From Science News: “Injecting a TB vaccine into the blood, not the skin, boosts its effectiveness”

From Science News

1.1.20
Tara Haelle

The BCG vaccine is notoriously bad at preventing the most common form of tuberculosis.

PET-CT scans of rhesus monkey lungs show spots of TB infection and tissue inflammation (red and orange). Monkeys that received a TB vaccine intravenously (bottom) were better protected than those who received it just under the skin (top). University of Pittsburgh School of Medicine.

Delivering a high dose of a vaccine against tuberculosis intravenously, instead of under the skin, greatly improves the drug’s ability to protect against the deadly disease, a new study finds.

Changing the typical dose and method of administration of the bacille Calmette-Guérin, or BCG, vaccine prevented TB in 90 percent of rhesus monkeys, researchers report online January 1 in Nature.

Most “astonishing” is that six of the 10 monkeys who received the IV vaccine never even developed an initial infection when exposed to TB, says Joel Ernst, an immunologist who specializes in TB at the University of California, San Francisco. Preventing infection, not just disease — called sterilizing immunity — is extremely rare with any TB vaccine, says Ernst, who was not involved in the study. Thwarting that infection means that no bacteria can reactivate to cause a latent or active TB infection.

The BCG vaccine has been around for nearly a century and is the only currently licensed TB vaccine. More than 150 countries, but not the United States, regularly use BCG to protect infants against some forms of TB. But the vaccine often fails to prevent the most common type of tuberculosis infection, in the lungs, in adolescents or adults.

Globally, TB infected 10 million people in 2018. It kills about 1.5 million a year, making it the most lethal infectious disease. Up to 13 million people in the United States have latent TB infection, which induces an immune response but hasn’t progressed to active tuberculosis. An experimental TB vaccine that could help protect people with the latent infection from developing active TB is in the works (SN: 9/25/18).

It’s been difficult to create an effective TB vaccine because the bacteria that cause the disease, Mycobacterium tuberculosis, enter cells, where they’re more protected from antibodies, which primarily attack outside cells. Fighting most intracellular infections requires immune cells called T cells to attack the infected cells, says immunologist Robert Seder of the National Institute of Allergy and Infectious Diseases Vaccine Research Center in Bethesda, Md.

Delivering the BCG vaccine just under the skin causes the body to make some T cells to fight TB. But not enough of these cells are created and get to where they need to be and stay there — the lungs, for example — limiting the vaccine’s effectiveness, says JoAnne Flynn, a microbiologist and immunologist at the University of Pittsburgh’s Center for Vaccine Research.

A malaria infection similarly requires T cells to fight the malaria parasite inside cells, Seder says. After his success with an intravenous malaria vaccine in another trial [Science], researchers wondered: If they injected BCG vaccine directly into the blood, where it could travel throughout the body, would it trigger the creation of enough T cells in the tissues where the cells need to be?

Flynn, Seder and their colleagues tested five BCG formulations in macaques: a standard under-the-skin, or intradermal, human dose; a high dose given under the skin (100 times greater concentration than the human dose); an aerosol high dose administered with a mask; an intravenous high dose; and a combination of high-dose aerosol and standard-dose intradermal. Six months later, the research exposed the five differently vaccinated groups of macaques and a sixth unvaccinated control group to TB.

All of the unvaccinated, standard-dose intradermal and aerosol-vaccinated macaques developed the bacterial infection. The eight macaques that received the intradermal high dose did not have significantly better protection than those that got the standard dose, Flynn says. All but one of those eight developed infection, though two monkeys cleared it several weeks later. In contrast, six of 10 IV-vaccinated macaques never developed a TB infection, and three had fewer than 45 individual TB bacteria in the lungs, a very low amount, and went on to clear the infection.

One possible reason that the vaccine worked better when given intravenously is the high number of T cells induced by the IV vaccine — 100 times as many in those macaques’ airways compared with the intradermal and aerosol groups. Potentially more important is the discovery that the vaccine induced production of tissue-resident memory T cells [Immunity], primed T cells in the tissue itself, not just the blood.

Punam Mangtani, an epidemiologist at the London School of Hygiene and Tropical Medicine, calls the research “a rare and exciting proof-of-concept study.”

Preventing TB in adolescents and adults is crucial, Flynn says, so the major question is whether this approach would be safe and effective in that target population. The only adverse effects seen in the macaques were a temporary, modest increase in inflammation. Ernst says one safety concern is whether intravenous BCG could induce a harmful inflammatory response in people with latent TB infection — about a quarter of the planet’s population. It’s not clear if this vaccine could help or harm those with latent infections, which the researchers plan to test in monkeys. If it could cause harm, screening before vaccination would be necessary.

For now, the next step is to test how low a dose still offers protection, Flynn says. “This study really provides us hope that a truly effective vaccine against TB is on the horizon,” she says. “I’ve been in the field for 30 years, and I feel we are making progress in really starting to understand the disease and vaccines that can prevent infection.”

See the full article here .

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From University of Washington: “Alzheimer’s study shows promise to protect brain from tau”

From University of Washington

December 18, 2019
Bobbi Nodell
bnodell@uw.edu
206.543.7129

Researchers discover impact of MSUT2 gene and binding protein, offering others a starting point for new therapeutics.

MedicalXpress

In the wake of recent disappointments over clinical trials targeting amyloid plaque build-up in Alzheimer’s disease, researchers are focusing more attention on misfolded tau protein, another culprit in brain diseases that cause dementia.

New research published in Science Translational Medicine finds that targeting abnormal tau through the suppression of a gene called MSUT2 (mammalian suppressor of tauopathy 2) shows promise.

Tau, like amyloid protein, is another substance that builds up in Alzheimer’s disease and damages brain cells. However, clinical trials targeting tau have been far less numerous in part because tau-targeted drugs have been hard to find.

In this study, researchers concluded that suppressing MSUT2 might protect people from Alzheimer’s disease as long as the RNA binding protein PolyA Binding Protein Nuclear 1 (PABPN1) is not depleted. MSUT2 and PABPNI normally work together closely to regulate the biology of tau in the brain.

“If you inhibit MSUT2 and don’t affect PABN1, that protects against the effects of tau pathology,” said senior author Brian Kraemer, a research associate professor of medicine in the Division of Gerontology and Geriatric Medicine at the University of Washington School of Medicine. He is also a scientist at the Veterans Affairs Puget Sound Health Care System.

Kraemer said his team sees their role as the person kicking the ball down field to provide other researchers and drug companies an opportunity to move the ball towards the ultimate goal: A treatment or cure for Alzheimer’s disease.

“Pharmaceutical companies have heavily invested in going after amyloid but so far these efforts haven’t moved the needle on dementia treatments,” he said. “I think the field needs to think about targeting amyloid and tau together because both amyloid and tau act together to kill neurons in Alzheimer’s disease.”

Senior author Jeanna Wheeler, a research scientist at the Seattle Institute for Biomedical and Clinical Research and the VA, said what’s novel about the study is the discovery of the role of the MSUT2 gene.

“We discovered MSUT2 originally in a completely unbiased way by looking for anything that could make worms resistant to pathological tau protein. Now we have shown that this gene can also affect tau toxicity in mice, and also that there are differences in MSUT2 in human Alzheimer’s patients,” she said. “If we can use MSUT2 in the future as a drug target, this would be a completely novel approach for treating Alzheimer’s and other related disorders.”

