Gene-editing damages DNA more than thought: study

Agencies
July 17, 2018

Paris, Jul 17:  A revolutionary gene editing technique hailed as the future of disease eradication and mooted for a Nobel Prize may be less precise and cause more cell damage than previously thought, researchers said Monday.

Lab experiments using mouse and human cells revealed that the CRISPR-Cas9 technique "frequently" caused "extensive" gene mutations, a study team reported.

"This is the first systematic assessment of unexpected events resulting from CRISPR-Cas9 editing," said Allan Bradley of the Wellcome Sanger Institute in England, where the team conducts research.

The research showed that "changes in the DNA have been seriously underestimated before now," said Bradley, who co-authored a study published in the journal Nature Biotechnology.

The mutations have not been shown to be harmful, nor benign.

"It is important that anyone thinking of using this technology for gene therapy proceeds with caution and looks very carefully to check for harmful effects," Bradley said in a statement issued by the institute.

First unveiled about six years ago, CRISPR-Cas9 allows scientists to insert, remove and correct a faulty sequence on a strand of DNA in a cell with pinpoint precision.

It has raised hopes that one-day disease-causing genes could be removed or altered before a baby is even born.

In recent years, CRISPR-Cas9 has repeatedly been predicted to win the Nobel Chemistry Prize.

CRISPRs -- clustered regularly interspaced short palindromic repeats -- are part of the immune defence system in bacteria, used to hone in on the exact spot on the genome where the cut should be made.

Cas9 is a protein used as "scissors" to snip through the faulty gene, which is then replaced or fixed by the cell's own DNA repair mechanism.

The technique's safety has not yet been proven, and it is not approved for use in human therapy.

So far, researchers have used it to improve hearing in mice going deaf and to fix a disease-causing mutation in cloned, early-stage human embryos.

But the new finding raises "safety implications," the team said.

They found "large genetic rearrangements such as DNA deletions and insertions" in cells, which could lead to important genes being switched on or off and causing dangerous changes.

The research also showed that standardized tests do not pick up damage to DNA caused by CRISPR-Cas9.

Experts not involved in the study said it was unclear how such large, unintended changes were not noticed before.

But, "the results give no reason to panic or to lose faith in the methods when they are carried out by those who know what they are doing," said Robin Lovell-Badge of The Francis Crick Institute, a biomedical research centre in London.

For Francesca Forzano, a consultant in clinical genetics and genomics with the Guy's and St Thomas' NHS Foundation Trust, the work showed that CRISPR-Cas9 "is much less safe than previously thought" and that safety-monitoring techniques were "not entirely adequate".

More research is needed before any clinical application of the method is considered, said Forzano.

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Agencies
May 8,2020

As Europe and the US loosen their lockdowns against the coronavirus, health experts are expressing growing dread over what they say is an all-but-certain second wave of deaths and infections that could force governments to clamp back down.

"We are risking a backslide that will be intolerable," said Dr Ian Lipkin of Columbia University's Center for Infection and Immunity.

Around the world, German authorities began drawing up plans in case of a resurgence of the virus. Experts in Italy urged intensified efforts to identify new victims and trace their contacts. And France, which has not yet eased its lockdown, has already worked up a "reconfinement plan" in the event of a new wave.

"There will be a second wave, but the problem is to which extent. Is it a small wave or a big wave? It is too early to say," said Olivier Schwartz, head of the virus unit at France's Pasteur Institute.

In the US, with about half of the states easing their shutdowns to get their economies restarted and cellphone data showing that people are becoming restless and increasingly leaving home, public health authorities are worried.

Many states have not put in place the robust testing that experts believe is necessary to detect and contain new outbreaks. And many governors have pressed ahead before their states met one of the key benchmarks in the Trump administration's guidelines for reopening -- a 14-day downward trajectory in new illnesses and infections.

"If we relax these measures without having the proper public health safeguards in place, we can expect many more cases and, unfortunately, more deaths," said Josh Michaud, associate director of global health policy with the Kaiser Family Foundation in Washington.

Cases have continued to rise steadily in places such as Iowa and Missouri since the governors began reopening, while new infections have yo-yoed in Georgia, Tennessee and Texas.

Lipkin said he is most worried about two things: the reopening of bars, where people crowd together and lose their inhibitions, and large gatherings such as sporting events, concerts and plays. Preventing outbreaks will require aggressive contact tracing powered by armies of public health workers hundreds of thousands of people strong, which the US does not yet have, Lipkin said.

Worldwide the virus has infected more than 36 lakh people and killed over a quarter-million, according to a tally by Johns Hopkins University that experts agree understates the dimensions of the disaster because of limited testing, differences in counting the dead and concealment by some governments.

The US has recorded over 70,000 deaths and 12 lakh confirmed infections, while Europe has reported over 140,000 dead.

This week, the researchers behind a widely cited model from the University of Washington nearly doubled their projection of deaths in the US to around 134,000 through early August, in large part because of the easing of state stay-at-home restrictions. Newly confirmed infections per day in the US exceed 20,000 and deaths per day are running well over 1,000.

