A Familys Race to Cure a Daughters Genetic Disease

One July afternoon last summer, Matt Wilsey distributed small plastic tubes to 60 people gathered in a Palo Alto, California, hotel. Most of them had traveled thousands of miles to be here; now, each popped the top off a barcoded tube, spat in about half a teaspoon of saliva, and closed the tube. Some massaged their cheeks to produce enough spit to fill the tubes. Others couldn’t spit, so a technician rolled individual cotton swabs along the insides of their cheeks, harvesting their skin cells—and the valuable DNA inside.

One of the donors was Asger Vigeholm, a Danish business developer who had traveled from Copenhagen to be here, in a nondescript lobby at the Palo Alto Hilton. Wilsey is not a doctor, and Vigeholm is not his patient. But they are united in a unique medical pursuit.

Wilsey’s daughter, Grace, was one of the first children ever diagnosed with NGLY1 deficiency. It’s a genetic illness defined by a huge range of physical and mental disabilities: muscle weakness, liver problems, speech deficiencies, seizures. In 2016, Vigeholm’s son, Bertram, became the first child known to die from complications of the disease. Early one morning, as Bertram, age four, slept nestled between his parents, a respiratory infection claimed his life, leaving Vigeholm and his wife, Henriette, to mourn with their first son, Viktor. He, too, has NGLY1 deficiency.

Grace and her mother, Kristen Wilsey.


The night before the spit party, Vigeholm and Wilsey had gathered with members of 16 other families, eating pizza and drinking beer on the hotel patio as they got to know each other. All of them were related to one of the fewer than 50 children living in the world with NGLY1 deficiency. And all of them had been invited by the Wilseys—Matt and his wife Kristen, who in 2014 launched the Grace Science Foundation to study the disease.

These families had met through an online support group, but this was the first time they had all come together in real life. Over the next few days in California, every family member would contribute his or her DNA and other biological samples to scientists researching the disease. On Friday and Saturday, 15 of these scientists described their contributions to the foundation; some studied the NGLY1 gene in tiny worms or flies, while others were copying NGLY1 deficient patients’ cells to examine how they behaved in the lab. Nobody knows what makes a single genetic mutation morph into all the symptoms Grace experiences. But the families and scientists were there to find out—and maybe even find a treatment for the disease.

That search has been elusive. When scientists sequenced the first human genome in 2000, geneticist Francis Collins, a leader of the Human Genome Project that accomplished the feat, declared that it would lead to a “complete transformation in therapeutic medicine” by 2020. But the human genome turned out to be far more complex than scientists had anticipated. Most disorders, it’s now clear, are caused by a complicated mix of genetic faults and environmental factors.

And even when a disease is caused by a defect in just one gene, like NGLY1 deficiency, fixing that defect is anything but simple. Scientists have tried for 30 years to perfect gene therapy, a method for replacing defective copies of genes with corrected ones. The first attempts used modified viruses to insert corrected genes into patients’ genomes. The idea appeared elegant on paper, but the first US gene therapy to treat an inherited disease—for blindness—was approved just last year. Now scientists are testing methods such as Crispr, which offers a far more precise way to edit DNA, to replace flawed genes with error-free ones.

Certainly, the genetics revolution has made single-mutation diseases easier to identify; there are roughly 7,000, with dozens of new ones discovered each year. But if it’s hard to find a treatment for common genetic diseases, it’s all but impossible for the very rare ones. There’s no incentive for established companies to study them; the potential market is so small that a cure will never be profitable.

Which is where the Wilseys—and the rest of the NGLY1 families—come in. Like a growing number of groups affected by rare genetic diseases, they’re leapfrogging pharmaceutical companies’ incentive structures, funding and organizing their own research in search of a cure. And they’re trying many of the same approaches that Silicon Valley entrepreneurs have used for decades.

At 10:30 on a recent Monday morning, Grace is in Spanish class. The delicate 8-year-old with wavy brown hair twisted back into a ponytail sits in her activity chair—a maneuverable kid-sized wheelchair. Her teacher passes out rectangular pieces of paper, instructing the students to make name tags.

Grace grabs her paper and chews it. Her aide gently takes the paper from Grace’s mouth and puts it on Grace’s desk. The aide produces a plastic baggie of giant-sized crayons shaped like cylindrical blocks; they’re easier for Grace to hold than the standard Crayolas that her public school classmates are using.

Grace’s NGLY1 deficiency keeps her from speaking.


At her school, a therapist helps her communicate.


The other kids have written their names and are now decorating their name tags.

“Are we allowed to draw zombies for the decorations?” one boy asks, as Grace mouths her crayons through the baggie.

Grace’s aide selects a blue crayon, puts it in Grace’s hand, and closes her hand over Grace’s. She guides Grace’s hand, drawing letters on the paper: “G-R-A-C-E.”

Grace lives with profound mental and physical disabilities. After she was born in 2009, her bewildering list of symptoms—weak muscles, difficulty eating, failure to thrive, liver damage, dry eyes, poor sleep—confounded every doctor she encountered. Grace didn’t toddle until she was three and still needs help using the toilet. She doesn’t speak and, like an infant, still grabs anything within arm’s reach and chews on it.

Her father wants to help her. The grandson of a prominent San Francisco philanthropist and a successful technology executive, Matt Wilsey graduated from Stanford, where he became friends with a fellow undergraduate who would one day be Grace’s godmother: Chelsea Clinton. Wilsey went on to work in the Clinton White House, on George W. Bush’s presidential campaign, and in the Pentagon.

But it was his return to Silicon Valley that really prepared Wilsey for the challenge of his life. He worked in business development for startups, where he built small companies into multimillion-dollar firms. He negotiated a key deal between online retailer Zazzle and Disney, and later cofounded the online payments company Cardspring, where he brokered a pivotal deal with First Data, the largest payment processor in the world. He was chief revenue officer at Cardspring when four-year-old Grace was diagnosed as one of the first patients with NGLY1 deficiency in 2013—and when he learned there was no cure.

At the time, scientists knew that the NGLY1 gene makes a protein called N-glycanase. But they had no idea how mistakes in the NGLY1 gene caused the bewildering array of symptoms seen in Grace and other kids with NGLY1 deficiency.

Wilsey’s experience solving technology problems spurred him to ask scientists, doctors, venture capitalists, and other families what he could do to help Grace. Most advised him to start a foundation—a place to collect money for research that might lead to a cure for NGLY1 deficiency.

As many as 30 percent of families who turn to genetic sequencing receive a diagnosis. But most rare diseases are new to science and medicine, and therefore largely untreatable. More than 250 small foundations are trying to fill this gap by sponsoring rare disease research. They’re funding scientists to make animals with the same genetic defects as their children so they can test potential cures. They’re getting patients’ genomes sequenced and sharing the results with hackers, crowdsourcing analysis of their data from global geeks. They’re making bespoke cancer treatments and starting for-profit businesses to work on finding cures for the diseases that affect them.

“Start a foundation for NGLY1 research, get it up and running, and then move on with your life,” a friend told Wilsey.

Wilsey heeded part of that advice but turned the rest of it on its head.

In 2014, Wilsey left Cardspring just before it was acquired by Twitter and started the Grace Science Foundation to fund research into NGLY1 deficiency. The foundation has committed $7 million to research since then, most of it raised from the Wilseys’ personal network.

Many other families with sick loved ones have started foundations, and some have succeeded. In 1991, for instance, a Texas boy named Ryan Dant was diagnosed with a fatal muscle-wasting disease called mucopolysaccharidosis type 1. His parents raised money to support an academic researcher who was working on a cure for MPS1; a company agreed to develop the drug, which became the first approved treatment for the disease in 2003.

But unlike Dant, Grace had a completely new disease. Nobody was researching it. So Wilsey began cold-calling dozens of scientists, hoping to convince them to take a look at NGLY1 deficiency; if they agreed to meet, Wilsey read up on how their research might help his daughter. Eventually he recruited more than 100 leading scientists, including Nobel Prize-winning biologist Shinya Yamanaka and Carolyn Bertozzi, to figure out what was so important about N-glycanase. He knew that science was unpredictable and so distributed Grace Science’s funding through about 30 grants worth an average of $135,000 apiece.

Two years later, one line of his massively parallel attack paid off.

Matt Wilsey, Grace’s father.


