Newcotiana project. Dr Orzez says that although lots of large farms exist, no one has yet put much effort into breeding the plants they use to improve their productivity he and his team are now doing just that.

They are working on two closely related plants. The first is Nicotiana benthamiana, a fragile, dwarf cousin of the tobacco plant, which is the species grown in most commercial molecular farms because it is so easy to genetically modify. The second is Nicotiana tabacum, the larger, hardy plant that is grown commercially for tobacco. The plan is to optimise both.

Tobacco

Theres a special reason why Dr Orzezwants to work with Nicotiana tabacum. He says that there are communities across Europe who have traditionally grown tobacco for use in cigarettes but face a certain stigma for doing so. Some such communities can be found in the relatively wet area of La Vera, in the Extremadura region of Spain, for instance. Many of these communities are keen to switch to growing tobacco that could be put to better use providing medicines rather than tobacco according to Dr Orzez.

Admittedly, theres a wrinkle in the plan because plants that have been genetically modified cant legally be grown outdoors in the EU because of the rules on genetically modified organisms. However, Dr Orzezsays he hopes to convince the authorities this ought to change. This is because the plants in his project, while officially classed as GMOs, have been produced by gene editing and they dont contain genes from other organisms as most GMOs do.

In the meantime, he says he has some encouraging results from his project. He has produced a cultivar of Nicotiana tabacum that does not flower, which means it cannot spread seeds or pollen and so should be safe to grow outside and separately a cultivar that produces an anti-inflammatory compound. The next step is to combine these into a single plant line. He also has improved versions of Nicotiana benthamiana in field trials.

In all of Dr Orzez's work the proteins are expressed in the plants leaves. But there are reasons why expressing them in other parts of a plant would be handy.

If you wanted to stockpile (a vaccine), for example, seeds would be brilliant, said Prof. Ma. They are natural protein storage organs and theyre incredibly stable. You could produce a barn full of seed and keep it almost forever.

Prof. Ma coordinates a project called Pharma-Factory, which is developing new farming platforms, so that proteins can be expressed in not just leaves but seeds, roots and algae. The project includes five small firms, and the plan is to have several protein therapeutics, including an HIV-neutralising antibody, developed to the point where they can be commercialised.

If you wanted to stockpile (a vaccine), for example, seeds would be brilliant.

Prof. Julian Ma, St Georges, University of London, UK

Coronavirus

So what of coronavirus? Several large molecular farming companies are already working on vaccines. For example, Medicago, headquartered in Quebec, has succeeded in directing plants to produce proteins that can be assembled into a virus-like particle, which is essentially the protein shell of the SARS-CoV-2 virus with nothing inside it. The company says results from tests in mice initiated the production of antibodies and it expects to begin phase I clinical trials in humans this summer.

For their part, the Newcotiana team released the genome sequence of Nicotiana benthamiana before being ready to publish it formally in an academic journal. Plenty of companies and academics will benefit from knowing as much as possible about the plants themselves through this genome, said Dr Orzez.

Dr Orzezalso says his team have pivoted to working on coronavirus, modifying some of their plants so that they produce the spike protein from SARS-CoV-2 virus. This spike protein is an important reagent in serological tests that determine if a person has developed Covid-19 antibodies.In plants, it can be produced quickly and easily in places where supplies of the protein are low. The team still need to work to make sure the proteins they produce are validated for safety but if they are, molecular farming could be a way of helping mass testing.

The fundamental attractions of molecular farming have not changed since the 1980s: it is cheap, its safe and it can be scaled up easily and quickly. As the coronavirus pandemic continues and the race is on to develop working vaccines, that last fact may prove to be extremely attractive, especially in poor parts of the world.

The research in this article was funded by the EU. If you liked this article, please consider sharing it on social media.

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We can programme plants to grow biomolecules. Is farming the future of vaccines? - Horizon magazine

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Global Single-cell Analysis Market 2020-2026: Expected to Grow by 17.1% CAGR to Surpass $2 Billion in 2026 – PRNewswire

DUBLIN, Aug. 25, 2020 /PRNewswire/ -- The "Single-cell Analysis Market by Product, Cell Type, Technique, End User, and by Geography - Forecast to 2026" report has been added to ResearchAndMarkets.com's offering.

