Hacking Your Genes Has Never Been Easier – Outside Magazine

Josiah Zayner and I are drinking fluorescent green beer at the ODIN, his Oakland lab. The tables are scattered with pipettes and disposable blue gloves, cases of Red Bull and Slim Jims are near at hand, and Drake is pulsing on the sound system. Its not St. Patricks Day, and the beer isnt really all that green. Its the ghostly luminescence of jellyfish pulsing through the depths. Thats because its chock full of glowing jellyfish protein.

But no jellyfish were harmed in the making of this beer. Zayner is the worlds most notorious biohackera new breed of garage tinkerer experimenting with DNA and biological systems outside the confines of traditional research. In this case, he genetically engineered a common brewers yeast by adding a jellyfishs green fluorescent protein (GFP) gene that he ordered online. As long as you know the DNA sequence of the gene you wantthe As, Cs, Gs, and Ts of the genetic codeyou no longer need the actual critter the gene came from. You just run off the code on a special DNA printer containing cartridges filled with liquid As, Cs, Gs, and Ts. Then you insert the new DNA into whichever organism you want to modify. The process is shockingly easy.

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I raise my glass and pause. Zayners yeast suffuses the beer with a gauzy haze. I have no idea which species of jellyfish the GFP gene came from, but my hunch is that it has never been a regular part of the human diet. Zayner assures me its safe. Genetic engineers love GFP because its such an easy visual. They include it with whichever other gene theyre trying to insert, and if their organism glows, they know the experiment worked without having to send off a sample for DNA sequencing. Scientists have engineered glowing cats and mice using GFP, he points out, and the creatures lived just fine.

I eye Zayner. He has drunk a fair amount of GFP beer himself, and while I wouldnt say he looks normalhe sports dozens of piercings, plugs in both earlobes, and a spike of bleached hair that is sometimes blue and sometimes whitehe seems healthy enough.

Dude, he assures me, we did all the normal FDA tests. Its nontoxic, nonallergenic. As further proof, he shows me his left forearm. Right next to the tattoo that says CREATE SOMETHING BEAUTIFUL is a row of four tiny wounds. I modified myself with it. Its fine.

Agar plates and vials of microbes at the ODIN lab. (Justin Kaneps)

Zayner claims he was the first to genetically modify himself with another speciess DNA. For what he would call a science experiment and I would call conceptual art, he removed dead skin cells from his forearm (just rub the same spot with a toothbrush 200 times) and used a tattoo needle to punch jellyfish DNA into his skin. The DNA was attached to a common virus that specializes in infiltrating human cells and parking itself there. Those skin cells then began manufacturing the GFP along with all their regular proteinsthough, to Zayners disappointment, not enough to see the glow with the naked eye. He also performed a DIY fecal transplant on himself, which was chronicled in the recent documentary Gut Hack, curing himself of years of irritable bowel syndrome.

Im not sure what I think about any of this, starting with my beer. I tend to favor pilsner over jellybrew, but Im trying to maintain my chill biohacker persona, so I chug. Weve spiked it with enough blood orange juice to cover any weirdness, and frankly it goes down pretty easy. Just like that, this crunchy Vermonter who always shunned GMOs filled his belly with them, and starts looking forward to the week ahead.

Id always thought of genetic engineering as something done in million-dollar labs by corporate powerhouses like Monsanto. Extracting the DNA from life forms and inserting it into other life forms seemed like the kind of thing that required high-tech machines and years of trial and error. And it used to. But that was before Crispr, Science magazines 2015 Breakthrough of the Year, an engineered protein that can snip out sequences of DNA wherever you want. Its like a search and replace function for genes. It works on bacterial cells, it works on mouse cells, and it works on human cells. Its been used to engineer immune cells that kill cancer, viruses that kill antibiotic-resistant bacteria, female mosquitoes that cant reproduce (to crash the population), and a yeast infused with genetic code from poppies and rats that makes opioids out of sugar in a tank. But the crazy thing about Crispr is that its so easy to use and cheap to make that it also allows any budding hacker with some basic biology and a mischievous mind to play God in their garage.

The only thing missing is someone to share this knowledge with the multitudes, and thats where Zayner comes in. He started out traditionally enough: wunderkind Ph. D. candidate at the University of Chicago and then research fellow at NASA, where he adapted organisms for life on Mars. But then, in 2015, he veered off to become the pierced Prometheus of genetic engineering, bringing it down to us mortals from the labs of academia. In this field, there are a bunch of people with a lot of knowledge and a bunch of people with a lot of crazy, he says with a smile, but there are very few with a lot of knowledge and a lot of crazy.

Not for the first time, I smile back at Zayner and try to gauge the crazy. For now Im coming down on the side of like a fox. Hes made a huge success of the ODINshort for Open Discovery Institute and inspired by the Norse godthe combination lab and mail-order business he founded in 2013 to make DIY bio accessible to everyone. The ODIN sells pre-engineered GFP yeast ($80) online, along with DIY Crispr kits ($150), fluorescent-yeast-engineering kits ($160), something called the Amino DNA Playground ($349), and a complete Genetic Engineering Home Lab Kit ($999) stocked with pipettes, tubes, scales, antibiotics, agar, light-activated bacteria, bioluminescent bacteria, Crispr, and a PCR machine, which makes copies of DNA through polymerase chain reaction. The ODINs clients include community colleges, high school kids, and mysterious individuals.

Jars of Crispr. (Justin Kaneps)

All ODIN kits are designed to engineer bacteria or yeast, the cheapest and simplest critters to work with, and they focus on obvious visuals like GFP. They are the Easy-Bake Ovens of genetic engineering. They offer quick success to rank amateurs like me and a tantalizing taste of the endless possibilities. Where we take it from there is up to us.

