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Genetic Linkage

Gastruloids Stand In for Early Human Embryos

Remember human embryonic stem (hES) cells? We don't hear much about them anymore. So I was surprised to see an application of the controversial cells to grow human embryo-like structures in a recent issue of Nature.

 

Human embryonic stem cells are not, and have never been, taken from human embryos. Instead, they're grown in laboratory glassware from cells that are sampled from the inner cell mass. The "icm" is the stage when the prenatal human is a smear of cells hugging the interior of a hollow ball of cells, the blastocyst. The icm expands and contorts, layering itself into embryohood, as the blastocyst gives rise to the nurturing extra-embryonic membranes.

 

In 2009 the National Institutes of Health issued guidelines forbidding researchers from using government funds to derive new hES cells, but the agency provides nearly 500 already-existing hES cell lines. They represent dozens of inherited diseases, from cancers to neurological conditions to connective tissue disorders – quite an eclectic list.

 

To continue reading, go to my blog DNA Science, where this post first appeared.

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A Tale of Two Clinical Trials: Gene Therapy for a Rare Disease and a Vaccine for COVID-19

Encouraging preliminary findings in a phase I clinical trial for a COVID-19 vaccine were widely reported as soon as the paper appeared in The New England Journal of Medicine July 14. Coverage of the recent deaths of two boys in a clinical trial to test a gene therapy for a rare, devastating muscle disease were more under-the-radar.

Comparing the two very different scenarios illuminates the scientific rigor behind the clinical trial process.

 

The boys had X-linked myotubular myopathy. MTM affects 1 in 50,000 male births. Seventy-five percent of boys die in weeks or months of respiratory failure; average life expectancy is 29 months. Given that prognosis, taking the risk of an experimental treatment in a clinical trial makes sense. Parents of participants as well as physicians know that children can die during the trial, due to the disease or to toxicity at higher doses of a treatment.

 

In contrast, volunteers in a clinical trial to evaluate a vaccine are healthy.

 

Although comparing MTM gene therapy and a COVID-19 vaccine is a bit of apples and oranges, those fruits are in the same bin in terms of progression through the three phases of development of a new treatment or preventative:

 

To continue reading go to my blog DNA Science, where this post first appeared. 

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Two Views of Leeches, A Century Apart

Two genome sequences of the European medicinal leech Hirudo medicinalis have just been revealed in a pair of papers, and the unexpected complexity may translate into new anti-coagulant drugs.

 

Some quick leech factoids: Of the 650 species, about 20 percent live in the ocean, where they feed on fish. The longest leech known extends 18 inches. A leech has 32 distinct brains and the genome extends about 230 million base pairs of DNA. Leeches belong to the same phylum as the earthworms, Annelida.

 

A Long History

 

The animals practice "hematophagy" – literally "eating blood." A leech will gorge itself to five times its weight until, satiated, it drops off its victim. The jaws are strong enough to penetrate a hippo's hide. Leeches have been used medicinally in bloodletting for thousands of years.

 

To continue reading, go to DNA Science, where this post first appeared.

 

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How an Antibody Cocktail Against COVID-19 Channels the 3 Stooges – But is a Great Idea

"You imbecile!" bellowed Moe Howard as he stuck a finger up the nose of Curly. Moe the bully would often flick his hand across an unsuspecting face or deliver a two-pronged eye poke to distract from a simultaneous, more serious blow, elsewhere.

 

Moe, Larry, and Shemp/Curly/Joe were the various incarnations of The Three Stooges, the famed comedy team, with roots in vaudeville, who made films and TV shows from 1922 until 1970. Many of us growing up in the sixties loved them, while many of our parents didn't. The 2012 film didn't do the original three idiots justice.

 

An image of Moe poking Curly popped into my head while reading two new papers in Science that report teaming antibodies to tackle SARS-CoV-2, the virus behind COVID-19.

 

The papers describe the basis of two clinical trials that biotech company Regeneron is conducting to assess a pair of antibodies that work together, binding the viral spike protein where it contacts the human receptor (ACE2) and gains entry into our cells, but at different sites within the "receptor-binding domain." One antibody is a distractor of sorts, like Moe's finger-up-the-nose.

 

The key to the technology is in the coupling. "Our work inventing novel antibodies has shown that individual antibodies, no matter how good, are likely not enough against the devastating virus that causes COVID-19 and the ways it seeks to 'escape' being neutralized," said George D. Yancopoulos, MD, PhD, Co-Founder, President and Chief Scientific Officer at Regeneron.

 

An antibody cocktail – pitched as "antibody medicine" – provides short-term, passive immunity, as opposed to the lasting active immunity of a vaccine, in which the body learns to manufacture its own antibodies. The Chinese proverb "Give a man a fish and you feed him for a day. Teach a man to fish and you feed him for a lifetime" makes the distinction: an antibody cocktail is a fish, a vaccine the ability to fish. Both are needed desperately right now. Antibody protection would last weeks or months.

 

Viral Resistance is a Natural Consequence of Evolution

 

 

To continue reading, go to DNA Science, where this post first appeared.

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‘Humanized mice’: Chimeras fuel quest to treat chronic diseases, cancer and even COVID-19

Some medical conditions can't be ethically investigated in humans, so researchers are finding interesting ways to grow people parts in the bodies of other types of animals. Jian Feng and colleagues at the University at Buffalo recently engineered prenatal mice that have human cells in key parts of their anatomy. Their report appears in Science Advances.

