Random DNA mistakes are central to Darwinian evolution. Allegedly, the huge diversity of life on Earth (including all organisms that are now extinct) was made possible through the slow, incremental addition of rare beneficial mutations over hundreds of millions of years. The theory demands them, but how is a beneficial mutation defined and are there actual examples we can point to that should give pause for thought to biblical creationists?
Tim C. from the United Kingdom sent us the following question:
I have been searching (without any success) on the internet to find a Christian defence to this example of beneficial mutation: people with the PCSK9 mutation have as much as an 88% lower risk of heart disease. That’s taken from this article [link deleted according to feedback rules].
What is your defence to that?
Thanks for your question. The article in question1 itself refers to a news report on the news site Bloomberg2 about the attempts of pharmaceutical companies to exploit a mutation which reduces “heart attack risk by as much as 88 per cent.” According to the latter, those people with a normal PCSK9 gene produce a protein that prevents the liver from removing ‘bad cholesterol’ from the blood. In 3% of people, a mutated form of the gene reduces levels of the protein (according to the Bloomberg writer) and this is supposedly advantageous. As you perhaps read for yourself, it goes back to a 2006 study in The New England Journal of Medicine (NEJM)3 that found 2.6% of ‘black people’ had mutations that lowered ‘bad cholesterol’ by 28%, reducing heart disease risk by 88%. Correspondingly, 3.2% of ‘whites’ had mutations of the gene that lowered cholesterol by 15% and heart attack risk by 47%.4
Furthermore, cholesterol is not the whole picture. I’ve put ‘bad cholesterol’ in scare quotes partly for this reason. Two types of lipoproteins—Low Density Lipoproteins (LDLs) and High Density Lipoproteins (HDLs)—are known to be involved in the transport of cholesterol to and from the body’s cells. There are actually other subcategories of these too, plus heart disease experts also look at triglycerides and phospholipids. A significant number of researchers in the field are sceptical of the simplistic ideas of ‘bad’ and ‘good’ cholesterol, and the view that the ratio of the two is causally related to heart disease. However, LDLs are generally considered the ‘bad guys’, associated with increased risk of heart disease of various sorts. HDLs are often called ‘good’ by comparison. It’s important to realise that cholesterol is a major structural component of cell membranes, particularly in the central nervous system (brain and nerve tissues). It’s also an important precursor for many critical hormones. Very low cholesterol levels are associated with various diseases. So it’s not bad in and of itself. However, since it can be manufactured by your liver, arguably it’s not an essential dietary requirement.
Receptors on the surface of cells can bind to LDL but if there are not so many of these, it’s thought this contributes to higher LDL levels in the circulating blood, thus increasing the risk of things like atherosclerosis (since LDL is ‘bad’). In the Bloomberg article, Helen Hobbs (University of Texas), whose team published the NEJM paper, is referred to as follows: “Hobbs suspects the reason the patients have such a big reduction in heart attacks ‘is that these people have low LDL their entire life.’ This stops plaque from ever building up in the arteries, she said.” So, what’s going on?
For an article that’s highly relevant to your question, see the discussion of mutations affecting ‘bad’ cholesterol, here: A-I Milano mutation—evidence for evolution? A mutant protein involved in HDL production seemed to have gained advantageous anti-oxidant properties (although the facts are much less impressive) but there was a downside; and this is invariably the case with mutations—they damage existing function. The downside was a net loss of specificity of the mutant protein (i.e. it’s an enzyme), reducing its ability to produce HDLs (the ‘good’). That’s the problem with all claims of beneficial mutations when they’re looked at carefully and rigorously: any alleged benefit invariably involves a sacrifice elsewhere. Not only does this mitigate against any alleged positive selection in Darwinian terms, it represents a loss of function. In this case, with a loss of specificity, there is clearly a loss of information, but molecules-to-man evolution requires information-gaining mutations by the shed-load.
