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There is at least one example of a healthy adult who is compound heterozygous for loss of function in PCSK9 [1].

Also note that in the study linked in the main post, the gene itself is being base edited in the liver, not globally.

1 = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559532/




We don’t have the ability to measure health yet. People who are by all metrics healthy fall over dead all the time, or have inflammatory/autoimmune problems that get written off as psychosomatic. There are a lot of things that are considered normal today that will later be recognized as diseases.


>We don’t have the ability to measure health yet.

Ok I know what you mean, what you mean is that we don't have a formal definition. But I'd like to believe that a perceptive physician does know when people are unhealthy, i.e they observe the person physically, not merely look at numbers. Such physicians are a dying breed though.


What is your definition of healthy?


With that perspective, how does one ever go about developing a vaccine or a drug therapy?


I don’t understand your question. How do people make vaccines and drugs?

By the way, I would like to point out that your ilk have killed a great many people. For decades you have cracked people over the head with the idea that cholesterol is a health outcome and that saturated fat is bad for you. It turns out that cholesterol is a heuristic and that it’s been read wrong to boot. And it turns out saturated fat isn’t just not bad for you, it’s an important part of a healthy diet.

https://www.sciencedirect.com/science/article/pii/S073510972...

Dr. Shawn Baker and Dr. Paul Saladino ate nothing but red meat and saturated animal fat for two years and they had CAC scores of zero. There is testimony that someone’s CAC score went down after cutting out sugar and adding beef tallow.

Can you blame me for resenting the medical establishment?


My question about how one would ever go about developing drugs with "that perspective" is with regard to your statement that "We don’t have the ability to measure health yet." If you don't believe we can identify the difference between health and disease, how would you trust any process that is required for drug development?

Getting to your assertions about cholesterol, there is a chasm between "dietary recommendations for cholesterol" and "genetic and therapeutic modification of lipoproteins."

Re: dietary recommendations, which seems to be what you are referring to, I think that the evidence for or against specific dietary recommendations for many types of nutrient intake is hardly compelling. But it's also not an area of my expertise.

Re: therapeutic reduction of cholesterol, the results over decades are totally unambiguous: reducing LDL-cholesterol via statins and PCSK9 inhibition reduces cardiovascular disease and prolongs life. And those benefits are also conferred to people who have lower cholesterol throughout their life due to genetics.


If a healthy person is a person who is totally free of disease, then we do not have the ability to determine whether or not a person is healthy. That has nothing to do with developing drugs for and treating the subset of diseases that we know about because they present with obvious and intuitive symptoms relatively speaking.

I disagree about LDL. It’s not as simple as LDL. There are different kinds of LDL and some are worse than others as is pointed out in that link, I think. Medications that reduce LDL do other things too and it’s not clear that their effect on LDL is the real vector for their efficacy. And people with elevated LDL sometimes don’t develop the diseases that high LDL supposedly causes. It’s a broken model based on an overly intuitive interpretation of legitimate data.

I read a biochemistry textbook. The same one you guys read. The only time it mentioned ketosis, it was a brief footnote in effect saying “ketosis is a dangerous abnormality and results in diabetic ketoacidosis.” It was literally a sentence or two for the whole metabolic phenomenon of ketosis. A widespread textbook printed in the last 5 years if I recall. That’s when my eyes were opened to the possibility that the doctors have been making oversights. How could you blame a doctor for believing his textbook?


>Re: therapeutic reduction of cholesterol, the results over decades are totally unambiguous: reducing LDL-cholesterol via statins and PCSK9 inhibition reduces cardiovascular disease and prolongs life. And those benefits are also conferred to people who have lower cholesterol throughout their life due to genetics.

But if you look outside of the mainstream literature, it appears that that high LDL is protective. Also statins appear to cause more problems than they solve ( So has Aseem Malhotra been screaming about for nothing?). While I cannot quote 'studies' ( I do believe that you can find some if you searched ) , there are compelling anecdotes ( like that of Dr. Shawn Baker) which to me proves consensus on a topic need not necessarily mean that the view is correct. Ofcourse people quickly remind you that anecdotes are not data...




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