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Sickle Cell Therapy With CRISPR Gene Editing Shows Promise : Shots – Health News – NPR

Victoria Gray, who has sickle cell disease, volunteered for one of the most anticipated medical experiments in decades: the first attempt to use the gene-editing technique CRISPR to treat a genetic disorder in the United States. Meredith Rizzo/NPR hide caption

Victoria Gray, who has sickle cell disease, volunteered for one of the most anticipated medical experiments in decades: the first attempt to use the gene-editing technique CRISPR to treat a genetic disorder in the United States.

When Victoria Gray was just 3 months old, her family discovered something was terribly wrong.

"My grandma was giving me a bath, and I was crying. So they took me to the emergency room to get me checked out," Gray says. "That's when they found out that I was having my first crisis."

It was Gray's first sickle cell crisis. These episodes are one of the worst things about sickle cell disease, a common and often devastating genetic blood disorder. People with the condition regularly suffer sudden, excruciating bouts of pain.

"Sometimes it feels like lightning strikes in my chest and real sharp pains all over. And it's a deep pain. I can't touch it and make it better," says Gray. "Sometimes, I will be just balled up and crying, not able to do anything for myself.

Gray is now 34 and lives in Forest, Miss. She volunteered to become the first patient in the United States with a genetic disease to get treated with the revolutionary gene-editing technique known as CRISPR.

NPR got exclusive access to chronicle Gray's journey through this medical experiment, which is being watched closely for some of the first hints that changing a person's genes with CRISPR could provide a powerful new way to treat many diseases.

"This is both enormously exciting for sickle cell disease and for all those other conditions that are next in line," says Dr. Francis Collins, director of the National Institutes of Health.

"To be able to take this new technology and give people a chance for a new life is a dream come true," Collins says. "And here we are."

Doctors removed bone marrow cells from Gray's body, edited a gene inside them with CRISPR and infused the modified cells back into her system this summer. And it appears the cells are doing what scientists hoped producing a protein that could alleviate the worst complications of sickle cell.

"We are very, very excited," says Dr. Haydar Frangoul of the Sarah Cannon Research Institute in Nashville, Tenn., who is treating Gray.

Frangoul and others stress that it's far too soon to reach any definitive conclusions. Gray and many other patients will have to be treated and followed for much longer to know whether the gene-edited cells are helping.

"We have to be cautious. It's too early to celebrate," Frangoul says. "But we are very encouraged so far."

Collins agrees.

"That first person is an absolute groundbreaker. She's out on the frontier," Collins says. "Victoria deserves a lot of credit for her courage in being that person. All of us are watching with great anticipation."

This is the story of Gray's journey through the landmark attempt to use the most sophisticated genetic technology in what could be the dawn of a new era in medicine.

The study took place at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, in Nashville, Tenn., one of 11 sites recruiting patients for the research in the U.S., Canada and Europe. Meredith Rizzo/NPR hide caption

The study took place at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, in Nashville, Tenn., one of 11 sites recruiting patients for the research in the U.S., Canada and Europe.

Life filled with pain

When I first meet her, Gray is in a bed at the TriStar Centennial Medical Center in Nashville wearing a hospital gown, big gold hoop hearings and her signature glittery eye shadow.

It's July 22, 2019, and Gray has been in the hospital for almost two months. She is still recovering from the procedure, parts of which were grueling.

Nevertheless, Gray sits up as visitors enter her room.

"Nice to meet y'all," she says.

Gray is just days away from her birthday, which she'll be celebrating far from her husband, her four children and the rest of her family. Only her father is with her in Nashville.

"It's the right time to get healed," says Gray.

Gray describes what life has been like with sickle cell, which afflicts millions of people around the world, including about 100,000 in the United States. Many are African American.

In July, Gray was recovering after a medical procedure that infused billions of her own bone marrow cells back into her body after they had been modified using the gene-editing technique CRISPR. Her father, Timothy Wright (right), traveled from Mississippi to keep her company. Meredith Rizzo/NPR hide caption

In July, Gray was recovering after a medical procedure that infused billions of her own bone marrow cells back into her body after they had been modified using the gene-editing technique CRISPR. Her father, Timothy Wright (right), traveled from Mississippi to keep her company.

"It's horrible," Gray says. "When you can't walk or, you know, lift up a spoon to feed yourself, it gets real hard."

The disease is caused by a genetic defect that turns healthy, plump and pliable red blood cells into deformed, sickle-shaped cells. The defective cells don't carry oxygen well, are hard and sticky and tend to clog up the bloodstream. The blockages and lack of oxygen wreak havoc in the body, damaging vital organs and other parts of the body.

Growing up, Victoria never got to play like other kids. Her sickle cells made her weak and prone to infections. She spent a lot of time in the hospital, recovering, getting blood transfusions all the while trying to keep up with school.

"I didn't feel normal. I couldn't do the regular things that every other kid could do. So I had to be labeled as the sick one."

Gray made it to college. But she eventually had to drop out and give up her dream of becoming a nurse. She got a job selling makeup instead but had to quit that too.

