First U.S. Human Embryo Gene Editing Experiment Successfully “Corrects” a Heart Condition


IN BRIEF

A study published today in the journal Nature confirms earlier reports of the first-ever successful gene-editing of embryos in the U.S. Though controversial, the treatment could one day be used to address any of the 10,000 disorders linked to just a single genetic error.

CORRECTING MUTANT GENES

Last week, reports circulated  that doctors had successfully edited a gene in a human embryo — the first time such a thing had been done in the United States. The remarkable achievement confirmed the powerful potential of CRISPR, the world’s most efficient and effective gene-editing tool. Now, details of the research have been published in Nature.

The procedure involved “correcting” the DNA of one-cell embryos using CRISPR to remove the MYBPC3 gene. That gene is known to cause hypertrophic cardiomyopathy (HCM), a heart disease that affects 1 out of 500 people. HCM has no known cure or treatment as its symptoms don’t manifest until the disease causes sudden death through cardiac arrest.

How CRISPR Works: The Future of Genetic Engineering and Designer Humans
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The researchers started with human embryos created from 12 healthy female donors and sperm from a male volunteer who carried the MYBOC3 gene. The defective gene was cut out using CRISPR around the time the sperm was injected into the eggs.

 As a result, as the embryos divided and grew, many repaired themselves using the non-edited genes from the genetic materials of the female donors, and in total, 72 percent of the cells that formed appeared to be corrected. The researchers didn’t notice any “off-target” effects on the DNA, either.

The researchers told The Washington Post that their work was fairly basic. “Really, we didn’t edit anything, neither did we modify anything,” explained Shoukhrat Mitalipov, lead author and a researcher at the Oregon Health and Science University. “Our program is toward correcting mutant genes.”

A [CONTROVERSIAL] NEW ERA?

Basic or not, the development is remarkable.“By using this technique, it’s possible to reduce the burden of this heritable disease on the family and eventually the human population,” Mitalipov said in an OHSU press release.

However, gene editing is a controversial area of study, and the researchers’ work included changes to the germ line, meaning the changes could be passed down to future generations. To be clear, though, the embryos were allowed to grow for only a few days and none were implanted into a womb (nor was that ever the researchers’ intention).

In fact, current legislation in the U.S. prohibits the implantation of edited embryos. The work conducted by these researchers was well within the guidelines set by the National Academies of Sciences, Engineering, and Medicine on the use of CRISPR to edit human genes.

University of Wisconsin-Madison bioethicist Alta Charo thinks that the benefits of this potential treatment outweigh all concerns. “What this represents is a fascinating, important, and rather impressive incremental step toward learning how to edit embryos safely and precisely,” she told The Washington Post. “[N]o matter what anybody says, this is not the dawn of the era of the designer baby.”

Before the technique could be truly beneficial, regulations must be developed that provide clearer guidelines, according to Mitalipov. If not, “this technology will be shifted to unregulated areas, which shouldn’t be happening,” he explained.

More than 10,000 disorders have been linked to just a single genetic error, and as the researchers continue with their work, their next target is BRCA, a gene associated with breast cancer growth.

Mitalipov hopes that their technique could one day be used to treat a wide-range of genetic diseases and save the lives of millions of people. After all, treating a single gene at the embryonic stage is far more efficient that changing a host of them in adults.

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CRISPR, Life Altering Genetic Innovation


The scientific community is in the midst of a gold rush in new technological applications all made possible by the CRISPR/Cas9 system. CRISPR, short for “clustered regularly interspaced palindromic repeats” is quite possibly the biggest innovation in biological science since PCR was developed over three decades ago. This is literally life altering genetic innovation.

CRISPR_technology.png

Scientists have been modifying genomes for years, so what’s the big deal behind this new technology?

In the past, prior to 2010, in order to modify the genome of a mouse, researchers would transfer embryonic stem cells into a mouse embryo containing the genetic mutation of choice. It would then take three generations to see the desired mutation and actually start utilizing the mutation for research purposes. This resulted in large amounts of time and money spent on breeding two unnecessary generations of mice without the guarantee of success. If a researcher wished to modify five genes of interest, this process would be repeated, you guessed it, five more times.

Taking this into account, CRISPR only needs one generation. This system is precise, efficient, and flexible, allowing for multiple mutations to be made all at once. Its efficacy has been proven time and time again in mice, monkeys, and recently in non-viable human embryos by a group of researchers in China, which proves its potential to treat ANY genetic disease.

