Barranquitas is a small fishing town on the west coast of Lake Maracaibo, Zulia state. Hundreds of fishing boats rest across the shoreline, most of them idle since the oil spills that PDVSA fails to control have rendered their engines useless. Across the land, countless ranchos stretch for blocks and, inside one, rests Darío, a 40-something man who looks twenty years older.
Darío used to be a fisherman, but since his late thirties he’s been showing signs of the disease that’ll kill him. Today he’s laying on the ground, the light that filters through the tin roof with holes covering his house, revealing his arms and legs shaking constantly. In the dirt road outside, a man in his fifties fights to stay afoot, his body trembling from one side to another. A group of kids nearby kick a plastic bottle, ignoring how some of them may carry the dreaded disease.
Huntington’s Disease is a rare condition with the highest prevalence in the world reported in small villages off the Maracaibo coast.
Like his father and the man on the street, Darío suffers Huntington’s Disease, or Mal de San Vito (San Vito’s disease, as it’s colloquially known), a neurodegenerative disease in which the mutated form of a protein called “Huntingtin” (vital for the adequate functioning of neurons) accumulates inside the cells, leading to toxicity that mainly affects the basal ganglia, the area of the brain that controls the amplitude, force and speed of our movements. The basal ganglia also plays a key role in the developing and maintaining of cognitive functions; therefore, when affected, unsteady gait, involuntary movements and eventually dementia, appear. The protein mutation is mostly transmitted from parents to children, with a 50% probability of sickness.
Huntington’s Disease is a rare condition with the highest prevalence in the world reported in small villages off the Maracaibo coast. The reason for this isn’t fully understood, but it’s thought to date back to the early 1800s, when a Spanish sailor carrying the mutation arrived, forming a numerous family from which up to 14,000 people descend nowadays.
Barranquitas and nearby towns were pivotal in the study of Huntington’s, changing how we approached genetic disorders forever; known since the Middle Ages and thoroughly described by American physician George Huntington in 1872, little progress on understanding the disease would be achieved until 1968, when Milton Wexler, a California-based psychoanalist founded the Hereditary Disease Fund (HDF). By then, Venezuelan doctor Américo Negrette had reported the unusual figures of cases around San Luis, 30 minutes away from Maracaibo, so the search for a cure turned the spotlight to Venezuela.
Milton Wexler’s daughter, Nancy, then a 23-year-old neuropsychologist, travelled to Venezuela for the first time in 1979 and a joint project between the American National Institute of Health (NIH) and Universidad del Zulia (LUZ) was signed, creating the U.S.-Venezuela Huntington’s Disease Collaborative Research Group. Wexler, Negrette and over fifty American and Venezuelan scientists would visit Barranquitas, Lagunetas and other nearby towns, collecting over 4000 blood samples and identifying over 18,000 people at risk of carrying the mutation. By 1983, and using the blood of Venezuelan patients, the group identified genetic markers linked to the chromosome 4 of affected patients, developing new recombinant DNA-marking methods that would be used to complete the Human Genome Project. Ten years later, refined methods based on the same principles would locate the affected gene and the molecular characteristics of the mutation causing Huntington’s Disease, paving the first steps towards a cure. A diagnosis test was also developed, with a controversial impact, since a positive result means the patient will eventually develop Huntington’s Disease without any alternative to prevent or treat it.
Most of the patients visited by Dr. Wexler lived in extreme poverty.
Dr. Wexler’s team achieved one of the greatest genetic breakthroughs of the last fifty years, and it couldn’t be possible without thousands of Venezuelan patients. But their work didn’t end there.
Most of the patients visited by Dr. Wexler lived in extreme poverty, unable to work given their condition, so the team, headed by neurologist Margot de Young, convinced the government to acquire an old bar in San Luis, El Toro Rojo (Red Bull), which after ten years of top-to-bottom remodelling became the Casa Hogar: Casa de Amor y Fe.
According to the HDF, “(The house) was built to serve the community that so generously donated samples and provided key information leading to the discovery of the Huntington’s gene.” By early 2013, the nursing home housed over 65 Huntington patients, also giving free specialized healthcare to over 70 cases from across the country. It fed hundreds of affected people every day, a titanic task considering Huntington patients must eat up to seven times daily. The HDF, that Dr. Wexler currently presides, covered the full wage of all personnel, as well as food and medication; providing about 1,000,000 USD annually, private companies like oil giant Shell also contributed.
But not everything is sunshine, at least according to geneticist Lennie Pineda, current head of the Huntington Program in the Department of Medical Genetics at Universidad del Zulia, who found several ethical problems tainting the research since day one, summarized in a paper published by UNESCO in 2010.
“During the first visits in the early 80s, there were several acts that I disapproved” she tells me over the phone. Patients in the investigation, she says, weren’t properly informed about the nature of the research, with some (who couldn’t read or write) given printed information in English and signing the consent forms without understanding the true reach of the results. Some even believed they would be cured. “The research group would offer payments in dollars to get blood, skin and semen samples. They also used to bring toys and clothes in their yearly visits, of course people were delighted.”
Pineda’s concerns also stretch to the Casa Hogar, an institution whose ostracism occasionally worried the patient’s families. “I received complaints of people who were never informed of the kind of medications or care their relatives were receiving. Some even told me that when a patient died, their relatives were offered a full coverage of the funeral expenses in exchange for the patient’s brains.”
A new experimental drug showed astonishing early results in its first clinical trials, a sad twist considering how the small villages that made it possible are worse than ever.
This kind of economic incentives, especially when combined with poorly delivered information, have been a long-standing contentious aspect of bioethical discussions. We tried to contact Dr. Wexler to get her take on this, but it was impossible at the time of publication.
In any case, the research developed with Zulian patients has paid off: a few weeks ago, a major breakthrough was achieved, as a new experimental drug showed astonishing early results in its first clinical trials, a sad twist considering how the small villages that made it possible are worse than ever. After visiting Venezuela yearly, Dr. Wexler spent eight years without coming, as the hostile relationships between the Chávez and Bush administrations made cooperation particularly hard. She visited on July 2012 for the last time, and since then the conditions have worsened fast, as reported in a recent BBC work.
The Casa Hogar stopped housing patients in 2014, citing “food and security problems” as the main reason. “I heard they lost part of the private funding behind the project” Pineda tells me, “but no one really knows what happened.”
But beyond her ethical concerns, Dr. Pineda recognizes the virtues of the project: “Most of the patients I know desperately need the Casa Hogar opened again. It’s impossible for them to take care of their relatives without the HDF help, especially with the current economic crisis.”
With science moving fast, a cure for Huntington’s Disease seems closer by the day, a poor comfort for those whose blood made it possible and very few around the globe know about.