The significance of tau

The study also brings more attention to the role of tau pathology in Alzheimer’s disease.

The healthy human brain contains tens of billions of specialized cells or neurons that process and transmit information. By disrupting communication among these cells, Alzheimer’s disease results in loss of neuron function and cell death.

Previous studies have shown that abnormal tau burden correlates strongly with cognitive decline in Alzheimer’s disease patients, but amyloid does not. Some dementia disorders, such as frontotemporal lobar degeneration, may have only abnormal tau with no amyloid deposits.

“If you could protect the brain from tau alone, you may provide substantial benefit for people with Alzheimer’s disease,” Kraemer said. “Likewise, targeting tau in tangle-only Alzheimer’s disease-related dementia disorders, like frontotemporal lobar degeneration, will almost certainly be beneficial for patients.”

Study went from worms to mice

This study follows previous work by these researchers that showed very similar results using the worm C. elegans. Worms go from egg to adult in three days so it was easier to do experiments on the biology of aging rapidly. Although worms don’t have complex cognitive functions, their movement is affected by tau buildup. Researchers found that they could cure the worm by knocking out the worm sut-2 gene.

The more recent study applied the experiment to mice, whose evolutionary distance to humans is much smaller than the distance between worms and humans.

The researchers knocked out the MSUT2 gene in mice, thereby preventing the formation of the tau tangles that kill off brain cells. This lessened learning and memory problems as well.

While examining autopsy brain samples from Alzheimer’s patients, the researchers found that cases with more severe disease lacked both MSUT2 protein, and its partner protein, PABPN1. This finding suggests that neurons that lose the MSUT2 -PABPN1 protein partnership may simply die during a patient’s life.

Moreover, mice lacking MSUT2 but possessing a normal complement of PABPN1 were strongly protected against abnormal tau and the resulting brain degeneration. Therefore, the researchers concluded that the key to helping people with abnormal tau buildup is blocking MSUT2 while preserving PABPN1 activity.

The study was funded by the Department of Veterans Affairs and the National Institute on Aging ( grant nos. 101BX002619,101BX007080,RF1AG055474,R01NS064131,P01AG017856,P50AG05136). Research involved investigators from the University of Washington’s School of Medicine Alzheimer’s Disease Research Center, University of Pennsylvania Center for Neurodegenerative Disease, and Michigan State University.

See the full article here .

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From The New York Times: “Crisis Looms in Antibiotics as Drug Makers Go Bankrupt”

From The New York Times

Dec. 25, 2019
Andrew Jacobs

At a time when germs are growing more resistant to common antibiotics, many companies that are developing new versions of the drugs are hemorrhaging money and going out of business, gravely undermining efforts to contain the spread of deadly, drug-resistant bacteria.

Antibiotic start-ups like Achaogen and Aradigm have gone belly up in recent months, pharmaceutical behemoths like Novartis and Allergan have abandoned the sector and many of the remaining American antibiotic companies are teetering toward insolvency. One of the biggest developers of antibiotics, Melinta Therapeutics, recently warned regulators it was running out of cash.

Experts say the grim financial outlook for the few companies still committed to antibiotic research is driving away investors and threatening to strangle the development of new lifesaving drugs at a time when they are urgently needed.

“This is a crisis that should alarm everyone,” said Dr. Helen Boucher, an infectious disease specialist at Tufts Medical Center and a member of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria.

The problem is straightforward: The companies that have invested billions to develop the drugs have not found a way to make money selling them. Most antibiotics are prescribed for just days or weeks — unlike medicines for chronic conditions like diabetes or rheumatoid arthritis that have been blockbusters — and many hospitals have been unwilling to pay high prices for the new therapies. Political gridlock in Congress has thwarted legislative efforts to address the problem.

The challenges facing antibiotic makers come at time when many of the drugs designed to vanquish infections are becoming ineffective against bacteria and fungi, as overuse of the decades-old drugs has spurred them to develop defenses against the medicines.

Drug-resistant infections now kill 35,000 people in the United States each year and sicken 2.8 million, according a report from the Centers for Disease Control and Prevention released last month. Without new therapies, the United Nations says the global death toll could soar to 10 million by 2050.

The newest antibiotics have proved effective at tackling some of the most stubborn and deadly germs, including anthrax, bacterial pneumonia, E. coli and multidrug-resistant skin infections.

The experience of the biotech company Achaogen, is a case in point. It spent 15 years and a billion dollars to win Food and Drug Administration approval for Zemdri, a drug for hard-to-treat urinary tract infections. In July, the World Health Organization added Zemdri to its list of essential new medicines.

By then, however, there was no one left at Achaogen to celebrate.

This past spring, with its stock price hovering near zero and executives unable to raise the hundreds of millions of dollars needed to market the drug and do additional clinical studies, the company sold off lab equipment and fired its remaining scientists. In April, the company declared bankruptcy.

Public health experts say the crisis calls for government intervention. Among the ideas that have wide backing are increased reimbursements for new antibiotics, federal funding to stockpile drugs effective against resistant germs and financial incentives that would offer much needed aid to start-ups and lure back the pharmaceutical giants. Despite bipartisan support, legislation aimed at addressing the problem has languished in Congress.

“If this doesn’t get fixed in the next six to 12 months, the last of the Mohicans will go broke and investors won’t return to the market for another decade or two,” said Chen Yu, a health care venture capitalist who has invested in the field.

The former offices of Achaogen in South San Francisco. The company sold off the last of its lab equipment and fired its remaining scientists this past spring. Credit Brian L. Frank for The New York Times

First Big Pharma fled the field, and now start-ups are going belly up, threatening to stifle the development of new drugs.

Dr. Ryan Cirz, a microbiologist and a co-founder of Achaogen, a company whose drug, Zemdri, showed promise in treating U.T.I.s.Credit Brian L. Frank for The New York Times

The industry faces another challenge: After years of being bombarded with warnings against profligate use of antibiotics, doctors have become reluctant to prescribe the newest medications, limiting the ability of companies to recoup the investment spent to discover the compounds and win regulatory approval. And in their drive to save money, many hospital pharmacies will dispense cheaper generics even when a newer drug is far superior.

“You’d never tell a cancer patient ‘Why don’t you try a 1950s drug first and if doesn’t work, we’ll move on to one from the 1980s,” said Kevin Outterson, the executive director of CARB-X, a government-funded nonprofit that provides grants to companies working on antimicrobial resistance. “We do this with antibiotics and it’s really having an adverse effect on patients and the marketplace.”

Many of the new drugs are not cheap, at least when compared to older generics that can cost a few dollars a pill. A typical course of Xerava, a newly approved antibiotic that targets multi-drug resistant infections, can cost as much as $2,000.

“Unlike expensive new cancer drugs that extend survival by three-to-six months, antibiotics like ours truly save a patient’s life,” said Larry Edwards, chief executive of the company that makes Xerva, Tetraphase Pharmaceuticals. “It’s frustrating.”

Tetraphase, based in Watertown, Mass., has struggled to get hospitals to embrace Xerava, which took more than a decade to discover and bring to market, even though the drug can vanquish resistant germs like MRSA and CRE, a resistant bacteria that kills 13,000 people a year.

Tetraphase’s stock price has been hovering around $2, down from nearly $40 a year ago. To trim costs, Mr. Edwards recently shuttered the company’s labs, laid off some 40 scientists and scuttled plans to move forward on three other promising antibiotics.

