StemCell Therapy

BOSTON, March 25, 2020 /PRNewswire/ -- The burgeoning coronavirus (COVID-19) global pandemic has already killed thousands of people worldwide and is threatening the lives of many more. In an effort to limit the virus from spreading, Harvard University was among the first organizations to promote social distancing by requiring all but the most essential personnel to work remotely. However, labs that perform vital COVID-19-related research are permitted to continue their potentially life-saving work and many of these activities are currently ongoing at the Wyss Institute for Biologically Inspired Engineering.

Essentially all medical treatment centers impacted by SARS-CoV2 (CoV2), the SARS-family virus that causes COVID-19, are overstrained or unable to confront the virus, starting from their ability to diagnose the virus' presence in the human body, treat all infected individuals, or prevent its spread among those that have not been infected yet. Therefore, finding better solutions to diagnose, treat, and prevent the disease, is key to combating this menace and bringing this pandemic under control. Equally concerning, there are worldwide shortages on the front lines in hospitals in our region and around the world, including rapidly depleting supplies of personal protective equipment, such as N95 face masks, and nasopharyngeal swabs needed for COVID-19 diagnostic testing. Solving these challenges requires rapid responses and creative solutions.

"With our highly multi-disciplinary and translation-focused organization, we [the Wyss Institute] were able to quickly pivot, and refocus our unique engineering capabilities on much needed diagnostic, therapeutic, and vaccine solutions, and we hope to be part of the solution for many of the innumerable problems the present pandemic poses," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who also is the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). "We strive to make a major contribution to bringing this crisis under control, and are confident that what we accomplish under duress now will help prevent future epidemics."

Meeting challenges on the front lines of patient care

Many of the Institute's hospital partner institutions and government agencies have reached out to Institute leadership to assist in this rapidly escalating battle against COVID-19. Ingber's team is working closely with collaborators at Beth Israel Deaconess Medical Center (BIDMC), other Harvard-affiliated hospitals, and generous corporate partners to develop potential solutions to the increasing shortage of nasopharyngeal swabs and N95 face masks. Senior Staff Engineers Richard Novak, Ph.D., and Adama Sesay, Ph.D., and Senior Research Scientist Pawan Jolly, Ph.D., are working diligently with our clinical partners to help devise a solution as quickly as possible.

Diagnosing COVID-19 more quickly, easily, and broadly

With COVID-19 rapidly spreading around the planet, the efficient detection of the CoV2 virus is pivotal to isolate infected individuals as early as possible, support them in whatever way possible, and thus prevent the further uncontrolled spread of the disease. Currently, the most-performed tests are detecting snippets of the virus' genetic material, its RNA, by amplifying them with a technique known as "polymerase chain reaction" (PCR) from nasopharyngeal swabs taken from individuals' noses and throats.

The tests, however, have severe limitations that stand in the way of effectively deciding whether people in the wider communities are infected or not. Although PCR-based tests can detect the virus's RNA early on in the disease, test kits are only available for a fraction of people that need to be tested, and they require trained health care workers, specialized laboratory equipment, and significant time to be performed. In addition, health care workers that are carrying out testing are especially prone to being infected by CoV2. To shorten patient-specific and community-wide response times, Wyss Institute researchers are taking different parallel approaches:

Via one route, a team led by Wyss Core Faculty member

, Ph.D., and Senior Staff Scientist

, M.D., Ph.D., in the Institute's Molecular Robotics Initiative are developing a disposable test that makes use of a "lateral flow device" (LFD) much like a home pregnancy test easy to manufacture at a large scale, and able to be handled without special equipment or expertise. The team is adapting a suite of bioinspired DNA nanotechnology techniques that Yin's lab has previously developed to enable the detection of virus RNA or protein from simple nasopharyngeal swabs with high sensitivity and accuracy. In the handheld LFD device, these tools would enable users to transform the presence of viral RNA or protein in a sample into the formation of a colored line on a simple strip of nitrocellulose paper. Yin is one of the leaders of the Wyss Institute's Molecular Robotics Initiative and also Professor of Systems Biology at Harvard Medical School (HMS).Better viral RNA detection methods are also being pursued by

, a molecular diagnostics startup spun out of the Wyss Institute and Broad Institute in 2019. The company licensed the

developed by Wyss Core Faculty member

, Ph.D., and his group, including former Wyss Business Development Lead William Blake, Ph.D., who joined Sherlock Biosciences from the Wyss Institute as the company's CTO. Collins is a co-founder of Sherlock Biosciences, and also the Termeer Professor of Medical Engineering & Sciences at the Massachusetts Institute of Technology (MIT). According to Rahul Dhanda, M.B.A., the CEO and a co-founder of Sherlock Biosciences, the company is currently working on different solutions for diagnosing COVID-19, one of which deploys the INSPECTRTM technology. INSPECTRTM consists of DNA-based sensors, which can be programmed to detect CoV2 RNA with specificity down to a single one of its nucleotide building blocks; the sensors are coupled with paper-based synthetic gene networks that produce a bioluminescent signal. The signals can be generated at room temperature, captured on instant film and read from a simple device without sophisticated equipment, and the test is currently designed to perform similarly to an off-the-shelf pregnancy test. Like the LFD approach developed in Yin's group, INSPECTRTM technology can be readily adjusted to allow specific detection of the different continuously arising CoV2 variants, and to follow their spread through the population.In a different project led by Collins and spearheaded by Research Scientists

, Ph.D., and

, and former graduate student

at the Wyss Institute, the team is developing a rapid self-activating COVID-19 diagnostic face mask as a wearable diagnostic. Worn by patients or individuals at home with symptoms of the disease, the face mask could rapidly signal the presence of the virus without any need for hands-on manipulation so that patients can be quickly triaged for proper medical care, while healthcare workers and patients that are nearby are protected. Emerging from Collins' team's

created in the Wyss Institute's Living Cellular Devices Initiative, the approach will use highly sensitive molecular sensors that, coupled to synthetic biology networks, could enable the production of an immediately visible or fluorescent color signal in the event that CoV2 is encountered. The entire cell-free molecular machinery can be freeze-dried and integrated with the synthetic material on the interior side of face masks. Exposed to small droplets that are expelled by wearers during normal breathing, sneezing, and coughing, and the humidity of exhaled air, the reactions are re-hydrated and thus activated to produce a positive or negative signal within 1 to 3 hours.A method to capture CoV2 virus particles from human samples in a single step and identify them within 1 hour is being explored by Senior Staff Scientist,

, Ph.D., working on Don Ingber's Bioinspired Therapeutics & Diagnostics platform. The researchers are leveraging the Wyss Institute's

to bind CoV2 virus particles, which they hope to rapidly identify using mass spectrometry. FcMBL is a genetically engineered variant of the "Mannose Binding Lectin" (MBL) immune protein that binds to molecules on the surface of over 100 different pathogens, including certain viruses. Ingber's team has confirmed that FcMBL binds to a non-infectious pseudotyped CoV2 virus that displays the CoV2 Spike protein on its surface.Ultrasensitive assays to detect the levels of cytokines molecules that are secreted by certain immune cells to affect other cells are being developed by

, Ph.D., leader of the Wyss Diagnostics Accelerator, to help identify effective therapeutic interventions that can prevent the deadly cytokine storm that can be triggered by overproduction of immune cells. The lab is also developing a serological test to ascertain individuals who are not showing any symptoms yet, but have been exposed to virus and have mounted an immune response. Walt is also the Hansjrg Wyss Professor of Biologically Inspired Engineering at HMS, Professor of Pathology at Boston's Brigham and Women's Hospital, and Institute Professor of the Howard Hughes Medical Institute.

Advancing antiviral therapeutics on the fast track

To date there is no antiviral drug that has been proven to reduce the intensity and duration of the infection in more seriously affected patients, or protect vulnerable patients from CoV2 infection. Doctors can merely provide supportive care to their COVID-19 patients by making sure they receive enough oxygen, managing their fever, and generally supporting their immune systems to buy them time to fight the infection themselves. Research groups in academia and industry working at breakneck pace by now have compiled a list of candidate therapeutics and vaccines to could offer some help. However, given the high failure rates of candidate drugs in clinical trials, more efforts are needed to develop effective medicines for a world population that likely will vary with regards to their susceptibility and access to new therapeutic technologies.

The ongoing COVID-19 pandemic requires rapid action, and the fastest way to combat this challenge is by repurposing existing drugs that are already FDA approved for other medical applications as COVID-19 therapeutics. While clinicians around the world are attempting to do this, the approaches have been haphazard, and there is a great need to attack this problem in a systematic way.

Ingber's team, co-led by Senior Staff Scientist

, Ph.D. and Senior Research Scientist

, Ph.D., has developed a preclinical CoV2 infection model that leverages the Wyss Institute's human

(Organ Chip) in vitro human emulation technology. The team engineered a CoV2 pseudovirus that is safe to use in the laboratory and expresses the key surface Spike protein, which mediates its entry into cells. They also demonstrated that it successfully infects human Lung Chips lined by highly differentiated human lung airway epithelial cells, which the team previously has shown to recapitulate human lung pathophysiology, including responses to Influenza virus infection, with high fidelity. Other members of the team, including Senior Staff Engineer Richard Novak and Senior Staff Scientist

, Ph.D. are respectively using network analysis algorithms and molecular dynamic simulation-enabled rational drug design approaches to identify existing FDA approved drugs and novel compounds that can be tested in the Organ Chip-based COVID-19 therapeutic repurposing pipeline. Senior Staff Scientist

, Ph.D., working in the Wyss Institute's Predictive Biodiscovery Initiative led by Jim Collins is also applying new machine learning-enabled computational tools to confront this repurposing challenge. The team is now in active collaborations with researchers who can study the native infectious CoV2 virus in approved BSL3 biosafety laboratories, and they are working hard to rapidly identify existing FDA approved drugs and drug combinations that may be used as COVID-19 therapeutics, or as prophylactic therapies for healthcare workers or patients who are particularly vulnerable to this disease. Reilly, working with Senior Staff Scientist Ken Carlson, Ph.D., is also using his molecular dynamics simulation approach to develop new broad spectrum Coronavirus therapeutics targeted against a conserved region of its surface Spike protein that would both help infected patients survive the current COVID-19 pandemic, and allow us to be prepared to prevent infections by related Corona viruses that might emerge in the future.Collins' team is also deploying computational algorithms to predict chemical structures that could inhibit different aspects of virus biology or disease pathology and be developed into therapeutics. In a collaboration with

, Ph.D., a Professor at MIT's Department of Electrical Engineering and Computer Science, his team is leveraging deep neural networks to develop therapeutic strategies that could help treat bacterial pneumonia, which can overlay pneumonia caused by the CoV2 virus and further endanger patients' lives. In a recent study, motivated by the present dearth of antibiotics, Collins' group successfully pioneered a deep learning approach to

that led the researchers to discover new molecules with antibacterial effects towards different pathogenic strains.Wyss Core Faculty member

, Ph.D., and his graduate student Kettner Griswold are taking yet another route. One way the CoV2 virus could be fought is to harness the power of the immune system. Church and Griswold are engineering antibodies that specifically bind to the virus and could enable a potent immune attack on it. Starting from an already existing "neutralizing antibody" that binds the Spike protein of the virus responsible for the 2003 SARS epidemic, they hope to make the antibody fit the closely related CoV2 virus. Such a neutralizing agent would be akin to treatments in which patients with infectious diseases receive "blood plasma" (the liquid part of blood that holds the blood cells) from individuals that have recovered from the infection, which contains neutralizing antibodies against the pathogen. However, an engineered antibody could be manufactured in large quantities and supplied to COVID-19 patients much more quickly and easily than blood plasma. Church is also Professor of Genetics at HMS and Professor of Health Sciences and Technology at Harvard and MIT.

In search of ultimate protection a vaccine

With no vaccine currently available, but several vaccine candidates being explored around the world, Wyss Institute researchers led by Wyss Core Faculty member David Mooney, Ph.D., are developing a material that could make vaccinations more effective. Previously, Mooney's team has developed implantable and injectable cancer vaccines that can induce the immune system to attack and destroy cancer cells.

A key ingredient in vaccines is a fragment of the infectious agent, called an antigen, but the immune response to many antigens is weak. The bioactive materials of the Wyss's vaccine are programmed with molecules that orchestrate the recruitment and stimulation of immune cells with presentation of the antigen. This results in robust responses that in relation to COVID-19, in theory, may enable the immune system to both kill the virus immediately in infected individuals, as well as create a memory in infected and uninfected individuals without the need of additional boosts. Given the material's highly modular structure, one can easily plug-and-play various antigens that are being identified by researchers across the world, optimizing the response to each. This approach may yield a highly versatile platform in the fight against future epidemics and many infectious diseases. Mooney leads the Wyss Institute's Immuno-Materials Focus Area and also the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

Understanding how COVID-19 develops and how to control it

COVID-19 does not strike equally strong in every individual that it infects. Independent of age, some are prone to become seriously ill, while others show an astonishing level of resilience against the disease. Figuring out the biological basis for these differences could lead to new protective strategies.

Church and Wyss Associate Faculty member

, Ph.D., are working with "

" (PGP), an international initiative that creates public genome, health, and genetic trait data to be mined by the biomedical research community for driving scientific progress in many areas. Wu is also Professor of Genetics at HMS. Church was instrumental in founding the initiative in 2005, and has been advancing its reach with key technological advances and his emphatic stewardship. The two Wyss researchers and their teams led by Sarah Wait Zaranek, Ph.D., Curie President and PGP informatics co-Director, are now launching a project to harness the PGP platform by comparing the genomes, microbiomes, viromes, and immune systems of consenting individuals with extreme COVID-19 susceptibility and individuals that exhibit resistance. Their far-flung systems biology approach could lead to unexpected insights about the disease, and reveal key levers that could be adjusted with existing drugs to control the infection, help prioritize individuals for urgent care, as well as provide guidance as to which healthcare workers would do better on the front-lines of care.Besides pursuing various COVID-19-focused activities in its laboratories, the Wyss Institute is working with the broader research, hospital, and public health communities to integrate its efforts nationally. For example, Church is fastening ties with his former Postdoctoral Fellow

, Ph.D., Professor of Genome Sciences at the University of Washington, Seattle, who leads the "

," which pivoted to COVID-19, as well as

, Ph.D., Director of the

in Seattle, and

, Ph.D., founder of life science company 4Bionics, among other companies, to develop a simple, yet different home test kit. On the national level, Walt is a member of a

started at the National Academies' newly formed "Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats." The committee is strongly focusing now on the present coronavirus pandemic to find ways to help the federal government consolidate and streamline efforts across the nation but will also work long-term to develop strategies and make recommendations for future health threats.

At the international level, the Wyss Institute functions as a Center of Excellence of the Global Virus Network (GVN), with Ingber as leader and the other Wyss Faculty as key participating members. The GVN is designed to integrate surveillance and response efforts for biothreats, epidemics, and pandemics by integrating efforts of top virus research institutions from around the world. Ingber is also currently working closely with the Defense Advanced Research Projects Agency (DARPA) and Bill & Melinda Gates Foundation, as well as in active discussions with the NIH's National Institute of Allergy and Infectious Diseases (NIAID), Biomedical Advanced Research and Development Authority (BARDA), and Public Health England, as they all try to align and coordinate efforts to meet this monumental health challenge.

"The Wyss Institute and its collaborators are taking exactly the type of comprehensive, integrated approach to addressing this pandemic that is required at local, national, and international levels," said Walt.

PRESS CONTACTS

Wyss Institute for Biologically Inspired Engineering at Harvard University Benjamin Boettner, benjamin.boettner@wyss.harvard.edu, +1 917-913-8051

The Wyss Institute for Biologically Inspired Engineering at Harvard University ( http://wyss.harvard.edu ) uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing that are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and formation of new startups. The Wyss Institute creates transformative technological breakthroughs by engaging in high risk research, and crosses disciplinary and institutional barriers, working as an alliance that includes Harvard's Schools of Medicine, Engineering, Arts & Sciences and Design, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, DanaFarber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, Charit Universittsmedizin Berlin, University of Zurich and Massachusetts Institute of Technology.

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The Harvard Wyss Institute's response to COVID-19: beating back the coronavirus - Champaign/Urbana News-Gazette

Sean Diehl likens the development of a new vaccine to the construction of a house. Before workers can turn a shovelful of dirt or hammer a nail, an architect must create a blueprint that shows how the building's thousands of components fit together and in what order.

Similarly, vaccine researchers trying to stop the spread of a deadly virus must start by mapping its messenger RNA. Decoding that genetic blueprint allows them to construct a safe and reliable vaccine that, they hope, will provide immunity for decades.

This time, researchers are racing to devise a vaccine that will stop a pandemic that's already upon us, using a never-before-tried method. It's akin to erecting a storm shelter using a new construction technique just as a Category 5 hurricane makes landfall.

Diehl is an assistant professor in the Department of Microbiology and Molecular Genetics at the University of Vermont's Larner College of Medicine. Since 2008, he's collaborated with the college's Vaccine Testing Center on projects involving infectious diseases, autoimmune disorders and vaccine development. In the past few years, Diehl's laboratory has focused on developing new protections against rotavirus, which is one of the most common and deadly causes of childhood diarrhea, and two mosquito-borne viruses dengue and Zika which infect tens of millions of people worldwide each year.

The 44-year-old Shelburne resident agreed to an interview with Seven Days months before the novel coronavirus made headlines. Since then, Diehl has joined the global effort to develop a vaccine against COVID-19.

On that front, researchers are already working at breakneck speed. They began in late December, when health authorities in Wuhan, China, first reported the outbreak of a viral pneumonia of unknown origin. On January 12, Chinese health authorities and the World Health Organization announced that they had mapped the entire sequence of the new coronavirus genome and shared it with researchers around the world.

On March 16, the National Institutes of Health announced the launch of a Phase 1 clinical trial to evaluate an experimental COVID-19 vaccine. In that study, being conducted at the Kaiser Permanente Washington Health Research Institute in Seattle, 45 healthy volunteers, ages 18 to 55, were injected with different doses of an experimental vaccine to evaluate its safety and efficacy in inducing immune responses.

Diehl is not involved in the Washington study. But, using the expertise he gained from researching dengue and Zika vaccines, he explained how a COVID-19 vaccine will be developed, how long it could last and how we can create more effective versions in the future.

"This is a brand-new approach," he said of the experimental coronavirus shot. "There is no current vaccine that's ever been developed this way."

How long before the public can be immunized? That's difficult to say. Diehl wouldn't offer a prediction beyond saying that "there are some aggressive timelines being talked about."

