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Evolution and Immunity: Same Story?

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March 23, 2013 Tags: Divine Action & Purpose
Evolution and Immunity: Same Story?

Today's entry was written by Kathryn Applegate. You can read more about what we believe here.

Note: Originally posted May 28, 2010.

I’ve had ample opportunity this week to reflect on God’s goodness in providing me a working immune system; I’m nearing the end (hopefully) of a bad cold. Normally I would bewail the havoc caused by the virus itself, but after writing my last post on how antibody diversity is generated, I have become increasingly grateful for this life-protecting process.

Antibody fine-tuning

At this moment, millions of B cells are patrolling my spleen and lymph nodes, each sporting a different antibody on its surface. If a foreign molecule from the cold virus happens to stick to an antibody on a particular B cell, the cell can get “activated.”

Pathogens are like cockroaches. If you see one roach, you can bet there are many more lurking under cupboards and between walls. Just as one shoe won’t kill them all, one B cell can’t make enough antibodies to deal with an infection. Activation causes the B cell to reproduce, creating more and more B cells that can produce the same kind of antibody.

As is typical during cell division, most of the DNA in dividing B cells is copied with extremely high accuracy. But in the gene segments coding for the variable region of the antibody, mutations accumulate about a million times more often than normal. Why would this be? Isn’t the point of B cell replication to make more identical antibodies?

Almost. It turns out that these frequent random mutations contribute to optimize the antibody. A shopping story helps to illustrate. I was recently at the mall and found a fabulous pair of shoes on sale. Sadly they were out of my size, but it was such a good sale that I decided to buy the half-size down, figuring the shoes might stretch out a little and grow more comfortable with time. Bad idea! That great bargain turned out to be pretty expensive when I got blisters and never wore the shoes again. Clearly this was not an optimized choice.

Just because you can get your foot into a shoe does not mean it fits. Likewise, just because an antibody binds to an antigen does not mean the two are perfectly complementary. Descendents of the activated B cell have a mechanism to induce mutations so each one can make a slightly different version of the antibody. If one of the resulting B cells makes a better-fitting antibody than its kin, it will have a selective advantage and proliferate. The other cells will not become activated as often and will end up dying by apoptosis, a kind of cellular suicide. This mechanism of mutation and selection, called affinity maturation, produces a highly specific, strong interaction between the antigen and the antibody.

Antibody production and evolution both involve mutation and selection

I believe God is sovereign over all of creation, but I don’t imagine he is presently curing my cold by directly controlling the specific gene rearrangements and optimizing mutations in each of the millions of B cells in my body. Could he do so? Of course! But if that were the case, why bother making billions of antibodies in the first place? The evidence suggests that God has chosen to work through a random process, one which involves the routine creation and destruction of millions of cells that never get used. This is the ordinary means by which God maintains our health. The miracles of healing recorded in the Bible are miraculous precisely because they don’t occur by this normal, natural process.

In my last post, I stated that the generation of antibody diversity is an example in which God uses a “blind” system to sustain and preserve life. I then suggested a link to evolution by asking, “If God uses natural mechanisms that work over short time scales (less than a week) to evolve life-giving solutions to disease, could he also use a similarly elegant approach to create life over long periods of time?”

Some may argue that a small-scale process like antibody production isn’t comparable to the processes of mutation and natural selection that are supposed to have caused macro-evolution. Intelligent Design proponent Michael Behe, for example, accepts that all creatures (including humans) have a common ancestor, but he believes random mutations are not powerful enough to have brought about the diversity of life we see today. He argues that there is an “edge” of evolution: mutation can bring about drug resistance and other small-scale adaptations, but beyond a certain point it can’t really produce anything new.

Clearly, antibody production creates something new: the random recombining of whole gene segments generates highly specific, never-before-seen protein functionality within just a few days. The body can respond to any foreign entity, simply by sorting through billions of ready-made possibilities. Furthermore, a pretty-good solution can be made even better by generating many variations on a theme and sorting through these for the optimal antibody.

Evolution works by the same kinds of mechanisms, except the mutations occur in germ cells (which give rise to egg and sperm) rather than in B cells, and the sorting (selection) process occurs at the population level rather than the cellular level.

