A Pill To Make Exercise Obsolete

11/24/2019 A Pill to Make Exercise Obsolete | The New Yorker
Annals of Science November 6, 2017 Issue
A Pill to Make Exercise Obsolete

What if a drug could give you all the bene ts of a workout?
By Nicola Twilley October 30, 2017
t was late summer, and the gray towers of the Salk Institute, in San Diego, shaded
I seamlessly into ocean fog. The austere, marble-paved central courtyard was silent
and deserted. The south lawn, a peaceful retreat often used for Tai Chi and yoga
classes, was likewise devoid of life, but through vents built into its concrete border one
could detect a slight ammoniac whiff from more than two thousand cages of laboratory
rodents below. In a teak-lined office overlooking the ocean, the biologist Ron Evans
introduced me to two specimens: Couch Potato Mouse and Lance Armstrong Mouse.
Couch Potato Mouse had been raised to serve as a proxy for the average American. Its
daily exercise was limited to an occasional waddle toward a bowl brimming with pellets
of laboratory standard “Western Diet,” which consists almost entirely of fat and sugar
and is said to taste like cookie dough. The mouse was lethargic, lolling in a fresh layer
of bedding, rolls of fat visible beneath thinning, greasy-looking fur. Lance Armstrong
Mouse had been raised under exactly the same conditions, yet, despite its poor diet and
lack of exercise, it was lean and taut, its eyes and coat shiny as it snuffled around its
cage. The secret to its healthy appearance and youthful energy, Evans explained, lay in a
daily dose of GW501516: a drug that confers the bene cial effects of exercise without
the need to move a muscle.
Exercise has its discomforts, after all: as we sat down to talk, Evans, a trim
sixtysomething in a striped polo shirt, removed a knee brace from a coffee table,
making room for a mug of peppermint tea; he was trying to soothe his stomach, having
picked up a bug while hiking in the Andes. Evans began experimenting with 516, as
the drug is commonly known, in 2007. He hoped that it might offer clues about how
the genes that control human metabolism are switched on and off, a question that has
occupied him forYoumost of his career.
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Mice love to run, Evans told me, and when he puts an exercise wheel in their cage they
typically log several miles a night. These nocturnal drills are not simply a way of
dealing with the stress of laboratory life, as scientists from Leiden University, in the
Netherlands, demonstrated in a charming experiment conducted a few years ago. They
left a small cagelike structure containing a training wheel in a quiet corner of an urban
park, under the surveillance of a motion-activated night-vision camera. The resulting
footage showed that the wheel was in near-constant use by wild mice. Despite the fact
that their daily activities—foraging for food, searching for mates, avoiding predators—
provided a more than adequate workout, the mice voluntarily chose to run, spending up
to eighteen minutes at a time on the wheel, and returning for repeat sessions. (Several
frogs and slugs also made use of the amenity, possibly by accident.)
Still, as the example of Lance Armstrong Human makes clear, sometimes exercise
alone is not enough. When Evans began giving 516 to laboratory mice that regularly
used an exercise wheel, he found that, after just four weeks on the drug, they had
increased their endurance—how far they could run, and for how long—by as much as
seventy- ve per cent. Meanwhile, their waistlines (“the cross-sectional area,” in
scienti c parlance) and their body-fat percentage shrank; their insulin resistance came
down; and their muscle-composition ratio shifted toward so-called slow-twitch bres,
which tire slowly and burn fat, and which predominate in long-distance runners. In
human terms, this would be like a Fun-Run jogger waking up with the body of Mo
Farah. Evans published his initial results in the journal Cell, in 2008. This year, he
showed that, if his cookie-dough-scar ng mice were allowed to exercise, the ones that
had been given 516 for eight weeks could run for nearly an hour and half longer than
their drug-free peers. “We can replace training with a drug,” he said.
The drug works by mimicking the effect of endurance exercise on one particular gene:
PPAR-delta. Like all genes, PPAR-delta issues instructions in the form of chemicals—
protein-based signals that tell cells what to be, what to burn for fuel, which waste
products to excrete, and so on. By binding itself to the receptor for this gene, 516
recon gures it in a way that alters the messages the gene sends—boosting the signal to
break down and burn fat and simultaneously suppressing instructions related to
breaking down and burning sugar. Evans’s doped mice ran farther, in part because their
muscles had been told to burn fat and save carbohydrates, which meant that they took
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longer to “hit the wall”—the painful sensation encountered when muscles exhaust their
glucose store.