As applications of this system are developed, many billion-dollar opportunities will arise. With this much money at stake along with world changing potential, rights to the invention are sure to create a heated patent battle at the USPTO, begging the question; who owns the technology anyways?

Professor Jennifer Doudna of UC Berkeley and Emmanuelle Charpentier from Umea University in Sweden filed on March 15, 2013 – one day before the first-to-file rule took effect – and claimed a priority date of May 25, 2012. On the other hand, Feng Zhang of the broad institute of MIT and Harvard in Cambridge, Massachusetts filed on October 15, 2013 under the accelerated examination program. The Broad Institute received patent No. 8,697,359 in April of 2014 claiming priority to a provisional application filed in December 2012.

As the Broad Institute continued to file applications for the technology, Doudna filed a Suggestion of Interference claiming that the Broad Institute Patents interfered with Doudna’s previous application. Pre AIA gives right to who created the invention first, unlike the first-to-file rules of today. An interference procedure is underway with oral arguments set for November 2016.

At stake are the rights to exclusively make, use, license, and sell the invention. The CRISPR/Cas9 system has the ability to completely alter how we treat genetic diseases, and may lead to the actualization of ‘designer babies’ – babies born with their traits hand picked by the parents. The discovery of a lifetime is up for grabs and it will be interesting to see who emerges with rights to the technology. Each party has issued liscences to large biotech companies ready to use the technology in grand-scale implication, however these projects have been delayed, pending the USPTO decision of this patent battle.

CRISPR Is Rapidly Ushering in a New Era in Science


A Battle Is Waged

A battle over CRISPR is raging through the halls of justice. Almost literally. Two of the key players in the development of the CRISPR technology, Jennifer Doudna and Feng Zhang, have turned to the court system to determine which of them should receive patents for the discovery of the technology. The fight went public in January and was amplified by the release of an article in Cell that many argued presented a one-sided version of the history of CRISPR research. Yet, among CRISPR’s most amazing feats is not its history, but how rapidly progress in the field is accelerating.

A CRISPR Explosion

CRISPR, which stands for clustered regularly-interspaced short palindromic repeats, is DNA used in the immune systems of prokaryotes. The system relies on the Cas9 enzyme* and guide RNA’s to find specific, problematic segments of a gene and cut them out. Just three years ago, researchers discovered that this same technique could be applied to humans. As the accuracy, efficiency, and cost-effectiveness of the system became more and more apparent, researchers and pharmaceutical companies jumped on the technique, modifying it, improving it, and testing it on different genetic issues.

Then, in 2015, CRISPR really exploded onto the scene, earning recognition as the top scientific breakthrough of the year by Science Magazine. But not only is the technology not slowing down, it appears to be speeding up. In just two months — from mid-November, 2015 to mid-January, 2016 — ten major CRISPR developments (including the patent war) have grabbed headlines. More importantly, each of these developments could play a crucial role in steering the course of genetics research.

Malaria

CRISPR made big headlines in late November of 2015, when researchers announced they could possibly eliminate malaria using the gene-editing technique to start a gene drive in mosquitos. A gene drive occurs when a preferred version of a gene replaces the unwanted version in every case of reproduction, overriding Mendelian genetics, which say that each two representations of a gene should have an equal chance of being passed on to the next generation. Gene drives had long been a theory, but there was no way to practically apply the theory. Then, along came CRISPR. With this new technology, researchers at UC campuses in Irvine and San Diego were able to create an effective gene drive against malaria in mosquitos in their labs. Because mosquitos are known to transmit malaria, a gene drive in the wild could potentially eradicate the disease very quickly. More research is necessary, though, to ensure effectiveness of the technique and to try to prevent any unanticipated negative effects that could occur if we permanently alter the genes of a species.

Muscular Dystrophy

A few weeks later, just as 2015 was coming to an end, the New York Times reportedthat three different groups of researchers announced they’d successfully used CRISPR in mice to treat Duchenne muscular dystrophy (DMD), which, though rare, is among the most common fatal genetic diseases. With DMD, boys have a gene mutation that prevents the creation of a specific protein necessary to keep muscles from deteriorating. Patients are typically in wheel chairs by the time they’re ten, and they rarely live past their twenties due to heart failure. Scientists have often hoped this disease was one that would be well suited for gene therapy, but locating and removing the problematic DNA has proven difficult. In a new effort, researchers loaded CRISPR onto a harmless virus and either injected it into the mouse fetus or the diseased mice to remove the mutated section of the gene. While the DMD mice didn’t achieve the same levels of muscle mass seen in the control mice, they still showed significant improvement.

