As the reviews of professor Behe’s new book Darwin Devolves continue, many who participate in the discussions on many blogs or websites may have noticed the seeming paradox involving high fat, high cholesterol diet and heart disease issues… Dr. Behe devoted a good portion of his book to the issue of the devolution of the polar bear, which supposedly evolved, or rather devolved according to Behe, to tolerate the drastic switch from the dietary habits of its ancestors some 400 000 years ago…This particular issue I’m planning to cover in one the upcoming OPs…
This OP is more of an introduction to the fat/cholesterol/heart disease issue that while it seems complicated at the first glance, it really isn’t…
Some members on TSZ have already alluded to this issue, so I will cover just the very fundamentals:
- cholesterol is a fatty substance produced by the liver (about 80%)
- only 20% of cholesterol enters the bloodstream via diet
- if more cholesterol is consumed, the liver slows down its production
- cholesterol is essential to life as cell membranes require it (among others)
- if cholesterol is not produced in sufficient amount by the liver the organism dies
- people who consume little cholesterol still develop heat disease, including atherosclerosis–the fatty deposits of cholesterol (and other, like calcium) in arteries
- people with low blood cholesterol levels develop heart disease;
patients with advanced heart failure often have low cholesterol, which is associated with a poor prognosis for survival
If people and many animals who consume little cholesterol develop heart disease, one might also ask whether people who consume a lot of fat and cholesterol are at the same risk…
The simplest answer is no.
That’s why the issue of high fat and cholesterol consumption diets in humans with low rates of heart disease have been labeled as the cholesterol paradox, because, from at least one point of view, it just doesn’t make sense…
As the side point, the great majority of Cell article Behe explores in his book Darwin Devolves is based on the assumption that high fat, high cholesterol diet causes heart disease (arteriosclerosis) therefore the polar bear must have evolved the adaptation to eat seal blubber and have no atherosclerosis…
Behe just plays along and simply exposes the assumptions that if polar bear evolved to eat high fat, high cholesterol diet, it has done so by breaking or blunting gene functions…This will be covered in the upcoming OP…
Why cholesterol paradox?
Because there are many groups of people (not as many anymore) all over the world that seem to be the exception to the assumed rule that high fat, high cholesterol diet cases heart disease, like atherosclerosis…Some of them are called hunter-gatherers but others, like Canadian Inuit, could be called seal blubber eaters, just like the lowly poplar bear at issue between evolutionists and ID…
Inuit eating seal blubber
If there are exceptions or paradoxes to the rule among those groups of people, are they due to adaptive mutations, just like it has been claimed in the Cell article that Behe explored regarding polar bears?
Or, is there another possible explanation?
You tell me… 😉
😉
What’s authors’ of the original paper in Cell conclusion regarding the effects of mutations in ApoB, which Swamidass also supports?
Can you quote it and explain?
BTW: Did you watch the webinar, especially at 1:44.00?
It’s all there… 😉
You’re confused.
You first need to find out what the ApoB gene actually does, and then you need to find out what the polar bear ApoB mutations do. Whether polar bears have high levels of LDL cholesterol and low levels of heart disease is besides the point.
The point is that the mutations are beneficial, fixed by natural selection. And that Behe thinks they somehow degrade the function of the ApoB in some way.
Do they? Are the ApoB mutations in polar bears reducing the function of the ApoB gene? To know that we need to know all the things ApoB do. ApoB is involved in more than merely affecting blood cholesterol levels, as it is also involved in all kinds of blood fat transport.
While polar bear cholesterol levels might be very high, it is entirely possible the polar bear beneficial mutations in the ApoB gene actually increase the overall fat transport capacity, which would make sense given the high fat contents of polar bear diets.
It is even possible some of those mutations increase fat transport capacity overall, while also degrading the LDL clearance. It’s a multifunctional gene and it’s entirely possible there are tradeoff functions at work, where increasing one function substantially which has a high fitness advantage, will come with a reduced function in another capacity with a much lower fitness cost(if any).
You have not even BEGUN to do the kind of work you hold in abiding faith will vindicate Behe.
Besides the point?! Boy!!!
