Tag: Rapamycin

Found on Easter Island

Amazing what science can find out.

But while the science is brilliant the social implications are not so good. Read on!

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A billion-dollar drug was found in Easter Island soil – what scientists and companies owe the Indigenous people they studied

The Rapa Nui people are mostly invisible in the origin story of rapamycin. Posnov/Moment via Getty Images

Ted Powers, University of California, Davis

An antibiotic discovered on Easter Island in 1964 sparked a billion-dollar pharmaceutical success story. Yet the history told about this “miracle drug” has completely left out the people and politics that made its discovery possible.

Named after the island’s Indigenous name, Rapa Nui, the drug rapamycin was initially developed as an immunosuppressant to prevent organ transplant rejection and to improve the efficacy of stents to treat coronary artery disease. Its use has since expanded to treat various types of cancer, and researchers are currently exploring its potential to treat diabetes, neurodegenerative diseases and even aging. Indeed, studies raising rapamycin’s promise to extend lifespan or combat age-related diseases seem to be published almost daily. A PubMed search reveals over 59,000 journal articles that mention rapamycin, making it one of the most talked-about drugs in medicine.

Connected hexagonal structures
Chemical structure of rapamycin. Fvasconcellos/Wikimedia Commons

At the heart of rapamycin’s power lies its ability to inhibit a protein called the target of rapamycin kinase, or TOR. This protein acts as a master regulator of cell growth and metabolism. Together with other partner proteins, TOR controls how cells respond to nutrients, stress and environmental signals, thereby influencing major processes such as protein synthesis and immune function. Given its central role in these fundamental cellular activities, it is not surprising that cancer, metabolic disorders and age-related diseases are linked to the malfunction of TOR.

Despite being so ubiquitous in science and medicine, how rapamycin was discovered has remained largely unknown to the public. Many in the field are aware that scientists from the pharmaceutical company Ayerst Research Laboratories isolated the molecule from a soil sample containing the bacterium Streptomyces hydroscopicus in the mid-1970s. What is less well known is that this soil sample was collected as part of a Canadian-led mission to Rapa Nui in 1964, called the Medical Expedition to Easter Island, or METEI.

As a scientist who built my career around the effects of rapamycin on cells, I felt compelled to understand and share the human story underlying its origin. Learning about historian Jacalyn Duffin’s work on METEI completely changed how I and many of my colleagues view our own field.

Unearthing rapamycin’s complex legacy raises important questions about systemic bias in biomedical research and what pharmaceutical companies owe to the Indigenous lands from which they mine their blockbuster discoveries.

History of METEI

The Medical Expedition to Easter Island was the brainchild of a Canadian team comprised of surgeon Stanley Skoryna and bacteriologist Georges Nogrady. Their goal was to study how an isolated population adapted to environmental stress, and they believed the planned construction of an international airport on Easter Island offered a unique opportunity. They presumed that the airport would result in increased outside contact with the island’s population, resulting in changes in their health and wellness.

With funding from the World Health Organization and logistical support from the Royal Canadian Navy, METEI arrived in Rapa Nui in December 1964. Over the course of three months, the team conducted medical examinations on nearly all 1,000 island inhabitants, collecting biological samples and systematically surveying the island’s flora and fauna.

It was as part of these efforts that Nogrady gathered over 200 soil samples, one of which ended up containing the rapamycin-producing Streptomyces strain of bacteria.

It’s important to realize that the expedition’s primary objective was to study the Rapa Nui people as a sort of living laboratory. They encouraged participation through bribery by offering gifts, food and supplies, and through coercion by enlisting a long-serving Franciscan priest on the island to aid in recruitment. While the researchers’ intentions may have been honorable, it is nevertheless an example of scientific colonialism, where a team of white investigators choose to study a group of predominantly nonwhite subjects without their input, resulting in a power imbalance.

There was an inherent bias in the inception of METEI. For one, the researchers assumed the Rapa Nui had been relatively isolated from the rest of the world when there was in fact a long history of interactions with countries outside the island, beginning with reports from the early 1700s through the late 1800s.

METEI also assumed that the Rapa Nui were genetically homogeneous, ignoring the island’s complex history of migration, slavery and disease. For example, the modern population of Rapa Nui are mixed race, from both Polynesian and South American ancestors. The population also included survivors of the African slave trade who were returned to the island and brought with them diseases, including smallpox.