In dozens of other ways, 516 triggers biochemical changes that take place when people
train for a marathon—changes that have substantial health bene ts. Evans refers to the
compound as “exercise in a pill.” But although Evans understands the mechanism
behind 516’s effects at the most minute level, he doesn’t know what molecule triggers
that process naturally during exercise. Indeed, one of the most signi cant challenges
facing anyone who wants to develop an exercise pill is that the biological processes
unleashed by physical activity are still relatively mysterious. For all the known bene ts
of a short loop around the park, scientists are, for the most part, incapable of explaining
how exercise does what it does.
he compound 516 was developed in the late nineties, in the laboratories of

T GlaxoSmithKline. Its creator, a chemical biologist named Tim Willson, was in
charge of a research group tasked with prospecting for chemicals that could bind to the
PPAR-delta receptor. The search had been prompted by an earlier discovery:
compounds that bound to a similar gene receptor were highly effective in treating
diabetics, the pharmaceutical industry’s most lucrative market. Willson’s team tested
516, rst in a test tube and then on middle-aged, obese monkeys, and the results were
exciting. “We got this dramatic increase in good cholesterol, and a commensurate
decrease in the bad kind,” he told me recently, noting that 516 also lowered insulin
levels and triglycerides. The combination of effects made 516 seem like a promising
treatment for what’s known as “metabolic syndrome,” a cluster of symptoms—
including obesity, high blood pressure, and high blood sugar—that is a precursor to
heart disease and diabetes. More than a third of adult Americans are estimated to have
metabolic syndrome, which made 516’s potential pro ts seem rather attractive.
GlaxoSmithKline took the drug all the way through Phase II clinical trials in humans,
successfully demonstrating that it lowered cholesterol levels without any problematic
side effects.
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But, in 2007, GlaxoSmithKline decided to shelve 516. The company was about to
embark on Phase III trials—the large, expensive, double-blind, placebo-controlled trials
that are required for F.D.A. approval—when the results of a long-term-toxicity test
came in. Mice that had been given large doses of the drug over the course of two years
(a lifetime for a lab rodent) developed cancer at a higher rate than their dope-free
peers. Tumors appeared all over their bodies, from the tongue to the testes. The results
made GlaxoSmithKline’s decision all but inevitable. If a large dose of the drug seemed
to increase the risk of cancer at the end of a mouse lifespan, the only way to
conclusively prove that even a lower dose would not have a similar effect on humans
would be to run a seventy-year trial. Without that proof, the F.D.A. would likely judge
the potential risks of taking the drug to be greater than the actual dangers of high
cholesterol.
Elsewhere, however, work on 516 persisted. Because Willson, in 2001, had published
his description of the chemical’s structure and clinical effects, other labs were able to
synthesize the chemical for research use. Ron Evans began his work on 516 at Salk the
same year that GlaxoSmithKline’s researchers abandoned theirs. Since then, he has
developed a less potent version that he hopes will also be less toxic.
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And 516 is not the only “exercise pill” in development. At the University of
Southampton, on England’s south coast, I met with a chemical biologist named Ali
Tavassoli, a lanky, youthful forty-two-year-old with a chilled-out demeanor, which
gives way to geeky enthusiasm when he starts explaining the particulars of protein
interactions. Tavassoli came across his drug, Compound 14, more or less by chance,
while designing a way to screen a new class of cancer drug, and he still seems
somewhat bemused by the fact that his lab is now a front-runner in the race to develop
an exercise pill. In a recent paper, he and his colleagues showed that Compound 14
caused the blood-glucose levels of obese, sedentary mice on a high-fat diet to approach
normal levels in just a week, while melting away ve per cent of their body weight. It
works, he explained, by fooling cells into thinking that they are running out of energy,
causing them to burn through more of the body’s fuel reserves.
Meanwhile, in Boston, Bruce Spiegelman, a Harvard cell biologist, has discovered two
potent exercise hormones. One of them, irisin, turns metabolically inert white fat in
mice into mitochondria-packed, energy-burning brown fat, and Spiegelman said that
he’s seen evidence that it may also boost levels of healthy proteins in the area of the
brain associated with learning and memory. He is now researching a third compound,
and when I visited his lab he invited me to look through a microscope at a petri dish of
sleek, round muscle bres—a kind of mouse tartare—awaiting treatment with the
chemical. They were twitching spasmodically. “It’s spontaneous,” Spiegelman said, as I
recoiled. “The membranes are electrically active, and it’s almost like static on a radio.
