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Two Australian ethicists on gene editing of human embryos

Wednesday, 27 September, 2017

An article was published today in The Conversation titled “UK gene editing breakthrough could land an Aussie in jail for 15 years: here’s why our laws need to catch up“. It was authored by two Australian ethicists, Christopher Gyngell and Julian Savulescu. who argue that gene editing for research purposes should be legal. The key argument is as follows

Many are worried about the long-term implications of such gene editing research, and claim it sets us on a path to “designer” babies. But in the UK where the Nikian study was performed, the laws make a distinction between the research and reproductive applications of gene editing.

Under the UK’s regulatory regime all reproductive applications of gene editing are banned. Such a distinction is also made in Australian laws between the use of cloning for reproductive purposes (which is prohibited) and cloning for research (which is permitted). Making a distinction between reproductive applications and research enables clearly beneficial research to proceed while preventing controversial applications.

I think this makes perfect sense. Many of the arguments used to justify a ban on gene editing of human embryos do not apply when those embryos are never implanted in a womb (and those that do apply to research on genetically-engineered embryos already apply to current research on non-edited embryos). So this distinction between reproduction and research is a sensible one to advocate.

There is, however, a telling implication in one section:

But such research is, at the very least, premature. Most experts agree gene editing science is far too immature for us to be thinking about reproductive applications in humans. But the technique can today be fruitfully used to study development, as the Niakan study shows.

The implication is that one day reproductive applications will be possible. And both authors have been on record advocating for gene editing of human embryos for reproductive purposes:

Germline Gene Editing (GGE) has enormous potential both as a research tool and a therapeutic intervention. While other types of gene editing are relatively uncontroversial, GGE has been strongly resisted. In this article, we analyse the ethical arguments for and against pursuing GGE by allowing and funding its development. We argue there is a strong case for pursuing GGE for the prevention of disease. We then examine objections that have been raised against pursuing GGE and argue that these fail. We conclude that the moral case in favour of pursuing GGE is stronger than the case against. This suggests that pursuing GGE is morally permissible and indeed morally desirable.

I happen to totally agree with these authors on both research and reproductive use of genetic engineering, but I know that people who oppose the reproductive use of genetic engineering will argue against this using a slippery slope argument. And given the two ethicists arguing for the meaningfulness of the distinction between reproductive and research uses of genetic engineering advocate for both sides of that distinction, it will be hard to refute that argument.

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No, gene editing won’t ruin human evolution

Friday, 13 January, 2017

An article published in TIME magazine by Jim Kozubek, titled “How Gene Editing Could Ruin Human Evolution” basically argues that it’s too risky to edit our genes. I’d agree with most of these risks, but none of these risks are insurmountable and none of them are good arguments for preventing gene editing entirely.

Genes are complicated, but not impossibly complicated

It is definitely true that most traits are controlled by many genes, and that many genes control many traits. As Kozubek says:

Biology is robust against breakdown. It straddles risk like a money manager, and that straddling of risk over the entire genome is one reason there are so few single “targets” for many of these psychological and cognitive traits. Indeed, many of these genetic variants may be pleiotropic, meaning they have different, often unrelated effects in different cells or tissues

This does certainly complicate any potential gene editing, as many areas of the genome would need to be edited and these might have unintended consequences. But this added complexity is still solvable. If gene editing technology is good enough, there’s no reason we can’t edit half a dozen areas of the genome instead of just one.

Furthermore, if one gene does have different effects in different tissues, that just increases the complexity of the genetic engineering problem but still doesn’t make it impossible. With somatic genetic engineering, one could target the genetic edit to just one organ (like the brain), without it effecting that gene in the rest of the body. One could also potentially duplicate the gene entirely and edit only one copy, plus adjust the regulatory sequences so that the edited gene is the only one expressed in the tissue of interest and the unedited gene is the one expressed in other tissues.

