Category Archives: Human Genetics

After Jennifer Doudna and other scientists improved the technology known as CRISPR to edit human genomes, a long-awaited, and sometimes feared, milestone arrived.

For the first time in human existence, it became practical to change genes throughout the entire human genome with high precision and accuracy. And today, a decade after the introduction of CRISPR, its newly apparent that such manipulations have been made to human embryos a feat achieved by scientists at the Salk Institute in La Jolla and elsewhere.

Tinkering with genetics, a system that has been produced through billions of years of evolution, takes humanity into unknown territory. This powerful technology can be used for many purposes, not just stopping disease. Alterations in an embryos edited genome would be passed along to generations of descendants for good or ill.

Doudna, a UC Berkeley molecular biologist, said during a visit to San Diego this week that society needs to catch up to this potentially world-transforming field of science. She has co-authored a book, A Crack in Creation, on the benefits, perils and ethics of what scientists call germline editing.

The question will be as the technology comes to fruition ... should we use it in that fashion? Doudna said about germline editing in a Monday interview at the American Association for Clinical Chemistrys scientific meeting in San Diego.

Its a question that has many facets to it, she said. Who decides who gets access, who pays for it and under what circumstances should that type of editing be done? These are important questions because the technology is already at the point where its possible to do this.

Her points were underscored by reports last week of a germline-editing study performed by a team in the United States (including the Salk researchers), China and Korea. The report showed that CRISPR could be used to repair a genetic defect in single-celled human embryos. The embryos were not allowed to develop beyond a few days.

This project received private funding, allowing it to sidestep government restrictions on such genetic editing.

The study was leaked to a British reporter and hasnt been published yet.

Doudna said she wasnt cognizant of the ethical issues when she and collaborator Emmanuelle Charpentier began exploring CRISPR.

Beyond the call for society to grapple with the ramifications of germline editing, Doudna said, its difficult to get more specific, except to exercise general caution.

In many cases, genetic defects dont even need to be repaired if multiple embryos are being generated, she said. These embryos could simply be screened for genetic defects, and a healthy embryo would be chosen.

In my opinion, we still need to respect the recommendations in the (National Academy of Sciences) report published in February that recommended refraining from clinical use of human germline editing until and unless theres broad societal consensus about the value, Doudna said.

The report available at j.mp/nasgene doesnt actually spell out how the technology should be used; it merely suggests a method for making decisions, Doudna said.

The challenge is how to actually implement discussions that might lead to a broad societal consensus. The debate is still out on how we might proceed.

International scientific organizations, leading research and medical groups in the United States, the Trump administration and others have neither taken the lead nor been able to unify the wide spectrum of parties to arrive at a joint set of standards.

Amid the political, ethical and cultural questions, Doudna emphasized that CRISPR also might transform human suffering by treating or even eradicating various diseases. The method can do so by altering the genome of non-reproductive cells, and these changes wouldnt get transferred to the next generation.

It's important to for people to appreciate that this is a powerful technology that has the potential to do a lot of good, to solve real-world problems not only in clinical medicine but also in agriculture and synthetic biology, Doudna said.

Untold millions of years ago, Mother Nature invented genetic editing.

Bacteria use CRISPR short for Clustered Regularly Interspaced Short Palindromic Repeats to fight viral infections.

The system contains an RNA sequence that can locate a complementary DNA sequence, along with an enzyme called Cas that acts as molecular scissors to cut up the DNA. The RNA matches sequences from previous infections, which the bacteria capture and incorporate into the CRISPR system.

Humans entered the picture when they realized that the RNA sequence could be swapped out with other sequences specifying various DNA segments of interest. This approach could be used to chop up a defective sequence.

Doudna said her lab is exploring genetic editing to treat diseases of the brain. This endeavor is strictly in the research stage, and much more testing will be needed before it can be considered for testing in people.

I think were still years away from having a clinical application, especially for things like Huntingtons disease, Doudna said.

In the end, she said, its important for the public to understand that all the good CRISPR might produce has emerged from basic research.

It really came about from fundamental science that was going on in international collaboration, that led to an understanding of a system that could be harnessed as a tool for gene editing, Doudna said. The value of fundamental research is really underscored when you look at what can happen when scientists are allowed to do creative work that is not applied in a particular direction.

bradley.fikes@sduniontribune.com

(619) 293-1020

Read this article:
CRISPR star Jennifer Doudna calls for public debate on embryo editing - The San Diego Union-Tribune

In recent days, countless media outlets have carried bold headlines alleging that a new study calls into question key details presented in the Bible.But theresa big problemwith that narrative:It simply isnt true.

