Category: Research

  • Skype A Scientist

    Skype A Scientist

    illustration of a scientist viewing a computer via skype

    Skype A Scientist

    This program, which has grown in 8 months from one graduate student in one lab at UConn to thousands of scientists across 12 time zones and all 50 states isn’t the answer to all the world’s woes ”” or is it?

     

    By Kim Krieger

    Illustrations by Kailey Whitman

    The first thing she showed them was a large, stuffed fruit fly. This impressed them. Then she flashed test tubes full of living flies. Fascination ensued, for she was obviously no ordinary person but rather someone with a deep grasp of what was important in life: stuffed animals and bugs.

    Later she told them she was a microbiologist who studied the germs living in the flies’ stomachs. That was when the questions started.

    “Where did you grow up?”
    “Why do moths eat clothes?”
    “Do aliens really exist?”

    The teacher of these kindergarteners says she has never seen them as engaged as this, when they got to Skype a scientist.

    Her kindergarten class is in Venice, Florida, and the scientist was Nichole Broderick, an assistant professor of molecular and cell biology, who was Skyping from her UConn Storrs office 1,300 miles away. Broderick is one of 497 scientists who talked with schoolchildren last semester through a project called Skype a Scientist, started by a third-year graduate student at UConn named Sarah McAnulty.

    Aliens loom large in kindergarteners’ minds, and Broderick was pleased to use the alien question to introduce the kids to invasive species, which, she explained, are just like aliens but from other ecosystems instead of other planets.

    In other classes in other places, other scientists discussed the social lives of ants with middle schoolers, introduced fourth graders to the extreme environment of a Yellowstone geyser, and talked with high schoolers about the environmental consequences of war. The researchers hailed from all over this country and the classrooms from as far away as Kyrgyzstan. But in every case they had been introduced by McAnulty.

    BLACK INK AND BLUE BLOOD

    McAnulty spends most of her time studying bobtail squid in Associate Professor Spencer Nyholm’s biology lab. She loves science and is, in Nyholm’s words, a phenomenal graduate student, a self-starter who raises money and bobtail squid with the same dedication, for the lab depends on a steady stream of both. Late last year, McAnulty began thinking about politics, too. Because politics had begun to impinge on science.

    The country was divided like never before in her lifetime. Anti-intellectualism seemed to be on the rise, and even truth itself seemed under attack. Academic research in the U. S. depends on public funding, and public funding depends on the goodwill of the people. And somehow, that goodwill seemed to be eroding.

    “As a community, we were realizing that people view scientists as aloof and cold,” says McAnulty. “Even suspecting we had ulterior motives for sharing our data!”

    She says this with shock, as if comparing scientists exchanging data sets to Big Tobacco manipulating medical trials is unthinkable. And until seven or eight years ago, it was. But something has changed in the public’s perception of scientists.

    “There’s a feeling that for U.S. science to survive, we really need to get people trusting scientists again,” says McAnulty. She’s chatting with me near the entrance to her lab in the Storrs biophysics building. Right next door is where she raises the bobtail squid. Bobtail squid are adorable, as cute as an invertebrate can be. Only a few centimeters long, with big eyes and eight short little legs, they can even glow in the dark, thanks to the colonies of bioluminescent bacteria that live symbiotically inside them. Nyholm’s lab focuses on the relationship between symbiotic bacteria and their hosts.

    McAnulty’s part of the research zooms in on the squid’s immune system and why it tolerates the glowing bacteria. Bacteria live in our guts, too, although they don’t make us glow in the dark. Studying the squid’s relationship with their symbionts could tell us more about ours. McAnulty has become an expert at drawing blood from the little mollusks. She says she doesn’t mind it nearly as much as she did when she worked with mice.

    “I felt bad doing experiments on mice. Something about their red blood. I don’t feel as bad with squid. And they usually come right back,” swimming off into their tank, leaving nothing but a vial of bluish-green blood behind.

    Wait ”” squid have blue blood?

    “It’s because of the hemocyanin,” she tells me. Like hemoglobin in our red blood cells, hemocyanin uses a metal to bind oxygen. But where we use iron, squid’s hemocyanin uses copper. As she explains this, the Pharmacy Building looms behind her. Its copper roof has oxidized to a rich bluish green color from exposure to rain and air. A similar chemical reaction accounts for a squid’s blue blood.

    Sarah McAnulty is a Ph.D. candidate in molecular and cell biology.

    ^ The bobtail squid she works with.

