TED Talk on CRISPR/Cas9 system of genetic engineering

Jennifer Doudna talks on the currently mainstream method of genetic engineering, using the site-specific CRISPR/Cas system.

In addition to the brief summary of how CRISPR works, she also talks about how genetic engineering is currently being used and predicts the first applications of gene therapy will be mostly for immune system diseases, as white blood cells can be removed from the body and modified ex vivo, or outside the body. I totally agree with this, with our current level of technology it’s far easier to engineer a cell outside the body rather than risk any of the adverse reactions to gene therapy in humans.

Most importantly for this blog, she talks about whether this technology could be used for genetic enhancement. She lists simple things that many of us might even consider no different to vaccines, like enhancing our resistance to cardiovascular disease, before quickly moving into the ‘designer humans’ idea of specifying or changing height or eye colour.

She backs up the moratorium on human germline genetic engineering that I have mentioned on this blog before. I have my objections to this idea (see my previous post for those details), but I have just thought of another problem. As mentioned, cells that can be removed from the body and modified in a dish are most likely the first ones we will be able to modify. In addition to blood cells, and perhaps therapies based on stem cells, our gametes (sperm and eggs) are cells that can be removed from the body (especially so with sperm) and modified outside the body, used to create embryos that can be re-implanted. Thus, it’s likely to be relatively easy to prevent certain genetic diseases before embryos with those disease genes are even created.

I suspect the pressure to cure diseases will be much greater than the pressures to create a clone, so a moratorium on human germline engineering is probably going to be more difficult to defend than the one on cloning.

Some scientists make no sense to me

There was an opinion piece published in Nature recently called Don’t edit the human germ line. It’s written by leading scientists (Edward Lanphier, Fyodor Urnov, Sarah Ehlen Haecker, Michael Werner& Joanna Smolenski) in somatic cell gene therapy, and to me it reads like they’re very concerned that the association between gene therapy in adults and the concerns about making designer babies would lead to public outcry over gene therapy. Basically they’re trying to shut down germline engineering so they don’t look guilty by association (especially given the same techniques would likely be employed).

The authors do point out a lot of technical issues with embryonic genetic manipulation, namely that any errors or side-effects might not appear until years later. Which is fair, in my opinion. I still think it’s pretty likely that people won’t genetically modify the human embryo until the technology for doing so in consenting adults is well established.

But in the article, the scientists make a few stupid statements. Like saying

We are not, of course, making a comparison between the replacement of faulty mitochondrial DNA in an egg or embryo with healthy DNA from a female donor and the use of genome-editing in human embryos. In mitochondrial transfer, the aim is to prevent life-threatening diseases by replacing a known and tiny fraction of the overall genome.

I don’t see why they wouldn’t make this comparison, because it seems basically identical to me. I will concede that editing the mitochondrial DNA component of the genome is technically a lot easier than editing a small component the nucleic DNA component (due the former already being isolated in the cytoplasm). But ethically, it doesn’t matter if you’re trying to edit the mitochondrial DNA or a gene contained in the nucleic DNA, you’re still aiming “to prevent life-threatening diseases by replacing a known and tiny fraction of the overall genome”.

The scientists also seem to tie themselves in a loop with two parts of their argument. The first is this:

Philosophically or ethically justifiable applications for this technology — should any ever exist — are moot until it becomes possible to demonstrate safe outcomes and obtain reproducible data over multiple generations.

Aside from the extreme lack of foresight in doubting the obvious benefits of germline genetic engineering*, this seems a fair point. While the science is in its infancy, it seems wise to be very cautious. But combine this point with a point made in their closing argument:

A voluntary moratorium in the scientific community could be an effective way to discourage human germline modification and raise public awareness of the difference between these two techniques.

Hardly a suprise, given the title of the article, that the scientists are against germline engineering. But how is anyone going to be able to :”demonstrate safe outcomes and obtain reproducible data over multiple generations” if there’s a moratorium and it’s illegal to do those experiments?

Basically these scientists, instead of trying to address the concerns the public has over the ‘scary’ idea of designer babies, are just trying to say “Yeah, designer babies are scary but that’s not what we’re doing at all, so please keep funding us”.

*There are a whole host of genetic diseases that have to be fixed before the development of organs and tissues, so our only option to cure these would be to edit the genome of a gamete (sperm or egg) or embryo. There would be no way to use somatic cell gene therapies after birth for these conditions, especially for those conditions that often result in death shortly after birth. In most but not all cases you could, as the authors suggest, use pre-implantation genetic diagnosis (PGD) to select only for embryos without these mutations. But in some cases both parents might be affected by a recessive genetic condition, so there would be no embryo without the mutation to choose, thus ruling out PGD as an option.

