Category Archives: Human Genetic Engineering

News that U.S. scientists led by Oregon Health and Sciences University biologist Shoukrat Mitalipov have used the gene-editing technique known as CRISPR to modify the DNA of human embryos has led to renewed debate over human genetic engineering. Although scientists in China and the United Kingdom have already used gene editing on human embryos, the announcement that the research is now being done in the United States makes a U.S. policy response all the more urgent.

The scientists created 131 embryos that carried a genetic mutation that causes hypertrophic cardiomyopathya condition that can lead to sudden and unexpected heart attacks but has few other symptomsand attempted to correct the mutation in 112 of them (leaving 19 as unmodified controls).By injecting the CRISPR complex together with the sperm cells that carried the mutation, rather than injecting CRISPR into already fertilized embryos, the scientists were able to successfully correct the mutated genes in 72 percent of the embryos.Whether the embryos were successfully or unsuccessfully treated, all were destroyed after the researchers were finished with the study.

Much of the debate over CRISPR has been framed around concerns over the creation of so-called designer babieschildren genetically engineered to possess desirable traits that will then be passed on to subsequent generations. Some science writers and journalists have tried to downplay these concerns by noting that the gene editing was done only for basic research, rather than as an attempt to create a genetically engineered human. Writing in The New York Times, Pam Belluck argued that even if scientists do modify the genes of human embryos, fears that embryo modification could allow parents to custom order a baby with Lin-Manuel Mirandas imagination or Usain Bolts speed are closer to science fiction than science.

Those downplaying concerns also argue that preexisting practices such as the abortion of fetuses diagnosed with Down syndrome or the selective discarding of embryos diagnosed with genetic disease through preimplantation genetic diagnosis (PGD) are exactly the reason gene-editing

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CRISPR and the Ethics of Human Embryo Research - Foreign Affairs

The DNA of early human embryos carrying a sequence leading to hypertrophic cardiomyopathya potentially deadly heart defecthas been edited to ensure they would carry a healthy DNA sequence if brought to term. The Nature paper announcing this has reenergized a terrific national and international debate over whether permanent changes in DNA that can be passed from one generation to another should be made. Bioethicists are asking, Should we genetically engineer children? while some potential parents are almost certainly asking, When will this technique be available?

The Should questions bioethicists are asking are probably not relevant. The only question whose answer ultimately matters is: Can techniques like CRISP-R be used to genetically engineer children safely? Because a variety of forces guarantee that if they can be, they will be.

The key questions reliable practitioners must answer are: Can we prove it works? Then: Can it be used safely?. If yes on these questions, then we will see: Who is marketing this technique to potential parents? Finally, we will learn: Where was it done, who did it, and who paid for its use?

We are closer than ever before to using CRISP-R to replace dangerous DNA sequences with those that wont keep a baby from being healthy. Fortunately, this Nature paper leaves many questions Unanswered because the embryos were not allowed to come to term.

Most importantly, we still dont know Could the embryos have developed into viable babies? Just as in 2015 when researchers at Sun Yat-Sen University in China didnt implant engineered embryos into a womans womb, the scientists who published in Nature recently didnt feel ready (and didnt have permission) to try this potentially enormous step. As experiments proceed, this question will, at some point, be answered.

It will be answered because there is an enormous, proven market for techniques that can be used to ensure that a baby will be born without DNA sequences that can lead to genetically-mediated conditions; many of which are devastating as we have been tragically reminded of late.

Under the best circumstances, in-vitro fertilization leads to a live birth less than half of the time. As a result, whoever tries to see if an embryo that has had targeted DNA repaired using CRISP-R will doubtless prepare a lot of embryos for implanting in quite a few women. When those women are asked to carry these embryos to term we will not know about it. We will probably not find out if none of the embryos come to term successfully.

We *will* know about this procedure if even one baby comes to term and is born with the targeted genetic sequence corrected as intended. Until now, (and maybe even with our new knowledge), any baby brought to term after CRISP-R was used to edit and replace unhealthy DNA would have almost certainly had other DNA damaged in the editing process. This near-certainty and other concerns have held people back from trying to genetically engineer an embryo that they would then bring to term. They could not, until recently, have confidence that only the sequence being targeted has been affected. With this new Nature report, this, at least, is changing.

