Ricki Lewis's Blog, page 2

The Sunflower House Reveals the Horror of Himmler’s Lebensborn Program

Hitler's "final solution" attempted to strip the German population of Jewish people and others deemed not white. At the same time, the Lebensborn program sought to purify the Aryan gene pool and counter a plunging birthrate through "homes" where "hereditarily healthy" Aryan women conceived, carried, and bore the "racially valuable" children of SS men.

 

Adriana Allegri's debut novel The Sunflower House (St. Martin's Press, 2024) captures the slow-building horror that unfolded at the Hochland Home in Steinhöring, the first facility in the program.

 

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

“De-extincted” Dire Wolf Pups Have a Few Genetic Tweaks – That’s It

The images of "de-extincted" fuzzy white dog-wolf pups festooning the media this week accompany reports that are so hyped that the technical feat is hidden in the hoopla.

Claimed the company, Colossal Biosciences:

 

"On October 1, 2024, for the first time in human history, Colossal successfully restored a once-eradicated species through the science of de-extinction. After a 10,000+ year absence, our team is proud to return the dire wolf to its rightful place in the ecosystem. Colossal's innovations in science, technology and conservation made it possible to accomplish something that's never been done before: the revival of a species from its longstanding population of zero."

 

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

Nixing the Newborn Screening Advisory Committee Is Ill-Advised

Next month, families affected by the rare genetic disease metachromatic leukodystrophy (MLD) will meet in Washington. They will be protesting the April 4 dissolution of the committee of experts that advises Health and Human Services (HHS) leadership on which conditions to include on the Recommended Uniform Screening Panel, aka the RUSP.

 

The List
RUSP is a state-by-state roster of up to 61 "actionable" metabolic conditions. If they are detected shortly after birth with a few drops of blood from the heel, treatment is possible. But it must begin ASAP.

 

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

Removing The CDC Vaccine Assessment Tool Will Do Harm

My daughter Carly has an annual physical approaching. With infectious diseases on the rise, she asked me to repost CDC's Adult Vaccine Assessment Tool. But if you click on the link, up comes a 404.

 

I'd put the valuable self-test on Facebook shortly after the presidential election amid rumors that RFK Jr. could head Health and Human Services, and friends asking me which vaccines they needed to update or get for the first time. I'm not an MD, so posted the assessment tool. Now that it's gone, Carly and her friends want to know how they can protect themselves. Yet despite the grinning new head of HHS next to his smiling boss on the opening webpage of HHS, with a banner that promises to "Make America Healthy Again," the tool to choose appropriate vaccines has vanished. With HHS overseeing FDA, NIH, and the CDC, I'm scared.

 

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

“The Dressmaker’s Mirror: Sudden Death, Genetics, and a Jewish Family’s Secret” Traces a Long-ago Tragic Accident to an Inherited Heart Disease

On a muggy midsummer morning in Brooklyn in 1916, 4-year-old Eugene was practicing somersaults, flipping and rolling, as nearby, his mother stitched white lace onto a blue dress. Next to her stood a tall, heavy mirror perched on a stand that the seamstress could rotate to view the garment from different angles.

 

Suddenly, as the boy was rolling upward, he careened into the mirror. Like tall grass in the wind, the mirror swayed for a moment, then came crashing down on the boy. He died instantly – or so went the family lore.

 

That tragedy lies behind the riveting medical detective story of "The Dressmaker's Mirror," an excellent new book by geneticist Susan Weiss Liebman, research professor at the University of Nevada, Reno.

 

Two More Cases

 

Eugene was Dr. Liebman's paternal uncle. But his early death wasn't the direct inspiration for the book – it was the sudden death of her niece Karen, 36 and pregnant with her first child.

 

While dining out with her husband, Karen suddenly jolted forward and collapsed. Her heart had stopped. She had been healthy, the only hint of illness a slight but persistent cough and breathlessness. In retrospect, Dr. Liebman realized these signs had been present for years. Karen's doctor had attributed the symptoms to the pregnancy.

 

Karen died on November 16, 2008 – coincidentally, the same date that Dr. Liebman's father had died 28 years earlier, at age 66, from a presumed heart attack.

 

Another piece to the emerging familial pattern was Karen's mother,  Dr. Liebman's sister Diane. After doctors persistently attributed Diane's fatigue, weakness, cough, and labored breathing to bronchitis, pneumonia, and a nebulous "virus," she was finally diagnosed with dilated cardiomyopathy (an enlarged heart) at age 57. Diane died from it at age 73, in 2016. Her enlarged heart had been an early incidental finding – a key clue that eluded physicians seeking horses, not zebras, the common mantra of diagnosis.

