The giant and mysterious stone heads looking down imposingly upon inhabitants and visitors to Easter Island were the immortal legacy of the various chieftains of the Rapa Nui people. Maybe those chieftains were onto something as Easter Island has newfound fame within scientific circles for an indigenous bacteria which produces the life extending compound Rapamycin.

 

The discovery of Rapamycin follows a series of fortuitous events which, were it not for the dedication of some key scientists, may have remained hidden to the world for many years to come.

 

Our story starts in 1964, when microbiologist Georges Nógrády collected soil samples as part of a Canadian expedition to Rapa Nui. Georges was seeking to understand why the indigenous population weren’t infected with Tetanus, spores of which should have been common in areas that had horses which outnumbered humans on the island. However, of the seventy samples Georges collected, only one contained tetanus spores.

 

As a good scientist, rather than ditch the samples, Georges sent them to Ayerst Pharmaceuticals in Montreal, whose team of scientists isolated the bacterium yielding the Rapamycin compound. The researchers discovered that Rapamycin was a powerful immunosuppressant, but more importantly from a life extending perspective, also prevented cells from multiplying.

Ageing is essentially the degradation of a cell’s ability to multiply into healthy cells of the same type over time, leading to age related complications and diseases such as tumours. Therefore, the discovery of Rapamycin opened the doors to a raft of anti-cancer drugs.

 

Then in 1982 Ayerst closed down its Montreal lab, laying off most of its staff with the remainder moving to New Jersey. All work on Rapamycin ceased and due to difficulties in formulating the drug for clinical trials, all knowledge would have remained in a dusty archive and lain forgotten. However, one man stepped in to keep the dream alive, Microbiologist Suren Seghal. Aware of the potential fate Rapamycin faced when the lab shut down, and convinced of the drugs potential, Sughel conducted a heist of the bacterium and took its containing vials home to be stored for six years in his freezer labelled ‘Do Not Eat’.

 

suren-seghal

Suren Seghal – Microbiologist and pioneer in Rapamycin research

In 1988, Rapamycin came out of the cold as Sughel convinced his new employers, Wyeth, of the possibilities Rapamycin presented. In the rising era of immunosuppressants and their ability to prevent rejection of organ transplants, Rapamycin garnered new found attention. As well as being formulated into immunosuppressants, the compound, its derivatives named Rapalogs, was also turned into an anti-cancer drug in 2007 named Torisel.

 

So how does Rapamycin work? The answer lies in a protein commonly called mTOR (mechanistic Target Of Rapamycin). In the way that a musical conductor regulates his orchestra, mTOR is responsible for directing a cell’s ability to grow, divide, survive, shutdown and pass on information. Rapamycin latches onto this protein and inhibits its ability to do all these. mTOR is also responsible for coordinating the growth of the body’s immune cells which likely account for its immunosupressant abilities.

 

Separately to the study of Rapamycin, genetic research was also being conducted on mTORs which found that repressing the proteins activity led to the increased survivability of yeast, nematode worms and fruit flies. When these results were shared, other researchers armed with the knowledge that Rapamycin had the same effect on the protein, began testing it on mice, administering it by drug. The results were amazing; the lifespan of mice given the drug was extended by 9% for the males and 14% for females.

 

Testing continues and even humans have undergone trials. Whilst it is far too soon to tell whether the drug has extended anyones life yet, the elderly patients administered the drug and then given a flu vaccination, produced much more flu antibodies than those who weren’t given the drug.

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There’s much more work to be done. As it stands, the biggest concern is that due to its immunosuppressant properties, the popping of a Rapamycin pill a day to keep death away is likely to increase the risk of infection. That said, all this is very exciting and with big Pharma working around the clock to find the next big marketable drug, we’re bound to see the pill of youth within our lifetime.

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