Gene editing isn’t about what is right, but what is right for each individual

Kozubek seems to to come very close to saying that scientists don’t understand evolution and that genetic diseases don’t exist, when he says:

Second, scientists tend to think of men as machines, genes as their broken parts and variations in life as problems to be solved—aberrations outside the normal curve. This assumes there is a right way for genes to be. In reality, Darwin showed us that evolution does not progress toward an ideal model or a more perfect form, but instead is a work of tinkering toward adaptation in local niches. Nowhere in nature does it say how a gene should function.

Genes have a fitness, which refers to how successfully those genes allow the organism to reproduce in a particular environment. But we, as humans, also can place value judgement on certain phenotypes (traits an organism possess) that may or may not correlate with fitness. For instance, a genetic disease that causes an increased chance of an early death decreases fitness and is something most humans don’t want. But sometimes a gene might increase your fitness, perhaps by making you super fertile, but you as a human still don’t like that trait. And some traits we might want, like to be able to eat as much we want without getting fat, may decrease our fitness in some environments where food is scarce or increase when food is plentiful. Basically, there’s not really a correlation between what evolution is aiming for and what we humans are aiming for.

The argument that scientists are trying to restore genes to their natural, correct or ‘healthy’ state is a fundamental misunderstanding of what most proponents of genetic engineering want. We want to be able to give people the freedom to choose what genes they, or their children, have. Indeed, this is one fundamental issue with the notion that we should only use genetic engineering to make people healthy but not do anything like enhancement: there isn’t universal agreement on what healthy is. What many of us might think as natural or ‘healthy, such as being able to hear, might be considered by some as an unwanted disability.

Diversity does not trump autonomy

Similar to the first argument, Kozubek argues that certain things thought of as diseases or disabilities can offer advantages in fitness in certain contexts.

Furthermore, genetic variants that predispose us to risk or supposed weaknesses are precisely the same ones that turn out to have small fitness advantages (they make us better at numbers, more sensitive, alter concentration…). This is one reason I am a “neurodiversity advocate.” Evolution works at the margins, and it does so through trade-offs: Often, you don’t get an advantage without risking a disadvantage. This is not trivial.

It is undoubtedly true that all advantages come with disadvantages, just as all drugs come with side-effects. As I alluded to above, a gene that increases risk of obesity in modern society might offer a significant advantage in a food-scarce environment. A genetic enhancement that allows humans to see in ultraviolet light might require allowing so much UV light into the eye that it increases the risk of macular degeneration. An enhancement that increases wound healing by preventing scar formation might increase the risk of infection.

One key point to this, however, is that these are all environmentally dependent. Our environment now is very different to what it was when we did most of our evolving, as we now have a lot more food, the ability to produce sunglasses to block UV light and enough antiseptics and antibiotics to prevent infections when they occur. I simply don’t see how somebody could argue that the mutation in the CFTR gene, which causes cystic fibrosis if you have two copies but resistance to tuberculosis if you have one copy, is a worthwhile trade-off in Western nations where tuberculosis is very rare.

The other key point point is that people should be informed of the risks and benefits and allowed to make their own choices for gene editing (within a broad ethical framework, of course), just as we do with pharmaceutical treatments. For example, some might see an increased risk of autism as a fair cost for greater mathematical ability, whereas others may not. Even if having a diverse set of genes in the population benefits the species somehow, I certainly don’t think we can use this to justify forcing people to keep, or pass on to their children, the genes they have. Are you really going to cite the need for genetic diversity in human evolution as a reason to deny a patient a gene therapy they desperately desire? Are you going to make somebody deaf in the hope they become a genius composer like Beethoven?

Evolution will continue

The final point, relating to the  later points, is that genetic engineering will break evolution:

And genetic risk variants remain in the population because they’re advantageous to certain people, given the right genetic background or conditions. Those risk variants are speculating—evolution, always and forever, takes chances.

