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Shrinking Bat DNA and Elastic Genomes – Quanta Magazine

Posted: August 2, 2017 at 11:47 am

Parsing the creatures 2 billion base pairs, Feschotte and his colleagues did stumble on something strange. We found some very weird transposons, he said. Because these oddball parasite sequences didnt appear in other mammals, they were likely to have invaded after bats diverged from other lineages, perhaps picked up from an insect snack some 30 to 40 million years ago. Whats more, they were incredibly active. Probably 20 percent or more of the bats genome is derived from this fairly recent wave of transposons, Feschotte said. It raised a paradox because when we see an explosion of transposon activity, wed predict an increase in size. Instead, the bat genome had shrunk. So we were puzzled.

There was only one likely explanation: Bats must have jettisoned a lot of DNA. When Kapusta joined Feschottes lab in 2011, her first project was to find out how much. By comparing transposons in bats and nine other mammals, she could see which pieces many lineages shared. These, she determined, must have come from a common ancestor. Its really like looking at fossils, she said. Researchers had previously assembled a rough reconstruction of the ancient mammalian genome as it might have existed 100 million years ago. At 2.8 billion base pairs, it was nearly human-size.

Next, Kapusta calculated how much ancestral DNA each lineage had lost and how much new material it had gained. As she and Feschotte suspected, the bat lineages had churned through base pairs, dumping more than 1 billion while accruing only another few hundred million. Yet it was the other mammals that made their jaws drop.

Mammals are not especially diverse when it comes to genome size. In many animal groups, such as insects and amphibians, genomes vary more than a hundredfold. By contrast, the largest genome in mammals (in the red viscacha rat) is only five times as big as the smallest (in the bent-wing bat). Many researchers took this to mean that mammalian genomes just dont have much going on. As Susumu Ohno, the noted geneticist and expert in molecular evolution, put it in 1969: In this respect, evolution of mammals is not very interesting.

But Kapustas data revealed that mammalian genomes are far from monotonous, having reaped and purged vast quantities of DNA. Take the mouse. Its genome is roughly the same size it was 100 million years ago. And yet very little of the original remains. This was a big surprise: In the end, only one-third of the mouse genome is the same, said Kapusta, who is now a research associate in human genetics at the University of Utah and at the USTAR Center for Genetic Discovery. Applying the same analysis to 24 bird species, whose genomes are even less varied than those of mammals, she showed that they too have a lively genetic history.

No one predicted this, said J. Spencer Johnston, a professor of entomology at Texas A&M University. Even those genomes that didnt change size over a huge period of time they didnt just sit there. Somehow they decided what size they wanted to be, and despite mobile elements trying to bloat them, they didnt bloat. So then the next obvious question is: Why the heck not?

Feschottes best guess points at transposons themselves. They provide a very natural mechanism by which gain provides the template to facilitate loss, he said. Heres how: As transposons multiply, they create long strings of nearly identical code. Parts of the genome become like a book that repeats the same few words. If you rip out a page, you might glue it back in the wrong place because everything looks pretty much the same. You might even decide the book reads just fine as is and toss the page in the trash. This happens with DNA too. When its broken and rejoined, as routinely happens when DNA is damaged but also during the recombination of genes in sexual reproduction, large numbers of transposons make it easy for strands to misalign, and that slippage can result in deletions. The whole array can collapse at once, Feschotte said.

This hypothesis hasnt been tested in animals, but there is evidence from other organisms. Its not so different from what were seeing in plants with small genomes, Leitch said. DNA in these species is often dominated by just one or two types of transposons that amplify and then get eliminated. The turnover is very dynamic: in 3 to 5 million years, half of any new repeats will be gone.

Thats not the case for larger genomes. What we see in big plant genomes and also in salamanders and lungfish is a much more heterogeneous set of repeats, none of which are present in [large numbers], Leitch said. She thinks these genomes must have replaced the ability to knock out transposons with a novel and effective way of silencing them. What they do is, they stick labels onto the DNA that signal to it to become very tightly condensed sort of squished so it cant be read easily. That alteration stops the repeats from copying themselves, but it also breaks the mechanism for eliminating them. So over time, Leitch explained, any new repeats get stuck and then slowly diverge through normal mutation to produce a genome full of ancient degenerative repeats.

Meanwhile, other forces may be at play. Large genomes, for instance, can be costly. Theyre energetically expensive, like running a big house, Leitch said. They also take up more space, which requires a bigger nucleus, which requires a bigger cell, which can slow processes like metabolism and growth. Its possible that in some populations, under some conditions, natural selection may constrain genome size. For example, female bow-winged grasshoppers, for mysterious reasons, prefer the songs of males with small genomes. Maize plants growing at higher latitudes likewise self-select for smaller genomes, seemingly so they can generate seed before winter sets in.

Some experts speculate that a similar process is going on in birds and bats, which may need small genomes to maintain the high metabolisms needed for flight. But proof is lacking. Did small genomes really give birds an advantage in taking to the skies? Or had the genomes of birds flightless dinosaur ancestors already begun to contract for some other reason, and did the physiological demands of flight then shrink the genomes of modern birds even more? We cant say whats cause and effect, Suh said.

Its also possible that genome size is largely a result of chance. My feeling is theres one underlying mechanism that drives all this variability, said Mike Lynch, a biologist at Indiana University. And thats random genetic drift. Its a principle of population genetics that drift whereby a genetic variant becomes more or less common just by sheer luck is stronger in small groups, where theres less variation. So when populations decline, such as when new species diverge, the odds increase that lineages will drift toward larger genomes, even if organisms become slightly less fit. As populations grow, selection is more likely to quash this trait, causing genomes to slim.

None of these models, however, fully explain the great diversity of genome forms. The way I think of it, youve got a bunch of different forces on different levels pushing in different directions, Gregory said. Untangling them will require new kinds of experiments, which may soon be within reach. Were just at the cusp of being able to write genomes, said Chris Organ, an evolutionary biologist at Montana State University. Well be able to actually manipulate genome size in the lab and study its effects. Those results may help to disentangle the features of genomes that are purely products of chance from those with functional significance.

Many experts would also like to see more analyses like Kapustas. (Lets do the same thing in insects! Johnston said.) As more genomes come online, researchers can begin to compare larger numbers of lineages. Four to five years from now, every mammal will be sequenced, Lynch said, and well be able to see whats happening on a finer scale. Do genomes undergo rapid expansion followed by prolonged contraction as populations spread, as Lynch suspects? Or do changes happen smoothly, untouched by population dynamics, as Petrovs and Feschottes models predict and recent work in flies supports?

Or perhaps genomes are unpredictable in the same way life is unpredictable with exceptions to every rule. Biological systems are like Rube Goldberg machines, said Jeff Bennetzen, a plant geneticist at the University of Georgia. If something works, it will be done, but it can be done in the most absurd, complicated, multistep way. This creates novelty. It also creates the potential for that novelty to change in a million different ways.