The results of these newly reported experiments are many steps closer to usability than the Chinese experiments reported in 2015. This is the nature of scientific experimentation, particularly when there is demand for the capability or knowledge being developed.

People try something. It either works or it doesnt. Sometimes when it doesnt work, we learn enough to adjust and try again. If it does work, it often doesnt function exactly the way we expected. Either way, people keep trying until either the technique is perfected or it ultimately proves to be unusable.

This Nature paper is an example of trying something and doing a better job than the first attempt. It does not represent a provably safe and reliable technique . Yet. If market driven research works as it often does, people will work hard to publish data (hopefully from reliable experimental work) suggesting they have a safe and effective technique. Doing so will let them tell some desperate set of wealthy prospective parents: We should be able to use this technique with an acceptable chance of giving you a healthy baby.

Princetons Lee Silver predicted parents desire for gene editing in his Remaking Eden, a book published in 1997. He argued this because people fear sickness or disability and feel strong personal, economic and social pressures to have healthy, beautiful children who should become healthy attractive adults.

People already spend a great deal on molecular techniques like pre-implantation genetic diagnosis (PGD). PGD is regularly used to reduce couples risk of having babies with known (or potential), chromosomal abnormalities and/or single gene mutations that can lead to thousands of DNA-mediated conditions.

As I showed in my Genetics dissertation published from Yale in 2004, different countries respond differently to controversial science like this. Similarly, different individuals responses are equally diverse. One poll indicates nearly half of Americans would use gene editing technology to prevent possible DNA-mediated conditions in their children. Policy makers who object to the technology therefore have a problem: if they succeed in blocking it somewhere, research and real world experience indicate other governments may well permit its use. If this happens, these techniques will be available to anyone wealthy and desperate enough to find providers with the marketingand hopefully scientificskill needed to sell people on trying them.

This gene editing controversy is a reminder that we are losing the capacity to effectively ask, Should we? As our knowledge of science grows, becomes more globalized, and is increasingly easy to acquire for people with different morals, needs and wants, we must soon be ready to ask, Can we? and ultimately, Will someone? Their answers will give us the best chance to ensure any babies that may come from any technique described as genetic engineering are born healthy, happy, and able to thrive.

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It's Time to Stop Asking Whether Human Genetic Engineering Should Happen and Start Planning to Manage it Safely - HuffPost

The idea of transplanting organs from pigs into humans has been around for a long time. And for a long time, xenotransplantsor putting organs from one species into anotherhas come up against two seemingly insurmountable problems.

The first problem is fairly intuitive: Pig organs provoke a massive and destructive immune response in humansfar more so than an organ from another person. The second problem is less obvious: Pig genomes are rife with DNA sequences of viruses that can infect human cells. In the 1990s, the pharmaceutical giant Novartis planned to throw as much $1 billion at animal-to-human transplant research, only to shutter its research unit after several years of failed experiments.

Quite suddenly, however, solving these two problems has become much easier and much faster thanks to the gene-editing technology CRISPR. With CRISPR, scientists can knock out the pig genes that trigger the human immune response. And they can inactivate the virusescalled porcine endogenous retroviruses, or PERVsthat lurk in the pig genome.

On Thursday, scientists working for a startup called eGenesis reported the birth of 37 PERV-free baby pigs in China, 15 of them still surviving. The black-and-white piglets are now several months old, and they belong to a breed of miniature pigs that will grow no bigger than 150 poundswith organs just the right size for transplant into adult humans.

eGenesis spun out of the lab of the Harvard geneticist George Church, who previously reported inactivating 62 copies of PERV from pig cells in 2015. But the jump from specialized pig cells that grow well in labs to living PERV-free piglets wasnt easy.

We didnt even know we could have viable pigs, says Luhan Yang, a former graduate student in Churchs lab and co-founder of eGenesis. When her team first tried to edit all 62 copies in pig cells that they wanted to turn into embryos, the cells died. They were more sensitive than the specialized cell lines. Eventually Yang and her team figured out a chemical cocktail that could keep these cells alive through the gene-editing process. This technique could be useful in large-scale gene-editing projects unrelated to xenotransplants, too.

