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Blogging on Peer-Reviewed Research Perhaps - if you're a mouse...

A couple of nights ago TV3 news treated us to a breathless little item about an antibiotic compound, rapamycin, that appears to promote longevity in mice. If it was applied to people, said the reporter, we could live for another 20 years or so!

Gosh.

Well, I can think of at least a couple of problems with the hype surrounding this apparent medical breakthrough.

Rapamycin is an antibiotic secreted by bacteria found in the soil of Easter Island (Rapanui - hence its name), perhaps to ward off competing fungi and bacteria. Like many such compounds, after its discovery rapamycin was evaluated for potential medical uses, & found to act as an immunosuppressant in humans by inhibiting a cellular signalling pathway. These days it's used for that purpose in organ transplant patients, under the name sirolimus. And to be fair, the news item I saw did mention - at the very end - that rapamycin had the effect of suppressing the activity of the immune system. This means, of course, that patients using a drug like this have to be quite careful about picking up infections, because something that most of us might shrug off in a few days could well be lethal to them if left unchecked.

Which really does make me wonder - why the original hyped news story? I suspect it's linked to the publication this week of a Nature paper entitled Rapamycin fed late in life extends lifespan in genetically heterogeneous mice (Harrison et al. 2009). Certainly mice fed rapamycin did live longer - 14% longer  in terms of mean lifespan for females & 9% longer for males - than untreated animals. The researchers commented that this gain might reflect a reduction in incidence of cancer (which tends to increase with age) or a delay in aging, or both. (It wasn't a dietary effect because both experimental & contral animals had the same food.) I did wonder about the reduction of cancer, given the role of the immune system in checking at least some tumours, although it does appear that rapamycin is being tested for anti-tumour activity. And I wonder even more about the impact of an immune suppressant in terms of an increase in opportunistic infections - not a lot of point in living longer if by doing so you have to up your intake of antibiotics & antivirals...

And besides - we are not mice but men. And this is another reason for caution - it's not always the case that what works in an animal model can be applied to humans (hence the lengthy series of tests, first on animals & then on humans) required before medical drugs can be licensed for use). Take saccharin, for example.

Saccharin (aka aspartame) is an artificial non-calorie sweetener that was widely used in foods from the early 20th century. (When my father went of a bit of a health kick in the early 1970s, I remember him using what I thought the vile-tasting combination of saccharin and low-fat milk in his daily cups of tea. I think now it was probably the milk that did it for me - low-fat milk back then was possibly a different thing from what we have today.) However, when a 1977 study indicated that saccharin could cause cancer, the US FDA banned it from the food supply - a ban which was subsequently reversed.

This was because subsequent studies found that saccharin caused cancer only in rats, not other species tested (including monkeys, mice, & guinea pigs). And its effects seemed to be sex-linked - it caused bladder cancer in male rats, but not females. In other words, we can't always be sure that something that's carcinogenic in one species will have the same effect in another organism. In fact, by the 1990s 392 different chemicals had been tested as potential carcinogens in both rats & mice. While 226 caused cancer in one of those species, 42% of these carcinogens affected ONLY one species. So caution is necessary in generalising from one species to another - and this is just as true for the possible anti-aging effects of rapamycin. But then, that doesn't make for such exciting headlines.

Of course, dose is also important, something to remember when distinguishing between 'carcinogens' & how scientists test chemicals for carcinogenicity. In the original saccharin work, the rats were getting the equivalent of someone drinking around 800 cans of diet coke every day. (Think of the burps if someone even tried!) Researchers use such high doses in order to reduce the number of animals used in their trials. But substances can have different effects at different doses - drink enough water fast enough, at one time, & you will be very ill indeed (& possibly even dead).

I guess all this goes to reinforce the message that in science things are not as simple as the media often make out, and that the answers we get depend on the questions that we ask :-)

DE Harrison, R Strong, ZD Sharp, JF Nelson, CM Astle, K Flurkey, NL Nadon, JE Wilkinson, CS Carter, M Pahor, MA Javors, E Fernandez & RA Miller (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature published on-line 8 July 2009. doi: 10.1038/nature08221

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