Monthly Archives: July 2017

A U.S. research team has reportedly edited the DNA of a human embryo just as a sperm fertilizes an egg, well before its eight-cell stage.

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By Kelly ServickJul. 27, 2017 , 2:30 PM

Since Chinese researchers announced the first gene editing of a human embryo 2 years ago, many expected that similar work in the United States was inevitable. Last night, the MIT Technology Review broke the news that such experiments have happened. The research, led by embryologist Shoukhrat Mitalipov of Oregon Health and Science University in Portland, also reportedly sidestepped problems of incomplete and off-target editing that plagued previous attempts, though details could not be confirmed since the work is not yet published and Mitalipov has so far declined to comment.

If a peer-reviewed paper bears out the news story, Its one more step on the path to potential clinical application, says bioethicist Jeffrey Kahn of Johns Hopkins University in Baltimore, Maryland, who served on a committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine in Washington, D.C., to address gene editing. The panels report earlier this year concluded that a clinical trial involving embryo editing would be ethically allowable under narrow circumstances.

The first published human embryoediting work, in 2015, used nonviable embryos and targeted a gene mutated in the heritable blood disorder beta thalassemia. But it revealed major shortcomings in applying the increasingly popular CRISPR gene-editing technology. The few embryos that took up the change made by CRISPR were a patchwork of edited and unchanged cells, and they bore unintended edits outside the targeted gene.

Another Chinese team, from Guangzhou Medical University, in March became the first to report repairing disease-causing mutations in viable embryos, but some still contained a patchy mix of edited cellsa phenomenon called mosaicism. In none of the Chinese efforts did the researchers go on to implant the manipulated embryos in women.

Sources familiar with the new work from Mitalipovs group told the MIT Technology Review that they had produced tens of successfully edited embryos, and had avoided the issue of mosaicism by injecting eggs with CRISPR right as they were fertilized with donor sperm. The Guangzhou team injected its CRISPR system into single-celled human embryosits not yet clear how much their timing differed from Mitalipovs. (The new research presumably relied on nonfederal government funding, since Congress prohibits the use of taxpayer funds on research that destroys human embryos.)

Concerns about mosaicism and off-target effects after the published work by the Chinese teams led some to conclude that CRISPR wasnt safe as a strategy for preventing a disease in a baby, much less adding some enhancement. But even with the apparent advance by the Oregon team, a U.S. clinical trial probably isnt imminent. Its noteworthy that theyve been able to make some of these claims, offers Michael Werner, executive director of the Alliance for Regenerative Medicine in Washington, D.C., who argued in a 2015 Nature commentary that ethical and safety issues should put germline editing research off limits. Its still a little premature to say that weve resolved all these safety issues now.

The NAS report notes that many inherited diseases can be prevented by selecting healthy embryos for in vitro fertilization, and that embryo editing might only be justified if it presents the only option for a couple to have a healthy biological child. Congress has meanwhile prohibited the U.S. Food and Drug Administration from reviewing applications for clinical trials involving embryo editing.

Read more from the original source:
First US team to gene-edit human embryos revealed - Science Magazine

China and India are vying for formal recognition from UNESCO of their cultural ties to ancient Tibetan medicine. Receiving UNESCO recognition could stimulate the Tibetan medicinal industrys growth in either country, but some experts are concerned that the practices would become watered down if produced on a massive scale. (New York Times)

Simulations suggest that nearly half of the matter in the Milky Way galaxy came from the gas of other galaxies.

Visual by NurPhoto / Getty

Those who can afford to outsource tasks they dislike probably should if they want to feel happier, according to a new study in the Proceedings of the National Academy of Sciences. The study found that many people of a variety of income levels stress about not having enough time, but are reluctant to pay others to do chores and tasks for them, which the researchers report decreases well-being. (BBC)

The sperm counts in men from North America, Europe, and Australia have dropped by more than 50 percent over the course of 40 years, according to a new meta-analysis. Because low sperm count can sometimes signify other health concerns, some experts are alarmed by the finding. (Washington Post)

A group of infectious disease experts in the U.K. are making the case against completing the course of prescribed antibiotics as a way to prevent antibiotic resistance in bacteria. The groups controversial stance, which also calls on physicians to stop sending the complete the course message to patients, is receiving some pushback within the medical establishment. (Scientific American)

Using the genome-editing technique CRISPR-Cas9, biologists in Oregon have successfully edited the DNA of viable human embryos, targeting a gene connected to a major disease. Though this type of DNA editing could be used to prevent parents from passing on deadly genetic mutations to their offspring, it faces regulatory obstacles in the United States, and the embryos were not permitted to develop past an early stage. (STAT)

Scientists have discovered that Japanese tits communicate using specific sequences of sounds to alert one another of predators. But the birds only understand the sounds if they are delivered in the proper order sort of like humans only understand sentences if the words are in the right places. (Science)

Almost half of the matter present in the Milky Way might have originated in other galaxies. New simulations have found that high-speed galactic winds could have pushed atoms in gaseous forms away from their home galaxies and into other galaxies such as ours. (Science News)

The ancient Canaanites, who the Bible says were annihilated by the Israelites and who left no textual records, seemed to have survived after all. A new genetic study found that present-day Lebanese people share enough DNA with Canaanite-related populations to be considered their descendants. (Independent)

See more here:
Abstracts: Milky Way, Medicine, and More - Undark Magazine

The genome-editing tool CRISPR has been put to good use so far for such things as creating monkeys with targeted mutations and engineering Malaria-proof mutant mosquitoes. But bring anything human under the purview of gene-editing and youre staring at an altogether different beast.

