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Genetic Linkage

Is COVID Optimism Finally Overtaking Pessimism? Harvard Experts Weigh In

Glimmers of hope are beginning to shine through the gloom of the past year. That was evident in a recent webinar that the Massachusetts Consortium on Pathogen Readiness (MassCPR) held to "demystify" the new viral variants. Each consists of several mutations.

 

Will the variants fuel "a novel stage of contagion, COVID 2.0?" opened George Daley, MD, PhD, dean of Harvard Medical School. "What has been unsettling is how many times mutations have cropped up independently in infected patients across the globe and in petri dishes. This is a consequence of Darwinian evolution by natural selection in real time," he added. The fact that the virus, SARS-CoV-2, has mutated in the same ways at different times and places suggests that the changes benefit the virus.

 

Also disturbing is that once variants appear, they proliferate. "That suggests the virus is more contagious, or replicates faster, so that it takes over the outbreak," said Jeremy Luban, MD, from the University of Massachusetts Medical School. Most mutations are neutral; we need to worry when they combine into "variants of concern," aka VOC. "They could permit the virus to escape immune control that's been established in a person from prior infection or from a vaccine," Luban added.

 

The "big three" variants of most concern now have hard-to-remember numerical names, which avoid stigmatizing a place: B.1.3.5.1 variant (South Africa), B.1.1.7 (UK), and P.1 (Brazil). The last one may be the worst to arise, so far. It first came to attention in Manaus, Amazonia. "Up to 70% of the population had been infected and they had developed what we'd consider herd immunity that would prevent new infection," Luban explained. The explosion of hospitalizations and deaths in December, a second wave, coincided with the appearance of the P.1 variant. "Many mutations in it raise concerns about whether the virus is resistant to the immune response against the first virus," he added.

 

Tackling variants requires asking three questions, Luban said:
• Do they enhance transmission?
• Do they permit reinfection?
• Do they decrease vaccine efficacy?

 

Fortunately, the vaccines so far are doing their job. Here are 6 pieces of good news.

 

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

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Rare Disease Day 2021: Gene Therapy Ups and Downs, Again

I can't believe it's been a decade since I researched and wrote The Forever Fix: Gene Therapy and the Boy Who Saved It. Since then I've shared stories of other families doing amazing things to help researchers develop treatments for their loved ones' rare diseases. The need is all the more compelling in these days of the pandemic.

 

Now entering its fourth decade, gene therapy continues along what seems at times a never-ending rocky road, riding the waves of fantastic success and plunging setbacks.

 

A Slow Start

 

The US has approved just two gene therapies. Luxturna has provided vision to patients with a form of retinal blindness (the basis of The Forever Fix), while Zolgemsa treats spinal muscular atrophy, a disease typically lethal in young children.

 

The latest in a series of setbacks, beginning in 1999 with the death of 18-year-old Jesse Gelsinger, came just yesterday. The FDA placed a clinical hold on two gene therapy trials for sickle cell disease, following reports of blood cancer in two trial participants. But that's not all.

 

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

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Evoking Jeff Goldblum’s ‘The Fly’: Does growing human ‘brains-in-a-dish’ and creating chimeras cross a bioethical line?

Bits of human brain growing in a lab dish can reveal a great deal about how a disease begins and unfolds. But because the brain is also the seat of our consciousness and individuality, does disembodying it for science's sake pose bioethical challenges? 

 

That's what Stanford Law School researcher Henry (Hank) T. Greely addressed in "Human Brain Surrogates Research: The Onrushing Ethical Dilemma" in the January issue of The American Journal of Bioethics. Will the technology reach a stage at which the brain model is perhaps too close a mimic for comfort?

 

"If it looks like a human brain and acts like a human brain, at what point do we have to treat it like a human brain — or a human being?" he asks.