Ordinarily, vaccines involve years of research before human trials begin. But advanced genetic technologies and reductions in bureaucratic red tape could significantly shorten that timeline for COVID-19, with some estimates saying a vaccine could be available as early as this fall.

Several methods are used to create a vaccine, Diehl said. Under normal circumstances, the most common is to start with an attenuated, or weakened, version of a virus. Scientists inject this weaker version into laboratory animals, typically mice and nonhuman primates, hoping to trigger an immune response that doesn't make the animal sick. Only after long and rigorous study do vaccine developers request approval from the U.S. Food & Drug Administration to move on to human trials.

Consider the lengthy path that brought researchers to a vaccine for just one of four serotypes, or strains, of dengue (known as "Dengue 1, 2," etc.). Versions of the deadly virus are found in more than 100 countries around the world, posing a risk to about 40 percent of the world's population, or 3 billion people. According to the U.S. Centers for Disease Control and Prevention, as many as 400 million people are infected with dengue each year, of whom 100 million get sick and 22,000 die.

Though dengue's mortality rate is about 0.1 percent, comparable to seasonal flu, Diehl pointed out that its symptoms are much worse. "Dengue" may derive from the Spanish word for fastidious or careful, which describes the gait of a patient suffering from the disease.

The disease causes a very high fever that progresses into terrible joint, muscle and bone aches hence its nickname, "breakbone fever." Patients feel that their eyes are about to pop out of their heads.

Dengue is a particularly complicated disease to combat because of its four serotypes; an immunity to one offers no protection against the other three. If a person contracts Dengue 1 in, say, the Dominican Republic, they may recover without even knowing they were infected. However, if that person later travels to Puerto Rico and contracts Dengue 2, they have a greater chance of getting sick from the second exposure.

"For dengue," Diehl said, "it's taken, so far, 20 years and several billion dollars to get to the point of [having] the one vaccine that's on the market right now, for a very limited use."

What does this mean to researchers racing for a coronavirus vaccine? Speaking in "really broad brushstrokes," Diehl said, the way genetic material is encoded in the coronavirus is "very similar" to the coding of dengue. Both viruses have one long, continuous string of nucleic acid, or mRNA, that is "read" as a series of letters representing its chemical components: adenine (A), guanine (G), cytosine (C) and thymine (T).

In the case of dengue, that string is 10,000 letters long. In COVID-19, Diehl said, it's 25,000.

Working with a much longer string of information naturally presents more challenges. But, Diehl said, COVID-19 researchers don't need a full understanding of how all 25,000 letters of the genome function. The novel approach they're using to develop a vaccine is focused on the 3,000 to 5,000 letters that they believe may induce an early protective immune response. If they can pinpoint those letters, they will, in effect, buy themselves more time.

By now, most people who are following news of the unfolding pandemic have seen images of the COVID-19 virus, which resembles a fuzzy tennis ball riddled with darts or crowns. Those darts, which are called spike proteins, enable the virus to attach itself to a target cell, pass along its genetic material and reproduce.

A vaccine is essentially useless, Diehl said, if it triggers an immune response "post-fusion," or after the virus binds to the cell. The aim of this experimental vaccine is to induce an immune response before fusion happens.

"If we can block that," he said, "the virus has nowhere to go, and it dies."

The good news: Vaccine developers now have machines that can rapidly synthesize and mass produce the crucial 3,000- to 5,000-letter sequences that can be used to induce a pre-fusion immune response.

The bad news: That immune response won't last for long, because the mRNA used to produce it is an unstable molecule that degrades quickly in the body. "A good vaccine will last decades. This is probably single years," Diehl said.

That may be enough, though. Here's where Diehl joins the global effort: He has submitted a protocol seeking permission to collect and study blood samples from patients who have recovered from COVID-19. Once researchers better understand how all 25,000 nucleotides work together, he said, they can move on to developing vaccine "versions 2.0, 3.0 and beyond" that will induce "immune memory."

It's no surprise that Diehl uses construction metaphors to describe the microscopic workings of cells and viruses; his father, who's now retired, worked for years in construction. To his mother, a nurse, Diehl attributes his desire to work in a public health field and help others.

A native of Rome, N.Y., Diehl earned a bachelor's degree in chemistry at the State University of New York Geneseo. There, he developed an interest in immunology, and a professor suggested he pursue a doctoral degree. The first member of his family to attend a four-year college, Diehl hadn't known until then that students could get funding to pursue graduate degrees.

Earning his PhD at UVM, Diehl met his now-wife, Sandra. When he completed the degree, they moved to the Netherlands, where Sandra was born and raised.

After spending 2003 to 2008 at the University of Amsterdam, Diehl returned to Vermont and joined the faculty at UVM, where he's been ever since. Sandra works as a pediatric nurse at the UVM Medical Center. The couple has two daughters, Jill, 11, and Vera, 9.

Diehl admitted that it's frustrating to see vaccines demonized by the public when he knows how much "blood, sweat and tears" go into making them. He sees them as a "miracle product" that saves lives. "And then some people just choose not to believe in them."

What keeps him interested in immunology?

"The fact that we'll never figure it all out," he said. Unlike the study of many processes in the human body, such as the cardiopulmonary system, immunology is constantly evolving and discovering new cell types. And those discoveries almost always have real-world health applications, whether it's combating an autoimmune disorder or working to end a global pandemic. Given its complexity, COVID-19 could keep researchers busy for years to come.

"At the root of it," Diehl said, "I always know that there's so much still to be learned."

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UVM Researcher Offers Insights on Vaccines and COVID-19 - Seven Days

Hurricanes, floods, drought and fire. Extreme weather events are becoming more frequent as the climate changes and can destroy entire landscapes both visible and invisible.

Like humans, microbes need disaster response strategies that facilitate the rescue and recovery of their ecologically crucial communities.

But what do microscopic rescue efforts look like, and can humans help?

In a new study, published in a special issue of Philosophical Transactions of the Royal Society B, researchers in the lab of Michigan State University microbial ecologist Ashley Shade put microbes under extreme heat to find out.

We know microbes provide crucial functions for maintaining the health of their ecosystems they cycle nutrients, carbon and have important feedback with climate change processes, said Shade, an assistant professor in MSU College of Natural Sciences Department of Microbiology and Molecular Genetics, whose research is supported by an National Science Foundation Early CAREER Award. We want to get a good handle on how their function might change by exploring how quickly microbes recover after the change takes place, and what we might we be able to do to manage them back to stability.

Between 20% and 80% of all microbes in the environment exist in a dormant state, like microbial sleeping beauties waiting for the right moment to wake up and function. In fact, dormancy is a widespread, bet-hedging strategy against famine and other suboptimal conditions that has evolved separately along every major branch of life. Some microbes can exist in this suspended, but viable, state for thousands of years.

We know that there are ways microbes recover after a disturbance by replenishing their populations through dispersal through air and water, Shade said. What is special about this study is that we looked at the contributions of dormant microbes as well.

Using sterilized canning jars filled with soil and their microbial communities, Shade and graduate student Jackson Sorensen designed three separate treatments.

The control received no treatment, but the second and third treatments were cooked to a sweltering 60 degrees Celsius the temperature of an underground coal fire in Centralia, Pennsylvania that Shade has been studying for six years. After cooling, the second treatment was given dispersed cells from the control jars to boost recovery.

We reproduced what would happen in the environment after a disturbance where dispersal is most likely from the next neighborhood over, Shade said. We used just a tiny bit of it, not comprising a substantial volume, and the microbes grew after the disturbance subsided, showing a little dispersal can go a long way.

The third treatment was denied outside assistance. Instead, Shade and her team watched the jars to see what role dormant microbes played in returning the microbial community to a healthy, stable state.

What we found was that both reactivation and dispersal contributed to how microbes respond to the extreme event, Shade said. This is an important finding because it suggests that it is not just outside cells rescuing the population but also dormant microbes in the disturbed environment that reactivate and support recovery.

The nearly yearlong experiment was not long enough to see the communities of microbes fully recover, even with the combined tools of dormant reactivation and outside dispersal. Still, Shade found value in what she describes as dormancy dynamics.

This experiment gives us another strategy to manage microbial communities, she said. Think about taking antibiotics for an ear infection that, as a side effect, kills beneficial microbes in the gut. Dispersal might be analogous to eating yogurt to recover those beneficial microbial functions, but another strategy could be to encourage the already existing, viable gut microbes to wake up and contribute to healthy functionality.

Rousing dormant microbes and understanding why they go into dormancy is an area of active research.

Controlling dispersal in the environment is hard, Shade said. Microbes can travel through water, the air, on insects and inside insect guts and by hitchhiking on other animals as well. But controlling when microbes wake up and go to sleep could be another interesting strategy for managing them to support a healthy environment as we face a changing climate. One day, we may be able to wake up local microbes to help environments recover even faster after extreme events.

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MSU scientists put the heat on microbes - MSUToday

The BioHealth Capital Region (BHCR) and its life science ecosystem have a rich and deep history of pioneering scientific innovation, research, development, and commercialization. The regions history has been written by life science anchor companies, scientific research universities, government research organizations, rich startup culture, and serial entrepreneurs, all of whom have played critical roles in transforming the BHCR into one of the most innovative and productive biocluster in the world.

Contributions to the BHCRs legacy of life science achievement have emerged from all staffing levels, various labs, countless executive teams, numerous entrepreneurs and biohub support organizations. Contributions have arisen from an intricate tapestry of backgrounds and cultures.

Women, in particular, have had a strong hand in shaping the history of the BHCR. In celebration of Womens History Month, were taking a closer look at the achievements of female life science leaders that have laid the groundwork for the next generation of women trailblazers in the BHCR and made the region what it is today.

Dr. Fraser is one of the most influential figures in BHCR history. In 1995, she was the first to map the complete genetic code of a free-living organism while at the Institute for Genomic Research (TIGR) in Rockville, Maryland. It was there that the automation of the DNA sequencing process made the idea of large-scale sequencing efforts tangible. As President and Director of TIGR, Fraser and her team gained worldwide public notoriety for its involvement in the Human Genome Project, which was completed in 2000 with the presentation of a working draft of the fully sequenced human genome.

As a leader, Fraser provided her researchers with the infrastructure to collaborate and apply multi-disciplinary team science and empowered them to think big. She is also most importantly known for how she challenged her team to ask the right questions, which is the root of scientific progress and success.

Her work at TIGR and as part of the Human Genome Project are foundational events in the regions history, as it marked the BHCR as the epicenter of genomic research and helped spark the regions biotech boom. In fact, it was a controversial partnership with TIGR that gave Human Genome Sciences(HGSi) the first opportunity to utilize any sequences emerging from TIGR labs. The mass of genetic information and sequences, especially that associated with diseases, that HGSi acquired catapulted them into biotech history and an important anchor company within the region.

Dr. Fraser is widely viewed as a pioneer and global leader in genomic medicine; she has published approximately 320 scientific publications and edited three books; she is also one of the most widely cited microbiology experts in the world. She founded the Institute for Genome Sciences at the University of Maryland in 1997. The institute currently holds 25 percent of the funding thats been awarded by the Human Microbiome Project and has been referred to as The Big House in genetics.

Dr. Judy Britz is yet another female life science pioneer that put the BHCR on the map. While working as a research scientist at Electro-Nucleonics Inc., Dr. Britz developed one of the first licensed blood screening tests for HIV, and launching a storied career that has spanned approximately 25 years. She is also a serial entrepreneur that has successfully raised $50M in capital and served as the top executive for two highly successful Maryland-located companies.

Dr. Britz was the first woman to lead the states biotech initiative as the first announced Executive Director of the Maryland Biotech Center. The center was launched under the Maryland Department of Commerce to deploy a strategic life science economic development plan under Governor Martin OMalleys $1.3B, 2020 Vision and to be a one-stop-shop and information center to promote and support biotechnology innovation and entrepreneurship in Maryland.

Judy was the first woman to lead Marylands life sciences initiative, bringing industry experience and perspective to the states economic development activities, a focus still maintained under Governor Hogans leadership today, shared Judy Costello, Managing Director, Economic Development BioHealth Innovation, Inc., who served as Deputy Director under Dr. Britz.

Much of the work done by Dr. Britz and her team laid the foundation and seeded the commercialization efforts that have blossomed into the thriving #4 Biotech Hub that we have today.

GeneDx was founded by Dr. Bale and Dr. John Compton in 2000. The company recently celebrated its 20th anniversary. Since its founding, GeneDx has become a global leader in genomics and patient testing. Under her leadership, the Gaithersburg, Maryland company has played an important role in the history of genetic sequencing and the rise of the BHCR as a global biohealth cluster.

GeneDx was the very first company to commercially offer NGS (Next Generation Sequencing) testing in a CLIA (Clinical Laboratory Improvement Amendments) lab and has been at the leading edge of genetic sequencing and testing for two decades. The companys whole exome sequencing program and comprehensive testing capabilities are world-renowned.

Prior to launching GeneDx, Dr. Bale spent 16 years at NIH, the last nine as Head of the Genetic Studies Section in the Laboratory of Skin Biology. She has been a pioneer during her storied career, publishing over 140 papers, chapters and books in the field. Her 35-year career includes deep experience in clinical, cytogenetic, and molecular genetics research.

Prior to being named CEO and Chair of the Board of Sequella in 1999, Dr. Nacy was the Chief Science Officer and an Executive VP at EntreMed, Inc. EntreMed was one of the most influential BHCR companies in the 1990s. EntreMed, MedImmune, Human Genome Sciences and Celera Genomics all played critical roles in creating the globally recognized, top biocluster that the BHCR has become.

After earning her Ph.D. in biology/microbiology from Catholic University, Nacy did her postdoc work at the Walter Reed Army Institute of Research in the Department of Rickettsial Diseases; her postdoc performance earned a full-time position at Walter Reed that started a 17-year career at the institute. After a highly successful run, Nacy left Walter Reed to join EntreMed.

Today, Dr. Nacy leads Rockville, Marylands Sequella, a clinical-stage pharmaceutical company focused on developing better antibiotics to fight drug-resistant bacterial, fungal and parasitic infections. Sequellas pipeline of small molecule infectious disease treatments have the potential to improve the treatment and outcomes for the over 3 billion people worldwide that are impacted by increasingly drug-resistant infectious diseases.

Emmes Corporation is the largest woman-led organization in the BHCR and is headed by Dr. Lindblad, who started her career at Emmes in 1982 as a biostatistician. She has been with Emmes for nearly 40 years, ascending to become VP in 1992, Executive VP in 2006 and ultimately the companys CEO in late summer of 2013.

Dr. Lindblad has published more than 100 publications and presentations has served as a reviewer of grant and contract applications for the National Institutes of Health (NIH) and has chaired or served on Safety and Data Monitoring Committees across multiple disease areas. Emmes is a life science anchor company for the BHCR, employing more than 600 staff globally with its headquarters in Rockville, Maryland.

Under Kings leadership, GlycoMimetics (GMI), an oncology-focused biotech, went public, secured an exclusive global licensing agreement with Pfizer and was instrumental in raising significant amounts of capital for the company. She was also the first woman Chair of Biotechnology Innovation Associations (BIO, 2013-14), where she still plays an active role on BIOs Executive Committee.

A graduate of Dartmouth College and Harvard Business School, King has had a celebrated career in both biopharma and finance. Prior to becoming CEO of GMI, King served as an Executive in Residence for New Enterprise Associates (NEA), one of the leading venture capital firms in the U.S. She has also held the position of Senior Vice President of Novartis-Corporation. King joined Novartis after a remarkable ten year run with Genetic Therapy, Inc. where she was named CEO after helping Genetic Therapy navigate the organization through various growth stages, including the companys sale to Novartis. King was named the Maryland Tech Councils Executive of the Year in 2013, the Top 10 Women in Biotech by FierceBio and has served on multiple boards across her career.

Dr. Connolly has had a pioneering career in the life sciences. She was the very first woman to graduate from Johns Hopkins Universitys Biomedical Engineering Doctoral Program in 1980. She was also a member of the first female undergraduate class entering Stevens Institute of Technology in 1971.

For decades, Dr. Connolly tirelessly worked to build up what is now known as the BHCR. In 1997, shortly before the region gained wider recognition as a biotech hub, she was the first person to be designated the state of Marylands biotechnology representative. Dr. Connollys career has spanned academia, government, and industry, including co-founding a startup and working as the Business Development Director for EntreMed, Inc., an original BHCR anchor company. She is the former Director of Maryland Industrial Partnerships Program (MIPS) and was inducted into the College of Fellows by the American Institute for Medical and Biological Engineering (AIMBE) in 2013.

Dr. Kirschstein played an enormous role in shaping the BHCR as NIH Deputy Director from 1993 to 1999 during the regions early formative years. She also served as Acting Director of NIH in 1993 and from 2000 to 2002. A pathologist by training, she received her medical degree from Tulane University in 1951 and went on to a long, successful career at the Division of Biologics Standards that lasted from 1957 to 1972.

While at the Division of Biologics Standards, Dr. Kirschstein played an important role in testing the safety of viral vaccines and helped select the Sabin polio vaccine for public use. She eventually ascended to Deputy Director of the group in 1972 and was later appointed the Deputy Associate Commissioner for Science at the FDA. In 1974 she became the Director of the National Institute of Medical Sciences at NIH and served in that role for 19 years.

Her awards and accolades are too numerous to list, but one notable honor came in 2000 when she received the Albert B. Sabin Heroes of Science Award from the Americans for Medical Progress Education Foundation.

Lastly, we want to recognize four additional women for their contributions to launching an organization that has impacted thousands of women by promoting careers, leadership, and entrepreneurship for women in the life sciences Women In Bio.

Women In Bio (WIB), one of the most important and influential support organizations for women in the life sciences, was founded in 2002 to help women entrepreneurs and executives in the Baltimore-Washington-Northern Virginia area build successful bioscience-related businesses. WIB started as a BHCR organization but has expanded its footprint to 13 chapters across the U.S. with 225 volunteer leaders and 2,600 members. The non-profit group has created a forum for female life science entrepreneurs and executives based on its core philosophy of women helping women.

WIB founders are Anne Mathias, a local venture capitalist and current Senior Strategist with Vanguard;

Elizabeth Gray, co-founder of Gabriel Pharma and current Partner at Willkie Farr & Gallagher LLP;

Robbie Melton, former Director of Entrepreneurial Innovation at TEDCO and current Director of Kauai County, Hawaiis Office of Economic Development;

and Cynthia W. Hu, COO, and General Counsel at CASI Pharmaceuticals.

In conclusion, we can not fairly capture the true history of life science and the BioHealth Capital Region without giving special recognition to Henrietta Lacks. In 1951 a Johns Hopkins researcher created the first immortal human cell line from cervical cancer cells taken from Lacks. That cell line, known as HeLa, is the oldest and most commonly used human cell line which was essential in developing the polio vaccine and has been used in scientific landmarks such as cloning, gene mapping and in vitro fertilization.

