Archive for January, 2009

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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

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

Saturday, 10 January, 2009

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.