Ricki Lewis

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? Read More 

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. Read More 

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. Read More 

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. Read More 

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.

JUST IN TIME
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. Read More 

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. Read More 

Inappropriate blood clotting can be a killer. Each year in the US, 300,000 to 900,000 people suffer a venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). African Americans have a 30–60% higher incidence of either or both than people of European ancestry.

The risk factors that come up on the usual health websites for VTE tend to be the environmental ones that apply to everyone. But mention of genetic factors tend to be those found primarily among people of European ancestry – even though African Americans are at higher risk. Read More 

I’ve been bombarded lately with news releases reporting links between behavior and DNA.

In simpler times, genes encoded proteins, and the actions or absence of those proteins caused the trait or disease. But today, investigations from outside genetics – reported in psychology and politics journals, for example – are assigning genetic explanations to everything from liberalism to feelings about the death penalty to whether the sound of someone chewing is annoying.

Strange things can happen when non-geneticists publish genetics papers. So I thought I’d mention a few intriguing reports and propose a behavior to investigate: nose-picking. Read More 

“Genotyping isn’t standard of care, so we don’t do it,” said the surgeon dismissively to me a week ago, as if I’d asked him to bleed my husband or feel his head bumps.

Since the surgeon had just removed a foot of Larry’s colon, I stifled the urge to shout Gleevec! Avastin! Herceptin! I’d asked about testing the cancer cells for variants of well-studied oncogenes and tumor suppressor genes. The mutational state of tumor cells at the time of removal, especially given the rarity of the cancer’s origin – the appendix -- might prove informative should further treatment become necessary, even if that’s not for many years. Read More 

I’ve often wondered what happens between the time an egg is fertilized and the time the ball of cells that it becomes nestles into the uterine lining. It’s a period that we know very little about, a black box of developmental biology, because observing or doing anything to even the earliest human embryos is frowned upon.

Every time I write the following paragraph in new editions of my textbooks, I try to picture what can go wrong during those first cell divisions.

“The birth of a healthy baby is against the odds. Of every 100 eggs exposed to sperm, 84 are fertilized. Of these 84, 69 implant in the uterus, 42 survive one week or longer, 37 survive 6 weeks or longer, and only 31 are born alive. Of the fertilized ova that do not survive, about half have chromosomal abnormalities that cause problems too severe for development to proceed.” Read More