This miscalculation undermined one of METEI’s key research goals: to assess how genetics affect disease risk. While the team published a number of studies describing the different fauna associated with the Rapa Nui, their inability to develop a baseline is likely one reason why there was no follow-up study following the completion of the airport on Easter Island in 1967.

Giving credit where it is due

Omissions in the origin stories of rapamycin reflect common ethical blind spots in how scientific discoveries are remembered.

Georges Nogrady carried soil samples back from Rapa Nui, one of which eventually reached Ayerst Research Laboratories. There, Surendra Sehgal and his team isolated what was named rapamycin, ultimately bringing it to market in the late 1990s as the immunosuppressant Rapamune. While Sehgal’s persistence was key in keeping the project alive through corporate upheavals – going as far as to stash a culture at home – neither Nogrady nor the METEI was ever credited in his landmark publications.

Although rapamycin has generated billions of dollars in revenue, the Rapa Nui people have received no financial benefit to date. This raises questions about Indigenous rights and biopiracy, which is the commercialization of Indigenous knowledge.

Agreements like the United Nations’s 1992 Convention on Biological Diversity and the 2007 Declaration on the Rights of Indigenous Peoples aim to protect Indigenous claims to biological resources by encouraging countries to obtain consent and input from Indigenous people and provide redress for potential harms before starting projects. However, these principles were not in place during METEI’s time.

Close-up headshots of row of people wearing floral headdresses in a dim room
The Rapa Nui have received little to no acknowledgment for their role in the discovery of rapamycin. Esteban Felix/AP Photo

Some argue that because the bacteria that produces rapamycin has since been found in other locations, Easter Island’s soil was not uniquely essential to the drug’s discovery. Moreover, because the islanders did not use rapamycin or even know about its presence on the island, some have countered that it is not a resource that can be “stolen.”

However, the discovery of rapamycin on Rapa Nui set the foundation for all subsequent research and commercialization around the molecule, and this only happened because the people were the subjects of study. Formally recognizing and educating the public about the essential role the Rapa Nui played in the eventual discovery of rapamycin is key to compensating them for their contributions.

In recent years, the broader pharmaceutical industry has begun to recognize the importance of fair compensation for Indigenous contributions. Some companies have pledged to reinvest in communities where valuable natural products are sourced. However, for the Rapa Nui, pharmaceutical companies that have directly profited from rapamycin have not yet made such an acknowledgment.

Ultimately, METEI is a story of both scientific triumph and social ambiguities. While the discovery of rapamycin has transformed medicine, the expedition’s impact on the Rapa Nui people is more complicated. I believe issues of biomedical consent, scientific colonialism and overlooked contributions highlight the need for a more critical examination and awareness of the legacy of breakthrough scientific discoveries.

Ted Powers, Professor of Molecular and Cellular Biology, University of California, Davis

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Ted Powers explains in the last paragraph: “Ultimately, METEI is a story of both scientific triumph and social ambiguities.” Then goes on to say: “I believe issues of biomedical consent, scientific colonialism and overlooked contributions highlight the need for a more critical examination and awareness of the legacy of breakthrough scientific discoveries.”

If only it was simple!

We want them to live forever!

Here’s an anti-aging project that we all wish for a successful outcome.

Despite the fact that one of the very important items that we learn from dogs is the certainty of death, there is not a single dog carer who doesn’t want them to live much longer lives.

Today’s post is the republication of a recent science report over on Mother Nature Network concerning a drug, rapamycin, that is hoped may give our wonderful dogs several more healthy years of life. As always, republished within the generous terms of MNN.

We wish the scientists much luck in achieving this outcome, without any deleterious side effects.

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Anti-aging project aims to extend dogs’ life spans

Researchers hope a drug called rapamycin can give dogs several more healthy years of life.
By: Russell McLendon, December 4, 2015,

Although some dogs have lived as long as 29 years, canine life spans are typically closer to half that length. (Photo: Shutterstock)
Although some dogs have lived as long as 29 years, canine life spans are typically closer to half that length. (Photo: Shutterstock)

Living with a dog can help humans in lots of ways, from reducing stress and anxiety to lifting our spirits and making us laugh. Yet despite the abundance of benefits dogs offer, they also come with a notable drawback: Their life spans are much shorter than ours, forcing us to deal with the sadness of their deaths every 15 years or so.