The world market is predicted to reach $2,005 million in 2026 from $763.4 million in 2020. The market is predicted to grow at a CAGR of ~17.1%.

The information collected from this analysis is significant for cancer research for the discovery of tumor cells and genetic diagnosis. The factors such as advanced technology in products of single-cell analysis, increasing preference for customized medicine and rapidly increasing various chronic diseases such as cancer, which fuel the demand for the single-cell analysis market. However, the expensive products in the single-cell analysis are restraining market growth.

In the product based segmentation consumables segment is expected to have the largest share in the market. The reasons for the demand for consumables products are regularly purchasing the consumables compared to the instruments and the significant usage of consumables in the research and genetic exploration and segregation of RNA and DNA.

Based on cell type segmentation, the human cell segment is having the largest share in the market. The human cell is greatly used in the research laboratories due to the rising incidence of infectious diseases in the elderly population and the high investments in stem cell research.

On the bases of technique, the next-generation sequencing segment is expected to have the largest share in the market due to the increasing chronic diseases and next-generation sequencing allowing researchers to perform various applications.

Further, based on end-user segmentation, the academic and research laboratories segment is expected to have the largest share in the market. The increasing number of colleges and universities of medical and high investments in life science research are the factors accelerating the demand for single-cell analysis.

Moreover, based on the geography Asia Pacific region is playing a vital role in the market share compared to other regions due to rising number of patients in countries such as China and India, growing investments in the research and development in this field and outsourcing of drug discovery services to the Asia Pacific region. In addition, North America is the second-largest contributor to the market due to the high expenditure in the research and development and increased scope for stem cell research in this region.

The single-cell analysis market is expanding globally due to the increasingly advanced technology in the single-cell analysis products. The major factors accelerating the single-cell analysis market include rapidly increasing chronic diseases and cancer cases all over the world, increasing biotechnology & biopharmaceutical industries, and life science research. Although, due to high competition, the persistence of new entrants and small players is difficult in the market, and this is a challenge for market growth. The emerging markets in Asia are the future opportunities for the market.

The key market competitors in the market are Becton, Dickinson and Company, Danaher Corporatio, Merck Millipore, Qiagen N.V., Thermo Fisher Scientific, Inc, General Electric Company, BARCO, Promega Corporation, Shanghai Goodview Electronics, Fluidigm Corporation, Agilent Technologies, Inc, Nanostring Technologies, Inc., Tecan Group Ltd, Sartorius AG, LUMINEX CORPORATION, Takara Bio Inc., Takara Bio Inc., Fluxion Biosciences and Menarini Silicon Biosystems.

Moreover, the single-cell analysis has the largest scope in cancer research for the detection of the various tumor cells, preimplantation, and genetic diagnosis as the drastic increase in the cancer cases globally. The government is also supporting financially for cell-based research.

The single-cell analysis market report provides the present drifts, opportunities, restraining factors, and the challenges.

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/ejoe46

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

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Global Single-cell Analysis Market 2020-2026: Expected to Grow by 17.1% CAGR to Surpass $2 Billion in 2026 - PRNewswire

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Adagio Therapeutics Announces Appointment of Howard Mayer, M.D., to its Board of Directors – Business Wire

WALTHAM, Mass.--(BUSINESS WIRE)--Adagio Therapeutics, Inc., a company focused on the development of best-in-class antibodies to provide broad protection against SARS-CoV-2, SARS-CoV-1 and additional circulating bat coronaviruses, today announced that Howard Mayer, M.D., Executive Vice President and Head of Research and Development at Ipsen Pharmaceuticals, has joined its board of directors.

We are delighted to welcome Dr. Mayer to Adagios board of directors particularly with his deep virology and infectious diseases expertise and clinical development track record, said Tillman Gerngross, Ph.D., CEO of Adagio. As a new company rapidly advancing potentially best-in-class antibodies against SARS-CoV-2 as well as future/impending coronaviruses, Dr. Mayers expertise will be invaluable.