Though she was a black tobacco farmer from southern Virginia, her impact on science and medicine is unquestionable. She never knew that the Doctor took a piece of her tumor that would be used by scientists who had been trying to grow tissues in culture for decades without success. For some reason, that is still unknown, but her cells never died and the first immortal human cell line was born.

Thank you to all of the women who have been so influential in shaping the field of science, the industry of biotechnology and the BioHealth Capital Region.

Steve has over 20 years experience in copywriting, developing brand messaging and creating marketing strategies across a wide range of industries, including the biopharmaceutical, senior living, commercial real estate, IT and renewable energy sectors, among others. He is currently the Principal/Owner of StoryCore, a Frederick, Maryland-based content creation and execution consultancy focused on telling the unique stories of Maryland organizations.

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Twelve Women Who Have Shaped The History of the BioHealth Capital Region - BioBuzz

NEW YORK, March 25, 2020 /PRNewswire/ -- Kallyope Inc., a leading biotechnology company focused on identifying and pursuing therapeutic opportunities involving the gut-brain axis, today announced a $112 million Series C financing. This financing will be used to advance its portfolio of programs and the company's first clinical trials, further establishing its leadership in the gut-brain axis field.

All investors from the Series B financing participated in the Series C round, including The Column Group, Lux Capital, Polaris Partners, Euclidean Capital, Two Sigma Ventures, Illumina Ventures, Alexandria Venture Investments, and Bill Gates. New investors include Casdin Capital, Greenspring Associates, and two unnamed leading institutional investors.

"Four years ago, we started our journey to build a preeminent biotech based in New York City as a first-mover in the gut-brain axis space. Now, this Series C financing will enable us to advance multiple programs to clinical development," said Kallyope CEO Nancy Thornberry.

The Series C financing comes after four highly productive years in which Kallyope has built a portfolio of programs directed to novel targets in a wide array of diseases. In support of these programs, the company has established industry-leading capabilities in designing oral small-molecule drugs that selectively target the gut but not the rest of the body.

The company today also announced its lead program targeting satiety circuits for weight loss, with clinical testing expected to begin later this year. A second program targeting gut barrier function with potential relevance for inflammatory bowel disease (IBD) and several other diseases is anticipated to enter the clinic soon after. In addition, the company continues to advance a broad portfolio of programs for gastrointestinal, CNS, and inflammatory disorders.

"Kallyope pursues programs where the company's platform provides an edge over other approaches and where we have an opportunity to deliver major clinical benefits rather than incremental improvements over current treatments. We are targeting neural and hormonal circuits, including novel vagal circuits, involved in a broad array of physiology and disease," said Thornberry.

"Kallyope has made significant progress since the company's inception in late 2015. Its platform is enabling a mechanistic understanding of the gut-brain axis, which in turn has revealed new, actionable biology that the company is now exploring in several promising programs. I believe that Kallyope's platform and rigorous approach to identifying, characterizing, and targeting gut-brain circuits with gut-restricted small molecules has greatly increased its odds of success in clinical studies," said Kallyope co-founder and board member Tom Maniatis, Ph.D.

About Kallyope Inc.

Kallyope, headquartered at the Alexandria Centerfor Life Science in New York City, is a biotechnology company dedicated to unlocking the therapeutic potential of the gut-brain axis. The company's cross-disciplinary team integrates advanced technologies in sequencing, bioinformatics, neural imaging, cellular and molecular biology, and human genetics to provide an understanding of gut-brain biology that leads to transformational therapeutics to improve human health. The company's founders are Charles Zuker, Ph.D., Lasker Award winner Tom Maniatis, Ph.D., and Nobel laureate Richard Axel, M.D. For more information visitwww.kallyope.com.

Contact

Morgan Warners (202) 337-0808mwarners@gpg.com

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Kallyope Inc. Announces $112M Series C Financing to Support First Clinical Trials and Advance Portfolio of Programs Targeting the Gut-Brain Axis - P&T...

When Mariana Wolfner, a Cornell geneticist and molecular biologist,learned March 15she needed to suspend all noncritical research as part of the universitys effort to stem thecoronavirus outbreak, she had two main concerns.

The first was how best to help her students.

Everyone is just stunned ..., obviously because of the coronavirus, but also because of their research suddenly stopping or slowing down, said Wolfner,the Goldwin Smith Professor of Molecular Biology and Genetics in the College of Arts and Sciences (A&S). She has emphasized staying in contact with her lab virtually, to create a sense of community and support.

Ciro Cordeiro, a postdoc in Scott Emrs lab in Weill Hall, organizes frozen cell samples.

The other thing thats been hard has been trying to figure out what to shut down without forgetting something critical to maintain, said Wolfner, a Stephen H. Weiss Presidential Fellow.

She and other researchers on campus have found that people are making extra efforts to help each other.

Everyone is working together, pitching in to find solutions to problems as they arise, saidScott Emr,the Frank Rhodes Professor of Molecular Biology and Genetics in A&S and director of the Weill Institute for Cell and Molecular Biology. The atmosphere in the lab is very collegial and supportive.

With universities across the country also suspending research, scientists have offered transition strategies on social media. Students in Wolfners lab also consulted friends at other institutions.

Using that, weve come up with a plan, Wolfner said. Her students canvassed lab members to determine what experiments were absolutely critical. A postdoctoral researcher made a shift schedule for the lab.

Laura Harrington, a professor of entomology whose research seeks to understand mosquito biology and use that knowledge to prevent them from spreading disease, has noticed small but meaningful acts of kindness. Students have made their own hand sanitizer and made it available. Entomology graduate students circulated a list of people willing to provide a room in their homes for students who had no place to go.

I was really touched by people reaching out, she said.

Another major consideration for researchers has been what to do with stocks of animals or cultures that are invaluable for their research.

Avery August, professor of immunology and vice provost for academic affairs, said maintaining animal models used in his lab will be essential for when lab members return to work.

We work a lot with animals, he said, adding that animals used in research can take months and even years to develop. Along with maintenance, research animals must continue to be bred. A lab member will come in regularly to make sure the animals are cared for, so that we dont lose six to nine months if we just stopped everything, August said.

Harrington and her lab colleagues are in a race to complete an essential research project theyve been working on for the last two years, on the acoustic behavior of disease-carrying Anopheles mosquitoes, a key for understanding how males hone in on females for mating. Weve got a whole bunch of really valuable mosquito strains that we need to maintain, she said.

Wolfners lab does pioneering work with fruit flies, which must be maintained and bred. One students entire doctoral thesis is based on a strain of flies the student created. To keep all the flies alive, a team is working at the lab in shifts, so theres only one person in the lab at a time.

Perhaps the biggest task for faculty has been supporting and guiding students during this transition.

A lot of people are upset, said Colin Parrish, the John M. Olin Professor of Virology at the Baker Institute for Animal Health. The students are trying to figure out what theyre going to do to finish their research projects, finish their theses.

Postdocs in Scott Emr's lab in Weill Hall work to freeze down cell samples to preserve the labs research.

Parrish has been helping his students come up with solutions ways they can be productive remotely, read papers and write. One of his students who was scheduled to travel for a job interview will now be interviewing online.

Its been especially hard for senior undergraduate students, because they are graduating, Harrington said.

One of her seniors was upset she was not able to finish her honors project research. I just told her, Youve done the best you can with the lab work, but it really is the experience that is the educational component rather than the end product, Harrington said.

Emrs group held a pre-graduation ceremony and celebration March 17, complete with a decorated sheet cake with an inscription, for two graduating seniors who feared they wouldnt have a graduation ceremony.

A one-hour pause in our day that made us all feel good, Emr said, especially the two seniors in my lab who are likely saying a final goodbye to Cornell when they leave Ithaca in the next three days.

As people leave campus, most lab groups have plans to stay in touch via regular Zoom meetings. Wolfners group has already held a Zoom lab meeting where they discussed a journal article just to do something normal, and it made us relax, she said. They plan to meet virtually three times a week.

Harringtons lab had its first virtual meeting on March 16. We tried to laugh about things, you know, talk to each other and share ideas, support each other, she said.

As a community, everyones done a great job, Parrish said. People are doing what they can to make it a smooth transition, and hopefully, in a month or two, when things settle down, well be able to start moving things in the other direction.

Research and lab work are being scaled down across Cornell Universitys campus to stem the spread of COVID-19. In Scott Emrs molecular biology and genetics lab, postdoctoral associates are putting most research on ice.

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Research interrupted: Lab groups find their way together - Cornell Chronicle

Essentially all medical treatment centers impacted by SARS-CoV2 (CoV2), the SARS-family virus that causes COVID-19, are overstrained or unable to confront the virus, starting from their ability to diagnose the virus' presence in the human body, treat all infected individuals, or prevent its spread among those that have not been infected yet. Therefore, finding better solutions to diagnose, treat, and prevent the disease, is key to combating this menace and bringing this pandemic under control. Equally concerning, there are worldwide shortages on the front lines in hospitals in our region and around the world, including rapidly depleting supplies of personal protective equipment, such as N95 face masks, and nasopharyngeal swabs needed for COVID-19 diagnostic testing. Solving these challenges requires rapid responses and creative solutions.

"With our highly multi-disciplinary and translation-focused organization, we [the Wyss Institute] were able to quickly pivot, and refocus our unique engineering capabilities on much needed diagnostic, therapeutic, and vaccine solutions, and we hope to be part of the solution for many of the innumerable problems the present pandemic poses," said Wyss Institute Founding Director Donald Ingber,M.D., Ph.D., who also is theJudah Folkman Professor of Vascular Biologyat Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). "We strive to make a major contribution to bringing this crisis under control, and are confident that what we accomplish under duress now will help prevent future epidemics."

Meeting challenges on the front lines of patient care

Many of the Institute's hospital partner institutions and government agencies have reached out to Institute leadership to assist in this rapidly escalating battle against COVID-19. Ingber's team is working closely with collaborators at Beth Israel Deaconess Medical Center(BIDMC), other Harvard-affiliated hospitals, and generous corporate partners to develop potential solutions to the increasing shortage of nasopharyngeal swabs and N95 face masks. Senior Staff Engineers Richard Novak, Ph.D., and Adama Sesay, Ph.D., and Senior Research Scientist Pawan Jolly, Ph.D., are working diligently with our clinical partners to help devise a solution as quickly as possible.

Diagnosing COVID-19 more quickly, easily, and broadly

With COVID-19 rapidly spreading around the planet, the efficient detection of the CoV2 virus is pivotal to isolate infected individuals as early as possible, support them in whatever way possible, and thus prevent the further uncontrolled spread of the disease. Currently, the most-performed tests are detecting snippets of the virus' genetic material, its RNA, by amplifying them with a technique known as "polymerase chain reaction" (PCR) from nasopharyngeal swabs taken from individuals' noses and throats.

The tests, however, have severe limitations that stand in the way of effectively deciding whether people in the wider communities are infected or not. Although PCR-based tests can detect the virus's RNA early on in the disease, test kits are only available for a fraction of people that need to be tested, and they require trained health care workers, specialized laboratory equipment, and significant time to be performed. In addition, health care workers that are carrying out testing are especially prone to being infected by CoV2. To shorten patient-specific and community-wide response times, Wyss Institute researchers are taking different parallel approaches:

Advancing antiviral therapeutics on the fast track

To date there is no antiviral drug that has been proven to reduce the intensity and duration of the infection in more seriously affected patients, or protect vulnerable patients from CoV2 infection. Doctors can merely provide supportive care to their COVID-19 patients by making sure they receive enough oxygen, managing their fever, and generally supporting their immune systems to buy them time to fight the infection themselves. Research groups in academia and industry working at breakneck pace by now have compiled a list of candidate therapeutics and vaccines to could offer some help. However, given the high failure rates of candidate drugs in clinical trials, more efforts are needed to develop effective medicines for a world population that likely will vary with regards to their susceptibility and access to new therapeutic technologies.

The ongoing COVID-19 pandemic requires rapid action, and the fastest way to combat this challenge is by repurposing existing drugs that are already FDA approved for other medical applications as COVID-19 therapeutics. While clinicians around the world are attempting to do this, the approaches have been haphazard, and there is a great need to attack this problem in a systematic way.

In search of ultimate protection a vaccine

With no vaccine currently available, but several vaccine candidates being explored around the world, Wyss Institute researchers led by Wyss Core Faculty member David Mooney,Ph.D., are developing a material that could make vaccinations more effective. Previously, Mooney's team has developed implantable and injectable cancer vaccinesthat can induce the immune system to attack and destroy cancer cells.

Understanding how COVID-19 develops and how to control it

COVID-19 does not strike equally strong in every individual that it infects. Independent of age, some are prone to become seriously ill, while others show an astonishing level of resilience against the disease. Figuring out the biological basis for these differences could lead to new protective strategies.

On the national level, Walt is a member of a COVID-19 discussion started at the National Academies' newly formed "Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats." The committee is strongly focusing now on the present coronavirus pandemic to find ways to help the federal government consolidate and streamline efforts across the nation but will also work long-term to develop strategies and make recommendations for future health threats.

At the international level, the Wyss Institute functions as a Center of Excellence of the Global Virus Network(GVN), with Ingber as leader and the other Wyss Faculty as key participating members. The GVN is designed to integrate surveillance and response efforts for biothreats, epidemics, and pandemics by integrating efforts of top virus research institutions from around the world.Ingber is also currently working closely with the Defense Advanced Research Projects Agency(DARPA) and Bill & Melinda Gates Foundation, as well as in active discussions with the NIH's National Institute of Allergy and Infectious Diseases(NIAID), Biomedical Advanced Research and Development Authority(BARDA), and Public Health England, as they all try to align and coordinate efforts to meet this monumental health challenge.

"The Wyss Institute and its collaborators are taking exactly the type of comprehensive, integrated approach to addressing this pandemic that is required at local, national, and international levels," said Walt.

PRESS CONTACTS

Wyss Institute for Biologically Inspired Engineering at Harvard UniversityBenjamin Boettner,[emailprotected], +1917-913-8051

The Wyss Institute for Biologically Inspired Engineering at Harvard University(http://wyss.harvard.edu) uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing that are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and formation of new startups. The Wyss Institute creates transformative technological breakthroughs by engaging in high risk research, and crosses disciplinary and institutional barriers, working as an alliance that includes Harvard's Schools of Medicine, Engineering, Arts & Sciences and Design, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, DanaFarber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, Charit Universittsmedizin Berlin, University of Zurich and Massachusetts Institute of Technology.

SOURCE Wyss Institute for Biologically Inspired Engineering at Harvard University

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The Harvard Wyss Institute's response to COVID-19: beating back the coronavirus - PRNewswire

The breeding program aims to develop heat tolerant germplasm, protocols for high-throughput screening and molecular tools to assist commercial what breeders.

MOST Australian wheat varieties already have a degree of heat tolerance, however new materials developed from extensive diversity suggest the levels could be significantly improved.

Initial results from a pre-breeding program, which is being led by The Plant Breeding Institute and the University of Sydney, were presented at the Grains Research Update, Perth, recently.

The research aimed to develop heat tolerant germplasm, protocols for high-throughput screening and molecular tools to assist commercial what breeders.

Professor of Plant Breeding Richard Trethowan said they had brought in genetics from Sudan, India and all over the world.

"We have been able to access all this diversity, understand it, cross it into some backgrounds that are meaningful for Australian conditions and hand that over to the commercial companies, along with the genetic information they need to put that into new varieties," Dr Trethowan said.

"We are using a genomic selection approach, so we're using the latest and most cutting edge plant breeding technologies in our pre-breeding work.

"Using these technologies is good because it means there is a seamless handover to the breeders who are also implementing these genomic selection technologies in their work."

While most of the research had been conducted at Narrabri in New South Wales, Dr Trethowan said the genetics they're putting together were working in other parts of Australia.

"The genes that are working around the world, that we have been able to test here at Narrabri, when you put them together you get a better response," he said.

"When we've checked that in the west at Merredin or up near Geraldton, we get to see the same responses, that's been good."

Dr Trethowan said the research was longer-term and a little more upstream, but that it is also fundamental for future cross breeds.

"We have an optimal flowering window for wheat in this country, and that window is getting narrower every year because of temperature, we need to use genetics to increase that window," he said.

"We've shown some of this material will flower and will set seed under higher temperatures giving growers a lot more flexibility."

Link:
Wheat breeding aims to improve heat tolerance - Farm Weekly

This post was updated March 16 at 11:08 p.m.

Classes will be moved online for all of spring quarter, one of several changes made to campus operations as the threat of coronavirus looms.

All UCLA libraries are now closed to the public. Students, staff and faculty with BruinCards will be allowed access, UCLA officials announced in an email Monday.

Powell Library, Charles E. Young Research Library and the Louise M. Darling Biomedical Library will be opened temporarily for the next three days, from 7 a.m. to midnight on Tuesday and Wednesday, and 7 a.m. to 5 p.m. on Thursday. They will close entirely after Thursday.

Residential restaurants have also shifted entirely to to-go operations. Food at each buffet station will be served in to-go boxes, and dining hall staff will encourage students in line to keep at least 6 feet apart, the email stated.

Associated Students UCLA food options on campus also have either closed or moved to takeout operations only.

Tables will be removed from on-campus dining locations to spread diners out, and signs will be posted reminding students and visitors to stay 6 feet apart, the email stated. Restaurants closing include Veggie Grill, Wolfgang Puck Express, Northern Lights, the Music Cafe and Cafe Synapse.

All nonessential meetings and events are now suspended through spring quarter as well, and student workers are encouraged to work remotely wherever possible.

The email also asked faculty to consider the impact of coronavirus on students when making final grade decisions.

UCLA made the announcement it would move classes online in a Friday email.

All students were encouraged to return to their homes with their personal belongings for the rest of the academic year, said Executive Vice Chancellor and Provost Emily Carter, Administrative Vice Chancellor Michael Beck and Student Affairs Vice Chancellor Monroe Gorden Jr. in the email.

Students are still allowed to remain in on-campus housing for the duration of spring quarter and can keep their belongings with them.

Students who live on campus but return home for spring quarter will be allowed to cancel their housing contracts early and be refunded for their spring quarter housing and meal plan expenses. Students who cancel their contracts must bring their personal belongings home with them, the email stated.

All remaining UCLA study abroad programs were canceled. UCLA also suspended all nonessential university international and domestic travel.

The campus will remain open for research and international students. However, UCLA Recreation announced Sunday it would be closing all facilities until further notice starting on Monday.

