New Ways to Engineer the Germline

Posted by Jessica Cussins December 18, 2013
Biopolitical Times

In 1998, a UCLA conference called "Engineering the Human Germline" brought together more than 1,000 people to discuss various emerging technologies and the challenges they faced. Gregory Stock, a co-organizer of the conference, told Nature at the time that, really, the goal of the event was to make the inheritable genetic modification (IGM) of humans “acceptable” to the public.

Over forty countries, and multiple international treaties, prohibit IGM due to the profound safety, social, and ethical implications of making permanent changes to the human germline. Opposition to IGM is widespread; the Center for Genetics and Society, for example, has long argued that “the case for allowing it is not compelling, and the potential harms of doing so are immense.”

Disturbingly, 2013 has seen a deluge of new efforts, more explicit than any since 1998, to ease public opinion towards allowing human germline engineering.

The big one for 2013, which I have written about before, is mitochondrial replacement. This is a technology that would in theory allow a woman with a particular kind of severe mitochondrial disease the chance to have a non-affected and mostly genetically related child. It would extract the nucleus from one of her eggs and insert it into an enucleated egg from a second woman, and then allow the resulting egg, containing nuclear DNA from the intended mother and mitochondrial DNA from a donor woman, to be fertilized. This crude technique poses severe risks to any resulting child, yet, with both the United Kingdom and the United States currently considering policy changes to allow clinical trials, it seems to be the world’s current forerunner for violating the international consensus against IGM.

But there are other developments worth keeping an eye on. One, a gene editing technique known as CRIPSR, has gotten a lot of attention recently because of its potential for permitting much more specific genetic alterations than can be accomplished with currently used methods. Researchers have had some success in mice and human stem cells, and a company called Editas that just launched intends to investigate and commercialize its human possibilities. Fortunately, the focus of CRIPSR is likely to dwell in the realm of gene therapy for critically ill consenting persons. Unfortunately, some scientists are also touting the possibilities of applying CRISPR to IVF embryos – in other words, of moving ahead to full-fledged inheritable genetic modification. 

It is still too early to know how effective and safe CRISPR could be; so called “off-target mutations” caused by its high mutagenic efficiency could mean that the technique would fix one problem, but introduce others. Furthermore, epigenetic changes caused by this technique seem inevitable, and yet would be very difficult to understand or predict ahead of time. However, if it is found to be safe and effective, it would be the most powerful tool for producing “designer babies” the world has seen to date. Unlike mitochondrial replacement, with its crude wholesale swap of one woman’s mitochondrial DNA for another’s, CRISPR could make it possible at least to try to alter specific genes for specific purposes.

Another procedure that was recently in the news is a method to genetically modify sperm. Scientists from the Royal Veterinary College in the United Kingdom used a viral vector to insert genetic material into mouse spermatozoa and found that it was still functional three generations later. However, while this technique introduces another method for creating transgenic animals, it seems that any human applications are vague and hypothetical at this point.

All of these techniques are biologically extreme processes that carry unknown impacts. But it’s important to remember that, even if they can be made to work, none of them alleviate the illnesses of people alive today. Instead, they are proposals for creating new people. They are often justified as a way to help couples who desperately want a genetically related child, but are concerned about passing on a debilitating illness to their children. But people in this situation already have a powerful tool at their disposal: preimplantation genetic diagnosis. Though embryo selection also raises concerns about “designer babies,” its design capabilities have nothing on these engineering techniques, and it carries substantially fewer risks to the resulting children.

It remains to be seen how the policy cards will fall on these novel attempts at IGM, and whether technical limitations or the impressive outpouring of criticism from varied sources around the world this year could be enough to fight back this particular wave of enthusiasm.

Previously on Biopolitical Times: