Ricki Lewis's Blog, page 26

When the Target Isn’t Really the Target: One Way Cancer Drugs Fall Out of Clinical Trials

Ninety-seven percent of potential new cancer drugs never make it to market, dropping out of clinical trials when they don't meet measures of safety or efficacy.

 

"Why that is, we don't really know. But I think that this extremely high failure rate suggests that there are some fundamental issues in how new drug targets are studied and how new drugs are characterized," said molecular biologist Jason Sheltzer, PhD, an Independent Fellow at the Cold Spring Harbor Laboratory on Long Island, NY.

 

He decided to investigate, and uncovered the potential power of publishing negative evidence.

 

CRISPR Improves Precision

 

The team reports in Science Translational Medicine on using the gene editing tool CRISPR-Cas9 to test whether 10 experimental cancer drugs work exactly how their developers predicted they would. And they found a tunnel vision in the way that drugs are targeted that might explain why certain patients do not respond as hoped.

 

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

Ancestry tests underreport African genetic diversity, limiting benefits of precision medicine for blacks. Here’s how we can change that.

We know that modern humans emerged about 200,000 years ago in Africa. So it's fair to say that African genomes are ancestral to us all – descendants of those who stayed in Africa as well as of those who left.

 

And yet people of African ancestry are astonishingly underrepresented in the genetic reference panels used to inform the "ethnicity estimates" that DNA testing companies return to customers who send in spit samples, hoping to trace their origins to something specific enough to compare to documents and family lore. A wider representation in the reference panels would also aid the interpretation of genetic information in developing new precision medical treatments.

 

New hope for rectifying this imbalance, in the form of the sequencing of 426 African genomes, was announced at the recent 2019 American Society of Human Genetics annual meeting in Houston. The talk's title encapsulated the vast scope of the work: "High-depth genome sequencing in diverse African populations reveals the impact of ancestral migration, cultural demography, and infectious disease on the human genome."

 

Right now, the colorful pie charts and polygons that depict customers' geographic origins skew heavily European.

 

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

Viewpoint: Netflix’s new horror movie ‘Eli’ is a fright. But why did they have to ‘tarnish gene therapy’?

he new horror flick on Netflix, Eli, released just in time for Halloween, borrows from The Exorcist and Rosemary's Baby, with touches of The Shining. And it all takes place in what looks like Downton Abbey with the cleaning staff gone.

 

"Eli" works; it's scary. But the set-up using gene therapy gone awry is unfortunate, superfluous, and even offensive. (Beware, spoilers ahead)

 

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

A New Meaning for Strip Steak: Making Red Meat Safer to Eat

Despite the rising popularity of plant-based burgers like the Impossible and Beyond, plenty of people still like the real deal.

 

Many studies have linked eating red meat (beef, pork, and lamb) to atherosclerosis, colorectal cancer, other ills, and shortened life. That's why experts quickly challenged conclusions of a new study that downplayed the danger. I stopped eating red meat two years ago.

 

Now researchers have zeroed in on a single type of carbohydrate on the surfaces of the cells of red meat that might trigger the chronic inflammation that lies behind the associated illnesses. And they've found an intriguing way to remove it.

 

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

Gene Therapy Update: Remembering Jesse Gelsinger

Like the mythological phoenix bird, gene therapy has risen from the ashes and is spreading its wings.

September 17 marked 20 years since the death of 19-year-old Jesse Gelsinger in a gene therapy trial. That tragedy halted the fledgling field, with the outlook worsening when, soon after, boys with an inherited immune deficiency developed leukemia when a gene therapy went off course. The momentum that had been slowly building since the first clinical trial in 1990 fizzled.

 

A Slow Comeback

 

Researchers rebuilt the viruses that ferry in working copies of genes, and gradually clinical trials resumed. But it took until late 2017 for the first FDA approval of a gene therapy: Luxturna, for blindness due to mutation of a gene called RPE65.

 

My book The Forever Fix: Gene Therapy and the Boy Who Saved It, from 2012, chronicles the history of the field as a backdrop to the Luxturna story. The "boy," Corey Haas, was 8 when he was treated in 2008. He's made amazing progress.

 

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

Did a ‘flawed’ bioterror plot doom Netflix’s ‘Designated Survivor’?

I was distressed to learn that Netflix cancelled Designated Survivor, after rescuing the show from ABC for a third season. Finally, the characters in the West Wing could speak realistically. But it didn't help.

 

I was thrilled at the bioterror-catalyzed plot, which borrowed Isaac Asimov's law of science fiction: change only one thing. But stronger science in the story could have built a compelling, biology-based case against white supremacy, because the weapon was to somehow seek the dark-skinned. Short-shrifting the science was a missed opportunity.