    Visit: Skype A Scientist

    Tumblr: Squid Scientist

    Do Aliens Really Exist

    Kids need to see theres a big bright world out there.”

    Ask Me Anything.”

    McAnulty put up a Tumblr page when she joined Nyholm’s lab. She posts about her research, science books she likes, marine biology in general, and loads of cute squid pictures. She also has an “Ask Me Anything” section. Readers ask all kinds of questions, as earnest as “How do you ethically source cuttlebone?” or “How do you pick the animal you want to study for the rest of your life?” and as ridiculous as “Do squids pass gas?” Sarah replies to that last with, “Well, yes and no. They do get air trapped in their mantles when they swim over a bubble, but they don’t pass gas from their digestive tracts as far as I know!”

    She says she enjoys the back-and-forth with readers, and her answers are always informed by her own experience.

    McAnulty has spent a lot of time talking to colleagues about the public perception of science. The problem seems clear: How can scientists remake their public image from aloof to approachable? Many scientists aren’t all that great at talking about their work with nonscientists. Sometimes it’s because they think no one else will be interested in hearing about it. Other times they’ve been holed up in their lab talking only to colleagues for so long they’ve forgotten how to communicate with regular folks. Get two researchers from the same subfield talking to each other excitedly, and even other scientists from another field can quickly lose the thread as the two specialists descend into a rarified dialect of Deep Geek.

    McAnulty, however, likes talking about her research with nonscientists. She also has an intuitive grasp of marketing and outreach. She’d started the Tumblr so she could share her work more broadly, and she’d picked Tumblr because it reaches a younger, more female audience than other social media favored by scientists. Still, she knew that her Tumblr page was preaching to the choir. You don’t seek out scientists who study bobtail squid unless you’re already interested in squid. Most people are firmly ensconced in their own little bubbles.

    Who has the most questions? Kids.

    But kids are different. Before grad school, McAnulty spent a year working in a diabetes biology lab in the Max Delbrück Center for Molecular Medicine in Berlin. The university hosts a “Long Night of Science” each summer, when it opens up the labs to the public and families participate in science activities until late in the evening. The kids were always curious about everything. What if she could talk to school-aged children, children who were probably apolitical and just interested in cool ideas?

    One day she was chatting with a bunch of biologists on Twitter when the idea of reaching out to classrooms via Skype came up. “We just decided to do it. What’s the worst that could happen? We make some teachers mad at us,” she recalls. And so Skype a Scientist was born.

    McAnulty began reaching out to teachers through Facebook. Would you like to have your class talk to a scientist? she asked. She aimed especially for teachers in geographic areas that might be pretty remote from real-life scientists, but she replied to any teacher who inquired. It quickly became apparent that making teachers mad was not going to be an issue.

    “I can’t wait to do it again! I’d recommend it to anyone in the school,” says Cathleen Francis, the kindergarten and first grade teacher in Venice, Florida whose class asked about aliens.

    “Skype a Scientist is great for me,” says Trudy Fadden, a middle school science teacher in Vermont. “You have to build a relationship. And you don’t want it to be a dog and pony show, you have to make connections between the kids and the science,” she says. That real person helps tremendously, she adds, even if they are only on a screen. Fadden had two scientists Skype her class, one from Rutgers University and the other from UConn, a graduate student in the Klassen Lab for molecular and cell biology named Emily Green. She has kept in touch with both researchers and plans to Skype them again next year.

    Answering Curiosity in Every Language

    Fadden and Francis were early adopters, part of the first wave of teachers who simply answered Facebook inquiries. McAnulty would manually match them with a scientist in the right discipline and time zone. The requests kept coming. And then a teacher mentioned Skype a Scientist publicly at a conference in Texas and the Google sign-up form McAnulty had slapped together “just blew up,” she says.

    Overnight, 200 classrooms signed up. Scientists showed equal enthusiasm. One would tell another, who would tell another, and by the end of July McAnulty had more than 1,740 classrooms signed up and 1,755 scientists, with participants hailing from 17 countries and all 50 states. More press followed, including a feature on NPR’s “Science Friday.”

    UConn scientists continue to be major players. CAHNR graduate student Mauri Liberati did a total of nine sessions with one school. Three UConn biology professors ”” Nichole Broderick, Susan Herrick, and Ken Noll ”” have participated, signed up for more sessions, and involved more professors for this fall. They all say it’s fun, and it’s easy. Broderick says she enjoyed her Skype session with the kindergarteners as much as Francis did. “Having to explain concepts to 5- and 6-year-olds really makes you think,” she says.