Likewise, the Arthur Ashe Student Health and Wellness Center and Counseling and Psychological Services will remain open.

F1 and J1 visas for international students will not be affected by the move online, the email read. Students receiving accommodations from the Center for Accessible Education have been informed of any changes or alternative accommodations, the email read.

UCLA had previously canceled in-person classes until just April 10, two weeks into spring quarter. Chancellor Gene Block announced Friday that he would be self-quarantining for 14 days after coming into contact with a person with the coronavirus.

Additionally, UCLA Health suspended all volunteer programs indefinitely.

The coronavirus first emerged in Wuhan, China, in December 2019 and has since spread to at least 140 countries.

Los Angeles County has 94 confirmed cases. LA mayor Eric Garcetti ordered that bars, restaurants, nightclubs and entertainment facilities close Sunday at midnight, in an attempt to slow the spread of the virus.

Ayla Dvoretzky, a second-year civil and environmental engineering student, said while attending lecture on Zoom, a video conferencing platform, sounded fun at first, it quickly lost appeal when she realized it was going to be used for the entire quarter.

Dvoretzky added that she plans to take four very difficult and very collaborative STEM classes next quarter, which she was planning to tackle by working with her peers.

I was already really worried about the workload, she said. And I was planning to rely a lot on getting the help and support of my peers. And I know that thats going to be a lot more difficult now.

She said the whole situation makes it difficult to focus on finals.

Im talking to my friends who I thought I was going to have another quarter with and trying to figure out whos leaving when and whos living where and how were going to see each other, Dvoretzky said. And its just a lot to think about and also worry about finals.

Dvoretzky said she thinks shes grown from the leadership positions shes taken on, the peers she has access to and the environment at UCLA, which can be lost in an online setting.

Much more of UCLAs value to me is that stuff thats not quite as quantifiable, rather than the academics of it, she said. And so I feel like Im losing the more important part of UCLA, like on paper, sure, Im still getting taught by UCLA professors, but I dont feel like Im getting the UCLA education that I worked and paid for.

Antonio Uyemura, a second-year microbiology, immunology, and molecular genetics student said he was particularly frustrated with the way the information was communicated to students since he is an out-of-state student from Texas.

After the first announcement that canceled classes through April 10, Uyemuras parents booked him a flight home for Saturday. However, since the second announcement that UCLA would be moving all of spring quarter online came on Friday, Uyemura was forced to move out in 24 hours.

It was slightly frustrating to see how fastly the response escalated because it didnt really feel calculated because it was like, if you already had the intention to put it off for two weeks, why wouldnt you keep that and then reassess afterwards? Uyemura said.

He added he is now considering whether to defer for spring quarter and enroll in summer session C instead.

I pay all this money to go to this school in California, he said. So why would I take the school in Texas?

Simon Zhang, a fourth-year applied mathematics student, said he was happy when he first heard the news, but slowly realized some of the larger consequences.

Slowly I realized that like, oh no, that means like I wont be able to experience everything in spring quarter as I would have, Zhang said.

He added there are a lot of moments that he is missing out in as a senior.

I always had this picture of what my last couple weeks of my UCLA experience would be like, but obviously thats not gonna happen, he said. I havent taken my grad photos yet. So I think thatll be really sad that I wont have photographed memories with my close friends. So its just a lot of moments that I would have wanted to experience for the last time that I wont be able to get anymore.

Students can view updated information on the UCLA website. Students can reach a student support line at 310-825-3894 starting Wednesday for any issues they face regarding COVID-19 and its impacts. It will be open on weekdays from 9 a.m. to 7 p.m.

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UCLA extends online instruction through end of spring quarter - Daily Bruin

Reuben Jacob and Fiona Kellas, Maucher Jenkins share their expertise on IP strategies and considerations for gene therapy inventions.

Gene therapy enables the treatment of a disorder or disease through the insertion of a gene into a patients cells instead of using drugs or surgery.This technique involves the introduction of genetic material into cells to compensate for abnormal genes in the patient or to make protein that will be beneficial to the patient.As an example, if a mutated gene causes a protein that is necessary for the correct functioning of cells to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein.Gene therapy is understood to be useful in the treatment of a range of conditions such as cancer, cystic fibrosis, muscular dystrophy and Alzheimers disease.

UK role in gene therapy techR&D

Gene therapy is considered to be very important to the future of medicine and as such, many companies are focussing their research and development into gene therapy technologies.The UK is a growing industry for research into these areas and it is anticipated that by 2035 the UK industry around cell and gene therapy technologies will be worth in the region of 10 billion.Gene therapy research is still at an early stage.Due to this length of time and the associated costs involved in developing an effective gene therapy and taking it through to approval, it will be important for companies working in this area to put into place an effective IP strategy that will provide protection for their inventions and assist them in maintaining their market position.In addition, the competitive nature of the gene therapy industry means that will be important for a company to obtain patent protection for inventions being developed, as well as reviewing the patent landscape to check that the company is free to operate in their chosen area.

What makes something patentable?

In order for an invention to be patentable, it must be new, inventive and capable of industrial application.In addition to the requirement that an invention meets the above requirements of patentability, it is also important that the invention does not contain subject matter that is excluded from patentability.One of the challenges associated with obtaining patent protection for gene therapy inventions is that the European and US patent systems include a number of exceptions to patentability that are relevant to biological material and natural products.In Europe, it is not possible to obtain patent protection for a method of treatment or surgery of the human body.Thus, the removal of cells from a patient would not be considered to be patentable in Europe.In addition, inventions relating to stem cells that are derived from the destruction of human embryos are not patentable in Europe.In the US, recent case law (Molecular Pathology v Myriad Genetics, Inc, 2013) has meant that inventions relating to natural phenomena and natural products must show characteristics that are different to their natural counterpart(s).

However, despite the above challenges, there are a number of aspects of the gene therapy technology that may be eligible for patent protection.Typically, the gene therapy procedure can involve performing the required modification procedure on cells that have been removed from a patient before reintroducing the cells into the subject to produce their modified effect.The process of modifying the cells may be patentable if it fulfils the above requirements of patentability.In addition, it may be possible to obtain protection for the methods that are used to culture, manipulate or modify the cells that are used for gene therapy.

At Maucher Jenkins, we have a team of attorneys who can provide IP advice and assistance in the area of patenting inventions involving gene therapy, molecular biology and biochemistry.

by Fiona Kellas, Reuben Jacob

16 March 2020

14:20

See original here:
Thinking out loud: IP strategies for gene therapy inventions - Med-Tech Innovation

I dont know if were more religious today, says Ken Bingman, who has taught biology in Kansas City public schools for 42 years, but I see more and more students who want a link to God.

While religion certainly looks to be on the upswing in the United States, theres a lot more to the resurgence of creationism than a rising tide of religious fervor. Received wisdom counsels little more than continued resistance against the Bible thumpers at the gates. Daniel Dennett, author of Darwins Dangerous Idea, is too busy excoriating creationists and scientific fellow-travelers to notice that the dominant biological theory of the day is inadvertently encouraging the creationist revival. The chief threat to Darwinian evolution is none other than neo-Darwinian evolution. As conceived by Austrian theorist August Weismann in the 1890s, neo-Darwinism shares fundamental features with creationism, not the least of which is reliance on blind faith rather than empirical fact. The creationist tide may never be stemmed until biology abandons Weismannian reductionism and returns to a more traditional Darwinian outlook.

Given the cultural atmosphere of his upbringing, Darwin could hardly have helped but absorb the lesson that an all-knowing, masculine deity commands the cosmos. At a time when science was still joined at the hip with religion, the modern prophets were Kepler, Galileo, Descartes, and Newton, whose mastery of mathematics gave them a communion of sorts with the Almighty, allowing them to receive the eternal equations supervising the operations of the universe. Newtons laws of motion were no less than Gods thoughts.

As above, so below. After establishing the heavens, the cosmic Mechanic fashioned each species of life according to a design of His choosing. According to theologian William Paley whose treatise, Natural Theology, had young Darwin temporarily hypnotized an organism is no different in principle than a watch. Just as a watch cannot come into being without the painstaking efforts of a craftsman, organisms are mechanisms constructed and wound up by God and left to play out their allotted time on Earth.

But Darwin was a true naturalist. Guided by his intuitive sense of nature, he gradually outgrew Paleys notion of divine authority over obedient matter. The naturalistic materialism of his mature years represented a total repudiation of theological mechanism, substituting divine creation with the creativity inherent in nature. His new understanding was prefigured in part by the deist teachings of his grandfather, Erasmus, who alleged that after devising the cosmic machine, the deity left the mundane affairs of terrestrial existence to their own devices.

Erasmus had a streak of the pagan in him. Though outwardly a scientific rationalist, he found religion in nature if not the Bible. Exploring a cave, he didnt just find a bunch of rocks but glimpsed the Goddess of Minerals naked, as she lay in her inmost bower. The earth wasnt just a passive depository for Gods will but Mother Earth, whose womb gave life and whose wrath in the form of floods, eruptions, and quakes could just as easily snuff it out. In contrast to the paternal principle of the heavens, the earth followed its own, darker, maternal principle.

Materialism is not so much a sophisticated modern philosophy as an ancient mythos that locates within the earth itself the source of life and its myriad forms. Etymologically, mother and matter are the same word, having evolved from the same Indo-European root. The materialist metaphysics signified by Mother Nature is not the reductionistic form were accustomed to today, in which particles are mere playthings of eternal laws of physics, but an expansive materialism in which matter is endowed with its own creative and destructive powers.

In response to the 1859 debut of Darwins theory of natural selection, Adam Sedgwick, an old-school geologist, accused the author of trying to render humanity independent of a Creator by breaking the chains that link all secondary causes to Gods ultimate cause. Though Darwins declaration of independence was a prerequisite to the scientific study of life, he was understandably anxious about turning his back on the Father. Caught in the pull of two opposing worldviews, he conceded that his theological opinions were hopelessly muddled. The same could be said of his views on physics and life.

The starting-point for the theory of descent with modification is not the equations of Kepler, Galileo, and Newton but the fecundity of living nature and the resulting struggle for existence in the face of finite resources. Though Darwin invoked the authority of natural law so as to eliminate the role of divine intervention in the creation of species, at the core of evolution is novelty, and by definition novelty is not pre-determined, either by God or physics. While pledging allegiance to Newton as final arbiter of everything under the sun, he set out on a course that would ultimately undermine physical determinism in biology.

Throw up a handful of feathers, he says in The Origin of Species, and all fall to the ground according to definite laws; but how simple is the problem where each shall fall compared to that of the action and reaction of the innumerable plants and animals which have determined, in the course of centuries, the proportional numbers and kinds of trees now growing on [Native American] ruins! The mathematical abstractions of physics had little to offer when it came to either ecology or the internal dynamics of organisms. Dissenting from T. H. Huxleys notion of animal automatism, Darwin stressed the importance of individual will in shaping behavior and maintained that a complex system of cells, tissues, and organs cant function properly without a coordinating power that brings the parts into harmony with each other. Such talk has no place in a purely mechanistic program.

While today evolution is generally thought to result from the purely mechanical interplay of natural selection and genetic mutation, Darwin explicitly rejected this view, assigning only a marginal role to the spontaneous variations (mutations) arising from the germ-plasm (genome). The variations subject to natural selection did not emerge from the germ-plasm buried deep within the organisms cells but from its day-to-day struggle to survive in the face of competition and limited resources. Darwinian evolution is a model of clarity, elegance, and common sense: the adaptations made by organisms are transmitted to their progeny, and these adaptations become more ingrained and more pronounced with each passing generation until a new species emerges from the old.

Ordinarily written off as Lamarckian, this view is incidental to Lamarcks theory, according to which evolution, from the beginning, was divinely guided toward the emergence of Homo sapiens. As for the capacity of plants and animals to inherit traits taken up by their ancestors during their life-struggles, Darwin concurred. I think there can be no doubt that use in our domestic animals has strengthened and enlarged certain parts, and disuse diminished them; and that such modifications are inherited. He cited examples of animals that clearly inherited traits from their ancestors, such as young shepherd dogs that know, without training, to avoid running at sheep. He explained that domesticated chickens have no fear of cats or dogs because their ancestors became accustomed to common pets and lost their fear of them. Ostriches cant fly because they inherited weak wing muscles and strong legs from their ancestors who learned to kick their enemies instead of taking flight. A similar effect in ducks may be safely attributed to the domestic duck flying much less, and walking more, than its wild parents.

Darwin was skeptical of the notion that examples such as these and there are literally countless more could all result from genetic mutation. Why attribute a given trait to a mysterious and random process taking place in the depths of the body when theres a perfectly obvious explanation involving the life-circumstances of ancestors? Everyone knows that hard work thickens the epidermis on the hands; and when we hear that with infants, long before birth, the epidermis is thicker on the palms and the soles of the feet than on any other part of the body we are naturally inclined to attribute this to the inherited effects of long-continued use or pressure.

The meaning of evolution is that species are not created so much as self-created in the act of living and adapting. Regarding the origin of sea mammals, Darwin writes, A strictly terrestrial animal, by occasionally hunting for food in shallow water, then in streams or lakes, might at last be converted into an animal so thoroughly aquatic as to brave the open ocean. Due to the variability of bone structure in youth, newly-acquired behaviors can gradually result in structural modifications, such as flat-fish that pushed their eye sockets a little further up their skulls with each passing generation. The tendency to distortion would no doubt be increased through the principle of inheritance.

The key is that offspring inherit adaptations at the same age or younger than the age at which their parents originally made the adaptation. The alternative that such changes result only from random genetic mutations fails to explain the changes but merely surrenders the issue to chance. Rather than account for the fact that camels, which often have to kneel on sandy terrain, begin developing padded tissue on their knees while still in the womb, we simply say that it happened by chance, and this explanation repeats for every species on Earth in regard to any trait that might otherwise be attributed to the living adaptations of organisms in their struggle to survive.

Finding this prospect intolerable, Darwin insisted on the centrality of the inheritance of adaptations, emphasizing that the young play a central role in this process. For if each part [of the body] is liable to individual variations at all ages, and the variations tend to be inherited at a corresponding or earlier age, propositions which cannot be disputed, then the instincts and structure of the young could be slowly modified as surely as those of the adult; and both cases must stand or fall together with the whole theory of natural selection. The primary source of variations to be selected or rejected is the will of the organism to survive and reproduce.

But what if Darwin was wrong? He certainly stumbled with his fanciful theory of pangenesis, whereby each cell sloughs off tiny gemmules that reflect changes occurring in the body and transmit those changes to the reproductive organs. Pangenesis was intended to provide a mechanism enabling adaptations to be passed along to the next generation. According to Neal Gillespie, Darwins theory assured him that a capricious deity could be excluded from the process of heredity as well as from speciation. Unfortunately, another capricious deity, DNA, eventually took its place.

August Weismann was absolutely correct when he concluded that organisms cannot affect the determinants (genes) in their reproductive cells. If genes are the sole vehicle of hereditary information, as Weismann assumed, then acquired characteristics cannot be inherited, and Darwinian evolution, with its typically English sentimentalism, must yield to a more precise, mechanistic form.

But Weismann was very clear that his theory was not based on evidence and could never be tested. Cutting off the tails of mice and finding that their offspring still had tails proved nothing, as Weismann himself readily admitted. Though he claimed his argument was ironclad, he offered nothing to support it beyond the fact that he simply couldnt imagine how hereditary information could be transferred by any means other than the passage of genes from parents to offspring. We accept it, not because we are able to demonstrate the process in detail but simply because we must, because it is the only possible explanation that we can conceive. As neo-Darwinist Richard Dawkins likes to point out, the inability of creationists to imagine how the species of life could have emerged without Gods help does not make creationism a scientific theory. What he fails to realize is that his argument applies with equal force to his own favored view.

Darwinian evolution can be expressed as a form of local creationism. Rather than products of a universal creator, species are shaped by their pragmatic adjustments to local environments. Thus, by emphasizing that evolution boils down to the purely mechanical interaction of genes and environment, neo-Darwinism reverses Darwin's innovation and restores the creation of species to universal causes. Whether theological or mathematical, mechanistic determinism is universal creationism.

As Darwin observed on the Pacific islands, its no accident that frogs, which cant survive seawater, are found only on the islands where they evolved, whereas birds, which can fly from one island to the next, are found everywhere. When confronted with this fact, a creationist might say, It pleased the Creator to place those frogs on some islands and not others. Of course, this fails to explain the situation but merely restates the facts. Similarly, the neo-Darwinian reliance on genetic mutation as the source of heritable variations merely restates the fact that a transformation has taken place and that it has become biologically ingrained within the species.

Neo-Darwinsim shares many features with creationism. First, it is faith-based and untestable. It simply must be true. Second, it is universalist: the source of species is not local conditions and creative adaptations but transcendent principles that merely manifest locally. Third, like the exhortation that God did it, neo-Darwinism makes use of a generic, all-purpose explanation instead of tailoring its account to particular situations faced by particular organisms. Fourth, it is anthropomorphic. In place of a human-like God, a human-like language or code inscribed in DNA is responsible for shaping organisms. Fifth, it is mechanistic: we are machines assembled according to a blueprint or design. Whether this design is a soul crafted by God or a genome forged beneath the blind forces of mutation and natural selection, the body is a mechanism constructed from specifications of one sort or another. Finally, as with creationism, the power of speciation is appropriated from the species themselves and refashioned as an external, mechanical process.

The shift from Darwinism to neo-Darwinism is pure atavism, a reversion to the transcendent determinism previously found only in creationist dogma. The law-giver may have been airbrushed out, but the law remains. Trouble is, with its cosmic Mechanic, creationism is clearly the strong form of mechanism, while neo-Darwinism though obviously much closer to the truth must remain the weak form. In the struggle between intelligent design and blind design, is it any wonder that creationism has proved so resilient?

Since the 1972 publication of Jacques Monods Chance and Necessity, the mechanistic theory of life has been known as reductionism. But what, precisely, is life being reduced to? Though often mistaken for the monistic doctrine of materialism, reductionism is a dualistic theory that reduces life not to matter but to physics. We have, on the one hand, the passive material constituents of the organism; on the other, the laws of physics that provide order and necessity to the otherwise chance motions of atoms and molecules.

According to Stephen Rothman, a professor at UC San Francisco and an experimental biologist for 40 years, reductionistic bias has severely impaired the ability of researchers to accurately assess the operations of cells and bodies. Rothman offers the vesicle theory of protein transport as an example of the reductionistic approach at work. The vesicle theory is stupendously unwieldy and implausible, requiring 15 to 30 mechanisms to move proteins a few microns. None of the experiments cited in support of the theory can prove that these mechanisms actually exist but only what they would look like if they did. Proponents have never put their theory to the test, never saying, If the theory is true, then such and such should happen. Yet they remain implacably confident in themselves. Why? Because their supposition is the only way to account for the movement of protein on the view that cellular activities are completely lost without the guidance of physical and chemical principles.

