Nothing in Medicine Makes Sense Except in the Light of Evolution

 My post title comes from a 2012 Journal of Molecular Medicine article [1] by physician, scientist and UC San Diego professor Ajit Varki [2] in which he stresses the critical importance of evolutionary biology for medicine to the point where he argues it needs to be included in the medical curriculum as one of the basic clinical science, a view that others such as psychiatrist Randolph Nesse have also made. [3] Ignoring the clinical applications of evolutionary biology in areas ranging from epidemiology to oncology, a mastery of evolutionary biology allows one to make sense of the bizarre, maladaptive features of the human body from the gross anatomical down to the genomic which make perfect sense given the vagaries of an evolutionary process that only selects for what works at the moment, withougt thought for how those initial choices will impact the descendant of that organism. More importantly from a theistic perspective, as evolutionary biologist John Avise [4] has pointed out, this frees God from the very real problem of the obviously maladaptive design in the human body by ascribing it to the evolutionary process rather than the direct hand of God.

Anatomical Mistakes

There's no denying that the human body is capable of many amazing things, but its anatomy betray its evolutionary origins, as shown by numerous anatomical features which an omnipotent intelligent designer able to design from clean sheet would not do. I'm writing this from the middle of the southern hemisphere winter, and sinusitus is one problem that becomes apparent at this time of year. One huge problem which predisposes us for sinus infection is that the sinus drainage holes are in the wrong position for a biped, but make sense in a quadruped design. Cell and molecular biologist Nathan Lents writes

There are a variety of reasons for why we're so susceptible to sinus infections, but one of them is that the mucous drainage system is not particularly well designed. Specifically, one of the important drainage-collection pipes is installed near the top of the largest pair of cavities, the maxillary sinuses, located underneath the upper cheeks. Putting the drainage-collection point high within these sinuses is not a good idea because of this pesky thing called gravity. While the sinuses behind the forehead and around the eyes can drain downward, the largest and lowest two cavities must drain upward. Sure, there are cilia to help propel the mucus up, but wouldn't it be easier to have the drainage below the sinuses rather than above them? What kind of plumber would put a drainpipe anywhere but-at the bottom of a chamber? [5] (Emphasis in the original)

Evolutionary contingency readily explains our poor sinus drainage, but the advocate of intelligent design is forced to explain why the creator could not have sorted out sinus drainage in humans properly in the first place.

Sinusitus. Image source - Centers for Disease Control and Prevention

 

The classic example of poor design is of course the vertebrate retina [6] which has the light-sensing cells pointing away from the light, rather than towards it as in cephalopods like the octopus. The immediate problem here is that there will be a blind spot in the vertebrate retina where the nerves and blood vessels exit and enter. This fundamenally broken architecture results in more than just a blind spot:

• It increases the risk of retinal detachment since the retina is not firmly anchored to the eyeball
• It increases the risk of visual impairment from retinal haemorrhage and diabetic retinopathy
• To compensate for the limitations of the inverted retina, evolution has produced a small area where the nerve and blood vessels are swept aside as much as possible and the densisty of light-sensing cells is at its highest to give our high-resolution vision. Having this high-resolution zone in a small spot means that if it is affected in diseases such as macular degeneration, our high-resolution vision is lost. This would not be needed if we had the cephalopod architecture

There is no argument that over time evolution has optimised the bad hand it was given via the contingency of the common ancestor of vertebrates electing to use the inverted retina architecture to produce a design which is highly optimised, but this is akin to marvelling at the high quality of spectacles given to someone with pronounced astigmatism, myopoa and an inability to collimate distant faint objects (I speak as someone so cursed). Getting the design right in the first place would have made for a superior design.