    Can it really be this easy to change the public’s perception of science? Other scientists are running for political office, or demonstrating in political rallies like the March for Science last April. McAnulty attended the march. She says she wasn’t sure how she felt about it going in, but thought it was important to attend.

    “Finding truth is impartial, as far as left and right. But as long as the government funds science, and you have a political system opposed to truth, being on the side of truth is a political act,” she explains.

    But how does she, or anyone in science, know they really are on the side of “truth”? Science corrects itself and reverses course constantly. Bubbles burst. Paradigms shift. It’s an intrinsic part of the scientific endeavor that science is self-correcting. But this also is part of what makes the general populace distrust scientists; one day something is heralded as empirical truth that we should all heed. The next, it’s contradicted by a new piece of evidence.

    And it’s true that even though Skype a Scientist has national reach, one could argue it’s not reaching kids who need it most. Just to start, you need to have a science-positive teacher who’s comfortable bringing a scientist “into” the classroom. One teacher admitted that her colleagues and school administrators regularly discuss what they would do if a parent questioned what they were teaching. But she’s never seen anything from students but love for science. And just because you can’t help everybody doesn’t mean you shouldn’t try. A Vermont parent put it very bluntly:

    “This town is in the thick of the opiate epidemic. Three people died down the street from me this year. We’re a very rural school. Kids need to see there’s a big bright world out there.” People might distrust scientists as elitist, she continued, but people also want their kids to expand their horizons.

    McAnulty gets it. One summer she worked surveying bat populations in Pennsylvania and West Virginia, scoping out the site of a proposed wind farm. She saw the economic challenges in the region. She chatted with some of the locals. She knows that any national distrust of scientists is part of a much bigger malaise.

    “I don’t think this is the problem with the U.S. But this is a problem. I feel equipped, and I’ll try to fix it,” she says.

    And with a little luck, these Skype sessions will make an impression. And some school kids in West Virginia and Missouri and Florida and Vermont and all the other classrooms will grow up with the knowledge that science is a quest for truth about the natural world. It’s done by real people just like them. And because of that, science is imperfect and can always be worked on. If the kids believe it, they’ll grow into adults who support it.

    Maybe they’ll participate in the research enterprise, or use the scientific method in their daily lives. Or maybe they’ll just remember that day in fourth grade that they got to ask a real scientist whether squids fart, and that she laughed with them, not at them. And that might be the best outcome of all.

    squid
  • Avery Point Lighthouse

    Avery Point Lighthouse

    On Campus

    Avery Point Lighthouse

    In early spring, Penny Vlahos, associate professor of marine sciences, replaces a seasonal cartridge on an air sampling device attached to the Avery Point Lighthouse. The samplers are changed every three months and analyzed for persistent organic and emerging pollutants. UConn Avery Point is celebrating its fiftieth anniversary this year.

    Peter Morenus

  • Science to Startup

    Science to Startup

    Science to Startup

    A Connecticut company plays the startup game in the land of innovation

    BY COLIN POITRAS ’85 (CLAS)

    ILLUSTRATIONS BY KATIE CAREY

    Game board pieces of biochemist, Mark Driscoll, and business partner, Thomas Jarvie. Illustrations by Katie Carey

    Biochemist Mark Driscoll is trying to crack open a stubborn microbe in his lab at UConn’s technology commercialization incubator in Farmington, Connecticut.

    He needs to get past the microorganism’s tough outer shell to grab a sample of its DNA. Once he has the sample, Driscoll can capture the bacterium’s genetic ”˜fingerprint,’ an important piece of evidence for doctors treating bacterial infections and scientists studying bacteria in the human microbiome. It’s a critical element in the new lab technology Driscoll and his business partner, Thomas Jarvie, are developing.

    But at the moment, his microbe isn’t cooperating. Driscoll tries breaking into it chemically. He boils it. He pokes and pushes against the outer wall. Nothing happens. This drug-resistant pathogen is a particularly bad character that has evolved and strengthened its shell over generations. It isn’t giving up its secrets easily.

    Stymied, Driscoll picks up the phone and calls Professor Peter Setlow at UConn Health. A noted expert in molecular biology and biophysics, Setlow has been cracking open microbes since 1968.

    A few hours later, Driscoll jumps on a shuttle and takes a quarter-mile trip up the road to meet with Setlow in person. He explains his predicament. Setlow nods and says, “Here’s what I would do.”

    And it works.

