The Dirty Drug and the Ice Cream Tub. Rapamycin Discovery Out!

• Rapamycin Discovery: Explore how this Easter Island discovery became a medical marvel in its potential as a longevity remedy.
• Sehgal’s Save: Dr. Sehgal’s fight secures rapamycin’s future as a powerful drug.
• mTOR Mystery: Unveiling how rapamycin targets cell growth, hinting at its genuine and affordable potential for aging and disease.
• Island Lessons: The story connects Rapa Nui’s past with rapamycin’s impact, revealing how scarcity shapes survival.

The Radiolab podcast uses special storytelling techniques to take listeners on fascinating adventures. In this episode, curiosity takes the lead, sparking a craving to know more. Radiolab contributor and narrator Avir Mitra takes us on an amazing journey. It begins with a sample of soil taken from a patch of land in a far-off part of the globe. Yes, soil, but not just any dirt—this is the rapamycin discovery, a substance that has since saved many lives. But wait, there’s more. This soil sample may also hold the key to living longer with better health.

The podcast introduces key characters, like the immigrant scientist Suren Sehgal and his family. You will be gripped by the occasions that led to the drug’s discovery and development. Mitra’s storytelling skills combine historical background, personal tales, and scientific breakthroughs. His creative method offers a captivating, understandable narrative of how a powerful molecule revolutionized biology and medicine.

Ajai Sehgal’s Upbringing and Family Journey

Ajai Sehgal, the son of Suren Sehgal (a gifted microbiologist), talks about an important moment in his life. It was 1982, and Ajai was serving in Germany when a telegram came through informing him that his father had been relocated with his work. This meant that the whole family had to pack up and move to the USA.

Ajai, being the good son that he was, returned home to help with the stressful move. It was a time when he learned that his normally law-abiding father had taken a huge risk by deciding to smuggle laboratory substances across the US border.

“My dad is stealing this stuff from his lab… I went to the grocery store, bought some dry ice, and we put this compound into an ice cream container, then into another container.”

Ajai Sehgal

But before we get into what happened next, let’s wind the clock back to the 1960s’

The Mystery of Rapamycin’s Easter Island Origins

Radiolab co-host Latif Nasser explains the rapamycin discovery and its impact.

In the 1960s, a Canadian mission to Easter Island collected a soil sample, not knowing the astonishing discovery it would lead to. Back in Canada, the microbiologist Suren Sehgal and his colleagues studied the sample. What they uncovered was a clear, white, crystalline compound unlike anything previously encountered. This was their rapamycin discovery, also known as Rapa, a substance that would change the course of medical history.

“We isolated a compound that was not seen before, and it had a very interesting molecular structure.”

Suren Sehgal recounted

Unveiling a Remarkable Compound

Suren and his team had made a critical discovery in their Easter Island soil sample. The substance—named rapamycin (Rapa) after the Polynesian name for the island, Rapa Nui—possessed a special ability to halt the growth of immune cells and fungi. Being able to prevent cell division implied important therapeutic uses.

This amazing finding signaled the start of a truly monumental scientific leap. Indeed, research on the compound’s full potential is ongoing.

Putting the Rapamycin Discovery to the Test

Ajai Sehgal draws our attention to his father’s rigorous testing process. He tells how Suren and his team began extensive testing on rapamycin. Initial simple tests against fungal diseases showed promise, leading to more intricate experiments on dogs and lab mice. Suren’s dedication even extended to treating a friend’s wife, who had a persistent fungal illness. The treatment was a total success, proving Rapa’s therapeutic potential.

“It’s fascinating to think about how a simple soil sample could lead to such a groundbreaking discovery in medicine.”

Host Julia Longoria

Roadblocks at Ayerst Laboratories

Ajai describes his father’s sheer determination during a challenging period.

In the early 1980s, Ayerst Laboratories decided to close its Montreal office, discarding years of research and rapamycin samples. Despite this, Suren remained excited about the drug’s potential. He covertly saved the samples from the garbage, storing them in his freezer and ensuring the continuation of rapamycin’s research.

“We have to save this; I have a feeling about this drug.”

Ajai remembers his father saying

Suren Sehgal’s Tenacity and the Secret Trip

Uma Sehgal—the wife of Suren— recalls the family’s involvement in this crucial task.

Uma describes the lengths her husband, Suren, took to save the samples. He placed them in a yogurt container with a “DO NOT EAT” sticker. He then wrapped them in dry ice, ready to smuggle his treasure across the US border. This daring move, along with a belief in the drug’s potential, saved it from being lost forever.

“He brought it home and said, Uma, put this in the freezer.”

Uma Sehgal

Suren Vision for Rapamycin

Suren knew rapamycin had great potential. It was first known for fighting fungi, but even then, it had some challenges as it suppressed the immune system. But Suren saw potential beyond that early discovery. He thought rapamycin could change medicine in big ways. This belief really inspired him to keep working on it and support research. Thanks to his efforts, rapamycin is now widely used in organ transplants and other medical areas.