Configuration of the cephalopod and vertebrate eye. From Novella (2008)

 

Another quirk of anatomy shared by a class of organisms in which a decision made by its common ancestor left it with flawed anatomy is the path of the recurrent laryngeal nerve in tetrapods, including humans. This nerve, a branch of the vagus nerve innervates the larynx, but instead of connecting to it passes by it, down the neck and under the aorta, ascending up the neck to finally innervate its target organ. This needless detour is shared by all tetrapods, including the giraffe which has metres of wasted nerve. 

By Jkwchui - Based on drawing by Truth-seeker2004, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=30998747

This anatomical flaw is readily explicable when we consider our fishy ancestors, in which the nerve passed on one side of an artery, which when the tetrapod descendents of fish grew long necks was dragged down into the chest. Evolutionary biologist Mark Ridley writes

In humans, the detour looks absurd, but is only a distance of a foot or two. In modern
giraffes, the nerve makes the same detour, but it passes all the way down and up the
full length of the giraffe’s neck. The detour is almost certainly unnecessary and probably
imposes a cost on the giraffe (because it has to grow more nerve than necessary and
signals sent down the nerve will take more time and energy). Ancestrally, the direct
route for the nerve was to pass posterior to the aorta; but as the neck lengthened in the
giraffe’s evolutionary lineage the nerve was led on a detour of increasing absurdity. If a
mutant arose in which the nerve went directly from brain to larynx, it would probably
be favored (though the mutation would be unlikely if it required a major embryologic
reorganization); the imperfection persists because such a mutation has not arisen (or it
arose and was lost by chance). The fault arose because natural selection operates in the
short term, with each step taking place as a modification of what is already present. This
process can easily lead to imperfections due to historic constraint a though most will
not be as dramatic as the giraffe’s recurrent laryngeal nerve. [7]

Evolution of the recurrent laryngeal nerve - Ridley (2009)

The fact that this same design flaw is repeated over and over again in tetrapods is inexplicable from a special creationist perspective, but when one recognises the evolutionary origins of tetrapods, including humans, from a fishy ancestor, the anatomical flaw becomes readily understandable.

Many other human design flaws exist including the abdominal wall weakness that predisposes men to hernias as a result of the descent of the testicles to their external position, something that would not exist if spermatogenesis was designed to take place at blood heat, the risk of urinary retention and death from renal failure that results from running the urethra through the prostate, an organ that in age swells and reduces urinary flow in men, the risk of gut obstruction from ring pancreas, a condition where the fusion of the pancreas from two embryonic buds goes astray and constricts the duodenum, something that would not occur if the pancreas arose from one embyonic bud, the risk of choking that exists from the close proximity of oesophagus and trachea, and disc prolapse arising from coopting a spine designed for quadrupeds for bipeds. [8] 

Genetic Errors 

While gross anatomical design flaws are easy to see, arguably the most compelling evidence for evolution from medicine comes from human genomics. If we were specially created, then it is reasonable not to expect genetic evidence confirming common ancestry with other animals. However, a careful examination of our genome provides this evidence in abundance. The best-known example is the GULOP pseudogene, [9] the functioning version of which codes for L-gulonolactone oxidase, the terminal enzyme in the biosynthetic pathway for vitamin C. Humans, apes and monkeys do not have a functioning version of this gene, which raises the question of why an intelligent designer would create some animals with a fully-functional vitamin C biosynthetic pathway, but create others with a broken biosynthetic pathway. Given that vitamin C deficiency causes scurvy which is fatal if not treated, this is a serious question for creationists to face. Where this troubling problem becomes a knock-down argument for human-ape common ancestry is that the GULOP pseudogene is broken in exactly the same way in humans, apes, and monkeys. Furthermore, given that the GULOP pseudogene is no longer under selection, it is free to pick up mutations at the background rate, and we see that in primate species which are closely related their GULOP genes differ by fewer point mutations than primates which are distantly related. This is precisely what we would expect if humans, apes, and monkeys share a common ancestor in which the GULO gene was incapacitated, and this pseudogene was free to acqiuire mutations, with the number of mutations proportional to the time since those two shared a common ancestor. Special creation is forced to postulate God created humans, apes, and monkeys with a broken GULO gene, then inserted exactly the right pattern of point mutations to simulate what would happen if humans, apes, and monkeys shared a common ancestor.