 

It was Diane's daughter-in-law, a newly-minted physician, who advised consulting a cardiologist. Then things finally sped up. An echocardiogram revealed an enlarged left ventricle. And Diane's ejection fraction – the percentage of blood that the left ventricle pumps out, typically 54% to 74% for a woman - was only 19% - well below the 30% considered severely abnormal.

 

Diane was, and had been, in heart failure. The correct diagnosis finally came in 2001: dilated cardiomyopathy, DCM.

 

"When we got Karen's autopsy report on her heart two weeks after her death, early December 2008, and it said dilated cardiomyopathy, we immediately connected this information to her mother's, my sister Diane's, diagnosis of DCM 7 years earlier. With the report on Karen's heart it now was clearly genetic. But we didn't know if it was a new mutation in my sister or inherited from one of our parents," Dr. Liebman said.

 

Genetic Analysis

The next step: identifying the gene that, when mutant, caused the family's heart condition. Researchers are continually discovering and "curating" (describing) gene variants – aka mutations. The National Institutes of Health maintains a database of gene variants, ClinVar.

 

An initial blood test for the ten known mutations for DCM at the time of Karen's death was negative. A further round of tests on other genes also didn't identify anything.

 

And that's when Dr. Liebman's expertise came in. Although her research uses yeast, not humans (just as mine was in fruit flies), the principles of inheritance are the same in any organism. She knew the search for causative genes hadn't been exhaustive.

 

So she contacted Dr. Elizabeth McNally, a specialist in genetic heart disease at the University of Chicago. Dr. McNally checked Diane's DNA for new mutations as they were discovered. But still no hits.

 

Gene Discovered: FLNC

 

Waiting for discoveries of new mutations to trickle in wasn't fast enough. So, in 2014, Dr. McNally sequenced Diane's exome – the protein-encoding portion of the genome – and finally zeroed in on the gene. She began testing how this mutation affected cardiac muscle cells cultured from the sisters' reprogrammed blood cells. But this didn't give her direct evidence that a mutation in this gene lay behind the family's DCM.

 

About then Dr. McNally changed institutions and Dr. Liebman's requests for follow-up were lost. She had no idea that progress had been made.  

 

In fact, Dr. McNally's group had published a report in 2014 in Circulation: Genomic and Precision Medicine that had named the hypothesized causative gene, FLNC.  

 

FLNC encodes a protein, filamin C, which maintains the precise crosslinking of actin protein filaments into sarcomeres, the tiny units of skeletal and cardiac muscle. Without filamin C, heart muscle slowly falls apart. But the implication of the gene remained tentative until by 2016 experiments with model organisms strengthened the link.

 

Diane had had the mutation; her sister does not. And the nature of the mutation in the Liebman family explains why it is so devastating – it is tiny, but with a huge impact.

 

Genes come in pieces. Exons are regions that are transcribed and translated into the corresponding amino acid sequences of proteins. Introns – short for "intervening sequences"-  are cut out before a protein forms. The Liebman's mutation changes a single DNA base that borders on an intron and prevents the intron from being cut out properly. This disrupts the proper synthesis of the protein. 

 

Medical Detective Work Uncovers a Founder Effect

 

Dr. Liebman got to work, reading technical reports and contacting researchers and families to find other affected families.

 

"Two families with the mutation were Ashkenazi Jewish. Since my family is also Ashkenazi, this suggested the mutation might be a founder mutation," Dr. Liebman shared with me.

 

As the name suggests, founder mutations are brought into an area from a few settlers. and then come to not only persist, but comprise more of the population, if people have children among themselves. Today's Ashkenazim descend from as few as 350 or so individuals, population bottlenecks that by chance retained certain individuals with rare mutations. These mutations then comprise more of the population if people have children among themselves.

 

Bottlenecks have strangled our genetic diversity over time, the echoes of reverberating hate (See The Genomic Scars of Antisemitism).

 

After consulting the most complete DNA databases at the time, Dr. Liebman discovered that one in 800 Ashkenazim had the mutation. And it didn't appear in any other ethnic groups.

 

"So now I knew the mutation was not new to my sister. It had been around for centuries," Dr. Liebman told me.

 

Identifying the Correct Branch of the Family Tree

 

Which parent had transmitted the mutation to Diane, who passed it to Karen?