Writing for GizmodoGeorge Dvorsky said, “For the first time ever, scientists have used the CRISPR gene-editing tool to successfully treat a genetic muscle disorder in a living adult mammal. It’s a promising medical breakthrough that could soon lead to human therapies.”

Blindness

Only a few days after the DMD story broke, researchers from the Cedars-Sinai Board of Governors Regenerative Medicine Institute announced progress they’d made treating retinitis pigmentosa, an inherited retinal degenerative disease that causes blindness. Using the CRISPR technology on affected rats, the researchers were able to clip the problematic gene, which, according to the abstract in Molecular Therapy, “prevented retinal degeneration and improved visual function.” As Shaomei Wang, one of the scientists involved in the project, explained in the press release, “Our data show that with further development, it may be possible to use this gene-editing technique to treat inherited retinitis pigmentosa in patients.” This is an important step toward using CRISPR  in people, and it follows soon on the heels of news that came out in November from the biotech startup, Editas Medicine, which hopes to use CRISPR in people by 2017 to treat another rare genetic condition, Leber congenital amaurosis, that also causes blindness.

Gene Control

January saw another major development as scientists announced that they’d moved beyond using CRISPR to edit genes and were now using the technique to control genes. In this case, the Cas9 enzyme is essentially dead, such that, rather than clipping the gene, it acts as a transport for other molecules that can manipulate the gene in question. This progress was written up in The Atlantic, which explained: “Now, instead of a precise and versatile set of scissors, which can cut any gene you want, you have a precise and versatile delivery system, which can control any gene you want. You don’t just have an editor. You have a stimulant, a muzzle, a dimmer switch, a tracker.” There are countless benefits this could have, from boosting immunity to improving heart muscles after a heart attack. Or perhaps we could finally cure cancer. What better solution to a cell that’s reproducing uncontrollably than a system that can just turn it off?

CRISPR Control or Researcher Control

But just how much control do we really have over the CRISPR-Cas9 system once it’s been released into a body? Or, for that matter, how much control do we have over scientists who might want to wield this new power to create the ever-terrifying “designer baby”?

The short answer to the first question is: There will always be risks. But not only is CRISPR-Cas9 incredibly accurate, scientists didn’t accept that as good enough, and they’ve been making it even more accurate. In December, researchers at the Broad Institute published the results of their successful attempt to tweak the RNA guides: they had decreased the likelihood of a mismatch between the gene that the RNA was supposed to guide to and the gene that it actually did guide to. Then, a month later, Nature published research out of Duke University, where scientists had tweaked another section of the Cas9 enzyme, making its cuts even more precise. And this is just a start. Researchers recognize that to successfully use CRISPR-Cas9 in people, it will have to be practically perfect every time.

But that raises the second question: Can we trust all scientists to do what’s right? Unfortunately, this question was asked in response to research out of China in April, in which scientists used CRISPR to attempt to genetically modify non-viable human embryos. While the results proved that we still have a long way to go before the technology will be ready for real human testing, the fact that the research was done at all raised red-flags and shackles among genetics researchers and the press. These questions may have popped up back in March and April of 2015, but the official response came at the start of December when geneticists, biologists and doctors from around the world convened in Washington D. C. for the International Summit on Human Gene Editing. Ultimately, though, the results of the summit were vague, essentially encouraging scientists to proceed with caution, but without any outright bans. However, at this stage of research, the benefits of CRISPR likely outweigh the risks.

Big Pharma

“Proceed with caution” might be just the right advice for pharmaceutical companies that have jumped on the CRISPR bandwagon. With so many amazing possibilities to improve human health, it comes as no surprise that companies are betting, er, investing big money into CRISPR. Hundreds of millions of dollars flooded the biomedical start-up industry throughout 2015, with most going to two main players, Editas Medicine and Intellia Therapeutics. Then, in the middle of December, Bayer announced a joint venture with CRISPR Therapeutics to the tune of $300 million. That’s three major pharmaceutical players hoping to win big with a CRISPR gamble. But just how big of a gamble can such an impressive technology be? Well, every company is required to license the patent for a fee, but right now, because of the legal battles surrounding CRISPR, the original patents (which the companies have already licensed) have been put on hold while the courts try to figure out who is really entitled to them. If the patents change ownership, that could be a big game-changer for all of the biotech companies that have invested in CRISPR.