It all started with a newly released study published in theAmerican Journal of Human Genetics that claimed to find some intriguing information aboutthe Canaanites, an Old Testament people group that inhabited Palestine before the Hebrews conquered them and claimed the biblical promised land.

READ: Trumps Most Powerful Cabinet Members Are Making History With Weekly Bible Study

Titled, Continuity and Admixture in the Last Five Millennia of Levantine History from Ancient Canaanite and Present-Day Lebanese Genome Sequences, thereportpurports to show that present-day Lebanese derive most of their ancestry from a Canaanite-related population. On the surface, thats pretty interesting stuff.

But heres why the studys claim of finding Canaanite ancestors really made such a splash:Deuteronomy 20:17 discusses Gods call to utterly destroy the Canaanites, leading some reporters to make some inaccurate claims aboutwhat really happened.

The versereads, Completely destroy them the Hittites, Amorites, Canaanites, Perizzites, Hivites and Jebusites as the LORD your God has commanded you. And Joshua 10 does proclaim that there were no survivors during the conquests, but there are anumber of theoriesinvolving the language used that could help explain that proclamation.

Either way, many in the media simply stopped there, purporting that any modern day evidence of Canaanite DNA must mean that the Bible is incorrect.

Rather than media outlets digging deeper into the truth about whats in the biblical texts, writerDavid Klinghoffer accused culturally illiterate science reporters of using the study to slap [the] Bible around. Klinghoffer, writing for Evolution News,compiled a listof the media headlines that emerged in the wake of the studys release:

Theres a major problem with all of these gotcha Bible headlines, though: Some of them are pretty inaccurate.

AsKlinghoffer noted, the Bible makes it clear in the Book of Judges that the Canaanites lived on beyond the invasion. In fact, the first chapter (verses 28-33)says it all:

When Israel became strong, they pressed the Canaanites into forced labor but never drove them out completely.Nor did Ephraim drive out the Canaanites living in Gezer, but the Canaanites continued to live there among them.Neither did Zebulun drive out the Canaanites living in Kitron or Nahalol, so these Canaanites lived among them, but Zebulun did subject them to forced labor.Nor did Asher drive out those living in Akko or Sidon or Ahlab or Akzib or Helbah or Aphek or Rehob.The Asherites lived among the Canaanite inhabitants of the land because they did not drive them out.Neither did Naphtali drive out those living in Beth Shemesh or Beth Anath; but the Naphtalites too lived among the Canaanite inhabitants of the land, and those living in Beth Shemesh and Beth Anath became forced laborers for them.

After realizing that there were some major errors in their reporting, some journalists issued retractions. The Telegraph was among those that published an honest assessment of the previously incorrect information in the outlets initial report.

The original version of this story erroneously said the Bible claimed the Canaanites were wiped, a correctionreads at the end of the story. However, elsewhere in the Bible, it says the elimination was not successful.

Its possible that some of the confusion could have emerged from the DNA study itself, as there are some lines of text in the report about the so-called destruction of the Canaanites.

Uncertainties also surround the fate of the Canaanites: the Bible reports the destruction of the Canaanite cities and the annihilation of its people; if true, the Canaanites could not have directly contributed genetically to present-day populations, the textreads. However, no archaeological evidence has so far been found to support widespread destruction of Canaanite cities between the Bronze and Iron Ages: cities on the Levant coast such as Sidon and Tyre show continuity of occupation until the present day.

So, there you have it. Unfortunately, its yet another example of journalists misunderstanding biblical details and making claims that simply dont add up to the facts.

Some might call it fake news, though others would simply attribute it to laziness. Either way: the record has now been cleared.

Here is the original post:
'The Bible Was WRONG!': Media Massively Bungle Bible Story and Are Forced to Issue Corrections - CBN News

Scientists from U.S Have Successfully Edited Human DNA By using CRISPR technology, a team of scientists from Oregon has edited the genes in human embryos and made huge steps in reaching new results. They tried to eradicate genetically transmitted diseases.

CRISPR isnt a new technology but it has started being used in human genetics recently. CRISPR is a DNA sequence that was found in bacteria and could protect the immune system, detecting and destroying invaders such as viruses that try to infect the bacteria. Scientists try to use CRISPS so that they target mutations that would cause diseases, this way treating them from the root of DNA encoding.

Major issues were solved using gene-altering technology.

The lead researcher Shoukhrat Mitalipov from the Oregan Health and Science University stated that they solved their previous problems they had with CRISPR gene-altering technology. In 2015 they faced a problem using this technology, resulting in embryos suffering a condition named mosaicism due to CRISPR that aligned edited and unedited cells.