For Melinta Therapeutics based in Morristown, N.J., the future is even grimmer. Last month, the company’s stock price dropped 45 percent after executives issued a warning about the company’s long-term prospects. Melinta makes four antibiotics, including Baxdela, which recently received F.D.A. approval to treat the kind of drug-resistant pneumonia that often kills hospitalized patients. Jennifer Sanfilippo, Melinta’s interim chief executive, said she was hoping a sale or merger would buy the company more time to raise awareness about the antibiotics’ value among hospital pharmacists and increase sales.

“These drugs are my babies, and they are so urgently needed,” she said.

Coming up with new compounds is no easy feat. Only two new classes of antibiotics have been introduced in the last 20 years — most new drugs are variations on existing ones — and the diminishing financial returns have driven most companies from the market. In the 1980s, there were 18 major pharmaceutical companies developing new antibiotics; today there are three.

“The science is hard, really hard,” said Dr. David Shlaes, a former vice president at Wyeth Pharmaceuticals and a board member of the Global Antibiotic Research and Development Partnership, a nonprofit advocacy organization. “And reducing the number of people who work on it by abandoning antibiotic R & D is not going to get us anywhere.”

A new antibiotic can cost $2.6 billion to develop, he said, and the biggest part of that cost are the failures along the way.

Some of the sector’s biggest players have coalesced around a raft of interventions and incentives that would treat antibiotics as a global good. They include extending the exclusivity for new antibiotics to give companies more time to earn back their investments and creating a program to buy and store critical antibiotics much the way the federal government stockpiles emergency medication for possible pandemics or bioterror threats like anthrax and smallpox.

The DISARM Act, a bill introduced in Congress earlier this year, would direct Medicare to reimburse hospitals for new and critically important antibiotics. The bill has bipartisan support but has yet to advance.

One of its sponsors, Senator Bob Casey, Democrat of Pennsylvania, said some of the reluctance to push it forward stemmed from the political sensitivity over soaring prescription drug prices. “There is some institutional resistance to any legislation that provides financial incentives to drug companies,” he said.

Washington has not entirely been sitting on its hands. Over the past decade, the Biomedical Advanced Research and Development Authority, or BARDA, a federal effort to counter chemical, nuclear and other public health threats, has invested a billion dollars in companies developing promising antimicrobial drugs and diagnostics that can help address antibiotic resistance.

“If we don’t have drugs to combat these multi-drug resistant organisms, then we’re not doing our job to keep Americans safe,” Rick A. Bright, the director of the agency, said.

Dr. Bright has had a firsthand experience with the problem. Two years ago, his thumb became infected after he nicked it while gardening in his backyard. The antibiotic he was prescribed had no effect, nor did six others he was given at the hospital. It turned out he had MRSA.

The infection spread, and doctors scheduled surgery to amputate the thumb. His doctor prescribed one last antibiotic but only after complaining about its cost and warning that Dr. Bright’s insurance might not cover it. Within hours, the infection began to improve and the amputation was canceled.

“If I had gotten the right drug on Day 1, I would have never had to go to the emergency room,” he said.

Achaogen and its 300 employees had held out hope for government intervention, especially given that the company had received $124 million from BARDA to develop Zemdri.

As recently as two years ago, the company had a market capitalization of more than $1 billion and Zemdri was so promising that it became the first antibiotic the F.D.A. designated as a breakthrough therapy, expediting the approval process.

Dr. Ryan Cirz, one of Achaogen’s founders and the vice president of research, recalled the days when venture capitalists took a shine to the company and investors snapped up its stock. “It wasn’t hype,” Dr. Cirz, a microbiologist, said. “This was about saving lives.”

In June, investors at the bankruptcy sale bought out the company’s lab equipment and the rights to Zemdri for a pittance: $16 million. (The buyer, generics drug maker Cipla USA, has continued to manufacture the drug.) Many of Achaogen’s scientists have since found research jobs in more lucrative fields like oncology.

Dr. Cirz lost his life savings, but he said he had bigger concerns. Without effective antibiotics, many common medical procedures could one day become life-threatening.

“This is a problem that can be solved, it’s not that complicated,” he said. “We can deal with the problem now, or we can just sit here and wait until greater numbers of people start dying. That would be a tragedy.”

See the full article here .

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From JHU HUB: “New ultra-miniaturized microendoscope produces higher-quality images at a fraction of the size”

From JHU HUB

12.6.19
Chanapa Tantibanchachai

The lensless scope is the width of a few strands of hair and able to capture images of live neuron activity.

The image above shows imaging results from the study. Images A through C show beads on a slide viewed through a bulk microscope. D through F show the beads as viewed through a conventional, lens-based microendoscope. G through I show the beads as seen by the new lensless microendoscope. These raw images are purposefully scattered, but provide important information about light that can be used in computational reconstruction to create clearer images, shown in J through L. Image credit: Courtesy of Mark Foster

Johns Hopkins engineers have created a new lens-free, ultra-miniaturized endoscope—the width of only a few human hairs—that is capable of producing high-quality images.

Their findings were published today in Science Advances.

“Usually, you have to sacrifice either size or image quality. We’ve been able to achieve both with our microendoscope,” says Mark Foster, an associate professor of electrical and computer engineering at Johns Hopkins University and the study’s corresponding author.

Microendoscopes are designed to examine neurons as they fire in the brains of animal test subjects, and accordingly must be minuscule in scale yet powerful enough to produce a clear image. Most standard microendoscopes are about half a millimeter to a few millimeters in diameter and require larger, more invasive lenses to achieve high-quality imaging. While lensless microendoscopes exist, the optical fiber that scans an area of the brain pixel by pixel frequently bends and loses imaging ability when moved.

In their new study, Foster and colleagues created a lens-free, ultra-miniaturized microendoscope that, compared to a conventional lens-based microendoscope, increases the amount researchers can see and improves image quality. To test their device, they examined beads in different patterns on a slide.

The researchers achieved this by using a coded aperture—a flat grid that randomly blocks light, creating a projection in a known pattern, akin to randomly poking a piece of aluminum foil and letting light through all of the small holes. This creates a messy image, but one that provides a bounty of information about where the light originates, and that information can be computationally reconstructed into a clearer image.

“For thousands of years, the goal has been to make an image as clear as possible,” Foster says. “Now, thanks to computational reconstruction, we can purposefully capture something that looks awful and counterintuitively end up with a clearer final image.”

Additionally, Foster’s team’s microendoscope doesn’t require movement to focus on objects at different depths; they use computational refocusing to determine where the light originated from in three dimensions. This allows their endoscope to be much smaller than traditional versions.

The researchers achieved this by using a coded aperture—a flat grid that randomly blocks light, creating a projection in a known pattern, akin to randomly poking a piece of aluminum foil and letting light through all of the small holes. This creates a messy image, but one that provides a bounty of information about where the light originates, and that information can be computationally reconstructed into a clearer image.

“For thousands of years, the goal has been to make an image as clear as possible,” Foster says. “Now, thanks to computational reconstruction, we can purposefully capture something that looks awful and counterintuitively end up with a clearer final image.”

Additionally, Foster’s team’s microendoscope doesn’t require movement to focus on objects at different depths; they use computational refocusing to determine where the light originated from in three dimensions. This allows their endoscope to be much smaller than traditional versions.

Looking forward, the research team will test their microendoscope with fluorescent labeling procedures, in which active brain neurons are tagged and illuminated, to determine the endoscope’s accuracy in imaging neural activity.