The sickle-shaped cells eventually damaged Gray's heart and other parts of her body. Gray knows that many patients with sickle cell don't live beyond middle age.

"It's horrible knowing that I could have a stroke or a heart attack at any time because I have these cells in me that are misshapen," she says. "Who wouldn't worry?"

Gray says she understands the risks involved in the treatment. "This gives me hope if it gives me nothing else," she says. Meredith Rizzo/NPR hide caption

Gray says she understands the risks involved in the treatment. "This gives me hope if it gives me nothing else," she says.

Gray married and had children. But she hasn't been able to do a lot of things most parents can, like jump on a trampoline or take her kids to sporting events. She has often had to leave them in the middle of the night to rush to the hospital for help.

"It's scary. And it affected my oldest son, you know, because he's older. So he understands. He started acting out in school. And his teacher told me, 'I believe Jemarius is acting out because he really believes you're going to die,' " Gray says, choking back tears.

Some patients can get help from drugs, and some undergo bone marrow transplants. But that procedure is risky; there's no cure for most patients.

"It was just my religion that kind of kept me going," Gray says.

An eager volunteer

Gray had been exploring the possibility of getting a bone marrow transplant when Frangoul told her about a plan to study gene editing with CRISPR to try to treat sickle cell for the first time. She jumped at the chance to volunteer.

"I was excited," Gray says.

CRISPR enables scientists to edit genes much more easily than ever before. Doctors hope it will give them a powerful new way to fight cancer, AIDS, heart disease and a long list of genetic afflictions.

"CRISPR technology has a lot of potential use in the future," Frangoul says.

To try to treat Gray's sickle cell, doctors started by removing bone marrow cells from her blood last spring.

Next, scientists used CRISPR to edit a gene in the cells to turn on the production of fetal hemoglobin. It's a protein that fetuses make in the womb to get oxygen from their mothers' blood.

"Once a baby is born, a switch will flip on. It's a gene that tells the ... bone marrow cells that produce red cells to stop making fetal hemoglobin," says Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's TriStar Centennial Medical Center.

The hope is that restoring production of fetal hemoglobin will compensate for the defective adult-hemoglobin sickle cells that patients produce.

Patients with sickle cell disease have blood cells that are stiff and misshapen. The cells don't carry oxygen as well and clog up the bloodstream, resulting in periodic bouts of excruciating pain. Ed Reschke/Getty Images hide caption

Patients with sickle cell disease have blood cells that are stiff and misshapen. The cells don't carry oxygen as well and clog up the bloodstream, resulting in periodic bouts of excruciating pain.

"We are trying to introduce enough ... fetal hemoglobin into the red blood cell to make the red blood cell go back to being happy and squishy and not sticky and hard, so it can go deliver oxygen where it's supposed to," Frangoul says.

Then on July 2, after extracting Gray's cells and sending them to a lab to get edited, Frangoul infused more than 2 billion of the edited cells into her body.

"They had the cells in a big syringe. And when it went in, my heart rate shot up real high. And it kind of made it hard to breath," Gray says. "So that was a little scary, tough moment for me."

After that moment passed, Gray says, she cried. But her tears were "happy tears," she adds.

"It was amazing and just kind of overwhelming," she says, "after all that I had went through, to finally get what I came for."

The cells won't cure sickle cell. But the hope is that the fetal hemoglobin will prevent many of the disease's complications.

"This opens the door for many patients to potentially be treated and to have their disease modified to become mild," Frangoul says.

The procedure was not easy. It involved going through many of the same steps as a standard bone marrow transplant, including getting chemotherapy to make room in the bone marrow for the gene-edited cells. The chemotherapy left Gray weak and struggling with complications, including painful mouth sores that made it difficult to eat and drink.

But Gray says the ordeal will have been worth it if the treatment works.

She calls her new gene-edited cells her "supercells."

"They gotta be super to do great things in my body and to help me be better and help me have more time with my kids and my family," she says.

Gray was diagnosed with sickle cell disease as an infant. She was considering a bone marrow transplant when she heard about the CRISPR study and jumped at the chance to volunteer. Meredith Rizzo/NPR hide caption

Gray was diagnosed with sickle cell disease as an infant. She was considering a bone marrow transplant when she heard about the CRISPR study and jumped at the chance to volunteer.

Concerns about risk

Other doctors and scientists are excited about the research. But they're cautious too.

"This is an exciting moment in medicine," says Laurie Zoloth, a bioethicist at the University of Chicago. "Everyone agrees with that. CRISPR promises the capacity to alter the human genome and to begin to directly address genetic diseases."

Still, Zoloth worries that the latest wave of genetic studies, including the CRISPR sickle cell study, may not have gotten enough scrutiny by objective experts.

"This a brand-new technology. It seems to work really well in animals and really well in culture dishes," she says. "It's completely unknown how it works in actual human beings. So there are a lot of unknowns. It might make you sicker."

Zoloth is especially concerned because the research involves African Americans, who have been mistreated in past medical studies.

