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While several vaccine developers have issued statements looking into the future -- setting possible timetables for study completion and vaccine manufacturing -- the ethicists and doctors say one group in particular stands out as being the most aggressive in painting the rosiest picture: the University of Oxford in England.

Oxford has recently walked back some of its optimism, but for months, it set a tone that its vaccine was the most promising, without any solid evidence that this was based in fact.

First, in a field fraught with potential failure, two Oxford researchers stated that they're "80% confident" that the vaccine will work, and that they might be able to complete large-scale clinical trials in just six weeks, a fraction of what some other vaccine companies estimate they can do.

Second, some experts have accused Oxford scientists of spinning results of their vaccine research in monkeys to make the vaccine look more powerful than it is, which Oxford denies.

Third, one leader in the Oxford team has gone so far as to denigrate other teams trying to get a Covid vaccine on the market, calling their technology "weird" and labeling it as merely "noise." Such name-calling is highly unusual and aggressive among scientists.

Dr. William Schaffner, an infectious disease expert at Vanderbilt University Medical Center, said he "sat straight up" when he heard one of the Oxford scientists talk about how well their vaccine is progressing.

"Some of us in the scientific community here in the US have been a little surprised at the sprightly competitiveness of some of the comments from our colleagues at Oxford. We don't usually see that in public pronouncements," said Schaffner, a longtime adviser to the US Centers for Disease Control and Prevention. "We've been grumpy with our national political leaders about providing inaccurate information, and we should hold scientific leaders to those same standards."

Dr. Paul Offit, a University of Pennsylvania pediatrician who developed a vaccine for rotavirus, agrees.

"At this point, the Oxford researchers have no idea whether they have something or not," Offit said. "You just get so tired of this 'science by press release.' "

But one of the leaders of the Oxford research team says he and his colleagues are just being straightforward.

"We're going to be first to finish," said Dr. Adrian Hill, one of the lead Oxford researchers. "How can you criticize us for giving our honest opinion?"

On April 16, CNN's Erin Burnett pressed Hill on his predictions.

"Do you have any concern that you're being overly optimistic, that that just seems, for lack of a better word, too good to be true?" Burnett asked.

"We don't think so," Hill answered.

Weeks later, Hill would have to backtrack on his own optimism, warning against "over-promising" and ratcheting down his expectations of success.

Most vaccine efforts will fail

Five Chinese companies have vaccines in human trials. Oxford is the only one in Europe. Worldwide, there are 114 more candidates in pre-clinical trial stages.

Vaccine development is a risky business. Sometimes even ones that get to large-scale clinical trials fail.

Even so, scientists from various experimental vaccine teams have made public statements about their interim results.

On May 18, Massachusetts-based Moderna put out a press release declaring that results in eight human study subjects showed that its vaccine "was generally safe and well tolerated."

Moderna CEO Stphane Bancel referred to the results as "positive interim Phase 1 data" and that "the Moderna team continues to focus on moving as fast as safely possible to start our pivotal Phase 3 study in July."

Moderna's stock soared, and the company was criticized for announcing results on just eight study subjects when the data hadn't even been peer-reviewed or published in a scientific journal.

The Oxford scientists have voiced less caution, frequently appearing in the media and making public proclamations that theirs will likely be successful and first.

On April 11, lead researcher Sarah Gilbert told The Times of London that she was "80% confident" that the Oxford vaccine will work.

Her own colleague questioned that statement a few weeks later.

But Hill, the director of the Jenner Institute at Oxford, which specializes in vaccine development, dismissed Bell's comments.

"It's like asking me about a renal drug, asking John about a vaccine. It's not what he does. It's what Sarah does every day and has done for 25 years," Hill said.

Bell did not respond to CNN's multiple requests for comments.

On May 19, Hill told CNN he stood by Gilbert's estimate.

"We did not exaggerate anything. We're not backtracking at all from the 80%," he said.

The wisdom of Spider-Man

Inovio and Moderna have said they expect their large-scale clinical trials, known as Phase 3 trials, to last around six months. Pfizer hasn't given a timetable for its Phase 3 trial.

On May 19, Hill told CNN that his group is planning to start its Phase 3 trial sometime before July 1, and that they could finish by the end of the July, which means the trial would be between a month and six weeks long, although he thought August or September was more likely.

"I've not seen anyone wrap up a Phase 3 trial in a month to six weeks," said Dr. Saad Omer, a Yale University infectious disease expert who's done clinical trials on polio, pertussis and influenza vaccines. "We need to benchmark this against realistic expectations."

Hill said he thought it was important to benchmark his trial progress because "it has huge public policy implications" for officials who are trying to make rules about when to open up communities.

But Omer said that's exactly why it's important to be realistic about how long the vaccine development process will take.

"I buy that this is a pandemic and we may need to show progress and show steps, and I'm OK with making forecasts if decision makers want that, but do it with a level of uncertainty, because that's what's warranted," said Omer, director of the Yale Institute for Global Health.

He said the issue isn't Oxford's specific vaccine technology -- he said they were "scientifically solid" -- but rather that unexpected events can happen during a vaccine trial.

One big stumbling block for any vaccine trial is that Covid-19 infection rates in many areas of the world are flattening out or declining. The point of Phase 3 is to vaccinate people and then see if they naturally become infected, and with lower rates of circulating virus, the study subjects are less likely to be exposed to the virus in the first place.

"Just because things have gone right does not mean the next steps will go exactly on time, and won't go sideways, even if eventually we'll get there," Omer said.

That's why he encourages humility in making any projections about reaching the finish line.

"As Spider-Man says, with great power comes great responsibility, and being responsible is not projecting things with more precision than the field and the history of vaccine development suggests," he added.

Oxford scientist insults other vaccine teams

Hill, the Oxford scientist, has several arguments about why he thinks his vaccine is more promising than the others currently in human clinical trials.

First, he cites his team's many years of research on the technology used in their Covid vaccine.

The Oxford vaccine uses what's called an adenovirus vector. Adenoviruses cause the common cold, but in this case, the adenoviruses are weakened and modified to deliver genetic material that codes for a protein from the novel coronavirus. The body then produces that protein and, ideally, develops an immune response to it.

Despite all this research, none of the Oxford vaccines has made it on the market, Hill said.

Still, Hill told CNN in the May 19 interview that his vaccine, plus one in China that also uses an adenovirus vector, are "the front runners" among the vaccines in clinical trials.

Hill then proceeded to disparage other teams' vaccines -- a highly unusual and aggressive move.

The four US vaccine candidates use a different technology -- or vaccine "platform" -- than Oxford.

Two of them, Moderna and Pfizer, use RNA vaccines, which inject a piece of genetic material from the novel coronavirus into human cells to stimulate immunity.

Hill described RNA vaccines as merely "noise from the new boys."

A Harvard University blog describes it differently.

Hill was particularly disparaging of Moderna, which he said has "weird and wonderful technology." When asked what he meant by "wonderful," Hill said, "I was being sarcastic."

"They've got an unproven technology," he said.

CNN asked Moderna for its response, as well as Pfizer.

"Our only competitors in this race are the virus and the clock. We are rooting for multiple vaccines to succeed because we believe no manufacturer can make enough doses for the planet," according to the Moderna statement.

"Our industry peers, the other pharmaceutical and biotechnology companies as well as health authorities, have come together like never before. We're acutely aware that we are all on the same side, and COVID-19 and other diseases are the enemy," Pfizer spokeswoman Amy Rose wrote in an email to CNN.

Hill also took a jab at Inovio, a US vaccine maker in clinical trials, saying "they can't scale up to get into phase three," clinical trials.

Inovio's technology uses a brief electrical pulse to deliver plasmids, or small pieces of genetic information, into human cells. Inovio says those cells then produce the vaccine, which leads to an immune response.

Jeff Richardson, a spokesman for the company said that "our competition is the virus, not other companies. There needs to be three or four winners to vaccinate the world. Most likely, there will be a number of vaccines that make it, and that's a good thing."

As for the four Chinese companies in clinical trials with a potential Covid vaccine, Hill said "they have a problem."

For a vaccine clinical trial to be successful, there needs to be sufficiently high levels of the virus circulating in the community. If there isn't enough virus around, it will be impossible to tell if the vaccine protected the study subjects, or if they were just never exposed to the virus.

"There's no Covid left in China. They can't finish," Hill said.

There is still a bit of Covid left in China, with a few dozen cases left, according to the latest briefings by the nation's National Health Commission. While this is likely not enough for a full-scale clinical trial, the researchers could conduct trials in other countries where the vaccine is still circulating more widely.

Oxford not in 'slam dunk' territory

The Oxford scientists have sometimes tempered their positive statements with more cautious ones.

"Nobody can be absolutely sure it's possible. That's why we have to do trials. We have to find out. I think the prospects are very good, but it's clearly not completely certain," Gilbert answered.

But the US and British media have focused more on the positive statements, often writing glowing reports about the vaccine's progress.

A few weeks ago, a headline in a US newspaper story proclaimed that the "Oxford group leaps ahead" even though it's not clear there's a single front runner among the vaccines.

"Should be careful when talking about #COVID19 vaccine progress. As a vaccine researcher, I am cautiously optimistic; but we must be mindful of projecting too much confidence. We are not in slam dunk territory," he wrote.

Oxford's monkeys, in particular, have received attention.

BioRxiv.org is a pre-print server, meaning the articles have not been reviewed by other scientists and have not been published in the medical literature.

After the monkeys were vaccinated and then exposed to the virus, they were euthanized and examined for lung damage. According to the Oxford study, none of the vaccinated animals had signs of pneumonia or other lung problems, but two out of three unvaccinated monkeys did develop some degree of viral pneumonia.

"We were very excited by seeing that in the first try," he added.

But William Haseltine, a virologist and former professor at Harvard Medical School, said Hill was being "misleading."

"In this interview Hill is like a magician who distracts the audience with one shiny object to detract you from the fact that his accomplice is picking your pocket," Haseltine told CNN in an email.

Also, he said the monkeys had just as much viral RNA in their nasal secretions compared to the unvaccinated monkeys, an indication to him that the vaccine didn't work and the monkeys could possibly spread the virus to others.

Thirdly, Haseltine pointed to neutralizing antibodies. A vaccine should elicit high levels of antibodies capable of disabling the virus and preventing it from infecting human cells. Haseltine said the level of these antibodies in the monkeys who received the Oxford vaccine was "extremely low."

Haseltine told CNN that the monkey study on the Oxford vaccine was an "outright failure."

The Oxford scientists quickly wrote a statement rebutting Haseltine's article. They had been given the novel coronavirus directly into their noses -- called an intranasal challenge -- and so the presence of virus in the nasal swabs "may reflect use of a very high intranasal challenge dose greater than that transmitted in natural infections," according to the statement.

They also wrote that there were neutralizing antibodies present in all the monkeys who were vaccinated, but not in the unvaccinated monkeys.

"The comment by Haseltine appears to misunderstand the impressive efficacy of the [Oxford] vaccine in the non-human primate model," according to the statement.

Offit, the co-inventor of the rotavirus vaccine, said he thinks it's not a deal breaker that the vaccinated monkeys got infected. People sometimes still get the flu when they get a flu vaccine, but they often get only mild symptoms. Children still can get rotavirus after getting his vaccine, but again, typically a milder version that's less life-threatening.

He said the fact that the monkeys did not develop pneumonia after receiving the Oxford vaccine is "encouraging," but he was not convinced that the Oxford vaccine would ultimately work, since vaccines that show signs of success in animals sometimes fail in humans.

"As vaccine researchers like to say, mice lie and monkeys exaggerate," Offit said.

Offit and others say they sometimes cringe when they hear Oxford scientists talk about their vaccine.

Bioethicist Alta Charo said sometimes scientists can become "overly optimistic" about their work, especially as they race to put an end to the pandemic.

"It is very easy to get caught up in the potential of a new medical product when early development and testing seem to show promise. It is very easy to believe in your own work," said Charo, a professor at the University of Wisconsin Law School.

Art Caplan, a bioethicist at NYU Langone Health and CNN medical analyst, said it's especially important to be circumspect about vaccines, since so many people have lost trust in vaccines and are hesitant to vaccinate their children, or downright refuse to do so.

"The world is watching, and if you're puffing something up that's uncertain, that's really troubling," he said.

On Saturday, after months of rosy predictions, Hill deflated his predictions of success considerably and softened his competitive tone.

In that interview, Hill warned against "over-promising" and said that developing a vaccine is "not a race against the other guys. It's a race against the virus disappearing, and against time."

Offit said this was much more realistic.

"This tells you he's starting to back away from his original statements, as he's noticed the impracticality of his original statements," he said.

Offit has some advice for Covid vaccine developers: Be quiet.

"Now researchers can't wait to step out to the microphone -- and there are so many microphones out there -- to say, 'I've got it! This looks really good!' " Offit said.

When he and his team were developing the RotaTeq vaccine, he said they didn't speak to the media until they received final approval from the US Food and Drug Administration in 2006.

Today that vaccine saves hundreds of lives a day worldwide, Offit said, mostly children under the age of 2.

"When we discovered our rotavirus vaccine was safe in mice, we didn't say anything. When we finished our Phase one clinical trials, we didn't say anything. We just moved forward," he said.

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With big talk and hurled insults, the gloves come off in the race for the coronavirus vaccine - CNN

For Sarah Bowen, it all started with a sore throat. Not the kind of searing pain shed feel with strep, she said, but a throat irritation that just didnt feel right.

By the end of the day, it just got a little worse and I didnt feel great. I felt like I might be coming down with something. And the next day, things got worse, Bowen, 31, of Portland, Oregon, said.

Full coverage of the coronavirus outbreak

Bowen works at a doctors office, where she was immediately able to get tested for COVID-19, on May 8. It came back negative, and her doctor said the symptoms were most likely allergies or another virus.

But from there, things snowballed. Bowen developed headaches, a stuffy nose, hot flash symptoms and constant headaches. By day six, she felt like she was hit by a truck. She had extreme fatigue and a burning sensation in her chest.

I started getting shortness of breath if I went upstairs to get water or something, Bowen said. It got worse when I moved around.

Two days later, she took another test for COVID. Again, it came back negative.

But despite her symptoms, her doctor didnt believe she had the virus, because there werent many cases in the Portland suburb where she lives. Frustrated, Bowen continued to isolate alone in the downstairs of her home. She didnt want to take any chances.

