CRISPR babies

One of my problems with resolving ethical questions is that I so often have a hard time deciding the difference between moral, ethical, reasonable, and justifiable, and figuring out where an issue lies on the spectrum thereof.

I've always had this problem.  There are things that in my view are always wrong -- harming or endangering a child comes to mind -- but the vast majority of issues lie in that immense field of gray areas.

Which is why I'm having a hard time deciding what to make of the bombshell announcement last week that a Chinese geneticist, He Jiankui, claims to have genetically altered a pair of human embryos -- and it resulted in the birth of twin girls who, if the gene editing was successful, will be resistant to HIV.

The technique involved was CRISPR-Cas9, a protein complex that allows for what amounts to cut-and-paste for your DNA.  What He did was to use CRISPR-Cas9 to selectively delete a gene for a  receptor called CCR5 that allows HIV to attach to cells.  Without that receptor -- He hopes -- the children will be genetically immune.

[Image is in the Public Domain]

When He made his announcement, the scientific community had a collective meltdown.  "The underlying purpose of doing the experiment was obviously to show that they could do gene editing on an embryo, but the purpose for the party involved does not make any sense," said Anthony Fauci, an HIV/AIDS researcher and head of the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.  "There are so many ways to adequately, efficiently, and definitively protect yourself against HIV that the thought of editing the genes of an embryo to get to an effect that you could easily do in so many other ways in my mind is unethical."

Okay, I'm not defending He.  The real issue here, in my opinion, is risk.  "Gene editing itself is experimental and is still associated with off-target mutations, capable of causing genetic problems early and later in life, including the development of cancer," said Julian Savulescu, an ethicist at the Oxford University.  "This experiment exposes healthy normal children to risks of gene editing for no real necessary benefit."

But the problem is that at some point, scientists were going to have to take the leap and do something like this.  Ever since Jennifer Doudna of UC-Berkeley developed CRISPR-Cas9 as a gene editing protocol in 2012, it's only been a matter of time.  Once a technique like this becomes possible, it becomes inevitable.

So sooner or later, someone was going to have to accept the risk of trying it on human embryos.  Animal models only get you so far.  The potential for eradicating genetic diseases is nothing short of astonishing; think of a world without cystic fibrosis, Huntington's disease, Tay-Sachs disease, sickle-cell anemia, hemophilia.  All of that is well within the realm of possibility now.

But.  Once you've started down that road, what's to stop people from altering other traits?  Appearance, personality, behavior... for me, this gets out onto some very thin ice.  When this Pandora's box is opened, there's no telling what dubiously ethical practices will escape.

There's also the problem that if such a technique really becomes capable of (relatively) risk-free editing out of deleterious genes, it's almost certain that it would be available only to the rich, further widening the gap between the privileged and the non-privileged.  The brilliant (and prescient) 1997 film Gattaca dealt with this very issue -- how genetic engineering of children could result in a new lower class, people conceived the old-fashioned way who didn't have the same opportunities for jobs, education, health care, and health insurance as the smarter, stronger, healthier "Valids."

So I'm of two, or more, minds about all of this.  First, the potential of the therapy is mind-boggling.  And the idea that once developed, researchers were going to hold off trying it out on human embryos, is naively optimistic about human nature.

But it comes back once again to the quote from scientist Alan Grant in Jurassic Park -- "You were so busy trying to figure out if you could, you never gave any thought to whether you should."  The thorny ethical issues this technique brings up go way beyond the potential risk to two baby girls in China.

All of which makes me glad that I'm not on the scientific regulatory boards who are wrestling with how to respond to He's announcement.

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Ever wonder why we evolved to have muscles that can only pull, not push?  How about why the proportions of an animals' legs change as you look at progressively larger and larger species -- why, in other words, insects can get by with skinny little legs, while elephants need the equivalent of Grecian marble columns?  Why there are dozens of different takes on locomotion in the animal world, but no animal has ever evolved wheels?