Since preparation of cell samples for viewing in electron microscopes inevitably distorts the final image, some proteins appear where theyre supposed to be, while others are phantoms. The resulting confusion allowsreductionist researchers to interpret all experimental results in their favor. Thus, if a protein appears where the vesicle theory predicts, its assumed to be in the correct place, and if not, its simply written off as a contaminant. As to predicted proteins that dont show up at all, these are assumed to have been lost in the sample preparation process.

Much like the automobile a soothingly familiar mechanism in our daily lives a vesicle is supposed to open up to allow proteins to enter it, then shut tight during transport and re-open upon reaching its destination. In the 60s, when Rothman demonstrated that proteins can freely enter and exit a vesicle even when its shut, most of his colleagues assumed his finding was flawed due to errors in sample preparation. In the 80s, when the brand new x-ray microscope proved him right, Rothman figured the vesicle proponents would admit their mistake. Hes still waiting. It seems that no amount of evidence, no matter how compelling, can falsify the vesicle theory.

A self-proclaimed biological skeptic, Rothman is not the first to call into question the final authority of physics over biology. Ernst Mayr noted that the property of individuality, which is utterly foreign to atomic physics and chemistry, places biology beyond the grasp of physical analysis. Though the late Mayr helped bring neo-Darwinian theory to fruition in the 30s and 40s with the modern synthesis of natural selection and Mendelian genetics, he was dismissive of efforts at physical reductionism. Attempts to reduce biological systems to the level of simple physico-chemical processes have failed because during the reduction the systems lost their specifically biological properties.

According to Niels Bohr the first of the quantum generation to investigate the potential for a physics of life a rigorous analysis of a cell would require knowing the initial values and positions of its constituent particles. Since measuring these particles disturbs them by breaking or dislocating bonds between them, its impossible to measure precisely the parts of a cell without altering it. Bohr compared this conundrum to his prior discovery that the momentum of an electron cannot be established once its position has been determined, and vice versa. Bohr called this complementarity, a principle he generalized to encompass all sufficiently complex systems, including cells and organisms. The more precisely we describe the parts, the cloudier the system as a whole becomes. Just as the quantum realm requires its own set of principles apart from classical physics, life, he concluded, is a primary phenomenon not subject to prior forms of analysis.

In 1944, the same year DNA was identified as the carrier of genes, Erwin Schrodinger published a short book called What Is Life? Taking a somewhat rosier view than his Danish colleague, Schrodinger proclaimed that the inability of current physics to account for life is no reason to doubt the eventual success of the project. The only catch is that a successful resolution will depend on other laws of physics hitherto unknown. We have no idea what these laws might be or how to find them. All we know for sure, said Schrodinger, is that the ordering of living matter is entirely different from the physical processes described by statistical mechanics. Despite imploring the reader not to accuse him of calling genes cogs of the organic machine, Schrodinger is commonly cited to this day as a physicist who lent support to reductionistic biology.

To date, the most sustained, in-depth examination of biology by a physicist was carried out by Walter Elsasser, another pioneer in quantum mechanics who later turned to geophysics and proposed against great opposition what eventually became the definitive theory of the earths electromagnetic field. Intrigued by the challenge of explaining organisms from a physical standpoint, Elsasser approached the issue in terms of precise point to point predictability of every step in a reaction chain that is both necessary and sufficient for a particular biological outcome. Yet this method, he discovered, has no applicability to organisms.

Quantum mechanics, the foundation of modern physics and the most thoroughly tested and successful theory of all time, is a statistical science, explaining the behavior of particles en masse rather than one quark at a time. What makes quantum mechanics a viable undertaking is that every particle of a given class is identical to every other particle of that class. As long as every proton is identical to every other proton, and every electron is identical to every other electron, etc., the averages obtained for a given class apply equally to every member within it.

By contrast, life is characterized by individuality, or radical heterogeneity, in Elsassers phrase. Macromolecules, organelles, cells, tissues, organs and organisms are never identical to other members of their class (not even in the case of identical twins). We are individualized right down to the chemistry of our blood and saliva. As a result, when it comes to living matter, averages dont apply equally to all members of a given class. Individuality short-circuits the statistical methods of quantum physics, rendering inoperative the differential equations that determine ordinary physical processes. Physics is simply not equipped to bridge the gap between the homogeneous safety of atoms and the heterogeneous stew of organisms.

As we learn from Ludwig von Boltzmann and the science of thermodynamics, physics can predict the motions of a cloud of gas taken as a whole but not the particles comprising it. So too, the interior of a cell consists primarily of free particles not subject to deterministic equations. The orderly processes that take place within cells are set against a backdrop of atomic and molecular randomness. With a trillion atoms per cell, many of them multi-bonding carbon, the number of possible molecular states compatible with the shapes and functions of a cell is far too great to yield to the yoke of mathematical physics. Though the patterned regularities of cells can be described in great detail, the ultimate origins of these processes are buried in unfathomable complexity. Elsasser declared biology a non-reductionistic science, fundamentally and qualitatively different from physical science.

Even if life really is reducible to physical principles, biological reductionism can be neither verified nor falsified and is thus not a theory in the scientific sense. Perhaps life emerged when God exhaled onto a lump of clay, but this too can never be proven or disproven.

Rather than accept that physicalist biology has no scientific meaning, reductionists settled on a jerry-rigged substitute theory based around genes. That life is a product of physics is taken on faith while the multi-level ordering of the organism is attributed to DNA, which is charged with the dual task of storing morphological information and coordinating (via RNA and protein) development from egg to adult. In place of true physical reductionism, we have a stop-gap genetic reductionism. Yet even the watered down physics of life is untenable.

By utilizing the mathematics of combinatorics, UC Berkeley biologist Harry Rubin has demonstrated that the precise combination of genes required for the mold Aspergillus to produce penicillin is transcalculational, or beyond the computational capacity of any conceivable computer in a finite amount of time. With 1000 genes influencing penicillin production and each gene having, at the very least, alternate wild and mutant states the minimum number of possible gene combinations is 2 to the 1000th power, or 10 to the 300th power. The magnitude of this number can be appreciated when we consider there are only 10 to the 80th particles in the universe. Yet the production of penicillin is a model of simplicity compared to the generation of the eye in the fruit fly Drosophila, which involves 10,000 genes. With two copies of each gene and multiple types of mutation for each, the number of possible combinations grows beyond our imaginative capacity. If organic structures really are built mechanically from genetic instructions, then genes must possess a magical power of computation.

The Boltzmann theorem, which limits deterministic equations to statistical aggregates of molecular events, poses an insurmountable problem for genetic reductionism. Whether in a gas cloud or a living cell, a free molecules behavior is always unique and nonrecurrent. Between the genes in the nucleus and the tissues and organs they allegedly determine lies an ocean of chaos called the cytoplasm. Deterministic processes, such as enzyme-driven reactions, are like rafts tossed about on giant waves in the vast cytoplasmic outback, every causal chain bound by a terminal point beyond which nothing can be predicted. Even if genes could miraculously express their inner blueprint, this information would quickly be swamped by the molecular pandemonium. In contrast to computers, which are designed so as to maintain an acceptable signal to noise ratio, organisms have no means of insulating against noise, particularly inside cells.

Oddly enough, instead of compounding the underlying error of physical reductionism, the error of genetic reductionism seems to cancel it out. Under the spell of DNA and its four nucleotide letters, we cant see that the ground has dropped out from beneath our feet, leaving neither reduction of organism to genome nor reduction of cell to physics. The endless stream of wordlets formed from the combinations of a, c, g, and t c is a kind of incantation that keeps the mind frozen in reverential awe at the keepers of the keys and their magic code. The Human Genome Project, intended to explain the mystery of life, merely completed the catechism.

This is not to deny the numerous effects that genes have on organisms. But the fact that genes distinguish one individual from another means only that they influence development not that they necessarily program and determine it every step of the way. That the gene-protein complex is necessary for the formation of organs and tissues doesnt mean its sufficient. As embryologist Paul Weiss observed, its a long way from determining eye color to actually building a pair of eyes. If genes determine multicellular structures, then why, asked Weiss, does embryogenesis begin indeterminately, differing from case to case, as if each embryo must improvise as it goes along? And why does organic form emerge top-down? Only when the body as a whole begins taking shape do the outlines of its organs emerge, and only then do cells begin conforming to characteristic types exactly the opposite of what we would expect from a process driven from within the dark recesses of our cells. As to DNA replication and other mechanical operations within organisms, Weiss contended that rather than controlling the living system, organic mechanisms are tools utilized by the system in its quest to maintain large-scale order in the face of small-scale disorder.

This is what Darwin was getting at with his coordinating power. The organism operates holistically, much like a magnetic field. It also adapts holistically. As Rothman points out, adaptive qualities belong to organisms, not genes. Its the organism as a whole that struggles to survive in the jungle or savanna, not genes tucked away in their cozy nuclear compartments. The question is not whether creatures pass on their living adaptations but how.

Toward the end of The Origin of Species, Darwin takes Leibniz to task for alleging that Newton introduced occult qualities and miracles into philosophy with his theory of gravity. As with Faradays undulatory theory of light, which Darwin cites as a fine example of scientific detective-work, Newtons theory of gravity suggests that matter possesses unexpected properties that do not conform to our standard notion of matter, i.e., contact mechanics. Weve known since Einstein that electromagnetism and gravity both allow matter to act at a distance without material mediation. Elsasser suggests that an unforeseen property of matter enables organisms to receive hereditary information from their ancestors at a distance over time. He calls this holistic memory, as opposed to the artificial, information-storage memory in computers.

The physics to which biology reduces itself is not the modern discipline of Einstein and quantum mechanics but the discredited variety that saw contact mechanics as the fundamental reality. Biologists today resemble theorists of the 19th century who still believed in a luminiferous ther that mediated the propagation of electromagnetic waves through space. As physicist James Croll averred in 1867, No principle will ever be generally received that stands in opposition to the old adage, A thing cannot act where it is not, any more than it would were it to stand in opposition to that other adage, A thing can not act before it is or when it is not. Having recognized that matter does indeed act where it is not, Elsasser began to wonder if it could also act when it is not.

Apart from allowing the transmission of acquired characteristics, holistic memory disposes of the need for a blueprint. Instead of following a pre-planned design, the embryo merely mimicks the developmental steps of its predecessors. If all they must do is combine as they always have in a given situation, genes have no need for magical powers of computation. But this does not mean the behavior of organisms is reducible to a new kind of physical determinism based on holistic memory in place of contact mechanics. Between the randomness of molecular events and the necessity of physical law lies a probabilistic gray area in which an organism may choose to follow its memory or if environmental conditions have changed sufficiently to select a new course of action. By contrast, if every creature is deterministically bound to its species memory, all the genetic mutations in the world cannot give rise to evolution. Elsassers organismic selection is the logical counterpart to Darwins natural selection.

Which option should cause us greater skepticism that a human being is a robot constructed through blind forces of nature and operated by remote-control from the nuclei of its cells or that once again matter turns out to be more versatile than wed previously imagined? Which is more plausible that the memory of how to grow from an egg to an inconceivably complex living system is somehow encoded in our genes or that nature has its own form of memory?

Darwins theory of evolution is true to life precisely because it shifts the focus from the timeless abstractions of physics to the irreducible powers of creativity and destruction that play out day by day in the natural world. As he wrote in the famous final passage of Origin, There is grandeur in this view of life, with its several powers such as growth, reproduction, variability, the will to live, and natural selection. Though he (tentatively) believed in a Creator who set it all in motion according to fixed, universal laws, in order to comprehend the ever-changing face of life, Darwin turned to Mother Nature. Instead of attaching biology to physics and thereby subsuming it to the Fathers mathematical idealism, he brought biology to life by animating it with a materialistic theory all its own.

As he observed in a letter to his friend, geologist Charles Lyell, it is absolutely necessary to go the whole vast length, or stick to the creation of each separate species. Its about time the Darwinian revolution was completed. Contrary to Weismann, not only can we conceive of alternatives to reductionism, but we have no choice, as the ghost of mechanism past will continue to haunt us until we reject mechanistic biology in all its forms.

Original post:
The Mother of Invention (March 9, 2005) - Anderson Valley

POSTPONED: The University Research Awards have been postponed in response to the coronavirus (COVID-19) pandemic.

Andrew Hartman of the Department of History and John Sedbrook of the School of Biological Sciences have been named Outstanding University Researchers. Melissa Oresky of the Wonsook Kim School of Art and Carl Schimmel of the School of Music will receive awards for Outstanding University Creative Activity. They will be honored at the University Research Awards at 6 p.m. Thursday, April 2, in the Hancock Stadium Club. Doors open at 5 p.m.

Ladan Bahmani of the Wonsook Kim School of Art will receive the Creative Activity Initiative Award. Research Initiative Awards will be presented to Matthew Aldeman of the Department of Technology; Tenley J. Banik of the Department of Geography, Geology, and the Environment; Jennifer Barnes of the Department of Family and Consumer Sciences; Ashley K. Farmer of the Department of Criminal Justice Sciences; Daniel G. Lannin of the Department of Psychology; Alice Y. Lee of the School of Teaching & Learning; Taeok Park of the Department of Communication Sciences and Disorders; Scott Pierce of the Department of Kinesiology and Recreation; and Lindsey J. Thomas of the School of Communication.

Also recognized at the event will be the winners of the James L. Fisher Outstanding Thesis Award, the Sorensen Dissertation Award, the Three-Minute Thesis winner, and the winners of the Image of Research competition.

Andrew HartmanDr. Andrew Hartman is a professor in the Department of History, where he teaches courses in U.S. history, the philosophy of history, and teaching methods. Hartman received his Ph.D. in history from George Washington University in 2006. He was the Fulbright Distinguished Chair in American Studies at the University of Southern Denmark in 2013-14, and he was the Fulbright British Library Eccles Center Research Scholar in 2018-19. He is an Organization of American Historians (OAH) Distinguished Lecturer for the 2015-2021 period. Hartman was also the founding president of the Society for U.S. Intellectual History (S-USIH), and he wrote for the Societys award-winning blog from 2007 until 2018. He has been published in a host of academic and popular venues, including the Washington Post, Baffler, The Chronicle of Higher Education, the Journal of American Studies, Reviews in American History, Salon, and Jacobin. He co-hosts a podcast dedicated to history titled, Trotsky and the Wild Orchids.

John SedbrookDr. John Sedbrook is a professor of genetics in the School of Biological Sciences at Illinois State University, having earned his Ph.D. in genetics at the University of Wisconsin-Madison and performed postdoctoral research at the Carnegie Institution at Stanford University. Sedbrooks research uses cutting-edge molecular methods including CRISPR gene editing to improve plants for their use in generating biofuels, food, feed, and industrial products. Sedbrook has secured millions of dollars in federal and private funding and published in prestigious scientific journals including Science and Nature. Sedbrook was a founding member of the Department of Energys Great Lakes Bioenergy Research Center (GLBRC), which receives $25 million annually to perform basic and translational research aimed at breaking barriers to generating liquid biofuels economically and sustainably. Sedbrook and students in his laboratory have been leaders in domesticating pennycress as an oilseed-producing cash cover crop to be grown throughout the 80 million-acre U.S. Midwest Corn Belt and beyond.

Melissa OreskyMelissa Oreskys art practice is rooted in painting and collage, and her primary production is mixed media works on canvas and paper. Oresky is interested in landscape, and considers it as a concept that bridges painting, lived experience, environmental consciousness, and imagination. Oresky has shown her work in painting, collage, and video nationally and internationally, with recent shows at Tripod Space Project, Busan, South Korea; Hyde Park Art Center, Chicago; Elmhurst Art Museum, Elmhurst, Illinois; Minnesota State University, Mankato; and K. Imperial Fine Art, San Francisco. She also co-organized and participated in the project Collage Office, an experimental, charitable platform for artists to make work for visitors by appointment at The Franklin, Chicago. Oresky holds a bachelors degree from the School of the Art Institute of Chicago, and an MFA from the University of Illinois at Chicago. She has attended residencies including Skowhegan School of Painting and Sculpture, Maine, and The Santa Fe Art Institute, New Mexico. Originally from Maryland, she lives and works in Normal, Illinois, where she is a Professor of Painting and Drawing at Illinois State University.

Carl SchimmelDr. Carl Schimmel was the winner of a 2018 Guggenheim Fellowship, Columbia Universitys Joseph Bearns Prize, the Lee Ettelson Award, a 2018 Commission from Harvard Universitys Fromm Foundation, and the 2017 Goddard Lieberson Fellowship from the American Academy of Arts and Letters, Schimmel has received honors and awards from many organizations, including the MacDowell Colony, Yaddo, Copland House, New Music USA, and ASCAP. Schimmel is an associate professor of music theory and composition and co-director of the RED NOTE New Music Festival at ISU. His works have been performed in Carnegie Halls Weill Hall, Merkin Hall in New York, Severance Hall in Cleveland, the National Arts Centre in Ottawa, St. Martin-in-the-Fields in London, Orchestra Hall in Minneapolis, and at other venues throughout North America, Europe, Australia, and Asia. He has received performances and commissions from the American Composers Orchestra, the Minnesota Orchestra, the Buffalo Philharmonic Orchestra, California EAR Unit, the Left Coast Chamber Ensemble, Alarm Will Sound, the Louisiana Philharmonic, the New England Philharmonic, the Mexico City Woodwind Quintet, and many others. Recordings of his music are available on the Albany Records, New Focus Recordings, Arizona University Recordings, Navona Records, Blue Griffin, and Crescent Phase labels. He earned a doctorate at Duke University with a masters degree from the Yale School of Music.

For additional information, contact the Office of Research and Sponsored Programs at ResearchOffice@IllinoisState.edu or (309) 438-2528.

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(POSTPONED) Hartman, Sedbrook, Oresky, Schimmel to be honored with research and creativity awards - News - Illinois State University News

In a talk at UAB on March 6, the NIH director shared his thoughts on exceptional opportunities for science and young scientists and highlighted several exciting UAB projects.

NIH Director Francis Collins, M.D., Ph.D., visited UAB on March 6. In addition to his public talk, Collins had breakfast with UAB medical students and met with groups of young researchers and other investigators across campus.Speaking to a packed University of Alabama at Birmingham audience March 6, Francis Collins, M.D., Ph.D., director of the National Institutes of Health, shared his picks of 10 areas of particular excitement and promise in biomedical research.