Bertozzi, a world-leading chemist, studies enzymes that add and remove sugars from other proteins, fine-tuning their activity. N-glycanase does just that, ripping sugars off from other proteins. Our cells are not packed with the white, sweet stuff that you add to your coffee. But the tiny building blocks of molecules similar to table sugar can also attach themselves to proteins inside cells, acting like labels that tell the cell what to do with these proteins.

Scientists thought that N-glycanase’s main role was to help recycle defective proteins, but many other enzymes are also involved in this process. Nobody understood why the loss of N-glycanase had such drastic impacts on NGLY1 kids.

In 2016, Bertozzi had an idea. She thought N-glycanase might be more than just a bit player in the cell’s waste management system, so she decided to check whether it interacts with another protein that turns on the proteasomethe recycling machine within each of our cells.

This protein is nicknamed Nerf, after its abbreviation, Nrf1. But fresh-made Nerf comes with a sugar attached to its end, and as long as that sugar sticks, Nerf doesn’t work. Some other protein has to chop the sugar off to turn on Nerf and activate the cellular recycling service.

Think of Nerf’s sugar like the pin in a grenade: You have to remove the pin—or in this case, the sugar—to explode the grenade and break down faulty proteins.

But nobody knew what protein was pulling the pin out of Nerf. Bertozzi wondered if N-glycanase might be doing that job.

To find out, she first tested cells from mice and humans with and without working copies of the NGLY1 gene. The cells without NGLY1 weren’t able to remove Nerf’s sugar, but those with the enzyme did so easily. If Bertozzi added N-glycanase enzymes to cells without NGLY1, the cells began chopping off Nerf’s sugar just as they were supposed to: solid evidence, she thought, that N-glycanase and Nerf work together. N-glycanase pulls the pin (the sugar) out of the grenade (the Nerf protein) to trigger the explosion (boom).

The finding opened new doors for NGLY1 disease research. It gave scientists the first real clue about how NGLY1 deficiency affects patients’ bodies: by profoundly disabling their ability to degrade cellular junk via the proteasome.

As it turns out, the proteasome is also involved in a whole host of other diseases, such as cancer and brain disorders, that are far more common than NGLY1 deficiency. Wilsey immediately grasped the business implications: He had taken a moon shot, but he’d discovered something that could get him to Mars. Pharmaceutical companies had declined to work on NGLY1 deficiency because they couldn’t make money from a drug for such a rare disease. But Bertozzi had now linked NGLY1 deficiency to cancer and maladies such as Parkinson’s disease, through the proteasome—and cancer drugs are among the most profitable medicines.

Suddenly, Wilsey realized that he could invent a new business model for rare diseases. Work on rare diseases, he could argue, could also enable therapies for more common—and therefore profitable—conditions.

In early 2017, Wilsey put together a slide deck—the same kind he’d used to convince investors to fund his tech startups. Only this time, he wanted to start a biotechnology company focused on curing diseases linked to NGLY1. Others had done this before, such as John Crowley, who started a small biotechnology company that developed the first treatment for Pompe disease, which two of his children have. But few have been able to link their rare diseases to broader medical interests in the way that Wilsey hoped to.

He decided to build a company that makes treatments for both rare and common diseases involving NGLY1. Curing NGLY1 disease would be to this company as search is to Google—the big problem it was trying to solve, its reason for existence. Treating cancer would be like Google’s targeted advertising—the revenue stream that would help the company get there.

But his idea had its skeptics, Wilsey’s friends among them.

One, a biotechnology investor named Kush Parmar, told Wilsey about some major obstacles to developing a treatment for NGLY1 deficiency. Wilsey was thinking of using approaches such as gene therapy to deliver corrected NGLY1 genes into kids, or enzyme replacement therapy, to infuse kids with the N-glycanase enzyme they couldn’t make on their own.

But NGLY1 deficiency seems particularly damaging to cells in the brain and central nervous system, Parmar pointed out—places that are notoriously inaccessible to drugs. It’s hard to cure a disease if you can’t deliver the treatment to the right place.

Other friends warned Wilsey that most biotech startups fail. And even if his did succeed as a company, it might not achieve the goals that he wanted it to. Ken Drazan, president of the cancer diagnostics company Grail, is on the board of directors of Wilsey’s foundation. Drazan warned Wilsey that his company might be pulled away from NGLY1 deficiency. “If you take people’s capital, then you have to be open to wherever that product development takes you,” Drazan said.

But Wilsey did have some things going for him. Biotechnology companies have become interested of late in studying rare diseases—ones like the type of blindness for which the gene therapy was approved last year. If these treatments represent true cures, they can command a very high price.

Still, the newly approved gene therapy for blindness may be used in 6,000 people, 100 times more than could be helped by an NGLY1 deficiency cure. Wilsey asked dozens of biotechnology and pharmaceutical companies if they would work on NGLY1 deficiency. Only one, Takeda, Japan’s largest drug company, agreed to conduct substantial early-stage research on the illness. Others turned him down flat.

If no one else was going to develop a drug to treat NGLY1 deficiency, Wilsey, decided, he might as well try. “We have one shot at this,” he says. “Especially if your science is good enough, why not go for it?”

“Matt was showing classic entrepreneurial tendencies,” says Dan Levy, the vice president for small business at Facebook, who has known Wilsey since they rushed the same Stanford fraternity in the 1990s. “You have to suspend a little bit of disbelief, because everything is stacked against you.”

At 11 am, Grace sits in a classroom with a speech therapist. Though Grace doesn’t speak, she’s learning to use her “talker,” a tablet-sized device with icons that help her communicate. Grace grabs her talker and presses the icons for “play” and “music,” then presses a button to make her talker read the words out loud.

The "talker" used for Grace’s therapy.


“OK, play music,” her therapist says, starting up a nearby iPad.

Grace watches an Elmo video on the iPad for a few moments, her forehead crinkled in concentration, her huge brown eyes a carbon copy of her dad’s. Then Grace stops the video and searches for another song.

Suddenly, her therapist slides the iPad out of Grace’s reach.

“You want ‘Slippery Fish,’” her therapist says. “I want you to tell me that.”

Grace turns to her talker: “Play music,” she types again.

The therapist attempts one more time to help Grace say more clearly which particular song she wants. Instead, Grace selects the symbols for two new words.

“Feel mad,” Grace’s talker declares.

Grace working with a therapist in one of their therapy rooms.


There’s no denying how frustrating it can be for Grace to rely on other people to do everything for her, and how hard her family works to meet her constant needs.

Matt and Kristen can provide the therapy, equipment, medicines, and around-the-clock supervision that Grace needs to have a stable life. But that is not enough—not for Grace, who wants "Slippery Fish," nor for her parents, who want a cure.

So last summer, Wilsey raised money to bring the Vigeholms and the other NGLY1 families to Palo Alto, where they met with Grace’s doctors and the Grace Science Foundation researchers. One Japanese scientist, Takayuki Kamei, was overjoyed to meet two of the NGLY1 deficiency patients: “I say hello to their cells every morning,” he told their parents.

And because all of these families also want a cure, each also donated blood, skin, spit, stool, and urine to the world’s first NGLY1 deficiency biobank. In four days, scientists collected more NGLY1 deficiency data than had been collected in the entire five years since the disease was discovered. These patient samples, now stored at Stanford University and at Rutgers University, have been divvied up into more than 5,000 individual samples that will be distributed to academic and company researchers who wish to work on NGLY1 deficiency.

That same month, Wilsey closed a seed round of $7 million to start Grace Science LLC. His main backer, a veteran private equity investor, prefers not to be named. Like many in Silicon Valley, he’s recently become attracted to health care by the promise of a so-called “double bottom line”: the potential to both to make money and to do good by saving lives.

Wilsey is chief executive of the company and heavily involved in its scientific strategy. He’s looking for a head scientist with experience in gene therapy and in enzyme replacement therapy, which Mark Dant and John Crowley used to treat their sick children. Gene therapy now seems poised to take off after years of false starts; candidate cures for blood and nervous system disorders are speeding through clinical trials, and companies that use Crispr have raised more than $1 billion.

Wilsey doesn’t know which of these strategies, if any, will save Grace. But he hopes his company will find an NGLY1 deficiency cure within five years. The oldest known NGLY1 deficient patient is in her 20s, but since nobody has been looking for these patients until now, it’s impossible to know how many others—like Bertram—didn’t make it that long.