When Yang and her team first inactivated PERV from cells in a lab, my colleague Ed Yong suggested that the work was an example of CRISPRs power rather than a huge breakthrough in pig-to-human transplants, given the challenges of immune compatibility. And true, Yang and Church come at this research as CRISPR pioneers, but not experts in transplantation. At a gathering of organ-transplantation researchers last Friday, Church said that his team had identified about 45 genes to make pig organs more compatible with humans, though he was open to more suggestions. I would bet we are not as sophisticated as we should be because weve only been recently invited [to meetings like this], he said. Its an active area of research for eGenesis, though Yang declined to disclose what the company has accomplished so far.

Its great genetic-engineering work. Its an accomplishment to inactivate that many genes, says Joseph Tector, a xenotransplant researcher at the University of Alabama at Birmingham.

Researchers like Tector, who is also a transplant surgeon, have been chipping away at the problem of immune incompatibility for years, though. CRISPR has sped up that research, too. The first pig gene implicated in the human immune response as one involved in making a molecule called alpha-gal. Making a pig that lacked alpha-gal via older genetic-engineering methods took three years. Now from concept to pig on the ground, its probably six months, says Tector.

Using CRISPR, his team has created a triple-knockout pig that lacks alpha-gal as well as two other genes involved in molecules that that provoke the human immune systems immediate hyperacute rejection of pig organs. For about 30 percent of people, the organs from these triple-knockout pigs should not cause hyperacute rejection. Tector thinks the patients who receive these pig organs could then be treated with the same immunosuppressant drugs that recipients take after an ordinary human-to-human transplant.

Tector and David Cooper, another transplant pioneer, were both recently recruited to the University of Alabama at Birmingham for a xenotransplant program funded by United Therapeutics, a Maryland biotech company that wants to manufacture transplantable organs.

Cooper has transplanted kidneys from pigs engineered by United Therapeutics to have six mutations, which lasted over 200 days in baboons. The result is promising enough that he says human trials could begin soon. These pigs were not created using CRISPR and they are not PERV-free, though recent research has suggested that PERV may not be that harmful to humans. It will be up to the FDA to decide whether pig organs with PERV are safe enough to transplant into people.

If it happens, routine pig-to-human transplants could truly transform healthcare beyond simply increasing the supply. Organs would go from a product of chancesomeone young and healthy dying, unexpectedlyto the product of a standardized manufacturing process. Its going to make such a huge difference that I dont think its possible to conceive of it, says Cooper. Organ transplants would no longer have to be emergency surgeries, requiring planes to deliver organs and surgical teams to scramble at any hour. Organs from pigs can be harvested on a schedule, and surgeries planned for exact times during the day. A patient that comes in with kidney failure could get a kidney the next dayeliminating the need for large dialysis centers. Hospital ICU beds will no longer be taken up by patients waiting for a heart transplant.

With the ability to engineer a donor pig, pig organs can go beyond simply matching a human organ. For example, Cooper says, you could engineer organs to protect themselves from the immune system in the long term, perhaps by making their own localized dose of immunosuppressant drugs.

'Big Pork' Wants to Get In on Organ Transplants

At last Fridays summit, Church speculated about making organs resistant to tumors or viruses. When an audience member asked about the possibility of genetically enhancing pig organs to work as well as Michael Phelpss lungs or Usain Bolts heart, he responded, We not only can but should enhance pig organs, even if were opposed to enhancing human beings ... They will go through safety and efficacy testing, but part of efficacy is making sure theyre robust and maybe they have to be as robust as Michael Phelps in order to do the job.

Xenotransplantation will raise ethical questions, of course, and genetically enhancing pigs might come uncomfortably close to the plot of Okja. These enhancements are hard to fathom for now because scientist dont yet know what genes to alter if they wanted to make, for example, super lungs. Its taken decades of research to pinpoint the handful of genes that could make pig organs simply compatible with humans. But the technical ability to make any editsor even dozens of edits at oncewith CRISPR is already here.

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Genetically Engineering Pigs to Grow Organs for People - The Atlantic

By Rebecca Cokley By Rebecca Cokley August 10

Rebecca Cokley is former executive director of the National Council on Disability. She served in the Obama administration from 2009 to 2017.