Speaking of someone being confused… 😉
Jock! Your customer… lol
Another fact to consider here is that LDL cholesterol is actually involved in fat transport too. And fat molecules in the bloodstream are actually carried by cholesterol molecules. So for a bear eating extreme amounts of fat, it will have high cholesterol simply because those molecules are synthesized so as to carry the fat around in the bloodstream.
Mutations in the ApoB gene might actually increase the fat transport and clearance capacity, even tough bears still have extremely high blood cholesterol, simply because the bears eat so much fat.
There is no reason to think the ApoB mutations increasing fat transport and clearance should cause polar bears to have lower levels of blood cholesterol compared to brown bears when polar bears still eat much, much more fat than brown bears.
If the clearance and transport capacity of the gene is increased by 15% (say), but polar bears eat (say) 300% more fat than brown bears, they are still going to have higher blood cholesterol than brown bears, even though they are also better at dealing with it.
You get it now?
As usual you have nothing to say but to drool and whinge. Responding to you IS like responding to Robert Beyers.
J-Mac is equating high serum cholesterol with reduced fitness. That’s a mistake.
Behe equates diet-induced hypercholesterolemia with reduced fitness; slightly better, but still a bridge too far.
Atherosclerosis is caused by plaque deposition.
The irony being that we know Behe is wrong about the effect of reduced ApoB function in the mouse (Huang is right and Farese is wrong: it leads to male sterility, amongst other things).
As Rumraket correctly notes, anyone who talks about the effect of those polar bear mutations in ApoB is speculating. A little bit of speculation is the reward you earn for putting in the work, like Liu et al did.
I do? I didn’t know that…😉
Stop misrepresenting my views and embarrassing yourself at the same time…😂
You’ve changed your mind, again?
I’m not speculating one bit… I know…😉
Did you Google what the plaque consists of other than “the killer cholesterol”???😉
No, but I did hear Michael Brown explain to Mark Bretscher why he does not eat egg yolks.
Can you figure out why, J-Mac?
😉
He doesn’t? Too bad… I eat 2-5 eggs almost every day… My buddy eats at least 8 eggs or more… as he is on full keto and hates cooking…Can you make a prediction regarding our cholesterol levels? 😉
Tip. Gregg’s one type of cholesterol carrier protein was either extremely low or extremely high as it was not detected by the test… The test needed to be repeated several times…Can you guess which one it was and whether it was high or low?🤗
Didn’t you say I was right? 🤔
If you wanna play the game, be specific! High or low serum cholesterol levels in relation to fitness?
Read this again and again and then try to figure it out why I don’t feel like responding to such nonsense… Can you? 😭
😂
How about this: We test it by analyzing the cholesterol levels in brown bears eating high fat diet in Alaska without the “beneficial mutations” in ApoB protein.
What is your prediction? 😉
I might not be aware that I disagree with Behe on more than one issue…I think he knows by now what they are…😉
It is already challenging to take anything you write seriously, please don’t make it harder than it already is.
Why should I take your speculative evolutionary science seriosly? Because you really wish it were true? That’s not science! Not to me…
Tell us more, age, family history, ratio of “ good “ and “bad”. What else do you eat?
My prediction is that J-Mac chasing disgruntled brown bears to take blood samples will be even more amusing to watch than him chasing chickens.
My prediction is that brown bears in Alaska will be highly polymorphic.
Here’s the research proposal:
Pick a tractable experimental animal (one where you can actually take sequential fasting blood samples), probably the dog, but the silver fox might be fun…
Replace it’s ApoB gene with the putative ancestral bear one (could default to the panda, I guess).
Research the cholesterol levels, diet-induced hypercholesterolemia and susceptibility to atherosclerosis and CHD in these animals for a variety of diets.
Introduce each of the five ApoB mutations that were fixed in the polar bear. Do all 32 possible alleles.
Research the cholesterol levels, diet-induced hypercholesterolemia and susceptibility to atherosclerosis and CHD for each of the 528 possible genotypes for a variety of diets.
You’ve got a lot of work ahead of you, J-Mac. Maybe your kids can help.
Well J-nut is fond of declaring that he’s got “contacts” that can “fund” these experiments.
I guess it could be squeezed in after they are done with the double slit experiment in the basement.
