Theres still a way to go from editing single-cell embryos to a full-term designer baby. Credit: ZEISS Microscopy, CC BY-SA

The announcement by researchers in Portland, Oregon that they've successfully modified the genetic material of a human embryo took some people by surprise.

With headlines referring to "groundbreaking" research and "designer babies," you might wonder what the scientists actually accomplished. This was a big step forward, but hardly unexpected. As this kind of work proceeds, it continues to raise questions about ethical issues and how we should we react.

What did researchers actually do?

For a number of years now we have had the ability to alter genetic material in a cell, using a technique called CRISPR.

The DNA that makes up our genome comprises long sequences of base pairs, each base indicated by one of four letters. These letters form a genetic alphabet, and the "words" or "sentences" created from a particular order of letters are the genes that determine our characteristics.

Sometimes words can be "misspelled" or sentences slightly garbled, resulting in a disease or disorder. Genetic engineering is designed to correct those mistakes. CRISPR is a tool that enables scientists to target a specific area of a gene, working like the search-and-replace function in Microsoft Word, to remove a section and insert the "correct" sequence.

In the last decade, CRISPR has been the primary tool for those seeking to modify genes human and otherwise. Among other things, it has been used in experiments to make mosquitoes resistant to malaria, genetically modify plants to be resistant to disease, explore the possibility of engineered pets and livestock, and potentially treat some human diseases (including HIV, hemophilia and leukemia).

Up until recently, the focus in humans has been on changing the cells of a single individual, and not changing eggs, sperm and early embryos what are called the "germline" cells that pass traits along to offspring. The theory is that focusing on non-germline cells would limit any unexpected long-term impact of genetic changes on descendants. At the same time, this limitation means that we would have to use the technique in every generation, which affects its potential therapeutic benefit.

Earlier this year, an international committee convened by the National Academy of Sciences issued a report that, while highlighting the concerns with human germline genetic engineering, laid out a series of safeguards and recommended oversight. The report was widely regarded as opening the door to embryo-editing research.

That is exactly what happened in Oregon. Although this is the first study reported in the United States, similar research has been conducted in China. This new study, however, apparently avoided previous errors we've seen with CRISPR such as changes in other, untargeted parts of the genome, or the desired change not occurring in all cells. Both of these problems had made scientists wary of using CRISPR to make changes in embryos that might eventually be used in a human pregnancy. Evidence of more successful (and thus safer) CRISPR use may lead to additional studies involving human embryos.

What didn't happen in Oregon?

First, this study did not entail the creation of "designer babies," despite some news headlines. The research involved only early stage embryos, outside the womb, none of which was allowed to develop beyond a few days.

In fact, there are a number of existing limits both policy-based and scientific that will create barriers to implanting an edited embryo to achieve the birth of a child. There is a federal ban on funding gene editing research in embryos; in some states, there are also total bans on embryo research, regardless of how funded. In addition, the implantation of an edited human embryos would be regulated under the federal human research regulations, the Food, Drug and Cosmetic Act and potentially the federal rules regarding clinical laboratory testing.

Beyond the regulatory barriers, we are a long way from having the scientific knowledge necessary to design our children. While the Oregon experiment focused on a single gene correction to inherited diseases, there are few human traits that are controlled by one gene. Anything that involves multiple genes or a gene/environment interaction will be less amenable to this type of engineering. Most characteristics we might be interested in designing such as intelligence, personality, athletic or artistic or musical ability are much more complex.

Second, while this is a significant step forward in the science regarding the use of the CRISPR technique, it is only one step. There is a long way to go between this and a cure for various disease and disorders. This is not to say that there aren't concerns. But we have some time to consider the issues before the use of the technique becomes a mainstream medical practice.

So what should we be concerned about?

Taking into account the cautions above, we do need to decide when and how we should use this technique.

Should there be limits on the types of things you can edit in an embryo? If so, what should they entail? These questions also involve deciding who gets to set the limits and control access to the technology.

We may also be concerned about who gets to control the subsequent research using this technology. Should there be state or federal oversight? Keep in mind that we cannot control what happens in other countries. Even in this country it can be difficult to craft guidelines that restrict only the research someone finds objectionable, while allowing other important research to continue. Additionally, the use of assisted reproductive technologies (IVF, for example) is largely unregulated in the U.S., and the decision to put in place restrictions will certainly raise objections from both potential parents and IVF providers.

Moreover, there are important questions about cost and access. Right now most assisted reproductive technologies are available only to higher-income individuals. A handful of states mandate infertility treatment coverage, but it is very limited. How should we regulate access to embryo editing for serious diseases? We are in the midst of a widespread debate about health care, access and cost. If it becomes established and safe, should this technique be part of a basic package of health care services when used to help create a child who does not suffer from a specific genetic problem? What about editing for nonhealth issues or less serious problems are there fairness concerns if only people with sufficient wealth can access?