 

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

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DNA Study Adds Branch to North American Mammoth Family Tree

An international team has assembled billions of DNA snippets from molars that three mammoths left in the permafrost of northeastern Siberia, at widely different times. The research reveals an unrecognized ancestor that contributed half of the genome of the mammoth species that came to North America some 1.5 million years ago. The report appears in Nature.

 

The timescale of the study paints a portrait of mammoth evolution, perhaps even capturing a glimmer of speciation. The finding also sets back the clock of ancient DNA analysis; a horse that lived 780,000 to 560,000 years ago holds the record.

 

The three mammoth specimens were excavated in the 1970s from different locations in Siberia, dating from half a million to roughly 1.2 million years ago. They reside at the Geological Institute, Russian Academy of Sciences, in Moscow. The permafrost helped to preserve the DNA.

 

The Land Bridge Where It Happened

 

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

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How My “Fruit Fly Love Story” Presaged The Rise of COVID-19 Viral Variants

I wrote "The Making of a Mutant" in 1978. Then a PhD student in the lab of Thom Kaufman at Indiana University, I snuck the story into a draft of a manuscript we were submitting to the journal Genetics – just to see if the boss was paying attention. The tale was about our research on the mutation Antennapedia in the fruit fly Drosophila melanogaster, which reroutes development so that legs grow where antennae normally extend.

 

My story was passed down to generations of graduate students, and read aloud at Thom's 60th birthday party many years later. I published "The Making of a Mutant" at Scientific American blogs in 2012, and then here at DNA Science in 2013. It's a geneticist's love story for Valentine's Day.

 

But never in a million years could I have imagined that my vision of a mutation that takes over a population would echo in the form of a novel coronavirus that is continually reinventing itself as it tears through human bodies and populations.

 

My story chronicles how the abnormal becomes the normal, and the new normal eventually spawns a new abnormal. That's what evolution is, change at the molecular level that reverberates up through populations of organisms – and viruses. The mutations in my imagined world in a milk bottle, home to the flies, were induced – in contrast to the situation for SARS-CoV-2.

 

We can't stop evolution. Mutation is a fundamental characteristic of a genetic material, endowing it with the plasticity that underlies adaptation, which fuels evolutionary change.

 

Evolution of SARS-CoV-2 in a Single Patient

 

 

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

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Getting a COVID Vaccine is More Transparent Than Eating a Hot Dog: Countering Vaccine Hesitancy

"So, you've been eatin' hot dogs and chicken nuggets all your life and you don't want the vaccine 'cuz you don't know what's in it??" asks a befuddled chicken in a meme.

 

Actually, plenty of information is out there about "what's in it."

 

Upon entering a vaccination center, you're handed a multi-page fact sheet that, among many other things, lists the chemicals about to be plunged into your arm.

 

The first two COVID vaccines are roughly the same recipe, adjusted for proportions and tiny details: mRNA, 4 fats (including cholesterol), a pinch of sugar, and a few salts. No eggs, preservatives, ricin, or leechee nut extract. (See The First COVID-19 Vaccines: What's mRNA Got to do With it?) Ingredient lists for hot dogs and chicken nuggets are far longer and complex.

 

Yet the comparative transparency of vaccine ingredient lists isn't enough to dispel the fear of something new and unfamiliar being jabbed into your body. For many people that fear arises against a backdrop of the history of dishonesty in medicine that has misled and mistreated marginalized groups, as well as the record of unethical clinical trials for some vaccines, notably influenza.

 

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

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Are We Hurtling or Hurdling Towards Herd Immunity for COVID-19?

Vaccines against COVID-19 were developed in record-smashing time, and now that the rollout has begun, attention is returning to herd immunity, in a real rather than hypothetical sense.

 

Herd immunity refers to the protection against an infectious disease that arises when a critical mass of individuals in a population becomes immune. The pathogen can't find welcoming bodies, and the epidemic dies out. Once herd immunity is attained, mitigation measures can be relaxed. But if society opens too soon, a second and even third wave of disease can ensue – as we've seen.