They just re occasionally.” The experiment—effectively, exercise in a dish—is an
efficient way of screening a large number of chemicals before selecting the most
promising candidates for trials on intact mice.
I noticed that the bres were a deep red, almost like raw tuna, and Spiegelman
explained that this is a familiar property of slow-twitch muscle, the fat-burning,
fatigue-resistant kind called upon during endurance training. Fast-twitch muscle,
which is more powerful but tires quickly, and which runs on carbohydrate, is pinker.
The piscine comparison is not incidental. During his research, Spiegelman discovered
that tuna have a mutation in a gene that plays an important role in determining
muscle- bre ratios. As a result, all the muscle in tuna is slow-twitch, which is the
reason for the distinctive color and meaty texture of a tuna steak. Spiegelman is now
collaborating with other researchers with theSubscribe
goal of now. Expand
inserting the tuna version of that
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gene into easily farmed sh, such as carp or salmon, in order to “tunafy” them and thus
ease demand for wild blue n.
Although Spiegelman, Evans, and Tavassoli study different compounds, they have all
followed what could be described as the metal-detector method of exercise-pill
development: scanning thousands of chemicals in order to nd one or two that convey
some of the bene ts of exercise. Other researchers are tackling the problem from the
opposite direction—attempting to document all the biochemical reactions that exercise
unleashes, which will create a sort of road map for drug development. Next year, the
National Institutes of Health will embark on an ambitious ve-year study to measure
every major molecule changed by exercise in approximately three thousand people of
both sexes and all age groups, and with a variety of preëxisting tness levels. Maren
Laughlin, who is leading the program, explained that the technology to create a
molecular snapshot of the human body in motion has only become available in the past
decade. “We’ve studied human metabolism for many, many years, but almost always at
rest,” she said. It is as if our knowledge of how the brain works had come from
observing only people who were asleep.
In Australia, a biologist named David James recently took the rst step in this
direction, studying muscle biopsied from four young, healthy men before and after ten
minutes of at-out cycling on an exercise bike. James and his colleagues itemized every
measurable difference in protein structure between the before and after samples. They
found more than a thousand changes, of which only ten per cent can be explained by
current medical science. For anyone wanting to develop an exercise pill, these new data
are both promising and daunting. “You know, people talk about exercise mimetics,”
James said. “But what are you going to mimic?”
he red double-decker buses of London are famous around the world. Less well
T known is the fact that the rst quantitative, systematic medical study of exercise
took place aboard them. In the late nineteen-forties, a young British epidemiologist
named Jerry Morris was looking through the postmortem folios of a hospital in the
East End when he noticed an alarming increase in the frequency of heart attacks
during the rst half of the twentieth century. Others had seen the same trend but
nobody had an explanation. Morris, however, suspected that the frequency of heart
attack might correlate with sedentary occupations, and so he turned to the double- Expand
decker bus. “If you’ve been to London, then you know,” Bill Hayes, a writer and
photographer who is at work on a history of exercise, told me. “The driver sits at the
front and drives the bus, and the conductor hops on and off the bus and climbs up and
down the stairs taking tickets and getting people to their seats.” Of the thousands of
drivers and conductors working on London’s buses at the time, the vast majority were
men, and most came from a similar social background. The only substantial difference
between them, in aggregate, was their daily activity levels.
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Morris spent hours on buses, monitoring how much time the drivers spent sitting
(ninety per cent of their shift, on average) and counting the numbers of steps the
conductors climbed each day (between ve hundred and seven hundred and fty).
Then, with the help of Britain’s newly established National Health Service, he went
through the busmen’s medical records. Morris was stunned by how powerfully the data
bore out his initial hypothesis: the sedentary drivers were almost twice as likely as the
mobile conductors to drop dead of a sudden heart attack. He followed up with what he
described as an “epidemiology of uniforms”—a painstaking comparison of the waist
size of trousers issued to both groups, at every age—which established that drivers were
signi cantly bulkier around the midsection than their conductor peers. Morris later
con rmed a similar correlation in postal workers, with sedentary counter clerks
showing a much higher incidence of cardiovascular disease than postmen, who did
their rounds on foot or by bike.
