This Resistance Fighter Invented Dialysis in Nazi-Occupied Holland
One of the Netherlands’ most famous pieces of pop culture is “Soldier of Orange.” It’s the title of the country’s most celebrated war memoir, movie and epic stage musical, all of which detail the exploits of the nation’s resistance fighters during World War II.
Willem Johan Kolff was a member of the Dutch resistance, but he doesn’t rate a mention in the “Solider of Orange” canon. Yet his wartime toils in a rural backwater not only changed medicine, but the world.
Kolff had been a physician less than two years before Germany invaded the Netherlands in May 1940. He had been engaged in post-graduate studies at the University of Gronigen but withdrew because he refused to accommodate the demands of the Nazi occupiers. Kolff’s Jewish supervisor made an even starker choice: He committed suicide.
After his departure from the university, Kolff took a job managing a small hospital in Kampen. Located 50 miles from the heavily populated coastal region, the facility was far enough away from the prying eyes of Germans that not only could Kolff care for patients, he could hide fellow resistance fighters and even Jewish refugees in relative safety. Kolff coached many of them to feign convincing terminal illnesses so the Nazis would allow them to remain in the hospital.
Despite the demands of practicing medicine and resistance work, Kolff still found time to conduct research. He had been haunted and inspired when, not long before the Nazi invasion, one of his patients died in agony from kidney disease. Kolff wanted to find a way to save future patients.
He broke his problem down to a simple task: If he could remove 20 grams of urea from a patient’s blood in 24 hours, they would survive. He began experimenting with ways to filter blood and return it to a patient’s body. Since the war had ground all non-military manufacturing to a halt, he was mostly forced to make do with material he could find at the hospital and around Kampen. Kolff eventually built a device from a washing machine parts, juice cans, sausage casings, a valve from an old Ford automobile radiator, and even scrap from a downed German aircraft.
The world’s first dialysis machine was hardly imposing; it resembled a rotating drum for a bingo game or raffle. Yet it carried on the highly sophisticated task of moving a patient’s blood through a semi-permeable membrane (about a 50-foot length of sausage casings) into a saline solution that drew out urea while leaving the blood cells untouched.
In emigrating to the U.S. to practice medicine, Kolff's intent was twofold: Advocate for a wider adoption of dialysis, and work on new projects. He wildly succeeded at both.
Kolff began using the machine to treat patients in 1943, most of whom had lapsed into comas due to their kidney failure. But like most groundbreaking medical devices, it was not an immediate success. By the end of the war, Kolff had dialyzed more than a dozen patients, but all had died. He briefly suspended use of the device after the Allied invasion of Europe, but he continued to refine its operation and the administration of blood thinners to patients.
In September 1945, Kolff dialyzed another comatose patient, 67-year-old Sofia Maria Schafstadt. She regained consciousness after 11 hours, and would live well into the 1950s with Kolff’s assistance. Yet this triumph contained a dark irony: At the time of her treatment, Schafstadt had been imprisoned for collaborating with the Germans.
With a tattered Europe struggling to overcome the destruction of the war, Kolff and his family emigrated to the U.S. in 1950, where he began working for the Cleveland Clinic while undergoing the naturalization process so he could practice medicine in the U.S. His intent was twofold: Advocate for a wider adoption of dialysis, and work on new projects. He wildly succeeded at both.
By the mid-1950s, dialysis machines had become reliable and life-saving medical devices, and Kolff had become a U.S. citizen. About that time he invented a membrane oxygenator that could be used in heart bypass surgeries. This was a critical component of the heart-lung machine, which would make heart transplants possible and bypass surgeries routine. He also invented among the very first practical artificial hearts, which in 1957 kept a dog alive for 90 minutes.
Kolff moved to the University of Utah in 1967 to become director of its Institute for Biomedical Engineering. It was a promising time for such a move, as the first successful transplant of a donor heart to a human occurred that year. But he was interested in going a step further and creating an artificial heart for human use.
It took more than a decade of tinkering and research, but in 1982, a team of physicians and engineers led by Kolff succeeded in implanting the first artificial heart in dentist Barney Clark, whose failing health disqualified him from a heart transplant. Although Clark died in March 1983 after 112 days tethered to the device, that it kept him alive generated international headlines. While graduate student Robert Jarvik received the named credit for the heart, he was directly supervised by Kolff, whose various endeavors into artificial organ research at the University of Utah were segmented into numerous teams.
Forty years later, several artificial hearts have been approved for use by the Food and Drug Administration, although all are a “bridge” that allow patients to wait for a transplant.
Kolff continued researching and tinkering with biomedical devices – including artificial eyes and ears – until he retired in 1997 at the age of 86. When he died in 2009, the medical community acknowledged that he was not only a pioneer in biotechnology, but the “father” of artificial organs.
