When I began my work in the lab of Prof. Al Levinson at Portland State University in the Winter of 1987, my goal was to research alkaloid biosynthesis routes for benzylisoquinoline alkaloids. A number of local plants were of particular importance to medical botanists due to their relationship with known cancer drug producers. Back east there was the Podophyllum peltatum which produced the cancer drug podophyllotoxin or podophyllin, a derivative of which, etoposide, was the most commonly used drug for treating certain types of cancer. This chemical, a member of a group known as neolignans, had a structure that told us its possible mechanism for chemotherapeutics, it had some sort of effect on either the intercalating disk process of cell division or the production of protein filaments constructed as a part of the cell division, chromosome-separation process.
There was no Podophyllum growing in the Pacific Northwest, but there was the ally of this plant, Vancouveria hexandra, which I decided to research for neolignan content and alkaloid content as well, since it was considered a part of the very alkaloid rich family–the Berberidaceae. Aside from Vancouveria there was Jeffersonia diphylla residing just north in Washington. This plant was already researched for potential medicines by a student at the University in Seattle. Finally, there were the local Calocedrus (Libocedrus) which I knew produced a variation of etoposide in its inner bark and two local Thalictrum spp which produced the cancer drugs thalictrine and thalicarpine.
By Spring of 1988, my lab projects were well underway. I was extracting the alkaloids from about 50 herbal medicine plants and then concentrating and separating them for identification of alkaloid types by genus and species. In the middle of winter 1987/8 I was approached by Dr. Levinson who wanted my impressions of a chronic lung disease local lumbermen were getting. After a few days of talking about this very well localized occupational disease, we agreed it was probably due to a sesquiterpene lactone (primarily his theory) creating an allergenic response deep in the lungs–close to or in the alveoli. The following were the probably causes, liverworts which when dry get powdered by the chain saws, this powder inhaled along with the sawdust.
- Frullania bolanderi
- Frullania californica
- Frullania nisquallensis – Hanging Millipede Liverwort
Frullania spp. of Oregon-Washington
What then followed was my first project handed to me as a phytochemist pertained to the Frullania growing on the Douglas Fir Old Growth forests in Washington, the western edge of the Rockies located inland in Oregon, and the Oregon Coastal Range. This Frullania was causing a serious lung disease mostly in lumberman whose job was to ascend the tree, top it, and cut the major trunk into parts while the tree was still standing. They would habitually breathe in the sawdust and powdered Frullania produced by their work. This physical substance made its way down past the bronchi and into the bronchioles, settling on the surface where it released frullaniosides, a particular class of sesquiterpene lactones that had the solubility required to create the allergic pulmonary response.
Frullaniosides
Soonafter the Frullania chemistry work was well underway, I was handed several cases related to local mushroom growers. One mushroom grower in particular approached me because he had invented a way to grow the chinese medicinal mushroom Shiitake in his modified works he’d (Lentinula edodes) (see http://www.christopherhobbs.com/website/library/articles/article_files/mushrooms_med_03.html).
By breathing in the spores of that fungus, he developed a case of occupational lung disease similar to pneumoconiosis, one of several topics that other chemists in my department were researching. I knew this Japanese man from the local mushroom society meetings and over the next fifteen years met up regularly with him at some of the local mushroom growers guilds. In time his ability to breathe was lessened considerably from his work.
The mechanisms of lung disease are numerous. There are physical effects that inhaled particulates can have on the mucosal membranes, especially down close to the alveoli where chemical effects can ensue. Different particulates inhaled into the lung have different physiological, histological and pathological effects upon the lung. The most famous of these types of pulmonary diseases in the miner’s lung that coal miners acquire over time. Another very common physical particulate disease, now prevalent for non-occupation reasons, is asbestosis, a condition in which the needle-like nature of the filamentous asbestos fibers result in repeated puncturing and irritation of the lung’s inner surface. The homes built in the early to mid-1900s commonly had asbestos, causing the disease in construction workers. Today, regular homeowners are at risk–three generations of occupations and living arrangements closely linked to the same disease, from miner, to homebuilder, to home owner.
It ends up that a lot of occupations have associated with them specific physical and chemically-derived chemical and particulate lung diseases. These causes also tend to have a very specific spatial distribution. The coal miner’s lung mostly depicts two linear tracks following our two major mountain ranges. Bagassosis and other organic crop based diseases tend to appear in farming regions of the state. Interestingly, the maple barker’s lung disease is not peaking in Maple tree territory, but instead at the south end of the Mississippi River valley. Bird Fancier’s Lung is highest where the importation of these caged animals takes place.
The following maps detail some of these diseases.
- Occupational Bronchi-Alveolar Diseases — http://youtu.be/UveOxuKXBqg
- Pneumoconiosis — http://youtu.be/b4n-741iLl8
- Mushroom Grower’s Lung — http://youtu.be/tSkT0yz-XM4
- Talcosis/Silicosis — http://youtu.be/A7pbHQ5LXz8
- Stannosis/Beryllosis — http://youtu.be/nqqhr4FC-Y0
- Coal Miner’s Lung — http://youtu.be/N7NN_mB0vrk
- Asbestosis — http://youtu.be/jIUOMVRhOs8
- Farmer’s Lung — http://youtu.be/ufsG5UfeRAM
- Bagassosis — http://youtu.be/bFajY0vbJAw
- Bird Fancier’s Lung — http://youtu.be/l2Ev_0YOLwU
These maps present us with several unique observations when mapping rare diseases or medical conditions.
The most important observation to make note of is the lack of randomness in the distribution of many of these diseases. This holds true for diseases no matter how they develop into their pathological state. Clustering is a phenomenon that impacts physically born and bred diseases just as much it impacts sociocultural and psychosocial defined disease patterns. In the case of physical illnesses, people have a habit of gathering together. Rare disease cases often attract others with the same condition. People who obtain that disease from a nearly identical cause have the disease due to a spatial relationship they have with the disease-causing place and substances. Ecology also defines the regionalism often seen with environmentally induced lung diseases and condition. (see link and my related maps)
If we look at the coal miner’s lung disease maps, the first map illustrates that are fairly well-dispersed, but clustering. When we look closer at this data and map out its adjusted rates based on local population size and features, we see the primary locations for this disease presented.
Mushroom Grower’s Lung is unique in that it has one or two midwestern peaks. There was once this Science article published on the largest organism known to live on this planet. It was identified as a large mycelial bed of the [Armillaria?] species in the Midwest. The Mushroom Grower’s Lung cluster in the midwest I expect to be occupation related, but may instead be environmentally-linked to this large mycelial bed. As mentioned in the introduction above with my work on mushroom growers lungs in the Pacific Northwest, the large number of cases noted in Portland, Oregon, are also well represented by this map (link to related news story, link 2).
Brian Altonen, MPH, MS 
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