New edition!!!

The Forever Fix gang: Corey Haas with book, surrounded by mom Nancy and dad Ethan Haas, Ricki Lewis on left next to Lori and Hannah Sames. At book signing 3/24/12, Barnes + Noble, Albany NY.


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

Genetic Linkage

How the Pangolin Got Its Scales – A Genetic Just-So Story

October 19, 2016

Tags: pangolin, genome

Everyone loves animal oddities.

Darwin and Lamarck pondered the advantages of the giraffe’s long legs and neck, while a few decades later Rudyard Kipling explained how the leopard got its spots. Today genome sequencing is fleshing out what we thought we knew about some distinctive animal adaptations, from the giraffe to the leopard.

Adaptations are inherited traits that increase the likelihood of an individual surviving to reproduce. A zebra's stripes rendering it invisible when it runs and the fennec fox's giant ears that dissipate heat and hear distant predators are adaptations.

A report in this month’s Genome Research provides the basis for a “just-so story” about how the pangolin – aka the scaly anteater -- got its scales. They protect, but in a way beyond the obvious. According to the genome, the armor of the pangolin replaced part of its immune response.

Why I Hate the Term “3-Parent Baby’”

September 29, 2016

Tags: mitochondrial DNA, 3-parent baby

A healthy baby boy has been born following mitochondrial manipulation technology (MMT). It was bound to happen, and might offer an alternative for some women who carry a mitochondrial disease.

The feat, accomplished by John Zhang, MD, PhD, medical director and founder of New Hope Fertility in New York City, but done in Mexico, will be presented at an upcoming conference and is abstracted in a medical journal (Fertility + Sterility), but hit the headlines first in New Scientist on Tuesday. An odd choice for an announcement, but the excellent article shows some restraint in using the term “3-parent technique”. Still, it unleashed a fresh barrage of “3-parent” and “designer” baby maddening memes.

The last time “3-parent baby” hit the media, I wrote "Mitohype: 3-Parent Designer Babies Who Will Change Human Evolution". I began that post, “If I turned in a 20,337 word article and the editor decided to replace 37 of those words, would I call her a co-author? Certainly not”.

In a nutshell, 37 genes do not a parent make. I say that as a parent, not a geneticist. (more…)

Finding The Famous Painting of the Blue People of Kentucky

September 22, 2016

Tags: methemoglobinemia, blue people of Kentucky, Walt Spitzmiller

The Blue People ©Walt Spitzmiller
Most stories about the blue people of Kentucky include an eerie, compelling drawing of a family, with the stark faces of 5 of the 9 members a striking bluish-gray, due to an inherited disease. Most stories also borrow heavily from a terrific article by Cathy Frost from Science 82, a long-gone magazine that I quite liked. Frost’s piece, “The Blue People of Troublesome Creek,” is usually credited, but the painting not, or misattributed to
ABC News, various newspapers, or simply deemed “unknown.”

The artist Walt Spitzmiller in fact painted the portrait of the Fugate family (see Walt Spitzmiller Fine Art). A Science 82 editor asked him in 1982 to draw a family, who lived in rural Kentucky, in which the father and some of the children had blue skin. “That’s all I knew about it. I did research on the period they talked about and took old photos and put them together. I added the hunting dog in the lower right, the rooster, that type of thing to add authenticity,” Walt told me.

The blue people of Troublesome Creek had methemoglobinemia, a metabolic condition affecting hemoglobin, the four-part protein that carries oxygen bound to an iron atom at each subunit’s core. (more…)

Genetic Choreography of the Developing Human Embryo

September 14, 2016

Tags: embryo

Years ago, when I was teaching at a state university, I had the privilege to show real human embryos and fetuses to my genetics classes. An obstetrician back in the 1950s had saved them after patients had miscarried, with permission I was told, and donated the collection to the biology department.

My students were astonished at the forms that floated in size order in their test tubes and flasks, culminating in an 8-month fetus in a mayonnaise jar. I handled them with great care and respect. (more…)

Eye Melanoma, Media Hype, and Genomic Medicine

August 31, 2016

Tags: melanoma, ocular melanoma, uveal melanoma

The brown area in the lower left of this eye is a melanoma.
Melanoma of the eye presents a case study in the value of diagnosing by phenotype (symptoms and physical presentation) versus by risk genotype – a discussion that may impact ongoing efforts to sequence gazillions of human genomes. One recent estimate predicts two billion done by 2025.

The big question: How much genome data will be clinically useful? (more…)

Three Gene Therapies Report Good News

August 18, 2016

Tags: gene therapy, giant axonal neuropathy, Spark Therapeutics, Sanfilippo syndrome

Eliza O'Neill received gene therapy -- a drip into her hand -- in May.
Here’s an update on some of the rare disease families I’ve blogged about as they travel the long and winding road from diagnosis to gene therapy.