Its one thing to get sick and know its a cold or the flu. But to get sick during a pandemic and to be kind of dismissed, makes you feel crazy, she said.

Bowens diagnosis remains unclear, but her experience raises questions about the accuracy of diagnostic tests for the disease. Indeed, as more and more people have access to testing, new data show that false negatives on COVID-19 tests may be more common than first realized.

And as the U.S. starts to reopen, accurate testing is one of the most important tools in states' arsenals to track and stop the spread of the coronavirus.

Since the pandemic started spreading across the United States in March, nearly 70 tests have received emergency use authorization from the Food and Drug Administration. Many of these tests were developed at a breakneck pace in an effort to get tests out to the American people.

But while no test is perfect, experts told NBC News that these particular tests used to diagnose COVID-19 may be missing up to 20 percent of positive cases.

One key reason behind these so-called false negatives may be how the testing samples are collected.

The false negatives are mainly due to specimen acquisition, not the testing per se, said Dr. Alan Wells, medical director for the University of Pittsburgh Medical Center clinical laboratories and a professor of pathology at the University of Pittsburgh.

Most tests use a method called polymerase chain reaction or PCR. It detects coronavirus genetic material thats present when the virus is active. Clinicians typically collect a sample for testing from the back of a persons throat where the virus is presumed to be with a long nasopharyngeal swab.

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But scientists say that collection method is ripe for error.

Youre sampling blindly. Youre hoping you get the right spot. Then as the disease progresses, the virus might migrate down into your lungs, Wells said, adding that once its in the lungs, that nasopharyngeal swab may not pick up any virus if its already been cleared from the throat.

You have to be at the right place at the right time, he said.

Another type of diagnostic test forgoes the uncomfortable swab altogether, and instead uses saliva collected in a test tube. Once the sample arrives in the lab, its tested the same way, with PCR.

But Wells said those tests could fare even worse.

The reason for pharyngeal swabs is the virus preferentially infects and replicates starting way back in the inner cavities of the nose and not out in front, where it may come into contact with saliva, he said, adding that saliva tests could end up missing up to 50 percent of asymptomatic positive cases.

Making things even more complicated, a May 13 study in Annals of Internal Medicine, from researchers at the Johns Hopkins Bloomberg School of Public Health in Baltimore, found that test timing is also essential to getting an accurate result.

Lead study author Dr. Lauren Kucirka, a medical resident at Johns Hopkins Medicine, said testing too early after exposure to the virus substantially raises the risk of a false negative.

If you have someone who has been exposed and theyve started to develop symptoms, it probably makes sense to wait a few days before testing, Kucirka told NBC News.

Her study found that three days after the onset of symptoms is when the test is most likely valid.

But besides issues with how and when test samples are collected, questions are also being raised about the quality of the diagnostic tests themselves.

The biggest problem with that is you create a false sense of security.

In other words, even if samples are collected perfectly, at the ideal time, the tests could turn up incorrect results. A commentary published in April in Mayo Clinic Proceedings criticized the reliance on PCR tests, saying that even when tests are 90 percent accurate, that still leaves a substantial number of false test results.

The articles co-author, Dr. Priya Sampathkumar, an infectious disease specialist at the Mayo Clinic, used California as an example in a statement: If the entire population of 40 million people were tested, there would be 2 million false negative results. Even if only 1 percent of the population was tested, there would be 20,000 false negatives.

The biggest problem with that is you create a false sense of security, Wells said.

Another type of COVID-19 diagnostic test, Abbott Labs popular ID NOW point-of-care test, has also come under fire in recent weeks, after the FDA issued an alert that it may not always be accurate.

The test, which uses a method different from PCR, called isothermal nucleic acid amplification, can deliver results in five to 13 minutes. Its used by doctors across the country and touted by the White House as whats used to test President Donald Trump and other staffers.

One small study by NYU Langone Health found that the test returned false negatives for nearly 50 percent of certain samples that a rival test had found to be positive. The study has not yet been peer-reviewed.

In response, Abbott last week released interim data on several of its own studiesfinding that accuracy was significantly better, in some cases nearly 100 percent, especially when performed in patients who were tested early after their onset of symptoms.

But anecdotal reports have also found issues with accuracy, leading some of the nations largest medical centers to stop or never even start using it.

NBC News spoke with 10 medical centers and hospitals across the country; seven said they werent using the Abbott test.

All seven cited issues with accuracy, including Jackson Memorial Hospital System in Miami, which said in a statement that they identified some issues with the accuracy, which is to be expected when the medical science is so new and evolving so quickly around this virus. The best fit for Jackson was to transition to other testing platforms that have high-quality accuracy rates and quick turnaround times for results.

A Vanderbilt University Medical Center spokesman told NBC News that No patient at Vanderbilt University Medical Center has been tested via the Abbott ID NOW rapid test. Here, there were concerns about the sensitivity of that test.

Some hospitals continuing to use the Abbott test, such as Sutter Health Hospitals in California, said they often will confirm any negative results with another PCR test if there is clinical suspicion of COVID-19.

Abbott told NBC News in a statement that to date, the company has delivered more than 2 million tests to all 50 states.

"Our customers are telling us that theyre seeing positivity rates from ID NOW testing at or above local community infection rates, which means that ID NOW is detecting the virus at the same level as lab-based testing," the statement said in part. "If there were any systemic problem with ID NOW producing false negatives, that wouldnt be the case."

The bigger issue may be that test manufacturers just havent caught up to science. Its not just COVID-19 tests that have issues with accuracy. In fact, diagnostic tests for all sorts of common diseases are not even close to perfect.

Take rapid strep throat tests, for instance. According to a Cochrane Review, those tests have a sensitivity of just 86 percent. The Centers for Disease Control and Prevention says rapid flu tests are even worse, with a sensitivity ranging from 50 to 70 percent.

Rapid strep and rapid flu tests look for antigens proteins made by the infectious pathogen rather than genetic material. The first antigen test for COVID-19 received an emergency use authorization from the FDA earlier this month, but questions have already been raised about its accuracy.

Taken together, its why Dr. Ania Wajnberg, associate director of medicine at the Icahn School of Medicine at Mount Sinai, said that diagnostic tests need to be put together with clinical suspicion.

We still have a lot to learn, but testing itself is hugely important, Wajnberg said. If its not perfect, it doesnt mean its not useful.

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Questions about COVID-19 test accuracy raised across the testing spectrum - NBC News

The Covid-19 coronavirus has knocked our world off its axis. We wont return to anything approaching normal that is, life without social distancing, quarantines, masks, school closures and other control measures until most of the world has been vaccinated against the virus. Everyone, therefore, has the same question on their mind: How fast will a vaccine be ready?

The history of vaccine development is not encouraging. Ive been working on vaccines for a long time, says Barney Graham, deputy director of the Vaccine Research Center at the US National Institute of Allergy and Infectious Diseases. Ive never seen one take less than about 20 years. It took 26 years to develop a vaccine for the human papilloma virus, for instance, and 25 years to secure one for rotavirus. And researchers have been trying for more than 50 years to find a vaccine against respiratory syncytial virus, one of the leading causes of infectious disease mortality in infants. Even after Grahams group figured out a better approach in 2013, the vaccine is still only in the testing phase.

These are not normal times, however, and a vaccine for the Covid-19 virus, formally known as SARS-CoV-2, is the focus of unprecedented research efforts. Already, over 100 research groups have vaccine candidates under development, and a few are already being tested in people. In mid-May, the US government announced Operation Warp Speed, an initiative that aims to have a vaccine ready for general use by the end of 2020.

Almost all experts say that target is too optimistic, generally citing the spring of 2021 as a best-case scenario. But to hit even that later target, a lot of things have to break right, and a lot of logistic hurdles have to be cleared away. Heres a look at some of the key issues in vaccine development.

All vaccines aim for the same goal: exposing the bodys immune system to protein or carbohydrate fragments, or antigens, displayed by a virus or other pathogen. If all goes as planned, memory cells within the immune system remember this introduction. If the vaccinated person is later exposed to the actual virus, these cells enable the immune system to react quickly, suppressing the disease or reducing its severity.

Where vaccines differ is in how they present those antigens. Some vaccines, such as ones against measles and polio, use the entire virus that has been either killed or damaged so that it no longer causes disease. Because these vaccines use the whole virus, researchers dont need to know as much about the virus and its proteins. But because a whole virus offers many antigens to the immune system and because of the slight risk that a live virus could become pathogenic again more can go wrong. So whole-virus vaccines need extensive safety testing, a process that can take years.

Other vaccines extract the viral gene that codes for the desired antigen and insert it into another, less harmful virus that is then delivered to the patient (the recently approved vaccine for Ebola is a case in point). Still others use bacteria or yeast to manufacture the antigen in fermentation vats. The antigen can then be injected directly, as in the hepatitis B vaccine, or used to build empty shells of viruses that lack genetic material, as in the vaccine against human papilloma virus.

Newer, more experimental vaccines are on the table too. They deliver not the antigen itself but the genetic material that codes for it, either as RNA or DNA, usually encapsulated in a fatty membrane. This enters the bodys cells and directs them to make the relevant protein themselves to trigger the immune response. Such vaccines could be quicker to create because genetic material is easier to mass-produce than proteins are. But RNA and DNA vaccines are so new that none have yet been approved for use by the general public.

Before a vaccine is ready for public use, researchers must prove to government regulators that it is both effective and safe to use. That takes time.

Like all medicines, after vaccines are tested in experimental animals, they go through three phases of testing in people. First, a few healthy volunteers receive the vaccine: This Phase 1 trial tests for safety and gives a rough idea of how much vaccine is needed. After that, researchers work out dosing and safety in more detail in a somewhat larger group the Phase 2 trial.

These preliminaries can be dealt with in a few months, if all goes well. But before a vaccine can be approved for general use, it must be given to a much larger group and compared with an unvaccinated control group, to see whether it really prevents disease. This Phase 3 trial is the most time-consuming step in testing, because researchers have to wait for enough participants to be exposed to a virus naturally. You cannot compress time when youre relying on a natural exposure to occur, says Michael Yeaman, an infectious disease specialist at UCLA and coauthor of a 2017 overview on vaccines in the Annual Review of Pharmacology and Toxicology.

Building manufacturing capacity also takes time. Vaccines for clinical trials are generally made in small batches in pilot facilities that arent capable of producing commercial quantities. But because very few candidate vaccines make it through clinical trials successfully Graham puts the number at less than 10 percent manufacturers are understandably reluctant to invest in large-scale production facilities until they know the vaccine will work. This adds an additional time lag to the vaccine-development process.

As of May 18, 2020, there were 169 Covid-19 vaccines under development, using a wide range of approaches. Heres a breakdown of those efforts. Columns indicate how far along each vaccine is: Preclinical means the vaccine is not yet ready for testing in people. Phase 1, 2 and 3 refer to the three phases of clinical trials in people (see text for more detail). Rows indicate type of vaccine: Live attenuated virus vaccines use live SARS-CoV-2 that has been weakened so it no longer causes disease; Inactivated virus vaccines use SARS-CoV-2 that is no longer viable. Viral vector vaccines put genes for SARS-CoV-2 antigens into another, nonpathogenic virus. Protein subunit vaccines use the antigens only, either injected directly or formed into empty protein shells. RNA and DNA vaccines are the newest kind. They deliver genetic material that codes for SARS-CoV-2 antigens, which the recipients cells use to make antigen. Note that most vaccine candidates are still in the earliest stages of development and none have yet entered Phase 3 trials, the most time-consuming step.

With Covid-19, scientists already have a big head start, because this isnt the first coronavirus theyve tried to make a vaccine for. They had begun making vaccines for SARS and MERS during their outbreaks in 2003 and 2012, respectively, only to abandon the efforts when the outbreaks receded.

So when Covid-19 came along, researchers already knew a good target for a vaccine: the spike protein that sits on the surface of the virus, and especially the part that binds to human cells, enabling the virus to gain entry. Researchers even knew how to stabilize that key part of the spike protein so it holds its shape during vaccine production.

This advance knowledge enabled the biotech company Moderna, in collaboration with the US governments Vaccine Research Center, to decide on a vaccine candidate within three days of the Covid-19 genome being sequenced. Thats nearly a year quicker than it took to find a candidate for a SARS vaccine in 2003-04.

Ideally, a steady stream of vaccine candidates should be entering clinical trials, so that each new trial can learn from its predecessors. If Im coming behind, I can design my studies better so I dont make the same mistakes, says Maria Elena Bottazzi, a vaccinologist at Baylor College of Medicine in Houston and coauthor of an article about vaccines for developing countries in the Annual Review of Medicine.

Graham is hopeful that vaccine developers can also speed through the time-consuming, large-scale Phase 3 trials by riding the wave of new Covid-19 infections that is widely expected this fall. By testing the vaccine in locations where large outbreaks are already occurring, researchers should be able to tell more quickly whether it really works.

Once testing shows that a vaccine candidate is safe and effective, regulators are likely to expedite its approval. Everyone recognizes that this is a crisis, including the regulatory authorities. In this case, the benefit of having a vaccine earlier is very high, Graham says. But that should not mean cutting corners on safety testing, he adds. We have to be cautious, even though we have to go fast. I think we can do those things together if we pay attention.

Its unwise to pin too much hope on any given vaccine, because most candidate vaccines Graham puts the number at more than 90 percent fail during their clinical trials, usually at early stages. Thats why its essential to have many potential vaccines to test. Youve got to try multiple shots on goal, and some of them will work, Yeaman says.

One big reason why vaccines fail is that they lead to the wrong kind of immune response. Theres a big difference between an immune response and a protective immune response, Yeaman says. To be effective, a vaccine must do more than merely provoke the body to make antibodies. Those antibodies must also be able to neutralize the virus so it can no longer invade host cells. A good vaccine should also prompt the right sort of activity from the bodys T cells, the part of the immune system thats responsible for orchestrating the bodys immune response to the virus. Vaccines that do these things well in lab animals often disappoint in human trials, and only testing can weed out these failures.

Sometimes, vaccines can even make a disease worse. Two different processes can cause this. In one, certain types of antibodies induced by the vaccine can help the virus more easily invade a host cell. They do so by attaching both to the virus and to a receptor for antibodies on the cell surface, serving as a bridge between the two.