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When the papers presenting these ndings appeared in The Lancet, Morris’s conclusion
—that exercise was medically important and that its absence resulted in death and
disease—was met with surprise and even disbelief. “Puzzling,” the Aberdeen Evening
Express declared, noting that Morris’s studies failed to take into account what were
then generally accepted risk factors for heart attack, such as a temperamental
propensity toward “nervous strain.” Mainstream medical wisdom held that heart
attacks were most likely the result of high blood pressure, and that physical activity had
nothing to do with either.
Up to this point, historical attitudes toward exercise had varied, according to Hayes.
The Ancient Greeks were fans. Plato, a former competitive wrestler, praised the
mental-health bene ts of physical exertion, and Hippocrates wrote, “Eating alone will
not keep a man well, he must also take exercise.” By contrast, medieval Europeans
tended to regard the body as a vessel for sin, and exercise as a distraction from the more
important work of improving the soul. “The spirit ourishes more strongly and more
actively in an in rm and weakly body,” the twelfth-century French abbot St. Bernard of
Clairvaux assured his followers. Avicenna, a Persian scientist whose view of bodily
health was substantially more enlightened than that of his European contemporaries,
took an intermediate view—advocating moderate exercise but warning of the dangers
posed by its heating effects and its capacity to spread preëxisting impurities throughout
the body.
There also seemed to be some confusion about what exercise actually was. Hayes
mentioned “De Arte Gymnastica,” a 1569 treatise by an Italian nobleman named
Girolamo Mercuriale, which is considered the rst book on sports medicine. The forms
of exercise Mercuriale discussed included being a passenger in a boat rowed by
someone else. “It’s kind of sweet,” Hayes said. “He believed that because it causes
movement and movement had an effect on the humors within the body, it would be a
good thing.” Until the Victorian era, when sporting activity came to be regarded as a
moral safeguard against dissipation, vigorous exercise was still cautioned against,
particularly in the case of women. It was thought to lead to strain, fatigue, and even
untimely death.
Of course, for most people, through most of human history, not moving has not been
an option. The illustrated exercises
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Renaissance princelings; the feudal peasants laboring on the nobility’s vast estates could
hardly avoid sustained and strenuous activity. Only since industrialization, which made
physical exertion a choice rather than a necessity, have scientists begun to quantify its
virtues—and, in the process, to increase the burden of guilt on those who fail to
squeeze in enough of it around the constraints of their sedentary jobs.
In the sixty years following Morris’s pioneering work, the bene ts of exercise have been
measured in study after study. Researchers soon silenced any remaining doubts over
Morris’s ndings, repeatedly demonstrating that physical activity helped reduce deaths
from heart disease and stroke. Subsequent studies—examining, variously, twins, the
Amish, Danish workers forced to take the elevator, and Dallas students prescribed bed
rest—showed that a lack of exercise was tied to the early onset of more than forty
chronic diseases or conditions, from constipation and colon cancer to depression and
diabetes. Today, more than a hundred thousand published papers testify to the
connection between exercise and health. Barely a week goes past without a headline
linking exercise to stronger bones, a reduced risk of dementia, the ability to learn new
languages, and, of course, better sex. Countless institutions, including the World Health
Organization and the Centers for Disease Control, recommend at least a hundred and
fty minutes of exercise a week. Such is the weight of medical evidence that, if
something could be developed to safely mimic the bene ts of exercise, it would likely
be the most valuable pharmaceutical in the world. Yet, at the same time, the sheer range
of those bene ts suggests that it is unlikely that any single drug could have such wide-
ranging effects.
he real problem, according to Ron Evans, lies in the term “exercise,” which is too
T general to be useful. “You have to be more granular about it,” he told me. He
suspects that a mere handful of biochemical pathways will prove to be responsible for
the majority of exercise’s bene ts. Among the current eld of exercise-pill competitors,
Evans is the closest to the nish line. He has set up a company, Mitobridge, to take his
improved version of 516 to market; this summer, it launched Phase I trials in humans.