Frangoul acknowledges that there are risks with experimental treatments. But he says the research is going very slowly with close oversight by the Food and Drug Administration and others.

"We are very cautious about how we do this trial in a very systematic way to monitor the patients carefully for any complications related to the therapy," Frangoul says.

Gray says she understands the risks of being the first patient and that the study could be just a first step that benefits only other patients, years from now. But she can't help but hope it works for her.

Dr. Haydar Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, is leading the study in Nashville. Meredith Rizzo/NPR hide caption

Dr. Haydar Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, is leading the study in Nashville.

She imagines a day when she may "wake up and not be in pain" and "be tired because I've done something not just tired for no reason." Perhaps she could play more with her kids, she says, and look forward to watching them grow up.

"That means the world to me," Gray says.

It could be many weeks or even months before the first clues emerge about whether the edited cells are safe and might be working.

"This gives me hope if it gives me nothing else," she says in July.

Heading home at last

About two months later, Gray has recovered enough to leave the hospital. She has been living in a nearby apartment for several weeks.

Enough time has passed since Gray received the cells for any concerns about immediate side effects from the cells to have largely passed. And her gene-edited cells have started working well enough for her immune system to have resumed functioning.

So Gray is packing. She will finally go home to see her children in Mississippi for the first time in months. Gray's husband is there to drive her home.

"I'm excited," she says. "I know it's going to be emotional for me. I miss the hugs and the kisses and just everything."

After living for months in Nashville, where the study was taking place, Gray packs her bags to finally go home to her kids and family in Forest, Miss. Meredith Rizzo/NPR hide caption

After living for months in Nashville, where the study was taking place, Gray packs her bags to finally go home to her kids and family in Forest, Miss.

Gray is wearing bright red glittery eye shadow. It matches her red tank top, which repeats "I am important" across the front.

She unzips a suitcase and starts pulling clothes from the closet.

"My goodness. Did I really bring all this?" she says with a laugh.

Before Gray can finish packing and depart, she has to stop by the hospital again.

"Are you excited about seeing the kids?" Frangoul says as he greets her. "Are they going to have a big welcome sign for you in Mississippi?"

Turns out that Gray has decided to make her homecoming a surprise.

"I'm just going to show up tomorrow. Like, 'Mama's home,' " she says, and laughs.

After examining Gray, Frangoul tells her that she will need to come back to Nashville once a month for checkups and blood tests to see if her genetically modified cells are producing fetal hemoglobin and giving her healthier red blood cells.

"We are very hopeful that this will work for Victoria, but we don't know that yet," Frangoul says.

Gray will also keep detailed diaries about her health, including how much pain she's experiencing, how much pain medication she needs and whether she needs any blood transfusions.

"Victoria is a pioneer in this. And we are very excited. This is a big moment for Victoria and for this pivotal trial," Frangoul says. "If we can show that this therapy is safe and effective, it can potentially change the lives of many patients."

Gray hopes so too.

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After Netflix show on rare illness, a new family bonds – West Central Tribune

It's a lesson Breteni Morgan-Berg has been learning again and again after a whirlwind year in the spotlight. Her 7-year-old daughter, Kamiyah, has an exceedingly rare gene mutation that causes her to collapse multiple times a day. Kamiyah's illness, a mutation of a gene known as KCNMA1, got diagnosed last year after extensive medical sleuthing.

Kamiyah's condition made her a star in an episode of "Diagnosis," the Netflix medical detective documentary series based on the New York Times column of the same name. But while her time in the limelight didn't cure her gene mutation that remains a work in progress. Instead, it grew her family: researchers dedicated to find her a treatment, and other families dealing with the same gene mutation who thought they too were alone.

The media exposure also gave Morgan-Berg and Kamiyah a louder voice. They're known now, Kamiyah's condition a known issue. That helps too, when seeking assistance, when Morgan-Berg is making another call for help, or one more emailed request.

If theres anything Netflix and the New York Times did for us granted I pushed myself to that point and thats how we got there but it makes it much harder to ignore," Morgan-Berg said.

Kamiyah, and her appearance on the Netflix show, has catalyzed a growing network of support in the medical community. Dr. Lisa Sanders, the model for the brilliant, medical mystery solving doctor-detective main character in the show "House, M.D.," featured Kamiyah in her Diagnosis column in the New York Times prior to the collaboration with Netflix. She's just a text message away.

Dr. Sotirios Keros was a early and crucial part of Kamiyah's medical family. He got to know her in 2018 after a colleague referred the child with the then-undiagnosed condition to him.

For Kamiyah, Keros couldn't have been at a better place in a better time. A New York resident, Keros regularly commuted to Sioux Falls to work as assistant professor in pediatric neurology at Sanford Childrens Hospital and the University of South Dakota, where there was a shortage of professionals with his expertise. His specialized background in neurology and ion channel physiology meant when he saw Kamiyah's condition, what she was suffering from was clear, he said.

