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Here’s Why Arrowhead Pharmaceuticals Is Soaring Today – The Motley Fool

Posted: December 5, 2019 at 6:49 am

What happened

Shares of Arrowhead Pharmaceuticals (NASDAQ:ARWR) gained as much as 14.4% today after the company announced a public stock offering. It seems counterintuitive, but investors appear to be excited about a snippet of text listing possible uses for the proceeds.

The company made the standard explanation that the cash will be used for general corporate expenses, to fund maturing clinical trials, and the like. But Arrowhead Pharmaceuticals also included a nonstandard detail in the press release for the public offering: "A portion of the net proceeds may also be used for the acquisition of complementary businesses, products and technologies, or for other strategic purposes."

Investors may be getting a little ahead of themselves here, but if Arrowhead Pharmaceuticals pulls the trigger on any strategic investment, then it's likely to be in one (relatively boring) category in particular.

As of 1:55 p.m. EST, the pharma stock had settled to a 10.2% gain.

Image source: Getty Images.

The developer of precision genetic medicines based on RNA interference (RNAi), a technique used to silence disease-driving genes, ended September with $221.8 million in cash and another $37 million in short-term investments. The proposed public offering of up to 4.6 million shares hasn't been priced yet; that information should be announced after market close today. But assuming an offering price of $60 per share, the business would raise up to $275 million in gross proceeds -- not a bad haul.

What could the cash be used for? Well, Arrowhead Pharmaceuticals decided to account for a $252.6 million up-front payment and equity investment, received from Johnson & Johnson subsidiary Janssen in late 2018, using the proportional accounting method. That allowed the business to count chunks of that total each quarter during its fiscal 2019, which resulted in full-year 2019 operating income of $61 million. It reported an operating loss of $55.9 million in fiscal 2018.

The proportional-accounting-method well will run dry in 2020, as there was just $77.8 million remaining against the up-front payment total at the end of September (the end of its fiscal year). In other words, the business is likely to report operating losses again in the near future.

What about a strategic investment, as hinted at in the press release for the public offering? That could happen, too. It may be a little less exciting than investors are imagining, however, because it's likely to be in drug manufacturing.

Arrowhead Pharmaceuticals spent $22 million on drug manufacturing in fiscal 2019, making it the single largest expense in the research and development category -- even more expensive than running clinical trials. The RNAi company has relatively strict manufacturing requirements, and the expense is starting to grow at a significant rate, so it may make sense to bring some of that expertise in-house with its own facility. Others in the precision-medicine space have done the same to reduce costs and operational risks. In fact, there's a manufacturing arms race in gene therapy right now.

The company is wisely taking advantage of a soaring stock price to pad its balance sheet. It will certainly need the cash to develop a maturing pipeline, and to fund operations once a lucrative collaboration revenue stream runs dry in 2020.

Whether Arrowhead Pharmaceuticals makes an acquisition of new technology or boring old manufacturing assets (or none at all), the company is correctly focused on the long term. That said, the company does appear to be a little expensive right now.

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Breakeven On The Horizon For Sarepta Therapeutics, Inc. (NASDAQ:SRPT) – Yahoo Finance

Posted: December 5, 2019 at 6:49 am

Sarepta Therapeutics, Inc.'s (NASDAQ:SRPT): Sarepta Therapeutics, Inc. focuses on the discovery and development of RNA-based therapeutics, gene therapy, and other genetic medicine approaches for the treatment of rare diseases. The US$8.4b market-cap posted a loss in its most recent financial year of -US$361.9m and a latest trailing-twelve-month loss of -US$620.3m leading to an even wider gap between loss and breakeven. The most pressing concern for investors is SRPTs path to profitability when will it breakeven? Ive put together a brief outline of industry analyst expectations for SRPT, its year of breakeven and its implied growth rate.

See our latest analysis for Sarepta Therapeutics

According to the 22 industry analysts covering SRPT, the consensus is breakeven is near. They expect the company to post a final loss in 2021, before turning a profit of US$676m in 2022. SRPT is therefore projected to breakeven around 3 years from now. What rate will SRPT have to grow year-on-year in order to breakeven on this date? Using a line of best fit, I calculated an average annual growth rate of 68%, which is rather optimistic! If this rate turns out to be too aggressive, SRPT may become profitable much later than analysts predict.

NasdaqGS:SRPT Past and Future Earnings, December 3rd 2019

Im not going to go through company-specific developments for SRPT given that this is a high-level summary, though, bear in mind that by and large a biotech has lumpy cash flows which are contingent on the product type and stage of development the company is in. This means, large upcoming growth rates are not abnormal as the company is beginning to reap the benefits of earlier investments.

One thing I would like to bring into light with SRPT is its relatively high level of debt. Typically, debt shouldnt exceed 40% of your equity, which in SRPTs case is 44%. Note that a higher debt obligation increases the risk in investing in the loss-making company.

