Love this... I use it every day when patients push back on sunscreen recommendations because they need vitamin D.
I remind them that we are now lucky to live long enough to die of skin cancer, and should take that into account when we buy our vitamin D supplements.
Thank you, Andrew. I agree that evolution is a valuable frame to understand disease. Even for conditions we label “genetic,” it was often environmental pressure that selected those traits in the first place. As an environmental epidemiologist, I can’t stop at the explanation that some conditions persist simply because they emerge after reproductive age. That may explain why natural selection doesn’t eliminate them. It doesn’t explain why they manifest — or worsen — when they do. So I add another variable: exposure. If amyloid serves protective functions under certain conditions, trouble may begin when susceptibility meets the wrong environment. ApoE4, for example, alters how the brain handles amyloid and increases vulnerability to Alzheimer’s disease. Add environmental stressors — such as lead exposure — and risk may rise further. The same pattern appears elsewhere. Cystic fibrosis is genetic, but exposure to secondhand smoke or elevated air pollution can make exacerbations more frequent and more severe.
Thanks, Bruce, for the additional thoughts and I totally agree. The ‘unmasking’ of disease/disease severity and disease susceptibility through genetics due to increased environmental exposures (pollution, lead, microplastics, etc.) cannot be excluded. It’s almost overwhelming to account for these variables. An example I keep in my mind is Parkinson’s disease: we know there are genetic susceptibilities to the disease but this risk can be significantly increased by environmental exposures to toxins (e.g. Agent Orange, arsenic, pesticides) that directly affect the nervous system but can also affect the immune system rendering them susceptible to pathogens that also increase the risk. It creates an interconnected/self-amplifying network for disease onset probability. Trying to study the underlying causative mechanisms in the lab is becoming increasingly challenging as more and more variables become apparent. But we try nonetheless! Thanks for reading.
New fan here. I love reading about how you think. Wish I worked with someone like you!
Would you be willing to spell out the acronyms the first time you use them? That would be helpful because Substack doesn't allow me to click on a word to define it or link to a web search. Thank you.
Is there any evidence of a declining occurrence of any pathological gene, protein, etc. (“PGP”) in the decades since modern medical research began discovering treatments for the threat in relation to which the PGP provided a benefit? Also, has anyone estimated the time required for evolution to eliminate a PGP where a successful treatment has obviated the need for the PGP’s benefits?
Love this... I use it every day when patients push back on sunscreen recommendations because they need vitamin D.
I remind them that we are now lucky to live long enough to die of skin cancer, and should take that into account when we buy our vitamin D supplements.
Thank you, Andrew. I agree that evolution is a valuable frame to understand disease. Even for conditions we label “genetic,” it was often environmental pressure that selected those traits in the first place. As an environmental epidemiologist, I can’t stop at the explanation that some conditions persist simply because they emerge after reproductive age. That may explain why natural selection doesn’t eliminate them. It doesn’t explain why they manifest — or worsen — when they do. So I add another variable: exposure. If amyloid serves protective functions under certain conditions, trouble may begin when susceptibility meets the wrong environment. ApoE4, for example, alters how the brain handles amyloid and increases vulnerability to Alzheimer’s disease. Add environmental stressors — such as lead exposure — and risk may rise further. The same pattern appears elsewhere. Cystic fibrosis is genetic, but exposure to secondhand smoke or elevated air pollution can make exacerbations more frequent and more severe.
Thanks, Bruce, for the additional thoughts and I totally agree. The ‘unmasking’ of disease/disease severity and disease susceptibility through genetics due to increased environmental exposures (pollution, lead, microplastics, etc.) cannot be excluded. It’s almost overwhelming to account for these variables. An example I keep in my mind is Parkinson’s disease: we know there are genetic susceptibilities to the disease but this risk can be significantly increased by environmental exposures to toxins (e.g. Agent Orange, arsenic, pesticides) that directly affect the nervous system but can also affect the immune system rendering them susceptible to pathogens that also increase the risk. It creates an interconnected/self-amplifying network for disease onset probability. Trying to study the underlying causative mechanisms in the lab is becoming increasingly challenging as more and more variables become apparent. But we try nonetheless! Thanks for reading.
Thank you for sharing this fascinating and mind-broadening perspective.
New fan here. I love reading about how you think. Wish I worked with someone like you!
Would you be willing to spell out the acronyms the first time you use them? That would be helpful because Substack doesn't allow me to click on a word to define it or link to a web search. Thank you.
Thanks Kai! Yes, I will update this and be more cognizant going forward. Thanks for reading.
Is there any evidence of a declining occurrence of any pathological gene, protein, etc. (“PGP”) in the decades since modern medical research began discovering treatments for the threat in relation to which the PGP provided a benefit? Also, has anyone estimated the time required for evolution to eliminate a PGP where a successful treatment has obviated the need for the PGP’s benefits?