Zayner and his fellow biohackers are big on genetic freedom. Everything your body makes or does is encoded by a gene. And the more we learn about the genetic basis of human processesfrom disease and life expectancy to athletic and mental performancethe closer we get to being able to reprogram our bodies. I think we could do substantial changes to ourselves right now, Zayner says. You could go a little more crazy than scientists have been willing to let on.

For years there have been rumors that people already are. Gene doping, as its called, could theoretically give anybody the ability to burn oxygen like a Tibetan mountaineer, to build muscle like LeBron James, and to never get heart disease. Its all in the genes. Its in the hard work and good habits, too, but without certain tools you can only go so far. And in either the shady present or the not so distant future, well all have access to those tools, which Zayner finds pretty exciting. This is the first time in human history that were no longer stuck with the genes we had at birth. It fucking blows your mind.

He sees no reason to let corporations and ivory-tower institutions have all the fun. Hence the Easy-Bake Ovens. Give a man a cookie and he eats for a day. Teach a man to cook and youve stolen fire from the gods.

Josiah Zayner. The name screams Marvel Comics. The backstory, too: Country childhood on an Indiana farm. Pentecostal parents. (His brothers are Micah, Zachariah, and Jedediah; the dog was named Jeremiah.) Missionary in Peru. Teenage member of the late-nineties hacker collective Legions of the Underground. Biophysics Ph.D. from the University of Chicago. Synthetic-biology fellowship at NASAs Ames Research Center. Then something goes horribly wrong.

In Zayners case, there was no lab explosion. No rampaging through the streets of Mountain View, paralyzing Google employees with jellyfish tentacles sprouting from his back. No, what went wrong is that Zayner discovered that NASA was deadly dull. Empty offices. Stultifying bureaucracy. A supervisor who actually told him to spend less time in the lab. Not the place for someone who wanted to change the universe. So he did what any budding superhero would do: he went rogue.

Crispr and pipettes. (Justin Kaneps)

As his two-year NASA fellowship neared its end in 2015, Zayner launched an Indiegogo campaign offering contributors their own DIY gene-editing kit. Hed learned just enough while getting his Ph.D. to realize that genetic engineering was way more accessible than most people knew, and he couldnt wait to liberate it from the elite labs he loathed and bring it to the people, because, as he told me, I was always that poor-as-dirt kid dreaming that he could do some great experiment. The pitch video featured shots of Zayner swigging from a flask at the lab bench (his kitchen counter) while the voiceover asked, If you had access to cutting-edge syntheticbiology tools, what would you create? The campaign raised more than $70,000.

It also freaked out critics. Zayners campaign is worrisome because it does not seem to comply with the DIYbio.org code of conduct, Todd Kuiken, a scholar in the Genetic Engineering and Society Center at North Carolina State University, wrote in Nature in 2016. He was referring to the nonprofit founded in 2008 to foster safe practices in DIY biology. For example, he noted, The video that accompanies his campaign zooms in on petri dishes containing samples that are stored next to food in a refrigerator. Kuiken also believes there needs to be a robust public dialogue about the responsible use of Crispr.

The refrigerator comment still annoys Zayner. So are you saying that being able to do science is a class thing? Only people who can afford second fridges should do science? But he got his act together and bought another fridge, in part because he was already under scrutiny from the FDA, which had threatened to seize his equipment because of his Internet sales. Zayner has also been warned of possible prosecution by officials in Germany, where biohacking is banned. But the practice is perfectly legal throughout the United States, mostly because it has never occurred to legislators to outlaw such a thing, and the ODIN is doing well. Zayner sells thousands of gene-editing kits globally every year, and he expects to gross at least $400,000 in 2017. The world wants this.

The workday at the ODIN starts late-morning. One employee is multi-tasking, packing kits for the days orders while he propagates new batches of microbes. Zayners brother Micah is scarfing Chinese takeout on the couch. The air is redolent with the funk of E. coli bacteria and young male. Zayner solders new wiring onto used PCR machines (There are few things Im one of the worlds leading experts on, but finding functional lab equipment on eBay is one of them, he says) while guiding me through an attempt to engineer antibiotic resistance into E. coli using Crispr. Despite the punk trappings, Zayner is gentle, kind, and a very good teacher.

We rehydrate some dried E. coli in a test tube, pour it into a petri plate containing nutrients, and set it aside overnight. In the morning, we have a flourishing colony of fuzzy white bacteria. We scrape it up, divide it into two plastic tubes of liquid, and to one tube add a few drops of Crispr programmed to change a single A to a C, which will flip the electrical charge of a protein in the bacteria from positive to negative at the point where streptomycin normally attacks it, repelling the antibiotic molecules. Then we pour the two batches onto fresh agar plates laced with streptomycin and incubate everything at 99 degrees for 24 hours.

Genetically modified beer. (Justin Kaneps)

The next day, I pull our agar plates out of the incubator and examine them. Eureka! The normal bacteria is stone-cold dead. But the plate with the modified bacteria is studded with survivor colonies. Weve created GMOs in a day. They and their trillions of descendants will be immune to streptomycin.

Or they would have been if we hadnt killed the whole colony with bleach and thrown it in the trash. As crazy as our creation sounds, it turns out that it was pretty innocuous. This particular version of antibiotic resistance is so simplejust a single changed letter of DNAthat bacteria come up with it on their own all the time. We werent introducing anything the world hadnt seen before, and anyway our weak lab strain was about as dangerous as a cocker spaniel. Yet I cant help but wonder about all the biohackers out there who arent bleaching their experiments. What could the wrong person do with this knowledge?

Thats what I asked Ed You, the biological-countermeasures specialist at the FBIs Weapons of Mass Destruction directorate. You is the governments point person on bioweapons; its his job to worry about this stuff, but he had bigger things on his mind than the ODIN. The most dangerous bioterrorist out there is Mother Nature, he told me over the phone. Were getting hit with emerging and reemerging infectious diseases all the time. Bird flu, MERS, SARS, Zika, West Nile. If you think about a clear and present danger, its that. So we absolutely need the innovation that comes from the life sciences, from DIY bio, to make sure we develop the right counters.

