He Poisoned Himself to Find a Cure for Stomach Ulcers -- And Won a Nobel Prize
[Editor's Note: Welcome to Leaps of the Past, a new monthly column that spotlights the fascinating backstory behind a medical or scientific breakthrough from history.]
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Until about 40 years ago, ulcers were a mysterious – and sometimes deadly – ailment. Found in a person's stomach lining or intestine, ulcers are small sores that cause a variety of painful symptoms, such as vomiting, a burning or aching sensation, internal bleeding and stomach obstruction. Patients with ulcers suffered for years without a cure and sometimes even needed their stomachs completely removed to rid them from pain.
"To gastroenterologists, the concept of a germ causing ulcers was like saying the Earth is flat."
In the early 1980s, the majority of scientists thought that ulcers were caused by stress or poor diet. But a handful of scientists had a different theory: They believed that ulcers were caused by a corkscrew-shaped bacterium called Helicobacter pylori, or H. pylori for short. Robin Warren, a pathologist, and Barry Marshall, an internist, were the two pioneers of this theory, and the two teamed up to study H. pylori at the Royal Perth Hospital in 1981.
The pair started off by trying to culture the bacteria in the stomachs of patients with gastritis, an inflammation of the stomach lining and a precursor to developing an ulcer. Initially, the microbiologists involved in their clinical trial found no trace of the bacteria from patient samples – but after a few weeks, the microbiologists discovered that their lab techs had been throwing away the cultures before H. pylori could grow. "After that, we let the cultures grow longer and found 13 patients with duodenal ulcer," said Marshall in a later interview. "All of them had the bacteria."
Marshall and Warren also cultured H. pylori in the stomachs of patients with stomach cancer. They observed that "everybody with stomach cancer developed it on a background of gastritis. Whenever we found a person without Helicobacter, we couldn't find gastritis either." Marshall and Warren were convinced that H. pylori not only caused gastritis and peptic ulcers, but stomach cancer as well.
But when the team presented their findings at an annual meeting of the Royal Australasian College of Physicians in Perth, they were mostly met with skepticism. "To gastroenterologists, the concept of a germ causing ulcers was like saying the Earth is flat," Marshall said. "The idea was too weird."
Warren started treating his gastritis patients with antibiotics with great success – but other internists remained doubtful, continuing to treat their patients with antacids instead. Making matters more complicated, neither Warren nor Marshall could readily test their theory, since the pair only had lab mice at their disposal and H. pylori infects only humans and non-human primates, such as rhesus monkeys.
So Marshall took an unconventional approach. First, he underwent two tests to get a baseline reading of his stomach, which showed no presence of H. pylori. Then, Marshall took some H. pylori bacteria from a petri dish, mixed it with beef extract to create a broth, and gulped it down. If his theory was correct, a second gastric biopsy would show that his stomach was overrun with H. pylori bacteria, and a second endoscopy would show a painfully inflamed stomach – gastritis.
Less than a week later, Marshall started feeling sick. "I expected to develop an asymptomatic infection," he later said in an interview published in the Canadian Journal of Gastroenterology. "… [but] after five days, I started to have bloating and fullness after the evening meal, and my appetite decreased. My breath was bad and I vomited clear watery liquid, without acid, each morning."
At his wife's urging, Marshall started on a regimen of antibiotics to kill off the burgeoning bacteria, so a follow-up biopsy showed no signs of H. pylori. A follow-up endoscopy, however, showed "severe active gastritis" along with epithelial damage. This was the smoking gun other clinicians needed to believe that H. pylori caused gastritis and stomach cancer. When they began to treat their gastritis patients with antibiotics, the rate of peptic ulcers in the Australian population diminished by 70 percent.
Today, antibiotics are the standard of care for anyone afflicted with gastritis.
In 2005, Marshall and Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery of H. Pylori and its role in developing gastritis and peptic ulcers. "Thanks to the pioneering discovery by Marshall and Warren, peptic ulcer disease is no longer a chronic, frequently disabling condition, but a disease that can be cured by a short regimen of antibiotics and acid secretion inhibitors," the Nobel Prize Committee said.
Today, antibiotics are the standard of care for anyone afflicted with gastritis – and stomach cancer has been significantly reduced in the Western world.
Fast for Longevity, with Less Hunger, with Dr. Valter Longo
You’ve probably heard about intermittent fasting, where you don’t eat for about 16 hours each day and limit the window where you’re taking in food to the remaining eight hours.
But there’s another type of fasting, called a fasting-mimicking diet, with studies pointing to important benefits. For today’s podcast episode, I chatted with Dr. Valter Longo, a biogerontologist at the University of Southern California, about all kinds of fasting, and particularly the fasting-mimicking diet, which minimizes hunger as much as possible. Going without food for a period of time is an example of good stress: challenges that work at the cellular level to boost health and longevity.
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If you’ve ever spent more than a few minutes looking into fasting, you’ve almost certainly come upon Dr. Longo's name. He is the author of the bestselling book, The Longevity Diet, and the best known researcher of fasting-mimicking diets.
With intermittent fasting, your body might begin to switch up its fuel type. It's usually running on carbs you get from food, which gets turned into glucose, but without food, your liver starts making something called ketones, which are molecules that may benefit the body in a number of ways.
With the fasting-mimicking diet, you go for several days eating only types of food that, in a way, keep themselves secret from your body. So at the level of your cells, the body still thinks that it’s fasting. This is the best of both worlds – you’re not completely starving because you do take in some food, and you’re getting the boosts to health that come with letting a fast run longer than intermittent fasting. In this episode, Dr. Longo talks about the growing number of studies showing why this could be very advantageous for health, as long as you undertake the diet no more than a few times per year.