“We don’t know what Grace’s lifespan is,” Wilsey says. “We’re always waiting for the other shoe to drop.”

But at 3 pm on this one November day, that doesn’t seem to matter.

School’s out, and Grace is seated atop a light chestnut horse named Ned. Five staff members lead Grace through a session of equine therapy. Holding herself upright on Ned’s back helps Grace develop better core strength and coordination.

Grace on her horse.


Grace and Ned walk under a canopy of oak trees. Her face is serene, her usually restless legs still as Ned paces through late-afternoon sunshine. But for a little grace, there may be a cure for her yet.

Read more: https://www.wired.com/story/a-familys-race-to-cure-a-daughters-genetic-disease/

The Second Coming of Ultrasound

Before Pierre Curie met the chemist Marie Sklodowska; before they married and she took his name; before he abandoned his physics work and moved into her laboratory on Rue Lhomond where they would discover the radioactive elements polonium and radium, Curie discovered something called piezoelectricity. Some materials, he found—like quartz and certain kinds of salts and ceramics—build up an electric charge when you squeeze them. Sure, it’s no nuclear power. But thanks to piezoelectricity, US troops could locate enemy submarines during World War I. Thousands of expectant parents could see their baby’s face for the first time. And one day soon, it may be how doctors cure disease.

Ultrasound, as you may have figured out by now, runs on piezoelectricity. Applying voltage to a piezoelectric crystal makes it vibrate, sending out a sound wave. When the echo that bounces back is converted into electrical signals, you get an image of, say, a fetus, or a submarine. But in the last few years, the lo-fi tech has reinvented itself in some weird new ways.

Researchers are fitting people’s heads with ultrasound-emitting helmets to treat tremors and Alzheimer’s. They’re using it to remotely activate cancer-fighting immune cells. Startups are designing swallowable capsules and ultrasonically vibrating enemas to shoot drugs into the bloodstream. One company is even using the shockwaves to heal wounds—stuff Curie never could have even imagined.

So how did this 100-year-old technology learn some new tricks? With the help of modern-day medical imaging, and lots and lots of bubbles.

Bubbles are what brought Tao Sun from Nanjing, China to California as an exchange student in 2011, and eventually to the Focused Ultrasound Lab at Brigham and Women’s Hospital and Harvard Medical School. The 27-year-old electrical engineering grad student studies a particular kind of bubble—the gas-filled microbubbles that technicians use to bump up contrast in grainy ultrasound images. Passing ultrasonic waves compress the bubbles’ gas cores, resulting in a stronger echo that pops out against tissue. “We’re starting to realize they can be much more versatile,” says Sun. “We can chemically design their shells to alter their physical properties, load them with tissue-seeking markers, even attach drugs to them.”

Nearly two decades ago, scientists discovered that those microbubbles could do something else: They could shake loose the blood-brain barrier. This impassable membrane is why neurological conditions like epilepsy, Alzheimer’s, and Parkinson’s are so hard to treat: 98 percent of drugs simply can’t get to the brain. But if you station a battalion of microbubbles at the barrier and hit them with a focused beam of ultrasound, the tiny orbs begin to oscillate. They grow and grow until they reach the critical size of 8 microns, and then, like some Grey Wizard magic, the blood-brain barrier opens—and for a few hours, any drugs that happen to be in the bloodstream can also slip in. Things like chemo drugs, or anti-seizure medications.

This is both super cool and not a little bit scary. Too much pressure and those bubbles can implode violently, irreversibly damaging the barrier.

That’s where Sun comes in. Last year he developed a device that could listen in on the bubbles and tell how stable they were. If he eavesdropped while playing with the ultrasound input, he could find a sweet spot where the barrier opens and the bubbles don’t burst. In November, Sun’s team successfully tested the approach in rats and mice, publishing their results in Proceedings in the National Academy of Sciences.

“In the longer term we want to make this into something that doesn’t require a super complicated device, something idiot-proof that can be used in any doctor’s office,” says Nathan McDannold, co-author on Sun’s paper and director of the Focused Ultrasound Lab. He discovered ultrasonic blood-brain barrier disruption, along with biomedical physicist Kullervo Hynynen, who is leading the world’s first clinical trial evaluating its usefulness for Alzheimer’s patients at the Sunnybrook Research Institute in Toronto. Current technology requires patients to don special ultrasound helmets and hop in an MRI machine, to ensure the sonic beams go to the right place. For the treatment to gain any widespread traction, it’ll have to become as portable as the ultrasound carts wheeled around hospitals today.

More recently, scientists have realized that the blood-brain barrier isn’t the only tissue that could benefit from ultrasound and microbubbles. The colon, for instance, is pretty terrible at absorbing the most common drugs for treating Crohn’s disease, ulcerative colitis, and other inflammatory bowel diseases. So they’re often delivered via enemas—which, inconveniently, need to be left in for hours.

But if you send ultrasound waves waves through the colon, you could shorten that process to minutes. In 2015, pioneering MIT engineer Robert Langer and then-PhD student Carl Schoellhammer showed that mice treated with mesalamine and one second of ultrasound every day for two weeks were cured of their colitis symptoms. The method also worked to deliver insulin, a far larger molecule, into pigs.

Since then, the duo has continued to develop the technology within a start-up called Suono Bio, which is supported by MIT’s tech accelerator, The Engine. The company intends to submit its tech for FDA approval in humans sometime later this year.

Ultrasound sends pressure waves through liquid in the body, creating bubble-filled jets that can propel microscopic drug droplets like these into surrounding tissues.
Suono Bio

Instead of injecting manufactured microbubbles, Suono Bio uses ultrasound to make them in the wilds of the gut. They act like jets, propelling whatever is in the liquid into nearby tissues. In addition to its backdoor approach, Suono is also working on an ultrasound-emitting capsule that could work in the stomach for things like insulin, which is too fragile to be orally administered (hence all the needle sticks). But Schoellhammer says they have yet to find a limit on the kinds of molecules they can force into the bloodstream using ultrasound.

“We’ve done small molecules, we’ve done biologics, we’ve tried DNA, naked RNA, we’ve even tried Crispr,” he says. “As superficial as it may sound, it all just works.”

Earlier this year, Schoellhammer and his colleagues used ultrasound to deliver a scrap of RNA that was designed to silence production of a protein called tumor necrosis factor in mice with colitis. (And yes, this involved designing 20mm-long ultrasound wands to fit in their rectums). Seven days later, levels of the inflammatory protein had decreased sevenfold and symptoms had dissipated.

Now, without human data, it’s a little premature to say that ultrasound is a cure-all for the delivery problems facing gene therapies using Crispr and RNA silencing. But these early animal studies do offer some insights into how the tech might be used to treat genetic conditions in specific tissues.

Even more intriguing though, is the possibility of using ultrasound to remotely control genetically-engineered cells. That’s what new research led by Peter Yingxiao Wang, a bioengineer at UC San Diego, promises to do. The latest craze in oncology is designing the T-cells of your immune system to better target and kill cancer cells. But so far no one has found a way to go after solid tumors without having the T-cells also attack healthy tissue. Being able to turn on T-cells near a tumor but nowhere else would solve that.

Wang’s team took a big step in that direction last week, publishing a paper that showed how you could convert an ultrasonic signal into a genetic one. The secret? More microbubbles.

This time, they coupled the bubbles to proteins on the surface of a specially designed T-cell. Every time an ultrasonic wave passed by, the bubble would expand and shrink, opening and closing the protein, letting calcium ions flow into the cell. The calcium would eventually trigger the T-cell to make a set of genetically encoded receptors, directing it it to attack the tumor.

“Now we’re working on figuring out the detection piece,” says Wang. “Adding another receptor so that we’ll known when they’ve accumulated at the tumor site, then we’ll use ultrasound to turn them on.”

In his death, Pierre Curie was quickly eclipsed by Marie; she went on to win another Nobel, this time in chemistry. The discovery for which she had become so famous—radiation—would eventually take her life, though it would save the lives of so many cancer patients in the decades to follow. As ultrasound’s second act unfolds, perhaps her husband’s first great discovery will do the same.

Read more: https://www.wired.com/story/the-second-coming-of-ultrasound/

The Most Promising Cancer Treatments In a Century Have ArrivedBut Not For Everyone

In 1891, a New York doctor named William B. Coley injected a mixture of beef broth and Streptococcus bacteria into the arm of a 40-year-old Italian man with an inoperable neck tumor. The patient got terribly sick—developing a fever, chills, and vomiting. But a month later, his cancer had shrunk drastically. Coley would go on to repeat the procedure in more than a thousand patients, with wildly varying degrees of success, before the US Food and Drug Administration shut him down.