Upcoming Concerns?

On January 14, a British court began reviewing a request by the Frances Crick Institute (FCI) to begin genetically modified research on human embryos. While Britain’s requirements on human embryo testing are more lax than the U.S. — which has a complete ban on genetically modifying any human embryos — the British are still strict, requiring that the embryo be destroyed after the 14th day. The FCI requested a license to begin research on day-old, “spare” IVF embryos to develop a better understanding of why some embryos die at early stages in the womb, in an attempt to decrease the number of miscarriages women have. This germ-line editing research is, of course, now possible because of the recent CRISPR breakthroughs. If this research is successful, The Independent argues, “it could lead to pressure to change the existing law to allow so-called “germ-line” editing of embryos and the birth of GM children.” However, Dr. Kathy Niacin, the lead researcher on the project, insists this will not create a slippery slope to “designer babies.” As she explained to the Independent, ““Because in the UK there are very tight regulations in this area, it would be completely illegal to move in that direction. Our research is in line with what is allowed an in-keeping in the UK since 2009 which is purely for research purposes.”

Woolly Mammoths

Woolly Mammoths! What better way to end an article about how CRISPR can help humanity than with the news that it can also help bring back species that have gone extinct? Ok. Admittedly, the news that George Church wants to resurrect the woolly mammoth has been around since last spring. But the Huffington Post did a feature about his work in December, and it turns out his research has advanced enough now that he predicts the woolly mammoth could return in as little as seven years. Though this won’t be a true woolly mammoth. In fact, it will actually be an Asian elephant boosted by woolly mammoth DNA. Among the goals of the project is to help prevent the extinction of the Asian elephant, and woolly mammoth DNA could help achieve that. The idea is that a hybrid elephant would be able to survive more successfully as the climate changes. If this works, the method could be applied to other plants and animal species to increase stability and decrease extinction rates. As Church tells Huffington Post, “the fact is we’re not bringing back species — [we’re] strengthening existing species.”

And what more could we ask of genetics research than to strengthen a species?

*Cas9 is only one of the enzymes that can work with the CRISPR system, but researchers have found it to be the most accurate and efficient.

CRISPR pioneer muses about long journey from China to pinnacle of American science


That’s because of CRISPR, the gene-editing technique that lets scientists manipulate the genetic code of organisms almost like revising a sentence with a word processor. Zhang was one of its pioneers, and on Wednesday he emerged victorious after a bitter patent dispute.The ruling, by judges with the U.S. Patent Office, declared that Zhang’s work on living plant and animal cells was sufficiently original to deserve its own protection. It was a decisive outcome that will surely prove lucrative for Zhang and the Broad Institute, but he did not do anything special to celebrate. He made no immediate public comment. He did not even read the news coverage, he said.

“The patent stuff is not so interesting, and it can be distracting,” the soft-spoken scientist offered a day later, finally addressing the case as he sat down with a Washington Post reporter for a previously scheduled interview. “Now we can get back to work.”

The patent dispute was closely followed in the triangle of geography marked by the institute, Harvard University and the Massachusetts Institute of Technology. Here, in what has become the Silicon Valley of the life sciences, Zhang and his colleagues have spun off ventures that can commercialize their inventions.

CRISPR is an all-purpose tool that promises great advances in the prevention of diseases caused by genetic mutations. In China, Zhang’s birth country, it is already being used in human clinical trials.

Yet the technique has also raised unsettling possibilities for cosmetic human enhancements and “designer babies.” Earlier this week, the National Academy of Sciences and National Academy of Medicine produced a long report on the ethics of gene editing, arguing for extreme caution when dealing with heritable human traits but leaving open the possibility of use to remove disease-causing genes.

Some critics worry about a slippery slope, but Zhang thinks the bioethics committee got it just right.

“I think these are important issues, but I don’t think right at this second we should be overly concerned about it. It’s too far off,” he said.

The politics of science

Even with the patent case behind him, however, there is another significant distraction these days. It arises not through the courts but from the White House.

Science is inherently an international enterprise, built around a universal language of discovery and methodology. Zhang’s lab, like similar facilities across the country, has a large percentage of foreign-born scientists drawn to research opportunities in the United States.