Back to your question, even if we accepted evolution had a mechanism (for the sake of the argument), are we to seriously believe that the PCSK9 gene, supposedly honed during millions of years of evolution to produce a highly complex protein, has lately been improved by a ‘lucky’ mutation? Actually the protein is also an enzyme, which thus binds with high specificity to a substrate; think of a lock-and-key. The idea is that the PCSK9 enzyme, by binding LDL receptors on liver cells, prevents them from removing LDLs from the blood (this, by the way, would be part of a designed homeostasis for balancing levels of LDL in blood)—the net result: more LDLs circulating in the blood. Hence, the mutant form of PCSK9 (in around 3% of people studied), presumably not binding as well to these receptors, is less effective at preventing the removal of LDLs from the bloodstream—the net result: more removed by liver cells, so a lower level of LDLs in the blood. Seemingly, this then results in a reduction of ‘bad’ cholesterol, which is thought to significantly lower heart disease risk. Based on this line of thinking, new pharmaceutical drugs are being developed (inhibitors of normal PCSK9) to treat the majority of people who lack the mutation, thus lowering circulating LDL-associated cholesterol—this, it is hoped, will be useful in treating cardiovascular problems and lowering heart attack risk.
But consider some obvious facts. What we broadly call heart disease particularly afflicts people in affluent, Western countries—where far too many of the population eat too much and eat unhealthily. Obesity is a huge problem in these countries and is a big risk factor for all sorts of chronic diseases, not only cardiovascular ones but also cancer, diabetes and more. (It’s true of course that, as a ‘Western lifestyle’ has been adopted by lower-and middle-income nations, such diseases have increasingly afflicted those nations too). In other words, in such an ‘environment’ it’s quite plausible that a mutation might be advantageous to a small subset of people—as seems to be the case with the PCSK9. However, ‘outside’ the context of dietary-related, higher-cardiovascular-risk populations, such effects would be negligible or non-existent (probably not measurable). Even in a fallen world (Genesis 3), following sensible guidelines for diet and exercise, both HDLs and LDLs are a good thing, part of the Creator’s superlative design. In the context of ill health (to whatever degree this has a hereditary, environmental or lifestyle cause), genetic variants of normal proteins may result in effects that superficially represent examples of ‘beneficial mutations’.
A well-known example is sickle-celled anaemia, often claimed in the past as an example of evolution. Not so. Being heterozygous for the sickle-cell gene (sickle cell trait; i.e. one good copy of the gene, one mutated copy) may give you protection from malaria (the much touted advantage), but you’ll still suffer from the effects of anaemia. Not only that, but approximately 25% of the children of parents who are both ‘carriers’ die of sickle-cell anaemia (they’re homozygous; i.e. two bad copies of the gene). And up to 25% die of malaria (they have two normal haemoglobin genes; but no protection from malaria). In any case, there’s no new information involved genetically. I remember my colleague Dr Don Batten drawing attention to a more subtle version of this 15 years ago—of relevance to this discussion. It was reported that a mutant form of the relevant haemoglobin gene (Hbc variant) provided 93% protection against malaria, even in the homozygous form (that’s to say, the gene on both matching chromosomes was mutated). Unlike the ‘standard’ sickle-cell mutation that is effectively fatal in the homozygous condition, this Hbc variant causes ‘very mild anaemia’. However, note that it does cause some anaemia, so it is still a defect. More importantly, it was still a loss of information. Dr Batten pointed out that this variant of sickle cell represented a ‘loss of specificity for iron in the haemoglobin and presumably therefore some loss in specificity for oxygen [and] loss of oxygen carrying capacity.’5
Without knowing more about the mutation in this PCSK9 gene, I cannot be dogmatic but I’d hazard a guess that, on closer examination, the reduced binding capacity of PCSK9 to LDL receptors is associated with a fitness cost, as in the other examples I’ve mentioned. For what it’s worth, although I am a biologist myself, I shared my response with another PhD biologist colleague. He agreed with my perspective and added “The bottom line is that, even if this is advantageous, it is still a modification to an existing gene, rather than creating anything fundamentally new. This does not provide a mechanism for microbes to microbiologists evolution. Evolution needs a mechanism for creating thousands of new gene families and mutations cannot do this. Evolution has no mechanism.”