Im inspired and excited to join Adagio to combat the most important medical challenge of our generation. This is a world-class team advancing world-class science at a breathtaking pace and I believe we have the opportunity to make a tremendous difference in stopping this pandemic and preventing future coronavirus pandemics, said Howard Mayer.

Dr. Mayer joined Ipsen in 2019 from Shire, where he was Chief Medical Officer, responsible for the hematology, immunology, oncology, genetic diseases, GI/metabolic, neuroscience and ophthalmology therapeutic areas. Previously, Dr. Mayer served as Chief Medical Officer at EMD Serono, a division of Merck KGaA. Prior to that, he held a variety of global roles at Pfizer, including Head, Clinical Development and Medical Affairs for Virology/Infectious Diseases. Prior to joining Pfizer, he served as Director of Clinical Research at the Infectious Disease Clinical Research Division of Bristol-Myers Squibb.

Dr. Mayer obtained his B.A. from the University of Pennsylvania and his M.D. from Albert Einstein College of Medicine, which was followed by an internship and residency at Mount Sinai Hospital and an Infectious Diseases fellowship at Harvard Medical School. He currently serves on the board of directors for Entasis Therapeutics. He was honored by PharmaVoice as one of the 100 Most Inspiring People in the Life Sciences Industry in both 2011 and 2017.

Dr. Mayer will join current board members Terry McGuire of Polaris Partners, Marc Elia of M28 Capital, Ajay Royan of Mithril Capital and Phillip Chase of Adimab, Rene Russo, CEO of Xilio Therapeutics and Tillman Gerngross, Adagios CEO.

About Adagio

Adagio is developing best-in-class antibodies that can broadly neutralize SARS-CoV-2, SARS-CoV-1 and additional potentially emergent coronaviruses. We believe our antibodies will match or exceed the potency and coverage of conventional SARS-CoV-2 antibody programs, and can be used as both therapeutic and durable prophylactic treatments. Our candidates are engineered using best-in-industry antibody discovery capabilities and are designed to maximize potency and duration of effect. Our portfolio includes multiple, non-competing antibodies with distinct binding targets, enabling a strategy that can avoid viral escape. Our lead program is expected to enter the clinic by the end of 2020.

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Adagio Therapeutics Announces Appointment of Howard Mayer, M.D., to its Board of Directors - Business Wire

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Functioning liver cells regenerate in pig lymph nodes, and a human trial is coming – FierceBiotech

Hepatocytes in the liver can naturally regenerate, provided the organ is completely healthy. But when the liver is diseased, it has too much scar tissue to nurture the environment hepatocytes need to replenish themselves.

In a new study published in Liver Transplantation, researchers led by the University of Pittsburgh School of Medicine demonstrated that pigs can grow functioning livers in their abdominal lymph nodes after their own hepatocytes are isolated and injected into them. A startup founded by three of the researchers, LyGenesis, is working to bring the method into human clinical trials.

Senior author Eric Lagasse, Ph.D., associate professor of pathology at Pitt, first demonstrated a decade ago that healthy liver cells injected into the lymph nodes of mice with malfunctioning livers would regenerate and take over normal liver functions. To further prove out the concept, Lagasse wanted to replicate the work in a larger model.

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So Lagasse and his team took pieces of healthy liver tissue from six pigs while at the same time cutting off the main blood supply to the organ. They then injected the cells into abdominal lymph nodes. All six animals were able to regain normal liver functions, they reported.

When they examined the lymph nodes, the researchers discovered a plentiful supply of hepatocytes, along with bile ducts and vasculature that had formed in the transplanted cells.

"It's all about location, location, location," Lagasse said in a statement. "If hepatocytes get in the right spot and there is a need for liver functions, they will form an ectopic liver in the lymph node."

RELATED: Liver-focused Ambys launches with $140M, Takeda partnership

Regenerative approaches to treating liver disease have generated enthusiasm among private investors. In 2018, for example, Third Rock Ventures launched Ambys Medicines, which is developing both cell and gene therapy approaches to regenerating hepatocytes.