Will this beast editing genes in human embryos be friendly or hostile? That has been the critical question facing scientists and policy makers in the field. But even as the debate rages on, a report of creating genetically modified human embryos using CRISPR technology in the United States has now emerged.

According to MIT Technology Review, Shoukhrat Mitalipov and his team at Oregon Health and Science University have fertilised human eggs with sperm known to carry inherited disease-related mutations. These mutations were then corrected using CRISPR and the embryo was allowed to develop over the next few days. Importantly, it was not implanted. (If not implanted, embryos dont develop into babies.) Results reportedly displayed successful modifications for the large part with few errors in editing.

This exercise is only the second instance of gene-editing in human embryos anywhere; the first such case was reported in China.

CRISPR, or clustered regularly interspaced short palindromic repeats, allows for modification of DNA sequences and gene function. The technology, which is a natural defence mechanism of bacteria, promises to correct genetic defects with excellent efficiency and precision.

Gene-editing, however, raises important ethical questions as even small errors could possibly lead to permanent problems in the human gene pool.

In February this year, an American science policy group instituted by the National Academy of Sciences and National Academy of Medicine okayed gene-editing in human embryos so long as it was used to prevent babies from being born with diseases or disabilities and when there was no reasonable alternative.

There was no clarity on the nature of the procedure how safe was it? or which exact genetic modifications were pursued by Mitalipov and team. This lack of transparency, as Wired has pointed out, doesnt help quell concerns about the exercise. It now remains to be seen what the next step is and how far we are from engineering disease-free humans.

Also Read: Genome Editing: The Benefits And The Ethics

Read this article:
US Scientists Modify Genes In Human Embryos Using CRISPR - Swarajya

Injectinga smaller but functional form of the dystrophin gene, called microdystrophin, intodogs naturally affected by Duchenne muscular dystrophyallowed them to recover muscle strength and stabilized their overall disease symptoms, a new study shows.

This preclinical study demonstrates the safety and efficacy of microdystrophin, and makes it possible to consider developing a clinical trial in patients, Caroline Le Guiner, first author of the study, said in a news release.

Indeed, this is the first time that it has been possible to treat the whole body of a large-sized animal with this protein. Moreover, this innovative approach allows treatment of all patients with Duchenne muscular dystrophy, regardless of the genetic mutation responsible, Le Guiner added.

The study, titled Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy, was featured in the journalNature Communications.Researchers used a delivery system based on a viral vector, a strategy commonly used in gene therapy, to inject the engineered microdystrophin in 12 Golden Retrievers naturally affected by DMD.

DMD is a rare inherited disorder caused by mutations in the gene that encodes the protein dystrophin, which is essential for normal muscle function. It is one of the longest human genes, which makes therapeutic usein its natural form technically impossible. To overcome this limitation, researchers created the new variant called microdystrophinthat is shorter, but retains the function of the protein.

The results demonstrated microdystrophins potential as a gene therapy for people with DMD. The treatment increased levels of dystrophin protein in the dogs and significantly restored muscle function. Clinical symptoms of DMD in the dogs were stabilized for more than two years following treatment. No significant adverse side effects associated with the treatment were observed, demonstrating that it can be a safe treatment strategy.

This is tremendously exciting progress towards a gene therapy for DMD, said George Dickson, senior author of the study and researcher at Royal Holloway, University of London. The studies in [Golden Retrievers naturally affected by DMD) have been spectacular and exceeded our expectations.

The study also provided important data to support the therapeutic potential of this new gene therapy for DMD in children.

This new evidence of the efficacy of gene therapy in Duchenne muscular dystrophy strengthens the therapeutic arsenal developed (exon skipping, CRISPR Cas-9, pharmacogenetics, etc.), and the first results are there. We need to forge ahead to complete the final phase and transform these scientific advances into drugs for children, said Serge Braun, scientific director of AFM-Telethon.

The study resulted from the collaborative work between researchers from Genethon, the AFM-Telethon laboratory, Inserm (Nantes), and the University of London (Royal Holloway), and was supported by donations from the French Telethon.

My team has worked for many years to optimize a gene therapy medicine for DMD, and now the quite outstanding work of colleagues in France, in Genethon, in Nantes, and in Paris has taken us close to clinical trials in DMD patients, Dickson said. I pay thanks also to the amazing and steadfast support of this research by AFM-Telethon and MDUK (Muscular Dystrophy UK) which has been essential to this achievement.

Original post:
Microdystrophin Gene Therapy Shows Promise in Dogs with Duchenne Muscular Dystrophy, Study Shows - Muscular Dystrophy News

A tumor is a trove of data.