See the full article here .

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About the Hub
We’ve been doing some thinking — quite a bit, actually — about all the things that go on at Johns Hopkins. Discovering the glue that holds the universe together, for example. Or unraveling the mysteries of Alzheimer’s disease. Or studying butterflies in flight to fine-tune the construction of aerial surveillance robots. Heady stuff, and a lot of it.

In fact, Johns Hopkins does so much, in so many places, that it’s hard to wrap your brain around it all. It’s too big, too disparate, too far-flung.

We created the Hub to be the news center for all this diverse, decentralized activity, a place where you can see what’s new, what’s important, what Johns Hopkins is up to that’s worth sharing. It’s where smart people (like you) can learn about all the smart stuff going on here.

At the Hub, you might read about cutting-edge cancer research or deep-trench diving vehicles or bionic arms. About the psychology of hoarders or the delicate work of restoring ancient manuscripts or the mad motor-skills brilliance of a guy who can solve a Rubik’s Cube in under eight seconds.

There’s no telling what you’ll find here because there’s no way of knowing what Johns Hopkins will do next. But when it happens, this is where you’ll find it.

Johns Hopkins niversity opened in 1876, with the inauguration of its first president, Daniel Coit Gilman. “What are we aiming at?” Gilman asked in his installation address. “The encouragement of research … and the advancement of individual scholars, who by their excellence will advance the sciences they pursue, and the society where they dwell.”

The mission laid out by Gilman remains the university’s mission today, summed up in a simple but powerful restatement of Gilman’s own words: “Knowledge for the world.”

What Gilman created was a research university, dedicated to advancing both students’ knowledge and the state of human knowledge through research and scholarship. Gilman believed that teaching and research are interdependent, that success in one depends on success in the other. A modern university, he believed, must do both well. The realization of Gilman’s philosophy at Johns Hopkins, and at other institutions that later attracted Johns Hopkins-trained scholars, revolutionized higher education in America, leading to the research university system as it exists today.

From Lawrence Berkeley National Lab: “News Center Rare Disease Q&A: What Rare Diseases Are and Why That Matters”

From Lawrence Berkeley National Lab

December 3, 2019
Aliyah Kovner
akovner@lbl.gov
510-486-6376

Rare diseases are … rare, right? Not as rare as you might think. As much as 10% of the population is thought to have a “rare disease.” Unfortunately, due to a lack of understanding, many rare diseases remain very difficult to diagnose and treat.

Inspired by the enormous unmet needs of people with rare diseases, a group of scientists from across the globe has teamed up to develop open-access tools and resources for sharing disease characteristics and treatment information. The research is centered around an artificial intelligence-enabled catalog of disease descriptions called Mondo, which, like a Wikipedia for rare diseases, can be added to and improved by the scientific and medical community.

In a recent commentary in Nature Reviews Drug Discovery, the group explained how agreeing on precise definitions of each rare disease can lead to more accurate diagnoses and better treatments. They also shared results from a preliminary analysis that suggests that the number of different rare diseases may be higher than previously estimated.

The project team, led by Melissa Haendel of Oregon Health & Science University, and Tudor Oprea of the University of New Mexico, includes Lawrence Berkeley National Laboratory (Berkeley Lab) researchers Chris Mungall, Nomi Harris, Deepak Unni, and Marcin Joachimiak. We spoke with Chris and Nomi about the project and why they are participating in it.

How do we decide what qualifies as a rare disease?

Nomi: There’s no single definition of “rare disease” because it depends on which region or group you’re talking about. In the U.S., a rare disease is legally defined as one that affects fewer than 200,000 people; in the EU, a rare disease is one that affects fewer than 1 in 2,000 people. Some diseases are rare in some groups but common in others – for example, Tay-Sachs disease is rare in the general population, but much more common in Ashkenazi Jews, and tuberculosis is rare in the U.S. but is one of the top 10 causes of death worldwide.

All of us almost certainly know someone who has a rare disease, though they may be undiagnosed.

How are the current systems or protocols for classifying rare diseases translating into problems in patient care?

Nomi: To diagnose and treat a disease, we need to know how to define and characterize the disease. For common diseases, there are many cases to observe, so we have a pretty good idea of what that disease looks like – what the symptoms are, how to test for it, how to treat it. For rare diseases, there may be only scattered information – maybe one physician in South America has seen a case, and one researcher in China, but they aren’t sharing their information, so we don’t have a complete picture of what that disease looks like. And if we can’t precisely define a disease, then it’s hard to reliably diagnose it, and even harder to treat it optimally.

Our preliminary analysis, included in the commentary, suggests that the number of rare diseases may be higher than we thought – maybe around 10,000 different diseases, rather than the 5,000-7,000 that has previously been estimated. That means that distinct rare diseases (for example, different varieties of thyroid cancer) have probably been lumped together, when there might be different subtypes that benefit from different treatments.

What needs to be done to improve and expedite rare disease research, diagnosis, and treatment?

Chris: As Nomi mentioned, it’s hard to come up with the best treatment for a disease if you’re not even sure what exactly that disease looks like, or if it is confused with a similar disease. To address this, our team is working to catalog the whole landscape of rare diseases. We’re bringing together separate efforts in rare disease research, and developing computational tools to help experts come up with a precise definition for each rare disease. We developed a new artificial intelligence algorithm that helps disambiguate and unify the disease definitions from different databases and reference sources. We call this unified set of disease definitions “Mondo,” from the Italian word for “world,” because it brings together information from all over the world.

To accelerate this important work, we hope that funding and regulatory agencies, patient advocacy groups, and biomedical researchers will join together to support a coordinated effort to build a complete catalog of rare diseases.

How can Berkeley Lab play a role in this effort?

Chris: Berkeley Lab has been at the forefront of efforts to establish standards for representing and sharing biomedical data. My specialty is ontologies, which are like specialized vocabularies for precisely describing a class of things, such as symptoms, diseases, biochemical processes, or even entire ecological systems. One of the most widely used ontologies in biological science, the Gene Ontology, was launched by a team that included several Berkeley Lab researchers. My group has helped to build many other important biomedical ontologies, including Mondo, and we write computational tools to help others build, use, and expand ontologies.

There are many advantages to engaging in this type of work at Berkeley Lab, including the presence of leading researchers in computer science, biology, and other relevant fields, and also a commitment to open science – meaning that anyone in the world is free to not only use the resources we develop, but also to contribute to them. When we’re attacking a big problem like accurately defining all rare diseases, we can use all the help we can get!

Berkeley Lab is a great place to engage in this research, but I also want to recognize the key contributions of our talented Mondo collaborators at Oregon State University, the Jackson Laboratory, the European Bioinformatics Institute, and many others.

What motivated you both, personally, to join this project?

Chris: One of my main areas of research is characterizing and interpreting regions of the genome using ontologies. Many rare diseases are Mendelian, which means the cause of the disease can be traced back to changes within or affecting parts of the genome. Other rare diseases may be environmental, or a mixture of environmental and genetic, and I’m very interested in how the environment influences the health of complex organisms like humans. This led to the creation of Mondo as a way to annotate genomes and environments. My role was developing the algorithms that used different kinds of reasoning to bring together multiple sources of information and organize it coherently.

Nomi: My master’s thesis involved applying artificial intelligence techniques to predict the risk of inheriting genetic disorders. After that, I worked for years on bioinformatics projects that didn’t directly relate to human health. I was excited to have a chance to get back into the medical realm and contribute to a project that we hope will ultimately help to improve the prospects of those with rare diseases.