This article is not intended to be a comprehensive analysis on SRPT, so if you are interested in understanding the company at a deeper level, take a look at SRPTs company page on Simply Wall St. Ive also put together a list of relevant aspects you should look at:

If you spot an error that warrants correction, please contact the editor at editorial-team@simplywallst.com. This article by Simply Wall St is general in nature. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. Simply Wall St has no position in the stocks mentioned.

We aim to bring you long-term focused research analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Thank you for reading.

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NIH taps Tulane neuroscientist to lead effort to standardize research in genetic aging – News from Tulane

Posted: December 5, 2019 at 6:49 am

Tulane University neuroscientist Dr. Stacy Drury will launch the Telomere Research Network to establish best practices for measuring telomere length and how it can be used as a sentinel of aging-related disease risk. Photo by Jennifer Zdon.

The National Institutes of Health awarded a $2.9 million grant to Tulane University neuroscientist Dr. Stacy Drury to lead a research network that will set methodological standards for studying a part of the chromosome that scientists increasingly recognize as an important biological marker of aging and age-related diseases.

Drury will launch theTelomere Research Network to establish best practices for measuring telomere length in population-based studies. Telomeres are the caps at the end of chromosomes that keep them from shrinking when cells replicate. Shorter telomeres are linked to higher risks for heart disease, obesity, cognitive decline, diabetes, mental illness and poor health outcomes in adulthood.

The network willdefine the extent to which telomere length can be effectively applied as a sentinel of aging-related disease risk and an indicator of environmental and psychosocial stress exposure across the life span, said Drury, the Remigio Gonzalez, MD, Professor of Child Psychiatry at Tulane University School of Medicine. We are charged with bringing together all of the international experts in the field and becoming a central focus for this research across the globe.

There has been an explosion in telomere research within the last decade. But scientists have used different measurement criteria, leading to problems replicating research results in some studies.

As it becomes clearer that it is a very powerful marker, the rigor of the science has to get better, Drury said. Because so many people are studying it in so many different ways, we don't want to dilute the impact by having lots of people using methodology that isnt the best.

The network will define the extent that telomeres can be used as a marker of environmental exposures, psychosocial stress and disease susceptibility. It will also provide a forum for researchers to share samples, research data, study protocols and discussions on best practices for the field.

The network will convene for its first meeting Dec. 5-6 in Washington, D.C. The event will be streamed online athttps://tulane.zoom.us/j/258026269.

Weatherhead Professor of Pharmacology John McLachlan is a co-investigator on the grant. Drury will be working with collaborators at the University of Groningen, University of California at San Francisco, Georgetown University, Pennsylvania State University and Rutgers University.

The NIHs National Institute on Aging and the National Institute of Environmental Health Sciences funded the initiative under grant award No.U24AG066528.

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What we’ve learnt from building Africa’s biggest genome library – The Conversation Africa

Posted: December 5, 2019 at 6:49 am

The human genome was first sequenced in 2003 by multiple research centres across the world. The breakthrough was hailed as the dawn of a new era. Genetics would swiftly transform our response to disease and lead to personalised medicine.

In the past decade there has been substantial progress in terms of studying genetic factors giving rise to disease. But much of this has been focused on European populations. Little progress has been made in examining the factors associated with disease among Africans.

Until very recently, only a few hundred whole genome sequences of individuals within Africa had been completed. Researchers largely relied on genetic data from African-Americans. These have provided many new insights. But they dont reflect the continents full genetic diversity.

Africa is known to be where humans originated. From Africa, they migrated to other parts of the world. This makes it the most genetically diverse region in the world. Diversity among other populations represents a subset of the diversity within Africa.

This genetic diversity provides unique opportunities to examine genetic factors associated with disease that cant be examined in Europeans where diversity is much lower. This highlights the need for much larger studies of genetic causes of disease within Africa.

We conducted a study to build one of the largest genome resources from within Africa. We developed a rich, diverse resource using genome wide data from 6,400 Ugandans the Uganda Genome Resource. It included whole genome sequencing of nearly 2,000 people.

The study built on the long standing research programme of the Medical Research Council Uganda and Uganda Virus Research Institute. Its aim has been to establish a clinical and genomic data resource to understand population health and disease in the region.

The team also incorporated data on 14,000 individuals from different parts of the continent. It did this in collaboration with the University of KwaZulu-Natal and the Centre of Genomics and Global Health, National Institutes of Health. This allowed us to examine genetic determinants of traits within the population.

Around a quarter of the genetic variation identified had not been discovered before. We found a higher level of genetic diversity in the Ugandan population than seen in similar studies of European populations.

Modern Uganda appears to be a complex mosaic of genetic flow from many different communities that have migrated from surrounding regions within Africa and from Europe or the Middle East. This gene flow appears to have occurred repeatedly, dating back from around 100 years ago to as long as 4,500 years ago.

Our work is an important step forward in African medical genetics research. But much more research is needed to understand how these genetic variants affect disease traits. That means looking at the functional effects of genomes on gene expression and protein levels.