President Trump’s executive order banning entry from seven Muslim-majority countries has alarmed this global community. The Broad, as it is commonly called, put out a statement of opposition, saying the order “turns its back on one of America’s greatest sources of strength: the flow of visitors, immigrants and refugees who have enriched our nation with their ideas, dreams, drive, energy, and entrepreneurship.”

 Zhang talks of his own life story when asked about Trump’s action.

“From my own experience, America has been an amazing place,” he said. “And it sort of gives opportunities for immigrants to realize what they want to do, to reach for their potential, and also, by doing that, make the world a better place. I’m very fortunate to have had the opportunity to move here.”

He was 11 when he first came to the United States in 1993. He spoke almost no English, arriving with his father to at last rejoin his mother. The teeming city of Shijiazhuang, in the north of China, was replaced by the alien landscape of Des Moines.

His mother had not intended to stay following her studies here, but Iowans embraced her. She got a good job with a company called the Paper Corp. She decided to start a new life and bring her son and husband to the United States. They each received a series of visas and green cards. She eventually became a citizen, as did her son. Her husband remains a Chinese citizen.

“I never felt I was discriminated against. I never felt we weren’t welcome there,” Zhang said of his youth in the heartland. And there were other immigrants, too, many of them Vietnamese refugees from war zones. He spent half the day learning English and then playing word bingo to hone his vocabulary.

He hung out with other kids interested in science. “We were all nerds,” he said. As a teenager, he got a position working after school at the Human Gene Therapy Research Institute. He could call himself a bench scientist, often working late into the evening while his mother waited for him in the parking lot.

Elite institutions soon recognized his brilliance. His résumé includes a degree from Harvard, then a doctorate from Stanford. He learned about the natural bacterial immune system, CRISPR, an acronym for clustered regularly interspaced short palindromic repeats.

Bacteria evolved a defense mechanism against viral invaders that would insert genetic material into bacterial DNA. The system functions like molecular scissors, snipping away the invasive material.

Two other researchers, who would become rivals in the patent case, published the first paper describing the gene-editing technique and applied for patents. Jennifer Doudna and Emmanuelle Charpentier showed how to turn the natural bacterial system into a laboratory tool, but initially they did not apply it to plant and animal cells. That was Zhang’s breakthrough, published in 2013 at the same time as a similar paper by Harvard geneticist George Church.

“Feng was very early in recognizing the importance of reducing it to practice in mammalian cells,” Church said this week.

Doudna and Charpentier can still receive patents on their original discovery. In an email Friday to The Post, Doudna wrote, “Obviously the Broad Institute is happy that their patent didn’t get thrown out, but we are pleased that our patent can now proceed to be issued.”

But she raised another concern. The judges’ decision was based in part on public comments she made, expressing uncertainty about whether CRISPR would work in cells with nuclei. Because of that, she fears the ruling could have a chilling effect on scientific communication.

“Must every scientist now factor in a potential patenting strategy and alter how transparent they are about their work?” Doudna wrote.

Doudna and Charpentier have already received the $3 million Breakthrough Prize funded by Silicon Valley tech tycoons. Then earlier this year they won the Japan Prize, each receiving the equivalent of about $420,000.

And lurking out there somewhere is the Nobel.

‘Why do we age?’

On Thursday, the morning after the ruling, Zhang drove his 2004 BMW to work as always, arriving at 7:30 to meet with a student and help him prepare for a class presentation. Then he had a call with an oil executive in the United Arab Emirates who is funding research on a genetic disease that affects the executive’s daughter.

He still has a spot in his lab for experiments, though he does those during the summer since right now he’s busy teaching two classes. The lab work is in the hands of about 20 researchers, some already with doctorates and medical degrees.

CRISPR gets all the publicity these days, but it is not the only game in town. Life is a complex chemical system that over billions of years has developed all sorts of tricks and mechanisms. Most of the microbes in the human gut have never been cultured or characterized. Basic questions remain unanswered.

“Why do we age?” Zhang asked.

The CRISPR system is itself a work in progress. It’s an inexact editor still.

“It cuts very well,” he said. “To insert something, it doesn’t work very well at all.”

But he’s working on that. Everyone stand by.

Source:www.washingtonpost.com

A new CRISPR breakthrough could lead to simpler, cheaper disease diagnosis


Scientists say SHERLOCK is a ‘game changer’

Scientists say SHERLOCK, a new CRISPR breakthrough and diagnosis tool, could be a game changer for the ability to identify infectious diseases like Zika.

