Is Parkinson’s Disease an Industrial Disorder of Our Making?

Source: Ghulam Ahmad Shahid/Unsplash

A disease in the smog

This is a story about the identification of a disease, a South American sojourn, our understanding of biology, and environmental effects on our body. Embedded in the story is a core question: are we apart from nature or are we a part of nature?

In 1817, Dr James Parkinson described six men in London who had tremors, a bent posture, an unsteady gait, and a tendency to fall (Parkinson, 2002). At the time, England was flourishing economically; the industrial age had unleashed steam engines, iron smelters, and textile mills to make London one of the wealthiest cities in the world. The city was also deeply polluted. Foul air, toxic waste, and poor sanitation was the price of prosperity.

Romantics respond to the enlightenment and Alexander von Humboldt travels afar

The late 18^th and early 19^th century was a time of profound scientific, cultural, and political upheaval in Europe. Reason reigned over emotion. Science replaced superstition. The world was graspable. Nature could be measured and quantified. Properties of heat, light, steam, electrical, and magnetic forces were harnessed. Nature was manipulated and resources were extracted for the betterment of humanity. This enlightened view believed implicitly that humans are divorced from and have dominion over nature.

The Romantics responded to this rational distancing of nature by emphasizing feelings, aesthetic experiences, and our connection to nature. The world, they thought, was an organism not a machine. Humboldt was arguably the most celebrated scientist in the world. He made his reputation from an expedition to South America between 1799 and 1804, as Parkinson was developing his clinical acumen five thousand miles away.

Humboldt merged the careful measurement and observation of an enlightened scientist with a romantic conception of the cosmos as one integrated whole (Wulf, 2015). His views were informed by explorations across Venezuela, Columbia, Ecuador, and Peru. He walked the bleak grasslands of the Llanos, paddled the Orinoco in the rainforest, and climbed the rugged Andes. He collected 45 crates of specimens, including 60,000 plant samples, gathered data relevant to astronomy, biology, geology, meteorology, and oceanography, and generated 4,000 pages of notes in travel diaries (McMullen, 2020).

Humboldt introduced the concept of isotherms, lines on a map connecting points of the same temperature across the world. He recognized that comparable climate zones across continents harbored similar flora and fauna. At Lake Valencia, he observed the effects of agriculture and deforestation on climate change. He recognized how these practices threatened biodiversity and would affect generations to come. He was the first scientist to link social and economic factors to environmental concerns. When climbing to just below the peak of what was considered to be the world’s highest mountain, Chimborazo, he had an epiphany from this high vantage—all life is unified and interconnected (Wulf, 2015).

Our bodies, the environment, and Parkinson’s disease

Fast forward two hundred years. What does Humboldt’s view of nature have to do with Parkinson’s identification of a disease? Our current understanding of biology makes explicit the fact that we are deeply integrated with nature. When we consider the border between our body and the environment, we typically think about our skin and maybe the lungs. Our skin touches the world outside us and our respiratory system inhales this environment into us.

Less obvious, our gastrointestinal (GI) tract is a major channel in contact with the environment. Our bodies are a complicated donut with the GI tract as its long and convoluted hole. Is the GI tract in or outside us? The bacteria that form the microbiome lining our gut further break down this division. The fact that our gut harbors around the same number of bacteria as there are cells in the body (something not known as recently as when I was in medical school in the early 1980s) blurs the distinction between the inside of our bodies and the outside environment and the separation between our lives and those of other living organisms. Deep within us lives a community of alien life forms that is affected by what we eat and drink and which in turn affects our physical and mental health.

Parkinson’s disease (PD) is profoundly connected to the environment we have made. This point is outlined eloquently in a recent book, Ending Parkinson’s Disease: A Prescription for Action (Dorsey et al., 2020). PD is the fastest growing neurological disease in the world, with over 200 people diagnosed every day. The book outlines how the disease is a consequence of our industrial manipulations of nature in the service of the betterment of humanity.

The epidemiologic evidence is clear. Countries with the least industrialization have the lowest rates of the disease and countries like China, with its rapid industrial transformation, have the highest rise. Farmers, mechanics, children exposed to pesticides sprayed in neighborhoods, people exposed to industrial solvents, air pollution, heavy metals, or the deadly herbicide Agent Orange, and people who drink well water or work near contaminated sites are more likely to develop PD. The pesticide paraquat and the solvent trichloroethylene are major contributors; their use is not prohibited in the US.

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The final link connecting the environment and PD comes from a remarkable observation about its neuropathology. PD is characterized by the misfolding of a cellular protein, alpha-synuclein. These misfolded proteins form clumps called Lewy bodies that affect the functioning of neurons. If environmental toxin exposure causes the misfolding, then Lewy bodies should be evident at interfaces between our bodies and the environment. It turns out that alpha-synuclein malformations occur first not in the brains of people with PD but in nerve cells in the nose (Ross et al., 2006) and in the GI tract (Stokholm et al., 2016). These harbingers of disease then presumably travel to the brain from the ports of entry.

Certainly, much work needs to be done to better understand the precise mechanisms by which the toxins produce Lewy bodies, their relation to the microbiome, and how their formation is related to genetic factors. However, it is becoming abundantly clear that PD is an industrial disease of our making, wrought by our disconnection from nature. The consequence of an attempt to exploit the environment for short term betterment, as was true in the time of Parkinson, it is literally stopping us in our tracks.

A coda to this story. The same year that Parkinson described his six cases, Humboldt visited his older brother, Wilhelm, in London. Wilhelm went on to develop PD. Between 1828 and his death in 1835, he described in letters the first detailed subjective account of a “special clumsiness“ (Horowski et al., 1995).