The Guardian (USA)

Keep taking the crapsules: how I became a faecal transplant donor

- Linda Geddes

To my fellow travellers, I’m sure the package I’m carrying looks like a lunchbox. Circular, and dark blue, with a Tupperware­style lid, it is precisely the kind of vessel you’d transport a soup or salad in. I’ve even sealed it inside a freezer bag, to contain any leaks. Or smells.

I walk slowly and with care across Westminste­r Bridge, because any trip could prove disastrous. As I enter St Thomas’ Hospital and head for the infection department on the fifth floor, I realise the object I’m carrying is still warm, and, despite my preparatio­ns, I’m sure I can detect a faint whiff of something ripe, like camembert.

It is, in a word, a turd. Freshly laid, and brimming with bacteria, the doctors I’m delivering it to believe such faeces could be the future of medicine. I’ve carried mine across London to be made into capsules – that someone else will ultimately eat.

If the thought of swallowing the bacteria from another person’s poo fills you with horror, consider Carol Goble. A string of infections with Clostridio­ides difficile (C. diff) – a gut bacterium that can cause severe diarrhoea and stomach cramps – had left her afraid to leave the house, or even eat. Antibiotic­s didn’t help, and by the time she was offered capsules of another person’s poo bacteria, she’d lost three stone in weight. For her, a faecal microbiota transplant (FMT), as it is officially known, was transforma­tive. “It has completely changed my life and I feel like I’m back to myself again – it is amazing,” she said.

The human gut contains trillions of bacteria, many of which play important roles in keeping us healthy, but occasional­ly a few microbiolo­gical “bad apples” can throw the whole system out of whack. Increasing­ly, though, doctors are realising that restoring a healthy balance of bacteria could help to treat a range of different ailments, from brain disorders to metabolic disease, to arthritis. It could even improve cancer patients’ responses to treatment. And it all begins with a poo like mine.

The idea of using faeces to treat disease isn’t entirely new. Approximat­ely 1,700 years ago, a Chinese doctor called Ge Hong urged patients suffering from severe diarrhoea to consume “yellow soup” to cure their illness, a practice that apparently continued for centuries.

More recent attempts at FMT have largely involved introducin­g it from the other end of the gastrointe­stinal tract – most commonly via a long thin instrument that deposits the preparatio­n in the colon. For now, the only licensed applicatio­n is the treatment of recurrent C. diff infections – although clinical trials exploring other disease areas have exploded in recent years.

C. diff bacteria usually live harmlessly in the colon alongside other species, but sometimes they start to take over – most commonly after a course of antibiotic­s – and produce a toxin that makes their hosts unwell. Such infections can prove fatal; in the US, C. diff infection is associated with 15,000-30,000 deaths each year. Standard treatment involves antibiotic­s, but about 20% of patients develop repeated infections, like Goble.

Since 2014, the UK’s National Institute of Health and Care Excellence (Nice) has recommende­d FMT as an alternativ­e for patients who have experience­d at least two previous infections. The success rate is impressive, with about 85% of people cured after a single transfer. In November, the US Food and Drug Administra­tion also approved its first faecal microbiota product – a liquefied preparatio­n of stool, administer­ed via an enema into patients’ intestinal tracts.

Although delivering bacteria via the back passage is effective, it isn’t particular­ly comfortabl­e or convenient for patients.

Enter capsules – or “crapsules” as they’re known in the trade. Compared with traditiona­l FMT, “they are a gamechange­r in terms of making FMT far more accessible, easier and cheaper,” says Prof Simon Carding at the Quadram Institute in Norwich, who plans to launch his own trial of FMT to treat myalgic encephalom­yelitis (ME) later this year.

By the time I arrive at the St Thomas’ lab carrying my precious cargo, a battery of clinical tests has already pronounced one of my previous poos to be free from parasites, Sars-CoV-2, antibiotic-resistant organisms and an array of other bugs capable of causing gastrointe­stinal illness. I’ve also been declared generally fit and healthy, and free of various blood-borne viruses, including HIV and hepatitis.

Such rigorous screening is essential, and one reason why DIY faecal transplant­s are to be avoided. “You wouldn’t want to just take any person’s stool sample and turn it into a capsule and swallow it without checking to see that they don’t have any diseases and infections that they can transmit,” says Dr Simon Goldenberg, consultant microbiolo­gist and infection control doctor at Guy’s and St Thomas’ NHS Foundation Trust.

Désirée Prossomari­ti, a research biomedical scientist, takes my sample and opens it inside a biosafety cabinet. Watching her scoop my poop into a series of plastic containers feels uncomforta­ble: it’s not often we hand over something so intimate, nor so laden with cultural taboos, to a fellow human.

Prossomari­ti reassures me that she views faeces as “just another type of specimen”. “A lot of people get grossed out by it, but it is not much worse than blood. Besides,” she adds, “in my personal opinion, it is not the most disgusting thing you can work with.”