 

Family history pointed to the paternal side: Diane and Dr. Liebman's father had died of what was deemed a heart attack at age 66, and his mother died in her sleep at 59. That suggested autosomal dominant inheritance – male or female can pass on the trait, and only one mutation is necessary to develop symptoms.

 

Dr. Liebman got to work.

 

She used google, 23andMe, and Ancestry.com to fill in the branches and leaves of the family tree, to find and alert relatives and advise them to have frequent diagnostic tests as well as genetic testing. Her efforts remind me of when, coincidentally at about the same time, I discovered that I have a dozen or more half-siblings, thanks to a long-ago mystery sperm donor. I told my story in a New York Times Modern Love podcast.

 

Other cases emerged as Dr. Liebman widened her circle of contacts.

 

Then in 2017, a chance conversation at a cousin's 50th birthday party revealed his version of the dressmaker's mirror accident. He'd been told that the mirror fell when their grandparents weren't home, and had left Dr. Liebman's father in charge.

 

The differing tales sent Dr. Liebman to hunt down her uncle Eugene's death certificate, which is reprinted in the book. And she discovered that the cause hadn't been an accident or injury at all, but congestive heart failure following five days in the hospital. A second mutation in another gene might explain the onset in a very young child..

 

"I read the cause of death in December 2020 and was shocked to see heart failure. This clinched it. The mutation was very likely from my father," Dr. Liebman said.

 

But why the invented story?

 

"I think they did it to protect their surviving son, my father, and their later issue, Uncle Cyrus, from being shunned by potential marriage partners. It was common for Jews to hide suspected hereditary defects," Dr. Liebman wrote.

 

In 2021, she and her colleagues published a Comment in the International Journal of Cardiology, "A founder mutation in FLNC is likely a major cause of idiopathic dilated cardiomyopathy in Ashkenazi Jews." And so FLNC can now be added to lists of genes to screen in Ashkenazi populations.

 

Should We Sequences Genomes of All Newborns?

 

Dr. Liebman sent me her book shortly after my most recent post at DNA Science, A Genetic Crystal Ball: When Newborn Genome Sequencing Findings Explain Illnesses in -Relatives. And so I asked her whether she thought that the whole genome (or exome) DNA sequencing that led to solving her family's mystery should be done routinely, and broadly, on infants in the general population. Would that lead to diagnoses, or cause undue stress?

"I applaud the idea of universal sequencing in infants for genes that are actionable in infancy or childhood."

 

Liebman also pointed out that "most pathogenic mutations just increase the chance of disease, they do not guarantee disease. The FLNC mutation in my family can cause DCM or sudden death depending on other genes in the person and environmental factors."

 

Karen's pregnancy might have been a contributing factor that enabled the family's mutation to become deadly.

The American College of Medical Genetics and Genomics maintains a list of "actionable' conditions detected with exome and genome sequencing. That is, a genetic disorder is valuable to detect if treatment is possible.

CODA

 

In addition to the riveting family story, The Dressmaker's Mirror is a page turner.

 

I was skeptical when I received it – I've written and read many genetics books over the years, and expected to be bored or to find oversimplification errors. But once I picked the book up, I couldn't put it down, even when knowing the outcome from the press release the publisher, Rowman & Littlefield, had sent.

I share Ashkenazi ancestry with Dr. Liebman, as well as growing up on the same Brooklyn streets. We have an astounding number of other coincidences. I applaud her efforts to get to the bottom of a family mystery. Including her family's gene on testing panels for heart disease will undoubtedly save lives.

 

AI Tool CHIEF Paints a Landscape of a Cancer, Refining Diagnosis, Treatment, and Prognosis

A diagnosis of stage IV cancer used to mark the beginning of the end. Today for many patients, it is the beginning of taking a series of drugs that specifically target the errant cells by blocking the signals that fuel their runaway cell division, while sparing healthy cells. Stage IV cancer patients can live years, even decades, sometimes succumbing to something else.

 

Now there's hope even for patients whose cancers become resistant to targeted drugs – using artificial intelligence to probe cancer cells and their surroundings to identify novel points of vulnerability. Researchers from Harvard Medical School describe a new ChatGPT-like model that can guide clinical decision-making to diagnose, treat, and predict survival for several types of cancer. Their report appears in Nature.

 

The new approach complements targeted drugs by going beyond a cancer cell's surface and biochemical pathways within, to also probe the microenvironment – the immediate surroundings – through image analysis. If deployed early, AI might identify drugs unlikely to work more effectively than can genetic and genomic testing. It is a "can't see the forest for the trees" strategy, revealing the landscape of a cancer.