In hard-hit New York City, which has managed to bring down deaths dramatically even as confirmed infections continue to rise around the rest of the country, Mayor Bill de Blasio warned that some states may be reopening too quickly.

"My message to the rest of the country is learn from how much effort, how much discipline it took to finally bring these numbers down and follow the same path until you are sure that it is being beaten back," he said on CNN, "or else, if this thing boomerangs, you are putting off any kind of restart or recovery a hell of a lot longer."

A century ago, the Spanish flu epidemic's second wave was far deadlier than its first, in part because authorities allowed mass gatherings from Philadelphia to San Francisco.

"It is clear to me that we are in a critical moment of this fight. We risk complacency and accepting the preventable deaths of 2,000 Americans each day," epidemiologist Caitlin Rivers, a professor at Johns Hopkins, told a House subcommittee in Washington.

President Donald Trump, who has pressed hard to ease the restrictions that have throttled the economy and thrown more than three crore Americans out of work, pulled back Wednesday on White House plans revealed a day earlier to wind down the coronavirus task force.

He tweeted that the task force will continue meeting indefinitely with a "focus on SAFETY & OPENING UP OUR COUNTRY AGAIN".

Underscoring those economic concerns, the European Union predicted the worst recession in its quarter-century history. And the US unemployment rate for April, which comes out on Friday, is expected to hit a staggering 16 per cent, a level last seen during the Great Depression of the 1930s.

Governors continue to face demands, even lawsuits, to reopen. In Michigan, where armed demonstrators entered the Capitol last week, the Republican-led Legislature sued Democratic Governor Gretchen Whitmer, asking a judge to declare invalid her stay-at-home order, which runs at least through May 15.

In hard-hit Italy, which has begun easing restrictions, Dr Silvio Brusaferro, president of the Superior Institute of Health, urged "a huge investment" of resources to train medical personnel to monitor possible new cases of the virus, which has killed about 30,000 people nationwide.

He said that contact-tracing apps which are being built by dozens of countries and companies are not enough to manage future waves of infection.

German Chancellor Angela Merkel said after meeting with the country's 16 governors that restaurants and other businesses will be allowed to reopen in the coming weeks but that regional authorities will have to draw up a "restriction concept" for any county that reports 50 new cases for every 100,000 inhabitants within a week.

Lothar Wieler, head of Germany's national disease control centre, said scientists "know with great certainty that there will be a second wave" of infections.

Britain, with over 30,000 dead, the second-highest death toll in the world behind the US, plans to extend its lockdown but has begun recruiting 18,000 people to trace contacts of those infected.

In other developments, the US Centers for Disease Control and Prevention said nearly 5,000 coronavirus illnesses and at least 88 deaths have been reported among inmates in American jails and prisons. An additional 2,800 cases and 15 deaths were reported among guards and other staff members.

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Agencies
July 15,2020

The first COVID-19 vaccine tested in the US revved up people's immune systems just the way scientists had hoped, researchers reported Tuesday -- as the shots are poised to begin key final testing.

No matter how you slice this, this is good news, Dr. Anthony Fauci, the U.S. government's top infectious disease expert, told The Associated Press.

The experimental vaccine, developed by Fauci's colleagues at the National Institutes of Health and Moderna Inc., will start its most important step around July 27: A 30,000-person study to prove if the shots really are strong enough to protect against the coronavirus.

But Tuesday, researchers reported anxiously awaited findings from the first 45 volunteers who rolled up their sleeves back in March. Sure enough, the vaccine provided a hoped-for immune boost.

Those early volunteers developed what are called neutralizing antibodies in their bloodstream -- molecules key to blocking infection -- at levels comparable to those found in people who survived COVID-19, the research team reported in the New England Journal of Medicine.

This is an essential building block that is needed to move forward with the trials that could actually determine whether the vaccine does protect against infection, said Dr. Lisa Jackson of the Kaiser Permanente Washington Research Institute in Seattle, who led the study.

There's no guarantee but the government hopes to have results around the end of the year -- record-setting speed for developing a vaccine.

The vaccine requires two doses, a month apart.

There were no serious side effects. But more than half the study participants reported flu-like reactions to the shots that aren't uncommon with other vaccines -- fatigue, headache, chills, fever and pain at the injection site. For three participants given the highest dose, those reactions were more severe; that dose isn't being pursued.

Some of those reactions are similar to coronavirus symptoms but they're temporary, lasting about a day and occur right after vaccination, researchers noted.

Small price to pay for protection against COVID, said Dr. William Schaffner of Vanderbilt University Medical Center, a vaccine expert who wasn't involved with the study.

He called the early results a good first step, and is optimistic that final testing could deliver answers about whether it's really safe and effective by the beginning of next year.

It would be wonderful. But that assumes everything's working right on schedule, Schaffner cautioned.

Moderna's share price jumped nearly 15 percent in trading after US markets closed. Shares of the company, based in Cambridge, Massachusetts, have nearly quadrupled this year.