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The Era of Human Gene Editing Is HereWhat Happens Next Is Critical – Singularity Hub

Posted: August 2, 2017 at 11:47 am

Scientists in Portland, Ore., just succeeded in creating the first genetically modified human embryo in the United States, according toTechnology Review. Ateam led by Shoukhrat Mitalipov ofOregon Health & Science Universityis reported to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

The U.S. teamsresults follow two trialsone last year and one in Aprilby researchers in Chinawho injected genetically modified cells into cancer patients.Theresearch teamsused CRISPR, a new gene-editing system derived from bacteria thatenables scientists to editthe DNA of living organisms.

The era of human gene editing has begun.

In the short term, scientists are planning clinical trials to use CRISPR to edit human genes linked to cystic fibrosis and other fatal hereditary conditions. But supporters of synthetic biology talk up huge potential long-term benefits. We could, they claim, potentially edit genes and build new ones to eradicate all hereditary diseases. With genetic alterations, we might be able to withstand anthrax attacks or epidemics of pneumonic plague. We might revive extinct species such as the woolly mammoth. We might design plants that are far more nutritious, hardy, and delicious than what we have now.

But developments in gene editing are alsohighlighting a desperate need for ethical and legal guidelines to regulate in vitro genetic editingand raising concerns about a future in which the well-off couldpay for CRISPR to perfect their offspring. We will soon be faced with very difficult decisions aboutwhen and how to use this breakthrough medical technology.For example, if your unborn child were going to have a debilitating disease that you could fix by taking a pill to edit theirgenome, would you take the pill? How about adding some bonusintelligence? Greater height or strength? Where would you draw the line?

CRISPRs potential for misuse by changinginherited human traits has prompted some genetic researchersto call fora global moratoriumon usingthe techniqueto modify human embryos. Such use is a criminal offense in 29 countries, and the United States bans the use of federal funds to modify embryos.

Still, CRISPRs seductiveness is beginning to overtake the calls forcaution.

In February, an advisory body fromthe National Academy of Sciences announcedthe academys support for usingCRISPR to edit the genes of embryos to remove DNA sequences that doctors saycause serious heritable diseases. The recommendation came with significant caveats and suggested limiting the use of CRISPR to specific embryonic problems. That said, the recommendation is clearly an endorsement of CRISPR as a research tool that is likely to become a clinical treatmenta step from which therewill be no turning back.

CRISPRs combination of usability, low cost, and power is both tantalizing and frightening, with the potential tosomeday enableanyone to edit a living creature on the cheap in their basements. So, although scientists might use CRISPR to eradicate malaria by making the mosquitoes that carry it infertile, bioterrorists could use it to create horrific pathogens that could kill tens of millions of people.

With the source code of life now so easy to hack, and biologists and the medical world ready to embrace its possibilities, how do we ensure the responsible use of CRISPR?

Theres a line that A Prairie Home Companion host Garrison Keillor uses whendescribing the fictional town of Lake Wobegon, whereall the children are above average. Will we enter a time when those who can afford a better genome will live far longer, healthier lives than those who cannot? Should the U.S. government subsidize genetic improvements to ensure a level playing field when the rich have access to the best genetics that money can buy and the rest of society does not? And what if CRISPR introduces traits into the human germ line with unforeseen consequencesperhaps higher rates of cardiac arrest or schizophrenia?

Barriers to mass use of CRISPR are already falling.Dog breeders looking to improve breedssuffering from debilitating maladies are actively pursuing gene hacking. A former NASA fellow in synthetic biology now sells functional bacterial engineering CRISPR kits for $150 from his online store. Its not hard to imagine a future in which the big drugstore chains carry CRISPR kits for home testing and genetic engineering.

The release ofgenetically modified organismsinto the wildin the past few years has raised considerable ethical and scientific questions. The potential consequences of releasing genetically crippled mosquitoes in the southern United States to reduce transmission of tropical viruses, for instance, drew a firestorm of concern over the effects on humans and the environment.

So, while the prospect of altering the genes of peoplemodern-day eugenicshas caused a schism in the science community, research with precisely that aim is happening all over the world.

We have arrived at a Rubicon. Humans are on the verge of finally being able to modify their own evolution. The question is whether they can use this newfound superpower in a responsible way that will benefit theplanet and its people. And a decision so momentous cannot be left to the doctors, the experts, orthe bureaucrats.

Failing to figure out how to ensure that everyonewill benefit from this breakthroughrisks the creation of a genetic underclasswho must struggle to compete with the genetically modified offspring of the rich. Andfailing to monitor and contain how we use itmay spell global catastrophe. Its up to us collectively to get this right.

This article was originally published byThe Washington Post. Read theoriginal article.

Stock Media provided by Skripko / Pond5

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In US first, scientists edit genes of human embryos – Indiana Gazette

Posted: August 2, 2017 at 11:47 am

For the first time in the United States, scientists have edited the genes of human embryos, a controversial step toward someday helping babies avoid inherited diseases.

The experiment was just an exercise in science the embryos were not allowed to develop for more than a few days and were never intended to be implanted into a womb, according to MIT Technology Review, which first reported the news.

Officials at Oregon Health & Science University confirmed Thursday that the work took place there and said results would be published in a journal soon. It is thought to be the first such work in the U.S.; previous experiments like this have been reported from China. How many embryos were created and edited in the experiments has not been revealed.

The Oregon scientists reportedly used a technique called CRISPR, which allows specific sections of DNA to be altered or replaced. It's like using a molecular scissors to cut and paste DNA, and is much more precise than some types of gene therapy that cannot ensure that desired changes will take place exactly where and as intended. With gene editing, these so-called "germline" changes are permanent and would be passed down to any offspring.

The approach holds great potential to avoid many genetic diseases, but has raised fears of "designer babies" if done for less lofty reasons, such as producing desirable traits.

Last year, Britain said some of its scientists could edit embryo genes to better understand human development.

And earlier this year in the U.S., the National Academy of Sciences and National Academy of Medicine said in a report that altering the genes of embryos might be OK if done under strict criteria and aimed at preventing serious disease.

"This is the kind of research that the report discussed," University of Wisconsin-Madison bioethicist R. Alta Charo said of the news of Oregon's work. She co-led the National Academies panel but was not commenting on its behalf Thursday.

"This was purely laboratory-based work that is incredibly valuable for helping us understand how one might make these germline changes in a way that is precise and safe. But it's only a first step," she said.

"We still have regulatory barriers in the United States to ever trying this to achieve a pregnancy. The public has plenty of time" to weigh in on whether that should occur, she said. "Any such experiment aimed at a pregnancy would need FDA approval, and the agency is currently not allowed to even consider such a request" because of limits set by Congress.

One prominent genetics expert, Dr. Eric Topol, director of the Scripps Translational Science Institute in La Jolla, Calif., said gene editing of embryos is "an unstoppable, inevitable science, and this is more proof it can be done."

Experiments are in the works now in the U.S. using gene-edited cells to try to treat people with various diseases, but "in order to really have a cure, you want to get this at the embryo stage," he said. "If it isn't done in this country, it will be done elsewhere."

There are other ways that some parents who know they carry a problem gene can avoid passing it to their children, he added. They can create embryos through in vitro fertilization, screen them in the lab and implant only ones free of the defect.

Dr. Robert C. Green, a medical geneticist at Harvard Medical School, said the prospect of editing embryos to avoid disease "is inevitable and exciting," and that "with proper controls in place, it's going to lead to huge advances in human health."