See the full article here .

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In the world of science, Lawrence Berkeley National Laboratory (Berkeley Lab) is synonymous with “excellence.” Thirteen Nobel prizes are associated with Berkeley Lab. Seventy Lab scientists are members of the National Academy of Sciences (NAS), one of the highest honors for a scientist in the United States. Thirteen of our scientists have won the National Medal of Science, our nation’s highest award for lifetime achievement in fields of scientific research. Eighteen of our engineers have been elected to the National Academy of Engineering, and three of our scientists have been elected into the Institute of Medicine. In addition, Berkeley Lab has trained thousands of university science and engineering students who are advancing technological innovations across the nation and around the world.

Berkeley Lab is a member of the national laboratory system supported by the U.S. Department of Energy through its Office of Science. It is managed by the University of California (UC) and is charged with conducting unclassified research across a wide range of scientific disciplines. Located on a 202-acre site in the hills above the UC Berkeley campus that offers spectacular views of the San Francisco Bay, Berkeley Lab employs approximately 3,232 scientists, engineers and support staff. The Lab’s total costs for FY 2014 were $785 million. A recent study estimates the Laboratory’s overall economic impact through direct, indirect and induced spending on the nine counties that make up the San Francisco Bay Area to be nearly $700 million annually. The Lab was also responsible for creating 5,600 jobs locally and 12,000 nationally. The overall economic impact on the national economy is estimated at $1.6 billion a year. Technologies developed at Berkeley Lab have generated billions of dollars in revenues, and thousands of jobs. Savings as a result of Berkeley Lab developments in lighting and windows, and other energy-efficient technologies, have also been in the billions of dollars.

Berkeley Lab was founded in 1931 by Ernest Orlando Lawrence, a UC Berkeley physicist who won the 1939 Nobel Prize in physics for his invention of the cyclotron, a circular particle accelerator that opened the door to high-energy physics. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab legacy that continues today.

A U.S. Department of Energy National Laboratory Operated by the University of California.

From Penn Today: “These overlooked global diseases take a turn under the microscope”

From Penn Today

December 4, 2019
Katherine Unger Baillie, Writer
Eric Sucar, Photographer

In rural areas of Nigeria, such as this small fishing village in the north, children are at risk of infection with hookworm as well as other parasites. De’Broski Herbert of the School of Veterinary Medicine is embarking on a study of the disease in Nigerian schoolchildren. (Image: De’Broski Herbert)

Most people don’t die from tropical diseases like hookworm, schistosomiasis, or even malaria. But these understudied diseases, often caused by parasites, rob people of health in sometimes insidious ways.

For example, schistosomiasis is a disease caused by a waterborne, snail-transmitted parasite, and it’s the research focus of the School of Veterinary Medicine’s Robert Greenberg.

Schistosomiasis, a disease caused by parasitic flatworms, has long been a research focus for Penn Vet’s Robert Greenberg. (Image: John Donges/Penn Vet)

“It’s not necessarily a death sentence, though there are fatalities” says Greenberg, a research associate professor of pathobiology. “But you get anemia, children get stunted in terms of growth and cognitive abilities. It’s a disease that keeps people in poverty.”

Such diseases, by and large, receive less financial support and, as a result, far less scientific attention than those that more often afflict residents of wealthier nations, such as diabetes and heart disease.

Penn Vet researchers, however, have committed attention to these diseases, which, taken as a whole, affect billions around the globe. Their work benefits from the niche strengths of the school, specifically in immunology and host-pathogen interactions.

“At the Vet School, a third of our funding supports infectious disease research,” says Phillip Scott, vice dean for research and academic resources and a professor of microbiology and immunology in the Department of Pathobiology. “That’s pretty amazing, given that the School is also awarded funding for regenerative medicine, for cancer, and for a variety of other areas.”

That strength is seen in the research portfolios of some of the more senior faculty, such as Christopher Hunter’s work on toxoplasmosis, James “Sparky” Lok’s studies of Strongyloides, Carolina Lopez’s investigations of lung infections, and Bruce Freedman and Ron Harty’s efforts against Ebola and other hemorrhagic viral diseases. It has attracted newer faculty members, like cryptosporidium expert Boris Striepen, to Penn Vet.

Parasitology professor James Lok’s studies of the development and basic biology of parasites, particularly the roundworm
Strongyloides, have implications for finding new drug candidates. Veterinary schools have traditionally been strongholds of parasitology research, and Penn Vet is no exception. (Image: Eric Sucar)

Raising awareness

Penn Vet’s De’Broski Herbert, for example, an associate professor of pathobiology, had held prior positions at Cincinnati Children’s Hospital and the University of California, San Francisco. He had felt called to work on hookworm, a parasite he first learned of growing up in the South from his great-grandmother, who warned him about walking around barefoot because of the risk of contracting the parasite. But at the medical centers where he worked, he shifted gears away from studying the parasite itself, instead focusing on related research in asthma and allergy.

As part of his hookworm research in Nigeria, Herbert (left), speaking with Babatunde Adewale of the Nigerian Institute for Medical Research, hopes to study the impacts of infection on the microbiome, the immune system, and more. (Image: Courtesy of De’Broski Herbert)

“Here, our veterinary students are likely to encounter parasites in their patients, so working directly on the parasite is easier to justify,” Herbert says.

This spring, Herbert traveled to Nigeria where, working with partners at the Nigerian Institute for Medical Research, he launched a study of hookworm in 300 school-aged children in five sites around the northern and central portions of the country.

“The goal is to first establish what the prevalence of the disease really is and draw attention to that,” Herbert says. “And secondly, this is a place where the World Health Organization is going in and doing mass treatments, so I’m also interested in learning something very novel about the association between the microbiome, tissue repair, immune suppression, and metabolism in these children in Nigeria.”

Pairing basic and translational science

Those insights could lead to treatments, but they will also likely shed new light on the basic science of how hookworms affect their host. This pairing of basic and applied work is characteristic of Penn Vet scientists. In Scott’s lab, for instance, which has long pursued studies of the tropical disease leishmaniasis, advances in basic science have unfurled alongside insights that stand to reshape treatment of this parasitic infection which, in its cutaneous form, can cause serious and chronic skin ulcers.

“When I was a postdoc at NIH, there’s something my boss used to say that I still use in my talks,” says Scott. “He said, ‘Leishmaniasis has done more for immunology than immunology has done for leishmaniasis.’ And you could substitute parasitology for leishmaniasis and it would be much the same quote.

The Leishmania parasite (in red), transmitted by a sandfly, can cause painful, disfiguring ulcers. Immunologist Phillip Scott and collaborators including Daniel Beiting have worked to understand the immune response to infection and better tailor treatment for those affected. (Image: Courtesy of Phillip Scott)

“What I think is exciting right now,” he adds, “is that that’s going to change.”

As part of this contribution toward advancements against parasitic disease, Scott has traveled regularly to a leishmaniasis clinic in Brazil to obtain samples for his research and, back at Penn, has paired up with dermatology and microbiome experts such as Elizabeth Grice in the Perelman School of Medicine, and Dan Beiting from Penn Vet’s Center for Host-Microbial Interactions to break new ground.

No vaccine exists for leishmaniasis and current therapies fail a substantial percentage of the time. But recent publications from Scott’s lab have revealed new information about how the disease and existing treatments work and when to predict when they don’t. At the same time, Scott and colleagues’ research into the immunology of the infection has identified ways that FDA-approved drugs could be leveraged to alleviate the most severe forms of leishmaniasis.

