12th edition of my human genetics textbook


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Glenn Nichols, surrounded by his hospice team. The author is in yellow.

Genetic Linkage

Is CRISPR Gene Editing Doomed, Even As Gene Therapy Enters the Clinic?

August 15, 2018

Tags: CRISPR, gene therapy

Anyone watching the recent 60 Minutes segment on CRISPR would conclude that the gene editing technology is on the brink of pouring forth a cascade of cures. But a recent study reveals a mess of missing and moved chromosome parts in the wake of deploying the famed “molecular scissors.”

Invented in 2012, CRISPR brilliantly borrows a bacterial defense against infection. The “clustered regularly interspaced short palindromic repeats” are simple DNA sequences that serve as landing strips in a genome where engineered “guide RNAs” deliver an enzyme to a desired gene, amending or obliterating it. When the enzyme snips across the double helix, natural DNA repair ensues. Cas9 is an oft-used enzyme.

Precision

Unlike conventional gene therapy that adds a gene, sometimes hovering in a DNA loop outside a chromosome, CRISPR swaps in or removes a gene at a precise spot. But it took 27 years for the FDA to approve the first gene therapy, Luxturna, to treat a specific form of hereditary blindness, last December. So CRISPRed drugs won’t be hitting CVS or Walgreen’s shelves anytime soon.

The new report, in Nature Biotechnology, from researchers at the Wellcome Sanger Institute, isn’t the first to find a CRISPR glitch, and it certainly won’t be the last.

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


DNA Testing to Reunite Separated Families—What We Learned from the Grandmothers of Argentina

August 15, 2018

Tags: immigration, separated families, Grandmothers of the Plaza de Mayos

The idea to use DNA testing to reunite families separated at US borders due to the Trump administration’s “zero tolerance” policy arose quickly. But confusion ensued when early media reports didn’t distinguish the types of tests, which have different implications for privacy.

On June 21, in response to the heart-wrenching separation stories pervading the media, California Representative Jackie Speier first floated the idea of direct-to-consumer (DTC) genetic testing companies like 23andMe donating kits. Nice idea or outrageous, depending on one’s viewpoint.

Either way, the heavily-advertised 23andMe testing kits aren’t valuable for reuniting families, because they don’t catalog the statistically powerful short tandem repeats (STRs) that the FBI and immigration authorities rely on to identify individuals. Desperate, distraught parents and crying, terrified kids — or children traumatized into eerie silence — aren’t going to find each other from cheek swabs at the border revealing visible traits, disease risks, earwax consistency, or whether cilantro tastes foul or yummy.

But testing DNA to reunite relatives has worked before, although under wildly different circumstances. A precedent is the Grandmothers of the Plaza de Mayos project. It began in 1977, a year into the eight-year “Dirty War” when the Argentinean military and police abducted at least 210 “niños desaparecidos,” selling them or giving them away. The Grandmothers project built cases using conventional evidence, such as documents, to attempt to reunite kidnapped children with relatives. Why grandmothers? Because so many mothers had been murdered.

But the evidence wasn’t enough.

So in 1984, the American Association for the Advancement of Science sent a team of geneticists to Buenos Aires to assist the Grandmother project, including Mary-Claire King, not yet famous for discovering the BRCA breast cancer genes.

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

How the Media Oversimplifies DNA Testing of Separated Families

August 7, 2018

Tags: DNA testing, STR, CODIS, immigrant DNA testing

Should DNA testing be used to help reunite separated immigrant families?
When the Genetic Information Nondiscrimination Act of 2008 (GINA) was passed to unify “the existing patchwork of State and Federal laws,” the language was broad enough to apply to just about any use of information gleaned from DNA. The law is meant to prevent discrimination in health insurance and employment based on results of a “genetic test,” defined as “an analysis of human DNA, RNA, chromosomes, proteins, or metabolites, that detects genotypes, mutations, or chromosomal changes.”

Use of “genotypes” alone covers any application of determining sequences of A, T, C, and G that I can think of, and if that’s not enough, the first sentence of the act mentions sequencing the human genome.

A decade ago also came the first direct-to-consumer (DTC) DNA tests, from a handful of companies. Since then the number and types of “spit” and cheek swab tests and companies offering them have mushroomed, probing traits, tendencies, risks of future illness, metabolic quirks, behavioral characteristics, carrier status for single-gene diseases, and of course ancestry. But with the spreading tentacles of DNA testing, a lack of precision in describing what, exactly, is being considered, can lead to misunderstanding. That’s apparent in the use of DNA testing to help to reunite children separated from their parents as part of the Trump administration’s “zero tolerance” policy at U.S. borders.

Don’t Echo Politicians Who Gloss Over the Science

Initial confusion about DNA testing unfurled June 21 when California Representative Jackie Speier called for DTC DNA testing company 23andMe to donate kits for swabbing children’s cheeks at the borders.

