At Kingston University in south-west London, a researcher in a white lab coat and safety goggles struggles to unscrew a large plastic jar full of cow eyes, fresh from the local slaughterhouse.
Eventually he succeeds in prising off the yellow lid, before plucking out one sizeable specimen and popping it on a black tray, which he holds flat on his palm like a waiter offering out canapés. Later, he’ll carefully cut away the cornea – the front surface of the eyeball – and place it alongside five others in a solution that will help keep the cells alive for longer. Then, he’ll infect them all with gonorrhoea.
The sexually transmitted disease affects around 78 million people each year, causing swelling, discomfort and a thick genital discharge. It can also infect the mouth, throat, anus and eyes, and if left untreated can cause infertility in both men and women, or lead to life-threatening ectopic pregnancies, when a fertilised egg gets stuck in the fallopian tubes. Babies born to mothers with gonorrhoea can develop an eye infection that causes permanent sight loss if not treated.
Since the 1940s, gonorrhoea has been treated with antibiotics. But, over time the Neisseria gonorrhoeae bacteria has developed resistance to the most commonly used drugs. And these resistant forms of the disease, dubbed ‘super-gonorrhoea’, are on the rise. The work at Kingston is part of a global effort to find new ways to diagnose and treat super-gonorrhoea before it’s too late.
Britain is practically oozing with ‘the clap’, which got its nickname either from an old French word for brothel (clapier), or from an archaic treatment method that involved slamming the penis between two hard objects to clear the discharge (this is no longer the recommended course of action). In 2016, the UK accounted for more than half of all the gonorrhoea cases in the European Union – and experts are concerned that the spread of a drug-resistant form of the bacteria would be difficult to stop.
Last year, a British man contracted what experts called the “world’s worst-ever” case of super-gonorrhoea during a trip to south-east Asia. In January 2019, two UK women were confirmed as the first people to contract the drug-resistant form of the disease without leaving the country.
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Right now, these cases of super-gonorrhoea are isolated incidents, and treatment with the recommended antibiotics ceftriaxone and azithromycin works for the majority. But resistant strains are starting to circulate. In 2017, the World Health Organisation (WHO) surveyed 77 countries and found that 81 per cent had detected gonorrhoea strains resistant to azithromycin, and two-thirds had strains resistant to one or both of the two ‘last resort’ antibiotics.
“It’s a little bit like the tip of the iceberg,” says Emilie Alirol, STI Project leader at the Global Antibiotic Research & Development Partnership (GARDP). “We have a few highly publicised cases associated with treatment failures, and globally the resistance to ceftriaxone and azithromycin is on the increase, but we don’t really understand how serious the underlying problem is.”
GARDP are working with pharmaceutical company Entasis to bring a new antibiotic, called zoliflodacin, to market. Preliminary tests have shown it to be highly effective against all strains, including resistant ones, and the next phase of clinical trials will start in the summer and run for 18 months. But, although this new drug attacks the bacteria in a completely different way, it’s likely that further measures will be needed to address the problem of super-gonorrhoea for good.
One of the reasons for the difficulty is that Neisseria gonorrhoeae is extremely good at developing resistance to all sorts of antibiotics. “It is known to be a very smart bug,” says Alirol. “If you look at the different resistance mechanisms that exist in bacteria, gonorrhoea has mastered all of them.” That’s the reason you hear about super-gonorrhoea, but not ultra-chlamydia or mega-syphilis. The gonorrhoea bacteria has the ability to exchange genes for resistance with other bacteria, in what’s known as horizontal gene transfer – it can absorb genetic material from non-pathogenic, ‘friendly’ bacteria and borrow their abilities.
That means there’s little point in just rolling out a new antibiotic like zoliflodacin on its own – gonorrhoea has already developed resistance to penicillin, spectinomycin, tetracycline and now ceftriaxone and azithromycin too. Within a few years, the bacteria would adapt, and we would find ourselves right back in the same situation.
Part of the problem is that those antibiotics have been wrongly prescribed and overused: a recipe for building resistance. Doctors have to rely on the symptoms that patients describe to determine which antibiotics to prescribe. But gonorrhoea has very similar symptoms to other STIs, such as chlamydia, which is more common.
This means they can sometimes end up prescribing the wrong antibiotic – either because the specific strain of bacteria is resistant, or because they’ve got the wrong disease entirely. “It’s like flipping a coin whether or not you’re going to get it right,” says Dr Cassandra Kelly-Cirino, director of emerging threats at the Foundation for Innovative New Diagnostics (FIND).
Often, doctors will make an educated guess based on what diseases are most prevalent in their area. They’ll prescribe an antibiotic for one disease or the other and wait to see if the patient responds. “But a lot of patients don’t come back,” says Kelly-Cirino. Those from poor and marginalised communities, such as sex workers, are less likely to return to the doctor if treatment doesn’t work, or they may bounce from one clinic to another.
FIND is coordinating development of new, easier ways of testing, backed by £5m of funding from the UK government. The goal is that when the new antibiotic zoliflodacin – which will be reserved specifically for gonorrhoea – does come onto the market in three to five years, it only gets used when it’s needed and doesn’t suffer the same fate as its predecessors. “This new antibiotic is a common good, a global good and we all have ownership over it,” says Kelly-Cirino. “We need to protect it so it lasts as long as it can, and diagnostics are the way to do that.”