In the early 2017 China went through a similar problem at the Hospital Guangzhou Medical University.

They tried to repair abnormal embryos and the results were not satisfying. They also used normal embryos resulted from immature eggs and fertilized them with sperm that carried genetic disease. Before the cell division started, they injected CRISPR and out of 6 embryos, half were repaired but with a problem: two of them were suffering from mosaicism.

New ground has been broken later by Mitalipov and his team.

In Oregon Mitalipov and his team were able to inject CRISPR into the eggs while they fertilized them with sperm and avoided moisaicism. They also solved the problem of genetic disease transmission, correcting the genes.

Were still waiting for official results from the Oregon Health and Science University and Shoukhrat Mitalipov through a published paper which will soon appear in a scientific journal.

See the original post:
Scientists from US Have Successfully Edited Human DNA - News4C

The Canaanites lived at the crossroads of the ancient world. They experienced wars, conquests and occupations for millennia, and as a result evolutionary geneticists expected that their DNA would become substantially mixed with incoming populations.

Astonishingly, new genetic analysis shows that scientists were wrong. According to a new study in the American Journal of Human Genetics, todays Lebanese share a whopping 93% of their DNA with the ancient Canaanites.

One of five Canaanites found buried in present-day Lebanon from which scientists extracted and sequenced DNA. Photo by Dr. Claude Doumet-Serhal/the Sidon excavation

Archaeologists at the Sidon excavation site have been unearthing ancient Canaanite secrets for the last 19 years in the still-inhabited Lebanese port city

They sequenced the whole genomes of five individuals found in Sidon who lived about 3,700 years ago. The team then compared the genomes of these ancient Canaanites with those of 99 Lebanese people currently living in the country, along with the previously published genetic information from modern and ancient populations across Europe and Asia.

This evidence supports the idea that different Levantine cultural groups such as the Moabites, Israelites, and Phoenicians may have had a common genetic background, the authors said.

The findings have powerful cultural implicationsIn a country struggling with the ramifications of war and a society fiercely divided along political and sectarian lines, religious groups have often looked to an uncertain history for their identities.

The GLP aggregated and excerpted this article to reflect the diversity of news, opinion, and analysis. Read full, original post: The DNA of ancient Canaanites lives on in modern-day Lebanese, genetic analysis shows

The rest is here:
Biblical mystery solved: Ancient Canaanites DNA lives on in Lebanese - Genetic Literacy Project

OXFORD, England When Charles Darwin published his landmark theory of evolution by natural selection in the 19th century, religious leaders were confronted with a powerful challenge to some of their oldest beliefs about the origins of life.

Then evolutionary theory was expanded with the insights of genetics, which gave further support for a scientific and secular view of how humans evolved.

Faith and tradition were forced further onto the defensive.

Now, exciting progress in biology in recent decades may be building up a third new phase in the scientific explanation of life, according to thinkers gathered at a University of Oxford conference last week (July 19-22).

Although this 21st-century wave has no single discovery to mark its arrival, new insights into developing technologies such as genetic engineering and human enhancement may end up giving another important boost to the belief that science has (or eventually will have) the answers to lifes mysteries.

Some scientists, theologians and philosophers see in this ever deeper knowledge of how genes work a possible alternative to the more reductive approach to evolution one that brings in a broader view that also considers the influence of the environment.

Dr. Donovan Schaefer. (Credit: Photo courtesy of University of Oxford.)

Unlike the earlier views, which seemed to lead toward either agnosticism or atheism, the theologians see this new biology or holistic biology as more compatible with religious belief.

Weve added definition to the picture of evolution that has deepened and enriched our understanding of biological processes, Donovan Schaefer, an Oxford lecturer in science and religion who co-organized the conference, told the opening session of the July 19-22 meeting.

But he added: It would be naive to imagine that the grander questions about biology, religion, the humanities and evolutionary theory generally have been put to death.

The achievements on their list include new fields like epigenetics, the science of how genes are turned on or off to influence our bodies, and advances in cognitive and social sciences that yield ever more detailed empirical research into how we behave.

Waiting in the wings are new technologies such as genome editing, which can modify human genes to repair, enhance or customize human beings. Scientists in China are believed to have already genetically modified human embryos and the first known attemptto do so in the United States was reported this week (July 26).

Schaefer compared todays deeper understanding of biology to the higher resolution that photographers enjoy now that photography has advanced from film to digital images.

Genes once thought to be fairly mechanical in influencing human development leading to the my genes made me do it kind of thinking have been found to be part of complex systems that can act in response to a persons environment.