The need for it is clear, he added: "Our research has suggested that there are far more disease-associated mutations in the general public than was previously suspected."

Hank Greely, director of Stanford University's Center for Law and the Biosciences, called CRISPR "the most exciting thing I've seen in biology in the 25 years I've been watching it," with tremendous possibilities to aid human health.

"Everybody should calm down" because this is just one of many steps advancing the science, and there are regulatory safeguards already in place. "We've got time to do it carefully," he said.

Michael Watson, executive director of the American College of Medical Genetics and Genomics, said the college thinks that any work aimed at pregnancy is premature, but the lab work is a necessary first step.

"That's the only way we're going to learn" if it's safe or feasible, he said.

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High school student gets an early start in stem cell research at USC – USC News

Posted: August 2, 2017 at 11:46 am

Even though Richard Lopez is still in high school, he can already tell you a thing or two about the ureteric bud, the metanephric mesenchyme and the developing kidney.

More impressively, he was familiar with these terms before starting his summer internship in the lab of Andy McMahon, kidney researcher and director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.

I knew I was going to come here, Lopez said. So from December on, I was just reading papers that were written by Dr. McMahons lab. And so I read about the development of the kidney, kidney organoids, experimental methods like in situ hybridization, immunohistochemistry, all that stuff. Im really glad I did all of that because now that Im here, I understand whats going on.

Lopez undertook this intense preparation as part of the Science Research Program at his Connecticut boarding school, Choate Rosemary Hall. In addition to familiarizing him with the McMahon labs research, the program provided experience with useful molecular biology techniques, ranging from gel electrophoresis to polymerase chain reaction.

Lopez didnt start his high school career at Choate. Growing up in Lennox near the Los Angeles International Airport, he attended local public schools until his sophomore year in high school. At that point, his exceptional scores on the California Standardized Test attracted the attention of the Young Eisner Scholar program, which empowers underserved students to fulfill their potential.

As an Eisner Scholar, he earned both admission and a full scholarship to attend Choate. But the decision to leave home wasnt easy.

I was terrified at first, leaving everything behind, he said. I talked to my mom about it, and at first she was hesitant because I was born and raised here, and Im the only child. But then she realized that this is an amazing opportunity, and I cant let it go by.

Lopez recalls that Choate was initially in a huge culture shock from the occasional Maserati to the international student body to the exceptional academic opportunities such as the Science Research Program that brought him to USC.

In the McMahon lab, Lopez has learned about the molecular signals that drive the branching development of the kidney, and he has practiced a wide range of lab techniques.

Im really excited about science because I know its potential.

Richard Lopez

Im really excited and passionate about science because I know its potential, he said. If you pair that with math, you have no boundaries. If you look at the lab where Im working right now creating kidney organoids, learning about kidney development, these kinds of things can solve really burdensome illnesses that are fatal to some people, like end-stage renal disease and polycystic kidney disease.

To get to the lab every day, Lopez bike commutes a total of 32 miles from his home in Lennox to USCs Health Sciences Campus. Hes run the Los Angeles Marathon once and the San Francisco Marathon twice. In November, hes planning to travel to Florida to celebrate his 18th birthday with his first Ironman Triathlon a 2.4-mile swim, 112-mile bike ride and 26.2-mile run.

Hes participating in these events not only for fun and fitness, but also as a way to give back. Hes currently raising sponsorship money for the Partnership Scholars Program, which provides underserved junior high and high school students with educational and cultural experiences, ranging from theatergoing to restaurant outings to college tours. His goal is to raise $54,000 to fund three new scholars.

I was very lucky, he said. So I want to raise money for the scholarships that have helped me out along the way.

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UCI stem cell therapy attacks cancer by targeting unique tissue stiffness – UCI News

Posted: August 2, 2017 at 11:46 am

Irvine, Calif., July 26, 2017 A stem cell-based method created by University of California, Irvine scientists can selectively target and kill cancerous tissue while preventing some of the toxic side effects of chemotherapy by treating the disease in a more localized way.

Weian Zhao, associate professor of pharmaceutical sciences, and colleagues have programmed human bone marrow stem cells to identify the unique physical properties of cancerous tissue. They added a piece of code to their engineered cells so that they can detect distinctively stiff cancerous tissue, lock into it and activate therapeutics.

Our new type of treatment only targets metastatic tissue, which enables us to avoid some of conventional chemotherapys unwanted side effects, Weian Zhao said. Steve Zylius / UCI

In a study appearing in Science Translational Medicine, the researchers report they have effectively and safely employed this stem cell-targeting system in mice to treat metastatic breast cancer that had spread to the lung. They first transplanted the engineered stem cells to let them find and settle into the tumor site where they secreted enzymes called cytosine deaminase. The mice were then administered an inactive chemotherapy called prodrug 5-flurocytosine, which was triggered into action by the tumor site enzymes.

Zhao said his team specifically focused on metastatic cancer, which comes when the disease spreads to other parts of the body. Metastatic tumors are particularly deadly and the cause of 90 percent of cancer deaths.

This is a new paradigm for cancer therapy, Zhao said. We are going in a direction that few have explored before, and we hope to offer an alternative and potentially more effective cancer treatment.

Zhao added that this stem cell-targeting approach can provide an alternative to many forms of chemotherapy, which has a number of bad side effects. While this widely used method is powerful enough to kill rapidly growing cancer cells, it also can harm healthy ones.

Our new type of treatment only targets metastatic tissue, which enables us to avoid some of conventional chemotherapys unwanted side effects, said Zhao, who is a member of the Chao Family Comprehensive Cancer Center and the Sue & Bill Gross Stem Cell Research Center at UCI.

This published work is focused on breast cancer metastases in the lungs, he added. However, the technology will be applicable to other metastases as well, because many solid tumors have the hallmark of being stiffer than normal tissue. This is why our system is innovative and powerful, as we dont have to spend the time to identify and develop a new genetic or protein marker for every kind of cancer.

So far, the Zhao team has done preclinical animal studies to demonstrate that the treatment works and is safe, and they hope to transition to human studies in the near future. They are currently expanding to include other type of cells, including cancer tissue-sensing, engineered immune-system T cells (called CAR-T) to treat metastasizing breast and colon cancers. They also plan to transform the technology for other diseases such as fibrosis and diabetes, which result in stiffening of otherwise healthy tissue.

Along with Zhao, UCI doctoral students Linan Liu and Shirley Zhang, are co-leading authors of the study. The National Institutes of Health, the Department of Defense, the American Cancer Society and the California Institute for Regenerative Medicine provided support.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.

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These People Are Making Money Off A Bogus Cancer Cure That Doctors Say Could Poison You – BuzzFeed News

Posted: August 2, 2017 at 11:46 am

John Richardson thought hed found a cure for cancer.

The San Francisco Bay Area doctor had been giving patients a therapy that is essentially a chemical compound found in apricot kernels and known by several names laetrile, amygdalin, vitamin B17. Richardson had been told it could attack tumors, naturally and precisely. It can also convert into potentially poisonous amounts of cyanide when eaten. But Richardson was a true believer.

Yes, the evidence that Vitamin B17 is natures control for cancer is quite overwhelming, he wrote in his book. So the next time you hear an official spokesman for orthodox medicine proclaim that there is none, you might tell him that such a statement is a self-evident absurdity and suggest that he do his homework before posing as an expert.