Keros got Kamiyah's gene mutation on a special rare disease database known as CoRDS, hosted by Sanford Health. He also co-founded a foundation the KCNMA1 Channelopathy International Advocacy Organization meant to help support the research into the KCNMA1 mutation and helping connect those with the condition with researchers and each other.

Kamiyah appearance on Netflix didn't trigger an avalanche of donations into the foundation ("Nope, nope, nope, nope"), said Keros. That funding might come in time, as a result of family fundraising and growing awareness of the condition. But the foundation is serving a more immediate purpose, acting as a crucial link between those struggling with the condition giving them a place to turn.

"The reason we started the foundation was this exact reason: to give people education and just a place to turn," he said. "Some diseases, like this one, there really isnt any treatment, but just being involved with other people is its own kind of help."

Another key member of Kamiyah's support team is Dr. Andrea Meredith, a researcher at the University of Maryland School of Medicine, who first heard about Kamiyah in Sanders' column. She was stunned to later learn the gene that causes Kamiyah's condition was the exact same one she was currently researching. Previously, she had only heard of one such patient an anonymous Chinese family documented in a 2005 paper.

"When Kamiyahs mom gave us genetics report I almost fell over because one of the mutations we had picked out of the publicly available database, with no other information other than the sequence change, ended up being the mutation that she had," Meredith said. Her work involves growing mice genetically modified with Kamiyah's condition, a key component of further research.

Meredith, too, has grown close to Morgan-Berg and her family, and helped co-found the KCNMA1 foundation with Keros. Kamiyah's photos are all over Meredith's lab, Morgan-Berg said. Meredith has a daughter who is slightly older than Kamiyah, and the two families met up in New York when Kamiyah and Morgan-Berg were making media appearances in connection to the Netflix show.

One of the most powerful things about meeting Kamiyah in person was the ability to see that sweetness and its amazing how she has that childlike innocence and sweetness, yet shes afflicted by these very powerful symptoms," Meredith said.

Meredith is now working to secure funding from the National Institutes of Health to expand her lab, due to the sheer volume of people contacting her seeking help.

"She has no idea what she means to us," Morgan-Berg said.

Also helping Kamiyah, quietly, is Massachusetts-based Q-State Biosciences. Q-State had no comment about its work with Kamiyah: "Q-State is still in the early stages of research on this project, and cannot provide details right now," said a spokesperson.

But Morgan-Berg said Q-State's work involves matching Kamiyah's genetic profile against available drugs to see if there's anything that could help possibly the most immediately promising work, if they find something.

With the good came the bad. Kamiyah's attention from the New York Times column and Netflix show brought out the worst in some people, Morgan-Berg said. Online trolls attacked Kamiyah's family, specifically her mother, accusing her of being a terrible wife, a fame-seeking welfare mom and worse.

"Terrible, horrible things you cant even make up yourself. Trolls just come out of the woodwork," she said.

Morgan-Berg locked down her Facebook account to shield herself from the worst commenters, but that didn't keep them all away.

She worried the Netflix show might make it seem that Kamiyah's condition was cured and everything was fine now. But she knows that's not the case, and she wishes others did, too.

The research grinds on, a silver-bullet solution hasn't shown up, and the big media exposure didn't solve her family's biggest immediate problem: negotiating the tangled web of bureaucracies to get Kamiyah help she needs now, trained care providers who can help take care of a growing girl, protecting her from her own body.

Its hard enough to be told that Kamiyah is going to die before they can help us, that the information that we give on Kamiyah could help someone else," said Morgan-Berg. "But the fact is that we cant even get help with the quality of life we have left.

Morgan-Berg is required to interview and hire the care providers first, then seek funding. But because Kamiyah's condition is so rare, it can be difficult to obtain what she needs through insurance. Morgan-Berg said she's applied for coverage from the care providers multiple times, and gotten turned down each time, putting her in a quandary: Let the caregivers go, or pay for them out of pocket?

It's an ongoing battle that makes her dream of moving to Denmark to be close to friends she met online, whose son Atle has the same condition as Kamiyah. She presses on, powered by her family, friends and the growing network of others with the same condition and medical professional dedicated to finding answers.

"I dont want to look back and think, 'I could have done more. I want to know Ive done everything humanly possible,'" Morgan-Berg said.

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3 trends in biotech to watch in 2020 – STAT

For biotech, 2019 ended like the penultimate episode of a prestige TV show. We got answers to some weighty questions, but mostly, the year left a breadcrumb trail to some major reveals.

The IPO window stayed open, helping scores of companies go public. Futuristic therapies proved their worth in clinical trials, pointing to a new era in medicine. And the markets ended the year on a high, buoyed by a Food and Drug Administration that seems ever more flexible when it comes to approving new drugs.

Now, with 2020, well get the more important answers. Sure, theres a lot of public biotech companies now, but what if thats a bad thing? Yes, cell and gene therapies look transformational, but what if they never make any money? And since when is everyone so confident they understand whats going on inside the FDA?


Here are three trends to watch in biotech in 2020, a year that looks to be laden with opportunities and stumbling blocks for the drug industry.