The Challenge

The rarity of many single-gene diseases complicates design of clinical trials for any type of treatment. How can researchers recruit a control group, when only a handful of patients have the disease? Many of these conditions affect very young children. (more…)

Summer Musings on the Deaf on Martha’s Vineyard and SevenEves

August 18, 2016

Tags: SevenEves, Martha's Vineyard, connexin, deafness

Deafness was normal on Martha's Vineyard in the 1800s
One recent morning, my husband and I hiked down to Great Rock Bight, our favorite spot on Martha’s Vineyard, before anyone else. When I first saw it years ago, I named it the Planet of the Apes beach after the huge rock that juts up a few hundred yards from shore, like Charlton Heston’s view of the remnants of the statue of liberty at the end of that film.

I had with me a sci-fi tome, "Seven Eves" by Neal Stephenson, and a glossy real estate magazine. Because our house is at the lower end of the price range, I like to ogle the spreads of zillion-dollar estates.

So I opened the magazine to "Historic Waterfront Chilmark Home," with a current image of a spectacular house on the left, and a view from 1901 on the right, behind owners Benjamin and Hattie Mayhew. The house was built in 1878 on 6 acres overlooking two big ponds. A mere $5 million.

Benjamin Mayhew was a descendant of Thomas Mayhew Sr, who "bought" the island in 1641, although the Wampanoag tribe of Gay Head and their ancestors had lived there for more than 10,000 years. Benjamin and his brother Jared were deaf, as were both of their parents, an uncle and two aunts, and many others.

I’d forgotten the wonderful story of the deaf community of Martha’s Vineyard, so thought I’d share it here. (more…)

Speedy the Tortoise and Altering the Genetic Code

August 6, 2016

Tags: sulcata tortoise, genetic code

Speedy the tortoise
Last week my sister sent me a great article from Buzzfeed on “a reptile dysfunction”. It’s about stupid people who buy cute little baby tortoises that, after a few sweet months, enter a growth spurt and rapidly begin toassume the dimensions of a dinosaur.

I did that.

An African Tortoise in Upstate New York

I got Speedy, an African spurred tortoise of species Centrochelys sulcata (they have their own closed Facebook group) at a reptile show when she was the size of an oreo. I should have realized that the fact that her natural habitat south of the Sahara was not exactly like that of the northeast US might be a limitation. But it was spring, and Speedy happily munched the lawn for months.

She grew. Fast. (more…)

Hannah Has Her Gene Therapy For GAN

July 25, 2016

Tags: giant axonal neuropathy, gene therapy, Hannah Sames, Steve Gray

Hannah Sames and the researcher who created her gene therapy, Dr. Steven Gray.
Last week, 8 years and $8 million fund-raised dollars after the Sames family of Rexford, NY, began their battle against giant axonal neuropathy (GAN), their daughter Hannah finally received gene therapy.

About 120 trillion viruses were injected into the fluid surrounding 12-year-old Hannah’s spinal cord, at the NIH Clinical Center. Each virus carries a working copy of the gene that encodes a protein called gigaxonin. When she awoke, the first thing Hannah said was "I'm hungry!" and soon after posted on Facebook, "I have an amazing family!" Indeed she does.

Although Hannah is the fifth child in the clinical trial, she’s the first whose body doesn’t make the protein at all, thanks to two deletion mutations. She required a separate protocol to suppress her immune system so that it would accept the treatment, which uses the harmless adeno-associated virus to deliver the genes. At one point, it seemed that the clinical trial wouldn't include her, despite the funding from Hannah's Hope Fund. (more…)

Prostate and Colon Cancer News: The 2-Hit Hypothesis Revisited

July 9, 2016

Tags: retinoblastoma, prostate cancer, Lynch syndrome, colon cancer, 2-hit hypothesis, tumor suppressor

The 2-hit hypothesis of cancer was based on retinoblastoma, the first example of a tumor suppressor mutation.
A report and a case published in two major medical journals this week suggest that relatives of certain people with cancer may be at higher risk, due to inherited (germline) mutations in DNA repair genes.

Only 5 to 10 percent of cancers are inherited. Such individuals inherit a cancer-predisposing mutation in all their cells, and then a somatic (body) cell undergoes a second mutation that initiates the disease. The second mutation may be spontaneous or in response to an environmental factor such as smoking.

The one-two punch of inherited cancers, called the 2-hit hypothesis, was first described in 1971. (more…)

Selected Works

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 10th edition.
DNA reflects who we are -- but it isn’t the whole story.

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