Charles Sabine, who spent more than two decades as a television reporter for NBC covering wars, revolutions and natural disasters, is familiar with something he calls “real fear.”
He’s seen it in the eyes of people about to die or be killed. It chilled his blood when a Bosnian guerrilla held a gun to his chest as he stood near a bullet-pocked execution wall. He felt it when he walked point for his camera crew in Baghdad during Iraq’s sectarian war.
But nothing terrified him like the news he got eight years ago after taking the gene test for Huntington’s disease, whose slow downward course toward death makes it one of mankind’s most dread afflictions.
“I learned that the disease that took my father and is inflicting on my brother the same terrible decline in his prime will take me, too,” said Sabine, 53, an Englishman who worked for NBC for 26 years.
And yet Sabine has turned that knowledge to a purpose that can only be called thrilling. He’s on a mission to make Huntington’s the model for a Hopeless Disease About Which There’s Hope.
He wants to put it at the forefront of the “patient-centered care” movement, the effort to always ask patients what they consider success or hope to get out of treatment. He wants to make sure there are Huntington’s patients ready for clinical trials that are just around the corner. He wants to get everybody to think a little more sophisticatedly about genetic testing. Closer to home, he’s turning the knowledge of his biological fate into a tool to help him savor every day, be a good father and husband, make amends, not deceive.
“The neurologist who gave me the result said, ‘There is nothing you can do about this disease. Just live your life as well as you can,’ ” Sabine said recently. “The reality is, there is everything I can do. The problem is finding the time to do it all.”
Huntington’s disease, first described by New York physician George Huntington in 1872, holds an unusual spot in the pantheon of pathology. Like amyotrophic lateral sclerosis (ALS), it is a degenerative neurological disorder. Like ALS, whose eponymous sufferer was baseball player Lou Gehrig, Huntington’s has a famous victim — the folk singer Woody Guthrie, who died in 1967. Both diseases proceed unabated once their symptoms appear. Neither has a cure in sight.
Huntington’s disease has particularly cruel features. Its symptoms are a trifecta of misery: cognitive changes (progressive dementia), behavioral problems (depression, often with angry outbursts) and motor effects (a swaying of the upper body and arms known as “chorea,” Greek for “dance”).
Unlike most cases of ALS, Alzheimer’s and Parkinson’s disease, Huntington’s disease is heritable. It descends in families, rarely arising de novo. If the ailment appears in one generation, it almost certainly existed in earlier ones, although its existence may have been hidden or denied. Children with a parent suffering from Huntington’s disease have a 50-50 chance of developing it themselves. But until the genetic test was developed, they couldn’t know their fate until symptoms surfaced, usually in their 40s or 50s.
Huntington’s arises from a defective version of a gene whose normal actions include helping nerve cells fire, cleaning up cellular debris and regulating the transcription of other genes. It is essential for life and found in organisms ranging from fruit flies and sea squirts to birds and mammals.
Huntington’s is a “dominant” disorder, which means that a person can develop the disease after inheriting the defective gene from just one parent. (In “recessive” genetic diseases, the defective gene is inherited from each parent). When the gene is inherited from the father, the disease often has earlier onset and worse symptoms in the next generation, a phenomenon known in genetics as anticipation.
The Huntington’s gene was found in 1993 after an epic search. The discovery led to a test that can identify who will develop the disease. Because it can be performed prenatally, the test allows a woman to choose to abort a fetus carrying the gene — to date, that is the only way of preventing the disease.
Two decades after the gene’s discovery, there’s still no way to cure or delay the disease. It has come to symbolize the limits of genomic knowledge. That was evident at a recent symposium at the National Institutes of Health examining scientific progress since the completion of the Human Genome Project 10 years ago. Several speakers noted that the gene test lets healthy people know they’re headed for a disaster they can’t do anything about.
“Nobody wants to know that, and we shouldn’t push it on anyone,” said one of the speakers, David Botstein of Princeton University, with just a bit of rhetorical exaggeration.
Charles Sabine agrees that the test shouldn’t be pushed on anyone. But after a long internal debate, he decided to take it.
Sabine learned that his father had Huntington’s disease in January 1994 as he was about to fly to Prague for a story for NBC. His father had developed a twitch and some odd, obsessional behaviors, and as part of the diagnostic work-up became one of the first people in the world to get the Huntington’s gene test. Sabine had never heard of the ailment. He was told only that it was incurable and that he and his brother had a 50-50 chance of getting it, too.