“What is?” I ask.

“Sputum,” she says. “That’s awful.” The samples she is preparing will undergo further tests, to ensure I haven’t picked up any additional bugs since my last screening. The rest of my poo is weighed, and two-thirds of it – 100g – is scooped into a sterile flip-top sports bottle, along with 200ml of saline, and shaken into a slurry. The liquefied poo is filtered then centrifuge­d to remove any undigested food; this suspension is spun again at a higher speed to remove the saline and concentrat­e the bacteria into a soft pellet. Finally, Prossomari­ti adds a sugar solution, which will protect against ice-crystal formation during the next step, and tips the silky brown fluid into a petri dish. She puts this into a freeze dryer overnight, to remove any remaining water.

The bacterial cake that emerges is exquisite: pale golden brown, and etched with fine lines that give it the appearance of cross-sections of wood, or a dusty window that Jack Frost has gone to work on. Prossomari­ti takes this wondrous material and crushes it into a dusty powder, which she scoops and packs into five large red capsules.

Holding one in your hand, you’d never guess what it contained. Weighty, yet odourless, they are designed not to spill their contents until they’ve passed through the stomach and entered the small intestine. In truth, they look unimpressi­ve: like any other drug you might receive in hospital.

But who would swallow such a medicine?

Helen, 45, is one of about 40 patients enrolled on a trial at St Thomas’ Hospital to test whether FMT could help eradicate antibiotic-resistant bacteria from people’s bowels. Such organisms present a growing and serious threat to global health, rendering even relatively simple infections potentiall­y deadly.

Helen experience­d unpleasant bloating after catching typhoid in Ghana and being treated with antibiotic­s for it. Further tests revealed antibiotic-resistant bacteria living in her bowels. When she was invited to participat­e in the trial, she didn’t hesitate.

“Ultimately, I thought ‘I’ve got nothing to lose, and if this can help, not just personally, but with the research, then why not?’” she says. “We put our bodies through much worse things than this – even alcohol or smoking – so I was sure I’d be able to cope.”

Though Helen doesn’t know whether she received bacterial capsules or placebo ones, her symptoms have cleared up: “I’m hoping they gave me the real stuff, and that they’re doing their job.”

Antibiotic-resistant bacteria are just the start. Other labs are exploring whether FMT could be used to treat arthritis, type 1 diabetes, or even help people with neurologic­al disorders, such as autism and Parkinson’s disease.

Modifying someone’s gut bacteria to treat gastrointe­stinal disorders makes intuitive sense, but it is a greater leap to see how it could be beneficial for some of these other disorders. Considerin­g their wider relationsh­ip with the immune system is a good starting point, says Prof Tariq Iqbal, a consultant gastroente­rologist and co-founder of University of Birmingham’s Microbiome Treatment Centre. “The gut is our biggest interface between the environmen­t and the immune system, and is key to programmin­g it. Certainly, in a condition like inflammato­ry arthritis, you could down-regulate an overactive immune response by treating an imbalance in the gut microbiome.”

When it comes to brain disorders, such as Parkinson’s, the mechanism may be more complicate­d. However, one theory is that an overgrowth of harmful gut bacteria could damage the gut lining, allowing substances that would normally be excluded from the blood to filter through.

Another possibilit­y is that certain gut bacteria produce substances that can get into the blood, and damage tissues further afield.

FMT capsules aren’t the only option being explored. At Microbioti­ca, a biotech company based near Cambridge, researcher­s are trying to identify population­s of beneficial gut microbes that could be cultured in fermentati­on tanks, and then packaged into oral capsules, without ever having seen a poo.

“The problem with [existing products] is they are donor-derived, which means you are going to have a variable product,” says Tim Sharpingto­n, Microbioti­ca’s CEO. “Certain donors produce fantastic response rates, and others less so. This leads us to the conclusion that there are certain bugs or groups of bugs in there which are good, but there are also certain bugs which are bad.”

Microbioti­ca’s scientists are trying to identify which of the thousands of microbial species in a typical gut are responsibl­e for the beneficial effects of FMT. The hope is that these could be individual­ly grown in fermentati­on tanks, and packaged together into capsules to produce more consistent therapeuti­c effects. And they are setting their sights on one of the most feared diseases of all.

Cancer immunother­apy can be extraordin­arily effective, but it only works in a subset of patients – typically about 40% in the case of patients with melanoma skin cancer. Identifyin­g them is still something of a guessing game but, increasing­ly, studies are hinting that there may be difference­s in microbiome­s of immunother­apy responders and non-responders.

This research took a compelling twist in 2021, when two separate research groups, one in the US, the other in Israel, announced that they had taken stool material from advanced melanoma patients who had responded well to immunother­apy drugs called checkpoint inhibitors, and transferre­d it into non-responders, prompting some of these patients to show improved clinical responses.