Wait a minute, I said. You actually want them out there tinkering? Yes, he replied. Biology is proliferating quickly, but how do we address security in a way that doesnt handicap forward progress? If you shut down DIY bio, then you run a completely different national-security problem. If you stifle innovation, then youre going to be missing out on opportunities to come up with new vaccines, new biodefense, new countermeasures, new businesses. And if that happens, then youve developed a whole different kind of vulnerability.

You pointed out that the field was moving so fast that agents could never keep up with the pace of the advances. Instead, hes cultivated a neighborhood-watch mentality among the countrys scientists and biohackers. Theyre best positioned to see where the advances are coming from, he said. If someone like Josiah gets a suspicious order of some kind, he knows that hes got a local coordinator in the San Francisco field office he can contact.

Agar plates. (Justin Kaneps)

It all sounded strangely progressive for a bunch of G-men, but every expert I consulted told me that they had no concerns about Zayner. Forget the garagistas, they told me; worry about the academics. Many labs now have the technology and know-how to make some fearsome beasties. Last year, a scientist in Canada shocked the world when he managed to bring to life horsepox, a smallpox cousin that went extinct in the 1980s, by synthesizing its DNA from a sequence stored in a computer database. Are we entering a new era of bioterror?

Probably not, Zayner told me. Lets imagine youre the worst person in the world and you want to hurt people with biologicals. First you have to have the knowledge. Then you have to have the facility. Then you have to think about how its going to spread. It would be an astounding feat. Could you kill one or two people? Sure. But you can do that with a fucking kitchen knife.

That night, Zayner and I celebrate our successful biohack over pig-ear fries and sake at a Korean joint before heading over to Counter Culture Labs, a communal biohacker space where he occasionally teaches. Amid the lab benches and anarchist posters are shelves of strange plants under grow lights and a pig heart in a vat. One woman is attempting to create vegan cheese by inserting cow milk-producing genes into yeast, while another man is quietly sequencing the DNA of the mushrooms he collects in Mexico each summer. A small team are hard at work designing an organism that can produce human insulin. In keeping with the hacker ethos, they will gift it to the world open-source.

There are dozens of biohacker enclaves like this around the globe, such as Genspace in Brooklyn, New York, where hipsters can take Crispr classes and attend Biohacker Boot Camp. The U.S. has been the hub, but now Europe is coming on strong. DIYbio.org has nearly 5,000 members in its Google Group and boasts 99 local chapters, from Madison to Mumbai. Most biohackers never get beyond simple experiments with microbes, but a few have taken it further. David Ishee, a dog breeder in Mississippi, is editing heritable diseases out of his dalmatians. Sebastian Cocioba, a plant hacker in New York, engineered a pioneering blue rose gene, using a DNA sequence from a tropical clam that produces an intensely blue protein, as well as a beefsteak tomato that produces cow protein in its flesh. Cocioba, who operates out of his 12th-floor apartment in Long Island City, is so skilled that he has been asked by MIT to spearhead a top-secret flower project, the details of which cant be shared except to say that in a few years it will capture the worlds attention.

And what about people? I ask. How long before cyclists start giving themselves the EPO gene to produce more red blood cells, or lifters start playing around with the gene for human growth factor?

Zayner laughs. Dude, either people are already doing that shit, or its going to start immediately. Id be very surprised if there isnt somebody out there doing it already. Its so hard to test for. What are you going to do, look for DNA? If a professional athlete came to me right now and said, Ill give you $100,000 to make me a piece of DNA, Id be like, Hell yeah.

Zayner believes we should all have access to DIY bio. (Justin Kaneps)

Surprisingly, this is perfectly legal, though its long been banned by sporting organizations. Athletes and life-extension buffs have been sniffing around gene-therapy clinics for years, ever since pioneering physiologist Lee Sweeney, from the University of Pennsylvania, showed that mice injected with the gene IGF-1, or insulin-like growth factor, significantly increased their muscle mass. Sweeney has also shown that mice injected with endurance genes were able to run 70 percent farther on the wheel than their unmodified peers, and that couch-potato mice ran 44 percent farther.

Just this June, a team of U.S. and Israeli scientists announced the discovery of a rare genetic mutation linked to ten years of extra longevity in men. And in 2015, Liz Parrish, the CEO of the startup BioViva, announced that she was the first person to attempt to reverse her own aging with gene therapy. I am patient zero, she wrote on Reddit. I will be 45 in January. I have aging as a disease. Parrish traveled to a clinic in Colombia (the therapy isnt approved in the U.S.) and received injections of one gene to extend the lifespan of her individual cells and another to block myostatin, the hormone that regulates muscle deterioration.

Myostatin is the holy grail of potential dopers who believe they can both arrest the natural deterioration of muscle and build more in their youth. Muscle is metabolically expensive to maintain, so myostatins job is to stop new muscle from being made once youve got enough and to atrophy muscle you arent using. You can find images online of dogs, cows, and people with a rare mutation that shuts down the myostatin gene and turns them into Incredible Hulks. Scientists in China recently used Crispr to turn off the myostatin gene in two beagles. The dogs look healthy, happyand ripped.

But Im less interested in what athletes are doing than in something Zayner said to me on my first day in the lab: This is the first time in history that were no longer stuck with the genes we had at birth. If Zayner has his way, well all be sculpting our own evolution.

Lets be clear: dont try this at home! Although hundreds of gene-therapy trials are under way, and many experts believe they will eventually transform almost every aspect of human health, few have been proven safe. When you start scrambling your DNA, very bad things can happen. You can get cancer. Your immune system can attack the unfamiliar DNA, as happened when an 18-year-old with a rare metabolic disorder died during a University of Pennsylvania gene-therapy trial in 1999.