 

Another example of pseudogenes confirming common descent is the haemoglobin gene family, and here we see yet another powerful example of primates sharing the same pseudogene in the same relative position in their genomes, entirely what one would expect if primates shared a common ancestor from which they inherited this broken gene. Biologist Daniel Fairbanks writes:

Let's now look at one of our oldest and best-studied duplication pseudogenes. As mentioned in the previous chapter, hemoglobin is a vital oxygen transporter in the blood. The human genome contains thirteen copies of the genes that encode hemoglobin, but only four of them function in adults. Of the remaining nine copies, four are pseudogenes, and five are active in the fetus and help the fetus obtain oxygen from the mother's blood during pregnancy. These fetal genes are turned off either before or shortly after birth. The hemoglobin genes and pseudogenes reside in two clusters, the alpha cluster with four genes and three pseudogenes, and the beta cluster with five genes and one pseudogene. Each of these clusters arose anciently from repeated tandem duplication of an original gene. 

The single pseudogene in the beta cluster is called the psi-beta pseudogene and it is full of mutations; about 30 percent of its DNA sequence is mutated when compared to its parent gene. To accumulate so many mutations, this pseudogene must have arisen through duplication and then been disabled a very long time ago. 

If we compare the beta cluster in six primate species, a fascinating pattern of evolution emerges. Figure 3.1 shows the alignment of genes and pseudogenes in the beta cluster of humans, chimpanzees, gorillas, baboons, New World (American) monkeys, and lemurs (small, rodent-sized primates that are neither apes nor monkeys). Humans, chimpanzees, and gorillas have the same copies of the genes and the psi-beta pseudogene in the same positions, so these three species must be closely related. Baboons have the same copies in the same positions but the delta gene mutated into a new pseudogene. New World monkeys have the psi-beta pseudogene, but humans, chimpanzee, gorillas, and baboons have one more hemoglobin gene than they do. The extra gene arose when the gamma gene duplicated into two copies in their common ancestor. In the lineage that led to lemurs, a piece of DNA was deleted between the psi-beta pseudogene and the delta gene. The deletion disabled the delta gene and fused a piece of it with a piece of the psi-beta pseudogene. The outcome was a new pseudogene called the psi-beta-delta pseudogene.
The presence of the psi-beta pseudogene, or a piece of it, in all primates reinforces the meaning of its large number of mutations: it became a pseudogene long ago in a common ancestor of all primates, whereas other pseudogenes arose more recently. [10]

 

Medical genetics provides even more compelling evidence for human evolution from the many endogenous retroviral elements humand and apes share at the same locations in their genomes. Endogenous retroviral elements occur when retroviruses integrate into the human genome and into the germline where they are inherited like any other genetic element. As they are selectively neutral, they will soon pick up mutations and become inactivated, so many are non-functional, degraded remains of their viral ancestors. Occasionally, a retroviral element will be coopted by evolution to perform another unrelated function such as the syncitin gene which has a critical role in regulating the formation of the human placenta, [11] but most are without function. Over 25 years ago, the virologists John Coffin and Welkin Johnson noted how endogenous retroviral elements could be used to generte reliable evolutionary family trees, noting:

Given the size of vertebrate genomes (>1 × 10⁹ bp) and the random nature of retroviral integration, multiple integrations (and subsequent fixation) of ERV loci at precisely the same location are highly unlikely. Therefore, an ERV locus shared by two or more species is descended from a single integration event and is proof that the species share a common ancestor into whose germ line the original integration took place. Furthermore, integrated proviruses are extremely stable: there is no mechanism for removing proviruses precisely from the genome, without leaving behind a solo LTR or deleting chromosomal DNA. [12]