Though often neutral or destructive, mutations sometimes create new functionality

Most people are familiar with point mutations, in which a single DNA “letter,” or base, gets changed. However, mutations come in several other varieties. Short sequences of DNA can be inserted or deleted at random. Chunks of DNA can get cut out and inserted in the opposite direction. Individual genes or even whole chromosomes can get lost or duplicated. In rare cases, the entire genome can get duplicated!

The effect of a mutation principally depends on where it occurs, not on the size of the DNA segment affected. A large deletion occurring within a long stretch between two genes may do nothing at all. On the other hand, a single point mutation within a critical gene may cause a devastating disease. There is also a third possibility though: new functionality may emerge as a result of a mutation.

Let’s consider the protein hemoglobin, for example, which binds oxygen and transports it throughout the body in the blood. Hemoglobin is made from two pairs each of two amino acid chains, called α and β (blue and red in the figure at right). The corresponding genes that code for α and β have similar sequences to each other, and are believed to have arisen when an ancestral globin gene (still present in marine worms, insects, and some fish) duplicated and slowly changed over time. While the ancestral form can bind oxygen just fine, the four chains of hemoglobin cooperate to do so even better.

Both the α and β genes have undergone further duplications followed by smaller mutations. As expected, many of the resulting genes have become irreparably damaged by mutations, but they continue to exist in the genome as inert DNA “fossils.” Others, however, remain active and now perform specialized functions. For instance, one set of β genes binds more tightly to oxygen than the others; it becomes active only during development to ensure that the fetus gets enough oxygen from the mother’s bloodstream. A few months after birth, fetal hemoglobin turns off and the adult form turns on.

To summarize, mutations come in many forms (e.g. rearrangements, insertions, deletions, duplications) and can lead to good, bad, or neutral effects within an individual. B cells depend on random mutations to produce novel antibodies. A few are productive, but the vast majority of B cells die unused. Yet the entire process works for our good! In the same way, mutations in germ cells can lead to no effect, disease, or new and better solutions, as we saw in the hemoglobin example. These are the ordinary (but masterful!) means by which God creates and sustains life.

Editor's Note: For more on the evolution of the immune system, read Randy's Isaac's post "Complex Specified Information Without an Intelligent Source" at the ASA website.

Kathryn Applegate is Program Director at The BioLogos Foundation. She received her PhD in computational cell biology at The Scripps Research Institute in La Jolla, Calif. At Scripps, she developed computer vision software tools for analyzing the cell's infrastructure, the cytoskeleton.

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Lou Jost - #77738

March 23rd 2013

This series is a beautiful, simple explanation of how the immune system works. I learned a lot! The comments about god, however, seem completely gratuitous. “This is the ordinary means by which God maintains our health.” You have just finished carefully explaining how unguided, random processes are sufficient to fight disease. So why claim that god is involved in this at all?

Merv - #77743

March 23rd 2013

I have appreciated and learned a lot from this series too, Lou.   Given that Dr. Applegate is program director for Biologos I suppose she must be monitoring these replies and can answer you.  On the other hand this was originally posted a couple years ago—it’s not freshly written, and maybe she’s away at the moment.  I’ll hazard an answer for now, hoping  still to hear an answer straight from her.

From a *strictly scientific* perspective, bringing God into it is unnecessary.  But from a theological perspective such as is assumed at Biologos, we (if I may presume to speak unofficially as a representative of most Christians lurking here) are interested in more than the mere science.  It is a given (our presupposition if you will) that God is involved and gives context, meaning, and cause for praise to the science discussed.  The science can still stand simply as science, of course, for those who are satisfied with that.  For those of us who look more deeply and broadly at life with a religious gaze, we bring the science into our context of praise for our Creator.  So for us, He is far from superfluous.  Science is our offering brought to the table, not the foundation on which the table or its Heavenly Host sits.  


Seenoevo - #77746

March 23rd 2013

“For more on the evolution of the immune system, read Randy’s Isaac’s post…”

I had a question that doesn’t seem to have been addressed in this article nor in Randy’s:

Given the limitless, and often deadly, germs and bacteria and viruses which have been floating around everywhere forever, how did any organisms ever survive before they evolved an immune system? (And how much time was required to evolve an immune system? Would have to be far less than a lifetime, yes?)