Less convinced were the police who, on June 2, 1972, barged into Richardsons clinic and jailed him on charges of medical quackery. He eventually lost his medical license and was charged with smuggling laetrile, an illegal drug, into the country.

Now, three decades after Richardsons death, his son, John Richardson Jr., is no stranger to apricot seeds. Through Apricot Power, his thriving e-commerce store, he sells bitter seeds ($32.99 for 1,500), seed extract-based tablets (up to $97.99 a bottle), and B17-infused anti-aging cream ($49.99). Recipes for apricot-seed pesto, egg nog, and marzipan offer a delicious and easy way to work the supposed superfood into your diet, and videos explain why the sites mission is to get B17 into every body! Though Richardson Jr. wont reveal revenue numbers, he says his family operation of around 10 employees has served thousands of customers all over the world since it launched in 1999.

But theres a key difference between his business and his fathers, Richardson Jr. told me: We dont mention the C-word in our company. Cancer, that is. If a customer review on Apricot Powers website even mentions the term, the company leaves a comment pointing out that it doesnt make any disease or illness-related claims about its products. Legally, it cant: The FDA prohibits companies from selling laetrile, under any name, as a cancer treatment, because studies have found it to be at best ineffective, and at worst toxic.

Of course, that doesnt stop dozens of internet entrepreneurs from exploiting regulatory loopholes to sell apricot seeds and B17 tablets, no claims attached and profiting off the efforts of believers who spread the truth about them far and wide. In laetriles heyday in 1981, a doctor called it the slickest, most sophisticated, and certainly the most remunerative cancer quack promotion in medical history. Three decades later, the internet has only spread the gospel, creating an unstoppable, hydra-headed ecosystem of buyers and sellers.

A variety of apricot seed products available online.

If youve never heard that apricot kernels kill and prevent cancer, thats because the government doesnt want you to, proponents say. Cancer, according to them, arises from the lack of a nutrient they call vitamin B17, so it follows that ingesting that nutrient would fight the disease. But regulators, pharmaceutical companies, and doctors cant patent and profit from a natural substance. So they keep it off the market and peddle toxic, invasive, costly, and unnatural chemotherapy and drugs at patients expense.

The internet has created an unstoppable, hydra-headed ecosystem of B17 buyers and sellers.

Or so the theory goes. Vitamin B17 Is Banned Because It Treats Cancer! a post on the site Healthy Food House proclaims; it has been liked, commented on, and shared on Facebook more than 47,000 times since September, according to the social mediatracking tool CrowdTangle. A post about the real story of laetrile, published on a site called The Truth About Cancer, has gotten more than 44,000 likes, comments, and shares since June 2015.

Yin Ling Woo, a gynecological oncologist, recently had to decline when three cancer patients asked her to inject them with liquid B17 vials. They buy it off the internet, it arrives, they have to get someone to administer it, said Woo, who works in Kuala Lumpur, Malaysia.

Over the last year and a half, public health agencies in the European Union, Canada, and Dubai have issued warnings about apricot kernels and kernel-derived supplements. Since Australia and New Zealand outright blocked the sale of raw kernels in late 2015, retailers have been fined for continuing to sell them. In April, the FDA fired off warning letters to the sellers of more than 65 illegal cancer treatments, including whole apricots and vitamin B17. All the regulators cite the internet as the main source of the problem. Due to the nature of online marketing, some companies attempting to avoid compliance with FDA law simply start new websites and rename fraudulent products, an FDA spokesperson told BuzzFeed News in an email.

In other words, the FDA lacks the power to systematically fix the underlying issue. It can go after apricot kernels advertised as a cancer cure. But it cant crack down when theyre advertised as supplements or plain old seeds. Nor can it control the Facebook posts, YouTube videos, blogs, and tweets that perpetuate the myth.

And when the FDA calls out problematic claims, all a company has to do to escape scrutiny is stop using the phrases in question. But the misimpression that their product is an effective cancer cure will remain out there, uncorrected, in the public eye, said Patti Zettler, an associate professor at Georgia State Universitys law school and a former associate chief counsel at the FDA.

Its no coincidence that B17 is enjoying a second life online, at this moment in time. The internet is rife with misinformation about science and health, and the nutritional supplements business as part of the larger wellness industry is worth billions. Meanwhile, cancer remains a little understood disease that causes nearly 1 in 6 deaths worldwide. So in a way, its comforting and intuitive to blame a fixable vitamin deficiency. Its also wrong.

Felicity Corbin-Wheeler of Jersey, an island south of England, credits intravenous infusions of B17 and a strict diet with shrinking her pancreatic cancer in 2003. She refused chemotherapy, which aligns with her belief that the Western diet has been so hijacked by processed foods, sugars, fats, and salts.

Im all for the natural things, she said, that we get back to a simple life.

Ernst T. Krebs Jr., seen in San Francisco in 1980, was an early promoter of laetrile as a cancer treatment.

A successful salesperson must buy into what theyre selling, and Richardson Jr. is all in. Growing up in the Bay Area suburb of Orinda, he and his seven siblings werent fed sugar or processed wheat, an abstention he keeps up to this day. He says he started eating apricot seeds for his health at age 5. Now 52, hes up to 40 a day.

The seeds contain amygdalin, a compound also found in apple seeds and almonds. In the 1950s, Ernst T. Krebs Jr., a self-described doctor and biochemist with no medical degree, patented a purified form of amygdalin that he called laetrile. He also promoted it as vitamin B17, although its not an officially recognized vitamin.

In 1971, Krebs Jr. shared with the elder Richardson his theory of how this nutrient could stop cancer growth. As Richardson later summarized: [N]atures mechanism will not work if one fails to eat the foods that contain this necessary vitamin, which is exactly what has happened to modern man, whose food supply has become further and further removed from the natural state.

In Richardsons day, laetrilists were just as controversial as the anti-vaccine movement is today. In the 1960s, the FDA banned laetrile and reported that there was no evidence it treated cancer. But over the next decade, more than 70,000 Americans took it anyway. Many of them crossed into Mexico for injections denied by their stateside doctors. Actor Steve McQueen secretly traveled to Baja in 1980 to receive laetrile, among other alternative remedies, for an advanced lung cancer. He died months later. In the mid-70s, a scientist at Memorial Sloan Kettering Cancer Center performed experiments that he said showed laetrile helped reduce tumors in mice. A media relations staffer then leaked the data, claiming that hospital executives had sought to cover up and discredit it. Hes been making that claim ever since, including in the 2014 documentary Second Opinion (for the conspiracy-minded only, the Los Angeles Times wrote), and now charges cancer patients $500 for hourlong phone consultations.

In the mid-'70s, laetrilists were just as controversial as the anti-vaccine movement is today.

When the elder Richardson was arrested in 1972 (on charges that were dropped), it prompted his fellow members of the John Birch Society, the far-right conspiracist group of the era, to start a lobbying group to legalize laetrile. Later, Richardson was fined $20,000 and placed on probation on charges of conspiracy to smuggle laetrile from Mexico to the US. Indictments against him and 18 other accused promoters noted that he had deposited $2.5 million in his bank account over two years.

