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Prescription poop is here: FDA approves fecal slurry for unshakeable diarrhea

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Enlarge / Laboratory technicians in France prepare stool to treat patients with serious colon infections by fecal microbiota transplantation (FMT), also known as gut flora transplant (GFT) in 2019.

For the first time, the US Food and Drug Administration has granted approval for a feces-based microbial treatment, which is used to prevent a recurring diarrheal infection that can become life-threatening.

The approval, announced Wednesday, is years in the making. Researchers have strained to harness the protective qualities of the complex, diverse, yet variable microbial communities found in healthy people’s intestines and stool. Early on, rich fecal matter proved useful for restoring balance and blocking infection in those whose microbiomes have been disturbed—a state called dysbiosis, which can occur from disease and/or use of antibiotic drugs. But, our understanding of what makes a microbiome healthy, functional, and protective remains incomplete.

Doctors, meanwhile, pushed ahead, informally trying an array of methods to transplant fecal microbiota from healthy donors to the guts of patients—via enemas, tubes through the nose, and oral poop-packed capsules. Fecal microbiota transplants (FMTs) have been used to treat various ailments, from obesity to irritable bowel syndrome, to mixed success. But it quickly became apparent that FMTs were most readily effective at preventing recurrent infection from Clostridioides difficile (C. difficile or just C. diff).

C. diff bacteria cause diarrhea and significant inflammation in the colon. Severe infections can be life-threatening. In people with dysbiosis, C. diff can proliferate in the intestines, producing toxins that can lead to organ failure. Older people, those who are hospitalized, and people with weakened immune systems are particularly susceptible to C. diff, which can recur over and over in some vulnerable patients. In the US, C. diff infections are associated with up to 30,000 deaths per year.

With the pressing need for effective treatments against C. diff, regulators were forced to wade through the mucky issue of regulating and standardizing something as unruly and myriad as fecal matter. It also led to years of microbial sleuthing, synthetic slurries, stool donations, and clinical trials.

Solid success

Now, a product has finally floated to the top: Rebyota, a blend of donor stool, saline, and laxative solution given in a single treatment as an enema. It’s teeming with heavily screened intestinal microbes at a concentration of 10,000,000 live organisms per milliliter. Its owner, Switzerland-based Ferring Pharmaceuticals, screens donors and their donated stool for a long list of infectious pathogens and other health factors.

In a Phase III clinical trial involving 262 participants—the results of which were published last month—Ferring’s scientists reported that treatment with Rebyota led to a higher prevention rate of recurrent C. diff infections than in a placebo group at a rate of 70.6 percent in the treatment group compared with 57.5 percent in the placebo group. Prevention of C. diff was defined as an absence of C. diff diarrhea for eight weeks following treatment or placebo. The treatment was well tolerated, with no serious side effects. The FDA noted that given the variability of fecal matter, there is a potential that it could contain an unforeseen infectious agent or food allergens.

The approval of Rebyota is “an advance in caring for patients who have recurrent C. difficile infection,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in an announcement. “Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening. As the first FDA-approved fecal microbiota product, today’s action represents an important milestone, as it provides an additional approved option to prevent recurrent CDI.”

Ferring—which acquired Rebyota in 2018 when it purchased its developer Minnestoa-based Rebiotix—also celebrated the approval.

“We believe this is a major breakthrough in harnessing the power of the human microbiome to address significant unmet medical needs. This is the first FDA approval of a live biotherapeutic and the culmination of decades of research and clinical development,” Ferring president Per Falk said. “Today’s announcement is not just a milestone for people living with recurrent C. difficile infection, but also represents a significant step which holds promise that many other diseases might be better understood, diagnosed, prevented, and treated using our rapidly evolving insights on the role of the microbiome in human health and disease.”

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US military shoots down Chinese balloon over coastal waters

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On Saturday afternoon, US jets intercepted the Chinese surveillance balloon as it was leaving the continental US. Live footage of the event shows contrails of aircraft approaching the balloon, followed by a puff of smoke that may indicate the explosion of some ordinance near the balloon’s envelope—a reporter is heard saying “they just shot it” in the video embedded below. The envelope clearly loses structural integrity shortly afterwards as it plunges towards the ocean. Reportedly, the events took place near Myrtle Beach, South Carolina.

