The Secrets of Easter Island
Imagine that you’re looking out at the ocean from a remote little island. Below, the waves beat rhythmically against the rocks. If you turn around, you will be greeted by a golden, rocky landscape with sporadic outcroppings of grass. There are no trees. Instead, the landscape is dominated by huge stone sculptures that keep watch over the island as if to guard its inhabitants.
The isolation is palpable – the nearest inhabited island is nearly 2,000km (1,242 miles) distant, and the mainland is even further away. You’re on Easter Island, where 8,000 inhabitants live surrounded by the Pacific Ocean as far as the eye can see. This isolated island may not be the most obvious place for our quest. There are no universities or biomedical laboratories, and the few scientists around are mostly interested in the stone sculptures called Moai. Myths claim that these huge people of stone have supernatural powers that can help fulfil any wish. Maybe someone once asked them for a longer life, because it turns out one of the ingredients is hiding in the very soil of Easter Island.
We know of this secret because a Canadian research expedition travelled to the isolated island in the 1960s to examine the soil. The Canadians were intrigued that islanders never got tetanus even though they were walking around barefoot. Tetanus is caused by a bacterial infection and is often associated with stepping on something sharp or a rupture of the skin. The bacterium involved releases a toxin into the bloodstream that makes all muscles contract to the point of being extremely painful, immobilising and even deadly.
Using soil samples from around Easter island, the Canadian researchers confirmed that there was no tetanus bacteria to be found. After that, their soil samples could easily have been thrown out or forgotten at the back of some dark university freezer. But instead, they ended up at the pharmaceutical company Ayerst Pharmaceutical, where their true secret was revealed: a bacterium called Streptomyces hygroscopicus. This bacterium produces a special molecule, which has been named ‘rapamycin’ after the indigenous name for Easter Island, Rapa Nui.
Rapamycin is actually a weapon used by this bacterium in the ancient battle against fungi. The molecule blocks – or inhibits – a specific protein complex in fungi called mTOR. Unfortunately, mTOR is not named after the God of Thunder, but just means ‘mechanistic target of rapamycin’. Despite the boring name, though, mTOR is a big deal. It is a kind of central command in the cell controlling growth. So the bacterium has an ingenious weapon at its disposal. Rapamycin dampens the growth of its enemy, fungi, and this gives the bacterium a leg-up in the fight for resources.
You and I don’t look much like fungi but they’re actually a distant relative of ours. That means we share many proteins with fungi, among them the ones making up mTOR. In fact, mTOR is the next step down our rabbit hole of growth signalling. First, we had growth hormone – inhibit it and prolong life. Then we reached IGF-1 – again, inhibit it and prolong life. And now we have mTOR. When IGF-1 binds to cell receptors, one of the main consequences is that the mTOR complex is activated. That means mTOR ‘wakes up’ and can in turn initiate many processes in the cell related to growth. For instance, production of new proteins and uptake of nutrients. Now, our version of mTOR is not identical to the ones in fungi but rapamycin still works the same way. So maybe you can guess where I’m going here. When scientists give rapamycin to laboratory animals it inhibits the growth-promoting mTOR and in turn extends their lives. Mice on rapamycin actually live twenty per cent longer than usual. That’s a pretty solid lifespan extension for a drug. If we transferred that twenty per cent difference directly to humans, that would be the difference between me dying while I was still a kindergartner, and me staying alive to write this book you’re now reading.
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Rapamycin is actually already approved for use in humans. The reason we’re not all using this drug to fight ageing already is that it was developed for a completely different purpose. The researchers from Ayerst Pharmaceutical knew nothing about its effects on ageing, but they discovered that rapamycin can be helpful during organ transplants. At high doses, rapamycin inhibits the immune system, which helps lower the risk that immune cells will recognise the new organ as something foreign and attack it with deadly consequences.
The good news is that this means rapamycin has been used for many years and we have ample safety data. We know there are no crazy side effects like brain damage or exploding. But that said, rapamycin at the doses used for organ transplantations is harsh on the body and not likely to be beneficial. Weakening the immune system is not good if you want to live a long life. Transplant patients using high doses of rapamycin are at a greater risk of infections, and, as the immune system is fighting with one arm tied behind its back, infections tend to become more severe as well.
Lower doses of rapamycin are more promising, though. Studies show that low doses can even improve immune function, perhaps due to hormesis. Despite this, we don’t know whether low doses of rapamycin can prolong life in humans. Yet. Several companies and research groups are currently working on various ways to find out. Most are trying to optimise rapamycin in some way, for instance by enhancing the effect, optimising dosing or working to limit side effects, all with the aim of making rapamycin the first widely used anti-ageing drug. Whether all this effort will pay off, time will tell. But besides companies and research groups, there are actually already various self-experimentalists who use rapamycin in an effort to fight ageing. Self-reports on the internet are positive but we probably wouldn’t hear about it if they weren’t. Unless you’re a little crazy, rapamycin is really more of a Hail Mary for now – that is, the long and risky last-minute pass in American football that is only fit for times of desperation. Instead, we should continue down our rabbit hole.
The sad thing about our best friends is that they don’t live very long. If we’re trying to extend our own lives, why not our dogs’ lives too? In fact, dogs are a great opportunity for ageing research. It is much cheaper and easier for scientists to set up animal trials than human ones, which means we can catch two birds with one stone. We can help our best friends live longer and at the same time get valuable lessons for future studies in humans.
In one dog study, for instance, scientists are giving rapamycin to forty family dogs. So far, the results are great, and the dogs have improved heart function compared to the beginning of the trial. Whether they will also live longer, time will tell.