Ricki Lewis

Five days ago, Sandy's husband allowed the staff in the ICU to turn off her life support, and COVID claimed yet another.

Sandy and her husband lived in a cabin nestled into a mountainside in a small town in the Rockies, next door to my daughter Sarah. I met Sandy last March, when Larry and I and our daughter Carly visited.

I'd heard about Sandy, how she helped Sarah deal with encroaching wildfires right after she moved in. But she wasn't what I expected.

Sandy looked younger than her 70+ years and remarkably like Stevie Nicks, pretty and vibrant and warm, with glimmering white-blond hair and beautiful permanent makeup that accentuated her eyes. She was owl-like. Her husband reminded me a little of a rumpled, flannel-shirted Eddie Vedder, or James Taylor with much better hair, an aging yet striking rock star couple.

We all clicked. Two friends dropped by, and we held an impromptu seder on that first night of Passover. We sang the traditional songs to our new Christian friends – Dayenu, Let My People Go – then inexplicably listened to Led Zeppelin's "Ramble On" playing on repeat.

It was exciting to gather after months of lockdown. Vaccination had just begun, and so my husband and I, our ages a risk factor, were the only ones who were fully protected. The neighbors weren't, tragically believing their isolation would keep them safe, although Sandy's husband went into town for work.

We all tried to warn them.

Sandy knew I was a biologist and wanted to know more about the vaccines, so I explained how they work. I told her that I couldn't imagine how a vaccine could be more harmful than the threat of what the virus could do. She asked insightful questions, many of them, but still looked skeptical.

And that triggered my younger daughter.

Carly tried to hold it in, but couldn't. And so she tearfully poured out what she had seen from her sixth-story window in Astoria, Queens during those horrid months as winter turned to spring in 2020, as the white-shrouded bodies were stacked up at the ambulance bay of the hospital right next door, like bleachers of death. It's an image she nor the rest of our family can never unsee.

But to Sandy, in her cabin in the woods, an inner city hospital must have seemed a million miles away. In March 2020, the mantra "it can't happen here" was still playing in many parts of the country.

Sandy remained unconvinced. Unvaxxed. I can only imagine where she got her information. Sarah persisted in offering to take her to get vaccinated, through the summer. But then Sandy cut her off completely over the issue, silencing Sarah's good intentions. Until that time, Sandy and I had talked and texted. We liked the same books, bands, and TV shows. We bonded. I considered her a friend.

Two weeks ago, Sandy got COVID. Her husband had brought it home.

I knew that Sandy wasn't stupid and that she knew biology – during the conversation on Passover she'd mentioned mitosis, cell structure, DNA. I see now that when it came to vaccination, she was simply scared. And her fear and denial cost her her life.

Statistics on the never-ending pandemic become obsolete almost as soon as they are compiled these days. It is undeniable that most COVID deaths are among the unvaxxed. There's no more hiding in the woods, especially now with omicron and its off-the-charts transmissibility.

Still, an astounding fifteen percent of the overall US population refuses vaccination, the percentages distributed unevenly among the states.

It is unfathomable to me that anyone could compare the graphs of hospitalizations for the protected versus the unprotected, the vaxxed a line hugging the X axis at the bottom and the unvaxxed a hockey stick of frightening exponential growth, and remain unconvinced.

I'll admit that I never saw this coming, the vaccine hesitancy that has catalyzed COVID, not only enabling a deadly virus but giving it room to evolve. The pandemic wasn't a surprise, as I suspect it wasn't to many other biologists. And I've always thought herd immunity – not a new idea – was more a theoretical ideal than an achievable goal in the real world. But I never imagined the politicization of a national public health crisis stemming from an infectious disease, nor the fear that spawns willful ignorance.

I'm trying now to understand why Sandy died, why she thought the government was trying to take away a "right" by offering, at no cost, something that could prevent her death. It's too late for Sandy, but perhaps someone will read this post and go roll up a sleeve. I can't wrap my head around the glaring fact that thousands have made the same stubborn choice as Sandy.

But Sarah found some closure the day after Sandy died, last Sunday. She and a friend were hiking in the spectacular mountains that are the backdrop to the log homes, some built onto cabins going back a century. She texted us images of a tree with a small, perfect, owl sitting on a lower branch.

"Last night! It was so beautiful, little, white, we got really close to her and she just stared right back for awhile. I know this sounds crazy but it felt like Sandy coming to see me! I really felt that and cried and said everything I wanted to say to Sandy, that I was sorry she was misled, sorry she suffered. And when I finished, she flew off."

So RIP Sandy from the Mountains who looked like Stevie Nicks.