    Breakthrough

    That brief encounter, that collaboration between a talented young scientist and a prominent UConn researcher working in Connecticut’s bioscience corridor, not only results in an important breakthrough for Driscoll’s and Jarvie’s new business ”” called Shoreline Biome ”” but also leads to a proposal for more research, a new finding, and at least one patent application.

    In a broader sense, it also exemplifies the collaborative relationships that UConn and state officials hope will flourish under the University’s Technology Incubation Program or TIP, which provides laboratory space, business mentoring, scientific support, and other services to entrepreneurs in Connecticut’s growing bioscience sector. At incubators in Storrs and Farmington, TIP currently supports 35 companies that specialize in things like health care software, small molecule therapies, vaccine development, diagnostics, bio-agriculture, and water purification.

    The program has assisted more than 85 startup companies since it was established in 2003. Those companies have had a significant impact on Connecticut’s economy, raising more than $50 million in grant funding, $80 million in debt and pay equity, and more than $45 million in revenue.

    “This is not a coincidence,” says Driscoll as he recounts his microbe- cracking story in a small office across the hall from his lab. “This is what government is supposed to do. It’s supposed to set up an environment where these kinds of things can happen.”

    Bold Moves

    Driscoll and Jarvie, a physical chemist and genomics expert, arrived at UConn’s Farmington incubator in June 2015 with a bold business concept but virtually no idea of how to get it off the ground. Both had worked in the labs at 454 Life Sciences in Branford, Connecticut, one of the state’s early bioscience success stories that ended up moving to the San Francisco area.

    Driscoll and Jarvie decided to stay in Connecticut. They had talked about starting a business based on new technology that would more quickly and precisely identify different strains of bacteria in the human microbiome, the trillions of good and bad microorganisms living in our bodies that scientists believe play an important role in our health and well-being. The study of the microbiome is a rapidly growing area of biomedical research. There are currently more than 300 clinical trials of microbiome-based treatments in progress, according to the National Institutes of Health, and the global market for microbiome products is estimated to exceed $600 million a year by 2023.

    “It’s the most frightening thing I have ever done,” says Driscoll with a chuckle. “As scientists, we know that nine out of 10 new companies fail. That sound you constantly hear in the back of your head is the ”˜hiss’ of money being burned. The pressure is intense. You have to reach the next level before your money goes to zero because when the money’s gone, you’re done.”

    Fortunately, Driscoll and Jarvie’s decision to launch a bioscience company came at a time when Connecticut and UConn were committing resources to strengthen the state’s bioscience research sector.

    As part of Gov. Dannel P. Malloy’s Bioscience Connecticut initiative approved in 2011, Connecticut’s legislature allocated $864 million to efforts that would position the state as a leader in bioscience research and innovation. That initiative included the expansion of UConn’s technology incubator site in Farmington, the opening of The Jackson Laboratory for Genomic Medicine (JAX), and major upgrades at UConn Health to boost its research capacity.

    monopoly styled game cards showing pitfalls and boons of science start-ups

    Those resources were tailor made for a fledgling bioscience company like Shoreline Biome. Driscoll and Jarvie remember the early days when company ”˜meetings’ took place at a local Starbucks, their official address and warehouse was Driscoll’s garage, and they didn’t even have a lab.

    But they did have a vision of what Shoreline Biome could be. They knew that George Weinstock, one of the world’s foremost experts in microbial genomics and one of their customers at 454 Life Sciences, had just arrived at Jax. They reached out to him with an offer to collaborate. Weinstock not only agreed, he became their principal scientific advisor.

    About the same time, Driscoll and Jarvie began exploring the possibility of renting space at TIP in Farmington because of its proximity to people like Weinstock and Setlow. “If you’re looking to start a bioscience company, in some parts of the state the cost for commercial space is going to be more than your will to live,” says Driscoll. “But here, the rent is graduated. So we were able stay here in the beginning for just a few hundred bucks a month.”

    The pair also obtained $150,000 in pre-seed funding from Connecticut Innovations, the state’s quasi-public investment authority supporting innovative, growing companies; and a $500,000 equity investment from the Connecticut Bioscience Innovation Fund (CBIF).

    Along with the pre-seed investment funds, CBIF’s staff helped guide Driscoll and Jarvie through the early stages of business development and introduced them to the investment community. AndCBIF member Patrick O’Neill took a seat on Shoreline Biome’s board. O’Neill’s business savvy has been crucial to the company’s early success, says Driscoll.