But sick people wont wait for years of trials, Zayner says. He hears regularly from people willing to roll the dice. Hes been consulting pro bono for a man using Crispr to treat his own Huntingtons disease and another who is treating his 32-year-old wifes advanced lung carcinoma with genetically engineered DNA vaccines. A lot of people contact me with stuff like thatIm suffering. Can you help?

Zayner sticks to the free advice, helping people figure out the sequence of the DNA they need without supplying anything himself, but he knows where this is headed. The only thing holding people back is morality. I have no doubt there are places in Singapore or Thailand or the Philippines doing it. They could totally create individualized cancer treatments right now. Clinics will pop up. Youll go to shops in the back alleys of Bangkok and hand $10,000 to a synthetic biologist and hell take a blood sample and make you up a vaccine in a couple of days.

Im flashing back to Blade Runners replicant shopsI just do eyeswhen Zayner gets a funny smile and cocks his head. Want to try something kind of creepy Ive been thinking about?

For our final piece of conceptual art, Zayner and I swab the crevices of our skin and inside our mouths with Q-tips and swirl the gunk into tubes of distilled water. We spread the contents over agar plates and incubate them overnight.

The next morning, Josiahthing is nearly barren, but Rowanthing is crawling with cells. Look at those big fat yeasties! Zayner mutters with envy. All I can think is, if this works, it will give new meaning to the term homebrew.

We scrape up some Josiahthing and Rowanthing and put each in its own microcentrifuge tube with some chemicals that soften up cell walls so new DNA can get inside. We pipette ten microliters of the jellyfish DNA into each tube, shake them up, let them sit for a few hours, then pour them across new agar plates and cross our fingers. If this actually works, I might make it a kit, Zayner muses.

By then I have to catch a flight home, so I tape up my petri plate and pack it, along with yellow-tint glasses and a blue LED, which makes the fluorescence easier to see. TSA doesnt bat an eye.

The next day I get an e-mail from Zayner: Any growth on that plate?

Yep! Four or five nice, puffy little white colonies.

Put on the glasses and shine blue light on them. Do they glow?

I don the glasses and hit the plate with the blue LED. There are a dozen tiny colonies that stay dull under the light, but there are also five large conical colonies fluorescing like the Green Goblin. Totally! I write back, and send a photo.

Amazing! So cool! So jealous. Mine didnt work.

I feel as proud as Victor Frankenstein. Ive created life from my own spit. In the following weeks, Rowanthing develops an apex so green you dont even need the glasses to see it. Whatever it is, its new to this planet, and its burbling away in my basement, waiting to meet the world.

Contributing editor Rowan Jacobsen (@rowanjacobsen) is a Knight Science Journalism Fellow at MIT. Justin Kaneps(@Justkaneps) is anOutsidecontributing photographer.

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Hacking Your Genes Has Never Been Easier - Outside Magazine

Quick Hits: Withdrawn Leukemia Drug Returning, Drugmaker in $58M Settlement Over Sales Reps, and More – MedShadow (registration) (blog)

The leukemia drug Mylotarg (gemtuzumab ozogamicin), which was voluntarily withdrawn from the market in 2010 over safety concerns and questions about its efficacy, is available again. The FDA has approved the biologic for adults with newly diagnosed acute myeloid leukemia and for patients at least 2 years old who have had a relapse or didnt respond to prior treatment. Mylotarg originally received accelerated approval in 2000 for older adults who had experienced a relapse. But it was removed from the market after patient deaths and a lack of clinical benefit were observed in confirmatory trials. With the new approval, Mylotarg now has a lower recommended dose, a different schedule of how often the drug is given, and a different patient population. Pfizer, Mylotargs manufacturer, presented the FDA with additional data, analysis and research from clinical trials that lasted for 10 years in support of re-approval. The FDA said it allowed Mylotargs return after careful examination and based on the benefits outweighing the risks. Posted September 1, 2017. Via FDA.

Novo Nordisk has agreed to pay $58 million over allegations that some of its sales representatives downplayed a cancer risk associated with its diabetes drug Victoza (liraglutide) in marketing to doctors. When Victoza was approved in 2010, the FDA mandated it come with a Risk Evaluation and Mitigation Strategy (REMS) that required the drugmaker to provide information regarding Victozas potential risk of medullary thyroid carcinoma (MTC) a rare form of cancer associated with the drug to physicians. According to a complaint filed by the US Department of Justice (DOJ), some Novo Nordisk sales representatives created a misleading impression that the cancer risk associated with Victoza was incorrect or unimportant. In addition, they failed to accurately report important data regarding the drugs safety and efficacy. The DOJ also noted that a survey in 2011 found that half of primary care doctors polled said they did not know about the MTC risk. Posted September 5, 2017. Via US Department of Justice.

The FDA has approved the first-ever gene therapy, Kymriah (tisagenlecleucel), as a treatment for children and young adults for a type of leukemia. The immunotherapy is considered a breakthrough since it is made using the patients own T-cells, white blood cells that are part of the bodys immune system that fight infections and cancer. Kymriah is custom-made for each patient. A patients T-cells are sent to a manufacturing facility and then modified genetically to include a gene that has a specific protein that tells the T-cells to find and kill leukemia cells. After the modification, the T-cells are infused back into the patient. Researchers found that Kymriah led to remission of acute lymphoblastic leukemia in 83% of 63 children and young adult patients within 3 months. Despite the benefits, the treatment carries risks, including a boxed warning about a potentially fatal immune reaction known as cytokine-release syndrome. Other severe side effects seen with Kymriah include serious infections, low blood pressure (hypotension), acute kidney injury, fever and decreased oxygen (hypoxia). Because of these risks, the FDA is requiring that hospitals and clinics that want to dispense Kymriah need to be certified and their staff involved in the treatment trained to recognize and manage symptoms. Posted August 30, 2017. Via FDA.

Alanna McCatty is a recent graduate of Pace University with a degree in communications. At MedShadow, she reports on new findings and research on the side effects of prescription drugs.