While every biotech startup is undoubtedly special in the eyes of the venture capitalists quoted in its press releases, 2020 could be a year marked by fatigue for the outside public.

More than 140 biotech companies have gone public since 2017, according to the analysts at Evercore ISI, and now theres upward of 500 of them trading on the Nasdaq. Keeping tabs on them all is essentially impossible, and its become fairly commonplace for biotech types to see the name of a given company for the first time by reading about its implosion.

Thats arguably a good problem to have in societal terms. More biotech companies means more efforts to treat human disease. But it could be problematic for the herd. Drug development remains an expensive proposition, and the majority of the biotech companies that went public in the past three years have negligible or nonexistent revenue. That means theyre going to have to go back to the market with follow-on offerings, and they may not like what they find.

According to Cowens biotech thermometer, a regular update on Wall Street sentiment, investors are increasingly selective when it comes to equity offerings, spooked by slumping IPO returns and a glut of supply. If that trend continues into 2020, some of those 500-plus biotech companies might need to look for other means of keeping the doors open, including mergers that thin the flock.

Much of the conversation around cell and gene therapies has focused on how much they cost, and understandably so. Two million dollars is, objectively, a lot of dollars. But the anxiety in biotech circles is a bit different: Is anyone going to make money on these things?

Take, for instance, CAR-T cancer therapy. For some patients, a single dose erases any trace of aggressive, otherwise untreatable cancer. For every patient, a single dose costs about $400,000. That sounds like a lot, but churning out a genetically engineered immune cell is hardly akin to widget manufacture. CAR-T companies dont disclose their underlying costs, but these therapies are understood to be low-margin products.

Theyre also considered commercial disappointments. The first two approved CAR-Ts, Kymriah and Yescarta, have underperformed analyst expectations to date. And that has stoked concern that a coming wave of gene therapies could face similar commercial difficulties.

Like CAR-T, gene therapy is costly to make, can be administered only at certain sites, and has made headlines for its six- or seven-figure list prices. Biotech companies and their investors have staked billions of dollars on the idea that such one-time treatments can become lucrative products. If that assumption is incorrect and the industry cant figure out how to make money in therapy, there could be a painful knock-on effect for biotech.

Handily, theres a one-company test case to follow in 2020. Novartis (NVS) sells a CAR-T in the form of Kymriah and a gene therapy called Zolgensma. Furthermore, thanks to a recent $9.7 billion acquisition, it will likely soon sell an RNAi treatment for high cholesterol. Each endeavor is a bet that futuristic science can turn into money-making medicines. By the end of the year, well have a decent idea of whether its a wise one.

Remember 2015, when the FDA would approve or reject a drug, and people would form an opinion and move on? That all changed the following year when the agency approved eteplirsen, now called Exondys 51, which is a treatment for Duchenne muscular dystrophy from a company called Sarepta Therapeutics (SRPT).

Without relitigating the whole ordeal, its fair to say Sareptas case relied on scant, debatable evidence from a small trial. To some, the FDAs decision to approve eteplirsen anyway was a sign of forward-thinking regulation that put patients first. To others, it was a dereliction of duty that threatened to erode decades of pharmaceutical jurisprudence. And to a great many, it was reason to get on the internet and be churlish, conspiratorial, and even threatening.

On Twitter, the fight over eteplirsen has never really ended, just taken on different forms, like a biotech analog to Gamergate. Earlier this year, the debate over a heart drug made by Amarin (AMRN) quickly metastasized into eteplirsen redux, with name-calling, accusations of bad faith, and armchair psychoanalysis of FDA staff. There were smaller but similar fights over Axovant Sciences, Clovis Oncology (CLVS), and nearly every biotech company with a sizable short interest.

Its at least somewhat understandable why eteplirsen marked such a shift in biotech discourse. Where FDA past decisions seemed to come down from Mount Sinai with little in the way of transparency, the messy eteplirsen process made public internal infighting and clashing personalities at the agency. The FDAs top drug evaluator even considered Sareptas balance sheet while evaluating the drug, a departure from the agencys hands-off approach to the business of biopharma and evidence that approval decisions can be about more than benefits and risks.

Theres no evidence that the FDA was fundamentally changed by a single decision, as organizations that employ 17,000 people rarely are. But that peek behind the curtain was enough to give credence to seemingly any biotech bull case online. Where the FDA once appeared monolithic, now there were heroes and villains within, actors whose imagined biases could support any conspiracy theory. Formerly anonymous public servants became the topic of vicious debate among strangers with alphanumeric Twitter handles and pictures of dogs as online avatars. One even got called a cuck.

With all that as a backdrop, next year, Biogen (BIIB) is going to ask the FDA to approve aducanumab, a treatment for Alzheimers disease. The supporting data are confusing, drawn from a pair of terminated trials with divergent results. The agencys decision will have major implications for the drug industry, the health care system, and the more than 5 million Americans with Alzheimers.

And, on the fractious little planet that is biotech Twitter, aducanumab presents an opportunity to play out the eteplirsen debate on the grandest scale yet, with more kremlinology, more circular logic, and more vitriol. Be nice to one another out there.