"And I saw my reflection in the snow-covered hills
'Til the landslide brought me down."

May your story save lives. We have the tools to hold off the landslide.

Originally posted at my blog DNA Science at Public Library of Science.

Next Tuesday, December 21, marks two years since the China CDC Weekly acknowledged the first "cluster of pneumonia cases with an unknown cause … in Wuhan."

On the Origin of COVID

Half of the two-page report from China is an illustration of seven colored ovals, each enclosing symbols for closely-related viruses. Within one oval, 3 of the 7 viral lineages bear asterisks. The trio includes what was then called 2019-nCoV.

In that initial report, China claims that the origin of the novel coronavirus "is still being investigated … all current evidence points to wild animals sold illegally in the Huanan Seafood Wholesale Market."

That's a little like saying the Beatles came from Hamburg because they played there often in their early days – rather than from Liverpool.

An alternate hypothesis of the possible origin, based on genome sequence evidence, unfolds in a report on bats from Cambodian caves collected in 2010, published recently in Nature. Predecessors of SARS-CoV-2 might have arisen in many places, such as southeast Asia, where investigators weren't looking. (I covered the bats in April when the study appeared in preprint form – the pandemic has instilled a never-ending sense of déjà vu to science journalists.)

The Cambodian bats are the closest known relatives to the enemy, yet they are curiously missing the precise part of the genome that encodes the region of the spike protein that the virus uses to grab onto and slip into our cells. Coincidence? Perhaps. Genetic material is well known to flit from genome to genome, crossing what we humans call species boundaries. But there are other hypotheses.

As Fox Mulder said often in The X Files era, the truth is out there. But we may never know it.

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

wo weeks after sperm fertilizes egg is a critical time in human prenatal development. Intricate waves of signals stamp cells with their eventual fates as part of a particular organ. But studying such early-stage human embryos is both technically and bioethically complex. 

Now a report in Nature from researchers in the UK and Germany provides an unprecedented view into the early human embryo – thanks to a woman who donated one after having an abortion. She donated through the Human Developmental Biology Resource, which provides automatic bioethical approval from the Institute of Human Genetics, Newcastle and the Institute of Child Health, London.

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

The tantalizing final sentence to James Watson and Francis Crick's landmark 1953 paper in Nature introducing the genetic material, DNA, is almost as famous as the report itself:

"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

That copying mechanism gone awry spawns the mutations that create new viral variants.

Mutation, Natural Selection, and Recombination, Oh My!

Like Dorothy of Wizard of Oz fame exclaiming "lions and tigers and bears, oh my!" three major forces of nature set the stage for genome evolution: mutation, natural selection, and recombination.

The virus we're battling has a single strand of RNA for its genetic material, and not the more familiar double-stranded DNA. But an RNA genome must also replicate – copy itself – when one virus becomes two. And mistakes, mutations, can happen when they do so, like perpetuating a typo when copying a document.

"Every chance a virus has to replicate it can come up with a new strategy to evade the immune system," said Bruce Walker, MD, Director of the Ragon Institute of MGH, MIT and Harvard, at a recent press briefing of the Massachusetts Consortium on Pathogen Readiness (MassCPR). That's too teleological an explanation for me – a virus doesn't intentionally change itself into a fitter form. Instead, mutations tend to arise at genome locations where the sequence is repetitive, like CGCGCGCG compared to ACGCCUCGAU. It's easier to mistype when "the" is next to "they" in a document, compared to "hippopotamus" next to "diarrhea."

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

Headlines often trumpet the latest in gene editing, RNA drugs, or gene therapy. The less buzzy, but more classic strategy of providing a nutrient that a genetic glitch blocks, has been quietly making strides against Menkes disease, which impairs copper absorption. November is Menkes disease awareness month.

Copper Deficiency

Menkes disease results from a mutation in a gene (ATP7A) on the X chromosome, so its affects boys. About 70% inherit the mutation from their mothers, who are carriers. The rest have a new mutation that arises in egg or sperm.

The healthy version of the gene encodes a protein that controls enzymes that shuttle copper from food through the lining of the small intestine into the bloodstream, and into the brain, where copper is vital for neural connectivity. The mineral is also essential for hair growth and pigmentation, which is why Menkes is also called kinky hair disease. Boys have sparse, pale, and twisty hairs.

Aside from the unusual hair, the child seems healthy until about 3 months. Then symptoms become increasingly noticeable: poor growth, developmental delay, seizures, weak muscles, and low body temperature. Many boys die before their third birthdays.