PNG - #77782

March 24th 2013

Immune systems are just ways of fending off pathogens. Pathogenicity is just a form of predation/competition. Somewhere back there some microbe came up with a way to kill or inhibit the growth of other microbes so it could win the competition and eat the dead microbes or have the nutrients all to itself. Some variant of the targeted microbe came along soon after that that had a way to resist the assault, and maybe a way to make an assault of its own. Antibiotics and antibiotic resistance weren’t “invented” recently - microbes have been waging war on each other and defending themselves  for a long time. Presumably in the beginning these things were very simple. So pathogens and defenses against them would have to arise at almost the same time. And so the arms race began, and at this point has become very sophisticated, with measures and countermeasures changing all the time, as we can see with the cycling of antigens on pathogens that happens even over very short time scales. When you look at the parts of the genome of animals that change the fastest, immunity genes are always among them, for this reason. When multicellular organisms arose (on numerous occasions) the cells would have already had defenses against attacks and it would be a good guess that they built on those subsequently.

Seenoevo - #77747

March 23rd 2013

“…Michael Behe … believes random mutations are not powerful enough to have brought about the diversity of life we see today. He argues that there is an “edge” of evolution: mutation can bring about drug resistance and other small-scale adaptations, but beyond a certain point it can’t really produce anything new.

“Clearly, antibody production creates something new…”

I guess that depends on how one defines “new”.

Here’s how I might define “new” in this context:

When the antibody production (or any other cellular/genetic activity) produces not a different characteristic/capability but rather produces a different type of organism. For example, when antibiotic-susceptible bacteria change not into antibiotic-resistant bacteria but rather change into parameciums or fruitflies, then I’d say we have something “new”. In fact, we’d have real “news”.

This article seems to be making the case for evolution with a modern science flourish: ‘Cellular and/or genetic changes lead to immunity to antibodies, THEREFORE, microbe-to-mosquito-to-monkey-to-man evolution is true.’

Darwin didn’t know of cells or genes or antibodies. But he had eyes and an imagination. So, he provided the old science flourish: ‘Depending on environmental changes, Galapagos finch beaks grew longer then shorter then longer, THEREFORE, microbe-to-mosquito-to-monkey-to-man evolution is true.’

Lou Jost - #77750

March 23rd 2013

Go read Dennis Venema’s excellent course on evolution, now in progress on this site, to learn how Darwin actually argued. You’ll find rich evidence that evolution did indeed go from basal vertebrate-> monkey-> man. There is really no reasonable doubt about that. We can still debate the mechanisms, of course.

Merv - #77753

March 23rd 2013

...and since we’re trying to get Seeno up to speed, I’ll also mention that actually Darwin never solved the mystery of the finches (and never mentions them in ‘Origin…’).  In fact he didn’t even realize how much of a puzzle they were yet going to become for his evolutionary theory when the finch research started in earnest with David Lack much after Darwin’s time.  Lack was the one who turned them into the iconic ‘Darwin’s Finches’ and put together how their development fit so well with evolutionary theory.  Biologos has a good series of articles on that here:  http://biologos.org/blog/david-lack-and-darwins-finches

Lou, you probably already know all about that, but you might find Burnett’s articles interesting too.


Lou Jost - #77754

March 23rd 2013

Thanks for the reference, Merv. It is remarkable how little attention Darwin payed to the finches when he was on the Galapagos, but they really did play an important role in his thinking later, after he had learned that they were all finches (he had initially thought that some were warblers, some were finches, and some were wrens—so great were their divergences from each other). He wrote about them, making an early reference to evolution, in the second edition of The Voyage of the Beagle (1845):  “Seeing this gradation and diversity of structure in one small, intimately related group of birds, one might really fancy that from an original paucity of birds in this archipelago, one species had been taken and modified for different ends”.

Lou Jost - #77760

March 24th 2013

I see this is all in that excellent article you cited, so you already knew that…

Merv - #77780

March 24th 2013

I continue to be fascinated by the history of the progression of science but my knowledge, while somewhat broad, doesn’t go very deep.  Articles like these help me go perhaps just a bit deeper but that is about the extent of it.  So it is good to hear a real biologist such as yourself confirm that they are indeed sound articles since I am in no position to discriminate on much of this other than to decide that I generally trust certain sources.