Coley’s experiments were the first forays into a field of cancer research known today as immunotherapy. Since his first experiments, the oncology world has mostly moved on to radiation and chemo treatments. But for more than a century, immunotherapy—which encompasses a range of treatments designed to supercharge or reprogram a patient’s immune system to kill cancer cells—has persisted, mostly around the margins of medicine. In the last few years, though, an explosion of tantalizing clinical results have reinvigorated the field and plunged investors and pharma execs into a spending spree.

Though he didn’t have the molecular tools to understand why it worked, Coley’s forced infections put the body’s immune system into overdrive, allowing it to take out cancer cells along the way. While the FDA doesn’t have a formal definition for more modern immunotherapies, in the last few years it has approved at least eight drugs that fit the bill, unleashing a flood of money to finance new clinical trials. (Patients had better come with floods of money too—prices can now routinely top six figures.)

But while the drugs are dramatically improving the odds of survival for some patients, much of the basic science is still poorly understood. And a growing number of researchers worry that the sprint to the clinic offers cancer patients more hype than hope.

When immunotherapy works, it really works. But not for every kind of cancer, and not for every patient—not even, it turns out, for the majority of them. “The reality is immunotherapy is incredibly valuable for the people who can actually benefit from it, but there are far more people out there who don’t benefit at all,” says Vinay Prasad, an Oregon Health and Science University oncologist.

Prasad has come to be regarded as a professional cancer care critic, thanks to his bellicose Twitter style and John Arnold Foundation-backed crusade against medical practices he says are based on belief, not scientific evidence. Using national cancer statistics and FDA approval records, Prasad recently estimated the portion of all patients dying from all types of cancer in America this year who might actually benefit from immunotherapy. The results were disappointing: not even 10 percent.

Now, that’s probably a bit of an understatement. Prasad was only looking at the most widely used class of immunotherapy drugs in a field that is rapidly expanding. Called checkpoint inhibitors, they work by disrupting the immune system’s natural mechanism for reining in T cells, blood-borne sentinels that bind and kill diseased cells throughout the body. The immune cells are turned off most of the time, thanks to proteins that latch on to a handful of receptors on their surface. But scientists designed antibodies to bind to those same receptors, knocking out the regulatory protein and keeping the cells permanently switched to attack mode.

The first checkpoint inhibitors just turned T cells on. But some of the newer ones can work more selectively, using the same principle to jam a signal that tumors use to evade T cells. So far, checkpoint inhibitors have shown near-miraculous results for a few rare, previously incurable cancers like Hodgkin’s lymphoma, renal cell carcinoma, and non-small cell lung cancer. The drugs are only approved to treat those conditions, leaving about two-thirds of terminal cancer patients without an approved immunotherapy option.

But Prasad says that isn’t stopping physicians from prescribing the drugs anyway.

“Hype has encouraged rampant off-label use of checkpoint inhibitors as a last-ditch effort,” he says—even for patients with tumors that show no evidence they’ll respond to the drugs. The antibodies are available off the shelf, but at a list price near $150,000 per year, it’s an investment Prasad says doctors shouldn’t encourage lightly. Especially when there’s no reliable way of predicting who will respond and who won’t. “This thwarts one of the goals of cancer care," says Prasad. "When you run out of helpful responses, how do you help a patient navigate what it means to die well?”

Merck and Bristol-Myers Squibb have dominated this first wave of immunotherapy, selling almost $9 billion worth of checkpoint inhibitors since they went on sale in 2015. Roche, AstraZeneca, Novartis, Eli Lilly, Abbvie, and Regeneron have all since jumped in the game, spending billions on acquiring biotech startups and beefing up in-house pipelines. And 800 clinical trials involving a checkpoint inhibitor are currently underway in the US, compared with about 200 in 2015. “This is not sustainable,” Genentech VP of cancer immunology Ira Mellman told the audience at last year’s annual meeting of the Society for Immunotherapy of Cancer. With so many trials, he said, the industry was throwing every checkpoint inhibitor combination at the wall just to see what would stick.

After more than a decade stretching out the promise of checkpoint inhibitors, patients—and businesses—were ready for something new. And this year, they got it: CAR T cell therapy. The immunotherapy involves extracting a patient’s T cells and genetically rewiring them so they can more efficiently home in on tumors in the body—training a foot soldier as an assassin that can slip behind enemy lines.

In September, the FDA cleared the first CAR-T therapy—a treatment for children with advanced leukemia, developed by Novartis—which made history as the first-ever gene therapy approved for market. A month later the agency approved another live cell treatment, developed by Kite Pharma, for a form of adult lymphoma. In trials for the lymphoma drug, 50 percent of patients saw their cancer disappear completely, and stay gone.

Kite’s ascendance in particular is a stunning indicator of how much money CAR-T therapy has attracted, and how fast. The company staged a $128 million IPO in 2014—when it had only a single late-phase clinical trial to its name—and sold to Gilead Science in August for $11.9 billion. For some context, consider that when Pfizer bought cancer drugmaker Medivation for $14 billion last year—one of the biggest pharma deals of 2016—the company already had an FDA-approved blockbuster tumor-fighter on the market with $2 billion in annual sales, plus two late-stage candidates in the pipeline.

While Kite and Novartis were the only companies to actually launch products in 2017, more than 40 other pharma firms and startups are currently building pipelines. Chief rival Juno Therapeutics went public with a massive $265 million initial offering—the largest biotech IPO of 2014—before forming a $1 billion partnership with Celgene in 2015. In the last few years, at least half a dozen other companies have made similar up-front deals worth hundreds of millions.

These treatments will make up just a tiny slice of the $107 billion cancer drug market. Only about 600 people a year, for example, could benefit from Novartis’ flagship CAR-T therapy. But the company set the price for a full course of treatment at a whopping $475,000. So despite the small clientele, the potential payoff is huge—and the technology is attracting a lot of investor interest. “CAR-T venture financing is still a small piece of total venture funding in oncology, but given that these therapies are curative for a majority of patients that have received them in clinical trials, the investment would appear to be justified,” says Mandy Jackson, a managing editor for research firm Informa Pharma Intelligence.

CAR-T, with its combination of gene and cell therapies, may be the most radical anticancer treatment ever to arrive in clinics. But the bleeding edge of biology can be a dangerous place for patients.

Sometimes, the modified T cells go overboard, excreting huge quantities of molecules called cytokines that lead to severe fevers, low blood pressure, and difficulty breathing. In some patients it gets even worse. Sometimes the blood-brain barrier inexplicably breaks down—and the T cells and their cytokines get inside patients’ skulls. Last year, Juno pulled the plug on its lead clinical trial after five leukemia patients died from massive brain swelling. Other patients have died in CAR-T trials at the National Cancer Institute and the University of Pennsylvania.

Scientists don’t fully understand why some CAR-T patients experience cytokine storms and neurotoxicity and others come out cured. “It’s kind of like the equivalent of getting on a Wright Brother’s airplane as opposed to walking on a 747 today,” says Wendell Lim, a biophysical chemist and director of the UC San Francisco Center for Systems and Synthetic Biology. To go from bumping along at a few hundred feet to cruise control at Mach 0.85 will mean equipping T cells with cancer-sensing receptors that are more specific than the current offerings.

Take the two FDA-approved CAR-T cell therapies, he says. They both treat blood cancers in which immune responders called B cells become malignant and spread throughout the body. Doctors reprogram patients’ T cells to seek out a B cell receptor called CD-19. When they find it, they latch on and shoot it full of toxins. Thing is, the reprogrammed T cells can’t really tell the difference between cancerous B cells and normal ones. The therapy just takes them all out. Now, you can live without B cells if you receive antibody injections to compensate—so the treatment works out fine most of the time.

But solid tumors are trickier—they’re made up of a mix of cells with different genetic profiles. Scientists have to figure out which tumor cells matter to the growth of the cancer and which ones don’t. Then they have to design T cells with antigens that can target just those ones and nothing else. An ideal signature would involve two to three antigens that your assassin T cells can use to pinpoint the target with a bullet instead of a grenade.