New diagnostics

A major hurdle to matching appropriate therapies with neglected disease comes at one of the earliest stages of medical intervention: diagnostics. Researchers at Penn Vet are employing innovative techniques to fill these unmet needs. Robert Greenberg is one who has crossed disciplinary boundaries to do so.

In a partnership between Greenberg and Haim Bau of Penn’s School of Engineering and Applied Science, the scientists are working to craft an improved diagnostic test for schistosomes, which can lead to schistosomiasis, causing anemia, tissue fibrosis and lesions, malnutrition, learning difficulties, and, depending on the parasite species, bladder cancer and heightened HIV risk.

Greenberg has studied the ion channels that govern key biological functions in schistosomes to potentially develop drug targets that paralyze and kill the organisms. And by adapting insights from other researchers about additional parasitic-specific targets, he’s helping Bau train his microfluidic, portable diagnostic system on schistosomes to one day help clinicians make point-of-care diagnoses and issue timely treatment for infected patients.

“The current diagnostics are pretty terrible,” Greenberg says. “We’re looking at some new approaches now that should give us a much earlier, more sensitive, and more specific diagnosis for individual patients that might be able to detect other coinfections simultaneously.”

At Penn Vet’s New Bolton Center, Marie-Eve Fecteau and Ray Sweeney are also taking part in the design of a 21st-century solution to diagnostics of an insidious and challenging disease, in this case, a disease that takes a particular toll on livestock: paratuberculosis, or Johne’s disease. Caused by the bacterium Mycobacterium avium paratuberculosis, the condition affects ruminants such as cows and goats and drastically decreases their weight and milk production.

Infectious diseases take a toll on livestock as well, indirectly impacting human health and livelihoods. Large animal veterinarians Marie-Eve Fecteau and Raymond Sweeney are making progress on a stall-side diagnostic system that could quickly identify calves infected with paratuberculosis, halting the spread of infection. (Image: Louisa Shepard)

“Ruminants are a very important part of survival and livelihood in developing countries,” says Fecteau, an associate professor of food animal medicine and surgery. “Families may rely on only one or two cows to provide for their nutritional needs or income, and if that cow is affected by Johne’s, that’s a serious problem.”

Paratuberculosis has been shown to be endemic in parts of India and elsewhere in Asia and is also a burden for U.S. farms, where 70% of dairy herds test positive for the infection. Separating infected animals from the herd is a key step to stem the spread, but the bacteria have proved difficult to grow in the lab, making diagnosis challenging.

Fecteau and Sweeney, the Mark Whittier & Lila Griswold Allam Professor at Penn Vet, are hoping to change that, working with Beiting and biotechnology firm Biomeme to develop a “lab in a fanny pack,” as they call it: A stall-side diagnostic test that relies on PCR to identify infected animals from stool samples within hours.

“This is the kind of technology that could be extremely valuable for use in areas where sophisticated technology is harder to come by,” says Sweeney.

Stopping disease where it starts

Elsewhere at Penn Vet, researchers are approaching globally significant diseases by focusing on the vector. In the insectary that is part of Michael Povelones’s lab, he and his team test methods to stop disease-transmission cycles within mosquitoes.

The tens of thousands of mosquitoes in Michael Povelones’s insectary enable new insights into how the disease vectors defend themselves against infection. (Image: Rebecca Elias Abboud)

In the work, which relies on disrupting the way that mosquitoes interact with or respond immunologically to the pathogens they pass on, Povelones, an assistant professor of pathobiology, has explored everything from dengue to Zika to heart worm to elephantiasis, and his discoveries have implications for targeting a much longer list of diseases. In a recent study, Povelones and colleagues developed a new model system for studying the transmission of diseases caused by kinetoplastids, a group of parasites that includes the causative agents of Chagas disease and leishmaniasis.

“We think this could be a model for a number of important neglected diseases,” Povelones says.

In the latest of his team’s work finding ways to activate mosquitoes’ immune system to prevent pathogen transmission, they’ve identified a strategy that both blocks heartworm and the parasite that causes elephantiasis.

“These two diseases have very different behavior once they’re in the mosquito, so we’re still figuring out why this seems to work for both,” says Povelones. “But we’re very encouraged that it does.”

Using these types of creative approaches is a common thread across the Vet School, and the researchers’ efforts and successes seem to be multiplying. To continue accelerating progress, the School is developing a plan to harness these strengths, working with existing entities such as the Center for Host-Microbial Interactions internally and cross-school units such as the Institute for Immunology.

“We are a key part of the biomedical community at Penn and bring a valuable veterinary component to the table in confronting diseases of poverty,” says Scott.

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

Academic life at Penn is unparalleled, with 100 countries and every U.S. state represented in one of the Ivy League’s most diverse student bodies. Consistently ranked among the top 10 universities in the country, Penn enrolls 10,000 undergraduate students and welcomes an additional 10,000 students to our world-renowned graduate and professional schools.

Penn’s award-winning educators and scholars encourage students to pursue inquiry and discovery, follow their passions, and address the world’s most challenging problems through an interdisciplinary approach.

From Rutgers University: “Better Biosensor Technology Created for Stem Cells”

Our Great Seal.

From Rutgers University

November 10, 2019

Todd Bates
848-932-0550
todd.bates@rutgers.edu

Rutgers innovation may help guide treatment of Alzheimer’s, Parkinson’s diseases.

This unique biosensing platform consists of an array of ultrathin graphene layers and gold nanostructures. The platform, combined with high-tech imaging (Raman spectroscopy), detects genetic material (RNA) and characterizes different kinds of stem cells with greater reliability, selectivity and sensitivity than today’s biosensors. Image: Letao Yang, KiBum Lee, Jin-Ho Lee and Sy-Tsong (Dean) Chueng

The technology, which features a unique graphene and gold-based platform and high-tech imaging, monitors the fate of stem cells by detecting genetic material (RNA) involved in turning such cells into brain cells (neurons), according to a study in the journal Nano Letters.

Stem cells can become many different types of cells. As a result, stem cell therapy shows promise for regenerative treatment of neurological disorders such as Alzheimer’s, Parkinson’s, stroke and spinal cord injury, with diseased cells needing replacement or repair. But characterizing stem cells and controlling their fate must be resolved before they could be used in treatments. The formation of tumors and uncontrolled transformation of stem cells remain key barriers.

“A critical challenge is ensuring high sensitivity and accuracy in detecting biomarkers – indicators such as modified genes or proteins – within the complex stem cell microenvironment,” said senior author KiBum Lee, a professor in the Department of Chemistry and Chemical Biology in the School of Arts and Sciences at Rutgers University–New Brunswick. “Our technology, which took four years to develop, has demonstrated great potential for analyzing a variety of interactions in stem cells.”

The team’s unique biosensing platform consists of an array of ultrathin graphene layers and gold nanostructures. The platform, combined with high-tech imaging (Raman spectroscopy), detects genes and characterizes different kinds of stem cells with greater reliability, selectivity and sensitivity than today’s biosensors.

The team believes the technology can benefit a range of applications. By developing simple, rapid and accurate sensing platforms, Lee’s group aims to facilitate treatment of neurological disorders through stem cell therapy.

Stem cells may become a renewable source of replacement cells and tissues to treat diseases including macular degeneration, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis, according to the National Institutes of Health.