“It was a terrible shock,” Sabine recalled. “But it isn’t a disease you can tell people about. It takes a very long time for the ramifications to sink in. ”
One of the ironies of Huntington’s is that while it is a disease of relentless generational recapitulation, it is often invisible in a family’s history because its sufferers were shunned or institutionalized. That was true in Sabine’s family.
“I used to hear, in my childhood, about this black-sheep uncle, but I never even saw a photograph of him. It was only much later that I found out he had died in a care home for people with this disease,” Sabine said.
Meanwhile, Sabine’s brother John, now 58, feared he was already showing signs of the disease. A litigator with a London law firm, he’d recently suffered stage fright in court — an uncharacteristic experience. Within a year of hearing of his father’s diagnosis, John got tested and found out that he, too, carried the mutant Huntington’s gene.
Charles, however, was in no rush to know. He was pursuing the adrenaline-
fueled life of a foreign correspondent, which was a good diversion from a messy present and an uncertain future. And all in good health.
He had married in 2001, but within months started an affair with a roving TV producer. Their assignations, sometimes months long, occurred in such as places Baghdad, Qatar, Cairo and the Palestinian territories. For several years, they met and parted, broke up and reconciled. And Sabine put off deciding whether to get tested.
“Most people probably look for excuses to not face difficult decisions, and I had a particularly good one.” he said.
The woman, named Nicole, didn’t push him to get tested. But she realized little would change until he was.
“Everything to do with this deplorable situation, at least as I understood it at the time, hinged on him not knowing whether he carried the gene or not,” she said.
Finally, in 2005, Sabine gave a blood sample for the gene test. He got the results from a clinic in London four days after returning from Baghdad, where Nicole, who is now 38, was finishing her assignment. He called her from a pub.
“He was very downbeat, sounded very crestfallen and defeated,” she recalled. “He said, ‘I have Huntington’s.’ ” she recalled. When she flew out of Baghdad the next day, “I had tears streaming down my face, knowing it was the end of an era. The end of innocence, end of somewhat unsavory chaos, end of living in somewhat ignorant bliss. And the start of some sort of profound change.”
Sabine divorced his wife. He and Nicole left NBC, and soon after, the television business altogether. They eventually got married. Their daughter, Sabrina, was born in 2008; their son, Roman, in 2011. Neither carries the Huntington gene.
Several years ago, they took a weekend trip to the Cotswolds and decided to stay. Once serious Londoners, they now live a country life, with a view of rolling hills, horses and cows.
A “cure” for Huntington’s disease, should it ever arrive, will probably take the form of delaying its onset indefinitely, as opposed to reversing the damage it wreaks.
Huntington is a “trinucleotide repeat” disease. It is caused by too many three-letter “words” in an otherwise normal gene. If some of those words could be edited out before the gene’s message is translated into protein, the disease might never develop. That strategy, called “RNA silencing,” is showing promise in mouse and monkey experiments.
But Sabine — who has no symptoms of the disease at the moment — isn’t holding his breath.
“I think they’re too late for me,” he said of this and other treatments in development. “But the next generation has every reason to believe that they do not have to fear this disease as much as I do.”
In the meantime, he believes there’s a lot to do.
On a recent trip to Washington, he was the keynote speaker at a fundraiser held by the local chapter of the Huntington’s Disease Society of America. While here, Sabine also met with the staff of the MedStar Georgetown University Hospital & Georgetown University Medical Center Huntington Disease Care, Education & Research Center, which opened last year. It has about 30 patients and hopes to eventually treat about 150. (About 1,400 people in the District, Maryland and Virginia have the condition.)
Caring for Huntington’s patients is exhausting, depressing and occasionally dangerous. That’s why in the past so many of its sufferers were institutionalized. Antidepressants, major tranquilizers and movement-controlling drugs have improved things. But families still need huge amounts of help to keep patients at home. Georgetown’s center — which is partly the result of a $1.1 million gift from Jack Griffin, a 72-year-old former real estate developer whose wife has Huntington’s disease — aims to make the task easier.
The program has psychiatrists, neurologists, a social worker, a neuropsychologist and a genetic counselor. To avoid frequent trips to the clinic, as many of these specialists as necessary can be seen in a single visit. On the day of Sabine’s meeting, the staff discussed using video telemedicine to evaluate patients at home. They talked about what constitutes adequate counseling before a gene test is done — something Sabine never received.
“I want to make sure you understand how exciting it is, what’s happening in this room,” Sabine told the team. “You are helping transform Huntington’s disease from being the basket case of health care to being what I think can be the benchmark of health care.”
Playing a small part in that evolution hasn’t taken away his sadness and fear, he said afterward. But it has given them more meaning than they had eight years ago when he learned his fate.