 

A relief from reality

 

The first episode of Designated Survivor aired September 21, 2016. With ten million viewers, many following star Kiefer Sutherland from his Jack Bauer/24 days, DS was quickly extended to a full season.

 

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

What sperm banks could learn from Fox’s ‘Almost Family’ and ‘The Handmaid’s Tale’ sequel ‘The Testaments’

I'm dreading the debut of the Fox TV series Almost Family on October 2. In it, Julia Bechley discovers that her dying dad, a famous fertility doctor, had made dozens of personal DNA donations that are now millennials, at least two of whom have unknowingly hooked up.

 

Many of us in the donor-conceived (DC) community have already seen the series as the Australian show Sisters on Netflix. I hope the new incarnation changes the ending, which was the worst since the supposedly-dead Bobby Ewing appeared in the shower in the 1986 finale of the TV series Dallas and revealed that the entire season, in which he'd died, had been a dream.

 

The 2013 film Delivery Man preceded both versions of Dr. Bechley's misadventures. In it, Vince Vaughan is the befuddled father of 533 twenty-somethings, thanks to long-ago sperm donations. A lot of them.

The danger of unintentional inbreeding.

 

 

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

A Child’s Unusual Chromosomes Illustrate the Value of Supportive Therapies

To a trained eye, the chromosome chart (karyotype) above has 4 irregularities, circled in red. They're chromosome pairs of uneven size.

 

The chromosomes represent genetic material missing or extra, but also a beautiful girl. Her father contacted me after he read my recent post about a friend's child with a rare mutation in a single gene, a more typical driver of so-called "diagnostic odysseys." Did I have any insight on treatments for his daughter? He'd send her lab reports.

 

The notations were in Hebrew, but the universal language of chromosome charts spoke clearly to me. The chromosome pairs are size-ordered, its members matching, but pairs 9, 14, 15, and 16 look like tall and short dance partners. This was something more profound than a single gene glitch, or even a missing or extra chromosome.

 

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

Retiring the Single Gay Gene Hypothesis

The once-prevailing concept of a sole "gay gene" dictating sexual orientation has been put to rest in a powerhouse study published in Science. The work illustrates the nature of science: evolving with the input of new data, especially the large-scale contributions of bioinformatics and crowd-sourcing.

 

"We formed a large international consortium and collected data for more than 500,000 people, comparing DNA and self-reported sexual behavior. This is approximately 100 times bigger than any previous study on this topic," said lead author Andrea Ganna, of the Institute of Molecular Medicine in Finland and an instructor at Massachusetts General Hospital and Harvard Medical School, opening a news conference earlier this week.

 

Human Sexuality is Nuanced and Complex

 

The investigation lowers the estimate of the genetic contribution to same-sex sexual behavior, thanks to analysis of a trove of data from the UK Biobank and the consumer genetic testing company 23andme.

I hope that the demonstration of a diminished role for genetics will counter the idea that having sex with a person of the same sex is something biologically broken that needs to be fixed. "Using these results for prediction, intervention, or a supposed 'cure' is wholly and unreservedly impossible," points out Melinda Mills, a sociologist from the University of Oxford in an accompanying Perspective.

 

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

Celebrating the Pioneering Experiments in Genetics

It seems that lately everything in genetics, which has morphed into genomics, is big, big, big.

Data on half a million people represented in the UK Biobank are highlighting genome regions associated with difficult-to-study traits, like sexuality and handedness.
The All of Us initiative at the National Institutes of Health, which plans to capture info on a million or more people, is ever-expanding, from embracing Native communities to welcoming health care providers.
A pair of articles in the latest Nature Genetics describes algorithms that shift the mindset from "the" human genome to the many variations on the theme. Capturing how we differ will speed diagnoses, ease the finding of relatives, and fill in our evolutionary trees.

Another new Nature Genetics report, "A reference genome for pea provides insight into legume genome evolution," took me back to the origins of genetics and Gregor Mendel, who deduced the two basic laws of heredity by breeding pea plants with a handful of distinctive characteristics. A way for the general public to better understand what science is and how scientists think would be to set aside the mega studies for a moment and look back at the brilliant experiments that built the field of genetics, from those of Mendel to the beginnings of molecular biology.

 

So here are six of my favorite experiments in genetics, from Mendel's peas to double helices, chosen for their insight and creativity. These are in addition to my DNA Science post about the 19-year-old college student who invented gene mapping, paving the way to genome sequencing and consumer DNA ancestry tests.

 

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