The controversial laboratory tool known as CRISPR may have found a whole new world to conquer. Already the favored method of editing genes, CRISPR could soon become a low-cost diagnostic tool that could be used practically anywhere to determine if someone has an infectious disease such as Zika or dengue.

CRISPR — which stands for Clustered Regularly Interspaced Short Palindromic Repeats — is basically a bacterial immune system that uses “molecular scissors” to snip away genetic material from invasive viruses. Early in this decade, researchers figured out how to exploit the natural system to craft a relatively cheap, remarkably easy-to-use technology for editing genetic codes almost as readily as using a word processor to revise a paragraph.

On Thursday, Feng Zhang, one of the pioneers of CRISPR, and 18 colleagues published a paper in the journal Science showing how they had turned this system into an inexpensive, reliable diagnostic tool for detecting nucleic acids — molecules present in an organism’s genetic code — from disease-causing pathogens. The new tool could be widely applied to detect not only viral and bacterial diseases but also potentially for finding cancer-causing mutations.

CRISPR has been a sensation in the world of molecular biology, but the powerful tool has incited fears that it could be misused. Ethicists earlier this year released a report saying it should be limited in humans to treating diseases or disabilities, and with special caution when genetic changes would involve eggs, sperm or embryos and potentially be inherited by future generations. But CRISPR is already widely used in laboratory studies and has shown great promise in revealing the genetic origins of diseases, including cancer. This new application would propel CRISPR into the much less controversial realm of point-of-care disease diagnosis.

The new study has a whiff of marketing about it: Zhang and his colleagues have named their new tool SHERLOCK — for Specific High Sensitivity Enzymatic Reporter UnLOCKing.

“Nature is really amazing. Over the course of billions of years, it’s come up with all these very powerful enzyme systems, and by studying the basic biology of these systems, some of them will give rise to important applications — like genome editing, like diagnostics,” Zhang, of the Broad Institute of MIT and Harvard, told The Washington Post.

Co-author Jim Collins, also of the Broad Institute, said, “In this diagnostic application we are really harnessing the power and diversity of biology. … I view it as a potentially transformative diagnostic platform.”

They report that their technique is highly portable and could cost as little as 61 cents per test in the field. Such a process would be extremely useful in remote places without reliable electricity or easy access to a modern diagnostic laboratory.

“We showed that this system is very stable, so you can really put it on a piece of paper and it will survive. You don’t have to refrigerate it all the time,” Zhang said.

“My head is spinning a little bit because this looks very, very provocative. And exciting,” said William Schaffner, a professor of infectious diseases and preventive medicine at Vanderbilt University Medical Center, who was not involved in the new research. “If you had something that could be used as a screening test, very inexpensively and rapidly, that would be a huge advance, particularly if it could detect an array of infectious agents.”

Collins said the scientists behind SHERLOCK have filed for patents on the technology, and are discussing ways to move their new tool from the laboratory to the clinical arena.

Zhang is one of the key figures in the CRISPR patent fight between the Broad Institute and the University of California at Berkeley, the latter the homebase of CRISPR pioneer Jennifer Doudna. The patent board ruled in favor of Zhang and Broad earlier this year. Doudna and another researcher had published their CRISPR discoveries first, but Zhang took the technique another step, into cells with nuclei, and the patent board ruled that the second step was sufficiently different that both could be eligible for patent protection. On Thursday, Berkeley and other interested parties filed an appeal of that ruling.

Scott Weaver, an infectious disease researcher at the University of Texas Medical Branch at Galveston, who was not involved in the new research, said after reading the study, “It looks like one significant step on the pathway which is the Holy Grail, which is developing point-of-care, or bedside detection, which doesn’t require expensive equipment or even reliable power.”

Harvard geneticist George Church is one of the lead researchers propelling CRISPR, a breakthrough gene-editing technique, into the future.
CRISPR is capable of preventing congenital disease.
Source:www.washingtonpost.com

Kazuo Ishiguro: Soon, We Will Be Able to Create Humans Who Are Superior to Other Humans


IN BRIEF
  • Author Kazuo Ishiguro believes we are unwittingly walking into a dystopian future because the world has yet to give science and technology more than just peripheral interest.
  • He believes that we have yet to engage in meaningful conversations about where scientific advancements will take us, and the kind of impact they will have on our lives.