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Quick Hits: Withdrawn Leukemia Drug Returning, Drugmaker in $58M Settlement Over Sales Reps, and More - MedShadow (registration) (blog)

FDA approves first cell-based gene therapy for use in the United States – Gears Of Biz

The U.S. Food and Drug Administration issued a historic action today making the first gene therapy available in the United States, ushering in a new approach to the treatment of cancer and other serious and life-threatening diseases.

The FDA approved Kymriah (tisagenlecleucel) for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).

Were entering a new frontier in medical innovation with the ability to reprogram a patients own cells to attack a deadly cancer, said FDA Commissioner Scott Gottlieb, M.D. New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses. At the FDA, were committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.

Kymriah, a cell-based gene therapy, is approved in the United States for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.

Kymriah is a genetically-modified autologous T-cell immunotherapy. Each dose of Kymriah is a customized treatment created using an individual patients own T-cells, a type of white blood cell known as a lymphocyte. The patients T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.

ALL is a cancer of the bone marrow and blood, in which the body makes abnormal lymphocytes. The disease progresses quickly and is the most common childhood cancer in the U.S. The National Cancer Institute estimates that approximately 3,100 patients aged 20 and younger are diagnosed with ALL each year. ALL can be of either T- or B-cell origin, with B-cell the most common. Kymriah is approved for use in pediatric and young adult patients with B-cell ALL and is intended for patients whose cancer has not responded to or has returned after initial treatment, which occurs in an estimated 15-20 percent of patients.

Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease, said Peter Marks, M.D., Ph.D., director of the FDAs Center for Biologics Evaluation and Research (CBER). Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials.

The safety and efficacy of Kymriah were demonstrated in one multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL. The overall remission rate within three months of treatment was 83 percent.

Treatment with Kymriah has the potential to cause severe side effects. It carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, and for neurological events. Both CRS and neurological events can be life-threatening. Other severe side effects of Kymriah include serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia). Most symptoms appear within one to 22 days following infusion of Kymriah. Since the CD19 antigen is also present on normal B-cells, and Kymriah will also destroy those normal B cells that produce antibodies, there may be an increased risk of infections for a prolonged period of time.

The FDA today also expanded the approval of Actemra (tocilizumab) to treat CAR T-cell-induced severe or life-threatening CRS in patients 2 years of age or older. In clinical trials in patients treated with CAR-T cells, 69 percent of patients had complete resolution of CRS within two weeks following one or two doses of Actemra.

Because of the risk of CRS and neurological events, Kymriah is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The FDA is requiring that hospitals and their associated clinics that dispense Kymriah be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administering of Kymriah are required to be trained to recognize and manage CRS and neurological events. Additionally, the certified health care settings are required to have protocols in place to ensure that Kymriah is only given to patients after verifying that tocilizumab is available for immediate administration. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Kymriah.

To further evaluate the long-term safety, Novartis is also required to conduct a post-marketing observational study involving patients treated with Kymriah.

The FDA granted Kymriah Fast Track, Priority Review, and Breakthrough Therapy designations. The Kymriah application was reviewed using a coordinated, cross-agency approach. The clinical review was coordinated by the FDAs Oncology Center of Excellence, while CBER conducted all other aspects of review and made the final product approval determination.

The FDA granted approval of Kymriah to Novartis Pharmaceuticals Corp. The FDA granted the expanded approval of Actemra to Genentech Inc.

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FDA approves first cell-based gene therapy for use in the United States - Gears Of Biz

Researchers point way to improved stem cell transplantation therapies – Medical Xpress

September 7, 2017 When transiently expressed in HSCs, BCL-XL temporarily protects the cells from apoptosis and enhances their ability to be transplanted from one mouse to another. This microscopy image shows the successful introduction of BCL-XL (green) into a cell labeled for its nucleus (blue) and mitochondria (red). Credit: Kollek et al., 2017

Researchers in Germany have demonstrated that hematopoietic stem cell (HSC) transplants can be improved by treatments that temporarily prevent the stem cells from dying. The approach, which is described in a paper to be published September 7 in The Journal of Experimental Medicine, could allow those in need of such transplants, including leukemia and lymphoma patients, to be treated with fewer donor stem cells while limiting potential adverse side effects.

HSCs give rise to the many different cell types found in blood and can be used to treat a variety of diseases, including multiple myeloma, leukemia, and blood disorders such as sickle cell anemia. HSCs can be harvested from a suitable donor and then transplanted into a patient, where, after establishing themselves in the bone marrow, they can generate healthy blood cells.

The transplantation process is stressful for HSCs, however, and many of them die before they can successfully ensconce themselves in the patient's bone marrow. This limits the effectiveness of HSC transplantation, delaying the resumption of blood cell formationincreasing the risk of infection or bleedingor even causing the transplant to fail completely. HSC death is a particular problem if the number of donor stem cells is low to begin with. Umbilical cord blood, for example, generally contains insufficient numbers of stem cells for it to be used as a source of HSCs for transplantation into adult patients.

HSCs die through a process called apoptosis, driven by two proteins called BIM and BMF. Permanently inhibiting these two proteins prevents HSCs from dying and improves the efficiency of HSC transplantation in mice. But mice receiving these apoptosis-resistant stem cells soon develop autoimmune disease and/or lymphomas because the HSCs, and the blood cells they produce, do not die when they are supposed to.

"Thus, inhibiting apoptosis transiently during the stressful period of transplantation could be an attractive strategy to improve transplantation outcome without increasing the risk of long-term adverse effects," says Dr. Miriam Erlacher of the University Medical Center of Freiburg.

Erlacher and colleagues isolated HSCs from mice and infected them with a genetically engineered adenovirus that transiently produces a human protein called BCL-XL that inhibits BIM and BMF. These virally infected HSCs were resistant to apoptosis for the 7-9 days that BCL-XL was expressed, and, upon transplantation into recipient mice, their ability to establish themselves in the bone marrow and produce new blood cells was greatly enhanced. Moreover, because the transplanted HSCs only expressed BCL-XL for a few days, they didn't promote the formation of lymphomas in recipient animals.