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

In March 2020, Eleanor A. had been sick for several days. Thinking it might be the new respiratory illness going around, she called her internist, who sent her for a COVID-19 test. She was positive. "Results didn't come back for six days, and Jesse and I shared a bed and bathroom during that wait time," she recalled. Both are in their 80s. 

Eleanor's case was harrowing, but fortunately she didn't need to be hospitalized. "I experienced overwhelming fatigue for much of the next ten days. I slept a lot. One night I got up and felt disoriented, hot and cold at the same time, and very unstable. I thought I wouldn't make it to the bathroom or back to bed. I kept calling for Jesse, but he was sound asleep and never heard me."

Fatigue and shortness of breath persisted. Scans revealed lung scarring, but Eleanor slowly recovered.

Through it all, Jesse never had a sniffle, cough, throat scratch or fatigue. Although he'd been beside his wife as the virus invaded her body for days, he never got sick. Later, his blood showed no antibodies against SARS-CoV-2, the virus that causes COVID. That meant that unlike people who are infected but then shake off the virus without getting sick, Jesse wasn't infected in the first place.

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

To most people the Twilight Zone evokes memories of Rod Serling's iconic TV series of the 1950s and 1960s, or the less tantalizing recent reboot. But the Twilight Zone project at the Woods Hole Oceanographic Institution isn't a peek at William Shatner seeing a monster on an airplane's wing or Billy Mumy turning an annoying adult into a jack-in-the-box.

The twilight zone is a layer of the ocean that encircles the planet, from about 200 to 1,000 meters (650 to 3,300 feet) deep. It's also called the mesopelagic or midwater region. The zone is cold and dark, with flashes from bioluminescent organisms that shield them from predators. Pressure reaches 1,500 pounds per square inch. The biomass of fish in the twilight zone may exceed that of the rest of the ocean – but we know little about their distribution.

Residents of the twilight zone range from tiny bacteria and plankton, to fish, crustaceans, squid, and all sorts of gooey variations on the animal theme, like jellyfish and comb jellies. Quadrillions of bristlemouth fish, named for their spiny teeth, live in the zone. And we don't even know how many species have yet to be described. The animals in the twilight zone support the vast food web, moving carbon from the surface to the depths, regulating climate.

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

I'm about to begin revising the 14th edition of my human genetics textbook. In normal times, I'd have amassed technical articles and case reports, as well as notes from meetings and interviews, choosing topics to add or ax and updating or replacing examples as the new edition takes shape.

But I haven't thought much about genetics in 18 months, instead obsessively reading, listening, and writing about COVID-19 and SARS-CoV-2, terms that didn't exist when the current edition was published in September 2019. The before time.

So much has changed since I published my first COVID article on January 23, 2020.

I'm relieved to focus once more on human genetics. A recent webinar from scientific publisher Elsevier, "20 Years of the Human Genome: From Sequence to Substance," has helped me get back on track and brought back memories.

Genetics Begat Genomics

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

I've admired the cockroach's ability to regrow lost legs since learning about them while working on my PhD in developmental genetics ages ago. Cut off a roach's appendage, and soon signals from the exposed cells stimulate division of neighboring cells at the injury site. And out grows a new leg.

The signaling pathways of both embryonic development and regeneration are common to many animal species, and are therefore ancient. The genes in control have intriguing names: Grainy Head, Notch, Wingless, Sonic Hedgehog, and even Hippo.

I remember reading about elegant experiments that moved the cells at the interface of an amputation in a model organism, such as the cockroach poster-child for regeneration. When a researcher rotated the cells at a cut site, a turned-around limb unfurled.

Salamanders can regenerate limbs too. Back in graduate school in Thom Kaufman's lab at Indiana University, we had two pet Mexican axolotls from the developmental biology group upstairs. Sally and Gerry Mander lived in a large rectangular tank above the vials of fruit flies, happily swimming, as amphibians do. And if a bit of a leg broke off from crashing into the side, the salamander could regrow it.

Of course humans can't regenerate missing limbs, or even toes. Our closest relatives that can are lizards (reptiles, not amphibians).

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

"Give us your antibodies" might be the mantra of the The CoVIC Consortium, a global group of eclectic experts who introduce a "framework for antibody cocktail selection" in the journal Science. They haven't just predicted which antibodies, alone or in pairs, can "neutralize" viral variants, including some that haven't even evolved yet, but have actually tested the tango between antibodies and their targets. From 56 labs on 4 continents, CoVIC has amassed more than 350 monoclonal antibodies against the spike protein with which SARS-CoV-2 latches onto and enters our cells.

As I read the paper, I envisioned a war room, where strategists scrutinize giant, detailed maps as they move symbols of troops and weapons into position, planning assaults from different directions.

Antibodies 101

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