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Science in the 2010s Medicine – Labmate Online

The past decade has seen some major advances for the medical industry, from cancer vaccines to CRISPR technology. Read on for a glimpse of the most memorable highlights.

Every year, Hepatitis C causes around 400,000 deaths around the world. In 2010 human trials started on a breakthrough medication called Sofosbuvir, which offered a 12-week treatment program that blocks the action of proteins and enzymes that support the virus.

In 2012, biologists Emmanuelle Charpentierand JenniferDoudnaproposed CRISPR-Cas9enzymes be utilised to edit genomes. This sparked the advent of the revolutionary gene-editing tool known as CRISPR and empowered scientists with the ability to modify DNA and genes. From managing malaria outbreaks to growing agricultural crops, CRISPR is one of the most significant scientific breakthroughs of the decade.

In 2013 researchers at Cornell University took 3D printing beyond consumer goods and branched out into human body parts. They successfully printed an outer ear that functioned and resembled the real thing. Later in the year researchers from the University of Pennsylvania printed 3D blood vessels. By 2020, San Diego based company Organovo is planning to print human livers.

Following a severe facial injury, American firefighter Patrick Hardison thought he would be left scarred and deformed for the rest of his life. In 2015 surgeons at the NYU Langone Medical Centre carried out the most advanced face transplant in history, using 3D modelling to replace ear canals, bones and other elements of the face.

2017 was a landmark year for gene therapy, with scientists harnessing the technology to treat diseases like cancer. Instead of treating the symptoms, gene therapy allows scientists to modify DNA to treat cancers like leukemia and breast cancer.

Stanford University made headlines in 2018 when a team of researchers announced they had successfully eliminated cancerous tumours in mice with a vaccine. "I dont think theres a limit to the type of tumour we could potentially treat, as long as it has been infiltrated by the immune system," said Ronald Levy, MD, senior author of the study and Professor of Oncology at the Stanford Health Centre.

Breast cancer claims more than 11,000 lives a year in the UK, though thanks to a new blood test developed by researchers at the University of Nottingham, experts are expecting the figure to fall. The test detects autoantibodies and could allow doctors to diagnose breast cancer as early as five years before a lump appears.

Want to know more about the latest medical breakthroughs? Don't miss 'A New Approach Concentration Measurement of Bases and Acids using a Refractometer' which spotlights the latest technologies from Austrian based company Anton Paar.

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Harvard geneticist George Church’s goal: to protect humans from viruses, genetic diseases, and aging – 60 Minutes – CBS News

Our lives have been transformed by the information age. But what's coming next is likely to be more profound, call it the genetic information age. We have mapped the human genome and in just the last few years we have learned to read and write DNA like software. And you're about to see a few breakthroughs-in-waiting that would transform human health. For a preview of this revolution in evolution we met George Church, a world leading geneticist, whose own DNA harbors many eccentricities and a few genes for genius.

We found George Church in here.

Cory Smith: Most of these are frozen George. Little bits of George that we have edited all in different tubes.

Church threw himself into his work, literally. His DNA is in many of the experiments in his lab at Harvard Medical School. The fully assembled George Church is 6'5" and 65. He helped pioneer mapping the human genome and editing DNA. Today, his lab is working to make humans immune to all viruses, eliminate genetic diseases, and reverse the effects of time.

Scott Pelley: One of the things your lab is working on is reversing aging.

George Church: That's right.

Scott Pelley: How is that possible?

George Church: Reversing aging is one of these things that is easy to dismiss to say either we don't need it or is impossible or both.

Scott Pelley: Oh, we need it.

George Church: Okay. We need it. That's good. We can agree on that. Well, aging reversal is something that's been proven about eight different ways in animals where you can get, you know, faster reaction times or, you know, cognitive or repair of damaged tissues.

Scott Pelley: Proven eight different ways. Why isn't this available?

George Church: It is available to mice.

In lucky mice, Church's lab added multiple genes that improved heart and kidney function and levels of blood sugar. Now he's trying it in spaniels.

Scott Pelley: So is this gene editing to achieve age reversal?

George Church: This is adding genes. So, it's not really editing genes. It's, the gene function is going down, and so we're boosting it back up by putting in extra copies of the genes.

Scott Pelley: What's the time horizon on age reversal in humans?

George Church: That's in clinical trials right now in dogs. And so, that veterinary product might be a couple years away and then that takes another ten years to get through the human clinical trials.

Human trials of a personal kind made George Church an unlikely candidate to alter human evolution. Growing up in Florida, Church was dyslexic, with attention deficit, and frequently knocked out by narcolepsy.

Scott Pelley: What was it that made you imagine that you could be a scientist?

George Church: The thing that got me hooked was probably the New York World's Fair in 1964. I thought this is the way we should all be living. When I went back to Florida, I said, "I've been robbed," you know? "Where is it all?" So, I said, "Well, if they're not going to provide it, then I'm gonna provide it for myself."