Its ironic that news of a breakthrough in human gene editing was released on July 26. That was the 27th anniversary of the Americans with Disabilities Act, the landmark civil rights legislation intended to remedy centuries of discrimination against 57 million disabled Americans. And yet the announcement served as another reminder that there is still much desire to put those rendered undesirable in our place.

Nearly 1 out of every 5 people in this country has a disability. What would it mean for society to render such a large group of people unfit for the human germline? Stories about genetic editing typically focus on progress and remediation, but they often ignore the voice of one key group: the people whose genes would be edited.

Thats my voice. I have achondroplasia, the most common form of dwarfism, which has affected my family for three generations. Im also a woman and a mother the people most likely to be affected by human genetic editing.

I remember clearly when John Wasmuth discovered fibroblast growth factor receptor 3 in 1994. He was searching for the Down syndrome gene and found us. I remember my mothers horrified reaction when she heard the news. And I remember watching other adult little people react in fear while average-height parents cheered it as progress.

How, if you are an average-height parent, do you explain to children whom youve spent years telling are beautiful the way they are, that if you could change them fix them in a minute you would?

People with disabilities have always played pivotal roles in society. People with dwarfism were hired as engineers to work in the engines of 747 jets. Deaf scientists Henrietta Swan Leavitt and Annie Jump Cannon created the field of astrophysics. And Dan Harmon, who has a form of Aspergers, makes us laugh with TV shows such as Community.

I am who I am because I have dwarfism. Dwarfs share a rich culture, as do most disability groups. We have traditions, common language and histories rich in charismatic ancestors. I can honestly say that I may not have been able to work in the White House doing diversity recruitment for President Barack Obama had I not been born a little person. It allowed me to understand discrimination, isolation and societys lowered expectations.

While non-disabled people fear a prenatal diagnosis of disability, disabled people think of the possibilities. How rich would our society be if we all did this? What if that child with osteogenesis imperfecta becomes a world-changing architect because they think differently about how the world is set up due to their disability?

Now think about the message that societys fear of the deviant that boogeyman of imperfection says to disabled people: We dont want you here. Were actively working to make sure that people like you dont exist because we think we know whats best for you. This is ableism. Its denying us our personhood and our right to exist because we dont fit societys ideals.

Proponents of genetic engineering deliberately use vague language, such as prevention of serious diseases, leading many people with disabilities to ask what, in fact, is a serious disease. Where is the line between what society perceives to be a horrible genetic mutation and someones culture?

We cannot look at this breakthrough without looking at the context. In times of economic and political uncertainty as we saw with the austerity measures that swept Europe in the past several years disability is often stigmatized in an attempt to cut costs. We can trace this historically to the growth of the eugenics movement in the 1920s.

Too often the media and society frame people with disabilities as takers, beggars and unworthy cost drivers for the rest of the public. Most recently, The Post published an article on the costs associated with people receiving Social Security Disability payments. These portrayals contribute to the myth of the Medicaid mama, reminiscent of the damaging welfare queen rhetoric of the Reagan era.

Such ableism adds to the notion that people with disabilities do not add to the fabric of society; that as lesser than sciences definition of what is normal, we have nothing to contribute; that our fight for equality is not as valid as other movements because with the right innovation, medicine could fix us.

Let us not forget that disabled Americans led the charge to save the Affordable Care Act for all Americans last month. It remains critical that we drive decisions about the future of disabled people and our health care. Many of us see our disabilities as a rich and diverse culture, many of us want to pass that culture down to our children through our genes, and many of us see no reason not to. We should have that right.

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Please don't edit me out - The Washington Post - Washington Post

Seen any clone armies in your backyard lately? Probably not. This might surprise you if you are old enough to remember the ethical panic that greeted the birth of Dolly the sheep, the first mammal cloned from an adult cell, in Scotland 21 years ago.

The cloned creature set off a crazy overreaction, with fears of clone armies, re-creating the dead, and a host of other horrors, monsters, abuses and terrors none of which has come to pass. That is why it is so important, amid all the moral hand-wringing about what could happen as human genetic engineering emerges, to keep our ethical eye on the right ball. Freaking out over impending superbabies and mutant humans with the powers of comic book characters is not what is needed.