A Brief History of Targeted Cancer Drugs

 

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

Genome Sequence of the Little Bush Moa Illuminates Avian Evolution

Since discovering my first fossils in a stream behind the Baseball Hall of Fame in Cooperstown, New York, when I was 10, I've been fascinated with clues to past life. I was so excited to find what turned out to be worm borings that my mother trekked me up to a researcher at the American Museum of Natural History, who took the time to identify my specimens. And the next day, I wrote an essay in class about wanting to become an invertebrate paleontologist, flummoxing the poor teacher charged with encouraging a budding nerd.

 

I still have those fossils, nestled in compartments I built into a tattered yellow cigar box.

I didn't grow up to become an invertebrate paleontologist, but a geneticist. And discovering the DNA sequence of a novel genome intrigues me in much the same way as those ancient worm borings did, but it's even more telling, because genetic information reveals clues to the past and connects the ancient species to their modern descendants. Evolution.

 

That's why a recent report in Science Advances captured my attention: "A nuclear genome assembly of an extinct flightless bird, the little bush moa."

 

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

How the Classic TB Vaccine Treats Bladder Cancer – Zebrafish Avatars Reveal Mechanism

Thanks to biotechnology, immunotherapy has become standard of care along many a cancer patient's journey, with many targeted drugs now available. One of the oldest and most successful immunotherapies is simpler: a tamed version of a classic vaccine, against the infectious disease tuberculosis (TB).

 

"BCG" is the "treatment" vaccine's technical name, for Mycobacterium bovis Bacillus Calmette-Guérin. Oncologists have used BCG to treat early stage bladder cancer for decades.

 

A research team led by Rita Fior at the Champalimaud Centre for the Unknown, Lisbon, Portugal, figured out how BCG decimates cancer cells. Their report appears in Disease Models and Mechanisms. First author is Mayra Martínez-López, who was a PhD student at the lab and is now at the Universidad de las Américas in Quito, Ecuador.

 

Immunotherapy Began with Coley's Toxins

 

Retooling vaccines to kill cancer cells is a classic tale in the history of medicine.

New Drug Miplyffa Approved for Rare Niemann-Pick Disease Type 3

October is Niemann-Pick Awareness Month. FDA approved a treatment for type 3 of the ultra-rare genetic disease September 20. The quest has been ongoing for three decades, said Laurie Turner, Family Services Manager of the National Niemann-Pick Disease Foundation.

 

Miplyffa (arimoclomol), an oral drug taken three times a day, is prescribed for patients with Niemann-Pick disease type 3, aka NPD3, two years of age and older.

 

NPD3 typically begins with enlarged liver and spleen and progresses to neurological symptoms. Average length of life is 13 years.

 

"Impacts on patients and families are enormous," said Janet Maynard, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine at FDA's Center for Drug Evaluation and Research. "Despite extensive research efforts, there have not been approved treatments to meet the significant needs of patients. The first-ever approval of a safe and effective drug option will undoubtedly support the essential medical needs of those suffering."

 

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

The Dangers of “Do Your Own Research” and “Believe in Science”

During the pandemic, we turned to our leaders for updates on the rapidly worsening, unprecedented situation.

 

As days turned to weeks, and the sick lined up outside city hospitals, we craved information. But much of it was in the unfamiliar language of virology and immunology, public health and epidemiology.

 

In those early days, politicians and government officials who'd never heard terms like "cytokine storm" and "RNA virus" were suddenly charged with explaining what was happening. Thankfully, informed voices emerged. Experts regularly held zooms with science journalists, providing technical updates that we used to inform our articles, blog posts, podcasts, and other means of communication.

 

"Do Your Own Research" Fuels Science Illiteracy

COVID reawakened the mantra DYOR: do your own research. According to AI, it isn't new:

 

"The phrase 'do your own research' seems ubiquitous these days, often by those who don't accept 'mainstream' science (or news), conspiracy theorists, and many who fashion themselves as independent thinkers. On its face it seems legit. What can be wrong with wanting to seek out information and make up your own mind?'"

 

But doing "research" by choosing what to read, watch, or listen to, is not at all the same as the research that scientists do. We don't pay attention only to the data that support our hypotheses – science is more about rejecting hypotheses, thinking more, and devising new experiments to investigate something in nature. Science is about data, not "content."

 

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