In handling some kinds of life-or-death medical judgments, computers have already have surpassed the abilities of doctors. Were looking at something like promise of self-driving cars, according to Zak Kohane, a doctor and researcher at Harvard Medical School. On the roads, replacing drivers with computers could save thousands of lives that would otherwise be lost to human error. In medicine, replacing intuition with machine intelligence might save patients from deadly drug side effects or otherwise incurable cancers.

Consider precision medicine, which involvestailoring drugs to individual patients. And to understand its promise, look toShirley Pepke, a physicist by training who migratedinto computational biology. When she developed a deadly cancer, she responded like a scientist and fought it using big data. And she is winning. She shared her story at a recent conference organized by Kohane.

In 2013, Pepke was diagnosed with advanced ovarian cancer. She was 46, andher kids were 9 and 3. It was just two months after her annual gynecological exam. She had symptoms, which the doctors brushed off, until her bloating got so bad she insisted on an ultrasound. She was carrying six liters of fluid caused by the cancer, which had metastasized. Her doctor, she remembers, said, I guess you werent making this up.

She did what most people do in her position. She agreed to a course of chemotherapy that doctors thought would extend her life and offered a very slim chance of curing her. It was a harsh mixture pumped directly into her abdomen.

She also did something most people wouldnt know how to do -- she started looking for useful data. After all, tumors are full of data. They carry DNA with various abnormalities, some of which make them malignant or resistant to certain drugs. Armed with that information, doctors design more effective, individualized treatments. Already, breast cancers are treated differently depending on whether they have a mutation in a gene called HER2. So far, scientists have found no such genetic divisions for ovarian cancers.

But there was some data. Years earlier, scientistshad started a data bank called the Cancer Genome Atlas. There were genetic sequences on about 400 ovarian tumors. To help her extract useful information from the data, she turned to Greg ver Steeg, a professor at the University of Southern California, who was working on an automated pattern-recognition technique called correlation explanation, or CorEx. It had not been used to evaluate cancer, but she and ver Steeg thought it might work.She also got genetic sequencing done on her tumor.

In the meantime, she found out she was not one of the lucky patients cured by chemotherapy. The cancer came back after a short remission. A doctor told her that she would only feel worse every day for the short remainder of her life.

But CorEx had turned up a clue. Her tumor had something on common with those of the luckier women who responded to the chemotherapy -- an off-the-charts signal for an immune system product called cytokines. She reasoned that in those luckier patients, the immune system was helping kill the cancer, but in her case, there was something blocking it.

Eventually she concluded that her one shot at survival would be to take a drug called a checkpoint inhibitor, which is geared to break down cancer cells defenses against the immune system.

Checkpoint inhibitors are only approved so far for melanoma. Doctors can still prescribe such drugs for other uses, though insurance companies wont necessarily cover them. She ended up paying thousands of dollars out of pocket. At the same time, she went in for another round of chemotherapy. The checkpoint inhibitor destroyed her thyroid gland, she said, and the chemotherapy was damaging her kidneys. She stopped, not knowing whether her cancer was still there or not. To the surprise of her doctors, she started to get better. Her cancer became undetectable. Still healthy today, she works on ways to allow other cancer patients to benefit from big data the way she did.

Kohane, the Harvard Medical School researcher, said similar data-driven efforts might help find side effects of approved drugs. Clinical trials are often not big enough or long-running enough to pick up even deadly side effects that show up when a drug is released to millions of people. Thousands died from heart attacks associated with the painkiller Vioxx before it was taken off the market.

Last month, an analysis by another health site suggested a connection between the rheumatoid arthritis drug Actemra and heart attack deaths, though the drug had been sold to doctors and their patients without warning of any added risk of death. Kohane suspects there could be many other unnecessary deaths from drugs whose side effects didnt show up in testing.

So whats holding this technology back? Others are putting big money into big data with the aim of selling us things and influencing our votes. Why not use it to save lives?

First theres the barrier of tradition, said Kohane, whose academic specialty is bioinformatics, a combination of math, medicine and computer science. Medicine does not understand itself as an information-processing discipline, he said. It still sees itself as a combination of intuitive leaps and hard science. And doctors arent collecting the right kinds of data. Were investing in information technology thats not optimized to do anything medically interesting, he said. Its there to maximize income but not to make us better doctors.

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Physicians arent likely to be replaced by algorithms, at least not right away, but their skill sets might have to change. Already, machines have proven themselves better than humans in the ability to read scans and evaluate skin lesions. Pepke ended her talk by saying that in the future, doctors may have to think less statistically and more scientifically. Her doctors made decisions based on rote statistical information about what would benefit the average patient -- but Shirley Pepke was not the average patient. The status quo is an advance over guessing or tradition, but medicine has the potential to do so much better.

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

To contact the author of this story: Faye Flam at fflam1@bloomberg.net

To contact the editor responsible for this story: Tracy Walsh at twalsh67@bloomberg.net

Read more:
Big Data Shows Big Promise in Medicine - Bloomberg