Hiatus: Pesticides and Parkinson’s – Arjan Singh Puniani

I have been performing clinical research via the medium of documentary film and thought I would share why it’s been a minute since I’ve updated the blog.

Decades after Article IV of the Constitution was invoked to acquire Guam, scientists were still unable to explain why the tiny western Pacific island was being rocked by a neurological disease causing uncontrolled trembling and paralysis. Derived from the Spanish word for weakness (paralytico), lytico-bodig is a severe form of Parkinson’s disease (PD) — an incurable neurodegenerative condition that slowly steals a person’s ability to walk, talk, and eat. At the peak of the lytico-bodig endemic in the mid-60s, the island natives, known as the Chammorro, were one hundred times more susceptible to the motor-neuron disease than the rest of the world. After genetics and infectious agents were ruled out, the island’s local cuisine became a leading hypothesis.

Cycads are berries bursting with beta-methylamino-L-alanine (BMAA), a bacterial toxin that selectively damages the brain and spine. Chammorros grind meticulously-washed cycad seeds to make tortillas. Though the berry-containing foods did not contain enough BMAA to damage animal models, ethnobotanists and neurologists suggested that another culinary staple was responsible: a cycad-eating flying fox. In a 2002 article published in Neurology, Oliver Sacks, MD at Albert Einstein College of Medicine proposed that the bats, which ate 2.5x their body weight in cycad seeds daily, accumulate BMAA in their fat stores. The Chammorro consume these fruit bats during special religious ceremonies, and as the flying fox population dwindled, the incidence (number of new cases of the disease) of lytico-bodig rose. After the bats were hunted to extinction, the incidence of lytico-bodig cratered and hardly anyone born after 1960 is diagnosed. Examined skin tissue from 50-year-old bats preserved at a museum in UC Berkeley was found to contain BMAA levels hundreds of times higher than any other Guamanian dish.

The potential for biomagnified toxins to kill neurons in Guam reveals how cultural practices interlaced with environmental triggers can cause neurodegenerative diseases elsewhere in the world. Globally, neurological disorders are the leading causes of disability, and of these, Parkinson’s disease (PD) is the fastest growing in prevalence, disability, and deaths. From 1990 to 2015, the US population increased by 10% while the Parkinson’s prevalence rate (the number of people living with the disease) doubled to more than six million. PD currently affects around one million Americans and tens of millions globally. By 2040, experts predict those numbers to double since the highest risk factor for PD is age (though chemical and pollutive byproducts of the Industrial Revolution, like pesticides, solvents, and metals are close behind). Rapidly industrializing countries like China are grappling with the swiftest increases in PD. While the causes are not fully understood, PD is typically viewed as stemming from a blend of environmental and genetic factors. When certain dopamine-producing neurons die, the brain’s ability to communicate with limbs is lost and the defining clinical phenotypes of PD become manifest: tremor, slow movement, rigidity, and balance issues. It is unclear why these brain cells in the basal ganglia are particularly sensitive to PD risk factors like pesticides. Conversely (and infuriatingly for many doctors), smoking is associated with decreased risk of PD by as much as 40%. Although a global health boon, declining smoking rates around the world may increase the incidence of PD. Technology, modern medicine, and health-conscious cultural norms are adding years to life expectancies; yet, as aging and industrialization rates climb while smoking levels fall, Parkinson’s is rising and may be a creation of our times.

As a pre-medical student, I once believed that illness was driven primarily by faulty genes; however, racial, physical, and social factors, such as a lack of access to primary health services, can influence disease outcomes. While documenting patient encounters as a medical scribe in a large Central Valley emergency department, I noticed that a majority of the patients who presented with PD were farmers or field workers. This clinical observation sparked my investigation on the link between rural living, pesticide application, and neurodegeneration. In the mid-1980s, a neurological team lead by Ali H. Rajput, MD of the University of Saskatchewan examined 20 young-onset Parkinson’s patients — those diagnosed before the age of 40 — living in the Canadian province. His team reported that patients spent 92% of their time in a rural environment, where they were exposed or handled a wide range of pesticides. From this modest start, epidemiological studies on the association between pesticides and Parkinson’s took off and a new risk factor seemed to appear annually. In 2011, Beate Ritz, MD, PhD at UCLA led a landmark study on 700 subjects living in one of the most farmed regions in the world, the Central Valley. Dr. Ritz found that living and working near agricultural operations, farms, and fields increases the risk of PD by 200 to 600%. Although farming as an occupation, exposure to farm animals, living on or near a farm (rural living), and drinking contaminated well water were all associated with PD, no risk factor was more strongly associated with Parkinson’s than the fungicide rotenone and the herbicide paraquat are.