Shortly afterwards, the US Department of Defense (DOD) released a statement attributed to its Secretary, Lloyd J. Austin III, that confirmed the interception was performed by US fighter jets on the order of President Biden. The DOD identifies the hardware as a “high altitude surveillance balloon,” and says that the President authorized shooting it down as early as Wednesday. The military, however, determined that this could not be done without posing a risk to US citizens, either due to debris from the balloon itself, or from the ordinance used to destroy it.

As a result, the military waited until the balloon was far enough offshore to no longer pose a risk to land, but close enough that it would fall within US territorial waters, ensuring that the country would be the first to recover any hardware that survived the plunge into the sea. Secretary Austin also thanked Canada for its assistance in tracking and intercepting the balloon through the countries’ cooperative North American defense organization, NORAD.

It’s unclear how much intelligence value there will be in any hardware that survives the fall to the ocean from that altitude. Of course, it was also unclear whether there was any intelligence value in the balloon’s flight across the US in the first place.

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The physics of James Joyce’s Ulysses

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Enlarge / An early edition of one of Dublin’s most famous literary masterpieces: Ulysses by James Joyce, published in 1922.

Fran Caffrey/AFP/Getty Images

Ulysses, the groundbreaking modernist novel by James Joyce, marked its 100-year anniversary last year; it was first published on February 2, 1922. The poet T.S Eliot declared the novel to be “the most important expression which the present age has found,” and Ulysses has accumulated many other fans in the ages since. Count Harry Manos, an English professor at Los Angeles City College, among those fans. Manos is also a fan of physics—so much so, that he penned a December 2021 paper published in The Physics Teacher, detailing how Joyce had sprinkled multiple examples of classical physics throughout the novel.

“The fact that Ulysses contains so much classical physics should not be surprising,” Manos wrote. “Joyce’s friend Eugene Jolas observed: ‘the range of subjects he [Joyce] enjoyed discussing was a wide one … [including] certain sciences, particularly physics, geometry, and mathematics.’ Knowing physics can enhance everyone’s understanding of this novel and enrich its entertainment value. Ulysses exemplifies what physics students (science and non-science majors) and physics teachers should realize, namely, physics and literature are not mutually exclusive.”

Ulysses chronicles the life of an ordinary Dublin man named Leopold Bloom over the course of a single day: June 16, 1904 (now celebrated around the world as Bloomsday). While the novel might appear to be unstructured and chaotic, Joyce modeled his narrative on Homer’s epic poem the Odyssey; its 18 “episodes” loosely correspond to the 24 books in Homer’s epic. Bloom represents Odysseus; his wife Molly Bloom corresponds to Penelope; and aspiring writer Stephen Daedalus—the main character of Joyce’s semi-autobiographical A Portrait of the Artist as a Young Man (1916)—represents Telemachus, son of Odysseus and Penelope.

In his paper, Manos notes that the fictional Bloom fancies himself a man familiar with science, but Joyce slyly shows his protagonist to be a dilettante whose knowledge stems primarily from the popular science books available at the time—which would certainly explain certain misconceptions Bloom holds. For instance, when Bloom invites Dedalus to his home, he tries to impress the young man by declaring that it is possible to see the Milky Way during the day if the observer were “placed at the lower end of a cylindrical vertical shaft 5000 ft [sic] deep sunk from the surface towards the center of the Earth.”

James Joyce with Sylvia Beach, owner of the Paris bookstore Shakespeare and Company, in March 1930. Beach was the first to publish <em>Ulysses</em> in 1922.
Enlarge / James Joyce with Sylvia Beach, owner of the Paris bookstore Shakespeare and Company, in March 1930. Beach was the first to publish Ulysses in 1922.

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This is false, of course; Manos writes that Rayleigh scattering would render the stars invisible—even from the bottom of a cylindrical vertical shaft or tall chimney. Where might Bloom have acquired this misconception? Manos notes that Sir Robert Ball, at the time director of the Dunsink Observatory just north of Dublin, had published two popular books. Dedalus spots one of them, The Story of the Heavens, in Blooms’s library, The other was called Star-Land, which talks about being able to see stars in daylight from the bottom of a mineshaft or tall chimney. If Bloom possessed the first book, it’s highly likely he would also have read Star-Land—hence his misconception.