Dr. Longo is the director of the Longevity Institute at USC’s Leonard Davis School of Gerontology, and the director of the Longevity and Cancer program at the IFOM Institute of Molecular Oncology in Milan. In addition, he's the founder and president of the Create Cures Foundation in L.A., which focuses on nutrition for the prevention and treatment of major chronic illnesses. In 2016, he received the Glenn Award for Research on Aging for the discovery of genes and dietary interventions that regulate aging and prevent diseases. Dr. Longo received his PhD in biochemistry from UCLA and completed his postdoc in the neurobiology of aging and Alzheimer’s at USC.
Show links:
Create Cures Foundation, founded by Dr. Longo: www.createcures.org
Dr. Longo's Facebook: https://www.facebook.com/profvalterlongo/
Dr. Longo's Instagram: https://www.instagram.com/prof_valterlongo/
Dr. Longo's book: The Longevity Diet
The USC Longevity Institute: https://gero.usc.edu/longevity-institute/
Dr. Longo's research on nutrition, longevity and disease: https://pubmed.ncbi.nlm.nih.gov/35487190/
Dr. Longo's research on fasting mimicking diet and cancer: https://pubmed.ncbi.nlm.nih.gov/34707136/
Full list of Dr. Longo's studies: https://pubmed.ncbi.nlm.nih.gov/?term=Longo%2C+Valter%5BAuthor%5D&sort=date
Research on MCT oil and Alzheimer's: https://alz-journals.onlinelibrary.wiley.com/doi/f...
Keto Mojo device for measuring ketones
Silkworms with spider DNA spin silk stronger than Kevlar
Story by Freethink
The study and copying of nature’s models, systems, or elements to address complex human challenges is known as “biomimetics.” Five hundred years ago, an elderly Italian polymath spent months looking at the soaring flight of birds. The result was Leonardo da Vinci’s biomimetic Codex on the Flight of Birds, one of the foundational texts in the science of aerodynamics. It’s the science that elevated the Wright Brothers and has yet to peak.
Today, biomimetics is everywhere. Shark-inspired swimming trunks, gecko-inspired adhesives, and lotus-inspired water-repellents are all taken from observing the natural world. After millions of years of evolution, nature has quite a few tricks up its sleeve. They are tricks we can learn from. And now, thanks to some spider DNA and clever genetic engineering, we have another one to add to the list.
The elusive spider silk
We’ve known for a long time that spider silk is remarkable, in ways that synthetic fibers can’t emulate. Nylon is incredibly strong (it can support a lot of force), and Kevlar is incredibly tough (it can absorb a lot of force). But neither is both strong and tough. In all artificial polymeric fibers, strength and toughness are mutually exclusive, and so we pick the material best for the job and make do.
Spider silk, a natural polymeric fiber, breaks this rule. It is somehow both strong and tough. No surprise, then, that spider silk is a source of much study.The problem, though, is that spiders are incredibly hard to cultivate — let alone farm. If you put them together, they will attack and kill each other until only one or a few survive. If you put 100 spiders in an enclosed space, they will go about an aggressive, arachnocidal Hunger Games. You need to give each its own space and boundaries, and a spider hotel is hard and costly. Silkworms, on the other hand, are peaceful and productive. They’ll hang around all day to make the silk that has been used in textiles for centuries. But silkworm silk is fragile. It has very limited use.
The elusive – and lucrative – trick, then, would be to genetically engineer a silkworm to produce spider-quality silk. So far, efforts have been fruitless. That is, until now.
We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
Spider-silkworms
Junpeng Mi and his colleagues working at Donghua University, China, used CRISPR gene-editing technology to recode the silk-creating properties of a silkworm. First, they took genes from Araneus ventricosus, an East Asian orb-weaving spider known for its strong silk. Then they placed these complex genes – genes that involve more than 100 amino acids – into silkworm egg cells. (This description fails to capture how time-consuming, technical, and laborious this was; it’s a procedure that requires hundreds of thousands of microinjections.)
This had all been done before, and this had failed before. Where Mi and his team succeeded was using a concept called “localization.” Localization involves narrowing in on a very specific location in a genome. For this experiment, the team from Donghua University developed a “minimal basic structure model” of silkworm silk, which guided the genetic modifications. They wanted to make sure they had the exactly right transgenic spider silk proteins. Mi said that combining localization with this basic structure model “represents a significant departure from previous research.” And, judging only from the results, he might be right. Their “fibers exhibited impressive tensile strength (1,299 MPa) and toughness (319 MJ/m3), surpassing Kevlar’s toughness 6-fold.”
A world of super-materials
Mi’s research represents the bursting of a barrier. It opens up hugely important avenues for future biomimetic materials. As Mi puts it, “This groundbreaking achievement effectively resolves the scientific, technical, and engineering challenges that have hindered the commercialization of spider silk, positioning it as a viable alternative to commercially synthesized fibers like nylon and contributing to the advancement of ecological civilization.”
Around 60 percent of our clothing is made from synthetic fibers like nylon, polyester, and acrylic. These plastics are useful, but often bad for the environment. They shed into our waterways and sometimes damage wildlife. The production of these fibers is a source of greenhouse gas emissions. Now, we have a “sustainable, eco-friendly high-strength and ultra-tough alternative.” We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
We shouldn’t get carried away. This isn’t going to transform the textiles industry overnight. Gene-edited silkworms are still only going to produce a comparatively small amount of silk – even if farmed in the millions. But, as Mi himself concedes, this is only the beginning. If Mi’s localization and structure-model techniques are as remarkable as they seem, then this opens up the door to a great many supermaterials.
Nature continues to inspire. We had the bird, the gecko, and the shark. Now we have the spider-silkworm. What new secrets will we unravel in the future? And in what exciting ways will it change the world?