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04/23/2015

Designer Embryos: The Future is Now

by Craig Klugman, Ph.D.

Oh, wonder!
How many goodly creatures are there here!
How beauteous mankind is! O brave new world,
That has such people in ’t! (Shakespeare, The Tempest, Act 5, Scene 1.

Nature News on Wednesday reported a group of Chinese researchers have successful genetically engineered a human embryo.

Researchers used “non-viable” embryos from fertility clinics. These embryos had an extra set of chromosome, having been fertilized by two sperm and containing three nuclei. Such embryos were chosen because of the impossibility of them gestating into a human being. The team then used the enzyme CRISPR/Cas9 which permit scientists to snip out genes and insert new ones. They edited the HBB gene that is responsible for β-thalassaemia. This genetic disease causes a range of blood disorders. Repairing the gene in an early stage embryo should theoretically remove the disease from the person the embryo will become and his or her future progeny.

The authors published their article in an online, open access journal, Protein and Cell after being rejected from Nature and Science for undefined ethical concerns. 86 early-stage human embryos were injected with CRISPR and after 48 hours the embryos reached the 8-cell stage. 71 embryos survived, 54 were tested, and 28 were successfully spliced. Many contained undesirable mutations, which the scientists say may have been a result of the unviable embryos used. Seven of those embryos contained the desired genetic switch. Thus the overall success rate was 8.1%.

The announcement comes a month after the Alliance for Regenerative Medicine called for a moratorium on genetic engineering in humans. A March 12, commentary in Nature responded to a March 5 story in MIT Technology Review that reported on rumors of such an experiment. The Nature commentary acknowledges that there are some powerful reasons to do such genetic engineering including treatment of genetic disease, cancer, and HIV. Much of this work has been on somatic cells, that is ones that are not passed on to future generations.

The authors express concern that changing an embryo’s genome would change the germ line cells and thus any changes would effect future generations. They are concerned that the technique may change DNA in unpredictable or unintended ways  that might not be known until birth. The writers state that until there is demonstration of safety and efficacy over several generations, the potential harm to current and future generations outweighs any benefit.

What they did not consider was the notion that there are living and will-be-living people with diseases that could potentially be eliminated. How might a parent feel whose child is born with β-thalassaemia, when the genetic problems that lead to that disease could have been prevented. If a technology that exists that could have prevented suffering in people, there is an obligation to use it. To ease (or in this case, prevent) suffering and to provide treatment when possible are core values in medicine. One could argue that not pursuing this technology is purposefully allowing future individuals to suffer when that state could have been prevented.

The Nature authors conclude by asking for a voluntary moratorium on human germline modification. This would permit research to continue on adult cells. Consider though, that engineering an embryo is more efficient, since only a few cells need to be altered and that change will automatically be replicated into future cells. To treat the same disease in a born human requires changing trillions of cells.

The voluntary moratorium had been broken before it was even expressed. In some countries, this technology is illegal. But if a voluntary ban is not effective, then perhaps a time-limited legal ban could provide some breathing room for the development of regulations and ethical guidelines.

Genetic engineering has been fodder for science fiction for decades from Aldous Huxley’s Brave New World, Gene Roddenberry’s Andromeda, the film GATTACA, and Margaret Atwood’s MaddAddam Series to name a few. In GATTACA , a two-class society evolves when genetic engineering allows parents to select the genes that their children will have:

We want to give your child the best possible start. Believe me, we have enough imperfection built in already. Your child doesn’t need any more additional burdens. Keep in mind, this child is still you. Simply, the best, of you. You could conceive naturally a thousand times and never get such a result. –GATTACA

In the MaddAddam trilogy, a new species is created that feeds on sunlight, self heals and lacks the “faults” of humanity such as lust, violence, and jealousy. At the same time, a disease is engineered to wipe out the human species, allowing nature to start again with the new creatures.

What these works of fiction have in common is their dystopic visions where messing with the human genome leads to science run amuck, the end of the human species and the world as we have known it.

Would such technology “cheapen” life. What happens to people already born with theses diseases or with being vertically challenged or having a disability? They may become further stigmatized and be looked down upon by a society that only knows these conditions as an “old people’s disease” since few young people would be born with them. And like in GATTACA their may be a whole new set of disabilities from when genetic engineering has unintended consequences: Such people may be made invisible in society.

The challenges of this new technology are potentially species-changing. Using these techniques to combat disease seems noble and without controversy. But consider that the same techniques that can combat illness can also make an infectious agent more virulent and deadly. What are the nefarious uses to which this technique might be used, like in MaddAddam

The Chinese scientists have reportedly stopped their work until they can figure out how to have a better success rate in the embryos. Instead of an 8.1% success rate, they would like to see closer to 100%. Even if these researchers stop, others know that genetic engineering in humans is possible and may continue their work.

Technologies themselves are not inherently good or bad—it is how they are used, and their very unintended consequences. However, humanities’ track record on such things as gunpowder (fireworks and firearms) and splitting the atom (power plans and bombs) is not inspiring. On the other hand, despite successful cloning of many animals, no one has, at least publicly, cloned a human being.

Like Pandora’s Box, this technology is out. Opening the Box unleashed all of the evils into the world and the only thing left was hope. And with this announcement, what we have is hope that we can learn to use this knowledge responsibly.

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