Designer babies are good, but don’t come with a satisfaction guarantee

There’s this story going around concerning designer babies, supposedly trying to show how horrible a future where babies can be designed can be. It goes something like this:

Mr. and Mrs. Jones want a baby. They visit a fertility clinic and announce: “We want a boy—blond hair and blue eyes, please. We want him to be at least six feet tall, good at sports and have great musical ability.”“No sweat,” the doctor says. Nine months later, baby Logan is born.But for Logan’s parents, things don’t work out quite the way they expected. Despite his outstanding physique, Logan has no interest in sports. He likes to write poetry instead. As for music—yes, he’s good at it, his genes have seen to that—but he’d much rather spend his time designing model airplanes.

Logan’s parents are furious. They paid good money for a son who would make them proud on the athletic field and in the concert hall! Plus—the final insult—Logan dyed his blonde hair purple.

There are a number of points to address here.

Most importantly, genetics can’t ensure anything, especially when it comes to personality. Personality, more than anything else, is the result of a complex interplay between genetics and environmental factors. It would be possible to use genetic modification increase the probability of athleticism and musicality in a child, but it can’t be guaranteed.

The story mentioned that Logan’s parents are furious, but it’s worth noting that they are unlikely to be furious at Logan – it’s not his fault – but are likely angry at the doctor for accepting their money and not delivering on his promise. A doctor will of course need to be sure to stress that he can’t ensure anything, because doctors who promise things they can’t deliver are risking lawsuits from frustrated parents. So that part of this story won’t happen, that’s for sure – no doctor will promise this, and only stupid parents would expect their doctor to do so.

What of the parental pressure? Well, parents like Mr. and Mrs. Smith already exist, putting pressure on their children to be top achievers at school, to do well at sports, and try to guide their children into what the parent dreams their child will be.  Designer babies won’t be adding anything new here, and may actually be able to help.

To demonstrate this, consider how the story could have been:

Mr. and Mrs. Jones want a baby. They have dreams of having a healthy baby girl, with soft brown hair and big dark eyes. They dream of her growing to be a tall and beautiful woman, going to the best college in the state, being outstandingly musical and perhaps becoming a successful lawyer or physician.But they don’t use any genetic interventions, because those are against the law in all nearby states and countries. They conceive naturally, and nine months later, a baby girl, named Lora is born.Her parents are ecstatic that without needing to choose their child’s gender, they were still gifted with a baby girl. But in other ways, Lora isn’t what her parents expected. She is short, and would much rather play sports, especially basketball, than go to school. Her parents try to encourage her to study, pushing her to try harder, but Lora has difficulty reading and paying attention in class. Lora loves music as much as her parents do, but she is almost tone deaf and she wasn’t selected for the school band.Lora’s parents eventually come to terms with the fact that Lora wasn’t born with the abilities they expected, and Lora accepts that her small stature will prevent her from fulfilling her dreams of being a star on the basketball court and her dyslexia will hold her back in college. Perhaps Lora will find a satisfying life despite this, but it’s likely she and her parents will spend the rest of their life in disappointment.

Amazingly, biotech could actually help here. Mr and Mrs Smith want a daughter who is tall, beautiful, musical and intelligent. Gene modification or selection could increase the chances that Mr and Mrs Smith have a daughter who is everything that her parents’ value. It’s still possible that their daughter won’t share the same interests as her parents. But if she does, she will avoid the same years of struggle and disappointment that Lora had coming to terms with her problems.

The very final point in the original story, where Logan dyes his hair purple, is a very poignant one. Gene interventions don’t actually intrude on the child’s freedom, as they are free to rebel. You can give a child a beautiful head of hair, but they will dye it and cut it a different way. You may give them the genetic basis of creativity in the hope they become a great musician, but they are free to use this creativity to write poetry and design model planes. And, it’s likely that the genetic technologies will exist to permit a child, once they reach the age of maturity, to undo the manipulations their parents had made.

All of us are born with genetic tendancies that shape who we are, and grow to have dreams and aspirations. In most of us, we struggle to find satisfication when we realise our abilities conflict with our desires – our own desires, and the dreams of our parents. The important part is that our parents still love their children, regardless.