In the other process, the vaccine primes the immune system too vigorously, so that an infection by the virus later on provokes an immune overreaction a cytokine storm that can prove lethal.

Both of these problems have been reported in the past with animal studies of coronavirus vaccines, including vaccines that were being developed for SARS and MERS. But there is as yet no indication that people would react in the same way. I dont think the risk is extremely high not as much as the risk of not having a vaccine and having the kind of mortality were going to have if everyone becomes infected with this virus, Graham says.

Its possible, but unlikely. There are a few viruses out there that have stubbornly resisted all efforts to develop a vaccine, including hepatitis C, herpes simplex and HIV. But many of these viruses have special features that help the virus evade a vaccine. There is no indication that the virus causing Covid-19 has any such features, Yeaman says.

On the positive side, veterinary researchers have successfully developed vaccines for other coronaviruses that infect livestock. And earlier attempts to develop vaccines for SARS and MERS both closely related to the Covid-19 virus showed promising initial results before those diseases receded and the vaccine programs were abandoned. Were hopeful that this virus is going to be amenable to vaccine, Graham says.

Indeed, in mid-May, Grahams group, working with Moderna, reported that eight healthy volunteers who received their candidate Covid-19 RNA vaccine developed a protective antibody response. (Much testing remains to be done, of course. It is still unknown whether the antibody response actually prevents disease, and Moderna has yet to share its full results.) Also in May, other researchers reported a promising T-cell response in patients who had recovered from Covid-19. Taken together, these results suggest that a vaccine is likely to succeed, Yeaman says.

Its still better than nothing. Some existing vaccines flu is a good example are useful even though vaccinated people still sometimes get sick, because they reduce the incidence of severe illness and death, Bottazzi says. Its also possible that a partially effective vaccine, in combination with a partially effective antiviral drug, could add up to nearly full protection, Yeaman points out.

Not yet. Even at the point when manufacturers are producing vast quantities of a vaccine, the job isnt done. A vaccine is not just going to magically appear in peoples homes, says Bruce Y. Lee, a vaccine logistics expert at the City University of New York. Coming up with a clear distribution and implementation plan is very important and its challenging.

Lee studies the supply chain for vaccines that is, the intermediary steps needed to deliver vaccines from the manufacturer to the point of vaccination. This chain can involve many layers. During the 2009 influenza pandemic, for example, vaccine manufacturers shipped to central hubs, which then delivered to individual states, and those state governments distributed the doses more locally. The system was plagued by mismatches between supply and demand, with far too little vaccine early on, and too much later.

At every step, this distribution process requires people, space and often refrigeration, because many vaccines are unstable at room temperature. A sudden surge of hundreds of millions, or even billions, of Covid-19 vaccine doses is likely to overwhelm the system, especially in lower-income countries where adequate refrigeration is already an issue. The existing supply chains are not ready for this, Lee says.

Even if vaccine production ramps up gradually, the supply chain will need to ensure that the vaccine initially goes to those in greatest need, such as health care workers, the elderly and others at higher risk. Health officials may also want to integrate vaccination with testing, Lee suggests, so that scarce vaccines do not go to people who have already had Covid-19.

Even something as simple as the size of vials for the vaccine and their packaging can make a huge difference in ease of delivery. Packaging for a rotavirus vaccine distributed in the early 2000s, for example, was so bulky that it clogged supply chains in Latin America and slowed distribution of all vaccines until manufacturers reformulated to allow smaller packaging, Lee says.

The problem gets even harder if the Covid-19 vaccine, like some existing vaccines, turns out to require two doses. Not only would that double the number of doses to be shipped, but front-line workers would need to do careful tracking to ensure that each recipient got exactly two doses, with the proper interval between them.

These logistical issues need attention now, not when the vaccine is ready, Lee says. Indeed, supply chain requirements might even affect which candidate vaccines we choose to pursue. A single-dose, unrefrigerated vaccine, for example, would be much preferable to a two-dose vaccine with strict refrigeration needs. This has to be looked at as a whole-system issue, Lee says.

In a sense, the world caught a break with Covid-19. We were lucky, in this case, that this was a coronavirus, because we sort of knew how to make an antigen, Graham said in an online lecture in April.

We might not be so lucky next time and there will be a next time.

To have the best chance of developing a vaccine quickly, experts should start now to develop at least one prototype vaccine for each virus family known to infect people, Graham says. (So far, thats only been done for about half of the roughly two dozen families.) That way, whatever virus emerges next, vaccine developers will have a known starting point, as they did with the Covid-19 virus. The more information you can have ahead of time, the better off youre going to be in responding, Graham says.

New vaccine technologies, such as RNA vaccines, would allow authorities to build vaccine factories that could quickly adapt to produce new vaccines, since the same production line could copy any RNA sequence, whereas producing proteins or whole viruses requires more bespoke production. This would eliminate the need for new construction. Such vaccines could also be made in smaller, more decentralized factories, which could ease supply-chain problems.

This time around, we probably wont have a vaccine until next spring at the earliest, or perhaps the fall of 2021. Eighteen months may seem like a long time to wait, but its worth remembering that if scientists hit that optimistic target, they will have developed a vaccine far faster than its ever been done before.

Bob Holmesis a science writer based in Edmonton, Canada. This article originally appeared inKnowable Magazine, an independent journalistic endeavor fromAnnual Reviews. Read the original storyhere.

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The Time of Trials: Waiting for a Coronavirus Vaccine - Discover Magazine

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Grants fund studies of parasitic infections affecting millions worldwide

Makedonka Mitreva, PhD, (right) works with Hyeim Jung, a doctoral student in her lab at Washington University School of Medicine in St. Louis. Mitreva has received two grants totaling $5 million to develop genomic tools to study two types of parasitic infection that are endemic in Peru and parts of sub-Saharan Africa. The research could help fight drug-resistant parasitic infections and build maps to track drug-resistant parasites.

Researchers at Washington University School of Medicine in St. Louis have received two grants from the National Institutes of Health (NIH) totaling more than $5 million to study two types of parasitic worm infection that cause devastating illness in millions of people worldwide.

The two infections are on the World Health Organizations (WHO) list of neglected tropical diseases, a group of about 20 illnesses that together affect more than 1 billion people. One project will focus on onchocerciasis, commonly known as river blindness, caused by a parasitic roundworm spread by black flies that live and reproduce near rivers. The second project will target fascioliasis, caused by a foodborne parasitic flatworm commonly found in cattle-farming operations.

Led by Makedonka Mitreva, PhD, a professor of medicine and of genetics, both projects involve large-scale genome sequencing of the parasites to develop genetic tools to help monitor the infections spread and track resistance these parasites already have developed against drugs intended to eradicate them. The genomic information also could lead to new therapies to combat the drug-resistant strains.

These parasites are becoming very good at evading the drugs that target them, and we have no idea how they are doing that, said Mitreva, also a research member of the McDonnell Genome Institute at Washington University School of Medicine. We need a better understanding of these parasites genomes so we can discover how they resist standard drugs. That knowledge then could result in identification of genetic markers that predict whether a drug will fail to effectively treat infected individuals, thus guiding the design of new treatments.

In collaboration with Miguel Cabada, MD, of the University of Texas in Galveston, Mitreva is studying fascioliasis in the highlands of Peru, where farmers and their families are often in close contact with infected livestock. Cabada, who also runs a clinic in Cusco, Peru, treats adults and children with fascioliasis infection, caused by the flatworm Fasciola hepatica. A drug called triclabendazole is the first-line treatment for fascioliasis, but resistance to the treatment is widespread in livestock and a growing problem among people who become infected.

This parasite burrows through the intestinal wall and makes its way to the liver and bile ducts, Mitreva said. It causes substantial liver damage. This sets up a long-term, chronic infection that can really have an impact on nutritional status, leading to anemia and weight loss.

Children are especially vulnerable to fascioliasis infections, which can contribute to malnutrition and lifelong consequences, including stunted growth, dysfunctional brain development and impaired immune systems. In the Andes Mountains of Peru and Bolivia, an estimated 70% of children are infected.

The researchers will sequence the genomes of fascioliasis parasites that are sensitive and resistant to triclabendazole in an effort to identify genetic reasons for the resistance and to develop a quick test to distinguish between drug-susceptible and drug-resistant worms.

In collaboration with Warwick Grant, PhD, of La Trobe University in Melbourne, Australia, Mitreva is studying river blindness in parts of sub-Saharan Africa. River blindness is caused by the parasitic roundworm Onchocerca volvulus, which is spread by black flies.

This roundworm can make its way to the eye and cause permanent blindness in some people, Mitreva said. The parasites migrate through the skin, causing nodules and extreme itching. Not all strains of the worm cause blindness that can depend on the geographic area that the worm comes from.

The drug ivermectin has been used to treat and prevent river blindness for decades. It is often given to entire communities as part of mass drug-administration programs to prevent the disease in areas where the parasite has a long history of being endemic.

We need better diagnostic tools to understand which strains dont respond well to ivermectin, identify where those strains are and develop maps of infection patterns, Mitreva said. We would like to develop ways to predict areas where the parasites are most likely to recur and, in contrast, areas where the disease is likely to be well controlled and public health officials can safely stop the long-running, mass drug-administration programs.

Being able to stop giving these drugs to entire communities may lift some of the evolutionary pressure that drives the development of drug resistance, according to the researchers. The tools they aim to develop will be suitable for genetic epidemiology. For example, should the parasite return after mass drug administration, such tools would allow the researchers to trace the likely source of the recurrence.

While these two parasites are very different in how they are spread and in the specific damage they cause, the human populations they affect overlap considerably, Mitreva said. We hope our projects can help understand these parasites better, so we can make meaningful contributions to reducing the devastating burden they place on so many people in developing countries worldwide.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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$5 million supports research into neglected tropical diseases Washington University School of Medicine in St. Louis - Washington University School of...

Why can some people eat as much as they want, and still stay thin?

In a study published today in the journal Cell, Life Sciences Institute Director Dr. Josef Penninger and a team of international colleagues report their discovery that a gene called ALK (Anaplastic Lymphoma Kinase) plays a role in resisting weight gain.

We all know these people, who can eat whatever they want, they dont exercise, but they just dont gain weight. They make up around one per cent of the population, says senior author Penninger, professor in the Faculty of Medicines department of medical genetics and a Canada 150 research chair.

Dr. Josef Penninger

We wanted to understand why, adds Penninger. Most researchers study obesity and the genetics of obesity. We just turned it around and studied thinness, thereby starting a new field of research.

Using biobank data from Estonia, Penningers team, including researchers from Switzerland, Austria, and Australia, compared the genetic makeup and clinical profiles of 47,102 healthy thin, and normal-weight individuals aged 20-44. Among the genetic variations the team discovered in the thin group was a mutation in the ALK gene.

ALKs role in human physiology has been largely unclear. The gene is known to mutate frequently in several types of cancer, and has been identified as a driver of tumour development.

Our work reveals that ALK acts in the brain, where it regulates metabolism by integrating and controlling energy expenditure, says Michael Orthofer, the studys lead author and a postdoctoral fellow at the Institute of Molecular Biology in Vienna.

When Penningers team deleted the ALK gene in flies and mice, both were resistant to diet-induced obesity. Despite consuming the same diet and having the same activity level, mice without ALK weighed less and had less body fat.

As ALK is highly expressed in the brain, its potential role in weight gain resistance make it an attractive mark for scientists developing therapeutics for obesity.

The team will next focus on understanding how neurons that express ALK regulate the brain at a molecular level, and determining how ALK balances metabolism to promote thinness. Validating the results in additional, more diverse human population studies will also be important.

Its possible that we could reduce ALK function to see if we did stay skinny, says Penninger. ALK inhibitors are used in cancer treatments already, so we know that ALK can be targeted therapeutically.

The study was supported by the Estonian Research Council, the European Union Horizon 2020 fund, and European Regional Development Fund, the von Zastrow Foundation, and the Canada 150 Research Chairs Program.

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UBC scientist identifies a gene that controls thinness - UBC Faculty of Medicine - UBC Faculty of Medicine

As coronavirus vaccines hurtle through development, scientists are getting their first look at data that hint at how welldifferent vaccines are likely to work. The picture, so far, is murky.

On May 18, US biotech firm Moderna revealed the first data from a human trial: its COVID-19 vaccine triggered an immune response in people, and protected mice from lung infections with the coronavirus SARS-CoV-2. The results which the company, based in Cambridge, Massachusetts, announced in apress release were widely interpreted as positive and sent stock prices surging. But some scientists say that because the data havent been published, they lack the details needed to properly evaluate those claims.

Tests of other fast-tracked vaccines show that they have prevented infections in the lungs of monkeys exposed to SARS-CoV-2 but not in some other parts of the body. One a vaccine being developed at the University of Oxford, UK, that is also in human trials protected six monkeys from pneumonia, but the animals noses harboured as much virus as did those of unvaccinated monkeys, researchers reported last week in a bioRxiv preprint. A Chinese group reported similar caveats about its own vaccines early animal tests this month.

Despite uncertainties, all three teams are pressing ahead with clinical trials. These early studies are meant mainly to test safety, but larger clinical trials designed to determinewhether the vaccines can actually protect humansfrom COVID-19 could report in the next few months.

Still, the early data offer clues as to how coronavirus vaccines might generate a strong immune response. Scientists say that animal data will be crucial for understanding how coronavirus vaccines work, so that the most promising candidates can be identified quickly and then refined. We might have vaccines in the clinic that are useful in people within 12 or 18 months, says Dave OConnor, a virologist at the University of WisconsinMadison. But were going to need to improve on them to develop second- and third-generation vaccines.

Modernas vaccine, which is being co-developed with the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, began safety testing in humans in March. The vaccine consists of mRNA instructions for building the coronaviruss spike protein; it causes human cells to churn out the foreign protein, alerting the immune system. Althoughsuch RNA-based vaccinesare easy to develop, none has yet been licensed anywhere in the world.

In its press release, the company reported that 45 study participants who received one or two doses of the vaccine developed a strong immune response to the virus. Researchers measured virus-recognizing antibodies in 25 participants, and detected levels similar to or higher than those found in the blood of people who have recovered from COVID-19.

Tal Zaks, Modernas chief medical officer, said in a presentation to investors that these antibody levels bode well for the vaccine preventing infection. If you get to the level of people who had disease, that should be enough, Zaks said.