No way?! Really?! 😉 That is hell of the thin, you know… 😉
We have already established that you’ve forgotten how to research the pubmed…
Now you have confirmed that you can’t google…
It took me 30 seconds to find this:
Brown bears (Ursus arctos) seem resistant to atherosclerosis despite highly elevated plasma lipids during hibernation and active state.
https://www.ncbi.nlm.nih.gov/pubmed/22686205
Give me one more reason why I should respond to your further comments?
Why should I waste my time?
The double slit ex is an old idea… Now you can buy equipment to test stimuli retroactively? 😉
I do…but why bother? 😉
Bears not bothered by diet high in saturated fats
Grizzlies show no clinical signs of disease following short-term consumption of saturated fats but scientists question long-term health
https://www.sciencedaily.com/releases/2017/10/171030084745.htm
I want focus on the new evolutionary theory with evidence gaps. No evidence for evolution? No problem. Maybe God guided it… 😉
Guided what? Evolution? But you just said there was no evidence for it.
Your position is as confused as I’m sure your children are.
Your actual level of commitment to the truth is thus revealed.
Actually, Byers made me think and can anyone guess?
Does the bible recommend eating fat, or prohibits it? 😉
Thank you Einstein!
Your actual level of commitment to cherry picking in order to distort the truth is thus revealed…
Further to testing the idea of whether J-Mac has any clue what he is talking about…
I was so entertained by Dr. Malcolm Kendrick’s use of the restricted mean survival time (RMST) statistic to quantify the benefit of statin therapy, so I did a “back of the cigarette packet” calculation of my own. Let’s see if fanboy J-Mac understands the stats…
His 15.6 day to 17 day reduction in RMST seen in the HPS and 4S studies implies that there is a roughly 0.5% per annum absolute mortality effect.
Sounds kinda lame ass, am I right?
But it isn’t:
0.5% p.a. absolute risk reduction would lead to an average lifetime benefit of 3.9 years for a 40-year-old man, 4.5 years for a woman.
The graph below (life curve for a 40-yo woman with or without an extra 0.5% mortality) shows why RMST is the wrong metric.
Pop quiz for J-Mac:
1. Describe in your own words how to calculate the RMST after five years from this graph.
2. Describe in your own words how to calculate the Hazard Ratio after five years from this graph.
E4typo 45 should read 40
Let’s review the conversation, J-Mac.
Behe has claimed that the five mutations that fixed during the evolution of the polar bear from the common ancestor with brown bears (specifically N716K,D749E, D2623N,T3920P, and L4418H) are mostly deleterious; that is, the polar bear evolved via a process of “blunting or breaking” gene functions.
Basically, he reached this conclusion because he mis-interpreted the meaning of the analysis in Liu et al 2014, in particular the application of the human-developed PolyPhen-2 algorithm to Bear genes. Only when the 3 Musketeers pointed out his errors did Behe realize his mistake; that’s when he latched onto Farese et al 1995. Farese et al made a disruption in the mouse ApoB gene and showed that (when homozygous) the mutation was embryonic lethal but the heterozygote, weirdly, showed a resistance to diet-induced hypercholesterolemia – suggesting (to Behe, at least) that reduced ApoB function could be adaptive for animals on a high fat diet. This is the entirety of his data to support his contention that the mutations in ApoB are “blunting or breaking”, and that they support the thesis of his book.
Suspiciously, this Farese reference is cited in the Wikipedia page on ApoB. This, combined with the fact that it is WRONG, leads me to suspect that Behe’s citing of Farese was a post-hoc rationalization. But I could be wrong about that, and it’s not important right now.
What is important is the fact that Huang et al 1995 (J Clin Invest. 96: 2152-2161) actually did the knock-out properly and found that the heterzygote led to male sterility, amongst other problems. As I noted, “That’s not going to be adaptive”.
After much teasing, you finally reveal that your ‘killer’ argument is the claim that Liu et al’s statement
is not well supported.
Well, to the extent that you have a fair criticism here, it goes double for Behe’s claims.
Your “support” for the “killer” nature of your position consists of noting that polar bears have elevated plasma cholesterol levels. “Extreme”, even.
Various posters have pointed out that this is a total non-sequitur, including (most recently, and most enjoyably) the poster J-Mac, who has cited a paper showing that Brown bears are resistant to atherosclerosis despite having high plasma cholesterol.