Continue reading at DNA Science, where this post first appeared.

Identical Twins, Physical Fitness, and Transgender Identity in the News

July 27, 2018

Tags: Three Identical Strangers, twins, transgender

The terrific new documentary "Three Identical Strangers" tells the remarkable tale of triplets separated in infancy who met for the first time at age 19, in 1980. Their matching faces, mannerisms, behaviors, and quirks reverberate throughout the film, astonishing because the triplets were raised in economically diverse families. The film pays less attention to what makes them different.

Identical Twins That Differ Markedly in Physical Fitness

Another intriguing case of nature vs nurture in identicals is published in the new issue of The European Journal of Applied Physiology. Katherine Bathgate, James R. Bagley, and Andrew J. Galpin and their colleagues, from a trio of California colleges, compared 52-year-old identical twins who differ greatly in their physical fitness level. “TT” is a runner and triathlete, “UT” a sedentary truck driver. Because they share all their genes, differences in physical fitness reflect what the twins do and have done, not what they inherited.

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

Natural Blood Doping and Rewriting the Textbooks

July 24, 2018

Tags: EPO, blood doping

The phrase “rewriting the textbooks” is more than a cliché to me, because that’s what I do. I revise each of my books every three years, updating the science.

I love to explain biology through cases and stories, and am disturbed when something changes – that is, when new evidence indicates that facts aren’t as they seemed.

Sometimes it’s hard for me to give up favorite stories. Worst was the case of Phineas Gage.

Phineas Gage

I used Gage’s strange tale to open a nervous system chapter in a few editions of Hole’s Human Anatomy and Physiology, up until 2010.

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

Alternate Facts: Why Are We Still Telling Women That Abortion Causes Breast Cancer?

July 20, 2018

Tags: abortion

On June 26th, the Supreme Court ruled in favor of crisis pregnancy centers that were challenging a California law, the Reproductive Fact Act, requiring clinic personnel to inform women of all family planning options — including abortion. The 5-to-4 vote put First Amendment rights of workers whose religion is against abortion above the rights of pregnant women to be told that California provides free or inexpensive family planning information, including abortion.

While critical information about abortion is omitted at many of the crisis pregnancy centers, misinformation is apparently readily dispensed. One popular mantra is that abortion causes breast cancer. It’s a claim likely to scare the daylights out of young, vulnerable women seeking help. But a deep-dive into studies published in the top medical journals shows it is untrue — but findings of those investigations tend not to be shared.

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

Telomere Testing: Science or Snake Oil?

July 16, 2018

Tags: telomeres

It seems lately that any biometric can inspire a test pitched to consumers, using jargony buzzwords and promises of health, wellness, and longevity. Measuring the length of telomeres, the short DNA sequences at the tips of chromosomes that whittle down as we age, is one such pseudoscience-based offering.

“The DNA test to help you stay younger longer,” and “control how well you’re aging based on your telomere length,” blares one website. Send in a swab and receive “your current telomere length reported as the age of your cells in TeloYears, and the option to work with an expert to develop a personalized lifestyle improvement plan based on telomere science.”

Not surprisingly, Telomere Support supplements are available to help achieve the promised stoppage of time. These include the usual suspects of vitamins and anti-oxidants, plus black tea extract and pygeum extract (from the African cherry tree, used to treat an enlarged prostate). Only $59 a month!

Another company offers to tell the consumer “physiological/biological age” via the mean length of the telomeres, with a deal to test four times a year for $299, to track changes.

I’m not buying any of it.

Yes, diseases can result from abnormal telomere maintenance, but that’s got nothing to do with what the companies are pitching. Two new articles in the Mayo Clinic Proceedings report on 17 patients with short telomere syndromes, while a third article, a commentary, tackles the commercialization of the science, "Telomeres in the Clinic, Not on TV".

Continue reading at DNA Science, my blog for Public Library of Science.





Hybrid White Rhino Embryos: Genetic Rescue, Part 2

July 10, 2018

Tags: rhinoceros

Two weeks ago, DNA Science covered the plight of the northern white rhino, suggesting assisted reproductive technologies (ARTs) that might preserve the genomes of the nearly-extinct subspecies. A paper published last week, in Nature Communications, reports creating embryos by injecting northern white rhino sperm nuclei into southern white rhino oocytes (unfertilized eggs).

The hybrid rhino embryos developed to a key early stage, the hollowed-ball blastocyst. If they can survive transfer to surrogate southern rhinos and continue developing, it would demonstrate that at least one route to salvaging the subspecies may be possible. But it might not be enough.