The problem with this is that it assumes that gene editing will somehow decrease the genetic diversity in the population.  As I briefly mentioned a while back in response to an SMBC comic, there is no reason to think this would be true. Yes, we’re likely to get rid of many of the genetic diseases that we can, because most people see those as bad things. But there are many traits where there is little consensus over which is better, and may companies may have different techniques to produce these traits, so diversity of these genes may increase.

We’re also likely to transfer genes from across the natural world (like fluorescent proteins from jellyfish) or create entirely new genes. This process of adding and editing our genome is vastly faster than waiting for mutations, so there will be ample variation in the population.

Human evolution will definitely be different, but it will still continue. But that’s no different to any other treatment or technological intervention that changes how often we pass on our genes. Whenever humans treat the sick or help our injured, we’re altering the progress of evolution. But this doesn’t make medicine or technology bad. In fact, these things are probably pretty good, even if they change evolution. And so, even if it changes our human evolution, I think gene editing will be pretty good too.

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Is germline genetic enhancement better than somatic genetic enhancement?

Monday, 25 July, 2016

design2

The various types of human genetic modifications can be divided along two lines – the therapy-enhancement divide and the somatic-germline divide. The former refers to whether a modification is therapeutic or enhances and the latter refers to whether a modification is affects children (by affecting reproductive cells or whole embryos) or just affects the body (without affecting reproductive cells).

We are therefore left with four categories (Resnik 2000):

1. Somatic gene therapy (SGT)
2. Germline gene therapy (GLGT)
3. Somatic genetic enhancement (SGE)
4. Germline genetic enhancement (GLGE)

What I want to explore is whether, in a world where adults can opt to be genetically enhanced, there would ever be any benefit to germline genetic enhancement. That is, can we avoid all the ethical issues with germline engineering and genetically enhance only consenting adults?

I think there are three general reasons why it might be beneficial to genetically modify the germline, rather than waiting until people are old enough to consent. (However, note that some of these benefits might be achieved by somatic engineering in infancy, which would essentially create a ‘designer baby’ while leaving the germline untouched. This wouldn’t side-step any ethical issues around consent so I’m ignoring this possibility)

1. GLGE could be in the child’s best interests

The vast majority of enhancements people would seek in adulthood would also be things people would want their children to have as they grow up. It is likely also that children themselves would choose (if they were legally able to consent) to go through school with improved intelligence, to play with better reflexes or to be physically attractive while experiencing the first teenage romance. And that’s not mentioning things like resistance to disease or faster wound healing that exist on the cusp of the therapy-enhancement divide.

2. GLGE may be technically superior to SGE

Some modifications may be technically difficult to achieve in an already developed body consisting of billions of cells, and may prove much easier when only single celled gamete or zygote is modified. It might be difficult to get the DNA to every cell that needs to be modified, and some modifications might, at least initially, only prove possible if the genes are edited before the body’s organs and systems develop.

However, it’s quite possible that an enhancement which was only possible with germline methods would 18 years later could be achieved – or even surpassed – by somatic methods. In this case, if you imagine persons could give consent at age 18 for somatic gene enhancement, then any advantages of GLGE over SGE would only be temporary ones during childhood and at the age of consent everyone would be on an equal playing field again.

A fast pace of biotechnological progress would also mean that inherited germline enhancements might be little benefit to future generations compared to somatic enhancements that exist by that time. If a mobile phone could survive over generations, you’d still not pass it down to your children because it would be hopelessly outdated. So barring major disasters that set humanity back into a dystopia with little technology, passing your enhancements on to your children would only be a benefit if germline enhancements remain far superior to somatic enhancements over that time.

3. GLGE can affect motivations

Though a person choosing a somatic enhancement will choose based on their wants, the effects of a germline enhancement can directly affect what it is that a person will want (once they are old enough to choose). To paraphrase German philosopher Arthur Schopenhauer: “Man can choose to do what he wants but he cannot choose what it is that he wills”. I should point out that genes cannot control everything, but they can have some affect on the future choices a person will make.