Rapa’s Transformation: From Fungus Fighter to Lifesaver

Suren Sehgal was right about rapamycin’s potential beyond a potent antifungal. In the 1980s, doctors discovered it could do much more. It helped people who had organ transplants by stopping their bodies from rejecting the new organs. Later, heart doctors used it to coat stents (tiny tubes used to help keep arteries open), with great outcomes. So, rapamycin went from fighting fungus to saving lives!

Student David Sabatini Joins the Rapamycin Puzzle

In 1992, medical student David Sabatini was looking for a dissertation topic, when he heard about the rapamycin discovery. It caught his interest right away, so he took on the challenge of studying the substance. Thanks to his research, experts now grasp how Rapa interacts with a key protein called mTOR. This finding was a major breakthrough. It has expanded the uses of rapamycin and improved scientific understanding of its processes.

Understanding mTOR and Rapamycin’s Grip

Thanks to Sabatini’s research, it became evident that mTOR was an essential protein in cells that senses nutrition and regulates growth. The beauty of rapamycin is that it tricks mTOR into slowing down cell growth. This process contributes to the explanation of why rapamycin is so successful in treating some illnesses and reducing organ rejection.

mTOR: The Food and Growth Gatekeeper

We can think of mTOR as the building site’s general contractor. The decision to stop growing or continue growing is made based on signals regarding the availability of nutrients like glucose and protein. Rapamycin blindfolds mTOR, making it think there is a lack of resources when it enters the picture. As a result, the cell stops growing and begins to concentrate on repair. Because of this ingenious mechanism, Rapa exhibits great efficacy in treating medical conditions like those mentioned earlier and even possible lifespan extension.

From Research to Reality: FDA Approval

That initial rapamycin discovery had to overcome many obstacles and years of devoted research before it was given the credit it deserved. When the FDA first authorized Rapa in 1999 for medical use, it was primarily concerned with preventing organ rejection in recipients of organ transplants. With this approval, the drug went from being a promising lab molecule to an essential tool in modern medicine, demonstrating its ability to save lives. This was a momentous milestone.

Suren Sehgal’s Personal Fight

Uma Sehgal shares insights into Suren’s courageous decision to use rapamycin.

Suren Sehgal was diagnosed with colon cancer and given six months to live, so he began taking rapamycin. It worked, and at one point, he stopped taking the drug to test its efficacy. The cancer returned, confirming Rapa’s impact. Suren’s self-experiment reinforced his commitment to his work, allowing him to live years beyond his prognosis.

Rapamycin’s Surprise Effect: Extending Lifespans?

Matt Kaeberlein, a professor at the University of Washington, discusses the potential implications of rapamycin on aging.

The question now was: Could the rapamycin discovery also hold the key to a longer life? Scientists are finding that this drug—first used to prevent organ rejection—may also slow down aging. In studies with mice, Rapa extended lifespans with all treatments, i.e., different doses and durations. The drug has since shown promise in other animal species, too. Researchers are now exploring its potential to delay aging in humans.

“There’s tons of data in mice that rapamycin can improve cognitive aging in mice.”

Kaeberlein

Rapamycin’s Impact on Aging: Beyond Treatment

David Sabatini explains how rapamycin affects cellular processes.

Rapa’s value in organ transplantation is undeniable, but it could also become a wonder drug in the fight against aging. It works by making cells believe they’re starving, which triggers a process called autophagy. The cells then begin to purge the damaged parts and other waste materials that have accumulated over time. This process not only extends life but also reduces or even prevents age-related illnesses.

So far, Rapa has improved the longevity of lab mice and other animal species. These exciting findings may soon revolutionize how humans approach age-related health.

“It tricks cells in your body into thinking there’s low nutrients when nutrients are there.”

David S

Island Statues and Rapamycin: A Powerful Analogy

Sergio Mata’u Rapu is a native of Easter Island. With his vast knowledge of the territory, he offers a lesson on the statues and a cultural perspective on resilience.

The giant statues of Easter Island were built during times of plenty, in stark contrast to the smaller, fragile statues built during times of scarcity. This mirrors how rapamycin works. When nutrients are plentiful, cells grow and become much stronger. But when nutrients are scarce, Rapa enables cells to clean and repair themselves. Both of these situations show resilience and adaptability, underscoring the far-reaching impact of this amazing drug.

“Having close to nothing is also positive in some ways. It reminds you of what you have.”

Sergio Mata’u Rapu said

Wrapping Up and Reflecting on the Rapamycin Discovery

Co-host Latif Nasser reflects on the broader implications of the rapamycin discovery.

Considering Suren Sehgal’s experience with rapamycin, it’s evident that his tenacity transformed medicine. His account is one of real passion and inventiveness. From smuggling the compound to witnessing it save lives, it’s an incredible story. Moreover, the discovery of rapamycin’s capacity to lengthen life expectancies is only getting started. It gives us all new hope for a healthier future.

“I think the story of Rapa Nui is a metaphor for what rapamycin does in your body. It reminds you of what you have.”

Radiolab contributor and narrator Avir Mitra says