Last year Lim launched a startup called Cell Design Labs to try to do just that, as well as creating a molecular on-off-switch to make treatments more controlled. Only if researchers can gain this type of precise command, says Lim, will CAR-T treatments become as safe and predictable as commercial airline flight.

The field has matured considerably since Coley first shot his dying patient full of a dangerous bacteria, crossed his fingers, and hoped for the best. Sure, the guy lived, even making a miraculous full recovery. But many after him didn’t. And that “fingers crossed” approach still lingers over immunotherapy today.

All these years later, the immune system remains a fickle ally in the war on cancer. Keeping the good guys from going double-agent is going to take a lot more science. But at least the revolution will be well-financed.

Read more: https://www.wired.com/story/cancer-immunotherapy-has-arrived-but-not-for-everyone/

The FDA has approved a blood sugar monitor that doesnt require a finger prick

Further proof the U.S. Food and Drug Administration has been warming up to modern technology — it has just approved the first continuous blood sugar monitor that doesn’t require the user to prick themselves over and over for a blood sample.

Today, the FDA cleared Abbot’s FreeStyle Libre Flash Glucose Monitoring System, a device that uses a small sensor wire inserted under the skin to determine glucose levels in adult diabetics. Another wand-like device is then waved over the sensor to measure and give a readout of those glucose levels.

This is a milestone move for the FDA as diabetes affects nearly 30 million people in the United States who currently have to test their blood sugar by pricking themselves several times throughout the day and every time they eat.

However, the idea for a prickless blood sugar monitor isn’t new. Tech companies have increasingly shown an interest in the massive diabetics market over the past few years. Apple is rumored to be working on such a device and its CEO Tim Cook has even been spotted wearing a possible prototype that could connect to the Apple Watch.

Other companies endeavor to build something similar, including Glucowise, which has a device still under development.

However, it seems it’s not so easy to create a needleless blood sugar detector. Google tried to build a contact lens that could detect glucose but it seems the project has gone nowhere since drug company Novartis licensed the tech in 2014. Another FDA-approved device for glucose monitoring without the prick called the GlucoWatch was approved in the early 2000’s, but consumers found it cumbersome and it happened to cause a bad rash in some.

But there’s new hope today that the Freestyle monitor has worked out all the kinks. The device is intended for those 18 and older and, after a 12-hour start-up period, can be worn for up to 10 days, according to a statement on the FDA’s website.

“The FDA is always interested in new technologies that can help make the care of people living with chronic conditions, such as diabetes, easier and more manageable,” said FDA spokesperson Donald St. Pierre. “This system allows people with diabetics to avoid the additional step of finger stick calibration, which can sometimes be painful, but still provides necessary information for treating their diabetes—with a wave of the mobile reader.”

Read more: https://techcrunch.com/2017/09/28/the-fda-has-approved-the-first-blood-sugar-monitor-that-doesnt-require-a-finger-prick/

You Lied Your Way Into A Job As A Surgeon! Can You Avoid Killing Anyone Long Enough To Collect Your First Paycheck?

Surgeons. The masters of the flesh. The gatekeepers of the organs. The doctors who get to shave patients.

These are the green-wearing gods who know that the human body is but a chessboard, and that the nipples are the king and queen, and the belly button is the opposing king or queen.

Today, finally, you are beginning your journey as one of them.

You have already gone through the arduous process of becoming a surgeon. After calling the hospital over and over every day for three weeks straight and praising Tylenol in the deepest voice you could muster to whoever picked up, being hung up on by countless doctors and nurses, you finally hit the big time.

Yesterday, you managed to get the chief of medicine on the line, who offered you a job after a mere 50 minutes of you bellowing to her about the white-and-red pill. Congratulations!

Okay. Being a surgeon is sweet as hell. You get to wear patients’ clothes around a hospital once the chemicals put them to sleep, you can eat as many tortilla chips as you want, and you can hide all of your favorite DVDs and family heirlooms inside toxic waste bins, the one place thieving pricks are too grossed out by to steal from.

Cool. But the best part of being a surgeon, bar none, is that incredible surgeon paycheck.

It’s no secret that surgeons are paid well, as every single day at 8 p.m., hardworking surgeons all over the world reap the fruits of their labor: a plastic bag filled with $600, given to them by their chief of medicine on their way out the door, in addition to a goodnight kiss on the forehead.

Exactly. So now that you’re a surgeon, you better do everything in your power to make it your $600 payday, because there is one universal stipulation that could jam you up: If a surgeon kills someone, everything completely goes to shit.

1) For starters, once a surgeon kills someone, they are NEVER allowed back in a hospital, ever. Even if you just want to go to hang out or to meet new lovers.

2) Your professional reference completely goes out the window. If a new job calls to ask about you, instead of a recommendation, the HR department hands the phone off to the absolute sickest pervert patient they have, and lets them air out whatever they’ve got kickin’ around up in their minds.

3) Lastly—and this one is the worst of all—you don’t get paid a dime, which would mean all of your efforts to become a surgeon were for NOTHING.

So, if you want to get to that sweet paycheck, you’re going to have to make it through one entire day as a surgeon without killing someone.

The hospital. The place where people come when they are bored to take off their pants and scream. This will be your new surgeon home, and today is your first day of work. As far as anyone inside is concerned, you are now a fully qualified surgeon, so if you want those 600 clams, you’re going to have to hold your own and stay off everyone’s radar.

“Please give me a surgery.”

Ah, shit. A sick kid is waiting for you right inside the lobby, and he looks all kinds of fucked up.

“I need a surgery pronto. I am dying, and it feels like none of my bones are connected to my other bones. I also have a rash that comes and goes. Please do surgery to me with your other doctor friends.”

“If you don’t give me a surgery right now, I will scream. I will scream so loud and for so long, and I will point at you the whole time. It will go on for so long that the rest of the doctors here will have no choice but to send you to jail.”

That was close. You’ve pissed your pants real good, and now you’re in the bathroom splashing your pants with water, the best way to clean pants that you’ve urinated in.

“You sure know your way around cleaning a pair of pissed pants, sport. Not bad at all.”

You look over and see that it’s the hospital’s janitor talking to you. He somehow opened the door in perfect silence while you were inside splashing your pants, and has been watching you for upwards of 90 full seconds.

“I’ve been watching you for upwards of 90 full seconds, and I can tell just by looking at you, you’re no surgeon.”

“Easy, easy. I’m not gonna rat you out. I’m gonna help you.

I take it that you’re in here lying to be a surgeon, hoping to get ‘The $600 Bag Treatment,’ huh? Well, you’ve got a friend in me. I’ve seen it before, and I’ll see it again. All you gotta do is make it until 8 p.m. without killing a soul and you’re in the clear. So whadya say you come lay low with me for the rest of the day, spend some time hanging with a new bud so you don’t end up killin’ no one before you get that money?”

“I, uh, how do you mean?” he says, visibly becoming self-conscious about the entire interaction so far. “I’m just tired today, so if I’m acting weird, that’s what that’s about, probably. Allergies are being weird, too.”

“Follow me!” the janitor says before sprinting down the hallway. You do your best to keep up with him as he weaves in and out of patients and doctors before you finally arrive at a huge metal door. He slides open the rusty door to reveal a set of long, winding stairs that lead to a dark, desolate basement, and turns to you with a half smile.

“It’s not delivery, it’s DiGiorno,” he says before letting out a quick, uncertain laugh, looking over his shoulder at you to kind of check in and see if you’re laughing or anything at what must have been some sort of joke.

“That was dumb, never mind,” the janitor says, shaking his head as his shoulders slump, trying to explain his joke before slowly progressing into full-blown self-deprecation. “I was thinking, like, how in the old commercials, I’d be the delivery guy and you’re the pizza—I don’t know, forget it. It was dumb. Sorry.”

You follow the janitor down the stairs and into the basement of the hospital, and lo and behold, it’s a full-blown bachelor’s pad! The janitor has stocked the place with some of the best things: a ping-pong table, a “Forever 27” poster, an old-timey popcorn machine, and a bunch of orange pill bottles filled with Frosted Cheerios.

“This is my chill zone. I’m down here almost all the time, which is why the hospital is filthy and patients always seem to get sick immediately after they get better.”

“We got all day, brother, so we could either sit down and talk about that important-looking guitar I have mounted on the wall over there, or we could stand near the stairs and wonder if Slash has ever signed a guitar and sold it for $20,000 online before, or maybe we could lay down on the ground and trade stories about the most expensive thing we’ve ever mounted on a wall. Your call.”