Grieving for our dogs is just part of life, and in the big picture, it’s a small price to pay. But according to researchers at the University of Washington (UW), there may be a way to help our best friends stay with us — and stay healthy — a little longer.

Dog aging varies widely by size and breed, with smaller dogs typically maturing more quickly, yet also living a few years longer on average. It’s also common for mutts to outlive purebred dogs, thanks to the perks of higher genetic diversity. But while almost any dog is considered elderly by age 15, some have been known to nearly double their expected life spans — including Bluey, an Australian cattle dog who famously lived to see his 29th birthday last century.

And now researchers at UW’s Dog Aging Project (DAP) are working to bring similar longevity to canines of all kinds. In addition to performing “the first nationwide, large-scale longitudinal study of aging in pet dogs,” this project involves efforts to improve dogs’ “healthy life span” via therapies that already work in lab settings.

“To be clear, our goal is to extend the period of life in which dogs are healthy, not prolong the already difficult older years,” the project’s website explains. “Imagine what you could do with an additional two to five years with your beloved pet in the prime of his or her life. This is within our reach today.”

If it pans out, this may also aid ongoing research into extending the lives of other animals, including humans. But for now, the therapy is focused on dogs.

Researchers think rapamycin might increase a dog's healthy life span by up to 5 years. (Photo: Shutterstock)
Researchers think rapamycin might increase a dog’s healthy life span by up to 5 years. (Photo: Shutterstock)

Namely, they’re testing the FDA-approved drug rapamycin (aka sirolimus) on middle-aged dogs. High doses of rapamycin are already used in humans to fight cancer and prevent organ-transplant rejection, but at low doses, it has also been shown to slow aging and extend life span in several animals with few or no side effects. In mice, for example, the immunosuppressant can lengthen lives by up to 25 percent.

“If rapamycin has a similar effect in dogs — and it’s important to keep in mind we don’t know this yet — then a typical large dog could live 2 to 3 years longer, and a smaller dog might live 4 years longer,” the project’s organizers write. “More important than the extra years, however, is the improvement in overall health during aging that we expect rapamycin to provide.”

Rapamycin trials have already begun on 32 middle-aged golden retrievers, Labrador retrievers and German shepherds. Ranging from 6 to 9 years old, these dogs will spend several months on a low-dose rapamycin regimen in which researchers study age-related metrics like heart function, immune response, physical activity, body weight and cognitive measures. They’ll also follow these 32 dogs throughout the rest of their lives, looking for any significant changes in aging or life span.

And in phase two of the study, a second group of middle-aged dogs will enter a longer-term, low-dose rapamycin regimen “designed to optimize lifespan extension.” Based on mouse studies conducted both at UW and elsewhere, they anticipate the drug “could increase healthy lifespan of middle-aged dogs by 2-5 years or more.”

Rapamycin isn’t a miracle drug, however, and high doses have been linked to side effects like immune suppression and delayed wound healing. But as the DAP website argues, “these are greatly mitigated at the doses used to extend longevity, and both animal and human studies indicate that even mild adverse events are rare.”

Regular exercise and outdoor time are great ways to boost a dog's quality of life. (Photo: Shutterstock)
Regular exercise and outdoor time are great ways to boost a dog’s quality of life. (Photo: Shutterstock)

While the idea of extending dogs’ lives is exciting, it’s important not to let quantity of life overshadow quality of life. We may never have full control over how long our dogs live, but we can make sure they live well while they’re here.

A good reminder of this comes from Pegasus, a Great Dane rescued from unscrupulous breeders in South Africa when she was 4 weeks old. Suffering from a pigment deficiency often associated with blindness and deafness, Pegasus wasn’t expected to live very long. Filmmaker Dave Meinert adopted her anyway, and decided to film her daily as she grew up. In May 2015, he released a time-lapse movie (see below) of her reaching adulthood that quickly went viral. And as he explains in the video, Pegasus’ prognosis only helped the pair live every day like it was their last.

“I still don’t know how long she is going to live,” Meinert admits. “But right now is pretty great.”

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Watching the video offers the most beautiful, and powerful, reminder of the unconditional love that we can share with our dogs! What a gift they give us!

Wouldn’t we all love a few more years of happy and healthy life for our beloved dogs.