But its not at all clear whether the responses are enough to protect people from infection, because Moderna hasnt shared its data, says Peter Hotez, a vaccine scientist at Baylor College of Medicine in Houston, Texas. Im not convinced that this is really a positive result, Hotez says. He points to a May 15bioRxiv preprint3that found that most people who have recovered from COVID-19 without hospitalization do not produce high levels of neutralizing antibodies, which block the virus from infecting cells. Moderna measured these potent antibodies in eight trial participants and found their levels to be similar to those in recovered patients.

Hotez also has doubts about the Oxford teams first results, which found that monkeys produced modest levels of neutralizing antibodies after receiving one dose of the vaccine (the same regime that is being tested in human trials). It looks like those numbers need to be considerably higher to afford protection, says Hotez. The vaccine is a made from a chimpanzee virus that has been genetically altered to produce a coronavirus protein.

Hotez says that the vaccine being developed by Sinovac Biotech in Beijing seems to have elicited a more promising antibody response in macaque monkeys that received three doses, as reportedin a May 5 paper inScience. That vaccine is comprised of chemically inactivated SARS-CoV-2 particles.

No one yet knows the precise nature of the immune response that protects people from COVID-19, and the levels of neutralizing antibodies made by the monkeys in the Oxford Study might be enough to protect people from infection, says Michael Diamond, a viral immunologist at Washington University in St. Louis, Missouri, who is a member of Modernas scientific advisory board. If not, a second injection would probably boost levels appreciably. What we dont know is how long theyll last, he adds.

Still more questions hover over experiments showing that vaccines can protect animals from infection. Moderna said its vaccine stopped the virus replicating in the lungs of mice. The rodents had been infected with a version of the virus that was genetically modified to let it attack mouse cells, which are not ordinarily susceptible to SARS-CoV-2, according to Zakss presentation. But the mutation affects the protein that most vaccines, including Modernas, use to stimulate the immune system, and this could change the animals response to infection.

The Oxford monkeys were given an extremely high dose of virus after receiving the vaccine, says Sarah Gilbert, an Oxford vaccinologist who co-led the study with Vincent Munster, a virologist at NIAIDs laboratories in Hamilton, Montana. This could explain why the vaccinated animals had just as much SARS-CoV-2 genetic materials in their noses as control animals, even though the vaccinated monkeys didn't develop any signs of pneumonia. Administering high doses ensures that the animals are infected with the virus, but it might not replicate natural infections. The Oxford study did not measure whether the virus was still infectious, Diamond says, and the genetic material could represent virus particles inactivated by the monkeys immune response, or the viruses the researchers administered, rather than an ongoing infection.

Still, the result is a concern that raises the possibility that vaccinated people could still spread the virus, says Douglas Reed, an aerobiologist at the University of Pittsburgh Center for Vaccine Research in Pennsylvania. Ideally, you want a vaccine that would protect against disease and against transmission, so that we can kind of break the chain, he says.

One way to find out whether vaccines can prevent transmission would be to study them in animals that are naturally susceptible to the virus and seem capable of spreading it, such as ferrets and hamsters, says Reed. He and other researchers also point out that macaques display only mild symptoms of coronavirus infection, and they wonder whether vaccines should be trialled in animals that develop more severe disease.

Although assessing vaccines potential efficacy is difficult, the latest data are clearer on safety, say researchers. The Moderna vaccine caused few severe and no lasting health problems in trial participants. The vaccinated Oxford and Sinovac monkeys did not develop an exacerbated disease after infection a key fear, because an inactivated vaccine for the related coronavirus that causes SARS (severe acute respiratory syndrome) showed signs of this in macaques.

Stanley Perlman, a coronavirologist at the University of Iowa in Iowa City, says that the animal studies conducted so far can tell vaccine developers only so much. People are doing as best they can, he says. None of the data that hes seen should dissuade developers from pressing on with trials in humans to determine whether the vaccines work, he says.

Moderna will soon begin a phase II trial involving 600 participants. It hopes to begin a phase III efficacy trial in July, to test whether the vaccine can prevent disease in high-risk groups, such as health-care workers and people with underlying medical problems. Zaks said that further animal studies, including some in monkeys, were under way, and that it wasnt yet clear which animal would best predict whether and how the vaccine works.

The Oxford team has already enrolled more than 1,000 people in its UK trial. Some volunteers have received a placebo, so the trial could allow researchers to determine whether the vaccine works in humans over the coming months. The lack of safety problems in the teams monkey study was reassuring, Gilbert says.

We dont really need any more data from animal trials to continue, she says. If we get human efficacy, weve got human efficacy, and thats what matters.

This article is reproduced with permission and wasfirst publishedon May 19 2020.

Read more about the coronavirus outbreak from Scientific American here. And read coverage from our international network of magazines here.

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Coronavirus Vaccine Trials Have Delivered Their First Results--But Their Promise Is Still Unclear - Scientific American

DNA may not be lifes instruction book, but just a jumbled list of ingredients.

University of Maryland researcher develops potentially revolutionary framework for heredity and evolution in which inheritable information is stored outside the genome.

The common view of heredity is that all information passed down from one generation to the next is stored in an organisms DNA. But Antony Jose, associate professor of cell biology and molecular genetics at the University of Maryland, disagrees.

In two new papers, Jose argues that DNA is just the ingredient list, not the set of instructions used to build and maintain a living organism. The instructions, he says, are much more complicated, and theyre stored in the molecules that regulate a cells DNA and other functioning systems.

Jose outlined a new theoretical framework for heredity, which was developed through 20 years of research on genetics and epigenetics, in peer-reviewed papers in the Journal of the Royal Society Interface and the journal BioEssays. Both papers were published on April 22, 2020.

Joses argument suggests that scientists may be overlooking important avenues for studying and treating hereditary diseases, and current beliefs about evolution may be overly focused on the role of the genome, which contains all of an organisms DNA.

DNA cannot be seen as the blueprint for life, Jose said. It is at best an overlapping and potentially scrambled list of ingredients that is used differently by different cells at different times.

For example, the gene for eye color exists in every cell of the body, but the process that produces the protein for eye color only occurs during a specific stage of development and only in the cells that constitute the colored portion of the eyes. That information is not stored in the DNA.

In addition, scientists are unable to determine the complex shape of an organ such as an eye, or that a creature will have eyes at all, by reading the creatures DNA. These fundamental aspects of anatomy are dictated by something outside of the DNA.

Jose argues that these aspects of development, which enable a fertilized egg to grow from a single cell into a complex organism, must be seen as an integral part of heredity. Joses new framework recasts heredity as a complex, networked information system in which all the regulatory molecules that help the cell to function can constitute a store of hereditary information.

Michael Levin, a professor of biology and director of the Tufts Center for Regenerative and Developmental Biology and the Allen Discovery Center at Tufts University, believes Joses approach could help answer many questions not addressed by the current genome-centric view of biology. Levin was not involved with either of the published papers.

Understanding the transmission, storage and encoding of biological information is a critical goal, not only for basic science but also for transformative advances in regenerative medicine, Levin said. In these two papers, Antony Jose masterfully applies a computer science approach to provide an overview and a quantitative analysis of possible molecular dynamics that could serve as a medium for heritable information.

Jose proposes that instructions not coded in the DNA are contained in the arrangement of the molecules within cells and their interactions with one another. This arrangement of molecules is preserved and passed down from one generation to the next.

In his papers, Joses framework recasts inheritance as the combined effects of three components: entities, sensors and properties.

Entities include the genome and all the other molecules within a cell that are needed to build an organism. Entities can change over time, but they are recreated with their original structure, arrangement and interactions at the start of each generation.

That aspect of heredity, that the arrangement of molecules is similar across generations, is deeply underappreciated, and it leads to all sorts of misunderstandings of how heredity works, Jose said.

Sensors are specific entities that interact with and respond to other entities or to their environment. Sensors respond to certain properties, such as the arrangement of a molecule, its concentration in the cell or its proximity to another molecule.

Together, entities, sensors and properties enable a living organism to sense or know things about itself and its environment. Some of this knowledge is used along with the genome in every generation to build an organism.

This framework is built on years of experimental research in many labs, including ours, on epigenetics and multi-generational gene silencing combined with our growing interest in theoretical biology, Jose said. Given how two people who contract the same disease do not necessarily show the same symptoms, we really need to understand all the places where two people can be differentnot just their genomes.

The folly of maintaining a genome-centric view of heredity, according to Jose, is that scientists may be missing opportunities to combat heritable diseases and to understand the secrets of evolution.

In medicine, for instance, research into why hereditary diseases affect individuals differently focuses on genetic differences and on chemical or physical differences in entities. But this new framework suggests researchers should be looking for non-genetic differences in the cells of individuals with hereditary diseases, such as the arrangement of molecules and their interactions. Scientists dont currently have methods to measure some of these things, so this work points to potentially important new avenues for research.

In evolution, Joses framework suggests that organisms could evolve through changes in the arrangement of molecules without changes in their DNA sequence. And in conservation science, this work suggests that attempts to preserve endangered species through DNA banks alone are missing critical information stored in non-DNA molecules.

Jose acknowledged that there will be much debate about these ideas, and experiments are needed to test his hypotheses. But, he said, preliminary feedback from scientists like Levin and other colleagues has been positive.

Antony Joses generalization of memory and encoding via the entity-sensor-property framework sheds novel insights into evolution and biological complexity and suggests important revisions to existing paradigms in genetics, epigenetics and development, Levin said.

###

References:

A framework for parsing heritable information by Antony M. Jose, 22 April 2020, Journal of the Royal Society Interface.DOI: 10.1098/rsif.2020.0154

Heritable Epigenetic Changes Alter Transgenerational Waveforms Maintained by Cycling Stores of Information by Antony M. Jose, 22 April 2020, BioEssays.DOI: 10.1002/bies.201900254

Research in Antony Joses laboratory is supported by the National Institutes of Health (Award Nos. R01GM111457 and R01GM124356). The content of this article does not necessarily reflect the view of this organization.

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DNA May Not Be the Blueprint for Life Just a Scrambled List of Ingredients - SciTechDaily

People who test positive again for the coronavirus, despite having already recovered from COVID-19, arent being reinfected, a new study finds.

Reports of patients dischargedfrom hospitals in South Korea testing positive after their apparent recovery hadraised concerns that people could get infected by the virus in the short term morethan once or that the infection could come back. But diagnostic tests for the coronavirus that causes COVID-19 rely on detecting theviruss genetic material (SN: 4/17/20).A positive result does not indicate whether a person is shedding virusescapable of infecting cells which would signal an active infection.

Now, a May 19 report from theKorean Centers for Disease Control and Prevention shows that samples fromreinfected patients dont have infectious viruses. The finding hints that the diagnostic tests are picking upon the genetic material from noninfectious or dead viruses. That lack of infectious virus particles meansthese people arent currently infected and cant transmit the coronavirus toothers, the researchers say.

Its good news, says AngelaRasmussen, a virologist at Columbia University. It appears people are notbeing reinfected, and this virus is not reactivating.

In thestudy, researchers tried to isolate infectious coronaviruses from samples takenfrom 108 people who retested positive. All of those samples tested negative. When the scientists examined 23 of those patients for antibodiesagainst the coronavirus, almost all had neutralizing antibodies that can stop the virus from getting intocells (SN: 4/28/20). That immuneresponse may protect a person from getting reinfected, at least in the short term.

The team also tracked down790 contacts of 285 people who retested positive. Of those contacts, 27 testedpositive for the coronavirus. Twenty-four of those were cases that officialshad previously confirmed. Officials also identified three new cases, all ofwhom either had contact with the Shincheonji religious group which was hit particularly hard inthe early days of the pandemic or aconfirmed case in their family. No new cases appeared to stem from repeatpositive patients, a sign those patients arent contagious.

Now, we can largely stopworrying about reinfection and address the next big questions, Rasmussen says.How protective are immune responses in recovered patients, and how long doesimmunity last?

Scientists and journalists share a core belief in questioning, observing and verifying to reach the truth. Science News reports on crucial research and discovery across science disciplines. We need your financial support to make it happen every contribution makes a difference.

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New data suggest people arent getting reinfected with the coronavirus - Science News

If youve ever been a newlywed, you know the tingly euphoria of saying I do and starting a life with your spouse. This is romantic love, Western style. We often chalk it up to chemistry, an ill-defined connection of hearts and minds. Groundbreaking research at UC Santa Barbara finds we were closer than we knew.

For the first time, researchers have explored the neural and genetic connections to romantic love in newlyweds. By using functional magnetic resonance imaging (fMRI) and genetic analysis of 19 first-time newlyweds, Bianca Acevedo and her collaborators showed that romantic love maintenance is part of a broad mammalian strategy for reproduction and long-term attachment that is influenced by basic reward circuitry, complex cognitive processes and genetic factors.

In short, were hard-wired to sustain romantic love to maintain a successful marriage and the family unit, thanks to neurotransmitters like dopamine and a suite of genetic mutations.

This is the first study to examine the neural and genetic correlates of romantic love maintenance, said Acevedo, a research scientist at UC Santa Barbaras Department of Psychological & Brain Sciences and the lead author of After the Honeymoon: Neural and Genetic Correlates of Romantic Love in Newlywed Marriages in the journal Frontiers in Psychology.

The study showed that the maintenance of love is not only associated with activation of subcortical regions but also higher order centers of the brain, she said. Also, for the first time we provide evidence that the propensity to sustain romantic love may be affected by genetic variability. Specifically, the genes we examined are associated with pair-bonding behaviors including fidelity and sexual behaviors; and social behaviors such as trust, eye-gazing and attachment.

To test their hypothesis that romantic love is a developed form of the mammalian drive to find and keep mates, the researchers performed fMRI scans of the brains of the members of the study group 11 women and eight men. Participants were shown alternating images of their partners and a neutral acquaintance they knew well.

At the start of each session, the subjects were instructed to recall non-sexual events with the person whose face was displayed. While still in the scanner, participants rated their moods to verify that the evoked emotions corresponded to the target image.

The participants were tested around the time of marriage and a year later.

In addition, they provided saliva samples for testing of vasopressin, oxytocin and dopamine genes implicated in pair bonding in non-human mammals, such as voles.

Our findings showed robust evidence of the dopamine reward systems involvement in romantic love, Acevedo said. This system is interesting because it is implicated in motivation, energy, working for rewards, and is associated with corresponding emotions such as excitement, euphoria and energy, as well as frustration if the drive is thwarted.

