Ricki Lewis

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.

In 1902's Just So Stories, Rudyard Kipling famously explained how the leopard got his spots in what would today be deemed an extremely racist fable. Now Christopher Kaelin, Kelly McGowan, and Gregory Barsh, from the HudsonAlpha Institute for Biotechnology, have discovered how the tabby cat got its stripes: from a signal in the fetus. Their findings appear in Nature Communications.

"The genes that control simple color variation, like albinism or melanism, are the same in all mammals for the most part. However, the biology underlying mammalian color pattern has long been a mystery, one in which we have now gained new insight using domestic cats," said Barsh, who is editor-in-chief of PLoS Genetics.

To trace the origins of the common striped coat pattern, the team analyzed gene expression in single skin cells from fetuses collected from feral cats in trap-neuter-release programs being spayed – half of such females are pregnant. The work revealed a novel mechanism behind the origin of stripes, like Jackie's in the photograph.

Alan Turing's Idea

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