In nearly every area, UAB scientists are helping to lead the way as Collins himself noted in several cases. At the conclusion of his talk, Collins addedhis advice for young scientists. Here is Collins top 10 list, annotated with some of the UAB work ongoing in each area and ways that faculty, staff and students can get involved.

I am so jazzed with what has become possible with the ability to study single cells and see what they are doing, Collins said. They have been out of our reach now we have reached in. Whether you are studying rheumatoid arthritis, diabetes or the brain, you have the chance to ask each cell what it is doing.

Single-cell sequencing and UAB:Collins noted that Robert Carter, M.D., the acting director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, was a longtime faculty member at UAB (serving as director of the Division of Clinical Immunology and Rheumatology). For the past several years, UAB researchers have been studying gene expression in subpopulations of immune cells inpatients with rheumatoid arthritis.

Join in:Researchers can take advantage of the single-cell sequencing core facility in UABsComprehensive Flow Cytometry Core, directed by John Mountz, M.D., Ph.D., Goodwin-Blackburn Research Chair in Immunology and professor in the Department of Medicine Division of Clinical Immunology and Rheumatology.

Learn more:Mountz and other heavy users of single-cell sequencing explain how the techniqueslet them travel back in time and morein this UAB Reporter story.

The NIHsBRAIN Initiativeis making this the era where we are going to figure out how the brain works all 86 billion neurons between your ears, Collins said. The linchpin of this advance will be the development of tools to identify new brain cell types and circuits that will improve diagnosis, treatment and prevention of autism, schizophrenia, Parkinsons and other neurological conditions, he said.

Brain tech and UAB:Collins highlighted thework of BRAIN Initiative granteeHarrison Walker, M.D., an associate professor in the Department of Neurology, whose lab has been developing a more sophisticated way to understand the benefits of deep brain stimulation for people with Parkinsons and maybe other conditions, Collins said.

Join in:UABs planned new doctoral program in neuroengineering would be the first of its kind in the country.

Learn more:Find out why neuroengineering is asmart career choicein this UAB Reporter story.

Researchers can now take a blood cell or skin cell and, by adding four magic genes, Collins explained, induce the cells to become stem cells. These induced pluripotent stem (iPS) cells can then in turn be differentiated into any number of different cell types, including nerve cells, heart muscle cells or pancreatic beta cells. The NIH has invested in technology to put iPS-derived cells on specialized tissue chips. Youve got you on a chip, Collins explained. Some of us dream of a day where this might be the best way to figure out whether a drug intervention is going to work for you or youre going to be one of those people that has a bad consequence.

iPS cells at UAB:Collins displayed images of thecutting-edge cardiac tissue chipdeveloped by a UAB team led by Palaniappan Sethu, Ph.D., an associate professor in the Department of Biomedical Engineering and the Division of Cardiovascular Disease. The work allows the development of cardiomyocytes that can be used to study heart failure and other conditions, Collins said.

Join in:UABs biomedical engineering department, one of the leading recipients of NIH funding nationally, is a joint department of the School of Engineering and School of Medicine. Learn more about UABsundergraduate and graduate programs in biomedical engineering, and potential careers, here.

Learn more:See howthis novel bioprinterdeveloped by UAB biomedical researchers is speeding up tissue engineering in this story from UAB News.

We have kind of ignored the fact that we have all these microbes living on us and in us until fairly recently, Collins said. But now it is clear that we are not an organism we are a superorganism formed with the trillions of microbes present in and on our bodies, he said. This microbiome plays a significant role not just in skin and intestinal diseases but much more broadly.

Microbiome at UAB:Collins explained that work led by Casey Morrow, Ph.D., and Casey Weaver, M.D., co-directors of theMicrobiome/Gnotobiotics Shared Facility, has revealed intriguing information abouthow antibiotics affect the gut microbiome. Their approach has potential implications for understanding, preserving and improving health, Collins said.

Join in:Several ongoing clinical trials at UAB are studying the microbiome, including a studymodifying diet to improve gut microbiotaand an investigation of the microbiomes ofpostmenopausal women looking for outcomes and response to estrogen therapy.

Learn more:This UAB News storyexplains the UAB researchthat Collins highlighted.

Another deadly influenza outbreak is likely in the future, Collins said. What we need is not an influenza vaccine that you have to redesign every year, but something that would actually block influenza viruses, he said. Is that even possible? It just might be.

Influenza research at UAB:Were probably at least a decade away from a universal influenza vaccine. But work ongoing at UAB in the NIH-fundedAntiviral Drug Discovery and Development Center(AD3C), led by Distinguished Professor Richard Whitley, M.D., is focused on such an influenza breakthrough.

Join in:For now, the most important thing you can do to stop the flu is to get a flu vaccination. Employees can schedule afree flu vaccination here.

Learn more:Why get the flu shot? What is it like? How can you disinfect your home after the flu? Get all the information atthis comprehensive sitefrom UAB News.

The NIH has a role to play in tackling the crisis of opioid addiction and deaths, Collins said. The NIHs Helping to End Addiction Long-term (HEAL) initiative is an all-hands-on-deck effort, he said, involving almost every NIH institute and center, with the goal of uncovering new targets for preventing addiction and improving pain treatment by developing non-addictive pain medicines.

Addiction prevention at UAB:A big part of this initiative involves education to help professionals and the public understand what to do, Collins said. The NIH Centers of Excellence in Pain Education (CoEPE), including one at UAB, are hubs for the development, evaluation and distribution of pain-management curriculum resources to enhance pain education for health care professionals.

Join in:Find out how to tell if you or a loved one has a substance or alcohol use problem, connect with classes and resources or schedule an individualized assessment and treatment through theUAB Medicine Addiction Recovery Program.

Learn more:Discover some of the many ways that UAB faculty and staff aremaking an impact on the opioid crisisin this story from UAB News.

We are all pretty darn jazzed about whats happened in the past few years in terms of developing a new modality for treating cancer we had surgery, we had radiation, we had chemotherapy, but now weve got immunotherapy, Collins said.

Educating immune system cells to go after cancer in therapies such as CAR-T cell therapy is the hottest science in cancer, he said. I would argue this is a really exciting moment where the oncologists and the immunologists together are doing amazing things.

Immunotherapy at UAB:I had to say something about immunology since Im at UAB given that Max Cooper, whojust got the Lasker Awardfor [his] B and T cell discoveries, was here, Collins said. This is a place I would hope where lots of interesting ideas are going to continue to emerge.

Join in:The ONeal Comprehensive Cancer Center at UAB is participating in a number of clinical trials of immunotherapies.Search the latest trials at the Cancer Centerhere.

Learn more:Luciano Costa, M.D., Ph.D., medical director of clinical trials at the ONeal Cancer Center, discusses the promise ofCAR-T cell therapy in this UAB MedCast podcast.

Assistant Professor Ben Larimer, Ph.D., is pursuing a new kind of PET imaging test that could give clinicians afast, accurate picture of whether immunotherapy is workingfor a patient in this UAB Reporter article.

The All of Us Research Program from NIH aims to enroll a million Americans to move away from the one-size-fits-all approach to medicine and really understand individual differences, Collins said. The program, which launched in 2018 and is already one-third of the way to its enrollment goal, has a prevention rather than a disease treatment approach; it is collecting information on environmental exposures, health practices, diet, exercise and more, in addition to genetics, from those participants.

All of Us at UAB:UAB has been doing a fantastic job of enrolling participants, Collins noted. In fact, the Southern Network of the All of Us Research Program, led by UAB, has consistently been at the top in terms of nationwide enrollment, as School of Medicine Dean Selwyn Vickers, M.D., noted in introducing Collins.

Join in:Sign up forAll of Usat UAB today.

Learn more:UABs success in enrolling participants has led to anew pilot study aimed at increasing participant retention rates.

Rare Disease Day, on Feb. 29, brought together hundreds of rare disease research advocates at the NIH, Collins said. NIH needs to play a special role because many diseases are so rare that pharmaceutical companies will not focus on them, he said. We need to find answers that are scalable, so you dont have to come up with a strategy for all 6,500 rare diseases.

Rare diseases at UAB: The Undiagnosed Diseases Network, which includes aUAB siteled by Chief Genomics Officer Bruce Korf, M.D., Ph.D., is a national network that brings together experts in a wide range of conditions to help patients, Collins said.

Participants in theAlabama Genomic Health Initiative, also led by Korf, donate a small blood sample that is tested for the presence of specific genetic variants. Individuals with indications of genetic disease receive whole-genome sequencing. Collins noted that lessons from the AGHI helped guide development of the All of Us Research Program.

Collins also credited UABs Tim Townes, Ph.D., professor emeritus in the Department of Biochemistry and Molecular Genetics, for developing the most significantly accurate model of sickle cell disease in a mouse which has been a great service to the [research] community. UAB is now participating in anexciting clinical trial of a gene-editing technique to treat sickle cellalong with other new targeted therapies for the devastating blood disease.

Join in:In addition to UABs Undiagnosed Diseases Program (which requires a physician referral) and the AGHI, patients and providers can contact theUAB Precision Medicine Institute, led by Director Matt Might, Ph.D. The institute develops precisely targeted treatments based on a patients unique genetic makeup.

Learn more:Discover how UAB experts solved medical puzzles for patients by uncovering anever-before-described mutationandcracking a vomiting mysteryin these UAB News stories.

We know that science, like everything else, is more productive when teams are diverse than if they are all looking the same, Collins said. My number one priority as NIH director is to be sure we are doing everything we can to nurture and encourage the best and brightest to join this effort.

Research diversity at UAB:TheNeuroscience Roadmap Scholars Programat UAB, supported by an NIH R25 grant, is designed to enhance engagement and retention of under-represented graduate trainees in the neuroscience workforce. This is one of several UAB initiatives to increased under-represented groups and celebrate diversity. These include several programs from theMinority Health and Health Disparities Research Centerthat support minority students from the undergraduate level to postdocs; thePartnership Research Summer Training Program, which provides undergraduates and especially minority students with the opportunity to work in UAB cancer research labs; theDeans Excellence Award in Diversityin the School of Medicine; and the newly announcedUnderrepresented in Medicine Senior Scholarship Programfor fourth-year medical students.

Join in:The Roadmap program engages career coaches and peer-to-peer mentors to support scholars. To volunteer your expertise, contact Madison Bamman atmdbamman@uab.eduorvisit the program site.

Learn more:Farah Lubin, Ph.D., associate professor in the Department of Neurobiology and co-director of the Roadmap Scholars Program,shares the words and deeds that can save science careersin this Reporter story. In another story, Upender Manne, Ph.D., professor in the Department of Pathology and a senior scientist in the ONeal Comprehensive Cancer Center, explains how students in the Partnership Research Summer Training Program gethooked on cancer research.

In answer to a students question, Collins also shared his advice to young scientists. One suggestion: Every investigator needs to be pretty comfortable with some of the computational approaches to science, Collins said. Big data is here artificial intelligence, machine-learning. We can all get into that space. But its going to take some training, and it will be really helpful to have those skills.

Join in:UAB launched aMaster of Science in Data Scienceprogram in fall 2018.

Learn more:Discover how UAB researchers areusing machine-learning in their labsand toimprove cancer treatment. Those looking for a free introduction cantake advantage of the Data Science Clubfrom UAB IT Research Computing.

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Looking to the future with Dr. Francis Collins - UAB News

In a laboratory in the depths of Imperial College London, all eyes are on a group of mice scurrying about their daily business. The rodents were injected a few weeks ago with a prototype vaccine which it is hoped will achieve what the world has so far singularly failed to do so far - stop the coronavirus Covid-19.

Progress, says Professor Robin Shattock of Imperials department of infectious disease, looks good. His team first started developingthe vaccine in mid-January and are working at record pace, taking just 14 days to get from the genetic sequencing of the virus to generating the trial vaccine in the laboratory. It relies upon a cutting-edge technique which injects new genetic code into the muscle, instructing it to make a protein found on the surface of coronavirus triggering a protective immune response. Should the mice trial prove a success then Prof Shattock hopes to be experimenting on humans in the summer and have a vaccine ready next year perhaps even the first in the world.

The laboratories at Imperial are part of the global fightback against Covid-19. At Oxford Universitys Jenner Institute, researchers are producing a vaccine seed stock, 1,000 doses of which will be manufactured in Italy for use in clinical trials. At present around 35 pharmaceutical companies are similarly working to develop a Covid-19 vaccine.

It is competitive in that people always like to be first but its a friendly competition, Prof Shattock explains. More a race against the virus than each other.

The problem is the virus is winning, coursing across the globe with a speed and severity that has shocked seasoned virologists. At a press conference on Friday afternoon, Dr Michael Ryan, head of the World Health Organisation emergencies programme, warned of a "major funding gap" for potential vaccines. Even if one does appear early next year, that would be scant defence against the months of unprecedented global devastation we are warned could lie ahead.the WHO's Dr Mike Ryan said that there is a major funding gap for potential vaccines against the virus.Even if a vaccine appears early next year, that would be scant defence against the months of unprecedented global devastation we are warned could lie ahead.

Another concern is Covid-19 has already evolved into two major lineages - dubbed L and S types. The older S-type appears to be milder and less infectious, while the L-type which emerged later, spreads quickly and currently accounts for around 70 per cent of cases. Health experts fear the virus could hit Britain in multiple waves meaning new vaccines might not work against mutated strains.

Accordingly this is a war now being waged on multiple fronts. Alongside vaccine development, researchers are focusing on antivirals to treat patients (of which currently there are none) either by hoping to create new antivirals in record time or dust off old drugs developed for previous outbreaks. At the same time scientists are working to develop better rapid diagnostics in order to more efficiently test large-scale populations for the virus something that has been hailed in South Korea for preventing its further spread.

In China alone, about 300 clinical trials are attempting to treat patients with standard antiviral therapies, while in the west attempts are being made to repurpose old treatments for Ebola, malaria and HIV to see if they can impact against Covid-19.

Many see a drug called remdesivir, originally developed to treat Ebola and production of which is currently being ramped up by the US pharmaceutical firm Gilead, as a frontrunner and one of the very few antivirals that has a reasonable prospect of helping patients in the near-term.

Should these old drugs fail then the scientific community will be required to think more creatively and it is here where a 39-year-old US tech genius called Jacob Glanville steps in. Born in Guatemala to US hippy ex-pat parents, Glanville is already something of an outlier in a field that is dominated by the pharmaceutical giants. But he is currently being backed by the US government to embark on super-accelerated engineering of antibodies produced during the SARS outbreak of 2002 to see if they might apply to the latest member of the same family of coronavirus.

It is a process that Glanville, chief executive of Distributed Bio, describes as taking five billion pieces of spaghetti and throwing them all against a wall to see what sticks.

Glanville appears in a recent Netflix series, Pandemic, which focused on a separate branch of his pioneering work to develop universal influenza vaccines. He is described as the David to the influenzas Goliath andwith Covid-19 he faces a similarly outsized challenge. Should his attempt to discover an antibody which reacts against Covid-19 prove a success then he says it is conceivable that a drug could be ready by September.

Even that would be too late for many. By next month, he is predicting 40,000 cases of Covid-19 in his home state of California overwhelming intensive care wards.

There is an enemy here and that is the virus, he says. We all want to protect our families.

Scientists across the world are indebted to their Chinese counterparts who on January 10 openly published the genetic sequencing of Covid-19. Organisations such as Cepi, set up in response to the lack of scientific progress during the Ebola crisis, are funding the rapid research of vaccines while governments are also pouring money into development.

At the University of Toronto, Sachdev Sidhu, a professor of molecular genetics, is leading a team part-funded by the Canadian federal government to develop successful antivirals. His work involves a pioneering technique he has developed to test millions of molecules stored in a library to assess whether one contains the crucial protease inhibitor for Covid-19 (which would help neutralise the virus).

He describes the rapid global progress that has been made so far as a triumph of science with the work that took a decade to understand the HIV virus being done in a month.

While he works on exploiting its Achilles heel, he says it is best to block out the human impact of Covid-19. You cant get emotional. That doesnt help. Our job is to figure out what it is, how it works, and shut it down.

Dunfermline-born researcher Kate Broderick is senior vice president of research and development at the US firm Inovio and admits she has averaged about two hours sleep each night since the virus first emerged.

As a scientist and also a mum Im extremely worried, says the 42-year-old. In my wildest nightmares I couldnt have predicted two months ago, one month ago, or even a week ago, that we would be in the situation were in today.

The day the Chinese authorities released the full genetic sequence of Covid-19, her company (which had previously worked on vaccines for the likes of Ebola, Sika, MERS and Lassa fever) designed a vaccine in just three hours and immediately started manufacturing small batches to test in the laboratory.

Inovio plans to begin testing the vaccine on humans in the US next month with parallel trials running in China and South Korea and will then move into phase two (of three) clinical trials experimenting on a wider group of people. She declines to put a timeline on when a vaccine might be ready but admits it will require at the very least tens of millions dollars in funding. Her team has been given a $9 million grant from the Coalition for Epidemic Preparedness Innovations, an initiative backed by Bill Gates, but far more investment is needed to make any vaccine widely available.

The crippling costs involved are where previous vaccines have faltered but with Covid-19 already proving to be like no virus the world has ever seen, precedent currently is being left by the wayside.

This virus is absolutely remarkable to me, she says, commenting on the speed and scale of the contagion. And I do think people should be taking this extremely seriously.

Back on the streets of London, thousands of volunteers are currently being assessed for their suitability for clinical trials of vaccine or antivirals for Covid-19. Hvivo (a subsidiary of the company Open Orphan) which has developed a rapid testing model has in recent days received 10,000 applications of those wishing to be injected with a close relative of Covid-19 to help discover an effective treatment.

Andrew Catchpole, a virologist and chief scientist at the firm, admits the offer of 3500 per person to spend two weeks in quarantine will be the prime motivation for some. But he detects in the surge in interest a wider appetite to pull together and be a force for societal good.

This is areal human emergency, he says. And a lot of people genuinely want to do their bit.

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The vaccine hunters racing to save the world from the coronavirus pandemic - Telegraph.co.uk

The first case of COVID-19 appeared in Italy on January 30th. A couple of Chinese tourists coming from Wuhan via Beijing were admitted to Spallanzani Hospital in Rome, highly specialised in infectious diseases.

The same day, the Minister of Health Roberto Speranza announced an air traffic embargo for flights coming to Italy from any Chinese city, including the autonomous regions of Hong Kong and Macau, in an attempt to block the spread of the infection.

In the days following the hospitalisation of the Chinese couple in Rome, a few new cases were detected in a group of Italians who were repatriated from the Wuhan region. Experts started to sigh in relief as all cases came from abroad and no local contagion seemed to show up.