Bacterial cultures can help confirm that an infection actually is gonorrhoea, while sophisticated molecular tests or DNA sequencing can identify whether the bacteria is vulnerable to the usual antibiotics, or whether new ones will have to be used. But these tests are lab-based, requiring careful handling and specialist training. Swabs have to be sent off, and it can take several days for results to come through.
Over the next few years, FIND will be working with industry to develop tests that can be carried out easily and cheaply in the community, and give results within one hour. “The technology should be a very compact user-friendly integrated solution. We don’t want a big machine that has a series of complex different steps,” says Kelly-Cirino.
But throwing more antibiotics into the mix may not be the answer. It’s possible that salvation from super-gonorrhoea will come from an unlikely source. In the 1990s, a meningitis outbreak in New Zealand led to a mass vaccination programme, with more than 80 per cent of under 20s receiving a vaccine. The bacteria that causes meningitis is 80 to 90 per cent identical to Neisseria gonorrhoeae. When a group of researchers looked back through historical records in 2017, they found that those who had been vaccinated against meningitis B were 31 per cent less likely to contract gonorrhoea, and that those who did contract it were 40 per cent less likely to develop a severe form of the disease.
Since then, “interest in the area has exploded”, according to Helen Petousis-Harris, one of the authors of that paper. A follow-up study by the same group found that the meningitis B vaccine was 24 per cent effective at preventing hospitalisation from gonorrhoea, and 47 per cent effective among young people vaccinated before they started having sex.
At Kingston, meanwhile, Dr Lori Snyder is in the early stages of developing a self-contained test for gonorrhoea that women can carry out themselves, like a pregnancy test. But the main focus of her work is on finding alternatives to antibiotics that can help stop babies going blind from gonorrhoea, which is why there’s a fridge in the corner of her lab full of bovine eyeballs (that would have otherwise been discarded by the abattoir).
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At the moment, gonorrhoea infections are treated with antibiotic ointments. But these can irritate the delicate eyes of newborn babies, and won’t work against resistant strains. Snyder is developing a new eyedrop-based treatment that should also work against super-gonorrhoea, inspired by a curious quirk of Neisseria gonorrhoeae.
When researchers grow bacteria in a petri dish, they start by making a medium – usually in the form of a jelly. It’s a lot like making jelly at home: there’s a powder, which is melted in water and then set. Normally, you can remelt and reset this jelly in the microwave, and bacteria will still grow on it. But gonorrhoea doesn’t. “It’s very fussy,” says Snyder.
When the jelly medium gets re-melted, it releases toxic fatty acids. These can kill bacteria by disrupting the cell membrane (“making the cell ‘pop’, essentially”), or affecting how they use energy. Unlike most antibiotics, they attack lots of different aspects of the cell’s functionality at once, which means it’s harder for bacteria to develop resistance.
Our bodies can produce these substances naturally on mucosal surfaces like the eyes, but gonorrhoea has long since developed ways to defend itself. Snyder started her career studying efflux pumps, which sit embedded in the wall of a bacterium, and literally pump harmful molecules such as antibiotics out of the cell. When a strain of bacteria is resistant to an antibiotic or toxic fatty acid, it’s partly because it has efflux pumps that can detect and eject that specific molecule.
So, Snyder and her team used genetic sequencing to identify what efflux pumps different strains of gonorrhoea have, and find toxic fatty acids that could potentially get past them. Then, they tested those fatty acids on gonorrhoea-infected cow corneas, watching under a microscope as the kidney-shaped bacteria quickly withered away. Now, they have identified a candidate that works well even in the high-calcium environment of the eyeball.
“We’ve developed an eye drop that can deliver the fatty acids in a concentration that we need for it to work, and we’ve established that it would not be irritating to the eye,” says Snyder. That involved small rubber rings, more cow eyes, the fluorescent dye that you might have encountered at the opticians, and also raw chicken eggs, which apparently serve as a good experimental substitute for the human eyeball.
Toxic fatty acids have shown promise against other bacteria species as well. Snyder stresses that right now they only work on topical infections where they can be directly applied. But eventually, given the right delivery mechanism, they could be a promising weapon for all sorts of bacterial infections.
Drug-resistant infections threaten to upend modern medicine. By 2050, they could be responsible for more deaths each year than cancer, according to the European Public Health Alliance. Gonorrhoea has been evading our antibiotics for decades, but finding new ways to beat it could yield crucial weapons for the high-stakes fight against the wider superbug menace.
This article is part of our in-depth series investigating how technology is changing love, sex and relationships.
From keeping an intimate secret from the internet to the battle to destroy super-gonorrhoea, we’ll explore the technologies and ideas changing how we all live and love – for better or worse.
Click here to read more articles from this series.
– Inside the strange world of China’s romantic video games
– What Jeff Bezo’s penis can teach us about online intimacy
– Why it’s so difficult keeping your unborn child a secret from the internet
This article was originally published by WIRED UK