Paraquat dichloride is the most acutely toxic herbicide in the world. Killing green plant tissue instantly on contact since the 50s, the weedkiller is a popular alternative to glyphosphate (more commonly known by its original brand name, Roundup) in the US and an agent of suicide in Asia. Paraquat poisoning (intentional and accidental) is exceedingly tragic and grim as there is no antidote. Paraquat’s first brush with notoriety occurred in the 1970s, after the US government paid to have it sprayed on Mexican marijuana plants. Citing mounting evidence that the potential harms outweigh the benefits, the European Union embargoed paraquat in 2011. As of 2019, 53 countries have joined the ban, including China, Serbia, and Zimbabwe. By far the biggest cause of non-occupational poisonings is intentional self-poisoning, i.e. suicide. After South Korea banned paraquat, suicide rates fell 10%. This problem is central to the problem of paraquat: if paraquat were banned worldwide and so no longer available, many thousands of lives would be saved, whether from occupational poisoning, suicide, or accidents to children.

As Europe and even nations not known for environmental regulation — like China — pivot away from paraquat, it continues to enjoy increasing use in the US and developing countries. American farmers applied more than seven million pounds of the poison across 15 million acres in 2015 (NYTimes, 2016). But as weeds are becoming increasingly resistant to Roundup, paraquat use is expected to command a larger share of the $54 billion pesticide market. Syngenta, a Swiss agrochemical giant, sells more than fourteen billion dollars of pesticides and funds research at over four hundred academic research centers globally. Switzerland banned the use of paraquat within its borders in 1989, but allows for the manufacture and sale of the chemical for export. Syngenta has been known for aggressively defending its products, including engaging in a bitter and public feud with an academic superstar whose research the company formerly backed.

The government requires farmers to report their pesticide use monthly and makes this data available to researchers through California’s Use Reporting Program. We hope to employ animated graphs and figures created in the Adobe production suite to bring actual science to life. On the basis of the results we wish to vividly illustrate, many in academia say the link between pesticides and Parkinson’s is clear and analogized ambient exposure to pesticides with a nonsmoker inhaling secondhand cigarette smoke. But others, including pesticide industry representatives, argue that these studies are fraught with bias and dispute the connection. Every fifteen years, the US Environmental Protection Agency (EPA) is required by law to re-approve all pesticides. The government agency is tasked with determining which of these chemicals are found to be generally considered safe by the scientific community following a systematic review of the relevant published literature. De-registration from the list bans its use effective immediately. On October 15, 2019, the EPA released its meta-analyses on some of the most widely-cited papers establishing the paraquat connection ever written. The EPA discounted the strong links to PD, echoing a familiar refrain seen in Syngenta-backed research studies: the sheer impossibility of controlling for every chemical a person is exposed to weakens any conclusion about elevated PD risk. The controversy highlights the nature of epidemiology: the science of observation. Serge Przedborski, PhD, a neuroscientist at Columbia, explains: “Epidemiology cannot give you a causal link. It can only say, ‘When I saw A, I see B.’” Nevertheless, the fact that cigarette smoking causes cancer now enjoys near universal acceptance built upon forty years of epidemiological and biological work. Prominent researchers at UCSF, Harvard, and Mayo Clinic argue that paraquat is too harmful for people’s health to allow continued usage, while Syngenta continues to assert that the health threats are easily mitigated with training, education, and proper protective equipment. Visualizing the proximity between large scale agricultural operations and impoverished communities requires various film techniques, like aerial footage captured by a drone.

Our exploration of the link between paraquat and PD will be told by a mosaic of characters in an effort to examine the cultural and biopsychosocial landscape of a region I was once so eager to leave behind. By interviewing physician-scientists, farmworkers, epidemiologists, lawyers, physical and speech therapists, landowners, politicians, corporate executives, police officers, college professors, caretakers, and pesticide applicators with differing views and stakes in the issue, we hope to illustrate the variety of perspectives represented in a balanced, fair, and scientific manner. We want to communicate the authenticity of real people grappling with real tragedies by inviting the audience to experience what PD means to normal, everyday Americans. By sifting through the latest research and alternatives, we want to deliver hopeful, helpful, extensive, and actionable information to all parties engaged in the discussion.

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Thanks !

Thanks for sharing this, you are awesome !

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