(It’s not just the level of LDL, it’s where it goes, apparently. ApoB does a bunch of things. That deep-sixes your simplistic argument. If you were capable of thinking this through, you would understand that the nature of the role of ApoB in controlling plasma cholesterol and the roles of ApoB in preventing atherosclerosis is entirely peripheral to the issue of whether ApoB in polar bears has evolved or “devolved”.)
I’ve even been trying to gently guide you to look at the LDL receptor (egg yolks and Nobel Laureates), which (unlike ApoB) IS involved in human cardiovascular disease. As are a bunch of other factors, like Lp(a) levels and PCSK9, too. It is very complicated.
On the other hand, you missed the bit about Brown Bears hibernating, apparently. Awkward. (There’s actually a rather cute, if contorted, argument to be made here in Behe’s defense. Let’s see if any of you guys is smart enough to spot it.)
Behe’s argument hinges on the effect of the specific mutations that fixed in the polar bear. No amount of mis-reading of the effect of HMG-CoA reductase inhibitors by loopy British PCPs (see above) will support that argument.
You are not fooling anyone. Not even the creationists.
I am quite confident that you are unable to comprehend the primary literature; you have given us no reason to think otherwise. You are painting your cause in a very poor light.
You keep thinking this is a question merely of the propensity of heart disease in bears. There are more factors at work here. Fat metabolism, transport, and storage, just to name a few. And these all have to be viewed in the context of the life-history evolution and development of polar bears and their ancestors.
It is difficult to overstate how much you have yet to grasp. I can only repeat myself: You have not even begun the kind of work it would require to parse out the biochemical or phenotypic effects of these mutations on the function the ApoB gene.
In what sense? What have I cherry picked? What is the full meaning of my quotation in it’s full context? What have I distorted? What is the truth?
I don’t expect you do answer this question, in a very real sense it’s purely rhetorical.
If there is no evidence for it, how can there be gaps in that evidence?
Do you think god guided evolution? If so, which god? And how do you know?
It’s “I want to focus”. Don’t you read what you write?
Actually, never mind…
This is BS Jock… lol
You set yourself up… Well I had… but you fell for it… 😉
Someone once told me:
“Do not let emotion to distort your judgment!”
If you really paid close attention to all the hints I have given you, you may have figured out the trap I was setting up right from the beginning…
You should have paid closer attention to one aspect of my Darwin Devolves review, where I clearly stated that I don’t agree with Behe on few things and that his views are often based on not “sound science”… 😉
I don’t! I never did. Is it against the rules of TSZ?
This seems to be the sock gnome argument.
1. You didn’t pay attention
2. ?
3. I’m right.
You need to give more attention to point 2.
I realize that Alan Fox and DNA Jock are too ignorant to figure out what I’m implying…So, yes, I’m suggesting that the famous 2014 Cell article was an evolutionary bluff…
Yes, I have evidence and DNA Joke has seen most of it…he is just to ignorant to acknowledge it…
Aw, don’t be so coy, J-Mac. We’re quivering in anticipation. Do tell us how you’ve overturned evolution!
Although, I would appreciate a pledge of faith:
1. Describe in your own words how to calculate the RMST after five years from the graph above.
2. Describe in your own words how to calculate the Hazard Ratio after five years from the graph above.
It’s basic stats for anyone who can read the clinical literature.
Right now, you appear uncannily like a complete bullshitter. Just a friendly heads-up.
😉
Here is my, or rather your, first problem:
“You are right, J-Mac!
The observation that polar bears have elevated plasma cholesterol completely refutes Behe’s argument re APOB.
I hope you understand my concern about your credibility first…
I don’t need to overturn anything… It does it by itself… 😉
All hat, no cattle.
According to Behe, polar bears have suffered a “blunting or breaking” of their ApoB gene. When challenged to explain how he can tell the difference between an “increase” in ApoB function and a “decrease” in ApoB function, Behe (on multiple occasions) hauls out the observation (Farese) that mice with a 50% reduction in ApoB function (the heterzygous null) have reduced plasma cholesterol levels.