“I can’t lift my arms above my waist because of a power-washer accident.”

“You got a good eye, kid,” he says as though you brought it up completely unprompted, proudly looking up at the guitar he somehow mounted unnecessarily high on his wall.

“Believe it or not, Slash signed that guitar, and I was lucky enough to spend all of the money I have on it. I usually don’t do this for anyone, but for you, I’ll climb all the way up there and get it if you want to hold it.”

“I’d climb anywhere for one of my boys.”

“I’ll put a very wet towel over them. I’m sure that will be fine.”

You’ve killed! You’ve killed!

You put the janitor in grave danger by selfishly asking him to grab his Slash guitar off the wall. After the janitor put a soaking-wet towel on top of his countless basement wires in order to walk over to the wall and begin his climb, he was immediately electrocuted and fell crashing to the ground without the ability to raise his arms and break his fall. It’s unclear if it was the electricity surging through his body that did him in, or if it was the way his neck snapped on a nearby stool because of the horrible, unnatural way he fell. But either way, he is definitely dead, and it is your fault.

You’re no longer a surgeon, and you can kiss that bag of $600 goodbye.

As you go back up the stairs and start heading toward the lobby, you can hear that he starts to follow you, but then locks himself in the bathroom you were in earlier and begins screaming at himself in the mirror for messing up what could’ve been a nice day. His screaming gets louder and louder before it comes to a halt after you hear the sound of him snapping his mop over his knee in fury.

“I need you to give me a surgery right now.”

Ah, damn. It’s the sick kid from earlier.

“I feel like I’m on a boat at all hours of the day, and my elbows are dry. I need you to cut me open and drain me out, if that’s what it takes, and to please get me home by later today.”

You pick the kid up, throw him over your shoulder, and walk through the hospital looking for a good room to cut him open in. After 20 minutes, you finally find the room with all of the surgeons in it, and you slam the kid down on the empty table they’re all staring at.

Now all eyes are on you. You’re going to have to step up and say something pretty incredible to get all of these surgeons on your side.

You’ve killed! You’ve killed!

After you said that ridiculous, dumbass comment, every surgeon in the room became furious at you and began hammering you with questions about your qualifications. You tried mumbling through more Tylenol facts, which went much worse in person than it did on the phone, and somewhere during your 25-minute verbal beatdown from the other surgeons, the kid died on the table.

You are no longer a surgeon, and you will never get a plastic bag filled with $600.

Share Your Results

Everyone starts nodding and smiling and patting each other on the back. Good shit.

“Ha, nice,” a woman says, whose voice you recognize from the phone as the chief of medicine at the hospital. She quickly anesthetizes the patient to finally stop him from grabbing and clawing at everyone’s surgical masks, and within seconds the little spaz is sleeping.

At that moment, the tallest doctor you’ve ever seen walks into the door wearing a backwards hat and confidently drinking Barq’s Root Beer out of a 2-liter bottle.

“I’ve never seen you around here,” he says after putting the root beer down firmly into the lap of the unconscious kid and eyeing you up and down suspiciously. “Enlighten us, fresh meat. Now, what surgery are we performing on this little man, exactly?”

Ah, this guy is onto you. Need something big here to throw everyone off your tracks.

“Doctors, you two can be mean to each other in the parking lot all day long if you want to, but that’ll be enough fighting in my hospital,” says the chief of medicine after banging her fist down onto the kid’s chest like a gavel to get everyone’s attention.

“This little boy is in dire need of a heart transplant. We need to start immediately.”

“Doctors, that’ll be enough talk about whether or not there are actually types of surgeries or not, because there simply is not a correct answer,” says the chief of medicine after banging her fist down onto the kid’s chest like a gavel to get everyone’s attention.

“This little boy is in dire need of a heart transplant. We need to start immediately.”

“Doctors, please stop winking at each other,” says the chief of medicine after banging her fist down onto the kid’s chest like a gavel to get everyone’s attention.

“This little boy is in dire need of a heart transplant. We need to start immediately.”

After noticing that no one is reacting to you pissing yourself, you look around and realize that every surgeon in the room has also already pissed themselves. Then you remember that surgeons are constantly pissing themselves during surgery, like bicyclists during races, for reasons completely unknown.

The chief of medicine takes out a toolbox from underneath the surgery-room sink and hands each surgeon a tool. She takes each tool out one by one and starts passing them down the line. One doctor gets a small shovel, one gets a large knife, another gets a pickax, and on and on it goes, until you finally end up with the flashlight!

“Um, yeah, that’s my flashlight, pal. I’m always the flashlight man around here,” says the root-beer doctor.

“No,” interjects the chief. “New guy can hold the flashlight today. I have a good feeling about this.”

Your new rival is stunned. He shoots you a dirty look, threateningly crosses his thumb over his neck, and then does it again with his other thumb, but slower. Then he quietly mouths something that you didn’t really get a good read on, but from what you did see, your best guess is that he was saying something like “Fracking mountains,” or “Simply delicious.” Then he is handed the worst tool: the blood napkin, the tool that wipes up all the loose goo and pus.

“Ah, c’mon, man. Quit it. What the hell.”

The surgery is now well under way. The chief is slicing and dicing and moving parts around left and right. It’s pretty much a one-woman show.

Most of the other doctors are using their tools just to kind of scrape some bones and stuff when they feel like they should get in the mix, usually after not doing anything for a couple minutes straight and getting nervous that someone will notice how they’re not really that crucial to the operation.

You’re getting bored by the whole thing at this point, but at least you’re holding your own with these docs and, most importantly, haven’t killed anyone yet.

Surgery still going. Getting kind of repetitive. A couple doctors shuffled out for a minute and came back with crackers, but the crackers are all gone now. You didn’t even notice they had crackers until there were only, like, four left in the sleeve, so at that point, asking for some really wouldn’t have been cool.

Surgery is getting boring.

Surgery is boring as hell.Your arms got tired from holding the flashlight up, so you put it down for a minute and no one seemed to notice. You’re back up now.

Kid woke up and started screaming LOUD, but now he’s sleeping again.

“You were scared!” “No, you were scared!” “I wasn’t scared, you were scared!” The surgeons are all ragging on each other and having fun again. Finally got some juice in the room. Whole crew got a good laugh out of that one.

Woah, wait a minute. Oh, man. You see something inside the kid’s body. Wedged deep in between his rib cage and his liver, there looks to be something shining and throbbing, and you’re pretty sure you’re the only one who sees it.

Two doctors broke away from the surgery about 15 minutes ago to arm wrestle on a nearby stool, and the rest of the surgeons have all one-by-one walked over to form a circle around them so they can gamble. Meanwhile, the chief is still hacking away at this kid’s organs with all of her might, and seems way too dialed-in to notice the game changer you’ve found.

You’ve killed! You’ve killed!

You thought you were being a hero by yanking out what you thought were some sort of wet, shining metals, but were actually the poor kid’s veins. You are no longer a surgeon, and can go ahead and kiss that sweet paycheck goodbye.

“Those are veins. They are not ‘evil copper and metals sticking out of this poor bastard’s guts.’ Do not call them that.”

Damn. Misread that one. The chief is totally onto you now.

“But I appreciate you speaking your mind when you think something is amiss,” she continues, looking up and making eye contact with you for the first time. “That takes a commitment to the job that some of my other doctors lack at times,” she says, motioning to the doctors across the room who are now attempting to disguise their arm-wrestling gambling ring by draping a hospital gown over the two meaty, dueling arms.

The chief reciprocates your unblinking eye contact and begins nodding in perfect unison with your nodding. This goes on for a good 20 seconds or so, the grunts of the two arm wrestlers and the slaps of cold, hard cash hitting the tile becoming the only sounds in the room.

At that moment, you and the chief simultaneously feel a romantic charge between you, and it feels beautiful and right. But that romantic feeling is immediately followed by a simultaneous paternal feeling, but it’s unclear who is the parent and who is the child. Then the two feelings of physical attraction and familial protectiveness fuse together into one singular emotion, and it feels disgusting to both of you.

“Yeah, yeah, go catch up with them. I’ll hold it down over here, cool,” the chief kind of half-mutters to herself and to you while shaking her head and getting back to surgery.

