Archive for the ‘Genetic Modification’ Category

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Boosting brainpower

Thursday, 14 May, 2009

The practical and ethical issues with intelligence enhancement are receiving more attention, with a recent article in New Scientist titled “Will designer brains divide humanity“.

For the most part, the article is quite basic, but I have an issue with one part in particular:

The next stage of brainpower enhancement could be technological – through genetic engineering or brain prostheses. Because the gene variants pivotal to intellectual brilliance have yet to be discovered, boosting brainpower by altering genes may still be some way off, or even impossible. Prostheses are much closer, especially as the technology for wiring brains into computers is already being tested.

This is none other than cybernetic favoritism! I mean sure, genes effecting intelligence aren’t obvious, but it’s also not obvious how and where to interface a brain chip to increase intelligence. And though neural prostheses are being tested, no neural prosthesis has increased any aspect of intelligence in any brain, whereas there have been 33 genetic alterations that increase the learning and memory of mice (not to mention that all the differences in intelligence between animals are genetic in origin). Considering the annoyance of having surgery for neural implants compared to the ease of a simple injection for genetic modification, I would personally put my money on the genetic enhancement of intelligence. Nonetheless, both avenues should be pursued, and might eventually complement one another.

Onto the ethical issues discussed in the article, most are fairly basic. Starting with human dignity, referring to comments made by Dietrich Birnbacher, a philosopher at the University of Düsseldorf in Germany:

One potential problem arises from altering what we consider to be “normal”: the dangers are similar to the social pressure to conform to idealised forms of beauty, physique or sporting ability that we see today. People without enhancement could come to see themselves as failures, have lower self-esteem or even be discriminated against by those whose brains have been enhanced, Birnbacher says.

These concerns are all quite valid, but aren’t necessarily impossible barriers. If enhancement technology was supported by the government, then no people wanting such technology would be left without it. And the discrimination I will deal with in a minute, after looking at the next section:

The perception that some people are giving themselves an unfair advantage over everyone else by “enhancing” their brains would be socially divisive, says John Dupré at the University of Exeter, UK. “Anyone can read to their kids or play them music, but put a piece of software in their heads, and that’s seen as unfair,” he says. As Dupré sees it, the possibility of two completely different human species eventually developing is “a legitimate worry”.

I do actually worry about enhancement being socially divisive, but I am not sure this would occur only by discrimination of the enhanced towards the un-enhanced. As I have argued previously, it’s entirely possible that the enhanced will be viewed as unnatural disgraces to humanity, and the pure, natural humans would discriminate against them because of it.

The rest of the article deals with issues such as brain plasticity, evolution and epigenetics. These are not particularly relevant to any ethical concerns and neither will they significantly enhance the intelligence of the average reader of this blog, so I’m not going to address them here.

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

Saturday, 11 April, 2009

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.

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Enhancing memory and learning in mice

Monday, 23 March, 2009

Recently, a review article by Yong‑Seok Lee and Alcino J. Silva was published in Nature Reviews Neuroscience, with the title ‘The molecular and cellular biology of enhanced cognition‘. If you are lucky enough to have a subscription, or know a library that can get this journal article for you, do.

The review lists 33 genetic modifications that lead to some level of enhanced memory and learning in mice. It also discuses the general methods by which these modifications work, focussing on enhancement of a form of neuronal plasticity known as long-term potentiation. NMDA receptors, the role of calcium as a messenger and the various enzymes and transcription factors that are recruited to create the cellular basis of a memory. The review also discusses other mechanisms, like epigenetics, growth factors, the involvement of glia, and also presynaptic signalling. Finally, the review looks at caveats in the current research in cognitive enhancement.

The authors also make a nod in the direction of bioethics, saying:

[I]t is also important to stress that memory enhancing manipulations raise a number of ethical issues that are outside of the scope of this Review, but that merit careful consideration and discussion170,171.

For interests sake, references 170 and 171 are:

170: Rose, S. P. ‘Smart drugs’: do they work? Are they ethical? Will they be legal? Nature Rev. Neurosci. 3, 975–979 (2002).
171. Farah, M. J. et al. Neurocognitive enhancement: what can we do and what should we do? Nature Rev. Neurosci. 5, 421–425 (2004).

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Homo evolutis – the backlash

Monday, 9 February, 2009

The old speciation argument has raised its head again, with Juan Enriquez (Chairman and CEO of a company called Biotechonomy), giving a talk at TED (Technology Engineering Design) this year. He argued that

humanity is on the verge of becoming a new and utterly unique species, which he dubs Homo Evolutis.