Story by Big Think
Our gut microbiome plays a substantial role in our health and well-being. Most research, however, focuses on bacteria, rather than the viruses that hide within them. Now, research from the University of Copenhagen, newly published in Nature Microbiology, found that people who live past age 100 have a greater diversity of bacteria-infecting viruses in their intestines than younger people. Furthermore, they found that the viruses are linked to changes in bacterial metabolism that may support mucosal integrity and resistance to pathogens.
The microbiota and aging
In the early 1970s, scientists discovered that the composition of our gut microbiota changes as we age. Recent studies have found that the changes are remarkably predictable and follow a pattern: The microbiota undergoes rapid, dramatic changes as toddlers transition to solid foods; further changes become less dramatic during childhood as the microbiota strikes a balance between the host and the environment; and as that balance is achieved, the microbiota remains mostly stable during our adult years (ages 18-60). However, that stability is lost as we enter our elderly years, and the microbiome undergoes dramatic reorganization. This discovery led scientists to question what causes this change and what effect it has on health.
Centenarians have a distinct gut community enriched in microorganisms that synthesize potent antimicrobial molecules that can kill multidrug-resistant pathogens.
“We are always eager to find out why some people live extremely long lives. Previous research has shown that the intestinal bacteria of old Japanese citizens produce brand-new molecules that make them resistant to pathogenic — that is, disease-promoting — microorganisms. And if their intestines are better protected against infection, well, then that is probably one of the things that cause them to live longer than others,” said Joachim Johansen, a researcher at the University of Copenhagen.
In 2021, a team of Japanese scientists set out to characterize the effect of this change on older people’s health. They specifically wanted to determine if people who lived to be over 100 years old — that is, centenarians — underwent changes that provided them with unique benefits. They discovered centenarians have a distinct gut community enriched in microorganisms that synthesize potent antimicrobial molecules that can kill multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. In other words, the late-life shift in microbiota reduces an older person’s susceptibility to common gut pathogens.
Viruses can change alter the genes of bacteria
Although the late-in-life microbiota change could be beneficial to health, it remained unclear what facilitated this shift. To solve this mystery, Johansen and his colleagues turned their attention to an often overlooked member of the microbiome: viruses. “Our intestines contain billions of viruses living inside bacteria, and they could not care less about human cells; instead, they infect the bacterial cells. And seeing as there are hundreds of different types of bacteria in our intestines, there are also lots of bacterial viruses,” said Simon Rasmussen, Johansen’s research advisor.
Centenarians had a more diverse virome, including previously undescribed viral genera.
For decades, scientists have explored the possibility of phage therapy — that is, using viruses that infect bacteria (called bacteriophages or simply phages) to kill pathogens. However, bacteriophages can also enhance the bacteria they infect. For example, they can provide genes that help their bacterial host attack other bacteria or provide new metabolic capabilities. Both of these can change which bacteria colonize the gut and, in turn, protect against certain disease states.
Intestinal viruses give bacteria new abilities
Johansen and his colleagues were interested in what types of viruses centenarians had in their gut and whether those viruses carried genes that altered metabolism. They compared fecal samples of healthy centenarians (100+ year-olds) with samples from younger patients (18-100 year-olds). They found that the centenarians had a more diverse virome, including previously undescribed viral genera.
They also revealed an enrichment of genes supporting key steps in the sulfate metabolic pathway. The authors speculate that this translates to increased levels of microbially derived sulfide, which may lead to health-promoting outcomes, such as supporting mucosal integrity and resistance to potential pathogens.
“We have learned that if a virus pays a bacterium a visit, it may actually strengthen the bacterium. The viruses we found in the healthy Japanese centenarians contained extra genes that could boost the bacteria,” said Johansen.
Simon Rasmussen added, “If you discover bacteria and viruses that have a positive effect on the human intestinal flora, the obvious next step is to find out whether only some or all of us have them. If we are able to get these bacteria and their viruses to move in with the people who do not have them, more people could benefit from them.”
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
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Embrace the mess: how to choose which scientists to trust
It’s no easy task these days for people to pick the scientists they should follow. According to a recent poll by NORC at the University of Chicago, only 39 percent of Americans have a "great deal" of confidence in the scientific community. The finding is similar to Pew research last year showing that 29 percent of Americans have this level of confidence in medical scientists.
Not helping: All the money in science. Just 20 percent of Pew’s survey respondents think scientists are transparent about conflicts of interest with industry. While this issue is common to many fields, the recent gold rush to foot the bill for research on therapies for healthy aging may be contributing to the overall sense of distrust. “There’s a feeling that at some point, the FDA may actually designate aging as a disease,” said Pam Maher, a neuroscientist who studies aging at Salk Institute. “That may be another impetus for a lot of these companies to start up.”