You walk over to the gambling circle and see the two exhausted surgeons pulling and pushing as hard as they can to win. The two doctors are so evenly matched that their arms aren’t moving or shaking in the slightest. If it weren’t for the veins about to explode out of their temples and the tears streaming down their faces, you’d have no idea how intense the duel was.

All of the other surgeons are quietly going apeshit. Almost all of them are either gently pounding their chests, gingerly slapping the ground, or shaking their fists in the air, all the while whispering bad arm-wrestling advice like “Win the skin!” or “Make him smooth!”

It’s definitely a pretty sweet scene, and you decide that you want to get in the mix.

As you go to ask the doctor next to you, your rival doctor steps in front and interrupts:

“Looking to get in on the action but lacking the funds, newbie? Don’t worry, fresh meat. I got you covered. Also, we’re rival doctors, just in case that wasn’t clear.”

Whoa, pretty cool to get a rival doctor on your first day on the job. That probably usually takes years.

“That’s my coat over there,” he says, pointing to a white lab coat being worn by one of the arm-wrestling surgeons. “Go ahead and take my wallet out of the pocket and take out as much money as you want.”

He then lets out a weird little laugh and looks around to see if anyone else is laughing. One other doctor did laugh, but he’s in the middle of a conversation with another surgeon, so you’re pretty sure the laugh had nothing to do with your rival.

“I have coats all over this hospital that you wouldn’t know a thing about,” he says, raising his fist up to your chin real quick, trying to get you to flinch. You stand your ground and don’t flinch at all, though, and he sheepishly brings his fist back down to his side.

You’ve killed! You’ve killed!

In a brilliantly executed scheme, your rival tricked you into reaching into the coat of one of the doctors who is arm wrestling. When the arm wrestler saw you trying to steal his wallet, his mix of adrenaline and dangerously high blood pressure caused his heart to explode.

Your misconduct has resulted in a death, meaning you can no longer be a surgeon, and you will never see that sweet, sweet bag o’ cash.

Trust me, I’m a fake doctor: how medical imposters thrive in the real world

Versions of Jodie Whittakers bogus TV medic do exist. But fantasists and charlatans tend to operate outside the hospital, where victims have been assaulted, misdiagnosed or offered false hope

Within the first half-hour of the BBCs psychological thriller Trust Me, Cath (a former nurse) had stolen her doctor friends identity, picked up some suturing skills from YouTube, and was handling a stethoscope like a pro. Before you could say: Adrenaline, STAT!, Cath (played by Jodie Whittaker) was a fake doctor at an Edinburgh hospital, yanking twisted ankles into place and shoving chest drains where they belonged.

It couldnt happen in real life, though, could it? It already has. Others with medical backgrounds have posed as fully fledged doctors before. Take Levon Mkhitarian who encountered 3,363 patients in two years, working across seven NHS trusts on oncology, cardiology, transplant and surgical wards as well as in A&E. Mkhitarian, originally from Georgia, had graduated from medical school in the Caribbean island of Grenada and received provisional registration from the General Medical Council (GMC) to work specifically under supervision here. But he failed to complete the year. He went on to fraudulently secure a job anyway, was caught, and then promptly struck off. Undeterred, he forged a host of documents including a medical degree and energy bills, stealing the identity of a genuine doctor. The IT department of the William Harvey hospital in Ashford, Kent, finally rumbled Mkhitarian when he applied for a security pass in the name of another doctor. He pleaded guilty to fraud charges and in July 2015 was sentenced to six years in prison.

Levon Mkhitarian worked as a locum, never staying in one hospital or one speciality too long. Photograph: Kent Police/PA

These sorts of hospital cases are uncommon the subterfuge required is substantial and most medical impostors thrive in the community (more of which later) or apply for non-clinical roles. Anecdotally, the GMC receives about half a dozen cases a year where details of a registered doctor (their name or GMC number) have been used illegally. According to the Crown Prosecution Service, 13 people were charged with pretending to be registered as a doctor since 2004 (under the Medical Act 1983) prosecution figures are unavailable and this omits those charged more broadly under the Fraud Act 2006.

How did Mkhitarian get away with it? He certainly capitalised on medicine generally being a team sport. There are (or always should be) senior decision-makers around medical training is an apprenticeship and so asking for assistance wouldnt necessarily raise a red flag. He may have had enough experience to coast at times, just as Caths nursing background helped in the first episode of Trust Me she quickly diagnosed a boxers fracture and deftly administered intravenous drugs. And Mkhitarian later worked as a locum, never staying in one hospital or one speciality too long.

He earned 85,000 during the two years, but undoubtedly sought more than financial gain. Steven Jay Lynn, professor of psychology at the State University of New York at Binghamton, believes a variety of motivations drive medical impostors: a grandiose fantasy of power, respect, authority and the social rewards of being a doctor.

Lynn also thinks that many are old-fashioned charlatans. Theyre likely not much different from conmen and women of different stripes who try to pull off scams in the business world, law and psychology, he says. Many could probably be described as callous, lacking in empathy, narcissistic, antisocial and even psychopathic, such that they can exploit people and treat them as objects without guilt or remorse.

Their hunting ground is often outside the hospital, away from the scrutiny of regulators or eagle-eyed IT departments. They prey upon impressionable, suggestible and vulnerable victims, perhaps not explicitly stating they are doctors, but professing medical knowledge all the same. Recently, 48-year-old Joseph Valadakis from Tottenham, north London, convinced his victims that he had treated the royal family, Barack Obama, Banksy, Robbie Williams, Theresa May and Russell Brand. One Hertford couple fell for Valadakiss claim of running a government laboratory he assured them he was allowed to treat commoners, too. Meanwhile, his website stated that he possessed a biophysics PhD: It gave him the credibility we were looking for at the time, one of the defrauded couple said. She and her husband received wrap treatments costing 1,600 each (made from the excrement of snails fed on lemongrass) and 2,000 massages with whale sperm. These treatments would prevent otherwise inevitable strokes, heart attacks and blindness, Valadakis insisted. He (incorrectly) diagnosed the husband with pancreatic cancer, cautioning him against obtaining a second opinion. The couple were ultimately conned out of 97,000. In 2015, Valadakis, who had no medical qualifications, was jailed on fraud charges for four years.

Other victims of medical impostors pay a different price. Sheffield civil servant Stewart Edwards posed as a GP for 34 years, targeting Asian families (initially following them home and looking up names on the electoral roll). He arrived at their doorsteps carrying a briefcase and stethoscope, claiming he had been sent from a local health centre. Unsuspecting families let him in; one treated him as their family GP for a decade. In 2011, Edwards pleaded guilty to 13 offences five indecent assaults, two sexual assaults on a child, three counts of sexual activity with a child and three sexual assaults on two women and a man, between 2000 and 2010. He was jailed for four years. But Edwards admitted to impersonating a GP since 1976, in London and Sheffield. His actual number of victims remains unknown.

The family of Angela Murray say medical deception hastened her death. Photograph: Collect/BNPS

Some victims forgo effective treatments or receive unnecessary ones. An ongoing Ohio lawsuit claims that dozens were given a false diagnosis of dementia by Sherry-Ann Jenkins who had no medical qualifications. The Associated Press reported that her patients had been planning their final years, preparing their children for the inevitable, quitting their jobs and selling their possessions. Attorney David Zoll tells me that many of his 65 clients are devastated; they had placed absolute faith in Jenkins. One developed depression after his diagnosis and took his own life. An autopsy showed no evidence of Alzheimers, his wife says. She, too, was mistakenly diagnosed with dementia by Jenkins.

Back in Britain, the family of Angela Murray say medical deception hastened her death. The lack of a transplant was going to kill Angie anyway, her brother said, but I am totally convinced her death was due to this. It took away her will to live.

She met Julie Higgins at Inspire beauty salon in Poole, Dorset. Higgins was a regular there, or at least visited whenever her hectic schedule allowed, she said. She claimed to be an oncologist at Great Ormond Street childrens hospital and a humanitarian aid worker. Occasionally she arrived in medical garb, apparently fresh from a volunteer shift at the local health centre, happy to dispense medical advice to other customers. Sometimes, she had her head shaved, too, later, saying it put her young cancer patients at ease.