Other physics examples reflect the accepted science of that time, even though subsequent advances rendered that science incorrect. For instance, Bloom ruminates on how heat is transferred through convection, conduction, and radiation while boiling water for tea, including a mention of how the Sun’s radiant heat is “transmitted through omnipresent luminiferous diathermanous ether.” At the time, some physicists still believed in the existence of a luminiferous ether that served as the medium through which light traveled. It was eventually disproved—thanks to the famous Michelson-Morley experiment in 1887 and Albert Einstein’s development of special relativity and his paper on the photoelectric effect in 1905 (his annus mirabilis). But Manos notes that a high school textbook contemporary with the novel’s 1904 setting still referenced the ether as a scientific fact.

In Chapter 15 (“Circe”), one of the characters says, “You can call me up by sunphone any old time”—a phrase that also appears in Joyce’s handwritten notes for the chapter. While Manos was unable to trace a specific source for this term, there was a similar device that had been invented some 20 years earlier: Alexander Graham Bell’s photophone, co-invented with his assistant Charles Sumner Tainter.

A photophone transmitter showing the path of reflected sunlight, before and after being modulated.
Enlarge / A photophone transmitter showing the path of reflected sunlight, before and after being modulated.

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Unlike the telephone, which relies on electricity, the photophone transmitted sound on a beam of light. Bell’s voice was projected through the instrument to a mirror, causing similar vibrations in the mirror. When he directed sunlight into the mirror, it captured and projected the mirror’s vibrations via reflection, which were then transformed back into sound at the receiving end of the projection. Bell’s device never found immediate application, but it’s arguably the progenitor to modern fiber optic telecommunications.

There are several other instances of physics (both correct and incorrect/outdated) mentioned in Ulysses, per Manos, including Bloom misunderstanding the science of x-rays; his confusion over parallax; trying to figure out the source of buoyancy in the Dead Sea; ruminating on Archimedes’ “burning glass”; seeing rainbow colors in a water spray; and pondering why he hears the ocean when he places a seashell to his ear. Manos believes introducing literature like Ulysses into physics courses could be a boon for non-majors, as well as encouraging physics and engineering students to learn more about literature.

In fact, Manos notes that an earlier 1995 paper introduced a handy introductory physics problem involving distance, velocity and time. Ulysses opens with Stephen Dedalus and his roommate, Buck Mulligan, standing at the Martello tower overlooking a bay at Sandy Cove. Mulligan is shaving and slyly performs an “apparent miracle”: he whistles, and a few moments later a passing mailboat whistles back. Mulligan had spotted the mailboat through his shaving mirror giving its usual two blasts at that time of the morning, about a mile away.

Using a simple equation (t = d/v), “Students can easily calculate that at the speed of light, Mulligan would have seen the steam in 5.4 ×10-6 s, with the whistle blast,” Manos wrote. “At 1100 ft/s, the sound would have traversed the mile to the Martello tower in 4.8 s, giving Mulligan time to whistle to the heavens and wait (“paused”) for the heavens (the mailboat’s departure whistle) to reply, thus pulling off his apparent miracle.”

DOI: The Physics Teacher, 2021. 10.1119/5.0028832  (About DOIs).

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Scientists grew mini human guts inside mice

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Your gut has an obvious job: It processes the food you eat. But it has another important function: It protects you from the bacteria, viruses, or allergens you ingest along with that food. “The largest part of the immune system in humans is the GI tract, and our biggest exposure to the world is what we put in our mouth,” says Michael Helmrath, a pediatric surgeon at Cincinnati Children’s Hospital Medical Center who treats patients with intestinal diseases.

Sometimes this system malfunctions or doesn’t develop properly, which can lead to gastrointestinal conditions like ulcerative colitis, Crohn’s disease, and celiac—all of which are on the rise worldwide. Studying these conditions in animals can only tell us so much, since their diets and immune systems are very different from ours.

In search of a better method, last week Helmrath and his colleagues announced in the journal Nature Biotechnology that they had transplanted tiny, three-dimensional balls of human intestinal tissue into mice. After several weeks, these spheres—known as organoids—developed key features of the human immune system. The model could be used to mimic the human intestinal system without having to experiment on sick patients.

The experiment is a dramatic follow-up from 2010, when researchers at Cincinnati Children’s became the first in the world to create a working intestine organoid—but their initial model was a simpler version in a lab dish. A few years later, Helmrath says, they realized “we needed it to become more like human tissue.”

Scientists elsewhere are growing similar miniature replicas of other human organs—including the brain, lung, and liver—to better understand how they develop normally and how things go awry to give rise to disease. Organoids are also being used as human avatars for drug testing. Since they contain human cells and display some of the same structures and functions as real organs, some researchers think they’re a better stand-in than lab animals.

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