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.

14 COMMENTS

  1. The advances there in genetic research probably have breakthrough effects reaching well beyond the remedy for Huntington’s.

    I’d dismiss the ethical concerns – they don’t sound like much. We all sign consent forms online that fewer than 5% actually read, and there are implicit agreements we make that few of us are even aware we made. E.g. when you keep a checking account, do you actually understand how it operates and what your rights are? You know some of them, but not all of them, and probably do not understand things like segregated funds, or that the bank actually only holds about 5% of the sum total of its demand deposits. Something like reading about the research Dr. Wexler did – we don’t really understand things outside our field, and even in our fields there’s a l-o-t we don’t know. Were any of the patients or test subjects harmed? Doesn’t sound like it. Consider the harm done to the unwitting tests subjects of Socialismo del Siglo XXI ….

    • A medical procedure, including the taking of a sample, in the absence of consent which requires that the person be adequately informed, may be considered a trespass or assault on that person.

      I’m not saying that this is what is going on here, but it is fair to point out that adequate information and consent is a significant concern in developed countries, and is not less important where organizations based in developed countries are conducting medical research or testing in the third world or with poor, uneducated populations. I think people can quickly imagine why this is the case.

      It sounds like this is great work being done by this Research Group, and thank you Mr. Gabaldon for providing us with this interesting story.

  2. I agree, they were not that grave, apparently at least. Also they happened at a time when ethical guidelines were not as clear as today. The subject is still very problematic nowadays. Still it’s important to keep a record so they are avoided in future works.

  3. Here we go again… The evil capitalists exploited these poor unfortunate souls.
    How about blaming the Chavistas for no treatment being available.
    This had the potential to be a longer and really interesting article, but it comes off as blaming the researchers/evil capitalists for the problems.
    And giving the Chavistas a pass.

    • To me it rings less as “poor people, bad capitalists” and more as “lest we forget”. Also a lot of medical advances in the past have come about not from the informed consent of participants to knowingly take part in advancement, but from the exploitation of people without the understanding (or knowledge, or agreement) of what they are doing. Also don’t forget that even if we had the shiniest government, these people would likely not see the benefits of the treatments that wouldn’t have happened without them, without them being fully aware their participation in research is not a promise of treatment or cure – the treatment would be developed and sold back. That’s disingenuous at best and unethical at worst.
      Chavistas being the absolute worst doesn’t mean everyone else is good just because they’re not as awful.

  4. I don’t really see it like that. The research Dr. Wexler made was remarkable, the Casa Hogar also helped these people a lot. The ethical concerns are also a part of the story, and although small they shouldn’t be simply ignored, they are common in every research. I don’t think the people there were “exploited by capitalists” I just find sad that they won’t probably benefit from the research as much as they thought they would. Actually their current situation worsened as a result of the economic crisis the Government unleashed over the whole country.

    • It brings up a whole round of questions. Do we always seek to keep our shoes shined, even when we know wer’e going out in rainy weather? Must we always be polite, even at the expense of telling someone who needs to be told to shut up, to shut up? Do we always try to raise our own standards, even as we forgive far worse offenses than dirty shoes?

      Taking it all up a notch to the societal levels, why is it that we persecute the very best and most courageous and noble, yet allow carnivorous, infected, rats into government? An example might be the “big controversy” over General Patton slapping a soldier, which led to his temporary removal from the front lines where he was very sorely needed to halt the abhorrent Nazi advance which was wholesale murdering hundreds of thousands of men, women, children. In an irony of ironies, it was Patton who was known for “spit and polish”, demanding his men be in proper dress and order, even as they were heading out to go knee-deep in mud and prone firing positions.

      How shiny is shiny?

      It isn’t just a rhetorical question. Too much “political correctness” just provides a forest of cover for outright “polite” lies. The real question is, I think, functionality. If one is going to a black tie gala, then yes of course, you shine your darn shoes (with a smile). But if you’re a surgeon you do NOT worry about unsightly stains on your scrubs!

      At what point does dress and order and discipline become a hindrance? I don’t know! Form v. function.

  5. Hola Rafael, muchas gracias. En la facultad de medicina nos habían hablado varias veces sobre la prevalencia de la enfermedad de Huntington cerca de Maracaibo. Hace unas dos semanas leí sobre la nueva droga experimental que acababa de arrojar muy buenos resultados en sus primeras pruebas y decidí investigar mas al respecto.

  6. I had read that one of the researchers that came from the US had one of her parents die due to Huntington disease, so she had a genuine interest in researching to help find the cause and a probable cure . Looking in Google confirmed that its Nancy Wexler.

  7. A fascinating story, Juan, and an example of what can be accomplished when Venezuela and the US combine talent and resources toward a common goal. Hopefully we will see that time come again.

    Good work. Always look forward to your articles.

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