The study’s co-lead authors are Letao Yang and Jin-Ho Lee, postdoctoral researchers in Lee’s group. Rutgers co-authors include doctoral students Christopher Rathnam and Yannan Hou. A scientist at Sogang University in South Korea contributed to the study.

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

Rutgers, The State University of New Jersey, is a leading national research university and the state’s preeminent, comprehensive public institution of higher education. Rutgers is dedicated to teaching that meets the highest standards of excellence; to conducting research that breaks new ground; and to providing services, solutions, and clinical care that help individuals and the local, national, and global communities where they live.

Founded in 1766, Rutgers teaches across the full educational spectrum: preschool to precollege; undergraduate to graduate; postdoctoral fellowships to residencies; and continuing education for professional and personal advancement.

As a ’67 graduate of University college, second in my class, I am proud to be a member of

Alpha Sigma Lamda, National Honor Society of non-tradional students.

From Harvard Gazette: “Why some people are resistant to Alzheimer’s”

Harvard University

From Harvard Gazette

November 4, 2019
MGH News and Public Affairs

Researchers find gene variants that may protect against the disease.

New study provides insights on why some people may be more resistant to Alzheimer’s disease than others. The findings may lead to strategies to delay or prevent the condition.

The study was led by investigators at Harvard-affiliated Massachusetts General Hospital (MGH), in collaboration with the University of Antioquia, Schepens Eye Research Institute of Massachusetts Eye and Ear, and Banner Alzheimer’s Institute.

According to researchers, some people who carry mutations in genes known to cause early onset Alzheimer’s disease do not show signs of the condition until a very old age — much later than expected. Studying these individuals may reveal insights on gene variants that reduce the risk of developing Alzheimer’s disease and other forms of dementia.

In their Nature Medicine study, Yakeel T. Quiroz, a clinical neuropsychologist and neuroimaging researcher at MGH, and her colleagues describe one such patient, from a large extended family with more than 6,000 living members from Colombia, who did not develop mild cognitive impairment until her 70s, nearly three decades after the typical age of onset.

Like her relatives who showed signs of dementia in their 40s, the patient carried the E280A mutation in a gene called Presenilin 1 (PSEN1), which has been shown to cause early onset Alzheimer’s disease. She also had two copies of a gene variation called ChristChurch, named after the New Zealand city where it was first found in the APOE3 gene (APOE3ch). The team was unable to identify any additional family members who had two copies of this variation who also carried the PSEN1 E280A mutation. In an analysis of 117 kindred members, 6 percent had one copy of the APOE3ch mutation, including four PSEN1 E280A mutation carriers who showed signs of mild cognitive impairment at the average age of 45 years.

Imaging tests revealed only minor neurodegeneration in the patient’s brain. Surprisingly, the patient had unusually high brain levels of amyloid beta deposits, a hallmark of Alzheimer’s disease; however, the amount of tau tangles — another hallmark of the disease — was relatively limited.

The investigators suspect that carrying two copies of the APOE3ch variant may postpone the clinical onset of Alzheimer’s disease by limiting tau pathology and neurodegeneration.

“This single case opens a new door for treatments of Alzheimer’s disease, based more on the resistance to Alzheimer’s pathology rather than on the cause of the disease. In other words, not necessarily focusing on reduction of pathology, as it has been done traditionally in the field, but instead promoting resistance even in the face of significant brain pathology,” said Quiroz.

APOE3 is one form of the APOE gene, the major susceptibility gene for late-onset Alzheimer’s. The APOE gene provides instructions for making a protein called apolipoprotein E, which is involved in the metabolism of fats in the body. Experiments revealed that the APOE3ch variant may reduce the ability of apolipoprotein E to bind to certain sugars called heparan sulphate proteoglycans (HSPG), which have been implicated in processes involving amyloid beta and tau proteins.

“This finding suggests that artificially modulating the binding of APOE to HSPG could have potential benefits for the treatment of Alzheimer’s disease, even in the context of high levels of amyloid pathology,” said co–lead author Joseph F. Arboleda-Velasquez of the Schepens Eye Research Institute.

The investigators suspect that carrying two copies of the APOE3ch variant may postpone the clinical onset of Alzheimer’s disease by limiting tau pathology and neurodegeneration.

“This single case opens a new door for treatments of Alzheimer’s disease, based more on the resistance to Alzheimer’s pathology rather than on the cause of the disease. In other words, not necessarily focusing on reduction of pathology, as it has been done traditionally in the field, but instead promoting resistance even in the face of significant brain pathology,” said Quiroz.

APOE3 is one form of the APOE gene, the major susceptibility gene for late-onset Alzheimer’s. The APOE gene provides instructions for making a protein called apolipoprotein E, which is involved in the metabolism of fats in the body. Experiments revealed that the APOE3ch variant may reduce the ability of apolipoprotein E to bind to certain sugars called heparan sulphate proteoglycans (HSPG), which have been implicated in processes involving amyloid beta and tau proteins.

“This finding suggests that artificially modulating the binding of APOE to HSPG could have potential benefits for the treatment of Alzheimer’s disease, even in the context of high levels of amyloid pathology,” said co–lead author Joseph F. Arboleda-Velasquez of the Schepens Eye Research Institute.

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

From Stanford University – Medicine: “Robots join workforce at the new Stanford Hospital”

From Stanford University – Medicine

11.4.19
Daphne Sashin

In the new Stanford hospital, the human employees will be joined by a fleet of robots programmed to take on some repetitive and mechanical tasks.

The more than 5,500 Stanford Health Care employees who work at the new Stanford Hospital will be joined by a fleet of robots programmed to deliver linens, packages and medical supplies, keep track of the hospital’s medication inventory and count out pills for nurses to administer.

The new hospital opens Nov. 17.

Tug robots will serve as autonomous couriers, hauling heavy loads of supplies between the central loading dock at 300 Pasteur Drive and the new hospital at 500 Pasteur Drive — a half-mile round-trip. Kevin Meynell Photography.

Handing off repetitive and mechanical tasks to machines — 23 delivery robots that will travel on pre-programmed routes throughout the hospital and three pharmacy robots that will store and package medication — will prevent employee injuries, reduce medication errors and free up staff to focus on the more valuable and satisfying work of assisting clinicians and caring for patients, said Gary Fritz, vice president and chief of applications for Stanford Health Care.

“The real value of pharmacists and pharmacy technicians comes when they use their clinical knowledge to care for patients, not to count pills,” Fritz said. “Similarly, in the supply chain, routine activities like pushing a cart 30 minutes in each direction isn’t really job enriching, but what is enriching is if those people can talk to patients or spend time figuring out how to get better supplies.”

Autonomous robots ‘TUG’ supplies

At 4 feet high, the TUGs will serve as autonomous couriers, hauling heavy loads of supplies between the central loading dock at 300 Pasteur Drive and the new hospital at 500 Pasteur Drive — a half-mile round-trip via tunnel. The TUGs move about 2 miles per hour and can pull more than half a ton.

“We’re automating the heavy movement across long distances to protect our employees,” said Shaheed Hickman, supply chain project manager at the hospital.

The robots use lasers and GPS to create a 3D map of their surroundings and determine if they need to stop or move to get around an obstacle. The robots convert that 3D map to a 2D image, so managers and staff can remotely track them in real-time. The TUGs have the capability to open doors wirelessly and stop when they sense movement that may interfere with their path. They can distinguish between stationary or moving obstructions within a 10-foot radius and alter their course accordingly.