An international team of scientists, led by researchers at the Oregon Health and Science University, has used genetic engineering on human sperm and a pre-embryo. The group is doing basic research to figure out if new forms of genetic engineering might be able to prevent or repair terrible hereditary diseases.

How close are they to making freakish superpeople using their technology? About as close as we are to traveling intergalactically using current rocket technology.

So what should we be worrying about as this rudimentary but promising technique tries to get off the launch pad?

First and foremost, oversight of what is going on. Congress, in its infinite wisdom, has banned federal funding for genetic engineering of sperm, eggs, pre-embryos or embryos. That means everything goes on in the private or philanthropic world here or overseas, without much guidance. We need clear rules with teeth to keep anyone from trying to go too fast or deciding to try to cure anything in an embryo intended to become an actual human being without rock-solid safety data.

Second, we need to determine who should own the techniques for genetic engineering. Important patent fights are underway among the technology's inventors. That means people smell lots of money. And that means it is time to talk about who gets to own what and charge what, lest we reinvent the world of the $250,000 drug in this area of medicine.

Finally, human genetic engineering needs to be monitored closely: all experiments registered, all data reported on a public database and all outcomes good and bad made available to all scientists and anyone else tracking this area of research. Secrecy is the worst enemy that human genetic engineering could possibly have.

Let your great-great-grandkids fret about whether they want to try to make a perfect baby. Today we need to worry about who will own genetic engineering technology, how we can oversee what is being done with it and how safe it needs to be before it is used to try to prevent or fix a disease.

That is plenty to worry about.

Arthur L. Caplan is head of the division of medical ethics at the New York University School of Medicine.

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Don't fear the rise of superbabies. Worry about who will own genetic engineering technology. - Chicago Tribune

Edited human embryos. Image: OHSYU

This week, news of a major scientific breakthrough brought a debate over genetically engineering humans front and center. For the first time ever, scientists genetically engineered a human embryo on American soil in order to remove a disease-causing mutation. It was the fourth time ever that such a feat has been published on, and with the most success to date. It may still be a long way off, but it seems likely that one day we will indeed have to grapple with the sticky, complicated philosophical mess of whether, and in which cases, genetically engineering a human being is morally permissible.

On the heels of this news, on Thursday a group of 11 genetics groups released policy recommendations for whats known as germline editingor altering the human genome in such a way that those changes could be passed down to future generations. The statement, from groups including the American Society for Reproductive Medicine, said that doctors should not yet entertain implanting an altered embryo in a human womb, a step which would be against the law in the United States. But they also argued that there is no reason not to use public money to fund basic research on human germline editing, contrary to a National Institutes of Health policy that has banned funding research involving editing human embryo DNA.

Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing, they wrote. There should be no prohibition on making public funds available to support this research.

Safety, ethical concerns and the impact germline editing might have on societal inequality, they wrote, would all have to be worked out before such technology is ready for the clinic.

Genetic disease, once a universal common denominator, could instead become an artifact of class, geographic location, and culture, they wrote. In turn, reduced incidence and reduced sense of shared risk could affect the resources available to individuals and families dealing with genetic conditions.

If and when embryo editing is ready for primetime, the group concluded that there would need to be a good medical reason to use such technology, as well as a transparent public debate. Some have questioned the medical necessity of embryo editing, arguing that genetic screening combined with in vitro fertilization could allow doctors to simply pick disease-free eggs to implant, achieving the same results via a method that is less morally-fraught.

In February, the National Academy of Sciences released a 261-page report that also gave a cautious green light to human gene-editing, endorsing the practice for purposes of curing disease and for basic research, but determining that uses such as creating designer babies are unethical. Other nations, like China and the UK, have forged ahead with human embryo editing for basic research, though there have been no published accounts of research past the first few days of early embryo development.

Given the way the culture, religion and regional custom impact attitudes toward genetically-engineering human life, its safe to say that this debate will not be an easy one to settle. As the policy recommendations point out, views on the matter vary drastically not just across the US, but around the world, and yet one nation making the decision to go ahead with implanting edited embryos will create a world in which that technology exists for everyone.

In the meantime, though, there are still more than a few kinks to work out in the science before were faced with these questions in the real world.

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Experts Call on US to Start Funding Scientists to Genetically Engineer Human Embryos - Gizmodo