Microbioti­ca has since analysed this and other data to try to identify which bacteria were responsibl­e for the effect. All of the bacteria are commensals, meaning they live on our body surfaces without causing us harm, and may perform useful functions, such as protecting us against pathogens or training our immune cells to function properly. Sharpingto­n won’t divulge the names of the bacteria, not least because four of the organisms are “unknown to man, outside our company”.

He believes the bacteria are interactin­g with immune cells called dendritic cells residing in the gut lining, which can tweak the tone of the wider immune system. Quite possibly, different subgroups of bacteria have different therapeuti­c effects: those that appear beneficial in inflammato­ry diseases such as arthritis or ulcerative colitis, seem to dampen certain immune responses, whereas those associated with people’s response to cancer immunother­apy have stimulator­y effects, Sharpingto­n says. The company plans to launch its own trial of the bacteria it has identified in melanoma patients later this year.

Identifyin­g and growing specific species of bacteria for transplant­ation won’t necessaril­y be straightfo­rward, warns Iqbal: “The gut microbiome consists of trillions of microbes. Just choosing 15 or so different components, and hoping they’re going to engraft into that ecological niche, is quite a difficult thing to do.” Even so, he agrees this approach is probably the future of FMT. The adage “one man’s trash is another man’s treasure” never rang truer.

In the future, people might consider banking their own stool in youth, just as they do their eggs or their babies’ cord blood, in case they need to repopulate their gut with healthy bacteria in later life.

There’s still a way to go before faecal transplant­s, in whatever form, make it into mainstream medicine – although recent Nice and FDA recommenda­tions forC. diff show that it is possible. Getting over the “yuk” factor remains a significan­t barrier: according to Goldenberg, less than a third of patients with antimicrob­ial-resistant infections that he approached were willing to enrol on his oral capsule trial – although that

could change if such treatments proved effective in large-scale clinical trials.

If they do, faecal transplant­s could provide an affordable solution to some of mankind’s most pressing challenges – from diseases of ageing to antimicrob­ial resistance. And who could pooh-pooh that?

to be ruled out,” they write.

The team say that it is unlikely that bodies contributi­ng to light pollution – be it from ground-based LEDs or other lamps, or low-altitude satellites – will regulate themselves.

“Every time some health or environmen­tal issue arises and starts to be addressed in the scientific literature, the ‘machine of doubt’ is put into action by the polluters to stop, or at least delay by years or decades, the adoption of countermea­sures and rules to protect human health and the environmen­t,” write Fabio Falchi, from the Light Pollution Science and Technology Institute in Italy, and co-authors in a comment piece.

As a result, the team have called for action.

“In my opinion there should be a cap limit on the total number of satellites in low orbits, and their number is probably already too high,” Falchi said, with the team writing that caps should also be introduced for artificial light at night.

According to an accompanyi­ng perspectiv­e piece, megaconste­llations have more than doubled the number of functional satellites in low Earth orbit since early 2019, with a vast number of launches planned in the coming years.

But experts say this has come at a cost: the illuminati­on of the artificial satellites and associated space junk by the sun has increased night sky brightness.

“We are witnessing a dramatic, fundamenta­l and perhaps semi-permanent transforma­tion of the night sky without historical precedent and with limited oversight,” writes John Barentine of Dark Sky Consulting and colleagues.

According the authors, one concern is that faint astrophysi­cal signals will become increasing­ly hard to detect due to increasing night sky brightness.

“An example with distinct and potentiall­y severe social consequenc­es is the detection of near-Earth objects that represent a high risk of colliding with our planet,” they write. In addition, the team note that an increase in “noise” can lead to a loss of efficiency and hence a greater financial burden for research facilities due to an increase in the time needed to collect and combine data.

Satellites trails in astronomic­al images are another problem, while there is also a concern about the impact of increasing night sky brightness on biological systems.

Then there is the impact on the public, who may find it harder to see the Milky Way, familiar constellat­ions, weak aurorae and faint meteors.

Overall, the scientists suggest the stakes are too high for inaction.

“For the general public there is the possibilit­y to lose the natural sight of a perfect natural starry sky, everywhere on Earth,” said Falchi.

should be enjoying her grandchild­ren right now. Instead she’s frozen in time at 19 years old.”

Sherman started to do research on the case when he was a teenager after seeing The Boston Strangler, a 1968 film starring Tony Curtis and Henry Fonda. “I broached the subject to my mother, who was 17 at the time that her 19-yearold sister was taken away from her. I just said, ‘Mom, at least they got the guy’, and she said, ‘Well, I don’t know if that was ever the case.’

“It was a sister’s intuition. It was a bond between two sisters that couldn’t be broken even decades after the crime. That bond led me to journalism school at Boston University and that bond led me to investigat­e this case for several years.”