This means that narrow-focus enhancements which are desired by only a few, or even undesirable to anyone who could choose, may be only be possible by way of modifying the germline (or somatic modifications in children). Portrayals of germline enhancement in science fiction often involve armies of soldiers or slaves engineered from conception or childhood to not only excel at their designated role but also to enjoy being perfectly obedient. These portrayals often involve growth rate enhancements to get around the reality that such such soldiers or slaves would take decades to ‘manufacture’. In practice, anyone with the power, resources and decades worth of time to commission and care for their own soldiers or slaves would either be ethically prepared to use somatic techniques to modify the desires of adults or be otherwise be able to pay/bribe adults to do the same job.

Because people sometimes make choices they regret or that aren’t in their best interests, there may be benefits to altering a person’s motivations. It may be reasonable to desire that your children make ethically good and smart choices once they become adults. So, if any germline enhancements can improve logical reasoning and moral motivations, children gifted with such enhancements will be in a better place to make wise choices, including when selecting which somatic enhancements they pursue as adults.

Conclusion

I think there are some very good practical reasons to pursue genetic enhancement of the germline and of children. There may still be ethical reasons to oppose it, but I think the potential gains are large enough some at least will feel it ethically acceptable (or ethically right) to pursue germline genetic enhancement even in a world where somatic genetic enhancement was possible. If parents are pursuing enhancements out of love, they may be prepared to do ethically questionable things to achieve what they believe is best for their children.

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Superhuman reflexes

Tuesday, 24 May, 2016

neo-dodging-bullets

Though perhaps best exampled by Neo in the 1999 film The Matrix, superhuman reflexes to some extent are an attribute of so many superheroes that it’s basically a default superpower. But just how realistic would it be for us to expect genetic enhancement to enable people to have such quick reflexes? That’s what I’m going to attempt to answer in this post.

First we need to define some terms. Biologically, a reflex is a simple and automatic response to a stimulus. If you touch something painfully hot you will automatically withdraw your hand, so it’s a reflex. You can still learn or unlearn a reflex, but the important thing is that a reflex is done without thinking: your brain isn’t really involved. If, out of the corner of your eye, you see something falling off a table and quickly grab it, that’s not a reflex. You don’t automatically grab any falling object, and if that object was a knife you’d leap away from the table rather than try to grab it, which is a sure sign your brain is processing the situation rather than it being automatic.

As you’re probably aware, there is a delay between the stimulus (e.g. touching something painful) and the response (e.g. pulling your hand away) of a reflex. The main factor determining this delay is how fast the signal can travel along the nerve cells (neurons) from the hand, to the spinal cord, and back down to the muscles (there’s a slight delay as the signals cross the synapse from one neuron to another, but its contribution is minor). In humans, the neuronal conduction velocity varies between different nerves, but let’s just look at the ones sending the signal from the hand to the spinal cord (which travel at about 50 meters per second) and those that send signals from the spinal cord down to the muscles (which travel at about 100 meters per second). So travelling a meter along your arm and then another meter back means the fastest possible reflex would occur after 30ms (it’s a bit slower than this in reality, but let’s go with this).

So the question now turns to how we can get neurons to conduct signals faster. There are three tactics that animals use to do this. The first is making the neurons thicker in diameter, which is why the neurons that control our muscles are the some of the thickest in our body at up to 20 micrometers. But some animals, like squid, have neurons that are are 500 micrometers, but our neurons are still 4 times faster. This is because animals like humans have a second strategy, which is to insulate the neurons with a substance called myelin. This allows the neurons to be much smaller while still being really fast, which is essential for packing as many brain cells as possible into a small skull. But the record for the fastest neuronal conductional velocity in the animal kingdom belongs to a penaeid shrimp, which not only has fairly big neurons (at 120 microns) and myelin insulation but also has a third mechanism where in between the neuron and the insulation is a gap filled with super conductive salty fluid that further speeds up how fast the signals can travel (for a discussion of these mechanisms, see Castelfranco & Hartline 2016). Their neurons can send signal at 200 meters per second, twice the speed of our fasted human neurons.