In our study, we discovered ten new associations with blood traits, liver function tests and indicators of diabetes. Most of these new associations relate to genetic variants that are unique to the Ugandan population or very rare in non-Africans. These would not have been discovered even in very large studies of Europeans.

For example, we identified an association between a genetic variant that causes alpha-thalassemia, a blood disorder that leads to anaemia, and glycated haemoglobin levels, which are commonly used for diagnosis of diabetes. This genetic variant is found in 22% of Africans. It has become very common in some regions within Africa because it also protects against severe malaria. It remains very rare in other populations where malaria isnt endemic. Our findings suggest that the utility of glycated haemoglobin as a diagnostic tool for diabetes may require re-evaluation in regions where alpha-thalassemia a blood disorder that reduces the production of haemoglobin is common.

The richness of the Uganda resource also offered us other opportunities. For example, we were able to study the extent to which genetic differences influence differences in traits among Ugandans relative to previous studies in European populations. We found that heritability the extent to which genetic differences encode differences in traits or diseases may differ between Ugandans and Europeans.

We also found that height is less genetically determined in rural Ugandans relative to previous European studies. We think that this might relate to differences in the impact of environmental factors between rural Ugandan and European populations. For example, the genetic influences on height might be more limited by nutritional influences in early childhood.

Our findings highlight the usefulness of examining genetically diverse populations within Africa. They underscore how this can lead to new discoveries and help us understand the genetic encoding of traits that may be different within Africa relative to other populations.

Africa is central to our understanding of human origins, genetic diversity and disease susceptibility. There is a clear scientific and public health need to develop large-scale projects that examine disease susceptibility across diverse populations across the continent. That work should be integrated with initiatives to improve research capacity in Africa.

We now need larger and more diverse studies of genetic causes of disease across the region. These will foster the development of new treatments that will benefit people living in Africa as well as people of African descent around the world.

Future work will look at individuals from other parts of Africa. The aim will be to get a deeper understanding of genetic diversity among indigenous hunter-gatherer populations. These include the Khoe-San populations in Namibia and South Africa and the rain forest populations in central Africa. In addition, we will be expanding current studies of genetic causes of disease to 100,000 individuals across the region.

The data was collected by researchers from universities and research institutes from Africa and the UK, including Queen Mary University of London, the University of KwaZulu-Natal, MRC/UVRI & London School of Hygiene & Tropical Medicine Uganda Research Unit, the US National Institute of Health and the University of Cambridge.

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2019: the year gene therapy came of age – FRANCE 24

Posted: December 5, 2019 at 6:49 am

Washington (AFP)

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome.

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

"I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email.

"Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

"But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

- Cures -

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union.

They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris.

"It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection.

"You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

- Bioterrorism -

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal -- and his excommunication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

"Not everyone is a biologist or scientist," she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops?

Charpentier thinks that technology generally tends to be used for the better.

"I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

2019 AFP

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Blood Test that Measures Expression of 5,000 Proteins Shows Potential as Disease Screening Tool – Clinical OMICs News

Posted: December 5, 2019 at 6:49 am

Specific patterns of protein levels in our blood could be used to provide a comprehensive liquid health check that gives a snapshot of health and potentially an indication of the likelihood that we will develop certain diseases or health risk factors in the future, according to research by scientists in the U.S. and U.K. working with SomaLogic. The results of their proof-of-concept study involving more than 16,000 participants, and published in Nature Medicine, showed that while the accuracy of models based on specific protein expression patterns varied, they were all either better predictors than models based on traditional risk factors, or would constitute more convenient and less expensive alternatives to traditional testing.

This proof of concept study demonstrates a new paradigm that measurement of blood proteins can accurately deliver health information that spans across numerous medical specialties and that should be actionable for patients and their healthcare providers, said Peter Ganz, MD, co-leader of this study and the Maurice Eliaser distinguished professor of medicine at UCSF and director of the Center of Excellence in Vascular Research at Zuckerberg San Francisco General Hospital and Trauma Center. I expect that in the future we will look back at this Nature Medicine proteomic study as a critical milestone in personalizing and thus improving the care of our patients. The teams published study is titled, Plasma protein patterns as comprehensive indicators of health.

Preventative medicine programs such as the U.K. National Health Services Health Check and Healthier You programs are aimed at improving individuals health and reducing the risk of developing diseases. While such strategies are inexpensive, cost-effective, and scalable, they could also be made more effective using personalized information about an individuals health and disease risk, the authors suggested. The application of big data in healthcare, assessing and analyzing detailed, large-scale datasets, makes it increasingly feasible to make predictions about health and disease outcomes and enable stratified approaches to prevention and clinical management. Protein scanning represents a potential approach to bridging the gap between the need for practicality and low cost, and the potential for personalized, systemic, and data-driven medicine.

Proteins regulate biological processes and can integrate the effects of genes with the effects of environment, age, existing diseases, and lifestyle behaviors, the authors explained. Our genomes contain about 19,000 genes that code for some 30,000 different proteins. Up to 2,200 of these proteins, including hormones, cytokines, and growth factors, are purposefully secreted into the blood, to orchestrate biological processes in health or in disease. Other proteins enter the blood through leakage from damaged or dead cells. Both secreted and leaked proteins can inform health status and disease risk.