Acevedos current research builds on her work on empathy and altruism and its correlates in the brain.

Empathy has its roots in social bonding, she explained. In our previous work we showed that although humans express sentiments such as empathy and altruism towards strangers and non-close others, brain responses to partners are stronger. Thus, there is specificity. Romantic love is somewhat different in that it may or may not include empathy or altruism, but in healthy partnerships it does.

For some romantics, it might seem a tad clinical to chalk up our feelings of love and commitment to biochemistry. Acevedo, however, said gene mutations and brain activity are only components of romance and belonging.

Humans are creative and clever, she said. Romantic love inspires people to know how to put a smile on their partners face. By making our partners happy we not only keep our relationships stable, but we also derive joy from such events.

In the brain, Acevedo continued, this is shown as increased reward activation when people are shown images of a partner smiling and they are told that something wonderful has happened to the partner. People know this intuitively. They know that romance goes a long way in finding and keeping a preferred mate. Thats why there is multibillion-dollar industry built on it from dating sites, to lingerie to Hallmark cards, chocolate and diamond rings.

And besides, our chemical impulses dont buy flowers or cook dinner.

Love is basic but complex, Acevedo said. We are wired to love, but it takes work to find and keep love alive."

Nancy L. Collins, a professor in UC Santa Barbaras Psychological and Brain Sciences, was a co-author of After the Honeymoon. She is also director of the UC Santa Barbara Close Relationship Lab. Other authors are Michael J. Poulin of the University of Buffalo and Lucy L. Brown of the Albert Einstein College of Medicine in New York.

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Are we wired for romance? - University of California

A girl in New Delhi gets a nasal swab to test for the new coronavirus. A rare Kawasaki diseaselike illness linked to the virus is sickening young people.

By Jennifer Couzin-FrankelMay. 21, 2020 , 4:10 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center.

Three children at one London hospital in mid-April, followed the next day by three at anotherfor Elizabeth Whittaker, a pediatric infectious disease doctor at Imperial College London, those first cases raised an alarm. The youngsters had fevers, rashes, stomach pain, and, in some cases, heart problems, along with blood markers that characterize COVID-19 in adults, including one associated with clotting. But in most, nasal swabs failed to reveal any virus.

I dont understandthey look like they have coronavirus, Whittaker recalls thinking. Doctors nonetheless suspected a link. Within days, a survey turned up 19 additional cases across England, and an alert on 27 April asked doctors to be on the lookout for such symptoms in children. Soon after, dozens more cases surfaced in New York along with smaller clusters elsewhere, bolstering a connection to the pandemic. Reports of children on life support and some deaths put parents on edgeand were especially disheartening after earlier signs that COVID-19 largely spares children from serious illness.

It is another surprise from a virus that hasproffered many, and projects worldwide are gearing up to study it. They are combing the blood and sequencing the genomes of patientsand the virus, if it can be isolated from themto search for clues to what makes some children susceptible and how to head off the worst symptoms. Theres hope that whats learned from young patients might help the many adults in whom COVID-19 also triggers a grievous overreaction of the immune system.

In some respects, Its absolutely not shocking to see this, says Rae Yeung, a rheumatologist and immunologist at the Hospital for Sick Children, whose center treated 20 children over the past 3 weeks with similar symptoms.Many pathogens occasionally trigger a similar hyperactive immune response in children, known as Kawasaki disease. Its symptoms vary but include rash, fever, and inflammation in medium-size blood vessels. Children can suffer heart problems. In rare cases, blood pressure plummets and shock sets in.

Doctors disagree on whether the variant linked to COVID-19 is Kawasaki disease or something new, with some experts calling it multisystem inflammatory syndrome in children. But as with Kawasaki disease, most recover with treatment, including steroids and immunoglobulins, which calm the immune system.

In linking the inflammatory syndrome to COVID-19,Were going on more than just a hunch, says Jesse Papenburg, a pediatric infectious disease specialist at Montreal Childrens Hospital, in a city thats seen about 25 children with the condition. Kawasaki disease is rare, ordinarily affecting just one to three in every 10,000 children in Western countries, though its more common in children with Asian ancestry. The spikes recorded so far, in COVID-19 hot spots like northern Italy and New York City, track the novel coronavirus march around the world. And although a minority of these children test positive for SARS-CoV-2, a studypublished inThe Lancetby a team in Bergamo, Italy, reported that eight of 10 children with the Kawasaki-like illness had antibodies to the virus, indicating they had been infected. Positive antibody tests have been reported in sick children elsewhere, too.

It was obvious that there was a link, says Lorenzo DAntiga, a pediatrician at the Papa Giovanni XXIII Hospital who led the study. The new coronavirus can elicit a powerful immune response, which he thinks may explain why shock and a massive immune reaction called a cytokine storm are more common in the COVID-19linked cases than in textbook Kawasaki disease. And a time lag between infection and the Kawasaki-like illness could explain why many of the affected children show no evidence of the virus. The immune systems overreaction may unfold over weeks, though virus could also be hiding somewhere in the body.

Theres clearly some underlying genetic component that puts a small number of children at risk, says Tom Maniatis, founding director of Columbia Universitys Precision Medicine Initiative. New York state is investigating 157 cases, and Maniatis is also CEO of the New York Genome Center, which is pursuing whole-genome sequencing of affected children and their parents, as well as sequencing the virus found in children, with family consent. Finding genes that heighten risk of the illness or of developing a severe case could point to better treatments or help identify children who may take a sudden turn for the worse.

Genetics may also help explain a puzzle: why the illness hasnt been reported in Asian countries, even though Kawasaki disease is far more common in children with Asian ancestry. The virus own genetics may be important; an analysis last month indicatedthe predominant viral variant in New York was brought by travelers from Europe. Its also possible that the Kawasaki-like illness is so rare that it only shows up in COVID-19 hotbeds. The areas that have been hardest hit by coronavirus are the areas reporting this syndrome now, says Alan Schroeder, a critical care physician at Lucile Packard Childrens Hospital at Stanford University, which has seen one potentially affected child, a6-month-old baby, who healed quickly.

Yeung is pursuing ways to flag children with COVID-19 who are at risk of this complication. She co-leads an international consortium thats banking blood from affected children both before and after treatment and screening for various markers, including the cytokine molecules that indicate a revved-up immune system. They are also searching for gene variants known to predict poor outcomes in Kawasaki disease. Theres also core COVID stuff that needs to be measured, Yeung says, such as markers of heart function and levels of D-dimer, a protein fragment in the blood that indicates a tendency toward clotting and that surges in many sick adults.

Another project, called DIAMONDSand originally designed to improve diagnostics of pathogens based on patterns of immune response in children with fevers,is recruiting children across Europe with the Kawasaki-like complication, along with those who have run of the mill COVID-19 symptoms. Scientists will study blood for pathogensnot just SARS-CoV-2and the behavior of immune cells such as T cells and B cells.

We have to do a deep dive into the immunology of those patients, says Elie Haddad, a pediatric immunologist and scientist at the St. Justine University Hospital Center who,with Yeung and Susanne Benseler at Alberta Childrens Hospital, is leading Canadian research efforts on the new syndrome. These deep dives may also clarify the immune system chaos seen in many sick adults. Children are cleaner, Haddad points outtheyre less likely to have other health burdens, such as diabetes or high blood pressure, that can make it harder to tease out the virus impact on the immune system.

Its possible, too, that the illness affects adults as well but is harder to tease out from their other symptoms. A global effort studying COVID-19 in adults, called the International Severe Acute Respiratory and Emerging Infection Consortium, will look at adults clinical data and blood samples,Whittaker says, to see, is this a uniquely pediatric problem?

Eager as they are to understand this new face of the pandemic, doctors want to avoid overstating the hazards. We need to identify early and we need to intervene early in treating these children, Yeung says. But she also urges calm. The kids were seeing so far, she stresses, they respond to the treatments were giving.

Read the original:
Doctors race to understand rare inflammatory condition associated with coronavirus in young people - Science Magazine

Have a question about coronavirus, also known as COVID-19?

We will ask the experts.

Send questions to tribdem@tribdem.com.

If a person had COVID-19 in the past, lets say in February, and takes the testagain in May, is the test going to show negative? In other words you could have hadcoronavirus in the past and it would test negative now?

So, the only way to find out if you had it in the past would be the antibody test, correct?

The answer:

Great questions, and it all comes back to testing and more frequent testing. Theres some very recent positive data out of South Korea which Ill discuss below.

Your questions refer to the different types of tests. One test is the molecular swab (Polymerase Chain Reaction PCR), which detects genetic RNA from SARS-CoV-2, also known as the COVID-19 virus. The other test is a blood IgG antibody, which determines if someone was previously infected, or was recently exposed to the virus 10-21 days ago.

If you had COVID-19 infection in February, the PCR swab test would probably be negative now, and the blood IgG antibody test would probably be positive (indicating prior infection). Recent data out of South Korea suggest that if the repeat PCR swab test is positive, that may be detecting dead virus, rather than indicating reinfection. And the positive IgG antibodies may provide some protection.

Because the pandemic is only a few months old, there is no data on long-term immune response.

Dr. David Csikos, chief medical officer, Chan Soon-Shiong Medical Center at Windber.

When older adults fly, canthey get tested upon arrival sothey dont need to be secluded for 14 days?

The answer:

The tests that are available on the market are antibody tests and SARS CoV-2 genome tests.

The antibody tests show if a person is having an adaptive or specific response to the virus; the genome test is indicative of an active infection, as viral RNA is present. These tests, particularly the genome test, give a snapshot of what is happening on that day.

Individualswho are exposed to SARS CoV-2 wont show symptoms for five to seven days, on average. A test upon landing would not be sufficient to say that the individual is not in the incubation period of COVID-19.

Theperson could have been exposed to the virus on the plane. This is why the 14-day quarantine is recommended.

Jill D. Henning, associate professor of biology, University of Pittsburgh at Johnstown.

My husband and I tested positive in March, then aftertwo weeks, we had no symptoms. We got retested last week and are both positive. Why would this happen?

The answer:

An excellent question that has relevant implications.

I assume the tests were molecular PCR (Polymerase Chain Reaction), which detects genetic RNA from the COVID-19 virus. If you and your husband dont have any symptoms or fever, this implies both are now asymptomatic carriers. It is not known how long you will remain a carrier without symptoms, and that may depend in part how long protective immunity will last.

I recommend you and your husband consider blood tests for IgG antibodies to SARS-CoV-2.

It is unknown if both are still contagious, and thats why its important to wear face masks in public and continue social distancing. While the evidence on reinfection is evolving, current data and experience from previous viruses without substantial seasonal mutation do not support this hypothesis.

Because the COVID-19 pandemic is only a few months old, there is no data on long-term immune response. It is also controversial when asymptomatic carriers may return back to work. I recommend both of you follow up with your primary care physician, and if necessary, consult an infectious disease specialist.

Dr. David Csikos, chief medical officer, Chan Soon-Shiong Medical Center at Windber.

I have read that scientists are working on testing community spread by testing water from the sewer.

Would it be possible to develop individual urine tests (akin to pregnancy testing)that could inform a person positive or negative for the virus on a daily basis?

The answer:

To my knowledge, there are only two kinds of tests for SARS CoV 2, a genomic RNA test and an antibody test. The RNA test is looking for viral genetic material in patients and the antibody test is looking for the presence of an immune response to the virus.

SARS CoV 2 has been detected in feces of infected patients, but it is not clear whether that virus is infectious. In addition, waste water has been shown to contain the virus, but standard municipal sanitation practices or use of a septic tank has been shown to inactivate the virus.

Urine contains waste products from the human body that can be dissolved in water. Hormones, sugar, vitamins and certain proteins can be found in urine. RNA and DNA can be found in urine as well.

Urine tests,such as those you mention in your question, require a high concentration of the substance to be in the urine.

A recent study out of China was able to detect SARS CoV 2 in urine of one patient out of 17 with confirmed disease. Other peer reviewed studies were unable to find viral RNA in urine. These studies used a technique called RT-PCR to detect the viral RNA. This technique amplifies minutely small quantities of viral RNA and brings the concentration up to detectable levels.

Who knows what the future holds? That is the beauty of science. But at present, we do not have the ability to detect the minuscule amount of viral RNA in urine without amplifying it first.

I am a cashier at Walmart. I had something similar to COVID-19 in December, however no breathing problems. Am I safe to visit my 2-week-old grandson? I shower, wash my hair and wear clean clothes and wash my hands when visiting. I also work daily, sanitize frequently and wash my hands every chance I can. I also wear a mask when working and visiting. Am I putting my grandson in danger?

The answer:

Social distancing is hard and it must be truly difficult when a new family member is born.

When we are first born and until we are about a year old, our immune systems are immature. The responses we build to microbes takes time and the littlest among us have not been around long enough to have the same responses that adults or even older children do. This makes infants more susceptible to infections.

In a recent study out of China, of more than 2,100 children with suspected or confirmed COVID-19 in between late December and early February showed that about 11% of infants had severe or critical illness. Children in other age groups had lower rates of severe or critical illness (about 7% for children ages 1 to 5, 4% for ages 6 to 10, 4% for ages 11 to 15).

Other studies are showing an inflammatory illness that may be linked to COVID-19. This response that is seen in children is severe and rare. It has to deal with an immune response that leads to a cytokine storm. Our innate response, the one we are born with, has the ability to make our blood vessels leaky in order to let white blood cells into our tissues where the infection is. It does this by releasing cytokines, proteins that allow the immune system to communicate with cells and tissue of the body. This response is usually localized, but in some children it becomes systemic causing the blood vessels all over the body to be leaky; this results in severe symptoms such as organ failure and shock.

From your question, it appears that you are doing things to reduce your risk of infection. If you feel that you had COVID-19 in December, I urge you to request an antibody test. This could help determine if you did have COVID-19.

With respect to visiting your newborn grandson, I support respecting the community directed stay-at-home orders. He is still developing his immune system and is in a risk group because of his age. You and your family can speak with the childs pediatrician to see what the case counts are in your area and then determine what level of risk is acceptable to you as a family.

Jill D. Henning, associate professor of biology, University of Pittsburgh at Johnstown.

Can you be a carrier ofCOVID-19 and not have any symptoms as in youre immune to the virus but still carry and spread the virus?