Even so, Richardson Jr. remembers his father, who died in 1988, as very principled, very honest, and very moral, and keeps a picture of him over his desk. Theres still people that contact me and tell me what a wonderful man he was and what a wonderful doctor he was, he said.

After long legal battles, the FDAs laetrile ban ultimately took effect in 1987. In 1999, Richardson Jr. started Apricot Power as an online-only store, but its branched out to health food shops over the last five years to meet customer demand. The company sources apricots from its farm and others in California, removes the flesh, air-dries the pits at the center, cracks them open, and sells the seeds inside.

A lot of the foods, the amygdalins been cooked out of it, said Richardson Jr., who also operates a real estate firm and a restaurant. And my dad believed a normal, healthy person should have 100 milligrams a day of amygdalin. Thats been our company motto since the beginning, is just getting amygdalin back into every body.

It took me no more than a few seconds to find apricot seeds online. A Google search led me to Amazon, where a European vendor was selling a 1-pound bag for $19.99 with this caveat: We do not treat, or aim to cure any disease. Still, its customers leave reviews like Raw Apricot Kernels help to stop Cancer in its tracks and I expect no miracles, but I dont want to die from chemotherapy. The seeds turned out to be chewy and tongue-curlingly bitter, with a long and unpleasant aftertaste.

Amazons algorithm recommended that I also buy the book thats the bible of this movement: World Without Cancer: The Story of Vitamin B17. First published in 1974 and now in its 24th printing, its by G. Edward Griffin, who has no scientific training, denies HIV, and pushes Sept. 11 conspiracy theories.

I tried to interview more than 35 e-commerce shops that sell seeds or supplements labeled as laetrile, amygdalin, or B17. Many declined to talk or never got back to me. A man at Raw Foods and Vitamins turned me down, explaining, The FDA and the government agencies have gone wild, theres so much money in Big Pharma. As soon as theres a little publicity, theyll be all over you. He did, however, text me pro-laetrile books and websites to look up.

Others were more open. Danny Hesman, who runs B17 USA full-time out of Los Angeles, said he has 5,000 repeat customers. I do tell people its not a magic pill, he said. But like some other vendors, hes had a personal experience with cancer in his case, a friend who died from it. I got a front-row seat to the suffering he went through with modern medicine, he said. I know these oncologists, I spoke to their team, they did everything. Its almost career suicide for professionals to even consider alternative therapies, which leaves [B17] in that fringe zone you see when you google vitamin B17. I wish there were some more professionals that would really work on that.

Many vendors, especially those in the US, repeatedly emphasized that they werent claiming to cure, treat, or prevent anything, as if the FDA were listening over the phone. But Our Fathers Farm in Ontario, Canada, sells kernels that may help with cancer prevention and symptoms. Vision B Seventeen in Kuala Lumpur, Malaysia, claims to have been successfully treating cancer and other degenerative diseases for more than 12 years now.

Regulators have tried to squash these kinds of vendors. Jason Vale, a professional arm wrestler in New York City, sold seeds as a cure on his website, Apricots From God, because he believed theyd healed his kidney cancer. He also spammed people with millions of email ads. But in 2003, Vale was sentenced to five years in prison for criminal contempt of a court injunction sought by the FDA to stop him selling.

Laetrile (i.e. Vitamin B17) therapy is one of the most popular and best known alternative cancer treatments.

B17 merchants may have been deterred by his conviction, but not defeated. Until recently, Oxygen Health Systems allegedly told customers, Laetrile (i.e. Vitamin B17) therapy is one of the most popular and best known alternative cancer treatments. This spring, the FDA slammed Oxygen with a warning letter for making that and other unsupported health claims. According to the agency, which sent similar warnings to 13 other businesses, Oxygen had also illegally described vitamin C, the fruit graviola, and flax seed oil as cancer therapies.

Owner Michael Carroll said by phone that many of his products personally helped him fight off non-Hodgkins lymphoma. He scrubbed the language targeted by the FDA. But he didnt seem too worried that his business would take a hit, or that his promises could have harmed someone.

Were continuing to work to make the best corrections to make our website as blah as possible, so consumers remain uneducated, said Carroll, who lives near Chicago. When we spoke in early May, Oxygen was still selling B17 bottles for up to $97; theyve since been taken down.

But you can still get them from Amygdalin Supply. Call to place an order and you might chat, as I did, with customer service rep Carlos Olguin in Guadalajara, Mexico. I asked him if, in his opinion, what he was selling could really treat cancer. His customers, he replied, were all the proof he needed.

If you go to a store and buy a product and the product doesnt work for you, would you buy again? he asked. Of course not, because the product does not work. Thats the thing I see. The same people who buy are the same people who are going to buy next and next and next.

Sandi Rog, a novelist outside Denver, Colorado, says that B17 saved her and can save others, too. She spreads the message on her blog, I Beat Cancer with Vitamin B17, and in three YouTube videos with a total of more than 956,000 views.

When Rog was diagnosed with non-Hodgkins T-cell lymphoma in late 2010, doctors put her through chemotherapy, radiation, and a stem cell transplant in an attempt to reinvigorate her immune system, she said. But tumors kept popping up. After a naturopathic doctor gave her dozens of supplements, she eventually narrowed them down to a regimen of juicing, pancreatic enzymes, and B17, which she began reading about and ordering online. She also stopped taking her prescribed immunosuppressant drugs. By the end of 2012, she said, the tumors were gone and she was in remission.

It makes me so angry, because people are being ripped off. "

All I know is Im cancer-free, she said, and its because of this.

Catherine Fox found Rogs videos very impressive when she started researching B17 as a preventative measure against cancer. Her parents, five aunts, and three uncles have all died of various cancers, she says. Then, about three years ago, she felt a lump in her breast the moment shed been dreading. So she started taking kernels. Thats likely why, she thinks, the lump ended up being harmless.

It seemed to just go down and go away, said Fox, who lives in Kells, Ireland, and, just to be safe, still eats two seeds every morning.

But Liz Beggs says that these stories offer a sense of false hope that harms people like her late niece, Charlene Campbell.

Campbell had a daughter who, not long after she was born, developed a rare, aggressive brain cancer and died. More than five years later, Campbell developed cancer, too, in her breast. Having watched her daughter undergo chemotherapy and radiation, she was determined to avoid them herself. So she started juicing, eating an all-vegetarian diet, and ordering cannabis oil and apricot seeds online. She said, This is my journey, its my body, I have to do it on my own, recalled Beggs, who lives in Northern Ireland. Youre either with me or against me.

Beggs understood why Campbell distrusted conventional therapies, but at the same time, we were so fearful, she said. Campbells tumor kept growing until she finally agreed to have a mastectomy. Then new tumors sprouted in her liver and spine.

Campbell died in October 2015, soon after her 33rd birthday. By the end, she was up to 40 apricot kernels a day, her aunt said.

It makes me so angry because people are being ripped off, Beggs said. That fear that engulfs a person when theyre diagnosed with cancer, they want to hold on to something thats positive, not the medical route. They want to hold on to this sick holistic path of believing in kernel seeds and whatever else across the internet.