The blastocysts are “the first in vitro produced rhinoceros embryos ever,” said co-author Thomas Hildebrandt, of the German Leibniz Institute for Zoo and Wildlife Research. The northern white rhino population is down to just two infertile females (Najin and her daughter Fatu). The last male, Sudan, died in March. The southern subspecies is some 21,000 animals strong. Yet ironically, the genomes of northern animals, albeit based on a handful of samples, are more diverse.

The hybrid embryos, harboring one southern and one northern genome, are halfway to the goal of re-establishing a founding population of the dwindling subspecies. Mating the hybrids for several generations, serially selecting offspring with the highest percentages of northern DNA, could approach reconstituting the genome of the northern white rhinoceros, given time and luck. This is classical genetics sprung from an assisted reproductive technology.

Continue reading at DNA Science, my blog for Public Library of Science.


The Genetic Power of Jurassic World: Fallen Kingdom

July 4, 2018

Tags: dinosaur, Jurassic Park

The latest installment in the Jurassic Park franchise, coming a quarter century after the first film, is about the “genetic power” of the cloned dinosaurs. Only it really isn’t.

The plot is superficially superficial – reviews seem more focused on Bryce Dallas Howard’s improved footwear from the last go-round, pointing out the thin plotline. But many missed the subtleties and subtext of the science.

I scribbled in the dark theater, as I did when reviewing the ridiculous Rampage a few weeks ago. Fallen Kingdom is much better – at least some thinking went into it.

Save the Dinosaurs!

When last we saw the dinos in 2015, they were running amok on Isla Nublar, 150 miles to the west of Costa Rica. Now a huge volcano has started to sputter. What to do? After all, we brought them back, posits Jeff Goldblum, reprising his mathematician-turned-biologist Ian Malcolm persona in the first scene, deploying multisyllabic words when addressing a befuddled senator. The beasts are facing an “extinction level event.”

Continue reading at DNA Science, my blog for Public Library of Science.

Battling Constipation with Synthetic Biology and DNA Manipulation

June 28, 2018

Tags: constipation, microbiome, synthetic biology

Worldwide about 15 percent of people suffer from constipation. Passing dry, compacted stools can be quite painful, but eating more fruit, drinking more water, and/or taking laxatives – common advice from friends and physicians alike – can lead to frustration rather than relief. And drugs such as linaclotide (Linzess) and plecanatide (Trulance), and even probiotics don’t work for everyone because our gut microbiomes (the bacteria in our stomachs and intestines) differ.

A few novel approaches are on the horizon, according to Clinicaltrials.com, including new laxatives, acupuncture, reflexology, Chinese herbs, and a Brazilian tea brewed from fruits of green anise and fennel and flowers of senna and elder tree. Old remedies are given new names, like "Movicol." It’s just sodium bicarb stabilized with the laxative polyethylene glycol (PEG), which is the infamous elixir taken the night before a colonoscopy. It works.

Other experimental strategies are more invasive. “Interferential therapy” zaps the abdomen with four electrodes, and is performed at home for an hour a day for two to three months. Another is a "vibrating capsule,“ presumably inserted into the anatomical area of concern. In another clinical trial, 100 people are testing “perineal self-acupressure,” massaging the anal area to break up and mobilize the stool. And fecal transplants are being tested too.

But a fecal transplant seems the opposite of precision medicine: receiving trillions of bacteria from someone else, each microbial species exuding its own smorgasbord of biochemicals. Although the approach is both ancient and effective, with such a mixed bag of ingredients, evaluation is largely empiric – it helps or it doesn’t, to treat recurrent Clostridium difficile infection and several other indications in clinical trials.

Biotech harnesses tryptamine
Purna Kashyap, M.B.B.S., associate director of the Mayo Clinic Center for Individualized Medicine and his colleagues sought to harness a specific molecule, tryptamine, to loosen stool and speed its transit from inside to outside. “Our goal with this research is to find treatments that act only in the GI tract without creating problems in other parts of the body,” he said. The work is published in the June issue of Cell Host & Microbe, including a video.

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

instruction
Project to engage students in helping families with rare genetic diseases
Book Club Reader's Guide
Many challenging questions to stimulate thought and discussion.
Instructor's Guide
38 discussion questions to get students thinking and talking about gene therapy, including the science, ethical issues, and the drug approval process.
Narrative science
The Forever Fix is the uplifting true story of 8-year-old Corey Haas, who was cured of hereditary blindness just 4 days after gene therapy.
College Textbooks
A spectacularly-illustrated, clearly written human anatomy and physiology textbook, used in pre-health profession programs throughout the U.S.
A highly engaging, clearly written, beautifully illustrated introduction to the science of human genetics for the non-scientist. Now in its 11th edition, 12th to be published in September 2018.
Nonfiction
An ideal starting point for anyone who wants to know more about genes, DNA, genomes, and the genetic ties that bind us all.

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