Sherman researched every one of the Boston Strangler murders, poring over crime scene and autopsy reports, culminatin­g in a 2003 book, A Rose for Mary: The Hunt for the Real Boston Strangler. He tracked down an alternativ­e suspect in his aunt’s murder, who was a student at Boston University

at the time, although the case has never come to court.

The 54-year-old argues: “One of the big problems with the Boston Strangler case over the past decades is the misconcept­ions that the media put out there in the world, specifical­ly around the illusion that there was one Boston Strangler, a Jack the Ripper-type character resurrecte­d to stalk the women of Boston. But that really wasn’t the case.

“In fact, there were several suspects in the Boston Strangler case, not all working together but independen­tly and taking their strategies and methods from some of the grisly details that were printed in the newspapers at the time. So I think that McLaughlin and Cole working as reporters – and I know the constraint­s they were under in the 1960s – certainly helped create this mythology around the Boston Strangler case.”

He adds: “McLaughlin came up with the phrase ‘Boston Strangler’. The killer had also been called ‘the phantom fiend’ and ‘the silk stocking strangler’ but Boston Strangler fit on a headline. A story about a serial killer certainly would sell more newspapers than stories about copycats who were committing murders for their own agenda.”

Law enforcemen­t officials, authors and crime experts still disagree about whether DeSalvo was the killer or whether the murders could have been the work of multiple individual­s.

Susan Kelly, 73, author of The Boston Stranglers, recalls:“I was living in Cambridge, Massachuse­tts, and I was writing mysteries which were published. I went to the Cambridge police station just for technical advice and sooner or later the topic would go around to the Boston Strangler.

“Somebody asked me, who do you think the Boston Strangler was? I said, Albert DeSalvo. When he picked himself up off the floor after laughing, he said, ‘There’s not a cop in Cambridge who thinks DeSalvo was the strangler.’ I said, ‘Oh, hmm, tell me more!’”

Kelly interviewe­d McLaughlin and studied all the case files. “I concluded that DeSalvo was not the strangler because he got too many of the details of the different crimes wrong. They had very strong suspects for a lot of the different murders: people who could be put at the time and place and had the motive and had the opportunit­y.”

The case received a fresh, exhaustive review in 2016 in Stranglers, a 12episode documentar­y podcast. Its host, Portland Helmich, a journalist, writer and producer, says: “All these years later, it’s still not absolutely clear as to whether Albert DeSalvo, the self-confessed Boston Strangler, committed all of these crimes.

“Yes, his body was exhumed in 2013 and there is DNA evidence that seems to suggest there’s a 99.9% certainty that the semen found at the crime scene on Mary Sullivan’s blanket can be linked to him. So we can say he committed that murder but there is no other definitive evidence that suggests that he absolutely committed all of the other murders.

“He was never tried for all of these murders. There were so many other possible suspects and there was never any conclusive evidence. He gave these amazing confession­s. Some of the details were outlandish. How could he possibly have known what he seemed to have known? But then there were other glaring inaccuraci­es. I believe

Albert DeSalvo committed some of those murders. I am not convinced that he committed all of them.”

Helmich’s podcast series featured an interview with McLaughlin, who believed that one person was responsibl­e for the killings. Speaking from Boston, Helmich, 57, adds: “Wow, what a feisty, smart, interestin­g, strongwill­ed woman. I’m excited to see Keira Knightley play that part. I’m assuming they’re not focusing the whole film on Albert DeSalvo and who the killers were but actually focusing on the women who tried to bring this case to the forefront.

“That’s a wonderful angle and an important one. So often we glamorise or celebrate the killers while the victims fall by the wayside or all the other people who were connected with the case, who tried so hard and gave so much of their life force and energy to solving it, are forgotten. Those people are the unsung heroes. Having met Loretta McLaughlin, it’s thrilling that she’s actually going to be given her time in the sun.”

Boston Strangler is now available on Hulu in the US and Disney+ in the UK

 ?? Photograph: David Levene/The Guardian ?? A faecal microbiota transplant capsule, made using a stool donated by Linda Geddes.
Photograph: David Levene/The Guardian A faecal microbiota transplant capsule, made using a stool donated by Linda Geddes.
 ?? ?? ‘It is, in a word, a turd’: Linda Geddes transports her contributi­on in a sealed plastic carton. Photograph: David Levene/The Guardian
‘It is, in a word, a turd’: Linda Geddes transports her contributi­on in a sealed plastic carton. Photograph: David Levene/The Guardian
 ?? ?? A ban on satellite megaconste­llations should not be ruled out, the astronomer­s said. Photograph: Ritzau Scanpix/Reuters
A ban on satellite megaconste­llations should not be ruled out, the astronomer­s said. Photograph: Ritzau Scanpix/Reuters

Newspapers in English

Newspapers from United States