Can man play God?

Dr. Andrea Bannert has been with since 2013. The doctor of biology and medicine editor initially carried out research in microbiology and is the team's expert on the tiny things: bacteria, viruses, molecules and genes. She also works as a freelancer for Bayerischer Rundfunk and various science magazines and writes fantasy novels and children's stories.

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For the first time it has been possible to successfully repair a genetic change in human embryos. But not only diseases can be cured with technology. The eye color and other features could also be predetermined in this way. Will the designer baby be around soon?

Simon K. * collapsed while exercising and never woke up again. Diagnosis: sudden cardiac death. The young, athletic man suffered from what is known as hypertrophic cardiomyopathy, or HCM for short. In this disease, the heart muscle tissue in the left ventricle thickens. The disorder is relatively common. One in 500 people is affected and many die from it.

Scissors seeks leaders

The special thing about HCM: The information, the so-called genetic code, is only changed at one point in a very specific gene. Scientists call this a mutation. There are around 10,000 other hereditary diseases that are triggered by mutations that are similarly isolated. Cystic fibrosis or sickle cell anemia - two equally life-threatening diseases. The obvious idea is to correct the serious genetic errors as early as possible.

An impossible endeavor until recently. Scientists know enzymes that can “cut” DNA, but these protein molecules do not speak the same language as genetic information. That is why they cannot track down the defect in the genome.

That changed with a spectacular discovery by the two scientists Jennifer Doudna and Emmanuelle Charpentier four years ago. By chance they found an enzyme in bacteria that can cut strands of DNA and carry a small snippet of genetic material with it like an interpreter. It can read the enormous amount of data in DNA and guides the molecular scissors exactly where they are supposed to cut. The scientists named the potent team “CRISPR / Cas9” - bacteria need it to defend themselves against viruses.

Hereditary disease nipped in the bud

A group of researchers from the Oregon Health and Science University in Portland used the gene scissors to erase hypertrophic cardiomyopathy very early in the genetic code - in embryos. Shoukhrat Mitalipov's team equipped the gene scissors with a genetic sequence that recognizes the exact location in the DNA at which the disease is programmed.

They applied their new super tool to 58 embryos, which were created from the sperm of a man suffering from HCM and the egg cells of a healthy woman. Such attempts are possible in the USA. In Germany, however, the Embryo Protection Act prevents human embryos from being used for research purposes.

Sensational success rate

The US experiment worked: the “interpreter” snippet guided the Cas9 molecular scissors precisely to the mutated DNA segment and separated it out. Now the cell's own repair mechanisms were able to restore the gene.

The success even amazed the scientists themselves: the pathogenic mutation disappeared in 42 embryos - a success rate of 72 percent.

"In cell cultures, however, CRISPR / Cas9 did not work as well as in living embryos for a long time," says Jun Wu, one of the authors of the study. The researchers suspect that the reason for this is the particularly well-functioning DNA repair machines in the early embryonic stages.

A previous experiment by Chinese scientists in April 2015 also worked significantly worse than the experiment by the US researchers. Unlike Mitalipov and his team, the Chinese only added the gene scissors to the fertilized egg with their interpreter - and not at the time of fertilization.

Scissors out of control

And the Chinese researchers had to struggle with another problem that did not occur in Mitalipov's experiment: so-called off-target mutations. They are considered to be the greatest danger when using CRISPR / Cas9.

Off-target means that the gene scissors also cut in other places than the desired one. And not everything can be put back together correctly by the cell's own repairs. Then new mutations arise that could trigger cancer, for example.

"We drive a car that we are still building."

With their attempt, Mitalipov and colleagues have rekindled the ethical debate as to whether humans are allowed to manipulate embryos. In Germany, only the so-called pre-implantation diagnosis is allowed so far. This involves examining the genetic material of embryos after artificial insemination outside the womb and only using healthy embryos - i.e. those that do not carry a serious hereditary disease such as HCM. And the method may only be used at all if there is a threat of a serious hereditary disease.

The CRISPR / Cas9 technique can also heal those embryos that would be selected during pre-implantation diagnostics. Theoretically. Because whether it is really better remains to be seen. The risks associated with gene scissors treatment cannot yet be definitively assessed - the scientists agree on this. Jacob Corn, Director of the Genomics Initiative at the University of California at Berkeley, said of the CRISPR / Cas9 research status: "We're driving a car we're still building."

Unknown dangers

Eleven major American science organizations call for "a cautious but committed approach" in the American Journal of Human Genetics. Until you know whether the benefits really outweigh the risks. The researchers therefore consider it “currently inappropriate” to insert a genetically modified embryo from a woman and bring about a pregnancy.

The CRISPR / Cas embryos from Mitalipov's experiment were destroyed after a few days. At this point in time, the embryo consists of a small, fluid-filled cell ball, the blastocyst. Scientists do not yet define this embryonic stage as human life. If the blastocyst does not implant itself in a uterus, “only” embryonic stem cells are created from it in the laboratory.

The question of when life begins can of course be argued. In Germany, for example, embryos may only be frozen in the so-called pronuclear stage and for the purpose of artificial fertilization and then destroyed at some point. With them, the nucleus of the egg cell has not yet completely fused with the semen. Many researchers are calling for such structures to be used for high-level research goals.

Designer babies?

But how far can one actually go in genetic research and therapy? CRISPR / Cas9 discoverer Doudna has concerns and says: "I have often asked myself what researchers would do with this technology, the existence of which I am partly responsible for." Perhaps they would create a designer baby that parents not only have decide about health, but also determine hair color, eye color, intelligence and character - if such an experiment is not prevented by law beforehand. It is high time to determine which risks researchers are allowed to take when genetically modifying embryos and which manipulations should be prohibited in principle.

* Name changed by the editor.

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