Now, I’ve no issue with him stating speciation may occur, because it might. What I feel is wrong, and what also rubbed a lot of other people the wrong way, is his reasoning for why. He was portrayed as saying:

What makes this species so unique is that it “takes direct and deliberate control over the evolution of the species.”

This sort of talk made George Dvorsky, a fellow futurist, quite uncomfortable. And it made biologist P.Z. Myers quite cranky at futurists.

The point is, Enriquez appears to not quite know what the usual definition of a biological species actually is. In strict biological terms, a species is defined as a “group of actually or potentially interbreeding natural populations, which is reproductively isolated from other such groups”. Having brain-interfaced cybernetic wings or genetic enhancements to your somatic cells won’t make you a new species any more than having a wooden peg leg and drinking rum make you a new species of human (Homo pirata?). To become a new species, you must be able to reproduce with some others, but not with natural humans. This specific desire to control evolution directly, as Juan is said to have discussed, would not do this. At most, it could reprsent some sort of difference in opinion within our one species – between humans who were for enhancement technology, and those who were against. It would be hard enough to even say this represents a new subspecies or even race of humans.

In Enriquez’s defense, after some degree of ‘taking deliberate control over evolution’, it is possible that this could lead to speciation. It could be as simple as restricting breeding through totalitarian reproductive regulations, as in the eugenics of the past, isolating a number of humans from one another until speciation occurred. Alternatively, genetic modifications to the germline could introduce a genetic incompatibility between engineered humans and normal humans (the most obvious example being the addition of an extra chromosome). It’s even possible for some form of simple modification to a structure involved in reproduction (i.e. genitalia) to introduce a physical incompatibility prohibiting easy mating. But merely taking such control over evolution doesn’t imply you actually guide evolution to the degree that speciation occurs.

All that said, I do feel it is difficult for the species concept to be applied rigidly to technologically-assisted reproduction. The definition of species specifies the population must be a natural population, so as to exclude inter-species matings caused by human intervention. But can human intervention be excluded from the definition of a human species? Is it natural for humans to technologically-assist in their own reproduction? These are important questions, because one must consider the advances in genetic technology which come to mind in this sort of dicussion; it is difficult to imagine how any human could not be able to potentially reproduce with any other human given access to sufficient technology. Yet by the same token, such technology may allow Homo sapiens to potentially interbreed with chimpanzees or gorillas (or even farther afield genetically!), so should we extend our species then? How much technological assistance do we allow into our definition of interbreeding?

These same sort of questions come up every time somebody dreams up a new idea for what humans will become, be it Homo superior, Homo artificialis, Homo novus or Homo evolutis.

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‘Genetic engineering’ implies an act of engineering

Friday, 6 February, 2009

The term genetic engineering, according to Wiktionary, is the “the deliberate modification of the genetic structure of an organism.” Other definitions, especially those used by biotechnology regulators and lawmakers, often specify that genetic engineering refers only to modifications made by recombinant DNA technology, but I prefer the more broad usage. Genetic engineering is, as the name implies, the engineering of genetic material in living cells.

There are two processes which, I believe,  are mistakenly called genetic engineering: artificial selection (aka selective breeding) and PGD (pre-implantation genetic diagnosis, also known as embryo screening). Artificial selection refers to selective breeding of organisms with the desired traits (and, it is hoped, the desired genes) in order to breed more organisms with the desired traits. Pre-implantation genetic diagnosis is the term for determining the genetic makeup of human embryos before they are implanted for IVF, and usually implies choosing to implant the healthiest or more desirable of embryos.

These are both selective processes, and are often likened to genetic engineering, but often for different reasons. Selective breeding is often considered to be genetic engineering by those defending genetic modification of crops and livestock, as surely the traditional farming methods of the past couldn’t have been wrong (*cough cough*). On the other hand, PGD is often maligned as genetic engineering by those opposed to the idea, as surely genetic engineering of humans is to be vehemently opposed (*cough cough*). In fact, some proponents of human enhancement could even make both leaps at once, claiming that genetic engineering is just like the evolutionary processes of nature (only faster) and therefore that techniques like PGD are likewise just speeding up the natural selection of human embryos that occurs naturally.

But I strongly believe that a selective process is not a form of engineering. In most cases of selection, genomes are not first intentionally modified by human actions. Instead, modifications happen mostly randomly due to mutations and the natural forms of genetic recombination that occur during reproduction. This provides the variety on which breeders, farmers and parents/reproductive specialists can act to select which will be kept and which will be discarded. So, while these selective processes are intentional modifications of the proportions of certain genetic material in a population, they do not entail any intentional modification the genetic material of any individual organism. Selection is no more an act of genetic engineering than going shopping is an act of manufacturing.