    Tracking the Bad Guys

    The lab kit Driscoll and Jarvie are currently testing is a low-cost, off-the-shelf tool that replaces hours of painstaking hands-on processing of patient samples for bacteria DNA testing. It’s about getting DNA out of the bacteria from a complicated environmental sample and doing that in a fast, cheap, and comprehensive way, explains Jarvie.

    Researchers and medical professionals have previously relied on targeted testing and laboratory cultures to identify different bacteria strains. But many bacteria species are hard to grow in the lab, making identification and confirmation difficult. Even when scientists can confirm the presence of a bacteria such as salmonella in a patient sample, the findings are often limited, which can impact diagnosis and treatment.

    “The DNA fingerprint region in a bacteria is about 1,500 bases long,” says Jarvie. “Most of the sequencing technologies out there are only getting a fraction of that, like 150 bases or 10 percent. It’s like relying on a small segment of a fingerprint as opposed to getting the entire fingerprint. You can’t really identify the organisms that well.”

    Jarvie describes the difference this way. Say you are running tests for mammals on three different samples. Current sequencing technology would identify the samples as a primate, a canine, and a feline. With Shoreline Biome’s technology, the results are more definitive. They would say, ”˜you have a howler monkey, a timber wolf, and a mountain lion.’

    Shoots and ladders styled game board showing pitfalls and boons of science start-ups

    That level of specificity is important to researchers and medical professionals studying or tracking a bacteria strain or disease. Driscoll says the kit is not limited to identifying harmful bacteria like salmonella, listeria, or MRSA. It also can assist researchers investigating the microbiome’s role in maintaining the so-called ”˜good’ bacteria that keeps us healthy as well as its role in other ailments such as diabetes, multiple sclerosis, and even mental health disorders like schizophrenia.

    For example, the kit easily lets a researcher compare 50 bacteria samples from individuals with multiple sclerosis and 50 samples from individuals who don’t have the disease to see whether the presence or absence of a particular bacteria in the microbiome plays a role in impacting the body’s nervous system.

    “If you don’t make it cost effective, if you don’t make it practical, people won’t do it,” says Driscoll. “It’s like going to the moon. Sure, we can go to the moon. But it takes a lot of time and money to build a rocket and get it ready. With our kit, all that stuff for the moon shot is already pre-made. We provide the whole system right off the shelf. You don’t need to know how to extract DNA fingerprints, or use a DNA sequencer, or analyze DNA. All you have to do is buy our kit and turn the crank.”

    As part of their product testing, Shoreline Biome is working with researchers at UConn Health and JAX to learn more about a particularly toxic and potentially fatal intestinal bacterium, Clostridium difficile, otherwise known as C.diff.

    “People who track this disease, especially in hospitals where it is a problem, want to know how it gets in there,” says Driscoll. “Does it come from visitors? Does it come from doctors? You have all these spores floating around. You can answer that by looking at the bacteria’s genetics. But if you can’t get to the bacteria’s DNA, you can’t identify it.

    “Our tool cracks open the microbes so you can get at their DNA and fingerprint the bugs to see what you have,” says Driscoll. “It lets people see everything. And we’ve simplified the software so you don’t have to be a skilled microbiologist to do it. A person in the lab can sit down and with just a few clicks, all of this stuff comes up and tells you these are the bad guys, the infectious organisms that are present, and these are the good guys.”

    “You can sit around and hope that companies form or you can try to make your own luck.”

    Deer In the Headlights

    While their focus is certainly on growing Shoreline Biome, Driscoll and Jarvie also have come to appreciate Connecticut’s broader effort in building a strong bioscience research core to help drive the state’s economy. Providing scientist entrepreneurs with an affordable base of operations, working labs, access to high-end lab equipment, and a cadre of science peers ready to help, takes some of the pressure off when launching a new company.

    “This is all part of a plan the governor and the legislature have put together to have this stuff here,” Driscoll says. “You can sit around and hope that companies form or you can try to make your own luck. You set up a situation where you are likely to succeed by bringing in JAX, opening up a UConn TIP incubator across the street, and setting up funding. Is that going to start a company? Who knows? But then you have Tom and I, two scientists kicked loose from a company, and we notice there are all these things happening here. We could have left for California or gone to the Boston-Cambridge research corridor, but instead, we decided to stay in Connecticut.”

    Mostafa Analoui, UConn’s executive director of venture development, including TIP, says the fact that two top scientists like Driscoll and Jarvie decided to stay in Connecticut speaks to the state’s highly skilled talent pool and growing innovation ecosystem.

    “Instead of going to Boston or New York, they chose to stay in Connecticut, taking advantage of UConn’s TIP and other innovation programs provided by the state to grow their company, create jobs, and benefit society with their cutting-edge advances in microbiome research,” says Analoui.

