Genetically Modified Monkeys: What's Next?

Researchers in China have used a new method to produce genetically modified monkeys.  Their purpose is to advance medical research by creating monkeys genetically predisposed to develop human diseases.  But the new method is so precise and so successful that one might imagine it leading to genetically modified humans.   

Caption: Researchers achieved precise gene modification in monkeys.  Credit: Cell, Niu et al.

According to a report published in the January 30 issue of the journal Cell, scientists used a new gene editing technique known as the CRISPR/Cas9 system.  The technique allows for very precisely targeted modification of DNA sequences. 

It also allows researchers to trigger more than one modification at a time. And it seems to avoid causing extraneous mutations where they are not wanted.  

With the CRISPR/Cas9 technique, researchers edited the DNA in monkey embryos at the one-cell stage.  As that cell multiplied, all the cells of the body contained the gene edits, probably including the cells the newborn monkeys might someday pass to their descendants. In other words, this is precise germline genetic engineering in primates.  

"Our study shows that the CRISPR/Cas9 system enables simultaneous disruption of two target genes in one step without producing off-target mutations," claimed Jiahao Sha, one of the lead authors at Nanjing Medical University.

The goal for now, Sha said, is to refine the technique and to be able to create "many disease models...in monkeys," according to the press release issued by the journal Cell.  

Just how refined will the technique become?  Consider that the first successful germline modified monkey was only reported in 2001. The current advance offers far more precision.  With enough precision, it might become possible to apply this technique to a single-cell human egg.  

The modification could be verified before the embryo is implanted, using the well-established technique of pre-implantation genetic diagnosis or PGD.  If implanted and brought to term, the human life created this way would have its germline DNA modified, meaning that the modification would pass to future generations.  

No one knows now whether this technique will offer the kind of precision that would be required to move from monkeys to humans.  But just how much precision is, in fact, required?  With PGD as a way to catch any "mistakes," might ethics committees, in a few decades or even sooner, permit couples and researchers to use this technique in order to avoid transmitting genetic problems to future generations?  Will it then be used to add something new or desirable to the genetic inheritance of our offspring?

The article, Niu et al., "Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos," is published in the January 30, 2014 issue of Cell.  

"Three-parent babies" and the Human Germline Modification Debate

Human germline modification is back in the news. The current round of public conversation was launched in the UK by the Human Fertilisation and Embryology Authority (HFEA). In the past few days, the media and the blogosphere have lit up with an intensifying debate. 

What HFEA wants people to consider is whether it is acceptable to use in vitro fertilization to try to avoid a specific category of genetic disease. Is it OK to help couples at risk for mitochondrial disorders by supplying donor mitochondria to the new embryo? If mom’s own mitochondrial DNA will lead to a disease, is it OK to add mitochondria from an outside donor?

PHOTO Transmission electron microscope image of a thin section cut through an area of mammalian lung tissue. The high magnification image shows a mitochondria. Source: Wikimedia. Credit: Louisa Howard, PhD. This work has been released into the public domain by its author.

Many refer to this as the “three-parent baby.” And for that reason alone, they object.

Others raise the stakes in the argument. They insist that the “three-parent baby” is just the tip of the looming germline modification iceberg. What’s really coming, they claim, is the era of “designer babies,” enhanced or improved versions of ourselves, a new form of high-tech eugenics.  And with that comes more mischief.

Consider what Stuart Newman (New York Medical College) had to say in his comment in The Huffington Post. Newman starts by asking whether the procedure is really as safe as it seems. Fair question. But then Newman writes that what is really going on here is “a new form of eugenics, the improvement of humans by deliberately choosing their inherited traits.” And then, a few short paragraphs later, he’s off to the Nazis, forced sterilization, and the Nurenberg Code.

Now it may be true that the “three-parent baby” is a pretty bad idea medically. But morally, is it really the fast-track to Nazi medicine?

Or consider Marcy Darnovsky’s comments in a press release from the Center for Genetics and Society:

“Changing the genes we pass on to our children is a bright ethical line that should not be crossed,” said Marcy Darnovsky, PhD, the Center's executive director. “It has been observed by scientists around the world, adopted as law by more than 40 countries, and incorporated in several international treaties. It would be wrong for the UK to disregard this global bioethical consensus, especially when there are safe alternatives available for the very few people who would be candidates for the procedures.”

The release concludes: “The Center for Genetics and Society calls for a domestic and international moratorium on approval of any procedures involving inheritable human genetic modification…”
Or consider the comment of David King of Human Genetics Alert as quoted by the BBC: 

Dr David King, the director of Human Genetics Alert, said: "Historians of the future will point to this as the moment when technocrats crossed the crucial line, the decision that led inexorably to the disaster of genetically engineered babies and consumer eugenics.

Is the “three-parent baby” really “crossing the germline barrier”? Back in 2001 when the first “three-parent babies” being created here in the US, Erik Parens and Eric Juengst wrote a response in the journal Science. They called it “Inadvertently Crossing the Germline.” Ever since then, many have agreed. Despite some really important distinctions, mitochondrial replacement is a kind of human germline modification.

A bit of a stretch, but OK, let’s call it that. But is that reason enough to condemn it? Is human germline modification itself morally wrong? It may be biomedically impossible. It may be excessively expensive considering all the other needs facing the world’s children. But is it intrinsically wrong? 

 

In 2008, I published an edited book that tried to take the temperature of religious opinions on the morality of germline modification. What I discovered surprised even me. Most religious scholars in my collection were not particularly troubled by the prospect of germline modification. Sure, they had their concerns—safety, social justice, over-controlling parents, an attitude of commodification. But in the end, almost without exception, they agreed: what can be religiously or morally wrong with wanting to use the latest technology to help parents have healthy children? For more on this, see Design and Destiny from MIT Press.

 

For many people, it comes as a total shock to hear that even some Vatican statements support the notion that germline modification is not inherently immoral—that, in fact, it could be “desirable.” The Vatican has specific constraints that must be met. No IVF, for one, so the “three-parent baby” strategy fails on that score. But if the means are acceptable, then the goal is laudable, at least according to this statement made by Pope John Paul II:

A strictly therapeutic intervention whose explicit objective is the healing of various maladies such as those stemming from chromosomal defects will, in principle, be considered desirable, provided it is directed to the true promotion of the personal well-being of the individual without doing harm to his integrity or worsening his conditions of life. Such an intervention would indeed fall within the logic of the Christian moral tradition.

I agree with the “three-parent” critics about the importance of the debate over human germline modification. For that very reason, I hope they tone down the rhetoric. This is not Nazi medicine.

 

There are sound moral reasons for wanting to move forward on human germline modification. Of course, there are incredibly important technical hurdles that must be overcome. Some of them, in fact, may prove impossible. If so, then of course human germline modification would be a bad idea because of the risks.

 

But if biomedical research can find its way through these technical barriers, what then? Yes, there are other objections, more religious or moral in nature, but there are also strong reasons for going forward. That, I suggest, is where the real discussion should focus.