In a proof-of-concept study based on five observational cohorts involving 16,894 participants, the researchers scanned 5,000 proteins in single blood plasma samples taken from each participant, to simultaneously capture the individualized imprints of current health status, the impact of modifiable behaviors, and incident risk of cardiometabolic diseases (diabetes, coronary heart disease, stroke, or heart failure).

To analyze the proteins in each sample the researchers used a technique that harnessed fragments of DNA known as aptamers, which bind to the target protein. In general, only specific fragments will bind to particular proteins. Using existing genetic sequencing technology, the researchers could then search for the aptamers and determine which proteins are present and in what concentrations. In total, the study carried out about 85 million protein measurements in the nearly 17,000 participants.

The researchers analyzed the results using statistical methods and machine learning techniques to develop predictive modelsfor example, that an individual whose blood contains a certain pattern of proteins is at increased risk of developing diabetes. The models covered a number of health states, including levels of liver fat, kidney function and visceral fat, alcohol consumption, physical activity, and smoking behavior, and for risk of developing type 2 diabetes and cardiovascular disease.

The accuracy of the models varied, with some showing high predictive powers, such as for percentage body fat. Other models demonstrated only modest prognostic power, such as that for cardiovascular risk, but even this was still modestly better than traditional risk factors and could also add value in overcoming the incomplete utilization of risk calculation in primary care, the team wrote. Many of the proteins measured linked to a number of health states or conditions. Leptin, for example, modulates appetite and metabolism, and was informative for predictive models of percentage body fat, visceral fat, physical activity, and fitness.

The researchers pointed out that a key feature of the study is that it used information from just one source, a single blood draw, for protein-phenotype models, the authors pointed out. This was a key objective of our health check proof of concept. The team didnt include demographic or known risk factors in their modelsunless absolutely necessary. They also didnt test whether they models could be improved by adding in other features, such as history, laboratory tests, or genetic information. It is possible that these multi-source models could improve absolute models performance, although their inclusion has potential implications for increasing costs and loss of convenience.

One difference between genome sequencing and proteomics approaches is that whereas the genome is fixed, the proteome changes over time, possibly as an individual becomes more obese, less physically active, or smokes, for example. These changes in proteins could be used to track changes in an individuals health status over a lifetime.

Proteins circulating in our blood are a manifestation of our genetic make-up as well as many other factors, such as behaviors or the presence of disease, even if not yet diagnosed, said Claudia Langenberg, M.D., from the MRC Epidemiology Unit at the University of Cambridge. This is one of the reasons why proteins are such good indicators of our current and future health state and have the potential to improve clinical prediction across different and diverse diseases.

While this study shows a proof-of-principle, the researchers acknowledged that there were limitations, and suggested that as technology improves and becomes more affordable, it is feasible that a comprehensive health evaluation using a battery of protein models derived from a single blood sample, could be offered as routine by health services. It is thus conceivable that, with further validation and the potential for expansion of the number of tests, a comprehensive, holistic health evaluation using a battery of protein models derived from a single blood sample could be performed. The next step is to test the applicability of the protein models that we have derived and validated in observational cohorts under research conditions in real-world healthcare systems.

Its remarkable that plasma protein patterns alone can faithfully represent such a wide variety of common and important health issues, and we think that this is just the tip of the iceberg, said study lead Stephen Williams, M.D., chief medical officer at SomaLogic, which is developing its SomaScan Platform and SomaSignal tests for a wide range of human diseases. We have more than a hundred tests in our SomaSignal pipeline and believe that large-scale protein scanning has the potential to become a sole information source for individualized health assessments.

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Transition to exhaustion: clues for cancer immunotherapy – 7thSpace Interactive

Posted: December 5, 2019 at 6:48 am

Transition to exhaustion: clues for cancer immunotherapy

Research on immune cells "exhausted" by chronic viral infection provides clues on how to refine cancer immunotherapy. The results are scheduled for publication in Immunity.

Scientists at Emory Vaccine Center, led by Rafi Ahmed, PhD, have learned about exhausted CD8 T cells, based on studying mice with chronic viral infections. In the presence of persistent virus or cancer, CD8 T cells lose much of their ability to fight disease, and display inhibitory checkpoint proteins such as PD-1 on their surfaces. PD-1 is targeted by cancer immunotherapy drugs, such as pembrolizumab and nivolumab, which allow CD8 T cells to regain their ability to attack and kill infected cells and cancers.

Those drugs are now FDA-approved for several types of cancer, yet some types of tumors do not respond to them. Studying exhausted CD8 T cells can help us understand how to better draw the immune system into action against cancer or chronic infections.

In previous research, Ahmed's lab found that exhausted cells are not all alike, and the diversity within the exhausted T cell pool could explain variability in responses to cancer immunotherapy drugs. Specifically, they observed that a population of "stem-like" cells proliferated in response to PD-1-blocking drugs, while a more differentiated population of exhausted cells stayed inactive. The stem-like cells are responsible for maintaining the exhausted T cell population, but cannot kill virus-infected or tumor cells on their own.