If so, you need to read Steven Vogel's brilliant book Cats' Paws and Catapults.  Vogel is a bioengineer -- he looks at the mechanical engineering of animals, analyzing how things move, support their weight, and resist such catastrophes as cracking, buckling, crumbling, or breaking.  It's a delightful read, only skirting some of the more technical details (almost no math needed to understand his main points), and will give you a new perspective on the various solutions that natural selection has happened upon in the 4-billion-odd years life's been around on planet Earth.

[If you purchase the book from Amazon using the image/link below, part of the proceeds goes to supporting Skeptophilia!]

Designer genes

In the movie Gattaca, the future has become a divided society -- split between the "valids" (people who were conceived through in vitro fertilization and genetic selection/modification) and "invalids" (people conceived the old-fashioned way).  The invalids, who have (as all of us currently do) a random mix of good and bad traits from the parents, can't get jobs, can't get insurance, have no access to higher education.  Why should the society put money and effort into people who are of average intelligence and have a much higher susceptibility to hereditary disease, when there are plenty of people who have already been screened -- actually, selected -- to be genetically superior?

Gattaca centers around one man, Vincent (played by Ethan Hawke) who is an invalid -- but is determined to rise above his station.  It's a beautiful, inspiring, and deeply troubling movie.  Because the underlying premise of the movie -- that humans can modify their own genetics at will -- is very close to being realized.

CRISPR-Cas9 is a genetic modification protocol that allows scientists to (more or less) edit DNA one gene at a time.  The medical implications are immediately obvious; this opens up the possibility of not just treating, but curing, such devastating genetic disorders as cystic fibrosis, Huntington's disease, and Duchenne muscular dystrophy.

[image courtesy of the Wikimedia Commons]

The ethical implications are equally breathtaking.  Once gene-by-gene editing becomes possible -- and we're nearly there -- what will stop people from modifying other genes, such as those for appearance, behavior, and intelligence?  Will we enter a brave new world of "designer babies," such as the ones in Gattaca?

Lest you think that I'm engaging in wild speculation, allow me to point out that the first CRISPR-Cas9 experiment on humans is already being conducted.

In the United States, there is an ongoing moratorium on genetic experimentation on humans, but no such restrictions exist in China.  And three weeks ago, man with an aggressive form of lung cancer was brought into West China Hospital in Chengdu, and was given a course of CRISPR-Cas9 modified cells -- his own cells that had been edited to alter their ability to mount an immune response against cancerous tissue.  The cells were introduced into his bloodstream, where (it is to be hoped) they will attack and destroy the tumors.

While details are still forthcoming, research team spokesperson Liao Zhilin has said that "Everything is going as planned."

As with most discoveries, this is a mixed bag.  The idea of being able to use genetic modification to combat cancer is certainly wonderful.  So is the potential for eradicating genetic diseases.  The ethics becomes a little murkier when you start looking at issues like extending longevity -- current research supports the idea that genetic longevity (i.e. independent of other considerations like lifestyle and avoidable risk factors) is controlled by a relatively small number of genes.  It is certainly not beyond the realm of possibility that those, too, could be modified by CRISPR-Cas9.

But is this a good idea?  It's one of those things that puts me in an ethical bind.  I'm 56, and frankly, I'm not looking forward to all of the age-related degradation that I have to look forward to in the next twenty years.  If I could do something that would give me another fifty or a hundred healthy years, I'd be all for it.  But the larger question is whether this sort of thing would be good for society if it became widespread.  It would require large-scale restructuring of how we approach such issues as career, insurance, and retirement, not to mention the fact that given that men remain fertile indefinitely if the plumbing still works, you could be looking at a world where guys could still be fathering children at double or triple the current age.

You think we have an overpopulation problem now?

Of course, this presupposes that such age-lengthening treatments would become widely available -- and this opens up another ethical issue, which is equity.  Especially at first, you'd have to expect such opportunities would only be available to the wealthy, further deepening the divide between the genetically-modified haves and the unmodified have-nots.

Gattaca is beginning to look kind of prescient, honestly.

The whole thing puts me in mind of a quote from Michael Crichton, which seems like a fitting place to end: "Science cannot help us to decide what to do with the world, or how to live.  Science can make a nuclear reactor, but cannot tell us not to build it.  Science can make pesticide, but cannot tell us not to use it.  What should we do with our power?  It is the very question that science cannot answer."