Given that we need to fit our nerves through the holes our vertebrae (the neural foramina), we can’t really rely on increasing the size of our neurons. And we’re already fairly well insulated. Maybe we could use some shortcuts like the penaeid shrimp do, but without the increase in size it’s unlikely we’d get to the velocities of 200 meters per second the shrimp achieve. Any genetic enhancement to human reflexes is realistically going to be much more modest.

But let’s say we do manage to double the speed of our neurons, what would that be like? Well, a simple doubling of conduction speed would more or less halve our reaction time. Our reflexes would be faster, but so too would the speed at which we could think and perceive things. Our sense of time wouldn’t change, but given the limitations of our current neurons the closest we can come to seeing what the world would look like with double speed neurons is watching a video at half speed (which you can easily do on YouTube). This would give a massive advantage in martial arts and many sports like sprinting, fencing, tennis, football and baseball.

But would this magnitude of reflex enhancement be enough to dodge a bullet? Almost certainly not, and not least because we have only speed up the nerves while leaving the muscles as slow as ever. The simplest test of visual reaction time of the sort you’d need to dodge a bullet is the ruler drop test, where you try to catch a measuring stick as quickly as you can after noticing it has been dropped. This therefore captures both the ability to visually detect movement and perform a simple movement (a pinch grip) in response. The average reaction time, on this test, for athletes is about 200ms. Even if your reaction time has been enhanced to be half that of a normal man, a Glock 17 has a muzzle velocity of 375m/s so in the 100ms it takes you to react by moving your muscles the bullet would have traveled 37.5 meters. The gunman would have to be quite a distance away to allow you to duck behind cover as soon as you see the gunshot. And the bullet would still be traveling too fast for you to see, because we only enhanced reflexes not your visual perception speed (which would involve making photoreceptors in the retina work more rapidly), so you would still be attempting to dodge a bullet that you cannot actually see.

So genetic enhancement of reflexes has many practical limitations in comparison to the fanciful portrayals we see in fiction, but would still be immensely advantageous in competitive sport or hand-to-hand combat where every millisecond matters.

In order to get extremely rapid reflexes, we’d need to do away with the limits of biological systems altogether and transmit signals through electronic circuits, which could a million times faster. When it comes to quick reaction times, robots or perhaps cyborgs will have a massive advantage. At the moment robots already have faster “reflexes” than humans, but the human brain still outperforms artificial intelligence if the stimulus requires complicated visual or spatial processing or if performing a novel movement requiring coordination. But maybe one day, robots won’t only be beating us at chess but also fencing, tennis, baseball and martial arts. And by then, maybe we’ll be able to implant that technology into our own body, and truly gain reflexes faster than anything the biological world can offer.

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UK approves experimental genetic engineering of human embryos

Saturday, 6 February, 2016

Good news from the United Kingdom, with the UK Human Fertilisation and Embryology Authority (HFEA) being the world’s first regulatory authority to explicitly approve genetic engineering of human embryos. There are other countries who haven’t banned the technology, but this is the first one to purposefully allow it.

Of course, these won’t be designer babies, as the experiment must cease after the embryos are about 256 cells (about two weeks old). But this is necessary to study the effects of the technology so that maybe one day it will actually be safe enough to use for therapeutic or reproductive purposes. See more about the story in Nature News, Wired and The Guardian.

You can also read some opposition to the decision, with Craig Venter writing in Time and Donna Dickenson in The Telegraph. Both pretty much argue that we don’t yet know enough and should be cautious, and with this I agree. But unless we take the few cautious steps forward by doing the research, we’ll never know enough to be able to edit human genomes. Somehow I think that’s precisely the outcome the opponents want.

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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.

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A comic I saw

Sunday, 4 October, 2015

THE SHOW MUST GO ON!

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.