Adenoviral infection is slightly toxic to HSCs, however, so Erlacher and colleagues developed an alternative approach in which purified BCL-XL could be introduced directly into isolated HSCs. This second method also provided temporary protection from apoptosis and improved the cells' ability to undergo transplantation.

"Our findings suggest that transiently inhibiting apoptosis by manipulating donor HSCs increases the fitness of these cells without elevating the risk of adverse pathology," Erlacher says. "Transient apoptosis inhibition is therefore a promising approach to reduce the risk of graft failure and improve HSC transplantation outcomes."

Explore further: Dose of transplanted blood-forming stem cells affects their behavior

More information: Kollek et al., 2017. J. Exp. Med. jem.rupress.org/cgi/doi/10.1084/jem.20161721

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Clarkson professor awarded $420000 grant to study development of intestinal stem cells using zebrafish vertebrate … – North Country Now

Clarkson University Associate Professor of Biology Kenneth Wallace showcases his subjects of study -- zebrafish -- a common aquarium fish who share more than 70 percent of their genes with humans.

POTSDAM -- Kenneth Wallace, associate professor of biology at Clarkson University, has been awarded a $420,000 grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development at the National Institutes of Health to investigate development of intestinal stem cells using the zebrafish vertebrate model system.

While much has been discovered about how stem cells are controlled during the adult phase, much less is known about the origins of these stem cell compartments. Little is known about when the stem cells form and how they are regulated. To uncover more about how stem cells are regulated during development of the intestine, Wallace will use zebrafish, which have become a widely-used vertebrate model system.

Zebrafish are a common aquarium fish, which are small easy to care for and have embryos that develop rapidly in an external environment. They also share more than 70 percent of their genes with humans, making them an excellent system to study both development and the origins of disease. Understanding of the genes and mechanisms involved in formation and regulation of the fish intestinal stem cells will provide information about how human intestinal stem cells are regulated.

Aside from the main research component, a secondary goal of the grant and project is to provide resources for undergraduate Clarkson University students to perform independent research on the molecular and cellular basis of embryonic development under Wallaces supervision. This will give them first-hand knowledge of developmental biology research practices and perhaps pique future interest in the field and research.

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Stem Cell Therapy: A Lethal Cure – Medical News Bulletin

Stem cell therapy is a two-step process. First, the patients blood cells are destroyed by chemotherapy, radiation therapy or immunosuppression. This conditioning process also eradicates any cancer cells that survived first-line treatment. Second, the patient receives stem cells harvested from a donors bone marrow or peripheral blood (circulating blood). While this can be an effective cure, it can cause graft-versus-host disease (GVHD) in up to 50% of patients. GVHD is more likely to develop in patients who have received a peripheral blood transplant and can kill 15%-20% of patients.

Two types of GVHD can develop, acute and chronic, and patients may develop either one, both or neither type. GVHD is less likely to occur and symptoms are milder if the donor cells closely match those of the patient. Acute GVHD can develop within 100 days of a transplant. The first step of stem cell therapy can cause tissue damage, and bacteria from the gut can escape into the bloodstream. This primes the patients antigen-presenting cells (cells that activate the immune response), which subsequently encourage donor T cells to proliferate and attack the patients tissues. Symptoms include vomiting, diarrhea, skin rashes, nausea, vomiting and liver problems. This can be resolved relatively quickly in one third of patients using immunosuppressive treatments, but some patients can progress to chronic GVHD.

The biological mechanisms responsible for chronic GVHD are not completely understood, but scientists believe that other immune system cells from the donor (B cells and macrophages) are stimulated and damage the patients tissues. Symptoms include dry eyes, mouth sores, muscle weakness, fatigue and joint problems.

Unfortunately, development of effective treatments for GVHD is not keeping up with the increasing number of GVHD patients or with advances in understanding this disease. At present, standard treatments include corticosteroids and drugs that reduce IL-2, an immune system chemical that helps T-cells multiply and diversify. These treatments have various side effects including suppressing the patients immune system, thereby increasing risk of infection.

One challenge stalling drug research is that a small degree of graft-versus-host response must occur for successful stem cell therapy: donor cells will destroy any cancer cells that remain after the first stage of therapy. This challenge is discussed in a recent article in Science Health.Although several treatments have been trialed, success is variable and often targets only acute GVHD or chronic GVHD. Biomarkers have also been detected that may help identify individuals at risk of developing severe GVHD, information that may aid the development of personalized treatment strategies. Drugs that have been approved for other diseases, but not for GVHD, show promise and include ibrutinib for chronic GVHD (approved for specific blood cancers) and ruxolitinib for acute GVHD (approved for bone marrow disorders).

The impact of stem cell therapy must not be underestimated: up to 50% of recipients will develop GVHD. Unfortunately, some individuals will develop chronic GVHD, a condition that is just as difficult to survive as cancer. This highlights the importance of developing continued care strategies for individuals receiving stem cell therapy as a final defence against cancer.

Written byNatasha Tetlow, PhD

Reference: Cohen J. A stem cell transplant helped beat back a young doctors cancer. Now, its assaulting his body. Science Health. 2017. Available at: DOI: 10.1126/science.aan7079

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Stem Cell Therapy: A Lethal Cure - Medical News Bulletin

Researchers Hope Zika Virus Can Treat Deadly Brain Cancer – Healthline

Researchers have discovered that the Zika virus can kill tumor cells from glioblastoma cancers. Heres how it does that.

The Zika virus is known to attack the developing brain of fetuses, leaving infants at risk for severe birth defects.

But scientists are now hoping they can harness this dangerous virus to reach the brain in adults and kill hard-to-treat tumors.

The Zika virus swept through the Western hemisphere last year infecting millions and resulting in thousands of infants being born with the birth defect microcephaly.