Then, quite abruptly, on February 20th at midnight, the Councillor for Welfare in Lombardy, Giulio Gallera, announced that Mattia, a 38-year-old Italian from the small city of Codogno, in Lombardy, was hospitalised for a severe case of atypical pneumonia and tested positive for coronavirus. He had not travelled to China nor had any contact with people coming from Asia. He was tested only because a young anaesthesiologist, faced with the worsening condition of the patient, broke protocol and asked for permission to test a patient with no apparent risk factors. Codogno was the focus of a local outbreak of the disease: new cases were identified in the following days and the whole area was put under strict quarantine for 2 weeks. But it was too late.

As of March 12th, Italy has 15,113 official cases, 1016 deaths and 1258 recovered patients. The whole country is on lockdown. Cities like Milan and Bergamo, in Lombardy, are facing an exponential growth of hospitalised people with COVID-19. Schools, universities, and most shops are closed (all except the ones selling basic goods like food, drugs, electronics, and warehouses) and the National Health System is trying to cope with the flood of patients needing ventilation support. Roberto Cosentini, head of the Emergency Department at Pope John XXIII Hospital in Bergamo, one of the most affected cities, has been living in the hospital for the last 3 weeks: "It's like a wave," he says. "We have now around 60-80 new COVID-19 patients per day coming to the emergency. Most of them are in severe conditions and they arrive all together between 4 and 6 pm. We learnt that the respiratory distress worsens at the end of the afternoon and we now know that we will have to deal with most of the severe cases showing up one after another in a short time, every day." But Italy learnt from the Chinese experience: Italian experts looked at Wuhan's management of the crisis and Foreign Minister Luigi Di Maio asked his Chinese counterpart Wang Yi for assistance with supplies. Other countries in Europe are looking at Italy in order to prepare for SARS-CoV-2,the virus which causes COVID-19.

"There is a huge debate about the way we test for the SARS-CoV-2 virus," explains Giovanni Maga, director of the Institute of Molecular Genetics of the Italian National Research Council in Pavia, in Lombardy. "Many countries test only people with symptoms. At the beginning of the crisis, we decided to test everyone who was in contact with a person infected with the virus and this is what WHO also recommends. But in the long run it became impossible and now we test only symptomatic people with severe impairment."

However, this makes the analysis of the epidemic trends quite challenging. "If you test everybody, you will find more positive cases, with mild symptoms," says Maga. The strategy for testing might heavily influence the visible part of the epidemic: "According to many epidemiologists, other countries could be in the same situation as Italy was a few weeks ago," continues Maga. "But since they do not check asymptomatic people, they just don't know it." The choice of testing strategies is a crucial one for preparedness. "There are pros and cons for any choice, but what is important is to try to be as consistent as possible on the criteria since the beginning of the outbreak," he says.

The COVID-19 outbreak is a stress test for health services. Italy's Health Service, which provides universal coverage for the whole population, is national, but the organisation is distributed to regional health authorities.

When the crisis became evident, the Government regained control of crucial decisions, such as the coordination of intensive care unit availability. Antonio Pesenti, the coordinator of the ICU network in Lombardy and head of the Crisis Unit explains how Italy is trying to cope with the situation. "Since the first days of the outbreak we established a protocol to transfer patients needing ICU for non-COVID-19 diseases to the regions in Central and Southern Italy using the Civil Protection CROSS system. We prefer not to transfer COVID-19 patients because they require special isolation." Italy has around 6000 beds for intensive care, which the government plans to increase to 9000 in the coming weeks, partly by repurposing and refitting operating rooms used for elective surgeries. According to Pesenti, the projected demand of ICU beds is up to 10 times the current availability: "The number of hospitalised patients expected by March 26th, in 2 weeks, is 18,000 just in Lombardy. Between 2700 and 3200 will require intensive care."

To face such a tsunami, Italy is learning from China. Intermediate care units will be opened both in the hospitals and in other areas, such as exhibition pavilions in the Bergamo and Milan Fair. They will be equipped with ventilators coming from China and with special helmets to facilitate non-invasive ventilation support that seems to be very useful for patients who can manage without invasive ventilation. "We need such tools because 33%of the people in intensive care are between 50 and 64 years old: they are fit people who do not have pre-existing conditions. If we put them in invasive ventilation, they occupy an intensive care unit for 2-3 weeks," says Pesenti. "Any alternative is useful to relieve ICUs."

Doctors also had to deal with ethical issues. The Italian College of Anaesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) published guidelines for triage when there's a shortage of ventilatorsto help with decision making in a critical situation. The authors chose "the most widely shared criteria regarding distributive justice and the appropriate allocation of limited health resources" to draw their recommendations. "Informed by the principle of maximising benefits for the largest number, the allocation criteria need to guarantee that those patients with the highest chance of therapeutic success will retain access to intensive care," the document says.

Epidemiological curves are the new weather forecast for citizens in quarantine. And policy makers rely on them to decide new policies for containment. "The available predictive models are based on data we got from China," explains Paolo Vineis, an Italian epidemiologist based at Imperial College in London, who is consulting for the scientific committee supporting the Italian Government in the decision-making process. "They mainly use the SIR model, that consists of three compartments: S for the number of susceptible, I for the number of infectious, and R for the number recovered (or immune) individuals. Any of those components can change during the epidemic, because of the local development. That's why data collection is extremely important for modelling." Italy had to face a challenge due to the regional nature of its health system: different regions used to collect data in different ways, using different templates. Regions like Lombardy, that were overwhelmed by the epidemic, had trouble feeding the databases with all the details, like comorbidities. "Epidemiological analysis needs to be centralised and properly supported to help the decision makers" says Vineis.

At first glance, the death rate from COVID-19 in Italy appears to be much higher than it was in China, but according to experts, this is likely to be due to a combination of several factors, ranging from the testing strategy to the advanced age and comorbidities of most patients. "The average age of deceased patients is over 80 years, but when one looks at the age-stratified data the lethality is very similar to China," explains Giovanni Rezza, epidemiologist and director of the Department of Infectious Diseases at the Higher Institute of Health in Rome, who sits on the scientific committee advising the Italian Government. Based on the analysis of medical records, the first 100 deceased patients had an average of 2.5 concurrent diseases. Still, in the Italian system they are accounted for when calculating the lethality of COVID-19. Another confounding factor is the testing strategy, which was concentrated on people with serious symptoms, worth being hospitalised. Those who had mild symptoms were recommended to stay at home, but were not systematically tested for SARS-CoV-2. "This has likely kept the denominator very low," explains Rezza.

Italian doctors followed the suggestions from China on the use of antiviral drugs that were already tested during the SARS epidemic, but are also working actively for new clinical trials. A phase III clinical trial with remdesivir, an investigational antiviral drug being developed by Gilead Sciences to treat Ebola, is being conducted on patients recruited in the main hospitals like Spallanzani Hospital in Rome, Pavia Polyclinic, Padua and Parma University hospitals and Sacco Hospital in Milan.

The drug is not yet approved for any indication globally but is provided for compassionate use. The US Food and Drug Administration (FDA) granted investigational new drug authorisation to study it in February 2020. The same hospitals will be involved in the trial using the antiviral combination lopinavir/ritonavir as COVID-19 treatment. Paolo Ascierto, from Fondazione Pascale Cancer Institute in Naples, announced on March 10th to have observed good results on two very critical patients receiving tocilizumab, a monoclonal antibody used in rheumatoid arthritis acting on IL6 cytokine and on the spike proteins of the virus. The drug is also used to reduce severe side effects in chemotherapies. After this anecdotal report, a proper clinical trial is being planned.

General practitioners have been hit hard, acting as a first line to identify patients with symptoms suggesting COVID-19. And they are paying a high price for the lack of training, appropriate tools and a proper plan. Filippo Anelli, president of the National Federation of the Orders of Doctors and Dentists (FNOMCeO) sent a letter to Prime Minister Giuseppe Conte asking permission to stop all outpatient health activities. "By March 11th, 50 doctors were infected by the virus and three of them died," he wrote. General practitioners face a shortage of protective tools like gloves, masks and disposable scrubs. And even when they have them, they are not trained to properly manage potentially infected clothes and tools, said Claudio Cricelli, president of the Italian Society of General Practice (SIMG).

Since the end of February, the hospitals in Northern Italy have been reorganised. Most of them have special areas for COVID-19 patients. In Milan, some hospitals are working as 'hubs' to collect patients with the same disease. Most of the outpatient clinics have been closed and non-urgent visits are postponed, to make resources available for the most severe cases. This was a good strategy to increase the availability in hospitalwards but a very challenging and stressful burden on general practice. Protocols for patients with flu-like symptoms have been established by the Health Authorities. The first evaluation is done by telephone or e-mail. In case of symptoms suggesting a possible COVID-19 infection, the patient is invited to stay home, isolated from the rest of the family. The GP monitors the evolution of the symptoms while avoiding as much direct contact as possible with these patients. In case of respiratory distress, a special hotline number has been set up to dispatch a team that can transfer the patient to the hospital. "This is the only way to guarantee a proper care of the patients with other diseases," says Cricelli.

A lockdown like the one Italy is experiencing, together with continuous news coverage on the epidemic risks, are not without mental health risks. On February 26th, the Lancet published a paper by Samantha Brooks and colleagues from King's College in London, reviewing studies on the psychological effects of quarantine and how to reduce it. "Most reviewed studies reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger.

Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma," the review said. "Some researchers have suggested long-lasting effects. In situations where quarantine is deemed necessary, officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Appeals to altruism by reminding the public about the benefits of quarantine to wider society can be favourable." Enrico Zanalda, president of the Italian Society of Psychiatry (SIP) confirms: "Patients with depression and OCD tend to relapse," he says. "And the general level of anxiety is very high." Children and adolescents are particularly at risk of post-traumatic stress disorder, according to the review. "A proper planning for psychiatric support and for the diagnosis of PTSD is necessary."

When the lockdown was extended to the whole country, the association of medical oncologists (AIOM, Associazione Italiana di Oncologia Medica) published a statement inviting specialists to reschedule all 'non-urgent' activities, such as cancer screenings and follow-up visits for successfully-treated patients, and in some cases adjuvant therapy.

"The rationale is to make sure that the oncology wards, especially in general hospitals that are also treating COVID-19-positive patients, can respect all the safety procedures, including social distancing, for cancer patients who are being treated or may need to start a new treatment," explains vice-president of AIOM Saverio Cinieri, who is co-director of Milan's European Institute of Oncology (IEO). "This also reduces the social interactions of immunocompromised persons who are at higher risk both of infection and of developing more serious symptoms." AIOM recommended contacting patients via phone or e-mail, to verify which patients may need to be visited, and is developing an app for video consultations.

Daniela Ovadia is a writer for Agenzia Zoe.

Brooks SK, Webster RK, Smith LE, Woodland L, Wessely S, Greenberg N, Rubin GJ. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020 Feb 26. pii: S0140-6736(20)30460-8. doi: 10.1016/S0140-6736(20)30460-8. [Epub ahead of print]

Adapted from Univadis from Medscape.

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COVID-19: What Can the World Learn From Italy? - Medscape

Researchers from the University of Torontos Donnelly Centre for Cellular and Biomolecular Research are working on developingantivirals that can combat thenovel coronavirus outbreak.

Led bySachdev Sidhu, a professor of molecular genetics, the team will apply their protein engineering technology to identify promising therapeutics.

We have diverse expertise on our team from across U of T and the University of Manitoba, which is renowned for its virology research, and we have already demonstrated that we can engineer proteins that inhibit MERS, a related coronavirus, says Sidhu, who, in addition to the Donnelly Centre holds cross appointments in the Faculty of Medicine and at the Institute of Biomaterials and Biomedical Engineering. We will now expand on this work to design therapeutics for COVID-19.

The team recently received almost $900,000 over two years from the federal government through a rapid funding competition announced on Feb. 10 to address the COVID-19 outbreak.

Sidhu is collaborating withRoman Melnyk, a senior scientist at the Hospital for Sick Children and assistant professor of biochemistry at U of T, andBrian Mark, a structural virologist and professor at the University of Manitoba. In a 2016 proof-of-principle study withMarjolein Kikkert, a virologist at Leiden University in the Netherlands, they applied a protein engineering pipeline developed by Sidhus team to create proteins that inhibit a related coronavirus that caused the Middle East Respiratory Syndrome (MERS) outbreak in 2012.

Wei Zhang, then a post-doctoral researcher in Sidhus lab and now an assistant professor at the University of Guelph,received a national innovation award for this research.

The researchers now plan to use the same strategy to battle the coronavirus behind the COVID-19global health crisis, which the World Health Organization today declared a pandemic.

Since the outbreak began in China in late 2019, the virus has spread to every continentexcept Antarctica, with more than 120,000 confirmed cases and more than 4,000 deaths, according to the latest figures. And while researchers around the world are racing to develop a vaccine, that is only a part of the solution, Sidhu says.

Even if a vaccine becomes available, not everyone is going to get vaccinated, says Sidhu. We see that with the flu the vaccination rates are far from 100 per cent. Should the virus become endemic and end up circulating in the population like the flu, medicines that stop the virus from replicating in an already infected person will be as important as vaccines, which prevent infection, according to Sidhu.

Jacky Chung, a research associate in the Sidhu lab, will spearhead the project by first engineering proteins that can inhibit the virus. The team will then search for small molecules that behave in the same way since they are easier to develop into therapeutics than proteins.

It's important to get the therapeutic inside the cells, which is where the virus replicates, says Chung. And small molecules can get into cells much more readily than proteins, which are much larger.

At the heart of the approach lies a protein called ubiquitin, named for being present in all plant and animal cells. Ubiquitin is an essential part of the cellular machinery that the virus hijacks for its own benefit. Upon infection, the virus releases proteins that interfere with human ubiquitin and allow it to bypass the hosts defence system and spread in the body.

To block the virus, the researchers will create synthetic ubiquitin variants (UbV) that thwart rather than aid its ability to replicate. By analyzing the molecular structures of different UbVs bound to the viral protein, they will gain clues into the kinds of small molecules that are most likely to be effective against the virus.

Sidhu says that, within two years, they should have candidate molecules that could be developed into therapeutics. We know there are literally armies of medicinal chemists and various companies that could then optimize the molecule into a drug that can be given to humans, says Sidhu who was previously at pharmaceutical giant Genentech and has founded six startups since joining the university.

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U of T researchers hunt for antivirals to treat COVID-19 patients - News@UofT

The genie is out of the coronavirus bottle and has officially arrived in Minnesota.

Although this particular genie is not easily seen based on clinical symptoms, fortunately, science has provided us with genie glasses. If you believe in that kind of thing you know science.

From a testing standpoint, viruses have always been hard to detect. Theyre difficult to grow in a culture, like we often do with bacteria, and checking for antibodies against a specific virus is often imprecise, particularly early in an infection, when the body hasnt had enough time to produce antibodies.

Then came reverse transcription-polymerase chain reaction (RT-PCR) testing, a lab technique that allows us to identify fragments of genetic material (RNA in the case of coronavirus) in a body fluid sample. Like giving a search-and-rescue dog a sniff of the victims clothing, a specific RT-PCR test has to be developed for each specific viral or bacteria: It has to be told what its supposed to be looking for. (Visit tinyurl.com/molecular-assays for more information.)

RT-PCR testing isnt exactly new, but like so many other things in modern life, technological advances have made it much more accessible and affordable. In scientific terms, its a damn good test. It rarely misses a virus thats there, and it rarely mistakes another virus (or something else) for the virus it was seeking. It wont mistake influenza or strep throat for coronavirus. RT-PCR testing isnt perfect, but its the best weve ever had.

Ideally, we would have made a lot of RT-PCR genie glasses before the genie actually arrived on our shores. The delay wasnt because we couldnt figure out the gene sequence of this new coronavirus. In a tribute to the stunning sophistication of modern genetics, scientists in China released the viruss mug shot its entire genome sequence on Jan. 10, a month after they became aware of the infection (or so we are told, China being China).

An aside here for freaky cool genome science: Because RNA viruses mutate at a somewhat predictable rate, scientists can use mutations to estimate the age of a virus, like counting growth rings on a tree stump. A young virus will have few if any extra mutations. Scientists believe the COVID-19 virus was born no earlier than Oct. 30, 2019, and no later than Nov. 29th (tinyurl.com/coronvirus-genome).

This genome map provides the template for developing both vaccines and RT-PCR testing. When Germany flew 126 of its citizens home from Hubei province on Feb. 1, they PCR-tested each of them. Two of the 126 tested positive, and they were not among the 11 people with symptoms.

In medicine, we are trained to avoid testing in situations where the likelihood of finding anything is low. Routine testing for rare or low-likelihood diseases, or in healthy people, just wastes a lot of money and generates more testing for those inevitable cases where the test returns falsely positive. It rarely saves lives. Men do get breast cancer, but not at a rate that justifies routine mammograms.

All that is different with the COVID-19 virus.

At the beginning of the outbreak, when the virus was thought to be isolated to a single province in China, travel history screening was an incredibly cheap and powerful test. But as the virus continues on its worldwide tour, travel history will become an increasingly nondiscriminating test (example: Have you or a close contact traveled to any one of the following 30-and-counting states?). And thanks to widespread RT-PCR testing in other countries, we now know that our other test signs and symptoms of an upper respiratory infection has been a crude one from the beginning. It appears that a majority of those infected have either no symptoms or minor symptoms and yet remain capable of passing the virus to others. Never mind that we are still in the midst of our winter cold and flu season, where COVID-19 impostors abound.

So now that we know travel history and signs/symptoms are no more than beer-goggle-quality tests, its time to break out the genie glasses: RT-PCR. If the airline industry alone stands to lose $100 billion, it could offer the Centers for Disease Control and state and private labs $20 billion to rev up RT-PCR production, and still save itself $80 billion.

I asked Joanne Bartkus, director of the Minnesota Department of Healths Public Health Laboratory, exactly how does a RT-PCR lab rev up capacity? Is it more machines, more reagents (substances used in chemical reactions), more staff?

Yes to all of those things, she replied as she went on to explain the COVID-19 virus testing process.

Somewhat surprisingly, the RT-PCR test itself is the simplest part of the process: The samples are placed in a machine called a thermal cycler, and in 2.5 fully automated hours, the data is ready to be interpreted. The rate-limiting, most-tedious part of the process is getting the specimens ready for the cycler.

As test kits arrive from around the state, each sample must be accessioned: Information such as patient identifiers, location and ordering physician must be logged into the computer, and the sample must be tagged with a bar code. It might sound mundane, but imagine the implications of attributing a particular test result to the wrong patient. This is serious stuff.

