StemCell Therapy

Scientists have successfully edited the DNA of human embryos to erase a heritable heart condition that isknown for causingsudden death in young competitive athletes, cracking openthe doors toa controversial new era in medicine.

This is the first time gene editing on human embryos has been conducted in theUnited States. Researcherssaid in interviews this weekthat theyconsider their work very basic. The embryos were allowed to grow for only a few days, and there was never any intention to implant them to create a pregnancy. But they also acknowledged that they will continue to move forward with the science, with theultimate goal of being able to correct disease-causing genes in embryos that will develop into babies.

News of the remarkable experiment began to circulate last week, but details became public Wednesday with a paper in the journal Nature.

The experiment is the latest example of how the laboratory tool known as CRISPR (orClustered Regularly Interspaced Short Palindromic Repeats), a type of molecular scissors, is pushing the boundaries of our ability to manipulate life, and it has been receivedwith both excitement and horror.

The most recent work is particularly sensitive because it involves changes to the germ line that is, genes that could be passed on to future generations. The United States forbids the use of federal funds for embryo research, and theFood and Drug Administration is prohibited from considering any clinical trials involving genetic modifications that can be inherited. A report from the National Academies of Sciences, Engineering and Medicine in February urged caution in applying CRISPR to human germ-line editingbut laid out conditions by whichresearch should continue. The new study abides by those recommendations.

This animation depicts the CRISPR-Cas9 method for genome editing a powerful new technology with many applications in biomedical research, including the potential to treat human genetic disease or provide cosmetic enhancements. (Feng Zhang/McGovern Institute for Brain Research/MIT)

Shoukhrat Mitalipov, one of the lead authors of the paper and a researcher at Oregon Health & Science University, said that he is conscious ofthe need for a larger ethical and legal discussion about genetic modification of humans but that his team's work isjustified because it involves correcting genes rather than changing them.

Really we didnt edit anything. Neither did we modify anything, Mitalipov said. Our program is toward correcting mutant genes.

Alta Charo, a bioethicist at the University of Wisconsin at Madison who is co-chair of the National Academies committee that looked at gene editing,said that concerns about the work that have been circulating in recent days are overblown.

What this represents is a fascinating, important and rather impressive incremental step toward learning how to edit embryos safely and precisely, she said. However, no matter what anybody says, this is not the dawn of the era of the designer baby. She said that characteristics that some parents might desire, such as intelligence and athleticism, are influenced by multiple genes and that researchers don't understand all the components of how such characteristics areinherited, much less have the ability to redesign them.

The research involved eggs from 12 healthy female donors and sperm from a male volunteer who carries the MYBPC3 gene, which causes hypertrophic cardiomyopathy. HCM is a disease that causes an abnormal thickening of the heart muscle butcan cause no symptoms and remain undetected until it causes sudden cardiac death. There's no way to prevent or cure it, and it affects1 in 500 people worldwide.

Around the time the sperm was injected into the eggs, researchers snipped out the gene that causes the disease. The result was far more successful than the researchers expected: As the embryo's cells began to divide and multiply, a huge number appearedto be repairing themselves by using the normal, non-mutated copy of the gene from the women'sgenetic material. In all, they saw that about 72 percent were corrected, a very high number. Researchers also noticed that theredidn't seem to be any off-target changes in the DNA, which has been a major safety concern ofgene-editing research.

Mitalipov said he hoped the technique could one day be applied to a wide variety of genetic diseases and that one of the team'snext targets may be the BRCA gene mutation, which is associated with breast cancer.

The first published work involving human embryos, reported in 2015, was done in Chinaand targeted a gene that leads to theblood disorder beta thalassemia. But those embryos were abnormal and nonviable, and there were far fewer than the number used in the U.S. study.

Juan Carlos Izpisua Belmonte, a researcher at the Salk Institute who is also a co-author on the new study, saidthat there are many advantages to treating an embryo rather than a child or an adult. When dealing with an embryo in its earliest stages, only a few cells are involved, while in a more mature human being there aretrillions of cells in the body and potentially millions that must be corrected to eradicate traces of a disease.

Izpisua Belmonte said that even if the technology is perfected, it could deal with only a small subset of human diseases.

Idont want to be negative with our own discoveries, but it is important to inform the public of what this means, he said. In my opinion the percentage of people that would benefit from this at the current way the world is rather small. For the process to make a difference, the child would have to be born through in vitro fertilization or IVF and the parentswould have to know the child has the gene for a disease to get it changed. But the vast majority ofchildren are conceived the natural way, and this correction technology would not work in utero.

For years, some policymakers, historians and scientists have been calling for a voluntary moratorium on the modification of the DNA of human reproductive cells. The most prominent expression of concern came in the form of a 2015 letter signed by CRISPR co-inventor Jennifer Doudna, Nobel Laureate David Baltimore and 16 other prominent scientists. They warned that eliminating a genetic disease could have unintended consequences on human genetics, society and even the environment far into the future.

On Wednesday,Marcy Darnovsky, executive director of the Center for Genetics and Society, warned that the O.H.S.U. research would result in fertility clinics offering genetic upgrades to those able to afford them.

Once those commercial dynamics kick in, we could all too easily find ourselves in a world where some peoples children are considered biologically superior to the rest of us, she said in a statement. We need to ask ourselves whether we want to add that new kind of excuse for extreme social disparities to the ones we already tolerate.

Researchers who worked on the heart-condition experiment appear to have differing views on where their work is headed.

Paula Amato, a reproductiveendocrinologist with O.H.S.U., was excited about the idea of being able to editout diseases before birth. She said that while pre-implantation genetic screening of embryos is now available, it isn't perfect.She talked about how one of her patients went through three cycles of in vitro fertilizationbut all theeggs that were harvested hadthegene mutation that causes diseases.

With gene correction technology, Amatosaid, we could have rescued some of those embryos.

ButIzpisua Belmonte said he is focusing on using thefindings from this study to further research into gene modifications during a pregnancy or after birth into adulthood.

Ifeel that the practical thing to do is deal with the diseases people have, not with the disease they may have, he said.

Mitalipov said he hopes regulators will provide more guidance on what should or should not be allowed.

Otherwise, he said, this technology will be shifted to unregulated areas, which shouldnt be happening.

This story has been updated.

Read more:

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

Scientists debate the ethics of CRISPR

Ethicists urge caution in applying CRISPR to humans

Jennifer Doudna ponders 'what it means to be human' on the frontier of gene editing

More:
First human embryo editing experiment in US 'corrects' gene for heart condition - Washington Post

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