The virus ability to reach the brain in utero has also led researchers to theorize it could potentially be used to fight a malignant form of brain cancer in adults, called glioblastoma.

In a new study, published in the Journal of Experimental Medicine, researchers from Washington University School of Medicine, the Cleveland Clinic, University of San Diego, and other institutions studied how human glioblastoma cells reacted to exposure to the Zika virus.

They also infected mice with glioblastomas to the virus to see if the infection affected the tumor.

Glioblastomas are the most common form of primary brain cancer, or cancer that has not metastasized from other areas of the body.

Every year approximately 12,000 people are diagnosed with the condition. This year Arizona Senator John McCain made headlines with his glioblastoma diagnosis.

Its a malignant form of cancer that kills most people within two years of diagnosis, even after surgery, chemotherapy, and radiation treatment.

In this study, the researchers wanted to see if Zika could potentially be used as a treatment to buy patients more time.

They exposed 18 mice with glioblastomas to the Zika virus and found that within two weeks the tumors were far smaller than those in the control group.

Additionally, they found that when they injected the virus into tumor cells, the virus infected and killed the stem cells in the tumor.

The findings are still preliminary, and the authors point out these findings would need to be replicated in patients with glioblastoma to verify the effects of the virus on these cancer cells.

Scientists hope these early results could mean that the Zika virus could be used in the future to help fight against glioblastoma.

We see Zika one day being used in combination with current therapies to eradicate the whole tumor, Dr. Milan G. Chheda, a senior author of the study and an assistant professor of medicine and neurology at Washington University School of Medicine, said in a statement.

Dr. Andrew Sloan, director of the Brain Tumor and Neuro-Oncology Center at University Hospitals Cleveland Medical Center, said that a patient with glioblastoma will usually have surgery to remove the tumor.

However, not even the best surgeon can get every microscopic cancer cell in the brain.

Ninety-eight percent of the patients will die of the tumor, and 90 percent will have the tumor grow back between 1 to 2 centimeters of the primary tumor, he explained.

Sloan explained that doctors believe its the stem cells which make up a small fraction of tumor cells that can cause the tumor to quickly grow back.

Cancer stem cells might compromise between 2 to 5 percent of all the cells in the tumor, Sloan told Healthline. But these are cells that are very resistant to radiation and chemotherapy, and these are the cells that give rise to new tumors.

Sloan said if the Zika virus targets the stem cells it might mean that the cancer doesnt return in patients after surgery.

Sloan said doctors have been hoping to find a way to harness a virus to prime the immune system to fight cancer, but so far nothing has been a game changer for glioblastoma treatment.

Theres been a lot of progress in immunotherapy, Sloan said. We think thats probably the best bet, but we havent hit anything over the fence.

He said he hopes that this early study could be the starting point for more research that could find a way to turn a deadly virus into a treatment.

Its very exciting and I think theres a lot of potential for it, he said.

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Researchers Hope Zika Virus Can Treat Deadly Brain Cancer - Healthline

‘Nanotransfection’ Turns Animal Skin into Blood Vessels and Brain Cells – Medical Device and Diagnostics Industry

Nancy Crotti

Researchers have developed tissue nanotransfection, a process for regrowing tissue inside the human body.

Researchers at Ohio State University have developed breakthrough stem cell technology that can regrow tissue inside the human body, rather than in a laboratory.

Their work has implications for critical limb ischemia, brain disorders, and possibly even organ engineering and bone regrowth, according to Chandan Sen, PhD, director of the Center for Regenerative Medicine and Cell-Based Therapies at Ohio State's Wexner Medical Center in Columbus. Sen led the team that developed the technology.

Here's how the process, known as nanotransfection, works: The scientists make synthetic RNA and DNA to match that of the patient. They load it into nanochannels inside tiny needles embedded in a chip and apply the chip to the skin. The needles electrocute about 2% of the cell surface with the patient's nucleic acid. The procedure takes 1/10th of a second, and has been shown to work with up to 98% efficiency.

In experiments on mice, the technology restored blood flow to injured legs by reprogramming the animals' skin cells to become vascular cells. With no other form of treatment, active blood vessels had formed within two weeks, and by the third week, blood flow returned and the legs of the mice were saved.

The researchers also induced strokes in mice and used the chips to grow new brain tissue from the animals' skin and transplant it to their brains. Bodily function damaged by the strokes was restored. The study of the technique, which worked with up to 98% efficiency, was reported in the journal Nature Nanotechnology.

The technology marks an advance over cell regeneration conducted in a laboratory, because those cells mostly underperform or die once transplanted into the body, according to Sen. The researchers use skin cells in their work because, as Sen explained, everybody has some to spare.

"We grow it in you and we move it over to the organ so you have your own cells populating your organ," he said. "It's all coming from you."

The synthetic RNA and DNA reprogram cells in the same way that fetal cells develop different functions to become different body parts, Sen added. The researchers worked on the technology for more than four years, also conducting successful blood flow restoration experiments on pigs. When they begin human trials, their first patients will likely be those whose critical limb ischemic has reached the stage where amputation is the only option.

The scientists' work has generated interest in Europe, Asia, the Middle East, and in the United States. Ohio State will decide where to pursue human trials first, and is searching for industry partners.

"The cost is extremely low and complexity-wise it is extremely low. I see very little barrier to take it to humans," Sen said.

The researchers' work marks another interface between silicon chips and biology. Other applications picked up by manufacturers include DNA sequencing machines, miniaturized diagnostic tests using disposable photonic chips, accurate body monitoring sensors, and brain stimulation probes.

Sen and his team acknowledge that their work will be met with skepticism.

"Whenever you do something that is sort of transformative, you will expect that," Sen said. "Therefore, we actually published this in the most rigorous journal possible. We went through 16 months of criticism and response, after which this was published."

Nancy Crotti is a freelance contributor to MD+DI.