The Radcliffe Camera, a reading room of the nearby Bodleian Library, at University of Oxford on July 22, 2017. The unique building originally housed the Radcliffe Science Library. All Souls College is in the background. (Credit: RNS photo by Tom Heneghan.)

Since scientists succeeded in sequencing the genome in the late 1990s, they have found that epigenetic markers that regulate patterns of gene expression can reflect outside influences on a body.

Even simpler living objects such as plants contain a complex internal genetic system that governs their growth according to information they receive from outside.

To theologians who see a new biology emerging, this knowledge points to a more holistic system than scientists have traditionally seen, one more open to some divine inspiration for life.

In this view, the fact that epigenetic markers can bring outside pressures to bear on the genome deep inside a human means genetics is not a closed system, but part of the wider sweep of nature in which they, as religious thinkers, also see Gods hand.

Professor Alister McGrath, director of the Ian Ramsey Centre for Science and Religion. (Credit: Photo courtesy of University of Oxford.)

Nature is so complex and rich and that prompts questions about why on earth is this the case? If youre an atheist, how do you explain a universe that seems to have the capacity to produce these things in the first place? asked Alister McGrath, an Oxford theologian who is director of the Ian Ramsey Centre for Science and Religion that hosted the conference.

This in turn opened a space for theologians to augment the discussion about the new biology, he said.

Massimo Pigliucci, a philosopher at New Yorks City College with doctorates in genetics and evolutionary biology, also said scientism the idea that science can answer all lifes important questions was too limited.

Science informs and grounds certain philosophical positions; it doesnt determine them, he said. But the data cant settle ethical questions.

Pigliucci agrees with the trend to use the evolutionary paradigm to analyze fields outside of biology, including topics such as ethics and morality.

The life sciences tell us that the building blocks of what we call morality are actually found presumably they were selected for in nonhuman social primates, he said. Science gives you an account of what otherwise looks like magic: Why do we have a moral sense to begin with? How did we develop it?

Not all present agreed that science could explain religion.

Some suspect that biology has triggered some kind of devotion and there are too many people who practice this cult, said Lluis Oviedo, a theologian at the Pontifical University Antonianum in Rome.

His own research has found at least 75 books and academic articles trying to explain religion through evolution and he knew of about 20 more on the way, he said.

Although he thinks, the time of explaining through radical reduction is over, he admitted few biologists seemed ready to accept the more holistic new biology.

Even some scientists at the conference, while ready to engage with the philosophers and theologians, showed less interest in discussions about whether a new biology was emerging.

A dawn fog on Christ Church Meadow obscures the view of the historic University of Oxord in England. (Credit: Photo courtesy of Creative Commons/Tejvan Pettinger.)

Im pragmatic, explained Ottoline Leyser of the University of Cambridge, whose lecture on plant genetics was one of the conferences highlights.

Theologians in the decades long science and religion debate, which argues the two disciplines complement each other, have also become more pragmatic as their dialogue proceeds.

Oxfords McGrath said the theologians had become more modest in the claims they made about what religion could contribute to this debate. Unlike some more doctrinaire scientists, he said, they did not think they had all the answers.

They dont say These observations in nature prove or disprove God, he said. Our religious way of thinking gives you a framework which allows you to look at the scientific approach to the world and understand why it makes sense, but at the same time also to understand its limits.

Those things need to be in the picture if were going to lead meaningful lives.

Read more here:
Scientists, theologians ponder if biology and religion go together - Crux: Covering all things Catholic

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, California, 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.

Marilynn Marchione can be followed at http://twitter.com/MMarchioneAP

Read more from the original source:
In US first, scientists edit genes of human embryos - ABC News

On any bustling city street, in the middle of the afternoon, its probably the case that half or more people are wearing earbuds, while the rest are abiding the noise pollution all around them. No one thinks twice about it, either.

The reality is that from a very young age, our hearing is now under assault.Little wonder that one in eight people in the United States aged 12 years or older has hearing loss in both ears, based on standard hearing examinations. By age 65, one in three people has hearing loss.

The problem will only grow as more people flock to city centers. According to recent United Nations data, roughly 54 percent of the worlds population lives in urban areas right now, and that number is expected to hit 66 percent by 2050, meaning cities could take in another 2.5 billion people, accounting for population growth.

With any luck, in our lifetimes, potentially soon, even, some of this hearing loss will be fixable not with hearing aids or cochlear implants, which arent available to everyone and dont work for a high percentage of people anyway. Scientists think instead that the combination of human genetics and single cell expression profiling has brought us to the point where medicine can help fix hearing. In fact, there are right now a small number of outfits quietly racing to develop the first approved drug for hearing loss, and if, like us, you live with a playlist unspooling in your ears part of each day, you should be rooting for them to succeed.