LyGenesis, which was founded in 2017, got a major boost in May of the following year when it pulled in $3 million in a series A round from Juvenescence, a U.K.-based fund that has raised $165 million to support longevity-focused companies. In October of last year, Juvenescence and Longevity Vision Fund handed LyGenesis another $4 million in private financing and convertible notes.

LyGenesis is gearing up to start a phase 2a clinical trial of its technique in people with end-stage liver disease later this year.

The new animal study follows previous work by Lagasse and colleagues demonstrating that liver tissue grown in the lymph nodes of pigs with a form of genetic liver disease could treat the condition effectively. The researchers believe the technique could ultimately help people with a wide range of liver-damaging diseases, including hepatitis and alcoholism.

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Functioning liver cells regenerate in pig lymph nodes, and a human trial is coming - FierceBiotech

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CRISPR cows could boost sustainable meat production, but regulations and wary consumers stand in the way – Genetic Literacy Project

When Ralph Fisher,a Texas cattle rancher, set eyes on one of the worlds first cloned calves in August 1999, he didnt care what the scientists said: He knew it was his old Brahman bull, Chance, born again. About a year earlier, veterinarians at Texas A&M extracted DNA from one of Chances moles and used the sample to create a genetic double. Chance didnt live to meet his second self, but when the calf was born, Fisher christened him Second Chance, convinced he was the same animal.

Scientists cautioned Fisher that clones are more like twins than carbon copies: The two may act or even look different from one another. But as far as Fisher was concerned, Second Chance was Chance. Not only did they look identical from a certain distance, they behaved the same way as well. They ate with the same odd mannerisms; laid in the same spot in the yard. But in 2003, Second Chance attacked Fisher and tried to gore him with his horns. About 18 months later, the bull tossed Fisher into the air like an inconvenience and rammed him into the fence. Despite 80 stitches and a torn scrotum, Fisher resisted the idea that Second Chance was unlike his tame namesake,telling the radio program This American Life that I forgive him, you know?

In the two decades since Second Chance marked a genetic engineering milestone, cattle have secured a place on the front lines of biotechnology research. Today, scientists around the world are using cutting-edge technologies, fromsubcutaneous biosensorstospecialized food supplements, in an effort to improve safety and efficiency within the$385 billion global cattle meat industry. Beyond boosting profits, their efforts are driven by an imminent climate crisis, in which cattle play a significant role, and growing concern for livestock welfare among consumers.

Gene editing stands out as the most revolutionary of these technologies. Although gene-edited cattle have yet to be granted approval for human consumption, researchers say tools like Crispr-Cas9 could let them improve on conventional breeding practices and create cows that are healthier, meatier, and less detrimental to the environment. Cows are also beinggiven genesfrom the human immune system to create antibodies in the fight against Covid-19. (The genes of non-bovine livestock such as pigs and goats, meanwhile, have been hacked togrow transplantable human organsandproduce cancer drugs in their milk.)

But some experts worry biotech cattle may never make it out of the barn. For one thing, theres the optics issue: Gene editing tends to grab headlines for its role in controversial research and biotech blunders. Crispr-Cas9 is often celebrated for its potential to alter the blueprint of life, but that enormous promise can become a liability in the hands of rogue and unscrupulous researchers, tempting regulatory agencies to toughen restrictions on the technologys use. And its unclear how eager the public will be to buy beef from gene-edited animals. So the question isnt just if the technology will work in developing supercharged cattle, but whether consumers and regulators will support it.

Cattle are catalysts for climate change. Livestockaccount for an estimated 14.5 percent of greenhouse gas emissions from human activities, of which cattle are responsible for about two thirds, according to the United Nations Food and Agriculture Organization (FAO). One simple way to address the issue is to eat less meat. But meat consumption is expected to increasealong with global population and average income. A 2012reportby the FAO projected that meat production will increase by 76 percent by 2050, as beef consumption increases by 1.2 percent annually. And the United States isprojected to set a recordfor beef production in 2021, according to the Department of Agriculture.