Tuesday's results only included younger adults. The first-step testing later was expanded to include dozens of older adults, the age group most at risk from COVID-19.

Those results aren't public yet but regulators are evaluating them. Fauci said final testing will include older adults, as well as people with chronic health conditions that make them more vulnerable to the virus and Black and Latino populations likewise affected.

Nearly two dozen possible COVID-19 vaccines are in various stages of testing around the world. Candidates from China and Britain's Oxford University also are entering final testing stages.

The 30,000-person study will mark the world's largest study of a potential COVID-19 vaccine so far. And the NIH-developed shot isn't the only one set for such massive U.S. testing, crucial to spot rare side effects. The government plans similar large studies of the Oxford candidate and another by Johnson & Johnson; separately, Pfizer Inc. is planning its own huge study.

Already, people can start signing up to volunteer for the different studies.

People think this is a race for one winner. Me, I'm cheering every one of them on, said Fauci, who directs NIH's National Institute of Allergy and Infectious Diseases.

We need multiple vaccines. We need vaccines for the world, not only for our own country. Around the world, governments are investing in stockpiles of hundreds of millions of doses of the different candidates, in hopes of speedily starting inoculations if any are proven to work.

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Agencies
April 21,2020

The Lockdown is not a cure but a critical strategy to prevent the geographical spread of COVID-19.

While pandemics at this level involves actual life threatening situations for individual's or significant others in one's immediate circle, it envisages a marked disruption in routine life. Even after the pandemic has been contained and will come to pass; it's aftermath will leave a trailblazer which demands planning and implementation of a post pandemic reconstruction of society with potentially traumatic experiences varying in intensity, multiplicity and duration.

Degree of Trauma

It would do well for each one of us to realise that the pandemic is "potentially traumatic", since not everyone will experience COVID -19 as a traumatic event in their lives. Yet, there will be those who may develop post pandemic stress reactions, depression and related dysfunction and pathological reactions while still other exhibit healthy reactions to the same set of circumstances.

"Psychological reactions to the pandemic can be distilled into four distinct prototypical patterns, namely, Resilience, Recovery, Chronic and Delayed patterns which may vary in intensity, multiplicity, and duration. Resilient individual have an ability to bounce back from adversity and experience modest or little disruption in normal functioning and are able to maintain a relatively stable, healthy levels of psychological functioning even after enduring the pandemic. Recovery pattern is characterised by relatively rapid reduction in symptoms and return to normal functioning whereas chronic pattern is characterised by symptoms and dysfunction of a long duration," says Pune-based military psychologist Lt Col Dr Samir Rawat.

Challenges at the Individual and Community Levels

From a psychological perspective, post pandemic reconstruction would entail catering to the problems, concerns and needs of those adversely impacted by the COVID -19 with stress symptoms typically characterised by individual's experiencing an overwhelming trauma of the pandemic (for example, recurring nightmares/ breaking into a cold sweat, flashback of stressful events, increasing irritability, low frustration tolerance or emotional numbing).

It could also manifest in depressive symptoms which may result in lack of interest or diminished pleasure in activities and things which you earlier liked to do, feelings of worthlessness or even survivor guilt in case of a loss of a loved one due to COVID-19, fleeting thoughts of death and suicidal ideation. Physical symptoms, on the other hand could be a decrease in appetite, weight and sleep problems, inability to focus and lack of concentration.

Undoubtedly, the pandemic will cause a financial loss of varying magnitude to many, especially the marginalised and economically disadvantaged strata of daily wage earners; it will also lead to loss of jobs (already beginning to show), homelessness, occupational difficulties and new challenges in interpersonal relations at work and on the home front, besides physical health problems and psychological barriers with new norms of accepted social behaviour (social distancing, handshakes, an obsession for cleanliness to name a few).

Emotional battles

Many factors may influence whether individuals come out stronger and more resilient or surrender to the pandemic. Emotion Regulation is one such long term critical factor that can play an important role in contributing to varying degrees of adaptation with negative or positive outcomes. While we know that primary emotions are fear, anger, disgust, joy, anticipation, acceptance, sadness and surprise, other basic emotions include wonder, love, desire, joy, hatred, sadness, attachment, disgust, rage and even expectancy .

To be able to regulate these emotions and avoid negativity , especially on social media platforms is likely to increase efforts in emotion regulation which involves initiating, increasing or maintaining an emotional response.

This means by regulating or on the other hand by stopping, decreasing or avoiding an emotional response, that is, by down-regulating, depending on the individual's objectives and goals or his /her ability to regulate emotions in the valued and given direction.

"One of the best ways to regulate emotions is through cognitive restructuring wherein we change the way we think; after all it is not the event but the interpretation of the event which is perceived as stressful and finding meaning promotes resilience and reduces risk and vulnerability to stress," advises Dr Rawat.

Adding, "Clearly, we need to have a psychological plan to prevent, mitigate and minimise negative outcomes by post pandemic reconstruction of society at an individual and community level all over the country; this has to be integrated by all leaders across verticals in diverse domains."

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