With work and repetition, he beat his disabilities and developed a genius for crystallography, a daunting technique that renders 3D images of molecules through X-rays and math. But in graduate school at Duke, at the age of 20, his mania for the basic structures of life didn't leave time for the basic structure of life.

Scott Pelley: You were homeless for a time.

George Church: Yeah. Briefly.

Scott Pelley: Six months.

George Church: Six months.

Scott Pelley: And where were you sleeping when you were homeless?

George Church: Well, yeah. I wasn't sleeping that much. I was mostly working. I'm narcoleptic. So, I fall asleep sitting up anyway.

His devotion to crystallography was his undoing at Duke.

George Church: I was extremely excited about the research I was doing. And so, I would put in 100-plus hours a week on research and then pretty much didn't do anything else.

Scott Pelley: Not go to class.

George Church: I wouldn't go to class. Yeah.

Duke kicked him out with this letter wishing him well in a field other than biology. But, it turned out, Harvard needed a crystallographer. George Church has been here nearly 40 years. He employs around 100 scientists, about half-and-half men and women.

Scott Pelley: Who do you hire?

George Church: I hire people that are self-selecting, they see our beacon from a distance away. There are a lot of people that are a little, you know, might be considered a little odd. "Neuroatypicals," some of us are called.

Scott Pelley: "Neuroatypical?"

George Church: Right.

Scott Pelley: Unusual brains?

George Church: Right, yeah.

Parastoo Khoshakhlagh: One thing about George that is very significant is that he sees what you can't even see in yourself.

Parastoo Khoshakhlagh and Alex Ng are among the "neuroatypicals." They're engineering human organ tissue.

Cory Smith: I think he tries to promote no fear of failure. The only fear is not to try at all.

Cory Smith's project sped up DNA editing from altering three genes at a time to 13,000 at a time. Eriona Hysolli went to Siberia with Church to extract DNA from the bones of wooly mammoths. She's editing the genes into elephant DNA to bring the mammoth back from extinction.

Eriona Hysolli: We are laying the foundations, perhaps, of de-extinction projects to come.

Scott Pelley: De-extinction.

Eriona Hysolli: Yes.

Scott Pelley: I'm not sure that's a word in the dictionary yet.

Eriona Hysolli: Well, if it isn't, it should be.

Scott Pelley: You know there are people watching this interview who think that is playing God.

George Church: Well, it's playing engineer. I mean, humans have been playing engineer since the dawn of time.

Scott Pelley: The point is, some people believe that you're mucking about in things that shouldn't be disturbed.

George Church: I completely agree that we need to be very cautious. And the more powerful, or the more rapidly-moving the technology, the more cautious we need to be, the bigger the conversation involving lots of different disciplines, religion, ethics, government, art, and so forth. And to see what it's unintended consequences might be.

Church anticipates consequences with a full time ethicist in the lab and he spends a good deal of time thinking about genetic equity. Believing that genetic technology must be available to all, not just those who can afford it.

We saw one of those technologies in the hands of Alex Ng and Parastoo Khoshakhlagh. They showed us what they call "mini-brains," tiny dots with millions of cells each. They've proven that cells from a patient can be grown into any organ tissue, in a matter of days, so drugs can be tested on that patient's unique genome.

Scott Pelley: You said that you got these cells from George's skin? How does that work?

Alex Ng: We have a way to reprogram essentially, skin cells, back into a stem cell state. And we have technologies where now we can differentiate them into tissue such as brain tissue.

Scott Pelley: So you went from George's skin cells, turned those into stem cells, and turned those into brain cells.

Alex Ng: Exactly. Exactly.

Scott Pelley: Simple as that.

Organs grown from a patient's own cells would eliminate the problem of rejection. Their goal is to prove the concept by growing full sized organs from Church's DNA.

George Church: It's considered more ethical for students to do experiments on their boss than vice versa and it's good to do it on me rather than some stranger because I'm as up to speed as you can be on the on the risks and the benefits. I'm properly consented. And I'm unlikely to change my mind.

Alex Ng: We have a joke in the lab, I mean, at some point, soon probably, we're going to have more of his cells outside of his body than he has himself.

Church's DNA is also used in experiments designed to make humans immune to all viruses.

George Church: We have a strategy by which we can make any cell or any organism resistant to all viruses by changing the genetic code. So if you change that code enough you now get something that is resistant to all viruses including viruses you never characterized before.

Scott Pelley: Because the viruses don't recognize it anymore?

George Church: They expect a certain code provided by the host that they replicate in. the virus would have to change so many parts of its DNA or RNA so that it can't change them all at once. So, it's not only dead. But it can't mutate to a new place where it could survive in a new host.

Yes, he's talking about the cure for the common cold and the end of waiting for organ transplants. It's long been known that pig organs could function in humans. Pig heart valves are routinely transplanted already. But pig viruses have kept surgeons from transplanting whole organs. Church's lab altered pig DNA and knocked out 62 pig viruses.

Scott Pelley: What organs might be transplanted from a pig to a human?

George Church: Heart, lung, kidney, liver, intestines, various parts of the eye, skin. All these things.