Promoters of this all-natural cure cant agree on one name for it amygdalin, laetrile, Laetrile with a capital L, B17? Nor do they agree on how much to take and how often. Nor is there a way to ensure that the many seeds, pills, powders, and liquids in which it can take form are chemically consistent. All these variables make it hard to study its supposedly wondrous effects.

A 2015 review looked at the available studies of laetrile and amygdalin in humans and found no reliable evidence that they could cure cancer. On the whole, it concluded, the chances of bad side effects made the risks unambiguously negative.

In 1982, the Mayo Clinic put 178 cancer patients on laetrile, enzymes, vitamins, and a restricted diet, a regimen based on several laetrile doctors recommendations. When it came to getting cured, seeing their symptoms improve or disease stabilize, or living longer, they didnt substantially improve. On average, they survived less than five months after starting treatment.

I do remember some of the patients wanting it to be continued, believing it was working even though their tumor had clearly grown, they had gotten weaker and clearly more sick, said Gregory Sarna, a study co-author who was a UCLA oncologist at the time. That did not dissuade some of them from their belief that it was working.

Several patients also showed signs of poisoning, like nausea and vomiting, and blood levels of cyanide known to be fatal.

It doesnt take much. More than three small kernels, or less than half a large one, can be unsafe for adults, according to a report for the European Food Safety Authority. Even one small kernel can be toxic for toddlers. From 2000 to 2004, there were reports of 260 children poisoned by kernels in Turkey, where they are a common snack. One 2-year-old girl was severely poisoned and died after she ate 10 seeds. Laetrile fans, however, tend to promote much higher doses: One blogger cites World Without Cancers recommendation of 3 to 5 seeds per waking hour to treat cancer, and 7 to 10 a day to prevent it.

None of these contradictions faze consumers, who say scientists and doctors design studies to fail. They question whether people have really gotten sick or died from apricot kernels and if they did, they probably took way too much. (I never had a bad experience, said Elif Ercanli, who grew up eating seeds in Istanbul, Turkey.) The most theyll admit to is a bad side effect here or there. Rog said she once took nine in a 12-hour span and my blood pressure crashed so low, I was in bed, I had tingling in my fingers and toes.

When I asked people to explain how amygdalin works, they paraphrased, or told me to look up, World Without Cancer. According to Griffin, when amygdalin dissolves in body fluids and produces hydrogen cyanide, the cyanide only goes after cancer cells because of a special enzyme they contain thats vulnerable to attack.

That explanation doesnt make sense to Sarna, who is now an oncologist at Cedars-Sinai Medical Center. He points out that cancer cells differ even within a single tumor which is usually why when a treatment destroys some cells, others remain untouched. To say [one enzyme] is a general characteristic of cancer would need a study of hundreds of thousands of fresh cancers, all different cancers, he said. Ive never seen that done.

Theres no doctor in the world who doesnt want to help their patient get better. I never quite understood why theres this conspiracy theory that doctors or pharmaceutical companies would have an interest in suppressing something that works."

Even if there were one magical mechanism that unlocked the cure to cancer, Wendy Chen, a breast oncologist at Dana-Farber Cancer Institute, takes offense at the notion that physicians would cover it up.

Theres no doctor in the world who doesnt want to help their patient get better, she said. I never quite understood why theres this common conspiracy theory that doctors or pharmaceutical companies would have an interest in hiding or suppressing something that works.

Nevertheless, Griffins theories still light up Facebook groups like Cancer! Is B17 the cure? Brandon Clark, who says apricot seeds and B17 tablets got rid of a skin cancer on his nose, moderates the 3,000-person group. When he started contributing, he read B17 books and talked to B17-prescribing doctors to make sure people had the best information possible. Clark, who lives near Tacoma, Washington, prefers to share that research on Facebook because its much more popular than Twitter and Myspace and anything else, he said. I felt like I could reach more people.

Hes not wrong.

Theyre preying on people who are vulnerable and ill, Beggs said of people like Clark. Its just so not right. It makes me angry. Theyre being brainwashed. Charlenes proof of that.

The bottom of Apricot Power's Ground SuperFood Mix.

Apricot kernel devotees are fond of a certain Bible verse, Genesis 1:29: Then God said, I give you every seed-bearing plant on the face of the whole earth and every tree that has fruit with seed in it. They will be yours for food. There is an intuitive appeal to this implicit idea, that a higher force designed a natural substance to fight off a devastating and inexplicable disease.

Cancer kills 1 in 4 men and 1 in 5 women in the US. And surgery, chemotherapy, and radiation can sound frightening on their own, since they involve cutting open the body and flooding it with drugs and X-rays. The side effects range from unpleasant to downright unbearable.

Theyre preying on people who are vulnerable and ill. Its just so not right. It makes me angry. Theyre being brainwashed."

So there has always been an appetite, to some degree, for alternative therapies. And because of the enormous power of placebos, people often do feel better after taking them. In 1979, when the Supreme Court ruled that terminally ill cancer patients did not have the right to access laetrile, it noted that entrepreneurs had long hawked cancer cures like liniments of turpentine, mustard, oil, eggs, and ammonia; peat moss; arrangements of colored floodlamps; pastes made from glycerin and limburger cheese; mineral tablets; and Fountain of Youth mixtures of spices, oil, and suet.

But in 2017, once-fringe natural remedies are no longer distinct from the mainstream obsession with wellness, now a $3.7 trillion industry spanning organic food, yoga, meditation apps, anti-aging lotions and dietary supplements. Lifestyle guru Gwyneth Paltrow and alt-right fearmonger Alex Jones peddle silver nanoparticles and obscure mushrooms. In addition to being taken by 150 million people in the US, supplements are barely regulated, can contain anything, arent proven to help health, and send at least 20,000 Americans to the emergency room annually.

The fact there is a resurgence of interest in selling and utilization of what is essentially an ineffective treatment is concerning, and it points to general problems with the supplement market, said Ameet Sarpatwari, an instructor at Harvard Medical School, of B17. The amount of money being spent out there in supplements is huge. You would think that it should be more well-regulated than it is.

The wellness industrial complex is built upon vague pronouncements and falsehoods about how nutrition and bodies work, like the (unsupported) myth that genetically modified food is unsafe to eat. But if you buy into that, then perhaps its not so crazy to also believe that, say, the Hunza, an indigenous group in northern Pakistan, are cancer-free thanks to their apricot-heavy diet. (According to anthropologists, there are no credible studies to support the claim, which is central to the B17 ideology.)

The fact there is a resurgence of interest in selling and utilization of what is essentially an ineffective treatment is concerning, and it points to general problems with the supplement market.

As the internet breathes new life into health myths, it complicates the relationship between patients and doctors. No longer are physicians the main or exclusive source of medical information when people can Google a remedy, buy it on Amazon, and tell their Facebook friends about it.

So when cancer patients get excited about laetrile, or any other alternative therapy, doctors must balance the evidence, or lack thereof, with the desperation of people often on the verge of death. People need control over something that they cannot control, and that is very, very frustrating, and I sense it with every person I treat, said Don Dizon, clinical co-director of gynecologic oncology at Massachusetts General Hospital Cancer Center and a spokesperson for the American Society of Clinical Oncology.