    UConn provides critical support to ventures at all stages of development, but it is especially important for startups, says Jeff Seemann, vice president for research at UConn and UConn Health.

    When asked if they still have those moments of abject fear that they aren’t going to make it, Driscoll and Jarvie laugh.

    “Every day is a deer-in-the-headlights moment,” says Driscoll. “Even when things are going well, it’s still a huge risk.”

    “It never goes away,” agrees Jarvie. But during a recent visit to the Shoreline Biome lab, both men are in good spirits.

    The company met the 12-month goals set in their CBIF funding agreement in just six months. For that effort, Driscoll and Jarvie received another $250,000 check, the second of their two CBIF payments.

    In the world of business startups, however, there is little time for extended celebration. The two scientists mark the milestone with smiles and a fist bump, then turn around and get back to work.

  • Free to Be Imperfect

    Free to Be Imperfect

    Free to Be

    Free to Be

    Free to Be

    Imperfect

    Imperfect

    Imperfect

    A beloved doctor’s patients convince him to move to UConn Health ”” where he plans to cure a rare liver disease

    By Julie (Stagis) Bartucca ’10 (BUS, CLAS)
    Photos by Peter Morenus

    Alyssa Temkin, age 11, pauses in the middle of a school basketball game to test her blood sugar.

    Imagine not being able to fall asleep watching your favorite movie because you might not survive the night. Or waking up every 90 minutes to make sure your daughter’s feeding pump is keeping her sugar stable enough that she won’t slip into a coma. Or dropping everything 16 times a day to test your blood and drink a formula that’s the caloric equivalent of half a pound of pasta. Or feeling hopeless about keeping your newborn twins alive because they can’t process food and no one can help.

    Gayle Temkin, a mom of two from West Hartford, hasn’t slept more than two hours at a time for 11 years. Her daughter, Alyssa, stops what she’s doing ”” dancing, guitar lessons, acting in a play, playing on her school’s basketball team ”” every 90 minutes to test her blood sugar and drink a special formula.

    For more than a year after giving birth to her twin boys, Kathy Dahlberg waited for liver transplants that could save them.

    Not long ago, a 13-year-old ”” who we won’t name to protect his family’s privacy ”” fell asleep in front of the TV, missed his therapy, and died.

    All are victims of Glycogen Storage Disease (GSD), a rare genetic liver disorder that leaves patients slaves to the clock because the only known treatment is taking a cornstarch mixture every few hours or less, depending on the patient. It’s a world where one mistake can be fatal.

    GSD affects only 1 in 100,000 people worldwide and long was considered a childhood illness because patients did not survive into adulthood. The life-saving cornstarch treatment that was discovered in the 1970s changed that, yet little progress in treating the disease has been made since. And then Dr. David Weinstein entered the picture.

    Weinstein, who in January moved his world-renowned GSD program from the University of Florida to UConn Health and Connecticut Children’s Medical Center, has spent the past two decades researching the disease. He’s the only doctor in the world dedicated to the illness, and is so beloved that his patients nominated him for the Order of the Smile, an international humanitarian award he shares with the likes of Oprah and Nelson Mandela. And now they have more reason to applaud him: He’s closing in on a cure.

    Weinstein and his team are on the verge of testing in a human clinical trial the first GSD gene therapy, which has worked for canines and mice with the illness. For the patients and their families who live in a constant countdown to the next feeding, the new therapy would mean freedom. A normal life, where mistakes can be made. Where they no longer have to be perfect.

    For Alyssa and mom Gayle, a typical day of trying to be as normal as possible involves Gayle at school in a room near the office, staying in touch with her daughter by walkie-talkie. Alyssa tests and doses herself in class, gym, and while playing on the school’s athletic teams. But GSD patients don’t feel the effects of low blood sugar until they are moments from a seizure, so Gayle stays close around the clock. Lily, 9, likes to tag along to appointments with Weinstein. “He’s her hero ”” he saved her sister,” says Gayle.

    Fatal Mistakes

    “The problem with this disease is that people need cornstarch every four hours. People have died because their parents overslept,” says Weinstein. One missed alarm and a patient could die. A malfunctioning piece of medical equipment could mean a dangerous seizure.

    In a healthy liver, excess sugar from food is stored as glycogen and released into our bloodstreams when we need it as glucose. For those with GSD, the liver fails to convert glycogen into glucose, causing the body’s blood sugar levels to drop dangerously low, which can lead to seizure or death.