Scott Pelley: What's the time horizon on transplanting pig organs into human beings?

George Church: you know, two to five years to get into clinical trials. And then again it could take ten years to get through the clinical trials.

Church is a role model for the next generation. He has co-founded more than 35 startups. Recently, investors put $100 million into the pig organ work. Another Church startup is a dating app that compares DNA and screens out matches that would result in a child with an inherited disease.

George Church: You wouldn't find out who you're not compatible with. You'll just find out who you are compatible with.

Scott Pelley: You're suggesting that if everyone has their genome sequenced and the correct matches are made, that all of these diseases could be eliminated?

George Church: Right. It's 7,000 diseases. It's about 5% of the population. It's about a trillion dollars a year, worldwide.

Church sees one of his own genetic differences as an advantage. Narcolepsy lulls him several times a day. But he wakes, still in the conversation, often, discovering inspiration in his twilight zone.

Scott Pelley: If somebody had sequenced your genome some years ago, you might not have made the grade in some way.

George Church: I mean, that's true. I would hope that society sees the benefit of diversity not just ancestral diversity, but in our abilities. There's no perfect person.

Despite imperfection, Church has co-authored 527 scientific papers and holds more than 50 patents. Proof that great minds do not think alike.

The best science can tell, it was about 4 billion years ago that self-replicating molecules set off the spark of biology. Now, humans hold the tools of evolution, but George Church remains in awe of the original mystery: how chemistry became life.

Scott Pelley: Is the most amazing thing about life, then, that it happened at all?

George Church: It is amazing in our current state of ignorance. We don't even know if it ever happened ever in the rest of the universe. it's awe-inspiring to know that it either happened billions of times, or it never happened. Both of those are mind boggling. It's amazing that you can have such complex structures that make copies of themselves. But it's very hard to do that with machines that we've built. So, we're engineers. But we're rather poor engineers compared to the pseudo engineering that is biological evolution.

Produced by Henry Schuster. Associate producer, Rachael Morehouse. Broadcast associate, Ian Flickinger.

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Harvard geneticist George Church's goal: to protect humans from viruses, genetic diseases, and aging - 60 Minutes - CBS News

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UCLA study shows inhibition of gene helps overcome resistance to immunotherapy – UCLA Newsroom

Cancer immunology drugs, which harness the bodys immune system to better attack cancer cells, have significantly changed the face of cancer treatment. People with aggressive cancers are now living longer, healthier lives. Unfortunately, cancer immunology therapy only works in a subset of patients.

Now, a new study from scientists at the UCLA Jonsson Comprehensive Cancer Center helps explain why some people with advanced cancer may not respond to one of the leading immunotherapies, PD-1 blockade, and how a new combination approach may help overcome resistance to the immunotherapy drug.

The UCLA study, published today in the inaugural issue of the new scientific journal Nature Cancer, showed that genetic and pharmacological inhibition of the oncogene PAK4 overcomes resistance to anti-PD-1 therapy in preclinical models.

One of the main reasons patients do not respond to PD-1 blockade is because the T cells never make it into the tumor to attack the cancer cells, said lead author Gabriel Abril-Rodriguez, a doctoral candidate in the departments of pharmacology and medicine in the David Geffen School of Medicine at UCLA. We found that biopsies of patients who did not respond to PD-1 blockade showed an overexpression of PAK4, so that led us to believe it played a role in suppressing the immunotherapy treatment.

PAK4 has been known previously to be involved in cell migration and proliferation. The new research from UCLA demonstrates that high expression of this oncogene also correlates with a lack of immune cells migrating into the tumors to destroy the cancer cells.

Using biopsies from people with advanced melanoma who received the immune checkpoint blocking antibody pembrolizumab, UCLA researchers performed RNA sequencing to characterize the phenotype of the tumors. They saw that the tumors that did not respond to PD-1 blockade had a high expression of PAK4 and were not infiltrated by immune cells, meaning that the immune cells had not found their way to the tumor to attack the cancer cells.

The team then inhibited PAK4 in cell lines by either using a drug inhibitor or a gene editing technique called CRISPR-Cas9. The scientists found that deleting PAK4 increased the migration of tumor-specific immune cells and sensitized tumors to PD-1 blockade immunotherapy,reversing the resistance.

Developing new and improved combination treatments like this one for people who do not initially respond to anti-PD-1 treatment is the next step forward in our efforts to make immunotherapy work better for more people, said Dr. Antoni Ribas, the studys senior author, a professor of medicine at the Geffen School and director of the Jonsson cancer centers Tumor Immunology Program. The results from this study could also be expanded to other tumor types that are notoriously resistant to PD-1 blockade, such as pancreatic cancer.

The PAK4 inhibitor used in the study is already being tested in a phase one trial. The combination treatment with anti-PD-1 will be tested in a clinical trial setting in the near future.

The study was funded in part by the National Institutes of Health and the Parker Institute for Cancer Immunotherapy.

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UCLA study shows inhibition of gene helps overcome resistance to immunotherapy - UCLA Newsroom

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