Embryo Editing to Cure Genetic Disease Has Advanced Considerably in 2017

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Soon, it will be possible to take an embryo that you created with your partner, screen all of its genes for errors that can cause disease, then edit out all of the disease-causing errors in every one of the embryo’s cells. Then, you could have the embryo injected into your uterus, knowing that it is free of any life-threatening genetic disease, but would you do it? Most people might be inclined to say yes. You want to have a healthy child, after all, and the prospect of using technology to correct genetic factors that cause suffering now beckons.

It beckons because of an editing system called CRISPR-Cas9 (CRISPR for short, pronounced KRISPER), a kind of immune system for microorganisms that scientists have hacked for biotechnology applications. Today, CRISPR tools allow line-item editing of genetic sequences in any organism, humans included. In contrast with other gene editing systems that scientists have used for a longer time, CRISPR-Cas9 is cheap and easy to use. It’s also programmable; the same system can be utilized to edit completely different genetic sequences by swopping strands of a molecule called RNA, with as much ease as you swap files of your favorite songs on an audio app. Think of it like a word processing program on your computer, except that the words are genes.

Sounds great, yet in 2015, scientists in China tried using CRISPR technology to cure beta thalassemia –a genetic blood disease that is common especially in people of Mediterranean origin– and they received a lot of flak. That was partly, because their experiments didn’t work so well, but also because CRISPR was very new. People were worried about a slippery slope where editing out diseases could lead to “designer babies”.

But this year, just a few months ago, scientists at Oregon Health Sciences University (OHSU) in Portland pulled off a similar feat as the Chinese researchers, but with much greater success. The Oregon team demonstrated that germline editing could become safe in the years to come. That was not the case in 2015, when the Chinese experiment demonstrated that the gene encoding the hemoglobin beta chain –the gene that’s defective in beta thalassemia– could be edited using CRISPR in an embryo, but not edited reliably in all of an embryo’s cells.

But through a series of technical innovations, the OHSU team was able to overcome the usual challenges and repair embryos afflicted with a different genetic disease that we’ll discuss below. They were able to do this in most of the embryos that they treated, and, importantly, they did it without so-called “off-target effects”. Also, they did it without leaving embryos as a mosaic, a mixture of cells with different genomes that would behave differently when the embryo matures into a child.

Let’s unpack what we mean by germline editing. Basically, it’s a kind of gene therapy. Normally, gene therapy involves changing genetics of particular body tissues in a child or adult, without changing the genetics of gametes, the cells that produce our children. In germline editing, the target is either the gametes, or embryos that are created from gametes of a father and mother. With the OHSU research, and with the early Chinese research, we are talking about the embryo type of germline editing.

Looking specifically at the experiments, the Oregon researchers have been interested in a mutation of a gene called MYBPC3. Eggs from healthy women were fertilized with sperm from men who carried the mutation in MYBPC3 that causes a heart condition called hypertropic cardiomyopathy (HCM). In HCM, the myocardium –the muscular wall of the heart—becomes increasingly thicker, which interferes with its function. About 1 in 500 people has HCM and if one parent has the gene, each child has a 50 percent chance of being affected.

Now, people with HCM often can live fairly normal lives, but in some cases it can progress to a point where it can cause sudden cardiac death. In about 6 percent of cases, a heart transplant is needed.

The work in Oregon has been generating waves through science news cycles around the planet, and not just because of concerns about a coming age of designer babies. The leader of the OHSU team, Shoukhrat Mitalipov, is a kind of science celebrity, famous for moving into work that is the center of public controversy. He cloned monkeys in 2007. Then, four years ago, he cloned human embryos and demonstrated that they could be used to generate lines of human embryonic cells. These, in turn, could be used to create new tissues, to repair organs and cure disease and aging, so the work has given a boost to the new field of regenerative medicine.

Today, you can find plenty of headlines using the Oregon story as a springboard to discuss feared era of designer babies, but such concerns are overplayed. People use eye color as an example of something that parents might wish to design, but genetic control of eye color is actually very complex. It doesn’t come down to only one gene –the gene for the pigment melanin— as suggested sometimes in high school biology in order to use eyes as an example of Mendelian inheritance. Eye color actually won’t be such an easy thing to change in one’s future children, nor, by the way, is height. Often, it’s genetic diseases that come down to a simple gene, so a good argument can be made that the humanitarian applications of CRISPR germline editing constitute a more realistic goal than the feared designer babies.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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