Some are further along than others, as a recent Xconomy piece observed. San Diego-basedOtonomyhas a drug for swimmers ear that could be approved this year. Meanwhile,Auris Medical, a Swiss biotech whose tinnitus candidate last year failed to beat a so-called dummy therapy in a Phase 3 trial, is currently working on other hearing loss conditions.

Both Otonomy and Auris Medical are publicly traded, but they have peers (and rivals) in the still-private world. Two young startups to watch they have strong founders and top venture backing on their side areFrequency Therapeutics and Decibel Therapeutics, both based in Boston.

Decibel Therapeutics was incubated by the powerhouse investment firm and incubator Third Rock Ventures. Along with SROne (a venture fund that counts GlaxoSmithKline as its sole investor), Third Rock provided the company with $52 million to get started in 2015, and it more recently raised an undisclosed amount of funding from GV.

Anthony Philippakis, a venture partner at GV who led the deal, says one aspect of Decibel that excited him is its portfolio approach, with some of its focus on single cell genomics, some on human genetics, some on direct-to-patient clinical trials and some on generating phenotypic data about the hearing system. (Philippakis seems to have embraced a portfolio approach to his own work. In addition to working with GV, hes a cardiologist at Brigham and Womens Hospital, and the chief data officer at Broad Institute of Harvard and MIT.)

As Decibels CEO, Steve Holtzman explains of the companys modus operandi: If you make investments in a broad discovery and translational medicine platform for drug discovery not just take a shot on goal with a single drug or assay you have a better chance to dominate the space.

Indeed, Holtzman who is focused first on hearing loss in millennials but who has ambitions to tackle hearing loss across the age spectrum says Decibel is working on drugs to reduce against drug toxicity [which can cause hearing loss], drugs to repair hair cells [in the inner ear] , drugs that are looking at other aspects of hearing that may involve the [central nervous system], and drugs focused on regeneration [versus just cellular repair].

Our play is much broader than that of any other firm, adds Holtzman, who has worked in the biotech industry for roughly 30 yearsand helped co-found the company with Third Rock.

Holtzman doesnt mention Frequency Therapeutics specifically, but its probably no coincidence that Frequency which recently raised $32 million in Series A led by CoBro Ventures, an investment firm formed by tech entrepreneur Marc Cohen and his brother Alain is taking a rather different approach.

The vision for the company started three years ago, says CEO David Lucchino. Bob Langer, a renowned biomedical engineer at MIT, had teamed up with peer Jeffrey Karp of Harvard Medical school on research showing that cells in the inner ear theyre called progenitor cells, and each of us is born with a fixed number of them could potentially be manipulated to create new inner ear cells.

Why thats important: these inner ear hair cells absorb sound and convert it to electrical impulses.

Frequencys lead program is focused on treating chronic hearing loss by regenerating cochlear hair cells with combinations of easily made drug molecules. But one challenge, among many, is whether this growth can happen in vivo. Why no one yet knows: Langer and Karps earlier findings involved human cochlear tissue that had been removed from a 40-year-old, whod had to have it removed in order for surgeons to get to a tumor.

Though the researchers witnessed an encouraging response from the tissue after dosing it with drugs, shooting medicine directly into someones ear and getting it to grow new cells is a giant leap from that starting point. Lucchino acknowledges, too, that determiningwhat amount of medicine to inject, or how often to inject it, would present a whole new host of other obstacles to overcome.

Given the various unknowns, its perhaps no surprise that Lucchino who worked as a venture capitalist with Polaris Partners before founding an earlier biosciences company 10 years ago says Frequency plans to focus on more than hearing eventually.

Its our first focus, but we view ourselves as a next-generation regenerative medicine player. And hearing is a wonderful place for us to start.

Either way, Frequency might find encouragement in other initiatives that are making meaningful strides. For example, two projects similarly involving endogenous cells (meaning already present in the body), are now in clinical development at the Swiss company Novartis.

The programs which came out of the small-molecule regenerative program of Scripps Research Institute of La Jolla, Calif. are focused on other areas, including treating multiple sclerosis and gastrointestinal problems. Some academics see the approach as potentially very powerful, however. If only it works. Stay tuned.

View post:
A race is underway to repair our hearing with medicine ... - TechCrunch

America reportedly has moved ahead in a controversial race to tinker with human DNA but the scientific feat is shrouded in unanswered questions.