DYSTOPIAN FUTURE

According to Kazuo Ishiguro, there are three areas of science that are set to transform how we live and interact with others over the next few decades: gene editing, robotics, and artificial intelligence (AI).

Ishiguro, granted, is best known as one of the most celebrated fiction writers today. He is behind the novel Never Let Me Go, the story of a dystopian future where humans are cloned to be organ donors. But the possibility of a future so fundamentally changed by scientific advancements could be more than the fruit of the author’s creativity and imagination.

Ishiguro

He cites CRISPR as a primary example. The discovery of this gene editing tool gives scientists the option to modify pieces of the genome, paving the way for unprecedented applications in medicine. Right now, we can replace faulty genes with working ones, which is a great accomplishment unto itself. But moving forward, as we learn more about this new technology, the option to enhance functional genes to create intellectually and physically superior humans becomes a real possibility.

Think of it as like a real world Gattaca, where society is divided into two classes. Half will be populated with humans with genetically engineered genes that makes them healthier, smarter, stronger—designer babies, essentially. And the other half, with humans whose genetic sequence has been left to chance, untouched, leaving them biologically inferior.

A NEW FOCUS ON SCIENCE

Ishiguro believes we are unwittingly walking into this dystopian future because the world has yet to give science and technology more than just peripheral interest. Sure, we celebrate the headlines and acknowledge the accomplishments, but we have yet to engage in meaningful conversations about where these advancements will take us, and the kind of impact they will have on our lives.

Developments in AI and robotics for instance, mean a major part of intellectual capital will shift to what he refers to as “the Silicon Valley masters of the universe”—it will no longer be under universities or government funded labs. The lack of regulation regarding these rapid developments is also cause for concern. And of course, there is the ongoing debate about the ethics behind advancements in genetic sciences, like CRISPR.

The relevance of Ishiguro’s musings about the future comes in time for the opening of a new permanent mathematics gallery at the Science Museum in London. Included in the exhibit is the author’s father, oceanographer Shizuo Ishiguro, who created a machine that can predict coastal storm surges.

The author however, hopes that exhibits such as this will prompt more discussion about the trajectory of science and spur deeper interest. These breakthroughs have real implications that deserve to be discussed.

Source:futurism.com

CRISPR pioneer Jennifer Doudna shines hope on the future of genetic modification at SXSW.


Jennifer Doudna, co-inventor of CRISPR Cas9 technology, or the ability to program genes using a special enzyme, spoke about the promises of this technology onstage at SXSW this afternoon. In a keynote today, Doudna noted that while this technology is very young (less than five years old), “it’s been deployed very rapidly for existing applications.”

For example, CRISPR Cas9 tech has important applications for treating diseases. One of the first applications we’ll see entering clinical trials, Doudna said, is using Cas9 gene editing tech to correct the mutation that causes sickle cell disease.

Another example is using the tech to create gene drives, which entails driving a trait through a population very quickly. Doudna said it’s already being deployed in the lab setting to make changes to insects that carry diseases, such as mosquitoes that carry certain pathogens.

“In the future, we could create mosquitoes impervious to infections and therefore prevent spreading diseases,” Doudna said.

Then, of course, there’s the use of gene editing in human embryos, which has attracted a lot of attention in the last few years. For example, the tech could be used to make changes to the immune systems of people with cancer, and make them more capable of fighting the disease.

The University of California Berkeley professor and founder of biotech startup Caribou Bioscience was until recently embroiled in a hotly contested two-year patent battle with the Broad Institute of MIT and Harvard over key portions of the technology, namely the ability to edit living cells.

 The Broad Institute won in that case last month, but, as Doudna pointed out to TechCrunch shortly after the decision went public, it still allows her team and the company she founded to work with the technology in a variety of ways.

CRISPR is a technology potentially worth hundreds of billions, if not trillions, as it could change entire industries. While the Broad Institute won the rights to its patent under a “no interference” ruling, UC Berkeley must still obtain the more basic CRISPR patent. Should that happen, companies interested in using the technology would likely have to pay both institutions for the rights.

During her keynote, Doudna noted how the development of this technology has been a very collaborative effort between professors, academic institutions, regulators, students, etc.

What ultimately creates the most stress for her is the fear that people will get out ahead of the tech, “getting so excited they start to deploy it before it’s even ready,” Doudna said. “I worry most about that kind of overextension that might lead to some sort of harmful effect that would then turn the public against it.”