So far the promise of genetic engineering for disease eradication has not lived up to its hype. Nor have many other milestones, like the 1996 cloning of Dolly the sheep, resulted in the feared apocalypse. The announcement of the Oregon study is only the next step in a long line of research. Nonetheless, it is sure to bring many of the issues about embryos, stem cell research, genetic engineering and reproductive technologies back into the spotlight. Now is the time to figure out how we want to see this gene-editing path unfold.

Explore further: In US first, scientists edit genes of human embryos (Update)

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Editing human embryos with CRISPR is moving ahead now's the ... - Phys.Org

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A team of researchers has created the first genetically modified human embryos, the MIT Technology Review reported this week.

If the achievement is true - the scientists in question have neither confirmed nor disputed the account - it could mark a milestone in preventing transmission of genetic diseases instead of just treating them.

It would also rev up debate about the safety and ethics of genetically changing human beings, including what laws exist to safeguard patients and what constitutes a medically legitimate genetic modification.

The technology could be used to alter people for nonmedical purposes such as making them taller, giving them a specific eye shape or switching out their black hair for a shade of blonde - decisions that could be seen as fundamentally upending the definition of human nature.

The Technology Review story said the scientists harnessed the gene-editing method called CRISPR, a milestone in its own right, to modify one-celled embryos and allow them to develop for a few days. Other news organizations have published their own articles about this purported accomplishment, including the well-respected biomedical website Stat.

Prominent biologist Shoukhrat Mitalipov of Oregon Health & Science University was the lead researcher on the study, according to the Technology Review and Stat stories. Both reports said he declined to comment.

"Results of the peer-reviewed study are expected to be published soon in a scientific journal," Oregon Health & Science spokesman Erik Robinson said Thursday. He declined to specify what the study discovered.

The Technology Review story also said Jun Wu of the Salk Institute for Biological Studies in La Jolla, Calif., took part in the research. On Thursday, the institute declined to discuss the study.

Mitalipov gained fame in 2013 for spearheading development of the first human embryonic stem cells genetically matched to specific living individuals. The method he and some colleagues employed, called somatic cell nuclear transfer, was originally used two decades ago to create Dolly the cloned sheep.

Those researchers had taken a nucleus from a donor cell in a sheep and transferred it into a sheep egg cell that had had its own nucleus removed. The combination cell acted like a normal fertilized egg, producing Dolly. That sheep had the DNA of the donor cell, so it was a nearly exact clone of the sheep where the donor cell was taken from.

Growing a creature in this way is called reproductive cloning, and the U.S. government bans such procedures on people. Mitalipov and colleagues performed what is called therapeutic cloning: They used the process to cultivate human embryonic stem cells, which are likewise genetically matched to the donor nucleus.

In theory, these stem cells could be grown into replacement tissues to repair disease or injury in the person with the matching DNA. Genetically matching the stem cells to a particular patient lowers the risk that tissue transplants would be rejected by the person's immune system.

Wu and other Salk researchers in the lab of Juan Carlos Izpisua Belmonte have collaborated with Mitalipov to explore somatic cell nuclear transfer as a therapy for mitochondrial diseases. Mitochondria are organelles that make most of the energy cells use and perform other vital functions. They carry their own DNA.

The scientists generated human stem cells in the lab, repaired mitochondrial defects and found that they were able to restore certain desired functions in cells.

They took human skin cells and inserted their nuclei into human egg cells with healthy mitochondria that had their own nuclei removed. Those manipulated egg cells were then grown until they produced embryonic stem cells, free of the defective mitochondria.

The United Kingdom has approved a method that resembles reproductive cloning to prevent inheritance of mitochondrial diseases. This process involves replacing the nucleus of an egg cell from a donor with healthy mitochondria with that from the egg cell of the mother-to-be with diseased mitochondria.

Whether the reports this week about genetically modified human embryos are true, the capability of genetically engineering human embryos is fast approaching, said a bioethicist and a stem cell researcher who have examined the issue.

But having the capability doesn't mean it should be done, said Michael Kalichman, co-founding director of the the Center for Ethics in Science and Technology at the University of California, San Diego.

Kalichman said society isn't ready for genetically modifying humans, and that it's time for the public to start paying attention to what has been considered a futuristic scientific issue.

The strongest argument for genetic modification is to stop diseases, he said. The strongest argument against the technology is that it might cause unanticipated problems.

Paul Knoepfler, a stem cell researcher at UC Davis, said no matter how much effort is spent to ensure patient safety, there are no guarantees.

"The bottom line is that we'll never really know until someone tries it," Knoepfler said. Potential harm might not emerge until adulthood or even until the genetically altered people have their own children, he added.

"The other big thing is, I am not really convinced we can draw a clear line between doing this for only medical purposes versus (cosmetic) traits," he said.

Finally, it's not clear why genetically editing human embryos would even be needed to prevent transmission of a genetic disease, Knoepfler said.

"We already have an existing technology which is basically embryo screening," he said. Multiple embryos can be generated through in vitro fertilization to find one that doesn't have the disease.

