Ricki Lewis

The COVID-19 pandemic is an unfolding story told in numbers. While news reports focus on the number of tests, cases, hospitalizations, and deaths undulating through time and space, an organization called the GISAID Initiative tracks the number of SARS-CoV-2 genome sequences that researchers have posted, from all over the world. It recently reached a milestone: 75,000.

Consulting genome sequences to follow and predict the spread of an epidemic or pandemic is called genomic epidemiology. It's important.

Public posting of the first genome of the novel coronavirus from researchers in China, back in early January, got the ball rolling in vaccine development. Some companies were able to plug the new genetic information into vaccine designs already in the works for other viruses.

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

In ordinary times, a new report describing experiments on bits of smallpox scabs nestled in Civil War museum artifacts would have been mildly interesting. But these days, clues in old poxvirus genomes are especially intriguing because they may explain how some people resist COVID-19, perhaps thanks to a past run-in with a different coronavirus. According to another recently published study, these individuals haven't tested positive for COVID-19 or SARS or had contact with people who have, yet they have immune memory – T cells that recognize a coronavirus that infects bats.

Could exposure to one type of coronavirus protect against infection by another?

"The origins and genomic diversity of American Civil War era smallpox vaccine strains," published in Genome Biology, looks at a possible precedent to answer that question. Such cross-reactivity happens when an antibody or T cell recognizes a surface molecule common to more than one species of pathogen. It's a little like recognizing Eric Clapton in different bands.

A Brief History of Smallpox Vaccination

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

As the days unfold with a seeming sameness in this odd summer of the pandemic, news of vaccine clinical trials begins to trickle in, and another buzzword from epidemiology is entering the everyday lexicon: durability.

To be successful, a vaccine's protection must last or booster shots periodically restore it. Some vaccines lose efficacy over time, including those for yellow fever, pertussis, and of course influenza.

For some vaccines, antibodies and the B cells that make them persist and protect for a long time. For other infectious diseases, like TB and malaria, T cells are needed in vaccines too. B and T cells (lymphocytes) are types of white blood cells, which are part of the immune system.

Antibody response may be ephemeral

"Give a man a fish and you feed him for a day. Teach him how to fish and you feed him for a lifetime," said Chinese philosopher Lao Tzu, founder of Taoism.

Tzu might have been referring metaphorically to the immune system's response to viral infection: an initial rush of antibodies that fades as a longer-lasting cell-based memory builds that primes the body to rapidly release antibodies upon a future encounter with the pathogen.

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

The discovery of a gene behind the absence of eyes in Mexican cavefish may suggest a new way to treat a rare but debilitating disease in humans – homocystinuria.

In homocystinuria, deficiency of an enzyme (cystathionine beta-synthase a, or CBS), blocks the breakdown of two protein building blocks, the amino acids methionine and serine, while a third, cysteine, diminishes. An array of signs and symptoms result.

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

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.

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. 

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.

"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.

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.

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.