Natural, though, does not mean safe. Toxins, cyanide included, abound in the natural world. All that matters is what are the benefits and harms, what is known for certain and what is merely unknown, said Vinay Prasad, a hematologist-oncologist at Oregon Health and Science University, by email.

One patient of Prasads wanted to try high doses of vitamin C, but resisted radiation therapy because it seemed unnatural. Of course, Prasad noted, both vitamin C and radiation are naturally occurring, and both high dose [vitamin C] and a radiation machine are a human manipulation of something natural, so I wasnt sure there is a difference.

Dizon isnt always confident that chemotherapy will work, particularly in people whose cancer has returned, so he encourages some of them to push back. Hes even seen some tumors shrink after patients have taken natural remedies and hes accepted that he cant explain why. Sometimes, doctors say, a person may not actually have cancer in the first place, due to an incorrect diagnosis or misinterpreted biopsy. Or tumors can shrink due to other therapies that a patient has forgotten about or hasnt revealed.

Regardless, a couple moving anecdotes arent license to recommend an unproven remedy. That would be wrong, because thats not data, Dizon said. Thats not the same thing as saying, Your mom has ovarian cancer. If shes taking treatment, she has a 30% chance of cure and an 80% chance of going quite some time, even maybe years, before her cancer comes back.

With alternative therapies, the success stories that people cling to tend to be more isolated than they think. Youre not hearing the other side of that the patients who took it and died within weeks or whose cancers really grew, he said.

Vitamin B17, by any name, will never disappear. Its story by now has taken on mythical proportions that cannot be censored.

New advances in cancer treatment may one day make apricot seeds obsolete. But until even if all these therapies become the new and highly successful standard of care, some segment of laetrile believers will continue to buy in.

At Apricot Power, Richardson Jr. is busy rolling out products such as chocolate bars with chopped-up apricot seeds. (What a tasty way to get natural B17 in your diet! the website proclaims.)

What would his father think of all this? Hed be happy, Richardson Jr. answered, because he predicted that someday people would discover that nutrition was the answer to healthy living. He added, Lots of people believe an ounce of prevention is worth a pound of cure.

Jul. 31, 2017, at 16:48 PM

This story has been updated to state that Felicity Corbin-Wheeler received B17 through intravenous therapy. An earlier version of this story misstated the method by which she received it.

Stephanie Lee is a senior technology reporter for BuzzFeed News and is based in San Francisco.

Contact Stephanie M. Lee at stephanie.lee@buzzfeed.com.

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These People Are Making Money Off A Bogus Cancer Cure That Doctors Say Could Poison You - BuzzFeed News

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PODCAST #33: The Wild West of stem cells – HealthNewsReview.org

Posted: August 2, 2017 at 11:45 am

Michael Joyce is a multimedia producer at HealthNewsReview.org and tweets as @mlmjoyce

Stem cell clinics are booming. And hurting people.

How can patients protect themselves in a marketplace where the Food & Drug Administration (FDA), Federal Trade Commission (FTC), and state medical boards have been ineffectual?

In this podcast youll hear from George Gibson (a patient left blind after a dubious stem cell intervention), Leigh Turner PhD (a bioethicist whos been following the stem cell marketplace closely), and Drs. Jeanne Loring and Paul Knoepfler two PhD stem cell researchers from California.

There are two websites that most of the people I interviewed for this story recommended as reliable and user-friendly places to go for further information on stem cells:

Although its directed at journalists, our 9 Writing Tips to Combat Stem Cell Hype in Your News Storiesalso will be of interest to most readers of health care news.Weve closely followedcoverage of stem cells for the past several years. Heres just a sampling:

Bioethicist Leigh Turner, who was interviewed for this podcast, has published two papers in the past year that may be of interest. The first was published in the summer of 2016 and was co-authored by Paul Knoepfler. It offers a compelling look into the number and locations of stem cell clinics marketing directly to US consumers.

This summer Turner published a study documenting the use of clinicaltrials.gov by clinics offering unregulated interventions. In this Q&A with Turner, he discusses much of the background leading up to the publication. Its a very interesting read.

Also quite provocative is this very concise call to action penned by Tim Caulfield, Douglass Sipp, and others published just last month. It offers an important perspective on whats needed to keep people from being harmed by unregulated stem cell therapies.

Finally wed like to continue the conversation and would love to hear from you during our upcoming Twitter chat!

You can listen to all our podcasts HERE.

A new study made global headlines last week with the claim that researchers can now

Paul Knoepfler PhD is "disturbed and concerned." Here's why. Knoepfler is a stem cell researcher

If you had been in Salt Lake City last month, savoringyour morningcoffee, and watching this

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A New Epigenetic Barrier to Induced Pluripotent Stem Cells – WhatIsEpigenetics.com

Posted: August 2, 2017 at 11:45 am

By adding theright concoction of ingredients, scientists can reprogram youreverydaysomatic cell intoan inducedpluripotentstemcell(IPSC) that is,aculturedcellthat has the ability todifferentiate into almost any othercelltypein response to specificenvironmentalfactors, similar to an embryonic stem cell. Thisinnovativetechnology allows the study of the molecularmechanismsofearlydevelopmentanddisease,withouttheethical restrictionsassociated withembryonic stem cells.

Not surprisingly, the possibility of utilizing induced pluripotent stem cells in the field of regenerative medicine is of important focus to many scientists. In a recent post, we touched on the potential ability of vitamins A and C to enhance the erasure of epigenetic memory required for cell reprogramming. Because these special types of cells can propagate indefinitely and form any other cell type in the body such as neurons, liver, and heart cells we may be able to replace lost organs, repair tissue, and even generate type O red blood cells, which can be used in transfusions for people with any blood type.

Greatso whats the problem?

Unfortunately, thereare drawbacksto this technology, namely the efficiency of reprogramming.Many IPSCsdo not actually gain completepluripotency. Epigenetic modifications are heavily implicated during the reprogramming process whereby the epigenetic makeup of the cell is completely overhauledto first encourage the expression of pluripotent genes and thenremodelled to encourage the expression of genes associated withthefinalcell typethattheIPSCwillbecome. As the epigenome plays a crucial role inreprogramming,inconsistenciesof pluripotencyacrossIPSClinesmaybedue toepigenetic barriers.

TRIM28: a novel epigenetic barrier

A team of scientists headed by Dr. Miles from The Netherlands Cancer institute recently uncovered a novel epigenetic barrier to the efficient induction of pluripotent stem cell reprogramming. Published in a recent issue of STEM CELLS, the paper highlights the use of a shRNA screen targeting over 670 epigenetic modifiers, revealing the involvement of TRIM28 in the resistance of cells transitioning from somatic to pluripotent state.

TRIM28, or Tripartite motif-containing 28, is involved in mediating transcriptional control by interacting with a certain domain in numerous transcription factors. Previous research shows that it plays a role in cellular differentiation and proliferation, DNA damage repair response, transcriptional regulation, and apoptosis.

By blocking the expression TRIM28 during reprogramming, the group demonstrated increases in the number of cells reaching pluripotency, as well as increased expression of a selection of 143 genes.

Analysis of the list of genes revealed the most statistically significant gene ontology term was unclassified. This result indicates TRIM28 does not regulate a specific pathway during reprogramming, states the authors.