I believe it was Polkinghorne who wrote that given what is generally acceptable  conversation (or not) around a typical dinner table; he finds it necessary to be a ‘missionary’ for both science and religion in much of our culture at large.  While I’m sure you agree with one side of that exhortation, I find it exciting as a teacher to be about disarming the culture wars so that we can push and challenge each other in respectful discourse without being so defensively threatened by and threatening with powerful political agendas.  Science will be among the many beneficiaries when the public square again enjoys that intellectual freedom.  I hope that those who consider themselves friends of science can glimpse that vision as well.


Lou Jost - #77803

March 25th 2013

Merv, I also wish the culture wars would go away, but (as you might expect) I see the fundamentalist religious side as largely responsible for the acrimony today. Scientists aren’t trying to get into churches and demanding equal time in the pulpit, but backwards creationists in the US have been trying for decades to force pseudoscience into public school science classrooms, and trying to make their personal religious ethical principles into secular law. Rational people (including hopefully many religious folk) really need to fight this, though of course with civility.

Merv - #77805

March 25th 2013


Your view, I’m afraid is all-too-accurate.  Of course each side can play the ‘he did it first’ game.  Fundamentalists would point to the Huxleys and even the higher biblical critics themselves as having fired the opening shots.  But it could be more than fairly pointed out that some of these ‘anti-religionists’ were only responding to a long history of oppression which often drew in whatever religion was at hand to help justify itself, and that provided fertile soil for the conflict.  We are reaping what was sown.


Lou Jost - #77806

March 25th 2013

Thanks for understanding my view.

melanogaster - #77826

March 25th 2013

You’ll find rich evidence that evolution did indeed go from basal vertebrate-> monkey-> man.”

Lou, evolution doesn’t go like a ladder. It is branched.

Lou Jost - #77858

March 26th 2013

Melanogaster, yes, it is branched. I was responding to Seenoevo above; the branch ending with man is the one he was focussed on.

melanogaster - #77905

March 27th 2013

Yes, but Seenoevo doesn’t know that. I’m 99.99% sure that Seenoevo would say that you see it as a ladder.

melanogaster - #77842

March 26th 2013

“I guess that depends on how one defines “new”.”

Ironically, Behe uses new binding sites as an “edge” of evolution. You can evolve a new binding site (an antibody) in two weeks with nothing other than variation and selection!

Do you not see how that refutes Behe’s book?

Seenoevo - #77821

March 25th 2013

PNG wrote in response: “Immune systems are just ways of fending off pathogens.” Sounds simple. Just need about five things: 1) Evolve a “desire” to defend oneself, a “will to live”, then 2) evolve a way to identify pathogens, then 3) evolve a way to perceive the harmfulness of pathogens, then 4) evolve a way to defend against them, then 5) make certain you evolve all of the above before you die pathogenetically. Yes, that’s all simple stuff. But, for example, the human immune system seems pretty complex. It involves a number of organs, and probably a number of processes and chemicals. All of which are integrated and working together: http://aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/hiv-in-your-body/immune-system-101/ So again, if we need such a complex system to survive now, then how did we survive during the alleged long-ages required to randomly evolve this complex system?
PNG - #77822

March 25th 2013

This is a silly straw man argument. (Did you think the large font would help?  As I said, pathogens and defenses co-evolved, as they still do today in a tit for tat arms race. Both sides started out simple and got complicated over time. There never were any long ages with pathogens and no defenses.

melanogaster - #77827

March 25th 2013

“So again, if we need such a complex system to survive now, then how did we survive during the alleged long-ages required to randomly evolve this complex system?”

So again, your understanding of evolutionary theory is way off the mark. If it’s so threatening to you, one would think that it would be worth the time for you to learn about it!

As was pointed out to you, there’s the whole coevolution thing that you’re missing. Also, before we had adaptive immunity, we had innate immunity. Tunicates have been a great model system for studying this transition; all the evidence suggests that the adaptive immune system evolved to prevent mixing of individuals in colonies, not to protect us from pathogens.

Also, you might think about the selective pressures on pathogens, which do not promote destruction, but reproduction. To think intelligently about that, you’d have to realize that selection is about reproduction, not survival.

Finally, selection isn’t random at all, so calling any evolution involving selection, whether of organisms or antibodies, your adjective “random” is simply false.

A God who is about truth doesn’t need falsehoods to defend Him.

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