This Resistance Fighter Invented Dialysis in Nazi-Occupied Holland
When Willem Johan Kolff invented dialysis, the "father" of artificial organs was just getting started.
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.
Urinary tract infections account for more than 8 million trips to the doctor each year.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
A surgeon at Massachusetts General Hospital prepares a pig organ for transplant.
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.