TED Talk on CRISPR/Cas9 system of genetic engineering

Sunday, 15 November, 2015

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.


A comic I saw

Sunday, 4 October, 2015


I think this Saturday Morning Breakfast Cereal comic is pretty good. Nicely shows the flaw in the argument that allowing human enhancement will reduce human diversity, and how it might very well increase it.

Any enhancements that have no downsides would naturally be the most popular, but many other enhancements would have at least some trade-offs (the monetary cost being one of them). Being very muscular might be something that some parents would choose for their children, but others might want them to be elite endurance athletes. So just like many people have the same iPhone but have very different choices of color and fancy patterned cases, many enhancements will be the same but they will have a few optional extras that increase diversity.


Some scientists make no sense to me

Saturday, 21 March, 2015

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.


Wednesday, 8 January, 2014


Many of the posts on my ‘Why Can’t I Have Wings?’ post remind me of this letter.


Man controls new prosthetic leg using leg muscles

Thursday, 3 October, 2013

Though reported as ‘man controls prosthetic leg using thought’, the man is controlling the prosthetic leg using his thigh muscles, which he is controlling using the nerves that used to go to his lower leg and foot (but were surgically re-routed to the thigh). The prosthesis detects the electrical activity in the muscles, rather than the nerves themselves.

So it goes like this:

brain → spinal cord → motor nerve → thigh muscle → EMG in prosthetic limb → movement

Not even interfacing with the motor nerves directly, let alone any kind of a brain-computer interface. This is NOT a mind-controlled prosthetic, any more than any other prosthetic.


Mitochondria transplants at risk of rejection

Tuesday, 1 October, 2013

Those mitochondrial transplants (or ‘three parent IVF’ as it is innaccurately called at times) that I’ve blogged about before (here, here and here) might have a few side effects on gene expression. Replacing mitochondria affected by a genetic disease with those from a gene free donor has been compared to replacing faulty batteries in a camera with fresh new ones. But a recent policy opinion piece published in Science (Reinhardt et al 2013) suggest this analogy might not be totally accurate. One of the authors, Edward Morrow, is quoted in New Scientist:

“For a modern camera you’ve not only got to have the right brand of battery, but the right size, shape and voltage. There are all these parameters you have to have right. You can’t just go into a shop and buy any old one.”

As explained in the piece in Science, the mitochondria of some organisms like fruit flies, mice and monkeys has been shown to interact with the genes being expressed in the nucleus, and thus it probably does the same in humans. Non-invasive methods of replacing mitochondria have been used in most of these studies, which involves mating a male mouse of one line with a female mouse of another line, to produce mice with the mitochondrial DNA of line 2. These offspring were then only crossed to line 1, which after a few generations produces mice that mostly have nuclear DNA of line 1 but the mitochondrial DNA (mtDNA) of line 2 (this is sort of similar to if your mother’s mother’s mother was from a totally different ethnicity to the rest of your family). The results of these experiments were that mice with a ‘mismatch’ had reduced exercise capacity (Nagao et al 1998) and reduced learning ability (Roubertoux et al 2003).

Thus, it’s at least theoretically possible these ‘rejection’ side effects might exist in humans too. We just don’t know, it’s a different species and a different method of mitochondria replacement to those studies. This therapy has been tentatively approved by the Human Fertilisation & Embryology Authority in the UK, and the UK government is drafting regulation for the use of this therapy. This paper shouldn’t change that, as any new treatment is likely to have side effects. The question is whether it’s worth it. I agree with how the Science piece concludes:

Assessing the costs and benefits of MR [mitochondrial replacement] treatment requires that prospective patients are as fully informed as possible. The difference across patients in the severity of expected offspring symptoms in the event that MR treatment is not taken will shape the decision of choosing the treatment versus waiting for the outcomes of further research. Some families who are predicted to be, or who have previously conceived offspring that were, severely afflicted by mtDNA diseases are more likely to be prepared to take the risk. Others whose children are expected to suffer less detrimental symptoms, cognition problems or infertility, may wish to wait for further empirical clarification of the risks involved.

This treatment is very promising for severe mitochondrial diseases. For milder conditions, it might not be worth the risk until we know how the mitochondria and the nucleus interact, and can better work out what mitochondria a good donor needs to have for any given patient.



Unfortunately i…

Friday, 27 September, 2013

Unfortunately it’s not at all uncommon for moral and scientific questions to get tangled up in this way. Let me give an example from a different domain—perhaps the most blatant example of all: the question of whether life begins at conception or at birth. That looks like a scientific question, but it really has no scientific content whatsoever. We understand the process of embryonic development in great depth and exquisite detail—attaching the label “life” at some timepoint would not add the slightest iota to our scientific understanding. We all know, of course, what this question is really about: it’s about whether abortion should be permitted. It is really a purely moral question, disguised as a scientific question.

Why do moral questions get disguised as scientific questions? Basically because it is useful as a debating tactic. Arguments about right and wrong often depend on axioms that are not shared by other people, so they tend to degenerate ultimately into hand-waving and shouting. If an argument is about objective truth, though, everybody who knows all the facts ought in principle to get the same answer. I’m not saying that people who argue about the beginning of life do this deliberately or understand what they are doing—obviously they don’t. But the upshot is the same.

William Skaggs (in “How Could We Recognise Pain in an Octopus? Part 2“, Scientific American Blog)

Basically saying that you do need to understand science in order to form a conclusion about the morality of it, but the moral conclusion you form isn’t a scientific conclusion. It’s informed by science, but science can’t answer moral questions for you.


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