The current paper defines a transitional stage in between the stem-like and truly exhausted cells. The truly exhausted cells are marked by a molecule called CD101, and are unable to migrate to sites of infection and contain lower amounts of proteins needed to kill infected or tumor cells.

"The transitional cells are not completely exhausted," says postdoctoral fellow Will Hudson, PhD, first author of the Immunity paper. "They are still capable of proliferating and performing their 'killer cell' functions. In our experiments, they contribute to viral control."

The transitional cells, lacking CD101, could be a good marker for response to PD-1 blocking drugs, Hudson says. Enhancing the proliferation or survival of these cells, or preventing their transition to lasting exhaustion, may be a novel therapeutic strategy for cancer.

"It is extremely exciting to have contributed to this project and know that our findings have the potential to inform cancer immunotherapy," says co-author Julia Gensheimer, an Emory graduate, now a MD/PhD student at UCLA.

The Immunity paper also includes systematic identification of other markers for CD8 T cells in various stages of exhaustion, which could be a guide to efforts to promote their activity.

###

Ahmed is a Georgia Research Alliance Eminent Scholar. Hudson was supported by a Cancer Research Institute Irvington Postdoctoral Fellowship, and Ahmed's lab was supported by the National Institute of Allergy and Infectious Diseases (R01AI030048, P01AI056299).

This story has been published on: 2019-12-04. To contact the author, please use the contact details within the article.

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Raiders Of The Lost Crops: Scientists Race Against Time To Save Genetic Diversity – NPR

Posted: December 4, 2019 at 7:44 am

Members of the Crop Wild Relatives project from the Crop Trust joined their research partners in Nepal on an expedition to collect wild relatives of rice, okra and eggplant in October 2017. Hannes Dempewolf of the Crop Trust says the elephants kept the researchers high enough off the ground that they didn't have to worry about any snakes that might be lurking. L.M. Salazar/Crop Trust hide caption

Members of the Crop Wild Relatives project from the Crop Trust joined their research partners in Nepal on an expedition to collect wild relatives of rice, okra and eggplant in October 2017. Hannes Dempewolf of the Crop Trust says the elephants kept the researchers high enough off the ground that they didn't have to worry about any snakes that might be lurking.

Call it a tale of science and derring-do. An international team of researchers has spent six years fanning across the globe, gathering thousands of samples of wild relatives of crops. Their goal: to preserve genetic diversity that could help key crops survive in the face of climate change. At times, the work put these scientists in some pretty extreme situations.

Just ask Hannes Dempewolf. Two years ago, the plant geneticist found himself in a rainforest in Nepal, at the foot of the Himalayas. He was riding on the back of an elephant to avoid snakes on the ground and to scare away any tigers that might be lurking about. Then all of a sudden came an attack from above.

"There were leeches dropping on us from all directions," Dempewolf recalls "bloodsucking leeches."

Now, this is far from where he thought he'd be when he got his Ph.D. But as a senior scientist and head of global initiatives at the Crop Trust, Dempewolf has been overseeing an ambitious international collaboration. More than 100 scientists in 25 countries have been venturing out to collect wild relatives of domesticated crops like lentils, potatoes, chickpeas and rice that people rely on around the world. The Crop Trust has just released a report detailing the results of this massive effort, which secured more than 4,600 seed samples of 371 wild relatives of key domesticated crops that the world relies on.

The "collecting teams are heading out into wild places and hard-to-reach corners within their countries to try to find and track down some of these wild species that have either never been collected before or are very underrepresented in seed banks," Dempewolf explains. So he says it's not surprising that many of the stories coming out of the project have an Indiana Jones-like sense of adventure to them.

Take, for example, an effort to collect Oryza glumaepatula, a wild rice species found in Latin America. Griselda Arrieta Espinoza, a crop genetics and biotechnology researcher at the University of Costa Rica, was part of a collecting team that set out to northern Costa Rica to collect a particular population of this wild rice that grows in a river. "Collecting it was quite the adventure," she tells me in Spanish because the river is also home to crocodiles.

While the effort was dangerous, Arrieta says it was also worth it, because Oryza glumaepatula is known to be resistant to a fungus that attacks domesticated rice grown around the world. And she notes that researchers in Brazil have already managed to cross Oryza glumaepatula with domesticated rice to improve crop yields.

Jamal Mabrouki, a technician with the International Center for Agricultural Research in the Dry Areas, works on a grasspea breeding project at ICARDA's facilities at Marchouch station, Morocco. Michael Major/Crop Trust hide caption

Jamal Mabrouki, a technician with the International Center for Agricultural Research in the Dry Areas, works on a grasspea breeding project at ICARDA's facilities at Marchouch station, Morocco.

The overall goal of the Crop Trust project is to make sure that this kind of valuable genetic diversity is preserved in seed banks before wild crop relatives disappear as urban development encroaches on once wild habitats. Dempewolf says that this is already happening.