Murray, a 59-year-old sales manager, was terminally ill with lung fibrosis and pulmonary hypertension. But Higgins carried hope when there was barely any to find she would source transplant organs, she assured Murray, on one occasion telling her to fast overnight as organs were in transit from Germany. Later, she sent texts from a supposed aid mission to Aleppo, promising to donate Murray her organs if she died. None of it was true.

Murrays family did become suspicious, but her brother, Dave Drummond, explained: Even when it was at its most unbelievable, I didnt want to say to Angie I think shes a conwoman. It would have just taken all the hope away from her.

Angelas husband, Gregory, told a local newspaper about how the eventual exposure of Higgins, in September last year, affected her: [Angelas] health deteriorated rapidly. Before then, she had said she was going to fight, but she lost hope. A month later she died in my arms.

Higgins claimed dissociative identity disorder and post-traumatic stress disorder were responsible for her actions. Earlier this year, she received a 12-month community order and was instructed to pay a 140 victim surcharge. Judge Donald Tait concluded that the Medical Act 1983 did not allow him to impose a prison sentence.

There was no real financial motive Higgins received free haircuts valued at 80. But she envisaged herself as Murrays saviour. I rang her twice a week to keep her going and support her, she told the Bournemouth Echo. She relied on me and said I was her sanity.

Murrays husband sees Higgins as anything but: To put my wife through what she put her through, Ive never met someone so evil. You see things on TV and you think how can people be so stupid. But if someone gives you that little bit of hope you grasp at it.

Criminals such as Edwards, Higgins and Valadakis who act outside hospitals never register with the authorities in the first place that is one of the secrets of their success.

But in case Trust Me has you worried about encountering a bogus hospital doctor, the GMC insists that it now conducts face-to-face identity checks for registration and cites a robust data-security system. Employers must take responsibility, they insist, for checking identification and qualifications. Abdul Pirzada became a locum GP in Birmingham after employers failed to challenge his misleading CV or confirm he had registered with the GMC (he hadnt).

You cant be worse than Brigitte! was how one character greeted Cath in Trust Me. Dan Sefton, doctor and writer of the series, said: For me, theres a delicious irony in the idea that the impostor doctor is better than the real thing, both clinically and with patients. Im still hoping Cath wont get away with it. That might be just the reassurance we all need.

  • Jules Montague is a consultant neurologist and writer.
  • Trust Me continues on BBC1 on Tuesday at 9pm.

Read more: https://www.theguardian.com/global/2017/aug/14/trust-me-im-a-fake-doctor-how-medical-imposters-thrive-in-the-real-world

ScriptDrop delivers your prescriptions with pizzazz

Larry Scott and Nick Potts worked at CoverMyMeds, a software solution for pharmacies. After connecting a bunch of pills with a bunch of pharmacists they started ScriptDrop, a service that helps pharmacists deliver those same prescriptions to your door. Its active in New York now but expanding into other areas soon.

The team, who hail from Nashville, settled in Columbus to work for CoverMyMeds. They quit to try something new and used many of the tricks they learned in the mother ship to build out their massive network of pharmacies. They have also created a system for med reminders that help pill takers remember to take their pills.

We are live with a pharmacy system that has 1,200 pharmacies. Two integrations are being completed that will give us access to 13,000 independent pharmacies, said Potts. We have pilot contracts with two national chains for delivery. For the med reminders, were piloting the text solution now to ensure the clinical decision tree is comprehensive.

The team learned a lot working at CoverMyMeds and the bigger company gave the pair their blessing to spin out and expand the features available to pharmacists.

Were integrated into the pharmacists workflow. The pharmacist doesnt have to download an app. They simply hit a button to request a delivery or setup medication reminders. We have a secondary solution if the pharmacy doesnt have the direct integration, said Potts.

Interestingly, over 25% of patients never bother to pick up the medicines prescribed them. The cost of picking and storing the medicine and then putting it back was $300 billion and offering a simple delivery service was the best way forward. The team uses local couriers to pick up and drop off the meds.

Through data, I noticed that patients were coming into pharmacies to fill a prescription and being told to come back a day later to pick it up. When this happened 25% of the time that patient never returns, said Potts. I worked closely with pharmacies and spoke to them about why they think that it happened. They listed a myriad of reasons. One offering would help to solve a lot of the issues.

The team has raised $1 million in seed and is looking for add-on funding.

Read more: https://techcrunch.com/2017/08/03/scriptdrop-delivers-your-prescriptions-with-pizzazz/

Birth control app Nurx now delivers to the contraceptive deserts of Texas

About half the counties in Texas dont have the number of public clinics required to meet the contraceptive needs of the population. So Nurx, an at-home birth control delivery app, decided to give women in the state the option to get birth control whenever they want and without ever needing to step into a clinic or even physically see a doctor.

Starting today, those in the Lone Star State will be able to tap the Nurx app and get contraceptives delivered straight to their door.

While Texas isnt the only state with a giant contraceptive desert, or an area withoutat least 1 clinic to every 1,000 women in need of publicly funded contraception, it is certainly the biggest area of land in the United States not meeting these needs.

And with Trumpcare looming, and Trumps recent Religious Freedom order, which allows businesses to deny birth control coverage based on religious reasons, many women could lose access to their publicly funded birth control pills and even more publicly funded clinics could go under, leaving a large and vulnerable population wide open to other, possibly dangerous methods of preventing birth.

While there are plenty of birth control delivery services out on the market, such as Maven, The Pill Club, Lemonaid and BirthControlBuzz, I had a hard time finding any that delivered in Texas (get at me if you do). Thats not to say they wont at some point, as each of them could easily open up shop in this area, but it does seem Nurx,which is not a free birth control delivery service, but does provide the pills at a reasonable cost, may havediscovered a goldmine of people in need, for the time being.

For instance, a little more than half of all pregnancies in Texas were unplannedin 2015, costing taxpayers $2.9 billion that year. However, according to a Guttmacher Institute report, the total gross public savings from preventing unintended pregnancies would have been $2.14 billion if women and couples could be empowered to prevent them. Couple that with the teen birth rate in Texas, which sharply declined by 56 percent over the last two decades, thanks in large part to contraceptives, according to the National Campaign to Prevent Teen and Unplanned Pregnancy.

Couple that with an additional estimate of more than 19 million women living in these contraceptive deserts nationwide and its easy to see adding these types of services could save money at the state level by removing middlemen and increasing access, as well as provide a lucrative area for Nurx and other birth control delivery apps to tap.

Read more: https://techcrunch.com/2017/06/05/birth-control-app-nurx-now-delivers-to-the-contraceptive-deserts-of-texas/

Topical Honey for Diabetic Foot Ulcers

Say Goodbye to High Blood Sugar Levels & Painful Insulin Shots!

diabetes image 2

The New Nutraceutical Breakthrough To Help You Manage Your Diabetes 

Click Here To Learn More!


1 2 3
What Is The Chinese
Secret To Optimum
Blood Pressure?
Why This Is The
Healthiest Oil On Earth?
Click To Learn More
Bring Your Old
Battery Back To Life!
4 5 6
How To Survive In
Bed & Nail Women
Like A Rockstar!
100% of Your
Vital Nutrition In
Just 30 Seconds
How A 2000-Year-Old
Nepalese Secret To Cure
Your Sciatica in 7

Dr. Jennifer Eddy of UW Health Family Medicine Eau Claire is running a clinical trial that investigates whether honey can help in the treatment of diabetic ulcers.

Diabetic foot examination – OSCE guide (New Version)

Say Goodbye to High Blood Sugar Levels & Painful Insulin Shots!

diabetes image 2

The New Nutraceutical Breakthrough To Help You Manage Your Diabetes 

Click Here To Learn More!


1 2 3
What Is The Chinese
Secret To Optimum
Blood Pressure?
Why This Is The
Healthiest Oil On Earth?
Click To Learn More
Bring Your Old
Battery Back To Life!
4 5 6
How To Survive In
Bed & Nail Women
Like A Rockstar!
100% of Your
Vital Nutrition In
Just 30 Seconds
How A 2000-Year-Old
Nepalese Secret To Cure
Your Sciatica in 7

To see the written guide alongside the video head over to our website

This video aims to give you an idea of what's required in the Diabetic Foot Examination OSCE.

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Always adhere to your medical schools / local hospital trusts guidelines when performing examinations or clinical procedures. Do NOT perform any examination or procedure on patients based purely upon the content of these videos. Geeky Medics accepts no liability for loss of any kind incurred as a result of reliance upon information provided in this video.