Then comes the process of extracting the viral RNA out of the immunological fog of war found in any snot sample. In the beginning, the RNA extraction process certified by the CDC was labor-intensive.

It really limited the number of samples we could turn around in a day, and thats one of the reasons that initial testing was limited to individuals with known risk factors, Barkus told me. But as we move toward community surveillance, well need higher throughput extraction methods, and who could ever argue with higher-throughput extraction methods? Good news: On the day I spoke with Barkus, the CDC had just greenlighted a technical change that will allow 96 tests to be done in a platform that previously handled 24.

So things are heating up at MDH labs, and elsewhere, too, as the Mayo Clinic and private labs like Quest Diagnostics and LabCorp have all recently rolled out their own RT-PCR testing. Under normal circumstances, every new RT-PCR would need to be tested and approved by the FDA, but under emergency conditions like COVID-19, the FDA can loosen the reins and allow labs to internally validate their new test and get the FDA seal of approval later.

All of that, and the prospect of broader testing, is welcome news. Then well have some real data to guide our containment strategy, rather than hunches and case reports, or the difficult, labor-intensive, gumshoe detective work by public health workers.

And then well have a much better chance of putting this genie back in the bottle.

Craig Bowron is a physician and writer in the Twin Cities. On Twitter: @billcarlosbills.

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OPINION EXCHANGE | The testing that can help us put the coronavirus genie back in the bottle - Minneapolis Star Tribune

Theres a lot that scientists know about the benefits of zinc. The essential nutrient boosts the immune system, heals wounds and supports brain development in children. We even need zinc to smell and taste. Dive a little deeper, however, and the real mysteries of zinc emerge.

One of them how zinc is distributed to tissues and cells is the root of Prof. Shannon Kellehers research, which aims to reveal the role that zinc plays in the development of inflammatory bowel disease and food allergies.

Zinc is critical for intestinal health, but we have little information on what it actually does in the intestine, says Kelleher, who is based in UMass Lowells Biomedical and Nutritional Sciences Departmentin the Zuckerberg College of Health Sciences. Our goal is to understand how zinc affects intestinal function, the gut microbiome and the risk for intestinal disease.

We asked her to explain.

Q. What do we know about zinc and its effect on intestinal health?

A. We know that the right amount of zinc is critical to intestinal health. If we consume too much or too little zinc, the intestinal barrier falls apart. An over- or underabundance of zinc can cause shifts in the gut microbiome, and cause diarrhea and inflammation.

The only way that people can consume too much zinc is through supplements. If you get zinc only through foods in your diet, then you really cant consume toxic amounts. However, if you only rely on your diet, then you may not be consuming enough. So finding the right balance is important.

Q. Is zinc deficiency a big problem?

A. One study from the National Institutes of Health shows that 35 to 45 percent of adults over 60 years old had lower-than-average zinc intakes. Scientists believe that about 7 to 10 percent of the U.S. population is severely lacking in the nutrient. Women of reproductive age are most likely moderately zinc-deficient due to menstruation and not eating the right foods. Symptoms of too little zinc include dry and itchy skin, loss of hair, reduced ability to taste food and a compromised immune system that leads to more colds.

Q. How much zinc should we be consuming?

A. The recommended daily allowances for zinc are 11 mg for men and 9 mg for women. Foods high in zinc include red meat, oysters, poultry, fish and some fortified breakfast cereals. But since excess zinc is also not healthy, dont overdo it with supplements.

Q. Why is it important to find out how zinc travels through our bodies and cells?

A. If we knew how zinc gets into our cells, where it goes in our cells and what it does, then we could use this information to develop new therapies to fight a variety of diseases. These could include new drugs, delivery systems or personalized dietary recommendations.

Q. What else could your research results be used for?

A. Our research could also inform personalized nutrition. I teach an undergraduate course about an emerging field called nutrigenetics. We are now able to sequence your DNA and, based on your genetic blueprint, assess your risk for nutritional disorders and develop personalized diets that match your genetics. It helps to understand why individuals who eat similar diets can have different health outcomes. Your genetics play a crucial role in how you respond to what you eat.

Q. How does your work differ from nutritional science?

A. Nutritional science is often thought of as studies that look at how diet and foods affect human health and the risk for disease. The type of research we do is referred to as molecular nutrition. My research dives a little deeper to understand how specific nutrients in this case, zinc affect cellular and molecular processes that then cause the positive or negative effects we see in the body.

Read more from the original source:
The Role of Zinc: It's More Important than You Think - UMass Lowell

Researchers from the University of Torontos Donnelly Centre for Cellular and Biomolecular Research are working on developing antivirals that can combat the novel coronavirus outbreak.

Led by Sachdev Sidhu, a professor of molecular genetics, the team will apply their protein engineering technology to identify promising therapeutics.

We have diverse expertise on our team from across U of T and the University of Manitoba, which is renowned for its virology research, and we have already demonstrated that we can engineer proteins that inhibit MERS, a related coronavirus, says Sidhu, who, in addition to the Donnelly Centre holds cross appointments in the Faculty of Medicine and at the Institute of Biomaterials and Biomedical Engineering. We will now expand on this work to design therapeutics for COVID-19.

The team recently received almost $900,000 over two years from the federal government through a rapid funding competition announced on Feb. 10 to address the COVID-19 outbreak.

Sidhu is collaborating with Roman Melnyk, a senior scientist at the Hospital for Sick Children and assistant professor of biochemistry at U of T, and Brian Mark, a structural virologist and professor at the University of Manitoba. In a 2016 proof-of-principle study with Marjolein Kikkert, a virologist at Leiden University in the Netherlands, they applied a protein engineering pipeline developed by Sidhus team to create proteins that inhibit a related coronavirus that caused the Middle East Respiratory Syndrome (MERS) outbreak in 2012.

Wei Zhang, then a post-doctoral researcher in Sidhus lab and now an assistant professor at the University of Guelph, received a national innovation award for this research.

The researchers now plan to use the same strategy to battle the coronavirus behind the COVID-19 global health crisis, which the World Health Organization today declared a pandemic.

Since the outbreak began in China in late 2019, the virus has spread to every continent except Antarctica, with more than 120,000 confirmed cases and more than 4,000 deaths, according to the latest figures. And while researchers around the world are racing to develop a vaccine, that is only a part of the solution, Sidhu says.

Even if a vaccine becomes available, not everyone is going to get vaccinated, says Sidhu. We see that with the flu the vaccination rates are far from 100 per cent. Should the virus become endemic and end up circulating in the population like the flu, medicines that stop the virus from replicating in an already infected person will be as important as vaccines, which prevent infection, according to Sidhu.

Jacky Chung, a research associate in the Sidhu lab, will spearhead the project by first engineering proteins that can inhibit the virus. The team will then search for small molecules that behave in the same way since they are easier to develop into therapeutics than proteins.

Its important to get the therapeutic inside the cells, which is where the virus replicates, says Chung. And small molecules can get into cells much more readily than proteins, which are much larger.

At the heart of the approach lies a protein called ubiquitin, named for being present in all plant and animal cells. Ubiquitin is an essential part of the cellular machinery that the virus hijacks for its own benefit. Upon infection, the virus releases proteins that interfere with human ubiquitin and allow it to bypass the hosts defence system and spread in the body.

To block the virus, the researchers will create synthetic ubiquitin variants (UbV) that thwart rather than aid its ability to replicate. By analyzing the molecular structures of different UbVs bound to the viral protein, they will gain clues into the kinds of small molecules that are most likely to be effective against the virus.

Sidhu says that, within two years, they should have candidate molecules that could be developed into therapeutics. We know there are literally armies of medicinal chemists and various companies that could then optimize the molecule into a drug that can be given to humans, says Sidhu who was previously at pharmaceutical giant Genentech and has founded six startups since joining the university.

View original post here:
University researchers hunt for antivirals to treat COVID-19 patients - Mirage News

The mammals of New Zealand have long posed a threat to native species. The Predator Free 2050program is an effort to rid the island of these invaders including using the tools of CRISPR-based genome editing to create a gene drive to jumpstart extinctions.

Its a very bad idea.

In the 1993 film Jurassic Park, mathematician Ian Malcolmlistens to arrogant dinosaur daddy John Hammond describe the islands supposedly all-female populations of the giant reptiles:

John, the kind of control youre attempting simply is its not possible. If there is one thing the history of evolution has taught us its that life will not be contained. Life breaks free, it expands to new territories and crashes through barriers, painfully, maybe even dangerously, but, there it is Im simply saying that life, uh finds a way.

The wise Dr. Malcolm may prove prescient when it comes to using gene drive technology to get rid of pesky species.

Today reptiles, albeit smaller ones than dinosaurs, are among the threatened natives of New Zealand. Prior to the arrival of people, only bats and marine species represented class Mammalia, except for a few archaic types a few million years ago. Then the Mori people introduced Polynesian rats and dogs in about 1250 CE, and Europeans five centuries later contributed mice, pigs, more rats (ship stowaways), possums, weasels, stoats, and ferrets. Native birds, reptiles, invertebrates, snails, insects, and even the forest canopies began to lose out in the competition for natural resources and to predation.

The New Zealand government painted the newcomers as pests, interlopers, invaders. Introduced predators: the bad guys, states one pamphlet.

In a simpler and perhaps more violent time, pests might have been shot, drowned, or poisoned. But a 2003 paper fromAustin Burt, a selfish gene proponent from Imperial College, London, proposed the concept of a gene drive.

A gene drive harnesses one of the ways that cells repair DNA, called homing, that snips out one copy of a gene and replaces it with a copy of whatever corresponding gene variant (allele) is on the paired chromosome. It would be like cutting out a word in this sentence and replacing it with a copy of the word below it. If done to a gene that affects fertility in a fertilized ovum aka the germline the intervention can lead, within a few generations, to mass sterility and a plummeting population a gene drive towards extinction.

A gene drive skews Mendelian inheritance. Instead of one of a pair of genes coming from the father and one from the mother, both copies are from one parent. In the language of genetics, the intervention can turn a heterozygote (2 different copies of a gene) into a homozygote (2 identical copies). Nature does this in several ways, but the tools of CRISPR-Cas9, first described in 2012,offer a faster route to a gene drive, and can target several genes at once.

Visions of vanquishing the mosquitoes that carry the malaria parasite or zika virus dampened initial scrutiny of gene drives. In 2016, the National Academies of Sciences, Engineering, and Medicine (NASEM) released a 200+ page reportthat discussed reasons to proceed with caution, but endorsed continued laboratory experimentation as well as limited field trials of gene drives.

In 2017, a short paper in Science responded to the NASEM report with Guiding principles for the sponsors and supporters of gene drive research. Ill return to the new recommendations after a trip down biotech memory lane what distinguishes this blog from the clonal regurgitations of aggregated science news.

I was in graduate school in 1976 when recombinant DNA technology was under heated debate. My mentor dubbed the rising public fear of genetics and biotech the triple-headed purple monster mindset.

In February 1975, a whos who of molecular biologists had convened at Asilomar, on Californias Monterey peninsula, to explore the implications of combining genes of two species, starting with insertion of a bacterial gene into a cancer-causing virus.

The 150 scientists discussed fail-safe measures to control recombinant organisms. The Asilomar conference begat guidelines for physical containment via specialized hoods and airflow systems and biological containment to weaken organisms so that they couldnt survive outside the lab.

Despite initial concerns, recombinant DNA technology turned out to be safer than expected, and it spread to industry fast and in diverse ways. A handful of important drugs, starting with human insulin, became safer and more abundant thanks to recombinant DNA techniques. In the agricultural arena, weve been eating GMO foods for decades, although the containment hasnt exactly worked, as the example of canolagrowing along the roadways of North Dakota illustrates.

In 1985geneticists met again to assess the safety, feasibility, and value of another huge project: sequencing the human genome. I doubt any of them could have foreseen a time when we would carry our genome sequences on our smartphones.

Back then, researchers packed a room at the Cold Spring Harbor Laboratory on New Yorks Long Island. At first those against outnumbered those for 5:1, ticking off their fears: shifting research from inquiry-based experimentation to data dumps, comparing the sequencing effort to climbing Mt. Everest just because its there, and diverting funds to fight HIV/AIDs. Finally, the National Academy of Sciences jumped in to debate both sides, and in 1988, Congress authorized the National Institutes of Health (NIH) and the Department of Energy to start sequencing. Foreshadowing of gene drives?

On the reproductive front, the first test-tube baby, Louise Joy Brown, was discussed as if she were a space alien until her ordinariness became apparent, and today more than 5 million folkshave been born beginning with in vitro fertilization. Similarly, one of the first families to speak to the media about their use of preimplantation genetic diagnosis (PGD) to select an embryo who would one day provide stem cells to save his sister was vilified PGD is now a common adjunctto IVF to select the healthiest embryos.

But a gene drive doesnt provide information, drugs, improved cabbages, or babies. It has the potential to tilt the biosphere.

When the inventors of a new biotechnology pull a 180 on applications of their brainchild, its time to take notice. Thats what Kevin Esvelt from MIT and Neil Gemmell from the University of Otago, Dunedin, New Zealand, did in their Perspective in the November 16, 2017 issue of PLOS Biology,Conservation demands safe gene drive. They shout out a warning.

Back in 2014, Esvelt and his colleagues suggested using self-propagating CRISPR-based drive systems for conservation.They also discussed variations on the theme, including a daisy drive systemthat sets up a series of interventions, like a series of locks on a bank vault, and the trojan femaletechnique that sneaks male infertility mutations into mitochondrial DNA.

Second thoughts about deploying gene drives were perhaps already lurking in the minds of people familiar with the nature of DNA, as Jurassic Parks mathematician intuited. DNA changes! Thats why its the genetic materialand why the idea that we arent still evolving is absurd.

A gene swapped into a rat or a possums genome to squelch fertility can change. Such spontaneous mutation happens because of the nature of the DNA molecule. Each of the 4 types of DNA bases exists, when unlinked, fleetingly, in a slightly alternate form. If a DNA replication fork should happen down the old double helix and catch a clinging base in its rare form, a base pair can be replaced with a different one creating a new allele. Its simply the chemistry of life.

A gene drive also assumes that one allele is predominant in a population, and that isnt necessarily the case. What if the harnessed repair mechanism lassos another variant of that gene, a rarer one? Different outcome.

The inherent changeability of DNA alerted the scientists at Asilomar and Cold Spring Harbor. We can never predict all risks, about anything, and surprises have consequences. Who would have thought wed all have to haul off our boots when checking in at the airport thanks to a lone shoe bomber?

DNA also flits from cell to cell, aboard elements called transposons or, more colorfully, jumping genes. Thats how bacteria share sets of antibiotic resistance genes. What if a CRISPR gene drive harpoons something other than its intended target? Goodbye beloved kiwi birds rather than the weasels that eat their eggs? What if a targeted species hitches a ride to other islands and continents before it eliminates the local population and extinguishes itself? Drs. Esvelt and Gemmell write.

The bottom line: gene drives may create the equivalent of the very thing they are being deployed to fight: invasive species. Write Drs. Esvelt and Gemmell of their former approval of gene drives for conservation, We now believe that inclusion was a mistake: such drive systems lack control mechanisms and are consequently highly invasive.

And so also in November of 2017, Dr. Esvelt, with Charleston Noble, Ben Adlam, George Church, and Martin Nowak from Harvard, published Current CRISPR gene drive systems are likely to be highly invasive in wild populations in bioRxiv. Their paper warns against even limited field tests because of mitigating factors, including scenarios as yet unimagined. They did a mathematical analysis to counter recent reports that downplayed the potential ecological danger of a gene drive by claiming that natural resistances will emerge to block the spread to untargeted wild populations. Sound familiar? Contrary to the National Academy report on gene drive, our results suggest that standard drive systems should not be developed nor field-tested in regions harboring the host organism, they conclude.

The guiding principles for the sponsors and supporters of gene drive research published in todays Science, from Claudia Emerson, Stephanie James, Katherine Littler, and Filippo Randazzo, are dj vu all over again for those of us who recall Asilomar circa 1975. Perhaps the principles are attempting to prevent the public outcry at town hall meetings and destruction of some GM crops (most notablyice minus bacteria on plants)that accompanied the entry and acceptance of recombinant organisms.

According to the principles, gene drive experiments should

have goals of social value and the public good take biosafety measures, comply with regulations, and conduct ecological risk assessment have transparency and accountability, with sharing of data engage the public

Dr. Emerson and her colleagues make a good case for the need to find new ways to limit the spread of vector-borne infectious diseases like malaria and zika. Lets hope that gene drive technology goes the successful way of recombinant DNA technology and not the way of GMO escapees in agriculture or in the hands of bioterrorists.

Lets listen to Dr. Malcolm.

[Editors note: Kevin Esvelt of MIT commented on this article on PLOS Blogs. He wrote:

Respectfully, this somewhat mischaracterizes our point.

We think it unwise to build gene drive systems capable of spreading indefinitely beyond the target population.

Because standard self-propagating gene drive systems can spread indefinitely, we think they should only be developed and used for a handful of applications such as malaria eradication, for which the target population includes every Anopheles gambiae s.l. mosquito in Africa.

In contrast, we feel that self-propagating gene drive should not be used for invasive species control because there is always a native population that could be affected.

Instead, we should focus on developing locally-confined drive systems that cannot spread indefinitely. Local drive systems could enable each community to make decisions about its own environment without necessarily affecting people far away. There are several forms that have been modeled or are under development, including Trojan female, killer-rescue, daisy drive, and threshold drive, and hopefully still better ones will be invented.

A final note: there is essentially no risk that transposons, a natural and nearly ubiquitous form of gene drive, will cause a CRISPR-based drive system to spread in another species. The reason is that CRISPR is highly specific and the target DNA sequences would not be present in the genome, so the system would not function exactly the same way that laboratory genome editing fails when there is a strain-specific mutation in the CRISPR-targeted sequence.

Life usually does find a way eventually; the question is how long it will take. We have a remarkable opportunity to address many serious ecological problems using natures own language. With care, humility, and collective scrutiny as obtained through open research and broadly inclusive societal discussions we have a chance to do so wisely. Sometimes, that means walking away from an exciting idea.]

Ricki Lewis is the GLPs senior contributing writer focusing on gene therapy and gene editing. She has a PhD in genetics and is a genetic counselor, science writer and author of The Forever Fix: Gene Therapy and the Boy Who Saved It, the only popular book about gene therapy. BIO. Follow her at her website or Twitter @rickilewis

A version of this article previously appeared on the GLP on December 7, 2017and was originally published on PLOS Blogs website as An Argument Against Gene Drives to Extinguish New Zealand Mammals: Life Finds a Way.

Link:
The risks of using gene drives to get rid of 'pesky species' - Genetic Literacy Project