Fertility clinic backs down from allowing cosmetic ‘design’ of babies

The Fertility Institutes LA, an American IVF clinic that recently announced that it would be offering parents the opportunity to use preimplantation genetic diagnosis (PGD) to select hair and eye pigmentation, has decided not to go ahead with this (excepting for selecting against albinism). The reason? Public opinion, of course.

[W]e […] feel that any benefit the diagnostic studies may offer are far outweighed by the apparent negative societal impacts involved.

A total shame, to let the public pressure decide what sort of children people can or can’t have. With all the cries that selecting one’s babies will lead to a situation like that portrayed in Gattaca, nobody seems to realise that the situation portrayed in that movie — public coercion to have a particular sort of baby — is already happening. The only difference is the ‘sort’ of baby that parents are being pushed, by social pressures, to have.

Significant minority favour designer babies

The results of a recent study into public opinion on reproductive genetics (reprogenetics) have been released. It’s promising, as the percentage of respondents who would consider using genetic testing to select for a child with increased athleticism or intelligence was in the double digits (10 and 12.6% respectively). In addition, the majority of respondents (52.2%) also said that there was no form of genetic testing that should be always off limits, meaning that genetic enhancement may be considered allowable if it was to be voted upon.

That said, the respondents were people who were visiting a genetic counsellor, and therefore the results may contain some bias towards acceptance of genetic testing or genetic enhancement.

For a longer and more in-depth analysis, read what George Dvorsky had to say on it.

Baby born with less chance of getting cancer, and people are upset

In the United Kingdom, a child has been born without a mutated allele of the BRCA1 gene, a gene known to create a risk for breast and ovarian cancer if it is mutated. Yet, because this baby was chosen as an embryo on the basis that it did not have this mutation (and other embryos, with the mutation, were not implanted), people are throwing the E-word left and right. Well, mostly just known bio-conservative Josephine Quintivalle:

Josephine Quintavalle, of the campaign group Comment on Reproductive Ethics, said: “This is nothing personal towards the girl, but I think we have gone too far. […] Underlying all this is eugenics.”

Whether PGD and selective implantation is eugenics depends on what is meant by this very loose term. If eugenics is to mean killing people because they are ‘unfit’ or controlling people’s reproductive lives, then this is surely not eugenics, as embryos are not yet people and this procedure was consented to by the parents. But, if eugenics is to mean attempting to improve on humans, then perhaps this is eugenics. The issue is, the E-word carries many implications of the former attrocities, and so I feel it is too misleading to be used here.

Mrs Quintavalle was then reported as saying the message was that

“you are better off dead, than being born with this gene”.

Of course, Mrs Quintivalle can now join other bio-conservatives, and Secretary-General of the UN Ban Ki-moon, as a member of the group of people who don’t realise that there is a difference between not existing and being dead. Although to be fair, these people do see the destruction of embryos as killing of people, so if they were right (but they are not) they might have a point. Although, such a point would best be expressed as ‘you are better off not being born at all, than being born with this gene’. But as embryos are not people, and can’t be called ‘you’ nor empathised with, there is no point.

This birth is a key one, as it represents the first use of preimplantation genetic diagnosis to prevent the mere risk of a disease, rather than the certainty. This is seen as being on the road to designer babies, but fortunately when it comes to using biotechnology to prevent or cure disease, many people are accepting of the idea. Let’s just hope they remain accepting of enhancing the speed and reflexes of a child, such as to reduce their risk of being in a car accident or being hit by a bus.

I think I want to move to New Zealand

Bioethicists must be sensible across the Ditch, because a New Zealand bioethics commission has released a report titled “Who Gets Born?” in which their first and foremost recommendation is:

Decisions about whether to have pre-birth testing, and what to do in light of the results, should be made by the parent(s) within the existing framework of the Code of Rights.

It’s just so sensible! Maybe not sensible enough for my own government (Australia) or the motherland (Great Britain), but sensible enough for the Kiwis (New Zealand) and Yankees (USA).

Also sensible is recommendation 8, which states:

The present distinction between using preimplantation genetic diagnosis to create embryos that are tissue-matched to sick siblings suffering from inherited conditions and using it to help siblings suffering non-inherited conditions should be removed. The only requirement should be that the sick sibling is suffering from a serious condition for which no other treatment is reasonably available.

Although I think that requirement is still too much, that is actually far more sensible than I’m used to hearing.