"Some of the populations that the [research teams] were hoping to collect, when they reached the areas where they had seen populations before, they had disappeared," Dempewolf says.

Steven Tanksley, a professor emeritus of plant breeding at Cornell University, who was not involved in the Crop Trust project, praised the effort. He notes that the domesticated crops we eat today were selected from wild plants over thousands of years. He says this "natural reservoir of diversity ... has allowed plant breeding to attempt to keep pace with the demands of the growing human population."

That diversity took shape over millions of years, molded by natural selection, so "when you lose it, you really can't repeat that process," says Tanksley, who is also chief technology officer for Nature Source Improved Plants, which focuses on the genetic improvement of plants.

In the past, he notes, breeders have used wild crop relatives to improve disease resistance in many domesticated crops, including tomatoes, potatoes, rice and wheat.

A growing global population and changing environmental conditions because of climate change present urgent new challenges for crop breeders, Tanksley says.

"If we're going to have a sustainable world with a sustainable environment, we have to produce a lot more food per hectare than we ever have in the past," he says, adding, "I think people don't really grasp that the urgency of it."

And without the genetic diversity of wild crop relatives, he says, the world will have little chance of keeping up with growing demand for food.

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Raiders Of The Lost Crops: Scientists Race Against Time To Save Genetic Diversity - NPR

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The thrill of genetic genealogical discoveries should be tempered by ethical concerns – The Jewish News of Northern California

Posted: December 4, 2019 at 7:44 am

In these times of alarming disregard for scientific data (were talking to you, climate change deniers), lets hear it for science, specifically the astonishing gains made in the field of genetics and genetic testing.

Our three-part Past Lives series highlights the extraordinary resources now readily available to anyone curious about their family ancestry. Easy access to family records on the internet and the mapping of the human genome allows us to peer into our genetic past to learn more about who we are. And we can do both kinds of research from the comfort of our own homes.

For Jews, this has been a blessing for the most part. Unlike those Americans descended from Western European populations who can turn to comprehensive written archives, such as baptismal and marriage records, most Ashkenazi Jews like African Americans and Hispanic Americans lack the paper trail to trace their ancestry back further than a few generations.

Now, with the evolution of genetic testing, we can pinpoint to a remarkable degree of precision the composition of our ethnicity and where we came from. And all it takes is a simple cheek swab.

For some, discovering Jewish roots opens the door to new connections and layers of spiritual meaning.

As our stories show, this technology is about more than percentages and places on the map. For some, discovering the very existence of Jewish roots is a personal marvel, opening the door to new connections and layers of spiritual meaning.

However, as with any technology, ethical concerns run rampant.

Are we now as a global kehillah to rely on DNA test results as a proving ground for belonging to the Jewish people? What about those who convert to Judaism and might hail from different backgrounds? When their DNA pie chart comes back with zero percent Jewishness, does that mean they are any less Jewish?

Though matrilineal descent long ago enshrined a genetic aspect to Judaism, have we not seen enough of eugenics, racism, white nationalism and hate-fueled violence to check a rush to embrace anything that smacks of genetic purity?

These concerns have come to the forefront in Israel, where for the past two years the Chief Rabbinate has been using genetic testing to confirm the Jewishness of immigrants from the former Soviet Union seeking marriage licenses, in cases where the applicants dont have sufficient documentation of their status. Dozens of young couples, and their close relatives, have been humiliated in this way, and the practice is now being challenged before Israels High Court, brought there by the largely immigrant Yisrael Beiteinu party.

Scientific discoveries often involve thorny ethical questions. They must be faced openly.

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China Uses DNA to Map Faces, With Help From the West – The New York Times

Posted: December 4, 2019 at 7:44 am

TUMXUK, China In a dusty city in the Xinjiang region on Chinas western frontier, the authorities are testing the rules of science.

With a million or more ethnic Uighurs and others from predominantly Muslim minority groups swept up in detentions across Xinjiang, officials in Tumxuk have gathered blood samples from hundreds of Uighurs part of a mass DNA collection effort dogged by questions about consent and how the data will be used.

In Tumxuk, at least, there is a partial answer: Chinese scientists are trying to find a way to use a DNA sample to create an image of a persons face.

The technology, which is also being developed in the United States and elsewhere, is in the early stages of development and can produce rough pictures good enough only to narrow a manhunt or perhaps eliminate suspects. But given the crackdown in Xinjiang, experts on ethics in science worry that China is building a tool that could be used to justify and intensify racial profiling and other state discrimination against Uighurs.

In the long term, experts say, it may even be possible for the Communist government to feed images produced from a DNA sample into the mass surveillance and facial recognition systems that it is building, tightening its grip on society by improving its ability to track dissidents and protesters as well as criminals.

Some of this research is taking place in labs run by Chinas Ministry of Public Security, and at least two Chinese scientists working with the ministry on the technology have received funding from respected institutions in Europe. International scientific journals have published their findings without examining the origin of the DNA used in the studies or vetting the ethical questions raised by collecting such samples in Xinjiang.