    “One of the parents was giving a talk recently and said, ”˜Do you know what it’s like to have to be perfect all the time?’” Weinstein says. “And that’s what these families live with. It’s extreme stress.”

    Weinstein and his team have made great strides. When he started studying GSD, the only long-term treatment was a liver transplant to combat complications. Now, patients are doctors, athletes, mothers ”” more than 50 babies have been born to mothers with GSD since the first in 2003. But they still live under constant pressure. The disease is relentless, unforgiving.

    When Gayle and Steve Temkin brought baby Alyssa home from the hospital at three days old, Gayle knew something was wrong with her daughter. By the time they got to a hospital that night, Alyssa was in full liver and renal failure. Her sugars were undetectable. Without intervention, she wouldn’t survive an hour, doctors said.
    It was six months, several hospitals, countless invasive tests, and second and third opinions before Alyssa was diagnosed with GSD at Mount Sinai Hospital in New York City.

    Alyssa is now 11, a smiling, soft-spoken sixth-grader who enjoys playing sports, acting in plays, and learning to play guitar and dance. She gets good grades and loves her friends. But every 90 minutes, every single day, she must check her blood sugar and drink Tolerex, a special formula that keeps her sugar up. Alyssa is the only known GSD patient who can’t tolerate cornstarch, and Tolerex doesn’t last as long, so the time between her treatments is even shorter than it is for most GSD patients.

    While the Temkins do everything they can to make Alyssa’s life normal, there are constant reminders that it is anything but.

    During the night, a pump attached to a feeding tube in her stomach feeds Alyssa dextrose (which is less filling than Tolerex, but metabolizes faster). Her parents wake up every 90 minutes to check her sugar, but her feeding is done automatically through the pump.

    Gayle spends every day at Alyssa’s school. For years, she would go into the classroom to feed Alyssa, first through her feeding tube and, more recently, with a drinkable formula. This year, Alyssa has gained some freedom. An Apple Watch reminds her when it’s time to test her blood and drink, and she reports her sugar level to her mom via a walkie-talkie. Gayle, a former social worker, stays close, just in case.

    If Alyssa’s sugar gets too low, she doesn’t feel it. Unlike most people, GSD patients don’t feel shaky or get headaches when their sugar drops ”” at least not until it’s too late. By then, they could be moments from having a seizure.

    “I sit in her school all day,” says Gayle. “I have a master’s. I’m a social worker. But I do what I have to do.”

    Because she knows too well what can happen.

    In February 2015, the family had returned from a trip to Italy and decided to “camp out” together in the same room. As Gayle and Steve dozed off, Lily Temkin, 9, stayed up, reading, unable to fall asleep.

    “I hear Lily saying, ”˜Alyssa, come on, want to play with me? Alyssa, you want to read with me? Alyssa, Alyssa.’ And then, screaming,” recalls Gayle.

    Alyssa’s pump had stopped working. She was having a seizure and remained unconscious at the hospital.

    “David [Weinstein] stayed on the phone with us the whole time,” says Gayle. “He was booking a flight to Connecticut. We really thought he was going to be coming for a funeral.

    “There is nothing about this disease that’s forgiving. It doesn’t matter what regimen you’re on; it could be a bad batch of something. We think we’re doing everything right, and the pump malfunctions.”

    There was no research going on anywhere in the world on this disease. And if there’s no research, that means there’s no hope.”

    Temkin with Dr. Weinstein

    Dr. Weinstein has treated Alyssa since she was six months old. The Temkins were instrumental in bringing him to Connecticut, where he is about to begin human clinical trials of a gene therapy they all hope will lead to a cure.

    Research = Hope

    Weinstein had no intention of dedicating his life to curing GSD. As a young physician at Boston Children’s Hospital specializing in sugar disorders in 1998, he was caring for just two patients with GSD when he was invited to a national conference of the Association for Glycogen Storage Disease.

    “I showed up at this meeting and was shocked by what I saw,” he says. The conference started with a moment of silence and a reading of the names of all the children who had died from GSD that year. The research presented was decades old. And the only treatment option being discussed was liver transplantation to combat complications from the disorder.

    “There was no research going on anywhere in the world on this disease,” Weinstein says. “And if there’s no research, that means there’s no hope.”

    A conversation with a mother there changed the course of Weinstein’s life. Knowing no one at the conference, he sat down for lunch next to Kathy Dahlberg, who had one-year-old twin sons already on the liver transplant list. She told Weinstein how sick her children were, and that her only hope was that they’d live long enough to get their liver transplants. Weinstein had a son at home a month younger than the twins.