[Image courtesy of THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER]

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Researchers Turn Skin Cells into Motor Neurons Without Using Stem Cells – Futurism

Cellular Renovation

Why build something from the ground up when one can just renovate an already existing structure? Essentially, thats what researchers from the University of Washington School of Medicine in St. Louis had in mind when they developed a method for transforming adult human skin cells into motor neurons in a lab. They published their work in the journal Cell Stem Cell.

In this study, we only used skin cells from healthy adults ranging in age from early 20s to late 60s, senior author Andrew S. Yoo said in a press release. Our research revealed how small RNA molecules can work with other cell signals called transcription factors to generate specific types of neurons, in this case motor neurons. In the future, we would like to study skin cells from patients with disorders of motor neurons. Our conversion process should model late-onset aspects of the disease using neurons derived from patients with the condition.

They did this by exposing skin cells in a lab to certain molecular signals usually found at high levels in the human brain. They focused on two short snippets of RNA: microRNAs (mRNAs) called miR-9 and miR-124, which are involved in repurposing the genetic instructions of the cell. These mRNAs, combined with certain transcription factors, successfully turned skin cells into spinal cord motor neurons within just 30 days. These new cells closely resembled normal mouse motor neurons in terms of which genes were turned on and off, and how they functioned.

Usually, when researchers find ways to replace damaged cells or organs, they resort to using stem cells. In particular, they use embryonic stem cells (a type of pluripotent stem cells) to grow the cells or organs needed.

While this type of stem cell has the potential to grow into whatever adult cell type is needed, the procedure carries some ethical concerns. In bypassing a stem cell phase, the new cell transformation technique doesnt have any of these ethical issues.

Keeping the original age of the converted cells can be crucial for studying neurodegenerative diseases that lead to paralysis, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy, the condition the new research focused on. In particular, researchers hope that it could enhance the understanding of these diseases in order to improve regenerative medicine.

Going back through a pluripotent stem cell phase is a bit like demolishing a house and building a new one from the ground up, Yoo explained. What were doing is more like renovation. We change the interior but leave the original structure, which retains the characteristics of the aging adult neurons that we want to study.

Like embryonic stem cells, the technique can also allow for converting human skin cells into other cell types by using different transcription factors. Before this technique can be applied to actual humans with neurodegenerative diseases, the researchers still need to find out how much the cells made in their lab match native human motor neurons. Still, its a promising start.

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Researchers Turn Skin Cells into Motor Neurons Without Using Stem Cells - Futurism

Transformative technology: Encapsulated human cells to … – Medical Xpress

September 7, 2017 Professor Che Connon and Dr Stephen Swioklo of Atelerix, a spin-out from Newcastle University, is offering the transformative hydrogel technology for the storage and transport of viable cells including stem cells and cell-based assays at ambient temperatures. Credit: Newcastle University

Atelerix, a spin-out from Newcastle University, UK is offering the transformative hydrogel technology for the storage and transport of viable cells including stem cells and cell-based assays at ambient temperatures. This overcomes the barriers presented by the current need for cryo-shipping as it is simple, cell-friendly and offers immediate access to stem cell therapy.

This opens up the market for the supply of cells and assays in a ready-to-use format, allowing suppliers to increase the range of assays available to consumers and to scale up their businesses.

The breakthrough, patented invention, provides dramatic improvements to an everyday process in a rapidly growing market.

Scientific founder, Professor Che Connon of Newcastle University, has been working on the underpinning technology for five years. He said: "Encapsulating cells in the alginate hydrogel is a simple, low cost system capable of preserving the viability and functionality of cells at temperatures between 4 and 21C for extended periods of time.

"Used as a method of cell storage and transport, it overcomes the acknowledged problems associated with cryo-shipping. Cells are encapsulated by in situ formation of the gel for shipping in plates or vials, and can be rapidly released from the gel by the addition of a simple buffer."

Atelerix is set to revolutionise the market with their use of encapsulated stem cells as Dr Mick McLean, CEO for Atelerix explained: "Understanding both the technology and its commercial potential is essential for the translation of great science into an exciting business opportunity.

"Putting these elements in place by working together with the expert scientific team means that Atelerix has a clear value proposition - we enable the transport and storage of human cells at room temperature."

The hydrogel technology allows immediate access to cells and can be used in a range of applications where high quality cells are essential.

Applications

The shipping of cells from one location to another for clinical and research use is a widespread and everyday practice, and consequently there are many potential commercial outlets for the hydrogel encapsulation technology.

Atelerix, the commercial spin-out from Newcastle University is targeting three key areas:

First Northern Accelerator spin-out company

Atelerix, is the first spin out company created under a new joint collaborative project between Newcastle and Durham Universities, UK.

The Northern Accelerator project, which is part-funded by the European Regional Development Fund (ERDF), is creating high technology spin-out companies by attracting talented business leaders to the innovative commercial opportunities both created and developed in the north east of England.

Through this, experienced life sciences business leader Mick McLean was brought in to work alongside the founder academics, Professor Che Connon and Dr Stephen Swioklo.

Dr McLean said: "Working alongside the University team on the strategy for the Intellectual Property and the corporate framework has really helped give the business a base from which to expand as it starts to move on from its academic roots."

David Huntley, Head of Company Creation at Newcastle University and overall Project Manager, said: "Atelerix is an excellent example of the clear benefits of the Northern Accelerator programme. By combining Mick's business skills with the technical excellence of the scientific team's world-leading background research, we have created a brand new technology business that we believe will make a real and significant commercial impact."

Explore further: Seaweed offers the solution to transporting stem cells and wound treatment

More information: Previous research: Stephen Swioklo et al. Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells, STEM CELLS Translational Medicine (2016). DOI: 10.5966/sctm.2015-0131

A new review is the first to directly examine the role of various stem cells in the healing of wounded cornea, the outermost part of the eye. In contrast with most other reviews, it covers all major corneal cell types in ...

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Transformative technology: Encapsulated human cells to ... - Medical Xpress