In papers, the Chinese scientists said they followed norms set by international associations of scientists, which would require that the men in Tumxuk (pronounced TUM-shook) gave their blood willingly. But in Xinjiang, many people have no choice. The government collects samples under the veneer of a mandatory health checkup program, according to Uighurs who have fled the country. Those placed in internment camps two of which are in Tumxuk also have little choice.

The police prevented reporters from The New York Times from interviewing Tumxuk residents, making verifying consent impossible. Many residents had vanished in any case. On the road to one of the internment camps, an entire neighborhood had been bulldozed into rubble.

Growing numbers of scientists and human rights activists say the Chinese government is exploiting the openness of the international scientific community to harness research into the human genome for questionable purposes.

Already, China is exploring using facial recognition technology to sort people by ethnicity. It is also researching how to use DNA to tell if a person is a Uighur. Research on the genetics behind the faces of Tumxuks men could help bridge the two.

The Chinese government is building essentially technologies used for hunting people, said Mark Munsterhjelm, an assistant professor at the University of Windsor in Ontario who tracks Chinese interest in the technology.

In the world of science, Dr. Munsterhjelm said, theres a kind of culture of complacency that has now given way to complicity.

Sketching someones face based solely on a DNA sample sounds like science fiction. It isnt.

The process is called DNA phenotyping. Scientists use it to analyze genes for traits like skin color, eye color and ancestry. A handful of companies and scientists are trying to perfect the science to create facial images sharp and accurate enough to identify criminals and victims.

The Maryland police used it last year to identify a murder victim. In 2015, the police in North Carolina arrested a man on two counts of murder after crime-scene DNA indicated the killer had fair skin, brown or hazel eyes, dark hair, and little evidence of freckling. The man pleaded guilty.

Despite such examples, experts widely question phenotypings effectiveness. Currently, it often produces facial images that are too smooth or indistinct to look like the face being replicated. DNA cannot indicate other factors that determine how people look, such as age or weight. DNA can reveal gender and ancestry, but the technology can be hit or miss when it comes to generating an image as specific as a face.

Phenotyping also raises ethical issues, said Pilar Ossorio, a professor of law and bioethics at the University of Wisconsin-Madison. The police could use it to round up large numbers of people who resemble a suspect, or use it to target ethnic groups. And the technology raises fundamental issues of consent from those who never wanted to be in a database to begin with.

What the Chinese government is doing should be a warning to everybody who kind of goes along happily thinking, How could anyone be worried about these technologies? Dr. Ossorio said.

With the ability to reconstruct faces, the Chinese police would have yet another genetic tool for social control. The authorities have already gathered millions of DNA samples in Xinjiang. They have also collected data from the hundreds of thousands of Uighurs and members of other minority groups locked up in detention camps in Xinjiang as part of a campaign to stop terrorism. Chinese officials have depicted the camps as benign facilities that offer vocational training, though documents describe prisonlike conditions, while testimonies from many who have been inside cite overcrowding and torture.

Even beyond the Uighurs, China has the worlds largest DNA database, with more than 80 million profiles as of July, according to Chinese news reports.

If I were to find DNA at a crime scene, the first thing I would do is to find a match in the 80 million data set, said Peter Claes, an imaging specialist at the Catholic University of Leuven in Belgium, who has studied DNA-based facial reconstruction for a decade. But what do you do if you dont find a match?

Though the technology is far from accurate, he said, DNA phenotyping can bring a solution.

To unlock the genetic mysteries behind the human face, the police in China turned to Chinese scientists with connections to leading institutions in Europe.

One of them was Tang Kun, a specialist in human genetic diversity at the Shanghai-based Partner Institute for Computational Biology, which was founded in part by the Max Planck Society, a top research group in Germany.

The German organization also provided $22,000 a year in funding to Dr. Tang because he conducted research at an institute affiliated with it, said Christina Beck, a spokeswoman for the Max Planck Society. Dr. Tang said the grant had run out before he began working with the police, according to Dr. Beck.

Another expert involved in the research was Liu Fan, a professor at the Beijing Institute of Genomics who is also an adjunct assistant professor at Erasmus University Medical Center in the Netherlands.

Both were named as authors of a 2018 study on Uighur faces in the journal Hereditas (Beijing), published by the government-backed Chinese Academy of Sciences. They were also listed as authors of a study examining DNA samples taken last year from 612 Uighurs in Tumxuk that appeared in April in Human Genetics, a journal published by Springer Nature, which also publishes the influential journal Nature.

Both papers named numerous other authors, including Li Caixia, chief forensic scientist at the Ministry of Public Security.

In an interview, Dr. Tang said he did not know why he was named as an author of the April paper, though he said it might have been because his graduate students worked on it. He said he had ended his affiliation with the Chinese police in 2017 because he felt their biological samples and research were subpar.

To be frank, you overestimate how genius the Chinese police is, said Dr. Tang, who had recently shut down a business focused on DNA testing and ancestry.