The MIT Technology Review published on Wednesday a news report about the first-known experiment to create genetically modified human embryos in the United States using a gene-editing tool called CRISPR.

Shoukhrat Mitalipov, director of the Oregon Health & Science Universitys Center for Embryonic Cell and Gene Therapy, reportedly led the new research. Mitalipov and the university would not confirm details of the research to CNN.

Results of the peer-reviewed study are expected to be published soon in a scientific journal. No further information will be provided before then, according to an emailed statement from the universitys press office. Another researcher cited in the MIT report, the Salk Institutes Jun Wu, did not reply to CNNs request for comment.

Mitalipov also declined to comment in the MIT Technology Review report, referencing the research results have not been published yet in a peer-reviewed scientific journal, which is considered the gold standard for scientific research. The author of the MIT report would not confirm to CNN whether he had seen the paper.

Previously, Mitalipov and his colleagues reported the first success in cloning human stem cells in 2013, successfully reprogramming human skin cells back to their embryonic state. In 2007, a research team led by Mitalipov announced they created the first cloned monkey embryo and extracted stem cells from it.

The MIT Technology Review reported the researchers in Portland, Oregon edited the DNA of a large number of one-cell embryos, specifically targeting genes associated with inherited diseases in those embryos. The MIT Technology Review could not determine which disease genes had been chosen for editing in the new research.

Im not surprised that they were looking at genetic diseases to try and see if they could target them, because thats exactly where I think the future inevitably leads, said Arthur Caplan, a professor and founding head of the division of bioethics at New York University Langone Medical Center, who was not involved in the research.

CRISPR research and controversy

Previously, scientists in China were the first in the world to reveal attempts to modify genes in human embryos using CRISPR. Three separate papers were published in scientific journals describing various studies in China on gene editing in human embryos.

When it comes to the new research, my reaction was this is an interesting incremental step and, boy, I bet its going to get blown up as being more important than it is, said Hank Greely, professor of law and genetics at Stanford University, who was not involved in the research. Its not the first time anybody has CRISPR-ed human embryos. Its not the first time anybodys CRISPR-ed viable human embryos. Its certainly not the first time people have CRISPR-ed viable mammalian embryos. Its the first time its been done in the US, but the embryos dont care where they are.

Yet, the research has already generated attention and controversy.

This is pushing the research faster than I thought we would see, said Dana Carroll, professor of biochemistry at the University of Utah, if the MIT Technology Review report rings true. Carroll has used CRISPR in his own studies but was not involved in the new research.

He pointed out the new research reportedly involved earlier, more delicate embryos, and CRISPR reportedly was still demonstrated as efficient.

From the perspective of research that would ultimately make germline editing safer and more effective, the earlier embryos will provide more relevant information, he said.

CRISPR an acronym for clustered, regularly interspaced, short palindromic repeats allows scientists to cut and edit small pieces of DNA at precise areas along a DNA strand, essentially modifying DNA.

Once scientists discovered they could develop a system that modifies pieces of DNA, they tested the gene-editing technology in microbes, then non-human mammals, then non-human primates and then, by 2015, human embryos.

The controversy surrounding gene-editing in human embryos partly stems from concern the changes CRISPR makes in DNA can be passed down to the offspring of those embryos later in life, from generation to generation. Down the line, that could possibly impact the genetic makeup of humans in erratic ways.

There is also considerable concern about off-target effects, such as making mutations at sites in the genome other than the intended target, Carroll said.

In other words, an edit made in one area of DNA possibly could cause problems in another, as a ripple or domino effect, which could be concerning.

Some CRISPR critics also have argued gene-editing may give way to eugenics and to allowing embryos to be edited with certain features in order to develop so-called designer babies.

Though, not all experts are too concerned.

Treating diseases

Some people are worried about wheres this all going to head? Are we going to wind up with super babies and eugenics? And, to me, I dont find that an interesting objection. Its too soon for that objection, Caplan said. Clearly, if were going to let this research proceed, its going to be to treat diseases and prevent diseases.

The enthusiasm surrounding gene-editing in human embryos partly stems from the promise CRISPR has shown in editing away and treating devastating intractable diseases. Earlier this year, the National Academies of Sciences, Engineering and Medicine published a report on human genome editing, addressing potential applications of gene editing, including the possible prevention or treatment of disease.

I hope the applications will be for the treatment of serious diseases and in cases where a sensible alternative is not available, as the National Academies report proposes, Carroll said.

Greely said: The National Academy of Sciences came out with a big report on Valentines Day this year about genome editing in humans, and I thought they very usefully divided it into three categories: basic research, treating living people and making changes that will pass down from generation to generation.