 

A vaccine, engineered to evoke a strong and diverse antibody response, is more likely to build herd immunity than is natural infection.

 

Establishing herd immunity against COVID-19 requires that a whole bunch of ducks align. The variables include:

 

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

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Marketers are beginning to use data mined from consumer DNA tests. Should we be worried?

(Angie Wang)

A woman lingers at a display of coffeemakers. Soon after, images of the very same contraptions festoon her Facebook feed, courtesy of her phone's GPS and store cameras.

 

A man diagnosed with a blood clot gets TV ads for a drug to prevent further episodes.

 

A person peruses ads for indoor herb gardens for a gift and is later bombarded with botanical options on social media.

 

People turn 65, and suddenly Joe Namath interrupts their favorite TV shows, with unending descriptions of Medicare Supplement plans.

 

Coincidences? Hardly. In this age of TMI, it can feel as if our very brains are being intrusively picked, constantly.

Even our DNA can be trolled for embedded preferences and habits, if we (sometimes unknowingly) provide permission.

 

How foreboding is the 'privacy crisis'?
Remi Daviet, Gideon Nave, and Jerry Wind, from the Wharton School of the University of Pennsylvania, dissect "Genetic Data: Potential Uses and Misuses in Marketing," in a report in a special issue of the Journal of Marketing.

 

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

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What Do Non-identical Identical Twins Have to do with COVID-19? Mutation!

Identical twins Stella and Desiree Vignes were born in 1938 in a Louisiana town so small that it wasn't on any maps. Light-skinned Blacks, the girls left town together at the age of 16 to head to New Orleans to work and escape a bleak future. Stella was mistaken for White at a job interview and continued the deception to get the position, eventually marrying her boss and leaving her sister behind. Stella experienced adulthood as White, Desiree as Black.

 

The Vignes sisters were born in the imagination of Brit Bennett, an extraordinary young writer. Her bestseller "The Vanishing Half" traces the experiences of the twins in a world where what happens to them depends upon how others perceive them – as Black or White. Of course, they go on to live starkly different lives, Stella in wealthy Brentwood, California, and Desiree back in her hometown waitressing in a diner. The drama intensifies when their grown daughters meet, one a pale blonde, the other "a dark girl" black as ebony.

 

Identical twins and higher multiples are, indeed, fascinating. The 2018 film Three Identical Strangers tells the tale of triplet brothers who met by chance at age 19 in 1980. It echoes the fictional film The Parent Trap, from 1961 with Hayley Mills and reborn in 1998 with Lindsay Lohan, each in dual roles.

 

Twin Studies

 

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

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A dangerous stage in the evolution of the novel coronavirus is upon us with the discovery of “escape mutations.” Artificial intelligence may be our best response

Real life with COVID-19 is now scarier than anything a sci-fi writer could envision. So-called "escape mutations" that can turn the virus into an out-of-control shape-shifter that hides from the immune system are now a frightening reality. And they can't be totally stopped with masks or social distancing, lockdowns or travel restrictions. Even if we could keep all viruses out, the ones already here are mutating in a direction that keeps them infectious and deadly. The battle between us and this often-lethal virus has just jumped to a new level. 

 

While it may take awhile to see whether these escape mutations will evade the vaccines approved or in the pipeline, Tyler Starr from the Fred Hutchinson Cancer Research Center and colleagues report in a new study in Science an effect on two already available treatments — monoclonal antibodies. They've identified an escape mutation with a single glitch that enables the virus to evade Regeneron's double-antibody REGN-COV2 "cocktail" (which Trump took) and a third antibody in Eli Lilly's LY-CoV016. The researchers found the escapee using a new lab mapping technique that displays viruses contorted with mutation, and then they found it in a patient who was still testing positive, 145 days after the first test.

 

What does this mean? The discovery of escape mutations derailing antibody treatments means that the companies' initial tests hadn't caught them all. And the escape mutations — the new mapping revealed three others — are already in circulation.

 

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

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