Therefore, according to Behe, polar bears’ elevated cholesterol must be a sign of elevated ApoB activity, thereby refuting his thesis.
Not to worry, he has both his facts and his logic wrong.
N.B. In my view, each of the phrases in quotes represents an incoherent concept. As a biochemist, Behe ought to know better.
Now it’s your turn, J-Mac
1. Describe in your own words how to calculate the RMST after five years from the graph above.
2. Describe in your own words how to calculate the Hazard Ratio after five years from the graph above.
DNA_Jock,
I would like to remind you, again, that I don’t agree with Behe on few things…
I have warned you many times not to commit yourself to the cholesterol/ApoB nonsense…
If the original Cell article is based on false premise, regarding the polar bear cholesterol adaptation, who is going to go down?
Evolutionary nonsense?
Behe’s book based on evolutionary nonsense?
Both?
Let me know which one you would like to see retracted first…
ETA: It can be tough to choose for both Darwinists and God lovers…
This is why J-Mac, and posters with a similar style should not be allowed to post a plethora of posts: we have covered this ground previously. He’s galloping.
Back in February, after much prodding, you finally offered up your big reveal that Liu et al merely suggested “that the shift to a diet consisting predominantly of fatty acids in polar bears induced adaptive changes in APOB, which enabled the species to cope with high fatty acid intake by contributing to the effective clearance of cholesterol from the blood”.
It’s a piece of speculation. And, as I have pointed out to you numerous times on various threads since then, if it is poorly supported, then Behe’s thesis is in even worse shape. You seem to fail to comprehend this.
Behe’s argument is in utter tatters.
Although you introduce a new failure in comprehension here. Liu et al’s suggestion re the effect of the ApoB mutations on cholesterol clearance is an aside, a speculation, a potential tentative conclusion. What it is not is a premise.
You are coming across as illiterate. Here’s your shibboleth:
1. Describe in your own words how to calculate the RMST after five years from the graph above.
2. Describe in your own words how to calculate the Hazard Ratio after five years from the graph above.
I predict you would rather continue to bluster incoherently.
Side note:
and
On the Lenski thread:
Are these two different attempts to mangle the idiomatic expression “That’s the hell of the thing!” ? As in “Ay, there’s the rub”?
Could you be any less coherent?
It looks like Dr. Lents can’t even read the papers he quoted or its your fault Jock with all this cholesterol paradox:
“To answer an earlier question in this thread, there are two important pieces of suggestive evidence that the cholesterol-clearing function of ApoB is enhanced in polar bears: one is that they eat a diet very high in saturated fats and yet have low LDL levels and do not develop cardiovascular disease. Their cholesterol clearance must be working very well and the ApoB gene harbors the second-most highly selected variants in polar bears – highly suggestive. Secondly, the variants themselves are mutations that cluster disproportionately in the domain that we know is involved in cholesterol clearance. Again, highly suggestive.”
https://discourse.peacefulscience.org/t/a-scholarly-discussion-of-apob/5483/13
The Cell article says polar bears’ cholesterol levels are extreme. Dr Lents says LDL cholesterol levels are low…
You said I was right about polar bears’cholesterol levels….now you seemed to have changed your mind….
Whatta bloody joke!😂
BTW : I’m taking screen pictures of all this nonsense…😉
Again, if the article in Cell Behe based his book on is bs (LYST seems ok), regarding the ApoB and cholesterol beneficial mutations, who is really responsible for the fabrication of the scientific evidence? Behe?
You do not appear to understand how evidence works. The data in Liu et al are the data. Liu made a comment about cholesterol clearance. Liu made a statement about plasma cholesterol levels, calling them “extreme” (referencing a Norwegian Ph.D. thesis; care to put some numbers on that?)
It is the data that matter. And the data fail to support Behe’s thesis (that polar bear evolution occured mainly via “blunting or breaking”).
No amount of whinging on your part changes this one iota.
And you continue to fail to demonstrate any ability to read the primary literature.
As I predicted, you continue to bluster incoherently.
Go ahead, if you understand the literature better than Lents, shock me —
1. Describe in your own words how to calculate the RMST after five years from the graph above.
2. Describe in your own words how to calculate the Hazard Ratio after five years from the graph above.
That’s a lot of hat for someone who lacks cattle.