It is known that TRIM28 gene encodes for a protein known to be involved in transcriptional regulation via the recruitment and formation of protein complexes that maintain repressive chromatin. Given this, researchers proposed the gene expression alterations, hence reprogramming differences, were likely to be associated with chromatin modification.

Subsequent tests supported this notion by establishing a proportion of the 143 genes to be located near H3K9me3 a repressive histone H3 modification which has shown to influence the transcription of genes that impedes the IPSC reprogramming process. When TRIM28 expression was blocked, the closer genes are to the H3K9me3 the greater the increase in expression. This suggests the role of TRIM28 in repressing the expression of genes involved in reprogramming via the maintenance of H3K9me3 heterochromatin site.

Whyis this important?

Due to the potential to produce almost anyothertype of cell, thetechnology ofIPSChas sparked excitement in the clinical sciences. The implementation ofIPSCto repair damaged or diseased tissue or to test/develop personalised medicines ison the horizon.By establishing barriers preventing the efficient transition of differentiated cells to pluripotent cells scientist canrefineIPSC generationto make the future clinical use ofIPSCsboth safe and efficient.

Source: Miles, D. C., de Vries, N. A., Gisler, S., Lieftink, C., Akhtar, W., Gogola, E., & Beijersbergen, R. L. (2017). TRIM28 is an Epigenetic Barrier to Induced Pluripotent Stem Cell Reprogramming.STEM CELLS,35(1), 147-157.

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Hypothalamic Stem Cells Could Provide New Insights Into Aging – Futurism

Posted: August 2, 2017 at 11:45 am

Hypothalamic Stem Cells

The hypothalamus is the region of the brain that helps to regulate internal conditions like body temperature and blood concentration, but new research shows that it may fail us as we age. The research indicates that as the hypothalamuss stem cells die off, the region actually starts to promote aging, causing mental and physical faculties to decline at a more rapid pace.

In the past, researchers have observed that the hypothalamus becomes inflamed over time. This lead them to posit that the area is connected to aging. Recent research on mice proved that reversing the inflammation in the hypothalamus increases the animals life span and slows physical deterioration. In this latest study, scientists focusedon the stem cells of the hypothalamus. In younger animals, these stem cells divide and replace damaged and dead cells. However, as this research shows, over time the number of stem cells present in the hypothalamus drops. Inold age, they are essentially gone.

The team believed they were on to something, but undertook some practical experiments to see if their ideas were borne out by the evidence. First, they altered mice genetically to ensure theyd be out of stem cells(at a point earlier than would occur naturally). Reducing the stem cells in the mice by around 70 percent meant a life span that was about 8 percent shorter. This accelerated loss of stem cells also caused a loss of coordination, endurance, and memory, as well as behavior that was less youthful, curious, and social. When the team injected stem cells into the hypothalami of middle-aged mice, those mice gained about about 10 percent more mental and physical capabilities compared to mice injected with regular brain cells.

Originally, scientists believed that the stem cell loss could besignificant because it meant the host was unable to repair and replace damaged and dead cells. However, when the hypothalami of middle-aged mice were injected with stem cells, they improved too rapidly for this to be thecorrect mechanism. Instead, the team suspected microRNAs might be at work.

The RNA molecules, called microRNAs, are manufactured and released by stem cells to carry messages to other cells. Practically, based on the messages they carry, microRNAs mayalter the proteins cells produce. The researchers discovered that the stem cells in the hypothalamus produce massive amounts of microRNAs contained in tiny exosomes. In fact, when they injected mice with exosomes packed with microRNA from young hypothalamus stem cells, the effects were almost as effective in slowing signs of mental and physical aging as injections of stem cells were.

Recent research has focused on the role of mitochondria in aging and on the use of induced pluripotent stem (iPS) cells in combatting aging in hematopoietic stem cells. Research from this year has also shown that cannabis-based treatment appears to reverse aging in the brains of mice. Concerning thisresearch, protecting or replacing the stem cells of the hypothalamus or somehow reinforcing or replacing the microRNA effects could slow aging in humans. This could mean testing current drugs such as acarbose (presently used to treat diabetes) to see if they can suppress the hypothalamic inflammation that causes the stem cells to die.

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Stem cell brain implants could ‘slow ageing and extend life’, study shows – The Guardian

Posted: August 2, 2017 at 11:44 am

Scientists have slowed down the ageing process by implanting stem cells into the brains of animals, raising hopes for new strategies to combat age-related diseases and extend the human lifespan.

Implants of stem cells that make fresh neurons in the brain were found to put the brakes on ageing in older mice, keeping them more physically and mentally fit for months, and extending their lives by 10-15% compared to untreated animals.

The work, described as a tour de force and a breakthrough by one leading expert, suggests that ageing across the body is controlled by stem cells that are found in the hypothalamus region of the brain in youth, but which steadily die off until they are almost completely absent in middle age.

Researchers at Albert Einstein College of Medicine in New York hope to launch clinical trials of the procedure soon, but must first produce supplies of human neural stem cells in the lab which can be implanted into volunteers.

Of course humans are more complex, said Dongsheng Cai, who led the research. However, if the mechanism is fundamental, you might expect to see effects when an intervention is based on it.

Previous experiments had already hinted that the hypothalamus, an almond-sized part of the brain in humans, played some role in the ageing process, but what it was remained unclear. The latest investigation from the US team pinpoints which cells are important and how they might work.

In the first of a series of experiments in mice, Cai showed that neural stem cells, which are found in a handful of brain regions at birth, disappear from the hypothalamus over time. The stem cells are known to form fresh brain cells in youth, but the process slows down dramatically in adults. Though small, the hypothalamus forms a crucial connection between the bodys nervous and hormonal systems.

To test whether the decline in stem cells was causing ageing, and not itself a result of old age, the researchers injected mice with a toxin that wiped out 70% of their neural stem cells. The effect was striking. Over the next few months the mice aged more rapidly than usual, and performed much worse than control animals on a battery of tests of endurance, coordination, social behaviour and ability to recognise objects. Behaviourally mice aged faster when these cells were removed during early ageing, Cai told the Guardian. The animals died months earlier than healthy control animals.

Next, the scientists looked at what happened when aged mice received injections of fresh neural stem cells. This time the mice lived longer than controls, typically several months more, an increase of about 15%. If a similar extension was achieved in humans, a person with a life expectancy of 80 years could live to 92.

Having proved that it was neural stem cells that were important for ageing, the scientists ran further tests to work out what the cells were doing. They found that molecules called microRNAs, or miRNAs, that are released from neural stem cells were responsible for most of the ageing effects. When the molecules are produced in the hypothalamus, they flow into the clear fluid in the brain and spinal cord and affect how genes operate.

The mechanism is partially due to these cells secreting certain miRNAs which help maintain youth, and the loss of these leads to ageing said Cai, whose study is published in Nature. The next step is to create human neural stem cells in the lab for testing.

It is a tour de force, said David Sinclair at Harvard Medical School. Its a breakthrough. The brain controls how long we live. I can see a day when we are implanted with stem cells or treated with stem cell RNAs that improve our health and extend our lives. I would love to know which brain stem cell secretions extend a mouses lifespan and if human stem cells make them too.

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