Finally, just because the public contributors weren’t enough like myself, we have recommendation 10, which reads:

The current provisions allowing the use of preimplantation genetic diagnosis (without the Ethics Committee on Assisted Reproductive Technology’s oversight) for late-onset or low-penetrance conditions be retained.

As anyone who reads this blog often will know, I am in favour of the use of PGD for any condition, be it gender, intelligence or albinism (with the sole exception of a condition causing so much pain as to make life not worth living, in which such a choice would be cruel).

Despite this last failing, I find myself in the unusual position of actually envying New Zealand.

Stop forgetting about somatic genetic modifications!

I swear, some people must just have a hard time getting their head around germline and somatic genetic engineering at the same time. It is often common to hear, in a discussion about inheritable genetic modifications, that such changes would be ‘permanent changes’ to the human germline. I’ll just give a few examples of some I have seen recently:

“More importantly, as scientists themselves have recognised, genetic engineering of human babies is too dangerous to contemplate because such changes, whether in embryos, sperm or eggs, would be irreversible in a recipient and inherited by all the baby’s descendants.” – New Scientist

“But to blindly compare transhumanist-style enhancements—especially those that produce irreversible changes to the human genome that will be passed from generation to generation—to routine activities and medicines is as misguided as saying that steroids are simply a more efficient alternative to weight lifting.” – Center for Genetics and Society

“It [Genetically engineered immortality] would represent, finally, the ultimate and irrevocable divorce between ourselves and everything else” – Bill McKibben, Enough: Staying Human in an Engineered Age (2003)

It’s utter nonsense. If you grow up to learn that your parents genetically engineered you to be a tall basketball player, and you don’t like that, you can just get those genes removed, or take drugs to counter it until you are fully grown (or even some to reverse it, if you only learn this later in life). If you have been genetically engineered to not age, and you end up actually wanting to die (or vice versa), you can just add the genes for ageing (or not ageing) later in life.

Because really, somatic genetic engineering is just changing the genes you were born with to be something different in all your somatic (body) cells. It doesn’t matter whether those genes you were born with were inherited from your parents or inserted as part of germline genetic engineering, if you want to change them you should be able.

And, if you do like what you have been germline engineered to be or do (even if that liking is itself a product of your genes), then what exactly would be the problem with staying that way for as long as you live?

Wednesday’s Words of Worry

I know I’m supposed to be giving you some Wisdom to counter last week’s Worry, but I’m afraid I need to point this particular quote out to you all. If I wasn’t so fond of the alliterative title, I would have called this ‘Wednesday’s Words of Utter Tripe’.

It comes from the UK, where if you’ve been following the biopolitical debates, the HFEA bill is causing controversy in the deaf community over a particular clause that rules it illegal to select a disabled embryo over a non-disabled embryo. So, this particular quote comes from Professor Peter Braude, of Guy’s and St Thomas’ Hospital in London, where he is the director of the Assisted Conception Unit.

“I have serious concerns about deliberately selecting a embryo for deafness. This is the same as taking a normal child and deliberately making it deaf so that it can fit in with a community. I don’t see how that can be acceptable.” (source: Telegraph)

I really hope that it is obvious to you all that this is not the case. Nobody is modifying any children, nor are there any children in this case to modify. They are embryos, and they are not genetically modified – their genome is exactly what they had since conception. Embryo selection merely chooses which are implanted and which are not. They are choosing to have a deaf baby, not making a baby deaf.

Consider other examples. Choosing not to have children because you want to focus on your career is not the same thing as killing a child because you want more time for work. Choosing to have a child free from Down’s syndrome is not the same thing as curing a child from Down’s syndrome. Choosing to have a boy is not the same thing as performing a sex-change on a girl.

I would have thought a Professor would have the brains to realise this, but obviously I am wrong.

Ron M. Green in the Washington Post

Ronald M. Green, the author of Babies by Design: The Ethics of Genetic Choice has a piece in the Washington Post called Building Baby From the Genes Up. Like the book, it’s written from a fair and unbiased view that sits partway in the middle of “bio-Luddite” and “transhumanist” (though perhaps leaning towards the latter in parts). Here is an excerpt:

“But why should we think that the human genome is a once-and-for-all-finished, untamperable product? All of the biblically derived faiths permit human beings to improve on nature using technology, from agriculture to aviation. Why not improve our genome? I have no doubt that most people considering these questions for the first time are certain that human genetic improvement is a bad idea, but I’d like to shake up that certainty.”

Read it in full here.