The F.D.A. doesn’t currently recognize metabolic syndrome, let alone lack of exercise,
as a disease. Anyone who wants to market an exercise pill must therefore get it
approved as a treatment for a disease that does meet the F.D.A.’s criteria, in the hope
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conditions. Evans pointed out that statins were initially approved, in the late eighties,
speci cally for people who had had a heart attack; three decades later, they’re routinely
prescribed for tens of millions of people who have only high cholesterol. With this
example in mind, Mitobridge is testing its drug as a treatment for Duchenne Muscular
Dystrophy, an incurable genetic disease that affects one in ve thousand males, causing
their muscles to break down and leading inexorably to death at an average age of
twenty-six. “The economics of getting a drug approved make Duchenne a good target,”
Evans said. “It’s a disease for which there are no good drugs, and the kids who have it
will all die young. That’s an easier sell to the F.D.A.”
Even if everything goes smoothly, however, 516 is multiple trials and several years away
from reaching the market. And although Evans is convinced that his improved version
of the drug is safe, any molecule that affects metabolic processes is necessarily
interacting with a variety of other molecules throughout the body, in ways that we don’t
yet understand. Nonetheless, Evans, James, and Spiegelman are all con dent that legal
drugs mimicking some of the effects of exercise are on their way, sometime within the
next ten to fteen years. Ali Tavassoli, the Southampton researcher, is more skeptical.
“Newspapers, the media—they always get me in to be the cynical Brit on this one,” he
said, laughing at the gung-ho attitude of his American colleagues. His main work lies
in cancer research, and he is all too aware that dramatic changes in cell metabolism are
linked to the growth of tumors. His fear is that arti cially increasing the rate at which
muscle cells burn energy cannot help but have long-term consequences elsewhere in
the body. “Not all of them are going to be good news,” he said.
All drugs have risks: the issue is whether the possible bene ts make the risks
worthwhile. For someone with Duchenne, taking 516 would make perfect sense. There
are a handful of other contexts where a short course of an exercise pill could be
extremely useful. Astronauts, for example, routinely spend two hours a day exercising
on equipment designed to mitigate muscle atrophy and bone loss caused by low gravity,
but they still return to Earth after a six-month space-station stint with mild
osteoporosis and signi cantly weakened muscles. Other people for whom an exercise
pill might be a gamble worth taking include patients recovering from surgery or
attached to a ventilator. Then, there are the elderly. After the age of forty, all of us, even
the athletic, lose about eight per cent of our muscle mass each decade, with a further
Expand
fteen-per-cent decline between the ages of seventy and eighty. The resulting frailty
can be lethal: nearly half of seniors hospitalized for a hip fracture never go home.
The cost-bene t analysis becomes murkier in the case of the estimated eighty per cent
of American adults who do not get their recommended hundred and fty minutes of
exercise each week. From a public-health perspective, physical inactivity is one of the
most signi cant problems of the twenty- rst century. One recent study found that, of
all the deaths in Europe in 2008, seven per cent could be attributed to inactivity—more
than twice as many as were caused by obesity. “So which is better for those people?”
Willson, the original developer of 516, asked me. “Being told—again—to exercise for
thirty minutes a day, or taking a pill?”
One could respond with another question: Why can’t humans just be more like mice?
Why do so many of us choose to skip exercise in favor of watching TV or catching up
on e-mail? I talked to Theodore Garland, a biologist at the University of California,
Riverside, who has studied variations in voluntary physical activity between species. He
pointed to theories that much of human development has been motivated by the
imperative to conserve energy, and suggested that, over evolutionary time, different
species tend to develop neurochemical reward systems that make movement more
appealing, or less, based on their survival needs. Instead of designing a pill to replace
exercise in humans, Garland favors a different pharmaceutical solution. “Personally, I’ve
been more interested in the possibility of drugs that would make us more motivated to
exercise,” he said.
taste for exercise, I gradually realized, was something that all the pill researchers
A had in common. Spiegelman follows a strict regimen of kickboxing, running, and
lifting weights. Tavassoli is a surfer and rock climber; Evans and James are cyclists.
Willson is a triathlete, who recently completed his eleventh Half Ironman. “I train
because that’s part of the way I live,” he said “It’s part of my personality. I love that
discipline of having to exercise regularly.” Taking a pill, he said, would feel like
cheating.
“In a lot of people’s eyes, the development of an exercise pill is a bad thing,” Evans said.