Cystic fibrosis, sickle-cell anemia could be corrected in embryos with new CRISPR variant.


Since the discovery of the genome-editing tool CRISPR/Cas9, scientists have been looking to utilize the technology to make a significant impact on correcting genetic diseases. Technical challenges have made it difficult to use this method to correct disorders that are caused by single-nucleotide mutations, such as cystic fibrosis, sickle-cell anemia, Huntington’s disease, and phenylketonuria. … [Researchers] have just used a variation of CRISPR/Cas9 to produce mice with single-nucleotide differences. The findings from this new study were published recently in Nature Biotechnology in an article entitled “Highly Efficient RNA-Guided Base Editing in Mouse Embryos.

The most frequently used CRISPR/Cas9 technique works by cutting around the faulty nucleotide in both strands of the DNA and cuts out a small part of DNA. In the current study, the investigators used a variation of the Cas9 protein (nickase Cas9, or nCas9) fused with an enzyme called cytidine deaminase, which can substitute one nucleotide into another—generating single-nucleotide substitutions without DNA deletions

“The next goal is to correct a genetic defect in animals. Ultimately, this technique may allow gene correction in human embryos,” [remarked senior study investigator Jin-Soo Kim].

The First Results of Gene Editing in Normal Embryos Have Been Released


Viable Editing

One of the most fascinating and promising developments in genetics is the CRISPR genome editing technique. Basically, CRISPR is a mechanism by which geneticists can treat disease by either disrupting genetic code by splicing in a mutation or repairing genes by splicing out mutations and replacing them with healthy code.

Researchers in China at the Third Affiliated Hospital of Guangzhou Medical University have successfully edited genetic mutations in viable human embryos for the first time. Typically, to avoid ethical concerns, researchers opt to use non-viable embryos that could not possibly develop into a child.

*5* Researchers Release Successful Results of First Genetic Edit of Viable Embryos

Previous research using these non-viable embryos has not produced promising results. The very first attempt to repair genes in any human embryos used these abnormal embryos. The study ended with abysmal results, with fewer than ten percent of cells being repaired. Another study published last year also had a low rate of success, showing that the technique still has a long way to go before becoming a reliable medical tool.

However, after experiencing similar results with using the abnormal embryos again, the scientists decided to see if they would fare better with viable embryos. The team collected immature eggs from donors undergoing IVF treatment. Under normal circumstances, these cells would be discarded, as they are less likely to successfully develop. The eggs were matured and fertilized with sperm from men carrying hereditary diseases.

Disease Sniper

While the results of this round of study were not perfect, they were much more promising than the previous studies done with the non-viable embryos. The team used six embryos, three of which had the mutation that causes favism (a disease leading to red blood cell breakdown in response to certain stimuli), and the other three had the mutation that results in a blood disease called beta-thalassemia.

The researchers were able to correct two of the favism embryos. In the other, the mutation was turned off, as not all of the cells were corrected. This means that the mutation was effectively shut down, but not eliminated. It created what is called a mosaic. In the other set, the mutation was fully corrected in one of the embryos and only some cells were corrected in the other two.

These results are not perfect, but experts still do find potential in them. “It does look more promising than previous papers,” says Fredrik Lanner of the Karolinska Institute. However, they do understand that results from a test of only six embryos are far from definitive.

Gene editing with CRISPR truly has the possibility to revolutionize medicine. Just looking at the development in terms of disease treatment, and not the other more ethically murky possible applications, it is an extremely exciting achievement.

Not only could CRISPR help eradicate hereditary disease, but it is also a tool that could help fight against diseases like malaria. There is a long road ahead for both the scientific and ethical aspects of the tech. Still, the possible benefits are too great to give up now.

A CRISPR first: editing normal human embryos.


In the first ever report of the CRISPR-Cas9 genome-editing tool being used on normal human embryos, a team of Chinese scientists had mixed results, New Scientist writes. The team first created embryos with genetic mutations that caused two different diseases: β-thalassemia and favism (an anemia caused by eating fava beans). When they tried correcting the mutations using CRISPR-Cas9, their success rate was one in four for β-thalassemia and two in two for favism, they report this month in Molecular Genetics and Genomics. That’s better than the 10% success rate for genetically abnormal embryos, but far more work needs to be done before the technique is ready for prime time, say other scientists.

CRISPR debate fueled by publication of second human embryo–editing paper