For Alison Van Eenennaam, an animal geneticist at the University of California, Davis, part of the answer is creating more efficient cattle that rely on fewer resources. According to Van Eenennaam, the number of dairy cows in the United Statesdecreasedfrom around 25 million in the 1940s to around 9 million in 2007, while milk production has increased by nearly 60 percent. Van Eenennaam credits this boost in productivity to conventional selective breeding.

You dont need to be a rocket scientist or even a mathematician to figure out that the environmental footprint or the greenhouse gases associated with a glass of milk today is about one-third of that associated with a glass of milk in the 1940s, she says. Anything you can do to accelerate the rate of conventional breeding is going to reduce the environmental footprint of a glass of milk or a pound of meat.

Modern gene-editing tools may fuel that acceleration. By making precise cuts to DNA, geneticists insert or remove naturally occurring genes associated with specific traits. Some experts insist that gene editing has the potential to spark a new food revolution.

Jon Oatley, a reproductive biologist at Washington State University, wants to use Crispr-Cas9 to fine tune the genetic code of rugged, disease-resistant, and heat-tolerant bulls that have been bred to thrive on the open range. By disabling a gene called NANOS2, he says he aims to eliminate the capacity for a bull to make his own sperm, turning the recipient into a surrogate for sperm-producing stem cells from more productive prized stock. These surrogate sires, equipped with sperm from prize bulls, would then be released into range herds that are often genetically isolated and difficult to access, and the premium genes would then be transmitted to their offspring.

Furthermore, surrogate sires would enable ranchers to introduce desired traits without having to wrangle their herd into one place for artificial insemination, says Oatley. He envisions the gene-edited bulls serving herds in tropical regions like Brazil, the worldslargestbeef exporter and home to around 200 million of the approximately 1.5 billion head of cattle on Earth.

Brazils herds are dominated by Nelore, a hardy breed that lacks the carcass and meat quality of breeds like Angus but can withstand high heat and humidity. Put an Angus bull on a tropical pasture and hes probably going to last maybe a month before he succumbs to the environment, says Oatley, while a Nelore bull carrying Angus sperm would have no problem with the climate.

The goal, according to Oatley, is to introduce genes from beefier bulls into these less efficient herds, increasing their productivity and decreasing their overall impact on the environment. We have shrinking resources, he says, and need new, innovative strategies for making those limited resources last.

Oatley has demonstrated his technique in mice but faces challenges with livestock. For starters, disabling NANOS2 does not definitively prevent the surrogate bull from producing some of its own sperm. And while Oatley has shown he can transplant sperm-producing cells into surrogate livestock, researchers have not yet published evidence showing that the surrogatesproduceenough quality sperm to support natural fertilization. How many cells will you need to make this bull actually fertile? asks Ina Dobrinski, a reproductive biologist at the University of Calgary who helped pioneer germ cell transplantation in large animals.

But Oatleys greatest challenge may be one shared with others in the bioengineered cattle industry: overcoming regulatory restrictions and societal suspicion. Surrogate sires would be classified as gene-edited animals by the Food and Drug Administration, meaning theyd face a rigorous approval process before their offspring could be sold for human consumption. But Oatley maintains that if his method is successful, the sperm itself would not be gene-edited, nor would the resulting offspring. The only gene-edited specimens would be the surrogate sires, which act like vessels in which the elite sperm travel.

Even so, says Dobrinski, Thats a very detailed difference and Im not sure how that will work with regulatory and consumer acceptance.

In fact, American attitudes towards gene editing have been generally positive when the modification is in the interest of animal welfare. Many dairy farmers prefer hornless cows horns can inflict damage when wielded by 1,500-pound animals so they often burn them off in apainful processusing corrosive chemicals and scalding irons. Ina study published last yearin the journal PLOS One, researchers found that most Americans are willing to consume food products from cows genetically modified to be hornless.

Still, experts say several high-profile gene-editing failures in livestock andhumansin recent years may lead consumers to consider new biotechnologies to be dangerous and unwieldy.

