Rapamycin: The “fountain of youth” from Easter Island?

Howard Fischer
Uppsala, Sweden

 

Moai heads emerging from the mountainside of a volcano on Easter Island, the island being where rapamycin was discovered

Moais at Rano Raraku volcano. Photo by Rivi, 2006, on Wikimedia. CC BY-SA 3.0.

“We know more about the movement of the celestial bodies than about the soil underfoot.”
– Leonardo DaVinci

 

In November 1964, the Canadian naval vessel HMCS Cape Scott left Halifax, Nova Scotia, to make a medical evaluation of Easter Island. The expedition was led by surgeon Stanley Skoryna and medical microbiologist Georges Nógrády,1,2 and consisted of thirty-eight researchers and more than 200 crew members. The goal of the expedition was to find the causes of human cancers associated with a modern lifestyle. They sought a place where the population was fully isolated from the outside world, where they could study health before and after the risks introduced by different foods, new carcinogens, and microbes. Such an isolated population was only to be found on Easter Island.

Easter Island belongs to Chile and is 3500 km from the Chilean coast. It was “discovered” by the Dutch explorer Jacob Roggeveen on Easter Sunday, 1722.3 Later, it was visited by James Cook, Peruvian slavecatchers, and by the Norwegian Thor Heyerdahl. Contact with the outside world was devastating for the islanders—it brought smallpox, tuberculosis, and leprosy. One-third of the population (1400 people) had been abducted in the 1800s by slavers. When the Canadian expedition arrived, there were 967 people on Easter Island. The only outside contact was a yearly visit by a Chilean cargo ship, which brought needed supplies. Soon this isolation was to end. Chile planned to build an airport on the island. The researchers sped up their plans when they learned about it. They got private funding and a grant from the World Health Organization to study the health of all the islanders and the island’s biosphere. Not much was known about the islanders’ lifestyles. In fact, more was known about Easter Island’s 30-foot-tall statues.4

On arrival, the researchers found that the islanders were not that “isolated.” They had radios, cigarettes, and cattle. The expedition published little after it was understood that the people were not isolated, non-exposed people. The whole expedition could have been “a fiasco” were it not for Dr. Nógrády.5 He took blood and saliva samples, and throat, nose, and rectal swabs from nearly the entire population.6 He also took blood and fecal samples from the cattle, as well as milk samples from the cows to test for bovine tuberculosis. He performed electrocardiograms on all adults over fifty. Adults received dental and chest X-rays, and children had hand and wrist X-rays to measure bone growth. During their two-month stay on the island, the mostly Canadian physicians provided medical care to the islanders, whose physician had recently left.7

Nógrády noted that there were more horses than people on the island. Where there are horses, there are tetanus organisms in the soil. The islanders went barefoot and had abrasions from the sharp rocks over which they walked. Here was a combination that “usually guaranteed a tetanus infection,”8 but the people did not get infected. Nógrády questioned whether this was because of something in the soil. He divided the island’s entire surface into sampling areas and collected 5000 soil samples. Only one sample contained tetanus spores, which supported the idea that some substance in the soil destroyed the spores.

In one soil sample Nógrády found a variety of the bacterium Streptomyces hygroscopicum, which produced an unknown substance. Not having the resources to go further, he gave the organism to two microbiologists who worked for Ayerst Pharmaceuticals. They isolated, crystallized, and purified the substance. This substance was the strongest antifungal agent ever seen. Its effectiveness against Candida species was greater than that of the very potent (and toxic) amphotericin B.9

They published their findings in 1975 and called the substance “rapamycin,” after the islanders’ Polynesian name for their island, Rapa Nui. When rapamycin was used as an antifungal agent, one of its side effects was suppression of the immune system. It was studied as a possible cancer treatment, but did not lend itself to intravenous use and was abandoned. Years later, Surendra Nath Sehgal, one of the two Ayerst microbiologists who first studied rapamycin—and always hoped it would have a medical use—studied its immunosuppressant effect.

Rapamycin inhibits antigen-induced T- and B- immune cell proliferation. It is a macrolide antibiotic now used to coat coronary artery stents, prevent organ transplant rejection, treat vascular tumors, and treat the rare disease lymphangioleiomyomatosis,10 in which excessive smooth muscle growth invades all lung structures and leads to progressive respiratory failure. It has also been found effective in treating autoimmune lymphoproliferative syndrome,11 a rare genetic disease marked by a persistent, unneeded, lymphocyte reaction to a resolved infection.

In the realm of speculation, rapamycin has even been found to be a “promising candidate to slow down aging and extend the lifespan.”12 Administration of rapamycin can extend the lifespan of mice,13 in one study14 by 9–15%. Twenty-four “middle-aged healthy dogs” given low-dose rapamycin for ten weeks had improved systolic and diastolic function after another trial.15

Although rapamycin cream removes wrinkles from people’s hands,16 the wrinkle in this story has just begun.

 

References

  1. Karin Lodin. “Rapamycin: Den osannolika historien om en medicinsk upptäck,” Läkartidningen, 119, 2022.
  2. Darren Hobby. “A treasure from a barren island: the discovery of rapamycin,” Clinical Kidney Journal, 15(10), 2022. doi: 10.1093/ckj/sfac116.
  3. V Rao. “Serendipity in splendid isolation: rapamycin,” Blood, 127(1), 2016.
  4. Rao. “Serendipity.”
  5. Lodin. “Osannolika historien.”
  6. David Stipp. “A new path to longevity,” Sci Am, 306(1), 2012.
  7. James Boutilier. “METEI: A Canadian medical expedition to Easter Island 1964-65,” Rapa Nui Journal: Journal of the Easter Island Foundation, 6(2), 1992.
  8. Lodin. “Osannolika historien.”
  9. Mohamed Mohamed et al. “Rapamycin golden jubilee and still the miraculous drug: a potent immunosuppressant, antitumor, rejuvenative agent, and potential contributor in COVID-19 treatment,”Bioresour Bioprogress, 9(1), 2022.
  10. “Sirolimus.” Wikipedia.
  11. Rao. “Serendipity.”
  12. Lodin. “Osannolika historien.”
  13. Stipp. “Longevity.”
  14. William Swindell. “Rapamycin in mice,” Aging, 9(9), 2017.
  15. Silvan Urfer et al. “A randomized controlled trial to establish the effects of short-term rapamycin treatment in 24 middle-aged companion dogs,” Geroscience, 39(2), 2017.
  16. Kristen Fuller. “Is rapamycin the new ‘fountain of youth’?” Psychology Today, 2021.

The National Film Board of Canada produced a short film (1966) about the medical expedition. “Island Observed” shows expedition members and islanders in a 1960s style documentary-travelogue.

 


 

HOWARD FISCHER, M.D., was a professor of pediatrics at Wayne State University School of Medicine, Detroit, Michigan.

 

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