As for the reported new research, this is category one. This is basic research, he said. Category three is the ethically crucial one; this isnt that. Were still a long way from that.

Whats next

Other strides have been made recently in CRISPR research. Scientists at the Memorial Sloan Kettering Cancer Center in New York used the technology to genetically engineer immune cells to target and kill tumor cells in mice.

The mouse study was published in the journal Nature in February. More research is needed to determine whether similar results would appear in humans.

Last year, scientists in the Netherlands published a study in the journal PLOS Pathogens demonstrating CRISPR could be used to edit the DNA of three types of herpes viruses in a petri dish. More research is needed to see whether this tool could be used to fight herpes in actual humans.

Other examples of diseases where CRISPR could show promise as a treatment or preventive approach in the future include cystic fibrosis, sickle cell, hemophilia and mitochondrial diseases, such as the rare degenerative condition that the terminally-ill British infant Charlie Gard has, Caplan said.

There are what are called point mutations where you can go in and fix one genetic error. The simpler the genetic error, the easier it might be to try to repair it using a CRISPR gene-insertion technique, Caplan said about genetic diseases. I think rather than trying to treat cystic fibrosis, or treat sickle cell, or treat hemophilia, it does make ethical sense to figure out ways to prevent it. Now, obviously if its too risky we wont do it. If its too dangerous or maybe it wont work, we still dont know. Were in the early, early days (of research), but I dont think its fear of eugenics that should stop us.

Continued here:
Report: Scientists edit human embryos for first time in US - kfor.com

Download PDF Missing link: Not all mutations that crop up in people with a condition actually contribute to it.

palau83 / iStock

A new method can help researchers and clinicians gauge the likelihood that a gene is associated with a particular condition. The strategy could help researchers focus their efforts on genes with a solid connection to a condition1.

Advances in sequencing technology are speeding the pace of gene discovery. But the strength of evidence for a genes role in a condition can vary. For example, the size of the study matters: Those involving rare diseases are often small. A control group is also critical to ensure that a mutation is rare in the general population.

In the new method, researchers evaluate a mutation by combing the literature for two types of studies: those that identify the mutation in people with a condition, and those that examine the genes function. The researchers assign a numerical rating to each study according to factors such as its size, the presence of a control group, and the statistical significance of the findings.

They then combine these ratings and adjust them for the number of studies. The process yields a combined score for each mutation between 0 and 18. If the supporting evidence has been replicated and the mutation has a score of 12 or higher, the association is deemed definitive.

Pairs of independent groups used the method to evaluate each of 33 gene-condition associations. They then compared their assessments and made a final classification in conjunction with experts on the conditions.

Both groups came to similar conclusions as each other and the experts for 29 of the 33 associations. For example, they all judged the gene FGFR3 as definitively involved in achondroplasia, a form of dwarfism. And they determined there is limited evidence that SCN4B is involved in a cardiovascular condition called long QT syndrome. The findings appeared 1 June in the American Journal of Human Genetics.

The method is optimized for conditions that arise from inherited mutations in a single gene. But future iterations could allow researchers to interpret the genetic contributions to complex conditions such as autism, the researchers say.

The researchers have put their assessments of the 33 associations into a database called ClinGen. They invite other researchers to add results for other associations.

More:
New method rates strength of ties between genes, conditions - Spectrum

As powerful as the gene-editing technique Crispr is turning out to beresearchers are using it to make malaria-proof mosquitoes , disease-resistant tomatoes, live bacteria thumb drives , and all kinds of other crazy stuffso far US scientists have had one bright line: no heritable modifications of human beings.

On Wednesday, the bright line got dimmer. MIT Technology Review reported that, for the first time in the US, a scientist had used Crispr on human embryos.

Behind this milestone is reproductive biologist Shoukhrat Mitalipov, the same guy who first cloned embryonic stem cells in humans. And came up with three-parent in-vitro fertilization . And moved his research on replacing defective mitochondria in human eggs to China when the NIH declined to fund his work. Throughout his career, Mitalipov has gleefully played the role of mad scientist, courting controversy all along the way.

Yesterdays news was no different. Editing viable human embryos is, if not exactly a no-no, at least controversial. Mitalipov and his colleagues at Oregon Health and Science University fertilized dozens of donated human eggs with sperm known to carry inherited disease-related mutations, according to the Tech Review report. At the same time, they used Crispr to correct those mutations. The team allowed the embryos to develop for a few days, and according to the original and subsequent reports a battery of tests revealed that the resulting embryos took up the desired genetic changes in the majority of their cells with few errors. Mitalipov declined to comment, saying the results were pending publication next month in a prominent scientific journal.