The answer:

Yes, there are asymptomatic carriers, however no one can truly determine the impact of asymptomatic cases on spread until theres more testing.

Can these people who are completely asymptomatic, who never develop any symptoms, transmit the infection? Thats still an open question, and no one knows for sure. Experts say these carriers without symptoms make it even more important for people to wear face masks in public.

Dr. David Csikos, chief medical officer, Chan Soon-Shiong Medical Center at Windber.

I was really sick with upper respiratory turned into bronchitis turned to pneumonia in late December to middle of February. Is it possible I had COVID?Would an antibody test still show antibodies if I did? I had almost all the symptoms.

The answer:

When did SARS CoV-2 emerge?

That is one of the big questions of 2020.

Science uses a method called the molecular clock to determine when new pathogens emerge.

SARS CoV-2 is an RNA virus. Ituses an enzyme to copy itself called RNA dependent RNA polymerase. This enzyme is sloppy in its copying. The rate of mistakes it makes is able to be tracked.

Using this technology, scientists at the Imperial College of London collaborated withthe World Health Organization to determine that SARS CoV-2 emerged between Nov. 6 and Dec. 13 in Wuhan, China. Couple the new respiratory virus with the ability to be anywhere in the world in 24 hours and ...

Testing can help sort out whether a person has recovered from COVID-19. The test that will determine if a person has had an immune response to the infection is the antibody test. IgG antibodies are present in a person aftershe or he has had an infection that resulted in an adaptive (specific) immune response.

If you are curious about your status, you can seek out an IgG antibody test. The more data that can be acquired about positive cases, in any stage, will help answer the question of when. It is possible, however, that we will never know when it emerged.

Jill D. Henning, associate professor of biology, University of Pittsburgh at Johnstown.

I am wondering how it could be possible to see my significant other during the coronavirus pandemic. We live separately, and I have been quarantined while he has continued to do basic things such as grocery shop and goes to work two times per week, always following recommended precautions. We are wondering if he were to do a PCR test for coronavirus RNA combined with an IgG and IgM antibody test, could this provide a sufficient picture upon which to base a decision to see one another, or not?

The answer:

Social distancing is so hard! All of us have someone we want to see.

In public health there is something called risk reduction. It refers to using strategies that minimize the risk or harm certain human behaviors come with for example, wearing a bicycle helmet when riding a bike. If you wear a helmet, you are less likely to have a traumatic brain injury if you wreck. You still ride the bike, just in a safer way.

With SARS CoV-2, becoming more lax on your social distancing is not the same as wearing a bicycle helmet when riding a bike. SARS CoV-2 is spread via airborne droplets by people who may not know they are sick yet. Even people who are practicing social distancing may not know they have been exposed because they could have come in contact with people who dont know they are infected yet.

Testing can help. The test for genomic RNA of SARS CoV-2 will let a person know ifhe or she is actively infected at that time. The antibody tests would show that you are in the first stages of an adaptive immune response (IgM) or that you are in the later stages or recovered from COVID-19 (IgG).

However, this is only a snapshot of the infection risk. It only says that at the time of the test, the individual is SARS CoV-2 free. If that individual goes out in the community the next day, he or she could be exposed to someone with the virus and become infected.

Until we have more testing,two-thirds of our population recovered, or a treatment is found, it is best to keep socially distant.

As always the risk assumption is yours; however, the recommendation is to maintain social distance.

Jill D. Henning, associate professor of biology, University of Pittsburgh at Johnstown.

Are drug users, especially intravenous, more likely to spread COVID-19 or other viruses and diseases than non-drug users?

The answer:

SARS CoV-2 is spread via respiratory droplets. Anyone can spread the infection if they have symptoms and we are seeing studies that show asymptomatic transmission in about 35% of individuals (recent studies from the New England Journal of Medicine).

Now is a good time to remind everyone that human behavior contributes to the spread of any infectious disease. When we consider COVID-19, we can reduce the spread by wearing a mask in public, washing our hands, and maintaining social distance.

Injection drug users are at a greater risk for blood-borne pathogens, such as Hepatitis and HIV, as well as having a greater risk for sepsis, a bacterial infection in the blood. As for other drug users, according to the National Institute of Allergy and Infectious Diseases, because SARS CoV-2 attacks the lungs it could be a serious threat to those who smoke tobacco or marijuana or who vape. People with opioid use disorder and methamphetamine use disorder may also be vulnerable due to those drugs effects on respiratory and pulmonary health.

In short, anything that decreases lung functioning can lead to more severe COVID-19 disease.

Jill D. Henning, associate professor of biology, University of Pittsburgh at Johnstown.

I am a nanny and was asked to enter the familys home wearing a mask. I assumed they (mom, dad and 41/2-year-old) would also be wearing masks. They did not. I wear one to protect them and vice-versa, correct?

The answer:

There are no formal guidelines on what should be done in this situation. Childcare is a necessity for many families, even if they are working from home. In this situation, I would recommend that you all (mom, dad, child and nanny) keep each other apprised of your health situation. Have a discussion about your exposures and risk factors for SARS CoV-2 (for example, do you live in a home with an essential worker) be truthful about each others movement (or lack there of) in the community. If you are nannying for another family, be sure to inform all parties involved.

After this conversation, decide together on a safety plan that makes everyone comfortable.

For example, everyone has their temperature taken daily before work starts. If symptoms become apparent, all are notified.

Maybe you have certain rooms that are for family only in the home, maybe you and the child remain in one area of the home.

Through working together as a unit, you can be sure to address all concerns and come to an agreement in which everyone feels safe.

Jill D. Henning, associate professor of biology, University of Pittsburgh at Johnstown.

The news keeps saying people under 18 rarely transmit the disease. However, what evidence is this based on? I read that children under 18 dont get the disease, or very mildly and dont transmit. But how many children have had the disease? How many children under 18 have actually been tested? If we do not have facts on children under 18 how can we say that they rarely get it and they do not transmit it?

The answer:

We dont have all the facts yet on how COVID-19 affects different populations, or know how many people have had the virus. And this is especially true with children.

It seems that children may not have symptoms that are severe, but we do know they get the virus. There have been a few cases (not locally) where kids are intubated, and respirators were used for children. Children can still pass the virus to their older family members who can have much more severe symptoms.

Everyone, including children, should follow the recommended precautions to prevent the spread of the virus.

Originally posted here:
Experts answer your COVID-19 questions: 'If a person had COVID-19 in the past, let's say in February, and takes the test again in May, is the test...

DUBLIN--(BUSINESS WIRE)--The "Global Genome Editing Market By Technique (CRISPR, Zinc Finger Nucleases, TALENs, Restriction enzymes, Others), By Applications (Synthetic Biology, Engineering Cell Line and Organisms, Others), By Source, By End-User, By Region, Forecast & Opportunities, 2025" report has been added to ResearchAndMarkets.com's offering.

The Global Genome Editing Market is expected to grow at a brisk rate during the forecast period owing to growing number of research activities for treatment of various chronic diseases using this technology. Further, increased government funding for genomics technology around the globe, growing preference for personalized medicine and increase in R&D expenditure are fueling the market growth of genome editing.

Genome editing is a way of making specific changes to the DNA of a cell or organism. It could be used to edit the genome of any organism. It uses a type of enzyme called an engineered nuclease' which cuts the genome in a specific place. After cutting the DNA in a specific place, the cell naturally repairs the cut. It finds application in large number of areas, such as mutation, therapeutics, and agriculture biotechnology. Moreover, rise in the number of chronic and infectious diseases is likely to fuel the market for genome editing in the coming years.

The Global Genome Editing market is segmented based on technique, applications, source, end-user and region. Based on applications, the market is segmented into synthetic biology, engineering cell line & organisms, therapeutic genome editing and others. Among them, the cell line engineering is expected to witness the highest growth rate in the coming years due to increase in the number of people suffering with genetic disorders and rising government funding for stem cell research.

Based on end-user, the Global Genome Editing Market is segmented into pharmaceutical & biotechnology companies, clinical research organization and research institutes. Pharmaceutical & biotechnology companies contribute to the largest share of revenue generation for the Global Genome Editing Market. Growing establishments of biotech and pharma companies in emerging economies and growing usage of gene editing technique in research activities undertaken by them to manufacture and develop drugs for rare diseases anticipated to fuel the market across the globe.

Companies Mentioned

Objective of the Study:

Key Topics Covered:

1. Product Overview

2. Research Methodology

3. Executive Summary

4. Global Genome Editing Market Outlook

4.1. Market Size & Forecast

4.2. Market Share & Forecast

4.3. Market Attractiveness Index

5. Asia-Pacific Genome Editing Market Outlook

5.1. Market Size & Forecast

5.2. Market Share & Forecast

5.3. Market Attractiveness Index

5.4. Asia-Pacific: Country Analysis

6. Europe Genome Editing Market Outlook

6.1. Market Size & Forecast

6.2. Market Share & Forecast

6.3. Market Attractiveness Index

6.4. Europe: Country Analysis

7. North America Genome Editing Market Outlook

7.1. Market Size & Forecast

7.2. Market Share & Forecast

7.3. Market Attractiveness Index

7.4. North America: Country Analysis

8. South America Genome Editing Market Outlook

8.1. Market Size & Forecast

8.2. Market Share & Forecast

8.3. Market Attractiveness Index

8.4. South America: Country Analysis

9. Middle East and Africa Genome Editing Market Outlook

9.1. Market Size & Forecast

9.2. Market Share & Forecast

9.3. Market Attractiveness Index

9.4. MEA: Country Analysis

10. Market Dynamics

10.1. Drivers

10.2. Challenges

11. Market Trends & Developments

12. Competitive Landscape

12.1. Competition Outlook

12.2. Players Profiled (Leading Companies)

13. Strategic Recommendations

14. About Us & Disclaimer

For more information about this report visit https://www.researchandmarkets.com/r/tgb83z

Go here to see the original:
Outlook on the Worldwide Genome Editing Industry to 2025 - Featuring Pfizer, Bayer Crop Science & Editas Medicine Among Others -...

Aggressive public health measures tostem the tidal wave of coronavirus infections have left people isolated,unemployed and wondering when it will all end. Life probably wont gocompletely back to normal until vaccines against the virus are available,experts warn.

Researchers are working hard on thatfront. At least six vaccines are currently being tested in people, says EstherKrofah, chief executive of the FasterCures center at the Milken Institute in Washington,D.C. We expect about two dozen more toenter clinical trials by this summer and early fall. That is a huge number,Krofah said at an April 17 briefing. Dozens more are in earlier stages oftesting.

In unpublished, preliminary results of a test of one vaccine, inoculated people made as many antibodies against the coronavirus as people who have recovered from COVID-19 (SN: 5/18/20). The mRNA-based vaccine induces human cells to make one of the viruss proteins, which the immune system then builds antibodies to attack. That study was small, only eight people, but a second phase of safety testing has begun.

But vaccinestake time to test thoroughly (SN: 2/21/20). Even with acceleratedtimelines and talk of emergency use of promising vaccines for health care workersand others at high risk of catching the virus, the general public will likelywait a year or more to be vaccinated.

In the meantime, new treatments may helpsave lives or lessen the severity of disease in people who become ill.Researchers around the world are experimenting with more than 130 drugs to findout if any can help COVID-19 patients, according to atracker maintained by the Milken Institute.

Some of those drugs are aimed atstopping the virus, while others may help calm overactive immune responses thatdamage lungs and other organs. Although researchers are testing a battery ofrepurposed drugs and devising new ones, there is still a great deal ofuncertainty over whether the drugs help, or maybe even hurt.

The wait is frustrating, but theres still much doctors and scientists dont know about how this new coronavirus affects the body. Getting answers will take time, and finding measures to counter the virus that are both safe and effective will take even more. Early results suggest that the antiviral drug remdesivir can modestly speed recovery from COVID-19 (SN: 5/13/20). It is not a cure, but the drug may become the new standard of care as researchers continue to test other therapies.

Scientists and journalists share a core belief in questioning, observing and verifying to reach the truth. Science News reports on crucial research and discovery across science disciplines. We need your financial support to make it happen every contribution makes a difference.

Antiviral drugs interfere with a viruss ability to replicate itself, though such drugs are difficult to create. Remdesivir is being tested in half a dozen clinical trials worldwide. The drug mimics a building block of RNA, the genetic material of the coronavirus (SN: 3/10/20). When the virus copies its RNA, remdesivir replaces some of the building blocks, preventing new virus copies from being produced, laboratory studies have shown.

Early results in COVID-19 patients given the drug outside of a clinical trial showed that 68 percent needed less oxygen support after treatment, as reported online April 10 in the New England Journal of Medicine (SN: 4/29/20). The drug went to very sick patients, including those who needed oxygen from a ventilator or through tubes in the nose. Other researchers have disputed those results, questioning the study methods and statistical analyses, which may have given an exaggerated impression of good outcomes. The studys authors say they have reanalyzed the data and still conclude that remdesivir has benefits.

Soon after, the U.S. National Instituteof Allergy and Infectious Diseases announced that hospitalized patients withCOVID-19 who got intravenous remdesivir recoveredmore quickly than those on a placebo: in 11 days versus 15. Those findingshad not been reviewed by other scientists at the time of the announcement. Thedug provides researchers with a baseline for comparing other treatments. Wethink its really opening the door to the fact that we now have the capabilityof treating, Anthony Fauci, director of the NIAID said April 29 in a newsbriefing at the White House.

Antiviral medications used against HIV are also being tested against COVID-19. The combination of lopinavir and ritonavir stops an HIV enzyme called the M protease from cutting viral proteins so that the virus can replicate itself. The SARS-CoV-2 virus produces a similar enzyme. But early results from a small study in China showed that the combination didnt stop viral replication or improve symptoms (SN: 3/19/20), and there were side effects.

For now, the Society of Critical CareMedicine recommendsagainst using the drugs, and the Infectious Diseases Society of Americasays patients should get the drugs onlyas part of a clinical trial. Several large trials may report results soon.

The HIV drugs may not work well against SARS-CoV-2, even though the viruses have similar M proteases: The coronaviruss enzyme lacks a pocket where the drugs fit in the HIV version of the enzyme.

This illustrates why antiviral drugs areso difficult to develop. Designing a drug requires knowing the 3-D structure ofthe viruss proteins, which can take months to years. But researchers arealready getting some close-up views of the new coronavirus. A team in Chinaexamined the structure of the coronaviruss M protease and designed smallmolecules that could block a part of the protein necessary to do its job. Theteam describedtwo such molecules, dubbed 11a and 11b, April 22 in Science.