    “Over lunch at that conference, I decided that somebody had to care about these children. The children shouldn’t have to suffer just because it was a rare disease,” Weinstein says. “The world didn’t need another diabetes doctor. This is where I could make a difference.”

    As soon as he returned to Boston, Weinstein shifted his research focus to GSD and built the program there before moving it to the University of Florida in 2005 in order to work with the veterinary program. He has successfully treated dogs with his gene therapy, turning a fatal disease into one where dogs born with GSD are thriving.

    Today, Weinstein sees 500 patients from 49 states and 45 countries. With help from Alyssa’s Angel Fund ”” started by the Temkins when Alyssa was a baby ”” and other charities, he has established centers all over the world.

    The world didn’t need another diabetes doctor. This is where I could make a difference.”

    The world didn’t need another diabetes doctor. This is where I could make a difference.”

    All the Way

    It was in her “little room” at Alyssa’s school that Gayle Temkin started toying with an idea.

    Sure, the charity her family started had enabled 100 patients to see their hero doctor. It had sent supplies to those in need and helped Weinstein establish centers to see patients and train doctors all over the world.

    But to accomplish the grand goal, to cure GSD, Temkin thought there was another thing she could do.

    She wanted Weinstein to come to Connecticut.

    Early last year when Weinstein was in the state for a speaking engagement, Gayle brought together a group in her family room that included prominent Hartford-area philanthropists Alan Lazowski, Eric and Jessica Zachs, and Pia and Mickey Toro. A 2012 fundraiser hosted by Lazowski had raised $470,000 in one night to support Weinstein’s research, and she wanted to provide an update on the work and how close the gene therapy was to being a reality. But the group also had come on board to push Gayle’s idea of having the doctor move to Connecticut.

    It became “almost like an intervention,” she says with a laugh. “We gave him a safe space to talk about what was working, what needs to be different, and what he thinks he can do with the program. We really wanted him to see what it’s like to have a community really embrace him. We made him understand this is where he needs to be.”

    The group tapped into connections at UConn and Connecticut Children’s. Within hours, Weinstein was on the phone with UConn School of Medicine Dean Dr. Bruce Liang. From there, the wheels were set in motion.

    In January, the GSD lab moved to UConn Health’s Farmington campus. At the same time, a clinical and research unit supported financially by the Temkins and other local philanthropists opened at Connecticut Children’s. Gayle Temkin, Alan Lazowski, and Barry Stein are the trustees for the Global Center for Glycogen Storage Disease, and through the new organization will continue to raise money to support Weinstein’s program. They are working to set up other forms of assistance for patients and their families, including a closet with free supplies at the clinic, and support programs for families once the clinical trials start.

    Because GSD patients are now surviving well into adulthood, the partnership between the two institutions makes great sense. “We’re much stronger working together,” says Weinstein.

    Although Weinstein is the only doctor in the world dedicated to curing GSD, he says he’s not doing it alone ”” far from it.

    “I’ve never seen a program like ours. I only do one disease. Everybody on my team does just one disease,” he says. “This is personal. Most people have a connection to the condition, and so they’ll work until everything’s done. It’s just a dedication that I’ve never experienced anyplace else.”

    The bulk of Weinstein’s Florida team came to Connecticut with him. His team includes GSD patients and parents, including several who have called him out of the blue to tell him all they want is to work with him.

    One, who moved to Connecticut from Minnesota to join the new center, is Kathy Dahlberg, the mother who changed Weinstein’s course all those years ago. Her twins are now sophomores in college.

    And, after nearly two decades of dedicated research, Weinstein’s next step is the one he’s been working toward all along. Human safety trials of his gene therapy, in conjunction with Dimension Therapeutics in Cambridge, Mass., are expected to start this year. UConn will coordinate the trials with collaborating centers all over the world. Full-treatment trials should start in 2020.

    The ultimate goal for the gene therapy, according to Weinstein, is to prevent low blood sugars, eliminate the dependence on cornstarch, and give patients normal lives where oversleeping isn’t a worst-case scenario.

    “If we can accomplish that, we’ve come all the way,” he says.

    “He knew he could do this,” says Gayle. “It’s all of the pieces falling into the puzzle in the right direction; it’s really like a miracle.

    “When we first brought Alyssa to him, he said, ”˜By her bat mitzvah, by the time she’s 12 or 13, we should be able to cure her.’ And she’s 11,” she says. “We’re almost there.”