Big if true, as the saying goes. Mitalipovs group never intended to implant the eggs into a womb, but the embryos were clinical quality and probably could have survived implantation. That makes this only the second time scientists anywhere have edited viable embryosif thats indeed what Mitalipov did. Maybe this news is important enough to make it to the popular press without a peer-reviewed, published paper, but without one its impossible to be definitive on what Mitalipov actually did versus what hes claiming to have done.

Lets say its all real. Is it creepy? Maybe. But its also legalat least in Oregon, where embryo research is kosher as long as it doesnt involve federal funding. Officials at OHSU confirmed that the work took place there, and that it met the universitys Institutional Review Board criteria for safeguarding the rights and welfare of subjects involved in human researchpresumably the donors of the eggs and sperm, in this case. No one on the outside knows which exact genetic tweaks the researchers actually made or how safe the procedure was. Tech Review was light on details.

That lack of transparency could turn into a real problem. These are special cells and they should have special considerations given to them if youre going to Crispr them, says Paul Knoepfler, a stem cell researcher at UC Davis who wrote a book on designer babies called GMO Sapiens . Knoepfler worries that incautious work like this could lead to political backlash against Crispr more broadly, like what happened to stem cell research in the 2000s under George W. Bush. We dont have an unlimited amount of time to talk about these things and figure them out, Knoepfler says. This stuff is moving at warp speed and we need to get our act together on establishing guidelines that are much clearer about what is OK and what isnt.

Not that scientists havent tried. In February the National Academy of Sciences produced a report with its first real guidelines for Crispr research. It did not go so far as to place a moratorium on gene editing of the human germlinemodifications that a persons offspring could inheritthough it did suggest limitations. Scientists are only supposed to edit embryos to prevent a baby from inheriting a serious genetic disease, and only if the doctors meet specific safety and ethical criteria, and if the parents have no other options.

Those obstacles arent insurmountable, and a particularly slippery slope winds between them. At the Aspen Ideas Festival last month, UC Berkeley biologist Jennifer Doudna , one of the people who discovered Crispr, stressed the need for a unified policy on germline editing before scientists really start doing it. Once that begins, I think it will be very hard to stop, she said. Itll be very hard to say, Ill do this thing but not that thing. And at that point, who decides?

In the US, itll probably be the federal government. Congress has already banned federal funding for the human testing of gene-editing techniques that could produce modified babies. That provision is tucked into an appropriations rider that has to be renewed each year, so its an annually moving target. Congress has also barred the US Food and Drug Administration from even considering clinical trials of embryo editing. But even if those laws did change, the FDAs approval process for these kinds of technologies is among the strictest in the world. They would require years and years of animal studies before the first test embryo could conceivably be conceived.

Sarah Zhang

Crispr Is Getting Better. Now It's Time to Ask the Hard Ethical Questions

Nick Stockton

Read This Before You Freak Out Over Gene-Edited Superbabies

Nic Cavell

The UK Just Green-Lit Crispr Gene Editing in Human Embryos

For this to be something other than just a reckless person doing something crazy, were looking at least a decade and maybe more of safety testing, says Hank Greely, a law professor and bioethicist at Stanford. In countries with laxer laws, it could happen soonerlike, say, China , where scientists have reported three attempts at using Crispr to modify human embryos.

The first two studies used genetically defective embryos that could never come to term, but the most recent, published in March, used viable embryos. And while all three studies produced mixed results, Crispr was most successful at repairing faulty genes in the normal embryos. Experiments are also moving forward in Sweden and the UK that use Crispr to knock out different genes in viable embryos to study effects on development.

Still, dont panic . Modifying embryos that are never going to be implanted is not close to the boundary, Greely says. Doing it in embryos you might want to implant is real close to the boundary and shouldnt be done without any discussion. But thats not what Mitalipov did. Maybe. All the institutions apparently involved with the research refused to comment citing an embargo, which would make sense if there were an embargo to break. There wasn't, according to Antonio Regalado, who covers genetics for Tech Review but didn't write this story. Consider it instead just a good new-fashioned leak.

If you think of viable-embryo Crispr research as a journey and not a destination, right now scientists all over the world are on the same path. But at some point the road will fork: Someone will implant an engineered embryo into a human womb. The work coming out of China and Mitalipov's lab has this implied assumption that someday it will wind up being used heritably in humans, Knoepfler says. And I think that requires a unique obligation for being more open about it. Mitalipov's research is not a good start.

See more here:
Scientists Crispr the First Human Embryos in the US (Maybe) - WIRED