The third and arguably most significant class of genomic element that demonstrates common ancestry are retroransposons, mobile genomic elemens related to retroviruses that blindly copy and paste themselves in the human genome. As with ERVs, occasionally retrotransposon elements are coopted by evolution for other uses [13] and have shaped genomic evolution, [14] but largely they are genomic dead weight, composing around 47% of the human genome. [15] As retrotransposons insert blindly, they can overwrite functional DNA causing genetic disease. Evolutionary biologist John Avise notes:

Mobile elements have the potential to cause human diseases by several mechanisms. When a mobile element inserts into a host genome, it normally does so at random with respect to whether or not its impact at the landing site will harm the host. If it happens to land in an exon, it can disrupt the reading frame of a functional gene with disastrous consequences. If it jumps into an intron or an intron-exon boundary, it may cause problems by altering how a gene product is spliced during RNA processing. If it inserts into a gene’s regulatory region, it can also cause serious mischief. The potential for harm by such insertional mutagenesis is great. It has been estimated, for example, that an L1 or Alu mobile element newly inserts somewhere in the genome in about 1–2% and 5%, respectively, of human births. Another problem is that when a mobile element lands in a functional gene, genetic instabilities are sometimes observed that result in deleted portions of the recipient locus. Several genetic disorders have been traced to genomic deletions associated with de novo insertions of mobile elements. Finally, mobile elements (or their immobile descendents that previously accumulated in the human genome) can also cause genomic disruptions via nonallelic homologous recombination. Serious metabolic disorders can result. [16]

Fairbanks also comments on the disease-causing capacity of retrotransposon insertion as well as noting how this retrotransposable element acts as a marker for common ancestry of humans, chimpanzees, gorillas, and orangutans:

Our third example highlights CMT1A, a duplicated segment of DNA with Alu elements on both ends. Humans and chimpanzees have two copies of the CMT1A segment at exactly the same places in their genomes. However, the gorilla and orangutan genomes each have only one copy of the CMT1A segment, in the same position as one of the CMT1A segments in humans and chimpanzees. The two copies of CMT1A in humans and chimpanzees are similar but not identical. In particular, an Alu element on the end of one of the copies is truncated (missing part of its DNA) in both humans and chimpanzees when compared with its corresponding Alu element in the other copy.

The presence of the duplicated segment in humans and chimpanzees, and its absence in gorillas and orangutans, suggests that the duplication happened in the common ancestor of humans and chimpanzees, most probably after that ancestor had separated from the ancestor of gorillas and orangutans. It implies that humans and chimpanzees are more closely related to each other than either is to gorillas or orangutans.

It's no coincidence that the duplicated CMT1A segment has retroelements on its ends. It is now well known that repeated sequences (such as retroelements) located close to each other target the DNA between them for duplication, which explains the duplication of CMT1A in humans and chimpanzees. The newly duplicated segments now predispose any DNA between them to further duplication. Duplication of the sequence between the two CMT1A adds another copy of a gene called PMP22 that lies between the two CMT1A segments. The two copies of this gene cause Charcot-Marie tooth disease, which has serious neurological consequences. In fact, the CMT1A segment was named after the disease (“CMT” in CMT1A stands for Charcot-Marie tooth disease). Because of the tendency of the segment containing PMP22 to further duplicate, this disease is relatively common, affecting about one in twenty-five hundred people, an unfortunate consequence of our evolutionary heritage. [17]

Conclusion

My opening remark that nothing in medicine makes sense except in the light of evolution is not a rhetorical flourish but a statement of the fact that the human body while in part honed by evolution over millions of years to perform admirably well nonetheless betrays its evolutionary origins in its bizarre anatomical and genetic quirks which can cause considerable morbidity and mortality, but which when understood in the light of evolution make perfect sense. The realisation that our bodies are in many ways deeply flawed does in the former creationist elicit a sense of profound unease at the thought we are in some way the product of a divine hand, though operating through evolutionary forces. However, as John Avise notes in the conclusion of his paper, evolution actually becomes a friend of theism. He writes:

Evolution by natural causes in effect emancipates religion from the shackles of theodicy. No longer need we agonize about why a Creator God is the world’s leading abortionist and mass murderer. No longer need we query a Creator God’s motives for debilitating countless innocents with horrific genetic conditions. No longer must we anguish about the interventionist motives of a supreme intelligence that permits gross evil and suffering in the world. No longer need we be tempted to blaspheme an omnipotent Deity by charging Him directly responsible for human frailties and physical shortcomings (including those that we now understand to be commonplace at molecular and biochemical levels). No longer need we blame a Creator God’s direct hand for any of these disturbing empirical facts. Instead, we can put the blame squarely on the agency of insentient natural evolutionary causation. From this perspective, the evolutionary sciences can become a welcome partner (rather than the conventionally perceived adversary) of mainstream religion. [18] 

References 

 

1. Varki A. Nothing in medicine makes sense, except in the light of evolution. J Mol Med (Berl). 2012 May;90(5):481-94. doi: 10.1007/s00109-012-0900-5. Epub 2012 Apr 27. PMID: 22538272.

2. https://cmm.ucsd.edu/research/labs/varki/index.html

3. Making evolutionary biology a basic science for medicine, Proc. Natl. Acad. Sci. U.S.A.107 (suppl_1) 1800-1807, https://doi.org/10.1073/pnas.0906224106 (2010).

 4. J.C. Avise, Footprints of nonsentient design inside the human genome, Proc. Natl. Acad. Sci. U.S.A. 107 (supplement_2) 8969-8976, https://doi.org/10.1073/pnas.0914609107 (2010).

5. Lents, Nathan H.. Human Errors: A Panorama of Our Glitches, from Pointless Bones to Broken Genes. United States: Houghton Mifflin Harcourt, 2018, 10 

6.  Novella, S. Suboptimal Optics: Vision Problems as Scars of Evolutionary History. Evo Edu Outreach 1, 493–497 (2008). https://doi.org/10.1007/s12052-008-0092-1

7.  Ridley, Mark. Evolution. United Kingdom: John Wiley & Sons, Incorporated, 2009, 282

8. Held, Lewis I.. Quirks of Human Anatomy: An Evo-Devo Look at the Human Body. United Kingdom: Cambridge University Press, 2009, 110-113 

9. Daniel J. Fairbanks, Relics of Eden: The Powerful Evidence of Evolution in Human DNA (Amherst, NY: Prometheus, 2019), 53-54 

10. ibid, p 54-55

11 Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S, Keith JC Jr, McCoy JM. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature. 2000 Feb 17;403(6771):785-9. doi: 10.1038/35001608. PMID: 10693809.

12. Johnson WE, Coffin JM. Constructing primate phylogenies from ancient retrovirus sequences. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10254-60. doi: 10.1073/pnas.96.18.10254. PMID: 10468595; PMCID: PMC17875, 10255 

13. Jianhua Wang, Guan-Zhu Han, Unearthing LTR Retrotransposon gag Genes Co-opted in the Deep Evolution of Eukaryotes, Molecular Biology and Evolution, Volume 38, Issue 8, August 2021, Pages 3267–3278, https://doi.org/10.1093/molbev/msab101 

14. Mita P, Boeke JD. How retrotransposons shape genome regulation. Curr Opin Genet Dev. 2016 Apr;37:90-100. doi: 10.1016/j.gde.2016.01.001. Epub 2016 Feb 6. PMID: 26855260; PMCID: PMC4914423.

15. Moran, Laurence A.. What's in Your Genome? 90% of Your Genome Is Junk. Canada: University of Toronto Press, 2023, 132 

16. Avise, op cit p 8975

17. Fairbanks, op cit p 41-42 

18. Avise, op cit p 8975