In test tubes, both molecules stopped the virus from replicating in monkey cells. In mice, 11a stuck around longer in the blood than 11b, so the researchers tested 11a further and found it seemed safe in rats and beagles. More animal tests will probably be needed to show whether it stops the virus, then multiple stages of human tests will have to follow. The drug development and testing process often takes on average 10 years or more, and can fail at any point along the way.

Meanwhile, hundreds of thousands of people worldwide have already recovered from COVID-19, and many are donating blood that might contain virus-fighting antibodies. Clinical trials are under way to test whether antibodies from recovered patients blood plasma can help people fight off the virus (SN: 4/25/20, p. 6). More such trials are planned.

Stopping the virus is only half the problem. In some people seriously ill with COVID-19, their immune system becomes the enemy, unleashing storms of immune chemicals called cytokines. Those cytokines trigger immune cells to join the fight against the virus, but sometimes the cells go too far, causing damaging inflammation.

Some of the drugs used to calm cytokines in cancer patients (SN: 6/27/18, p. 22) may also help people with COVID-19 ride out the storm, says cancer researcher Lee Greenberger, chief scientific officer of Leukemia and Lymphoma Society. Several of those drugs are being tested against the coronavirus now.

Hydroxychloroquine, a drug approved totreat autoimmune disorders such as lupus and rheumatoid arthritis, became ahousehold word after President Trump touted it as a possible COVID-19treatment.

The drug is being tested in numerouslarge clinical trials around the world to see if it might help calm cytokinestorms in COVID-19 patients as well. But so far, there is no solid evidence thatit works either to prevent infection in people or to treat people who alreadyhave the disease.

And in some studies the drug has caused serious side effects, including causing irregular heartbeats, says Raymond Woosley, a pharmacologist at the University of Arizona College of Medicine in Phoenix. People with heart problems, low potassium or low oxygen levels in their blood are at higher risk of these side effects, he says. And those are exactly the kinds of patients who are most vulnerable to COVID-19. So, the very sickest COVID patients are those at most risk for these life-threatening arrhythmias and cardiac effects.

Results of some rigorous clinical trialsof hydroxychloroquine are expected this summer. Meanwhile, the U.S. Food andDrug Administration allows the drug to be used when no other treatment isavailable and patients cant join a clinical trial.

Todays enthusiasm for any drug thatseems promising feels familiar, says Woosley. He remembers the excitement overAZT, the first drug used to fight HIV in the 1980s. It wasnt the best drug tocombat the AIDS epidemic, and better ones came later. Likewise, the firsttreatments for COVID-19 might be better than nothing, but not the best we willultimately get.

Meanwhile, we wait.

With hundreds of clinical trials going on around the world, some answers may come soon. But for now, keeping the coronavirus contained will probably require aggressive testing, tracing and isolating contacts of people who have the virus and continued social distancing.

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As we wait for a vaccine, heres a snapshot of potential COVID-19 treatments - Science News

The massive international effort to map the entire human genome, completed in 2003, opened a new field we now know as personalized medicine.

The breakthrough, which identified the location and function of every human gene, offered the promise of medical care tailored specifically to individual patients, based on their personal genetic makeup.

When researchers identified a gene associated with a 44 per cent risk of breast cancer in women, for example, it seemed that protecting them might be as simple as deactivating that gene.

But the promise of such personalized medicine has not fully materialized, say two McMaster researchers, because the full sophistication of the genetic blueprint has a more complex and far-reaching influence on human health than scientists had first realized.

In the hope of integrating genetics more closely with medical practice, McMaster evolutionary biologists Rama Singh and Bhagwati Gupta have carried out an exhaustive and critical review of decades of research in their field. They lay out their conclusions inan articlepublished today in the Nature Partner JournalGenomic Medicine.

The biochemical pathway that shapes evolution is dense with inherited redundancies, they explain. Genetic information from our ancestors trails along forever in an incremental physical record that interacts significantly with our own most recently evolved and internally complex genetic network, which in turn interacts with the environment, creating almost infinite combinations and potential health outcomes.

Individual genes do not determine sickness or health on their own, the authors say, but act in concert with groups of other genes all in various stages of mutation in ways that are just beginning to be understood.

Our bodies have an immense ability to change and to cope with issues that arise. Context matters in our genome, Gupta says. Even a simple single mutation can have a profound effect on the body, when acting in combination with others.

The scientists conclude that precision medicine is still critical to the future of medicine, but that the same technology that identified the necessary complexity of the genome also needs to be applied to the entire blueprint including the unnecessary elements creating a longer, more complicated road to the same destination.

Any disease we see is a result of the interactions between necessary and unnecessary complexity, says Gupta.

Nature does not go back in time. It goes forward, and as it encounters challenges, it comes up with solutions.

Our genes carry the history of all the changes that have occurred over many generations. It may not be necessary to our function today, but it is embedded in our genes.

Complexity is not a curse. Its a reflection of our evolutionary history, and it needs to be recognized as an important part of the body that medicine is trying to treat, Singh says. Beyond personalized medicine, complexity bears on the evolution of life itself.

Reference:Rama S. Singh, Bhagwati P. Gupta. Genes and genomes and unnecessary complexity in precision medicine. npj Genomic Medicine, 2020; 5 (1) DOI: 10.1038/s41525-020-0128-1.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Personalized Medicine Complicated by Overlapping Versions of Our Genetic History - Technology Networks

As with any medical procedure, to undergo genetic testing, informed consent must be given.According to the National Institutes of Health, informed consent (in the context of genetic testing) is the process of making sure that, wherever possible, a patient fully understands:

With this information, a patient can make an educated, voluntary choice i.e. they are informed to a level such that they can provide consent. This is usually a legal and ethical requirement in medicine.Whilst this might seem like a relatively simple concept, for genetic testing, informed consent suddenly becomes a whole lot more complex. Bioethicists, experts in the ethical practice of biology and medicine, often use case studies to explore these complexities and to discuss potential solutions to the dilemmas arising from them.

Jodie is a 28-year-old woman who is thinking about having children. However, she has a family history of limb-girdle muscular dystrophy and is considering undergoing genetic screening to determine if she is a carrier of any variants (a.k.a. mutations in her genome) associated with the disease.

Genetic Counselor Margarita Raygada, Ph.D., explains the role of a genetic counselor in cancer care and shares the benefits and implications of genetic testing for patients and their families.Genetic counselors are individuals educated in both medical genetics and counseling. This gives them the expertise to provide patients with the knowledge required to give consent, but also to offer guidance and support. As such, they are most likely the person who will be responsible for gaining informed consent from the patient.

Laura Hercher, Director of Research in Human Genetics at Sarah Lawrence College, has almost 20 years experience working as a genetic counselor. She emphasizes that the role of counseling goes far beyond testing alone:

Genetic counseling is about more than genetic testing. It can obviously be about that, and a genetic counselor would be a good person to discuss genetic testing with, but we meet with people where genetic testing isn't on the table at all.

I think that there is an element of education in many genetic counseling sessions or interpretation but also in many circumstances, theres what we call establishing a therapeutic relationship, where you do the counseling side of it.

Continuing on this theme, Hercher points out a key aspect of genetic counseling and something which is crucial to the consent process but often forgotten amongst the hype surrounding genetic testing.

We [genetic counselors] don't take for granted that somebody will want genetic testing. They have the right to say no these are shared norms in genetics in the UK and the US.

However, in Jodies case, she has expressed interest in genetic testing. How does a genetic counselor go about establishing informed consent for this?

You have to consider both of these two very basic things, Hercher begins. Make sure the person has an understanding of what genetic testing may tell them and also have an understanding of what genetic testing may not tell them.

These are very important to understand because, number one, you don't want someone to walk away from the experience saying, "Okay, great, I've been tested. I don't have a disease, if that isn't comprehensive.

Number two, we want to talk about what the test will show the patient, both in terms of setting up correct expectations that's consent but also by identifying additional things they might find out that are not necessarily the goals of testing.

The blood sample provided by Jodie undergoes whole exome sequencing. Upon sequence analysis, its found that Jodie does not have any of the variants currently associated with limb-girdle muscular dystrophy. However, the person analyzing the data also checks for other common disease-associated variants. They discover that Jodie has a mutation in BRCA2 that puts her at a higher risk of developing breast and/or ovarian cancer.

The discovery described above is known as a secondary finding, meaning that whilst its identification may not have been the main goal of the test, its presence was actively sought. This is different to an incidental finding, although the terms are often used interchangeably.The potential for secondary findings demonstrates how consent in genetic testing isnt as simple as a single yes or no answer. The decision to actively look for other variants and have them reported back provides an additional layer of consideration to the consent process.

In 2013, the American College of Medical Genetics and Genomics (AMCG) published recommendations for the responsible handling of incidental findings emerging from clinical exome or genome sequencing. This includes clinicians being responsible for alerting patients to the possibility that sequencing could result in incidental findings, and that these may warrant further investigation.1A proper informed consent for genetic testing would give the person a notion of what they might encounter as a part of testing, and what choices they have, about what [testing or results] they can get and what not to get, if there are choices available in the setting in which you're operating.

Jodie doesnt just have a decision to make about whether or not she wants the test, she also has to consider what results she would want reported back to her. The availability of choice is an important one because of the potential implications, both physically and mentally, of being given information you werent expecting or didnt want to receive.

Jodies results show that she, and potentially her first-degree relatives, are at a high risk of developing breast and/or ovarian cancer. Although it isnt a guarantee that she would develop those diseases, this knowledge could impact upon decisions she makes about her healthcare. For people carrying a disease-associated BRCA mutation, preventative, albeit drastic, surgical measures may be available, including mastectomies and oophorectomies.

Preventative surgery, or even just knowing that you may develop a disease can also take an emotional toll. In addition, a patient could find out that they have variation that means they will develop a condition at some point in their lifetime, such as Huntingtons disease. This may have an impact on mental health if there are currently very limited or no treatment options for the condition diagnosed, although further and continual research needs to be conducted to assess the extent of such an impact.

Secondary findings can also emerge with advances in research; a variant that may not have been considered a pathogenic variant before could be considered so in the future, or vice versa. Patients like Jodie would need to think about whether they would want to be re-contacted with new or updated information.

Thats a lot of factors for someone to consider before consenting. How can we simplify consent to account for all of those decisions and outcomes, if its even possible?

This requires time something which the healthcare system doesnt always have enough of. How do we create a process that works for both clinicians and patients?

The answers people are coming up with tend to be that we need better tools, Hercher tells me. And that includes online or digital tools that would allow people to interact with the information. You know, if you sit somebody down and spout off 15 minutes worth of information, dense information, you're not doing anything for them.

So, what's needed to improve the situation is new tools that allow people to tackle it over time, at their own pace, exploring what they want to and when. That would optimize the situation for both the caregiver and the patient. And allow them to go back to it [the information] to refresh their memory and so on. The optimal consent process is not "let's decide everything we can fit into this space of time consent, optimally, is an ongoing process.

Research conducted in the UK seems to agree. A recent report from the Joint Committee on Genomics in Medicine sums it up nicely:Consent may be more appropriately seen as an ongoing conversation that needs updating and clarifying where necessary, rather than as a single historical event that needs to be revisited.Reference

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Exploring the Ethics of Genetic Testing: What Does Consent Mean? - Technology Networks

Glaucoma is an eye disease affecting almost 80 million people and is the second leading cause of blindness worldwide.

Glaucoma results in progressive damage to the optic nerve head, which leads to a corresponding visual field loss and when severe, blindness. The pressure within the eye (intraocular pressure) is the only modifiable risk factor for glaucoma.

Glaucoma has a clear genetic component and tens of common genetic variants affecting intraocular pressure and/or glaucoma risk have been identified. The clinical impact of these results has, however, thus far been negligible.

In this study, published in the journal PLOS Genetics, researchers searched for less common genetic variants which might lower intraocular pressure and protect from glaucoma and focused on those with a clear effect on the function of the corresponding protein product. Such variants have particularly high therapeutic potential since they would highlight a specific gene and a genetic modification that protects from disease.

The results of the study are based on two big European cohorts with large-scale genome and health information data available. Altogether more than 514,000 individuals from the UK Biobank and the FinnishFinnGenstudies were examined. Both cohorts include thousands of individuals with a glaucoma diagnosis. Furthermore, over 120 000 UK Biobank participants have participated in the intraocular pressure measurement tests.

Both study cohorts provided independent, complementary and convincing evidence for the role of theANGPTL7gene in glaucoma. UK Biobank participants carried several rare genetic changes that were shown to reduce intraocular pressure, while FinnGen study provided very strong evidence of another variant specific to the Finnish population which significantly decreased glaucoma risk.

The variant we identified is more than 50 times more common in the Finnish population than elsewhere in the world. In fact, more than 8% of Finns carry it and have a substantially reduced risk of glaucoma. This again demonstrates how the population history of the Finns makes it much easier to identify clinically important genetic variants, said ProfessorMark Dalyfrom the Institute for Molecular Medicine Finland (FIMM), University of Helsinki who co-led the study.

With clinic-based recruitment focused on several areas including ophthalmology, and with more than 30 % of the participants being above age 70, FinnGen is particularly well-powered for aging-associated endpoints.

We often think of the body as a machine whereby taking a single bolt out of that machine and something could go wrong. In this study that hypothetical bolt made the machine work even better by protecting human individuals from glaucoma. Our results highlight the benefits of multi-cohort analysis for the discovery of rare protein-altering variants in common diseases, and ANGPTL7 provides the best therapeutic hypothesis out there for glaucoma, saidManuel Rivas,assistant professor of biomedical data science, Stanford Universitys School of Medicine, who co-led the study.

Importantly, cohorts such as FinnGen and UK Biobank make it possible for the researchers to assess whether the identified protective variants increase the risk of some other condition.

Using the comprehensive health information in the two population cohorts, we assessed the potential impacts of rare genetic variants inANGPTL7on a spectrum of human disorders. We did not find any severe medical consequences that would be of obvious concern in developing a therapeutic to mimic the effect of these alleles, saidYosuke Tanigawa,doctoral student, Stanford Universitys School of Medicine, the first author of the study.