"That would be much safer than actually doing an edit," he said.

Explore further: New research provides key insight about mitochondrial replacement therapy

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Scientists genetically modify human embryos for first time, reports say - Medical Xpress

WASHINGTON (AP) Altering human heredity? In a first, researchers safely repaired a disease-causing gene in human embryos, targeting a heart defect best known for killing young athletes a big step toward one day preventing a list of inherited diseases.

In a surprising discovery, a research team led by Oregon Health and & Science University reported Wednesday that embryos can help fix themselves if scientists jump-start the process early enough.

It's laboratory research only, nowhere near ready to be tried in a pregnancy. But it suggests that scientists might alter DNA in a way that protects not just one baby from a disease that runs in the family, but his or her offspring as well. And that raises ethical questions.

"I for one believe, and this paper supports the view, that ultimately gene editing of human embryos can be made safe. Then the question truly becomes, if we can do it, should we do it?" said Dr. George Daley, a stem cell scientist and dean of Harvard Medical School. He wasn't involved in the new research and praised it as "quite remarkable."

"This is definitely a leap forward," agreed developmental geneticist Robin Lovell-Badge of Britain's Francis Crick Institute.

Today, couples seeking to avoid passing on a bad gene sometimes have embryos created in fertility clinics so they can discard those that inherit the disease and attempt pregnancy only with healthy ones, if there are any.

Gene editing in theory could rescue diseased embryos. But so-called "germline" changes altering sperm, eggs or embryos are controversial because they would be permanent, passed down to future generations. Critics worry about attempts at "designer babies" instead of just preventing disease, and a few previous attempts at learning to edit embryos, in China, didn't work well and, more importantly, raised safety concerns.

In a series of laboratory experiments reported in the journal Nature, the Oregon researchers tried a different approach.

They targeted a gene mutation that causes a heart-weakening disease, hypertrophic cardiomyopathy, that affects about 1 in 500 people. Inheriting just one copy of the bad gene can cause it.

The team programmed a gene-editing tool, named CRISPR-Cas9, that acts like a pair of molecular scissors to find that mutation a missing piece of genetic material.

Then came the test. Researchers injected sperm from a patient with the heart condition along with those molecular scissors into healthy donated eggs at the same time. The scissors cut the defective DNA in the sperm.

Normally cells will repair a CRISPR-induced cut in DNA by essentially gluing the ends back together. Or scientists can try delivering the missing DNA in a repair package, like a computer's cut-and-paste program.

Instead, the newly forming embryos made their own perfect fix without that outside help, reported Oregon Health & Science University senior researcher Shoukhrat Mitalipov.

We all inherit two copies of each gene, one from dad and one from mom and those embryos just copied the healthy one from the donated egg.

"The embryos are really looking for the blueprint," Mitalipov, who directs OHSU's Center for Embryonic Cell and Gene Therapy, said in an interview. "We're finding embryos will repair themselves if you have another healthy copy."

It worked 72 percent of the time, in 42 out of 58 embryos. Normally a sick parent has a 50-50 chance of passing on the mutation.

Previous embryo-editing attempts in China found not every cell was repaired, a safety concern called mosaicism. Beginning the process before fertilization avoided that problem: Until now, "everybody was injecting too late," Mitalipov said.

Nor did intense testing uncover any "off-target" errors, cuts to DNA in the wrong places, reported the team, which also included researchers from the Salk Institute for Biological Studies in California and South Korea's Institute for Basic Science. The embryos weren't allowed to develop beyond eight cells, a standard for laboratory research. The experiments were privately funded; U.S. tax dollars aren't allowed for embryo research.

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Genetics and ethics experts not involved in the work say it's a critical first step but just one step toward eventually testing the process in pregnancy, something currently prohibited by U.S. policy.

"This is very elegant lab work," but it's moving so fast that society needs to catch up and debate how far it should go, said Johns Hopkins University bioethicist Jeffrey Kahn.

And lots more research is needed to tell if it's really safe, added Britain's Lovell-Badge. He and Kahn were part of a National Academy of Sciences report earlier this year that said if germline editing ever were allowed, it should be only for serious diseases with no good alternatives and done with strict oversight.

"What we do not want is for rogue clinicians to start offering treatments" that are unproven, as has happened with some other experimental technologies, he stressed.

Among key questions: Would the technique work if mom, not dad, harbored the mutation? Is repair even possible if both parents pass on a bad gene?

Mitalipov is "pushing a frontier," but it's responsible basic research that's critical for understanding embryos and disease inheritance, noted University of Pittsburgh professor Kyle Orwig.

In fact, Mitalipov said the research should offer critics some reassurance: If embryos prefer self-repair, it would be extremely hard to add traits for "designer babies" rather than just eliminate disease.

"All we did is un-modify the already mutated gene."

This Associated Press series was produced in partnership with the Howard Hughes Medical Institute's Department of Science Education. The AP is solely responsible for all content.

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First safe repair of disease-causing gene in human embryos - Virginian-Pilot