Further, I’d be inclined to argue that cloning is also not a form of genetic engineering, as the genetic material is replicated intact rather than modified. Cloning is really just a very effective form of selective breeding, where every piece of genetic material within a particular cell is replicated in the cloned organism. Cloning, therefore, is no more an act of genetic engineering than using copy+paste is an act of writing.

All of this is really just semantics and word games, because it doesn’t really affect the ethical discussions on these issues. Equivocation is avoided, certainly, but appeals to the past, appeals to tradition, slippery slope arguments or arguments rooted in repugnance are also dubious moral arguments. Every new technology will have consequences, some similar to those seen in other technologies and some completely novel. Each technology should be evaluated individually, with comparisons used only when necessary and not stretched beyond reasonable limits.

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Significant minority favour designer babies

Wednesday, 28 January, 2009

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.

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Lose weight with gene therapy

Monday, 12 January, 2009

Want to eat fatty food and tell your body to not bother storing that fat all over your body? Well, research recently published in the advanced online publication of  Nature Medicine has done just that, albeit in mice. They created knock-out mice, missing the gene Pla2g16, which codes for the enzyme adipocyte phospholipase A2. This enzyme, abbreviated to AdPLA, and other members of the PLA  (phospholipase A2) family, catalyse the first – and rate limiting – step in the production of eicosanoids, which are signalling molecules. As this enzyme was expressed in adipocytes (which are fat cells), the researchers hypothesised it would be involved in producing molecules that control adipose-specific processes, like lipolysis (fat breakdown).

It turns out they were right. Genetically obese (ob/ob) mice were found to be producing far more AdPLA and diabetic mice increased their AdPLA after receiving insulin. So, this molecules was sure to be involved in metabolising fat somehow.

The researchers made AdPLA-null mice, which lacked the gene to produce this enzyme. They fed these mouse a diet high in fat, and did the same to wild-type mice (which still had the gene). The two groups were not different in weight at weaning, but after 64 weeks of that diet, the AdPLA-null mice weighed an average of 39.1±0.2g in comparison to the average weight of 73.7±0.3g for wild-type mice. But, they didn’t eat any less (in terms of grams of food per gram of body weight). Further, the researchers knocked out the gene in a line of genetically obese mouse, and despite them eating more than any other mouse line, they were only slightly more overweight than wild-type mouse on an ordinary diet. And, the AdPLA mice weren’t exercising any more than the other mice either. A picture is given below:

Shows a genetically obese ob/ob mouse, and one with the same obese genes but with the AdPLA2 gene knocked out

A mouse with a genetic defiency of the appetite-supressor hormone leptin (left), and one with the same leptin-deficiency but with the AdPLA2 gene knocked out (right). From Jaworski et al, 2009

Further analysis revealed that this reduction in body mass was correlated with a reduction in the size of fat cells in AbPLA-null mice. This, in turn, was likely caused by the increased level of lipolysis and increased triacylglycerol production and turnover.  Therefore, the hypothesis is that AbPLA is involved in the regulation of lipolysis by catalysing a key step in the production of prostaglandins, and specifically PGE2. PGE2 has an anti-lipolytic, meaning it promotes fat to be stored rather than released. So, remove the enzyme that produces of PGE2, and the fat just isn’t stored.

In addition, the AbPLA-null mice were more insulin resistant, which makes sense. Insulin is responsible for stimulating the uptake and storage of food, so if mice are eating more and not gaining weight, they must be less sensitive to insulin. The study indicated AdPLA-null mice had 74% reduced insulin-stimulated glucose uptake in adipose tissue. In other words, they were eating lots of food, but it wasn’t being stored as fat. Where is it going? Researchers found the AdPLA-null mice had 37% increased oxidative metabolism, and therefore required more oxygen. This means that the fat cells are using the fat up, burning it rather than storing it. In addition, the researchers hypothesise that the free-fatty acids produced by the higher rate of lipolysis may not be significantly greater, as the fat cells aren’t taking up the fat, even before they get the chance to release it at the faster rate.

So, what does all this mean? The researchers hint at it:

Many questions remain regarding the effect of partial or total PLA2G16 gene ablation in humans

What questions? Well, for one, does this research mean that I can eat fatty foods and yet still not gain weight? I’d say it’s promising. Gene therapy seems a bit drastic at this early stage, so in the near future perhaps RNA interference, or a drug inhibiting this enzyme, will be a useful and reversible treatment for obesity. But, in the future, people will surely be tweaking their genes to ensure they remain at an optimum weight, regardless of how much more than the required intake of food is consumed. Bring on the deep-fried ice cream!

Reference: Jaworski et al, “AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency” Nature Medicine, AOP 11 January 2009 DOI: 10.1038/nm.1904