“They say we’re trying to undermine exercise in America.” The more accurate charge is
that Evans’s research may3 rede
You have ne exercise—for
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same way that other elds of metabolic Subscribe
research havenow.
gradually rede ned food. During
the nineteenth and twentieth centuries, as scientists discovered vitamins, minerals, and
phytochemicals, “food” was transformed into “nutrients.” That conceptual shift paved
the way for dietary pyramids, labelling laws, the rise of so-called superfoods, and even
wholesale food replacements such as Soylent. In the coming years, as research provides
us with new ways of understanding and quantifying physical activity, our relationship
with exercise will surely change. A morning jog will be reclassi ed as a good source of
bene cial chemicals; sports may be redesigned to optimize their molecular outcomes. A
scienti c understanding of the parts may well come at the expense of appreciating the
immeasurable whole.
lthough 516 has not been approved as a drug, plenty of people are taking it. Once
A the structure of a new compound has been published, chemical-supply
laboratories are free to synthesize it for sale, “for research purposes only.” 516 is easy
and relatively cheap to make, and it is readily available online. The earliest adopters
were élite athletes looking for an edge. The World Anti-Doping Agency added 516 to
its list of prohibited substances in 2009, and testing for it is now routine. Since then, at
least six professional cyclists have been suspended after being caught taking the drug.
More recently, 516 has become popular among the kind of men—and they are almost
all men—who frequent messages boards with names like “Think Steroids,” “Swol HQ,”
and “Juiced Muscle.” All across this peculiar corner of the Internet, guys whose avatars
typically feature headless sel es in body-building poses are dosing themselves with 516
and sharing their reactions—usually anonymously, using such screen names as
Macho313, nofatchix, and Big Beef.
I joined a couple of forums to ask these men about their experiences using 516. Most
were unwilling to talk, let alone be identi ed, but eventually a member of the
MuscleChemistry.com forum agreed to correspond with me, on the condition that I
refer to him only by his online handle, Iron Julius. He told me that he lived in a small
town in the South and was a father of three. He began taking the drug sometime in
2012, having heard about it on another board. “It wasn’t yet very popular but the little
info there was made it sound like something I might like,” he wrote. Iron Julius’s wife
had been nagging him to start running with her, but his bulk made him hesitate. Still,
he signed up for a ve-kilometre race, mostly to support her. He started taking 516 ve
days before the race. “I was just planning to walk a good bit,” he wrote. “But I actually
ran with her the entire time. It get
blew mytote.
a free mind how good
Subscribe now. I felt.”
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Iron Julius still takes 516, although lately he has noticed a decrease in the drug’s quality.
“I’m a volunteer re ghter so stamina at times is very important,” he explained. “If you
research, many police and re ghters are on some form of performance-enhancing
substance as the jobs are sometimes physically demanding.” Iron Julius told me that
around a third of the people he sees at the gym are using 516, without any side effects
that he’s heard about. When I asked whether he would recommend it, his response was,
“Hell yeah man, try it. It don’t mess with hormones and it increases performance.”
So I ordered some. A few weeks later, a twenty-milligram bottle of 516 arrived, taped
into a sealed Tyvek envelope. It was about the size of the complimentary shampoo you
get in hotels and contained a cloudy white liquid with a faint smell of nail-polish
remover. A label instructed me to “see accompanying information”—there wasn’t any—
for dosage instructions. Below that were two contradictory phrases: “Rx only” and “Not
for human consumption.”
I called Tim Willson, the drug’s designer, to ask whether he would take it. “No,” he
said, without hesitation. I contacted the other researchers and found that none of them
had ever taken an exercise pill, in any form. I put the bottle to one side of my desk
while I pondered not only the advisability of ingesting a likely carcinogen but also the
fact that I actually enjoy exercise and get plenty of it. Since then, the bottle has sat on
my desk, undisturbed. During the past month, its contents appear to have developed a
faint, yellowish tinge. ♦
Published in the print edition of the November

November 6, 2017 , issue, with the headline “The
Exercise Pill.”
Nicola Twilley began contributing to The New Yorker in 2014. She is a co-host of the podcast
“Gastropod” and is at work on two books: one about refrigeration and the other about
quarantine. Read more »
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11/24/2019 A Pill to Make Exercise Obsolete | The New Yorker

Annals of Science November 6, 2017 Issue

By Nicola Twilley October 30, 2017

he compound 516 was developed in the late nineties, in the laboratories of

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