In 2014, a Minnesota startup called Recombinetics, a company with which Van Eenennaams lab has collaborated, created a pair of cross-bred Holstein bulls using the gene-editing tool TALENs, a precursor to Crispr-Cas9, making cuts to the bovine DNA and altering the genes to prevent the bulls from growing horns. Holstein cattle, which almost always carry horned genes, are highly productive dairy cows, so using conventional breeding to introduce hornless genes from less productive breeds can compromise the Holsteins productivity. Gene editing offered a chance to introduce only the genes Recombinetics wanted. Their hope was to use this experiment to prove that milk from the bulls female progeny was nutritionally equivalent to milk from non-edited stock. Such results could inform future efforts to make Holsteins hornless but no less productive.

The experiment seemed to work. In 2015, Buri and Spotigy were born. Over the next few years, the breakthrough received widespread media coverage, and when Buris hornless descendant graced thecover of Wired magazine in April 2019, it did so as the ostensible face of the livestock industrys future.

But early last year, a bioinformatician at the FDA ran a test on Buris genome and discovered an unexpected sliver of genetic code that didnt belong. Traces of bacterial DNA called a plasmid, which Recombinetics used to edit the bulls genome, had stayed behind in the editing process, carrying genes linked to antibiotic resistance in bacteria. After the agency publishedits findings, the media reaction was swift and fierce: FDA finds a surprise in gene-edited cattle: antibiotic-resistant, non-bovine DNA,readone headline. Part cow, part bacterium?readanother.

Recombinetics has since insisted that the leftover plasmid DNA was likely harmless and stressed that this sort of genetic slipup is not uncommon.

Is there any risk with the plasmid? I would say theres none, says Tad Sonstegard, president and CEO of Acceligen, a Recombinetics subsidiary. We eat plasmids all the time, and were filled with microorganisms in our body that have plasmids. In hindsight, Sonstegard says his teams only mistake was not properly screening for the plasmid to begin with.

While the presence of antibiotic-resistant plasmid genes in beef probably does not pose a direct threat to consumers, according to Jennifer Kuzma, a professor of science and technology policy and co-director of the Genetic Engineering and Society Center at North Carolina State University, it does raise the possible risk of introducing antibiotic-resistant genes into the microflora of peoples digestive systems. Although unlikely, organisms in the gut could integrate those genes into their own DNA and, as a result, proliferate antibiotic resistance, making it more difficult to fight off bacterial diseases.

The lesson that I think is learned there is that science is never 100 percent certain, and that when youre doing a risk assessment, having some humility in your technology product is important, because you never know what youre going to discover further down the road, she says. In the case of Recombinetics. I dont think there was any ill intent on the part of the researchers, but sometimes being very optimistic about your technology and enthusiastic about it causes you to have blinders on when it comes to risk assessment.

The FDA eventually clarified its results, insisting that the study was meant only to publicize the presence of the plasmid, not to suggest the bacterial DNA was necessarily dangerous. Nonetheless, the damage was done. As a result of the blunder,a plan was quashedforRecombinetics to raise an experimental herd in Brazil.

Backlash to the FDA study exposed a fundamental disagreement between the agency and livestock biotechnologists. Scientists like Van Eenennaam, who in 2017 received a $500,000 grant from the Department of Agriculture to study Buris progeny, disagree with the FDAs strict regulatory approach to gene-edited animals. Typical GMOs aretransgenic, meaning they have genes from multiple different species, but modern gene-editing techniques allow scientists to stay roughly within the confines of conventional breeding, adding and removing traits that naturally occur within the species.

That said, gene editing is not yet free from errors and sometimes intended changes result in unintended alterations, notes Heather Lombardi, division director of animal bioengineering and cellular therapies at the FDAs Center for Veterinary Medicine. For that reason, the FDA remains cautious.

Theres a lot out there that I think is still unknown in terms of unintended consequences associated with using genome-editing technology, says Lombardi. Were just trying to get an understanding of what the potential impact is, if any, on safety.