 

The humanized mice may one day incubate human cells needed for treatments of chronic diseases like kidney failure and diabetes, and provide new and improved models of how the human body succumbs to various conditions, from cancer to degenerative conditions to COVID-19.

 

To continue reading, go to Genetic Literacy Project, where this post first appeared.

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Protests and the Pandemic: Will COVID-19 Resurge?

Events have collided in a way that even the most imaginative fiction writer couldn't have conjured up: a global assault by an enemy that no one can see, and a nearly-9-minute-long murder of a black man by a white police officer captured on video for the world to see.

 

At the protests that the killing of George Floyd triggered, responses as global as COVID-19, many people are wearing masks and distancing themselves as they march, kneel, or lie down chanting "I can't breathe." But some are not following public health recommendations. And many are shouting, as police hurl chemicals that make people cough. What will the consequences of the massive and necessary Black Lives Matter protests be on public health?

 

The mathematical models used to predict the next stages of the pandemic may factor in the expected – Memorial Day celebrations and phased reopenings. But they couldn't have foreseen the events of the past two and a half weeks. How can people in close proximity for extended periods of time, moving and outdoors but hollering and crying, even if masked, affect transmissibility of the coronavirus? That seems like too many variables to model, but some recent technical articles might provide some insight.

 

Mask Math

 

 

To continue reading, go to my blog DNA Science, where this post first appeared.

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Dr. Fauci Optimistic About COVID-19 Vaccine Progress

 

On June 2, JAMA (The Journal of the American Medical Association) held a Q+A for the media with Dr. Anthony Fauci, director of the NIAID, accessible here. JAMA Editor Dr. Howard Bauchner frequently interviews leaders in the quest to understand and combat COVID-19. The webinar series has been a huge help to the science journalism community.

 

Dr. Fauci was considerably more upbeat in early June than he was on a JAMA webinar March 23, soon after he was present for a White House press briefing at which more than 10 unmasked people standing close to each other addressed more than 10 journalists on matters of public health and the pandemic.

 

At that JAMA webinar, Dr. Fauci explained the vaccine timetable based on how things were done in the past, and predicted we'd have one in 12 to 18 months. He said, then, that there's "no vaccine in the immediate future, which tells us we need to rely on public health measures."

 

To continue reading, go to my blog DNA Science.

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The Fallacy of the “Make It So” Mentality to Rush a COVID-19 Vaccine

Taking a meatloaf out of the oven too soon is an inconvenience, easily corrected by shoving it back in until it's ready.

 

Marketing a vaccine for COVID-19 too soon could be a disaster, with massive, far-reaching consequences. But that's what the U.S. government's Operation Warp Speed might make happen, with the goal of having a vaccine ready for distribution by year's end.

 

The problem is that vaccines aren't "found" or "discovered," like pretty shells on a beach, and if you just look enough, you'll find one. Vaccines are invented, developed, and tested, tested, tested, and that takes time. Biological factors could even make a vaccine impossible.

 

Measures are already in place to speed things along.

 

The FDA is collapsing protocols normally conducted in tandem into overlapping or parallel designs. They're allowing clinical trials to begin sooner following preclinical (non-human animal and cell-based) studies, expediting formation of institutional review boards to speed set-up of clinical trials, shifting reviewers from non-COVID projects to COVID ones, and enrolling thousands of people into clinical trials rather than the typical hundreds.

 

But will these measures be enough to roll out a vaccine six months from now? I don't think so.

 

To continue reading, go to my blog, DNA Science, at Public Library of Science. 

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Microbiome Analysis of Ancient Feces

Sometimes it can be difficult to distinguish who left a pile of poop.

 

Humans who live in multi-cat or multi-canine households might run into this problem when trying to discover which diarrhea-stricken pet to haul off to the vet.

 

Similarly, a deposit of scat on a hiking trail can inspire vivid conversations on the origin of the feces. But an intrigued hiker without a phone or camera who wants to bring a friend back for a viewing may find the excrement dispersed beyond recognition from weather conditions and trampling. Only a DNA test might be able to identify the species of animal that left the deposit if contextual clues, like a nearby moose, aren't there.

 

CoproID

 

The microbial species found within excrement – the fecal microbiome – can reveal a lot about an animal.

 

To continue reading, go to my blog DNA Science, at Public Library of Science. 

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Will the COVID-19 Pandemic End Like War of the Worlds or Logan’s Run?

In moments when I am not obsessively reading technical reports on COVID-19, my mind drifts to science fiction plots involving invaders. Do these films offer clues to how we can defeat the novel coronavirus SARS-CoV-2?

 

With the government-ordered CDC guidance for reopening delayed, dumbed-down, cut by an order of magnitude, and ignored, we need help, from anywhere, in protecting the vulnerable while restoring some economic normalcy.

 

The space invaders of the classic depictions either succumb to slowly-emerging natural weaknesses or we blow them up. But the scariest sci-fi theme to me isn't about monsters or microbes at all.

 

In the film Logan's Run, people over age 30 sacrifice themselves to save resources for the others.

 

To continue reading, go to my DNA Science blog at Public Library of Science. 

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