Like other geneticists, Dr. Tang has long been fascinated by Uighurs because their mix of European and East Asian features can help scientists identify genetic variants associated with physical traits. In his earlier studies, he said, he collected blood samples himself from willing subjects.

Dr. Tang said the police approached him in 2016, offering access to DNA samples and funding. At the time, he was a professor at the Partner Institute for Computational Biology, which is run by the Chinese Academy of Sciences but was founded in 2005 in part with funding from the Max Planck Society and still receives some grants and recommendations for researchers from the German group.

Dr. Beck, the Max Planck spokeswoman, said Dr. Tang had told the organization that he began working with the police in 2017, after it had stopped funding his research a year earlier.

But an employment ad on a government website suggests the relationship began earlier. The Ministry of Public Security placed the ad in 2016 seeking a researcher to help explore the DNA of physical appearance traits. It said the person would report to Dr. Tang and to Dr. Li, the ministrys chief forensic scientist.

Dr. Tang did not respond to additional requests for comment. The Max Planck Society said Dr. Tang had not reported his work with the police as required while holding a position at the Partner Institute, which he did not leave until last year.

The Max Planck Society takes this issue very seriously said will ask its ethics council to review the matter, Dr. Beck said.

It is not clear when Dr. Liu, the assistant professor at Erasmus University Medical Center, began working with the Chinese police. Dr. Liu says in his online rsum that he is a visiting professor at the Ministry of Public Security at a lab for on-site traceability technology.

In 2015, while holding a position with Erasmus, he also took a post at the Beijing Institute of Genomics. Two months later, the Beijing institute signed an agreement with the Chinese police to establish an innovation center to study cutting-edge technologies urgently needed by the public security forces, according to the institutes website.

Dr. Liu did not respond to requests for comment.

Erasmus said that Dr. Liu remained employed by the university as a part-time researcher and that his position in China was totally independent of the one in the Netherlands. It added that Dr. Liu had not received any funding from the university for the research papers, though he listed his affiliation with Erasmus on the studies. Erasmus made inquiries about his research and determined there was no need for further action, according to a spokeswoman.

Erasmus added that it could not be held responsible for any research that has not taken place under the auspices of Erasmus by Dr. Liu, even though it continued to employ him.

Still, Dr. Lius work suggests that sources of funding could be mingled.

In September, he was one of seven authors of a paper on height in Europeans published in the journal Forensic Science International. The paper said it was backed by a grant from the European Union and by a grant from Chinas Ministry of Public Security.

Dr. Tang said he was unaware of the origins of the DNA samples examined in the two papers, the 2018 paper in Hereditas (Beijing) and the Human Genetics paper published in April. The publishers of the papers said they were unaware, too.

Hereditas (Beijing) did not respond to a request for comment. Human Genetics said it had to trust scientists who said they had received informed consent from donors. Local ethics committees are generally responsible for verifying that the rules were followed, it said.

Springer Nature said on Monday that it had strengthened its guidelines on papers involving vulnerable groups of people and that it would add notes of concern to previously published papers.

In the papers, the authors said their methods had been approved by the ethics committee of the Institute of Forensic Science of China. That organization is part of the Ministry of Public Security, Chinas police.

With 161,000 residents, most of them Uighurs, the agricultural settlement of Tumxuk is governed by the powerful Xinjiang Production and Construction Corps, a quasi-military organization formed by decommissioned soldiers sent to Xinjiang in the 1950s to develop the region.

The state news media described Tumxuk, which is dotted with police checkpoints, as one of the gateways and major battlefields for Xinjiangs security work.

In January 2018, the town got a high-tech addition: a forensic DNA lab run by the Institute of Forensic Science of China, the same police research group responsible for the work on DNA phenotyping.

Procurement documents showed the lab relied on software systems made by Thermo Fisher Scientific, a Massachusetts company, to work with genetic sequencers that analyze DNA fragments. Thermo Fisher announced in February that it would suspend sales to the region, saying in a statement that it had decided to do so after undertaking fact-specific assessments.

For the Human Genetics study, samples were processed by a higher-end sequencer made by an American firm, Illumina, according to the authors. It is not clear who owned the sequencer. Illumina did not respond to requests for comment.

The police sought to prevent two Times reporters from conducting interviews in Tumxuk, stopping them upon arrival at the airport for interrogation. Government minders then tailed the reporters and later forced them to delete all photos, audio and video recordings taken on their phones in Tumxuk.

Uighurs and human rights groups have said the authorities collected DNA samples, images of irises and other personal data during mandatory health checks.

In an interview, Zhou Fang, the head of the health commission in Tumxuk, said residents voluntarily accepted free health checks under a public health program known as Physicals for All and denied that DNA samples were collected.

Ive never heard of such a thing, he said.

The questions angered Zhao Hai, the deputy head of Tumxuks foreign affairs office. He called a Times reporter shameless for asking a question linking the health checks with the collection of DNA samples.

Do you think America has the ability to do these free health checks? he asked. Only the Communist Party can do that!

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