Bhanu Telugu, an animal scientist at the University of Maryland and president and chief science officer at the agriculture technology startup RenOVAte Biosciences, worries that biotech companies willmigrate their experimentsto countries with looser regulatory environments. Perhaps more pressingly, he says strict regulation requiring long and expensive approval processes may incentivize these companies to work only on traits that are most profitable, rather than those that may have the greatest benefit for livestock and society, such as animal well-being and the environment.

What company would be willing to spend $20 million on potentially alleviating heat stress at this point? he asks.

On a windywinter afternoon, Raluca Mateescu leaned against a fence post at the University of Floridas Beef Teaching Unit while a Brahman heifer sniffed inquisitively at the air and reached out its tongue in search of unseen food. Since 2017, Mateescu, an animal geneticist at the university, has been part of a team studying heat and humidity tolerance in breeds like Brahman and Brangus (a mix between Brahman and Angus cattle). Her aim is to identify the genetic markers that contribute to a breeds climate resilience, markers that might lead to more precise breeding and gene-editing practices.

In the South, Mateescu says, heat and humidity are a major problem. That poses a stress to the animals because theyre selected for intense production to produce milk or grow fast and produce a lot of muscle and fat.

Like Nelore cattle in South America, Brahman are well-suited for tropical and subtropical climates, but their high tolerance for heat and humidity comes at the cost of lower meat quality than other breeds. Mateescu and her team have examined skin biopsies and found that relatively large sweat glands allow Brahman to better regulate their internal body temperature. With funding from the USDAs National Institute of Food and Agriculture, the researchers now plan to identify specific genetic markers that correlate with tolerance to tropical conditions.

If were selecting for animals that produce more without having a way to cool off, were going to run into trouble, she says.

There are other avenues in biotechnology beyond gene editing that may help reduce the cattle industrys footprint. Although still early in their development,lab-cultured meatsmay someday undermine todays beef producers by offering consumers an affordable alternative to the conventionally grown product, without the animal welfare and environmental concerns that arise from eating beef harvested from a carcass.

Other biotech techniques hope to improve the beef industry without displacing it. In Switzerland, scientists at a startup called Mootral areexperimenting with a garlic-based food supplementdesigned to alter the bovine digestive makeup to reduce the amount of methane they emit. Studies have shown the product to reduce methane emissions by about 20 percent in meat cattle, according to The New York Times.

In order to adhere to the Paris climate agreement, Mootrals owner, Thomas Hafner, believes demand will grow as governments require methane reductions from their livestock producers. We are working from the assumption that down the line every cow will be regulated to be on a methane reducer, he told The New York Times.

Meanwhile, a farm science research institute in New Zealand, AgResearch, hopes to target methane production at its source by eliminating methanogens, the microbes thought to be responsible for producing the greenhouse gas in ruminants. The AgResearch team isattempting to developa vaccine to alter the cattle guts microbial composition, according to the BBC.

Genomic testing may also allow cattle producers to see what genes calves carry before theyre born, according to Mateescu, enabling producers to make smarter breeding decisions and select for the most desirable traits, whether it be heat tolerance, disease resistance, or carcass weight.

Despite all these efforts, questions remain as to whether biotech can ever dramatically reduce the industrys emissions or afford humane treatment to captive animals in resource-intensive operations. To many of the industrys critics, including environmental and animal rights activists, the very nature of the practice of rearing livestock for human consumption erodes the noble goal of sustainable food production. Rather than revamp the industry, these critics suggest alternatives such as meat-free diets to fulfill our need for protein. Indeed,data suggestsmany young consumers are already incorporating plant-based meats into their meals.

Ultimately, though, climate change may be the most pressing issue facing the cattle industry, according to Telugu of the University of Maryland, which received a grant from the Bill and Melinda Gates Foundation to improve productivity and adaptability in African cattle. We cannot breed our way out of this, he says.

Dyllan Furness is a Florida-based science and technology journalist. His work has appeared in Quartz, OneZero, and PBS, among other outlets. Follow him on Twitter @dyllonline

This article was originally published at Undark and has been republished here with permission. Follow Undark on Twitter @undarkmag

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CRISPR cows could boost sustainable meat production, but regulations and wary consumers stand in the way - Genetic Literacy Project

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