Better understanding of the genetic and pathological mechanism behind intraocular pressure can open up new ways of preventing or treating glaucoma. In this case, the genetic findings support inhibition or lowering the amount of ANGPTL7 as a potentially safe and effective therapeutic strategy for glaucoma.

Our results position angiopoietin like 7 as an appealing and safe target for glaucoma therapies. If a drug can be developed that mimics the protective effect of these mutations, intraocular pressure in at-risk individuals could be lowered, saidMark Daly.

Reference:Tanigawa et al. (2020).Rare protein-altering variants in ANGPTL7 lower intraocular pressure and protect against glaucoma. PLOS Genetics. DOI: https://doi.org/10.1371/journal.pgen.1008682.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Gene Variants That Protect Against Glaucoma Discovered - Technology Networks

- 70 sepsis risk genes identified from UK Biobank, 61% of which are present specifically in severe COVID-19 patients ('COVID risk genes')

- 13 'COVID risk genes' identified as known druggable targets

- 59 compounds and drugs identified with potential for accelerated drug discovery ('repurposing')

- Study also offers potential for identifying COVID-19 high risk biomarkers

OXFORD, England, May 6, 2020 /PRNewswire/ -- Data scientists from UK-headquartered AI precision medicine company, PrecisionLife, have used the Company's proprietary AI enabled precision medicine platform to identify 59 repurposing drug candidates that could be used to develop new therapeutic strategies to increase the survival rate of patients who develop sepsis while suffering from severe COVID-19.

Disease architecture of the sepsis cohort generated by the PrecisionLife platform. Each circle represents a disease associated SNP genotype, edges represent co-association in patients, and colors represent distinct patient sub-populations or communities'.

The new study, released today on Biorxiv sought to identify genetic risk factors for sepsis especially in the context of COVID-19, and to use these insights to identify existing drugs that might be used to treat life-threatening late-stage disease.

"Ours is the first study looking at host genomics and opportunities to treat later stage severe disease where host immune processes take over,"said Dr Steve Gardner CEO of PrecisionLife.

Like the initial genomic studies on COVID-19 patients, previous analyses of sepsis patients have failed to identify more than a handful of genetic variants that predispose individuals to developing the disease. By providing deeper insights, this study identifies novel approaches and hope for new therapies.

PrecisionLife analyzed patient datasets compiled by UK Biobank to identify genes associated with sepsis, which are also found in severe COVID-19 patients. Sepsis is observed in 60% of severe COVID-19 patients and is a life-threatening condition with a mortality rate of approximately 20%.

The team identified mutations in 70 sepsis risk genes, 61% of which were also present specifically in severe COVID-19 patients. Several of the disease associated genetic signatures found in both sepsis and severe COVID-19 patients have previously been linked to cancer, immune response, endothelial and vascular inflammation and neuronal signalling.

13 of the sepsis risk genes, which the study shows are also COVID risk genes, are known to be druggable i.e. targeted by active chemical compounds used to treat these other diseases and therefore represent potential drug repurposing opportunities. The study went on to identify 59 compounds and drugs that are known to be active against these 13 targets. These could form the basis for future drug trials and repurposing projects. They could also offer potential as COVID-19 high risk biomarkers.

"Our high-resolution genomic analysis tools have allowed us to develop new insights into two serious and complex diseases for which new therapeutic options are urgently required. We hope that these will lead to better understanding of what drives sepsis in COVID-19 patients and result in new ways to treat seriously ill patients," said Dr Gardner.

PrecisionLife is disclosing its new insights and will be working with international collaborators to investigate therapeutic strategies that may help to reduce the high mortality rates in patients who develop sepsis with or without the context of COVID-19.

Story continues

As more COVID-19 patient data become available in UK Biobank and other patient data sources, PrecisionLife will be able to analyze the clinical impact of these disease signatures in a larger group of patients.

For more information, please see http://www.precisionlife.com, or email covid-19@precisionlife.com.

Follow us on Twitter @precisionlifeAI and on LinkedIn http://www.linkedin.com/company/precisionlifeai

About PrecisionLife

PrecisionLife Ltd started in 2015, built on a shared vision to bring a new level of analytical capability to computational biology, genomic medicine and healthcare. Its powerful data analytics platform is built on a unique mathematical framework and over 30 years' experience in delivering new technologies and products to enable the discovery of richer and more useful links between patients, disease, targets and drugs.

Headquartered in the UK, PrecisionLife also has operations in the US, Denmark and Poland.

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AI Precision Medicine Company, PrecisionLife, Have Identified 59 Repurposing Drug Candidates That Could Be Used to Increase the Survival Rate of...

Higher alcohol consumption was shown to be associated with an increased risk of having a stroke or developing peripheral artery disease, according to new research published in Circulation: Genomic and Precision Medicine.While observational studies have consistently shown that heavy alcohol consumption is associated with an increased risk of certain cardiovascular diseases, they often use self-reported data and are unable to determine cause. Researchers in this study used a different technique called Mendelian randomization that identifies genetic variants with a known association to potential risk factors to determine the potential degree of disease risk.

Since genetic variants are determined at conception and cannot be affected by subsequent environmental factors, this technique allows us to better determine whether a risk factor in this case, heavy alcohol consumption is the cause of a disease, or if it is simply associated, said Susanna Larsson, Ph.D., senior researcher and associate professor of cardiovascular and nutritional epidemiology at Karolinska Institutet in Stockholm, Sweden. To our knowledge, this is the first Mendelian randomization study on alcohol consumption and several cardiovascular diseases.

Researchers analyzed the genetic data from several large-scale consortia and the UK Biobank, which follows the health and well-being of 500,000 United Kingdom residents. Results indicate that with higher alcohol consumption:

Higher alcohol consumption is a known cause of death and disability, yet it was previously unclear if alcohol consumption is also a cause of cardiovascular disease. Considering that many people consume alcohol regularly, it is important to disentangle any risks or benefits, Larsson said.Researchers noted that this study suggested the mechanism by which higher consumption was associated with the risk of stroke and PAD may be blood pressure.

According to a statement on dietary health, the American Heart Association believes that alcohol intake can be a component of a healthy diet if consumed in moderation (no more than one alcoholic drink per day for women and 2 alcohol drinks per day for men) and only by nonpregnant women and adults when there is no risk to existing health conditions, medication-alcohol interaction, or personal safety and work situations. One drink is equivalent to 12 ounces of beer (5% alcohol); 5 ounces of wine (12% alcohol); or 1.5 ounces of 80-proof distilled spirits (40% alcohol).

The study has some limitations. According to Dr. Larsson, the prevalence of heavy drinking in the UK Biobank was low, and it is unlikely that the burden of increased risk of cardiovascular disease is restricted to heavy drinkers alone. Also, the exact amount and frequency of alcohol consumed could not be quantified for this study. The researchers said the causal role of alcohol consumption on cardiovascular diseases other than stroke and peripheral artery disease requires further research.ReferenceLarsson et al. (2020). Alcohol Consumption and Cardiovascular Disease: A Mendelian Randomization Study. Circulation: Genomic and Precision Medicine. DOI: https://doi.org/10.1161/CIRCGEN.119.002814

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Genetic Study Links Higher Alcohol Consumption to Increased Stroke and PAD Risk - Technology Networks

New research suggests the prevalence of infection has links to the development of some types of cancer.

A new study has suggested that before developing some forms of cancer, people experienced increased rates of infectious diseases, such as influenza and pneumonia.

The study, published in the journal Cancer Immunology Research, might help develop diagnostic methods for detecting cancers.

Previous research has indicated that there is a link between immunity, inflammation, and cancer.

Inflammation can promote the development of cancers. This can compromise a persons immune system, which can, in turn, increase inflammation.

Dr. Shinako Inaida, a visiting researcher at the Graduate School of Medicine at Kyoto University in Japan and the corresponding author of the study, explains. Cancer can develop in an inflammatory environment caused by infections, immunity disruption, exposure to chemical carcinogens, or chronic or genetic conditions.

An individuals immunity is thought to be a factor in the development of cancer, but additional research is needed to understand the relationship [between] precancerous immunity, infections, and cancer development. This information may contribute to efforts to prevent or detect cancer.

Consequently, it may be valuable to investigate the relationship between immunity, inflammation, and cancers.

The researchers wanted to understand the relationship between the prevalence of specific infectious diseases that could cause inflammation and cancer development.

To investigate, the authors took their information from a 7-year Japanese social health insurance system database.

The researchers looked at data from 50,749 participants. All the participants were over the age of 30 and did not have any detected immunodeficiency.

The case group comprised 2,354 participants who had developed a form of cancer in the 7th year of the study. The control group consisted of 48,395 people who had no cancer diagnosis during the 7 years of the study, plus an additional final year.

The authors then calculated the prevalence of influenza, gastroenteritis, hepatitis, and pneumonia infections for the two groups.

The authors found a clear link between the prevalence of the four illnesses and the later development of cancer.

The case group experienced significantly higher infection rates than the control group in the 6 years before cancer diagnosis.

Members of the case group experienced higher rates of infection in the year before their cancer diagnosis than those in the control group. During this year, the case group experienced an 18% greater infection of influenza, 46.1% of gastroenteritis, 232.1% of hepatitis, and 135.9% for pneumonia than the control group.

The authors also noted that there was a relationship between different infections and different cancers.

For example, people who developed male germ cell cancers were more likely to have experienced influenza. People who developed stomach cancer were more likely to have had pneumonia, and people who developed blood or bone cancers were more likely to have had hepatitis.

However, as Dr. Inaida points out, [i]nterestingly, we found that infection afflicting a specific organ did not necessarily correlate with increased risk of cancer in the same organ.

The authors point out that the study had some limitations. For example, the data provided limited information on underlying genetic and medical conditions, as well as environmental exposures and different lifestyles. These may have affected the chances of infection and developing cancer.

Nonetheless, by making clear an association between infections, inflammation, immunity, and the development of cancers, future research can look in more detail at the precise mechanisms that govern these relationships.

This may then open the door to better diagnostic methods.

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Infection rates may have links to cancer - Medical News Today

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SAN RAFAEL, CA, USA I May 3, 2020 I BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced that the company has entered into a preclinical collaboration and license agreement with DiNAQOR AG (DiNAQOR), a gene therapy platform company, to develop novel gene therapies to treat rare genetic cardiomyopathies. DiNAQOR will receive an undisclosed upfront payment and is eligible to receive development, regulatory and commercial milestones on product sales in addition to tiered royalties on worldwide sales. The company did not disclose financial terms. BioMarin management reiterated its 2020 GAAP net income guidance of $20 to $80 million, inclusive of this collaboration.

The license initially covers DiNAQOR's lead program, DiNA-001 for MYBPC3 hypertrophic cardiomyopathy (HCM). Additionally, the companies will collaborate on several of DiNAQOR's other pipeline programs, and BioMarin has the option to extend the license to include these additional programs on similar terms. Reflecting the long-term commitment to the collaboration, BioMarin is simultaneously investing in DiNAQOR.

"With this agreement, BioMarin is continuing to apply its gene therapy know-how and manufacturing expertise in new areas like cardiology," said Jean-Jacques Bienaim, Chairman and Chief Executive Officer at BioMarin. "This collaboration extends our global leadership position in gene therapy and boosts our potential to transform the lives of patients worldwide with rare genetic cardiomyopathies."

"We are thrilled to collaborate with the researchers at DiNAQOR to conduct this pioneering work on the development of gene therapies for inherited cardiomyophathies," said Lon Cardon, Chief Scientific Strategy Officer and Senior Vice President at BioMarin. "We believe there is tremendous potential in combining our experience in gene therapy research and development with DiNAQOR's in-depth knowledge of genetic heart diseases."

DiNAQOR was founded and is led by several leading pharmaceutical and biotechnology executives and academics with deep cardiology and gene therapy expertise. The company's holistic approach to gene therapy is focused on gene therapies for the heart that deliver a medical solution that can safely deliver gene therapies to the heart muscle, ensure transduction of the cardiac cells, and limit the exposure of the therapy to other organs.

"BioMarin is a global leader in rare disease research, development and commercialization, and their commitment to DiNA-001 is a powerful validation of DiNAQOR's gene therapy platform," said Dr. Johannes Holzmeister, Co-Founder, Chairman and CEO at DiNAQOR. "We believe our platform has many potential applications and this milestone agreement will enable us to invest in expanding our genetic medicine pipeline."

"Momentum for gene therapies continues to build, and BioMarin has demonstrated tremendous scientific, clinical, and manufacturing leadership and expertise in the space," said Thomas Voit, M.D., Ph.D., Co-Founder and Chief Scientific Officer at DiNAQOR and Director of the Biomedical Research Centre at the Great Ormond Street Hospital and the UCL Institute of Child Health, University College London. "We are looking forward to combining our strengths to expand the promise of gene therapy treatments by targeting the heart muscle to treat rare genetic cardiomyopathies."

About HCM and MYBPC3

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic heart diseases, with about 500,000 patients diagnosed with HCM worldwide.Up to 60% of HCM cases have a genetic origin, and it is estimated that 40% of those have mutations in MYBPC3, the gene that encodes cardiac myosin-binding protein C (MyBP-C).

HCMaffects the heart muscle, causing the muscle to enlarge. HCM patients have an increased risk of developing heart failure and life-threatening arrhythmias. There are no approved pharmacological treatment options available that address the underlying disease biology of HCM and invasive surgery or heart transplantation may be the only options available for patients with advanced disease.

About BioMarin

BioMarin is a global biotechnology company that develops and commercializes innovative therapies for serious and life-threatening rare genetic diseases. The Company's portfolio consists of six commercialized products and multiple clinical and pre-clinical product candidates. For additional information, please visitwww.biomarin.com. Information on BioMarin's website is not incorporated by reference into this press release.

About DiNAQOR

Founded in 2019, DiNAQOR AG is a global gene therapy platform company focused on advancing novel solutions for patients suffering from heart disease. The company's lead preclinical program, DiNA-001 is focused on the treatment of MYBPC3-linked cardiomyopathy. DiNAQOR is headquartered in Pfffikon, Switzerland, with additional presence in London, England and Boston, Massachusetts (US). For more information visit http://www.dinaqor.com.

SOURCE: BioMarin Pharmaceutical

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BioMarin Extends Gene Therapy Leadership with DiNAQOR in a Preclinical Collaboration and License Agreement to Develop Gene Therapies for Rare Genetic...