Joel Rivera, a pharmacy technician, next to the PillPick robot, which can package 1,000 doses of medicine per hour. The same work would take a technician 10 hours to complete. Kevin Meynell Photography.

While you can’t have a conversation with them, they do speak a few phrases — including “crossing hallway” and “TUG has arrived” — and they stop the moment they are touched. If a fire alarm goes off, the robots pull off to the side of the hallway to get out of the way.

Initially, the TUGs will be used to carry carts full of small packages, bulk food, nonurgent medical supplies and linens to the basement level of the new hospital, where, for now, a staff member will get the items to their final destination. The TUGs also will haul dirty linens, used food trays and garbage from the new hospital and ferry it back to the dock.

In between jobs, the TUGs automatically return to recharge at their docking stations.

Robotic pharmacy

You won’t see many pills in the new hospital pharmacy. That’s because most of them are stored inside three giant robotic machines, which don’t get tired, rushed or make mistakes as they’re filling drug orders for patients.

Two of them, the BoxPickers, aren’t what you imagine when you think of a robot. They are more like giant cabinets with a computer interface on the outside. Inside, there are stacks of drawers containing boxes of medications and a mechanical arm, or picker, that moves up and down the aisles. The BoxPickers currently store nearly $5 million worth of medications — about 80 percent of what’s stored in the patient care unit’s medication dispensing cabinets, located in the medication areas on the hospital floors.

Each day, when it’s time to restock the dispensers with medications, the technician checks the BoxPicker’s computer to determine which are needed and in what quantities. On the other side of the cabinet, the arm locates the box containing that specific medication and moves it into a drawer that unlocks for the technician.

Besides the time-savings afforded by the pharmacy robots, the machines reduce the chance of pill-selection errors, said Douglas Del Paggio, PharmD, assistant director of pharmacy.

“Instead of me going over to a bin and pulling a drug and looking at it — and if I’m in a rush, I may accidentally pull the wrong one, or the wrong drug is in the wrong bin — in these robots, it is all bar-code scanned and checked, so it’s very accurate — like 99.9 percent,” Del Paggio said.

The BoxPickers also keep a running inventory and automatically generate new orders for the drug wholesaler on a daily basis.

“You have more seamless control of inventory, because you’re not just eyeballing and saying, ‘I think I need more of that,’ which is how we’ve been doing it for decades,” Del Paggio said.

Across the room, a third robot — a suction-powered machine called the PillPick — counts out bulk medications and slides them into individual, bar-coded packets.

When a physician puts a patient’s order into the electronic health record system for one of these drugs, the only human work required is for a pharmacist to verify the order. Then the robot goes to work, whirring and hissing. Within seconds, a day’s worth of medicine slides down a conveyor belt, organized on a plastic ring.

The PillPick can package 1,000 doses per hour — the same amount that it would take a pharmacy technician about 10 hours to pack by hand.

“This allows our pharmacists and technicians to instead spend more of their time with physicians, nurses, and most importantly,” Del Paggio said, “directly with patients and family members.”

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

Stanford Medicine integrates research, medical education and health care at its three institutions – Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children’s Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.

Stanford University campus. No image credit

Stanford University

Leland and Jane Stanford founded the University to “promote the public welfare by exercising an influence on behalf of humanity and civilization.” Stanford opened its doors in 1891, and more than a century later, it remains dedicated to finding solutions to the great challenges of the day and to preparing our students for leadership in today’s complex world. Stanford, is an American private research university located in Stanford, California on an 8,180-acre (3,310 ha) campus near Palo Alto. Since 1952, more than 54 Stanford faculty, staff, and alumni have won the Nobel Prize, including 19 current faculty members

From Rensselaer Polytechnic Institute: “Living Skin Can Now be 3D-Printed With Blood Vessels Included”

From Rensselaer Polytechnic Institute

Development is significant step toward skin grafts that can be integrated into patient’s skin.

Researchers at Rensselaer Polytechnic Institute have developed a way to 3D print living skin, complete with blood vessels. The advancement, published online today in Tissue Engineering Part A, is a significant step toward creating grafts that are more like the skin our bodies produce naturally.

“Right now, whatever is available as a clinical product is more like a fancy Band-Aid,” said Pankaj Karande, an associate professor of chemical and biological engineering and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS), who led this research at Rensselaer. “It provides some accelerated wound healing, but eventually it just falls off; it never really integrates with the host cells.”

A significant barrier to that integration has been the absence of a functioning vascular system in the skin grafts.

Karande has been working on this challenge for several years, previously publishing one of the first papers [Tissue Engineering Part C: Methods] showing that researchers could take two types of living human cells, make them into “bio-inks,” and print them into a skin-like structure. Since then, he and his team have been working with researchers from Yale School of Medicine to incorporate vasculature.

In this paper, the researchers show that if they add key elements — including human endothelial cells, which line the inside of blood vessels, and human pericyte cells, which wrap around the endothelial cells — with animal collagen and other structural cells typically found in a skin graft, the cells start communicating and forming a biologically relevant vascular structure within the span of a few weeks.

Watch Karande explain this development:

“As engineers working to recreate biology, we’ve always appreciated and been aware of the fact that biology is far more complex than the simple systems we make in the lab,” Karande said. “We were pleasantly surprised to find that, once we start approaching that complexity, biology takes over and starts getting closer and closer to what exists in nature.”

Once the Yale team grafted it onto a special type of mouse, the vessels from the skin printed by the Rensselaer team began to communicate and connect with the mouse’s own vessels.

“That’s extremely important, because we know there is actually a transfer of blood and nutrients to the graft which is keeping the graft alive,” Karande said.

In order to make this usable at a clinical level, researchers need to be able to edit the donor cells using something like the CRISPR technology, so that the vessels can integrate and be accepted by the patient’s body.

“We are still not at that step, but we are one step closer,” Karande said.

“This significant development highlights the vast potential of 3D bioprinting in precision medicine, where solutions can be tailored to specific situations and eventually to individuals,” said Deepak Vashishth, the director CBIS. “This is a perfect example of how engineers at Rensselaer are solving challenges related to human health.”

Karande said more work will need to be done to address the challenges associated with burn patients, which include the loss of nerve and vascular endings. But the grafts his team has created bring researchers closer to helping people with more discrete issues, like diabetic or pressure ulcers.

“For those patients, these would be perfect, because ulcers usually appear at distinct locations on the body and can be addressed with smaller pieces of skin,” Karande said. “Wound healing typically takes longer in diabetic patients, and this could also help to accelerate that process.”

At Rensselaer, Karande’s team also includes Carolina Catarino, doctoral student in chemical and biological engineering. The Yale team includes Tania Baltazar, a postdoctoral researcher who previously worked on this project at Rensselaer; Dr. Jordan Pober, a professor of immunobiology; and Mark Saltzman, a professor of biomedical engineering.

This work was supported by a grant from the National Institutes of Health.

See the full article here .

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Please help promote STEM in your local schools.

Stem Education Coalition

With 7,900 students and more than 100,000 living alumni, Rensselaer is addressing the global challenges facing the 21st century—to change lives, to advance society, and to change the world.

From renewable energy to cybersecurity, from biotechnology to materials science, from big data to nanotechnology, the world needs problem solvers—exactly the kind of talent Rensselaer produces—to address the urgent issues of today and the emerging issues of tomorrow.