But partnering with companies is an important incentive for researchers across biomedical fields. Many scientists – with and without financial ties and incentives – are honest, transparent and doing important, inspiring work. I asked more than a dozen bioethicists and researchers in aging how to spot the scientists who are searching for the truth more than money, ego or fame.
Avoid Scientists Who Sound Overly Confident in messaging to the public. Some multi-talented scientists are adept at publishing in both top journals and media outlets. They’re great at dropping science without the confusing jargon, in ways the public can enjoy and learn from.
But do they talk in simple soundbites, painting scientific debates in pastels or black and white when colleagues use shades of gray? Maybe they crave your attention more than knowledge seeking. “When scientists speak in a very unnuanced way, that can be irresponsible,” said Josephine Johnston, a bioethicist at the Hastings Center.
Scientists should avoid exaggerations like “without a doubt” and even “we know” – unless they absolutely do. “I feel like there’s more and more hyperbole and attention seeking…[In aging research,] the loudest voices in the room are the fringe people,” said the biogenerontologist Matt Kaeberlein.
Separate Hype from Passion. Scientists should be, need to be passionate, Johnston explained. In the realm of aging, for example, Leonard Guarente, an MIT biologist and pioneer in the field of aging, told me about his belief that longer lifespans would make for a better world.
Instead of expecting scientists to be lab-dwelling robots, we should welcome their passion. It fuels scientific dedication and creativity. Fields like aging, AI and gene editing inspire the imaginations of the public and scientists alike. That’s not a bad thing.
But it does lay fertile ground for overstatements, such as claims by some that the first 1,000-year-old has already been born. If it sounds like sci-fi, it’s probably sci-fi.
Watch Out for Cult Behavior, some experts told me. Follow scientists who mix it up and engage in debates, said NYU bioethicist Arthur Caplan, not those who hang out only with researchers in the same ideological camp.
Look for whether they’re open to working with colleagues who don’t share their views. Through collaboration, they can resolve conflicting study results and data, said Danica Chen, a biologist at UC Berkeley. We should trust science as long as it doesn’t trust itself.
Messiness is Good. You want to find and follow scientists who’ve published research over the years that does not tell a clean story. “Our goal is to disprove our models,” Kaeberlein said. Scientific findings and views should zig and zag as their careers – and science – progress.
Follow scientists who write and talk publicly about new evidence that’s convinced them to reevaluate their own positions. Who embrace the inherent messiness of science – that’s the hallmark of an honest researcher.
The flipside is a very linear publishing history. Some scientists have a pet theory they’ve managed to support with more and more evidence over time, like a bricklayer gradually, flawlessly building the prettiest house in the neighborhood. Too pretty.
There’s a dark side to this charming simplicity: scientists sometimes try and succeed at engineering the very findings they’re hoping to get, said Charles Brenner, a biochemist at City of Hope National Medical Center.
These scientists “try to prove their model and ignore data that doesn’t fit their model because everybody likes a clean story,” Kaeberlein said. “People want to become famous,” said Samuel Klein, a biologist at Washington University. “So there’s always that bias to try to get positive results.”
Don’t Overvalue Credentials. Just because a scientist works at a top university doesn’t mean they’re completely trustworthy. “The institution means almost nothing,” Kaeberlein said.
Same goes for publishing in top journals, Kaeberlein added. “There’s an incentive structure that favors poor quality science and irreproducible results in high profile journals.”
Traditional proxies for credibility aren’t quite as reliable these days. Shortcuts don’t cut it anymore; you’ve got to scrutinize the actual research the scientist is producing. “You have to look at the literature and try to interpret it for yourself,” said Rafael de Cabo, a scientist at the National Institute on Aging, run by the U.S. National Institutes of Health. Or find journalists you trust to distill this information for you, Klein suggested.
Consider Company Ties. Companies can help scientists bring their research to the public more directly and efficiently than the slower grind of academia, where “the opportunities and challenges weren’t big enough for me,” said Kaeberlein, who left the University of Washington earlier this year.
"It’s generally not universities that can take technology through what we call the valley of death,” Brenner said. “There are rewards associated with taking risks.”
Many scientists are upfront about their financial conflicts of interest – sometimes out of necessity. “At a place like Duke, our conflicts of interest are very closely managed, said Matthew Hirschey, who researchers metabolism at Duke’s Molecular Physiology Institute. “We have to be incredibly explicit about our partnerships.”
But the willingness to disclose conflicts doesn’t necessarily mean the scientist is any less biased. Those conflicts can still affect their views and outcomes of their research, said Johnston, the Hastings bioethicist.
“The proof is in the pudding, and it’s got to be done by people who are not vested in making money off the results,” Klein said. Worth noting: even if scientists eschew companies, they’re almost always financially motivated to get grants for their research.
Bottom line: lots of scientists work for and with companies, and many are highly trustworthy leaders in their fields. But if a scientist is in thick with companies and checks some of the other boxes on this list, their views and research may be compromised.