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Adaptive Immunity: Darwinism in Miniature or High-Tech Tinkering with Stasis?

[Editor’s Note: Today we present part five out of six in a series by microbiologist Donald L. Ewert. These posts are responding to the BioLogos Foundation’s blog where Kathryn Applegate argued that “random” processes that generate antibodies illustrate the creative power of Darwinian evolution. Previous installments of Dr. Ewert’s rebuttal can be found at the following links: Part One, Part Two, Part Three, and Part Four.]

Kathryn Applegate’s main point is that if “natural” processes — which she characterizes as “random” and “blind” — can be used to generate antibodies, the same mechanisms presumably could be used to “create life over long periods of time.”

The question addressed here is: Do the terms “random” and “blind” accurately describe the mechanisms for generating diversity via V(D)J rearrangement and affinity maturation by SHM? Based on our current knowledge about antibody development, briefly described above, I contend that what may appear to be a random process is actually highly orchestrated at many different levels — organismal (developmental), tissue (lymphoid tissues), cellular (B cells, helper T cells, antigen presenting cells), protein (MHC, enzymes, transcription factors, cytokines) and genetic (C and G placement, chromosomal accessibility). The function and structure of these highly specialized components must be coordinated to produce a specific antibody in response to an antigenic challenge. Independent developmental programs of the cell lineages, tissues, and organs must be controlled to ensure that their location and structure permit the interactions required for development of the B cell and antibody production. Therefore the combined functional and developmental aspects of antibody production involve a hierarchal matrix of regulatory controls that orchestrate the entire process. Antibody development is certainly not a “blind” or “random” process. What on the surface may seem like a random process is in fact an elegantly designed and regulated process.

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Not By Chance: Controlling Affinity Maturation

[Editor’s Note: This is part four of a six-part series from microbiologist Donald L. Ewert responding to Kathryn Applegate, of the BioLogos Foundation, in her arguments that the vertebrate adaptive immune system illustrates the claimed creative the Darwinian mechanism. Previous parts of Ewert’s response can be found at the following links: Part One, Part Two, Part Three.]

Pathogen-directed activation of the immune response

The initiation of an immune response is designed so that the cellular and molecular components that are best equipped to deal with a pathogen are engaged. There are basically three response pathways. Non-protein antigens that have repeating carbohydrate units on their surface, such as are found on bacteria, can directly activate B cells. These B cell do not go through affinity maturation or class switch since multiple binding sites on the antigen make a strong bond with the B cell and the IgM class of antibody that is produced which has five receptors per molecule.

Responses to protein antigens fall into two classes, depending on whether the pathogen is intracellular or extracellular. Since intracellular antigens such as viruses are not accessible to circulating antibody, they activate cytotoxic T lymphocytes that are best equipped to kill them. This activation is directed by the Class I MHC antigen that is attached to the antigens as they are processed in cells. Extracellular proteins, which are best dealt with by circulating antibody, activate B cells to begin the process of affinity maturation and class switch that leads to the production of a monomeric IgG class of antibody. This latter pathway requires the assistance of a class of T lymphocytes called T helper cells (TH) and the interaction of Class II MHC proteins.

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Who or What Plays the Music of DNA?

As I was driving in to work, the local NPR station had on an interview with a guy who’s involved with gathering billions of seeds of various plant varieties into a “doomsday vault.” It is on a remote Norwegian island and intended as a precaution against the presumed devastations of global warming. There were few surprises in the conversation — the grim mood was well suited to the NPR target audience, which eats this stuff up — apart from one rather interesting question from a listener. The guest, Cary Fowler of the Global Crop Diversity Trust, was asked why his group bothers with seeds. In the future, won’t we be able to reconstitute life from the digital code of DNA?

Not necessarily, explained Fowler. He offered a few cryptic but telling comments about the complexities of gene expression, and how simply knowing the DNA sequence of a plant (or animal) may never be sufficient to generate life. Why? Part of the answer, implying a strong challenge to materialist explanations of life’s evolution, is suggested in a recent and illuminating essay, “Getting Over the Code Delusion,” in the Ethics and Public Policy Center journal, The New Atlantis.

Rare is the technical if otherwise quite accessible article that gives chills like this one does. Steve Talbott, a senior researcher at the Nature Institute, takes aim at the still-widespread illusion that DNA maps the construction of a living creature. In a 1992 essay, Nobel Prize-winning geneticist Walter Gilbert crowed that the time will come when a person will be able to say, of a human DNA sequence inscribed on a computer disk, “Here is a human being; it’s me!” How utterly naíve that has since been revealed to be.

Richard Dawkins calls DNA “a remarkable feat of digital information technology,” on the model of a computer albeit one that programs itself. Yet the burden of Talbott’s article is to show why the whole computer metaphor is inadequate. If you want a better one, the really apt metaphor would be drawn from the art of dance — or I’d say, music — with all that implies by way of purpose, agency, and expression.

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Generation of Antibody Diversity is Unlike Darwinian Evolution

[Editor’s Note: This is part two of a response from microbiologist Don Ewert to arguments from BioLogos’s Kathryn Applegate that our immune system shows the creative power Darwinian evolution. Part one can be found here.]

The intricate mechanism for generating antibody diversity from very few germline (existing) genes was discovered over thirty years ago. It involves shuffling gene segments and then fusing them to produce new combining sites for the antibody receptor displayed on individual B cells. How much of this process is pre-programmed and how much is random? Is this an example of the use of a “‘blind’ system to sustain and preserve life,” as Kathryn Applegate suggests? The evidence from decades of research reveals a complex network of highly regulated processes of gene expression that leave very little to chance, but permit the generation of receptor diversity without damaging the function of the immunoglobulin protein or doing damage to other sites in the genome.

The most remarkable aspect of antibody production is the mechanisms that generate the binding site of the antigen receptor. The antigen receptor of B cells are proteins called immunoglobulins. They have an antigen combining site at one end that binds to foreign proteins (variable or V region) and a tail, or constant region (C region), at the other end that controls the interaction with other components of the immune system that are responsible for eliminating the foreign invader. The variable end of the BCR heavy chain is generated by the shuffling and joining of gene segments from separate pools of V (45), D (23), and J (6) segments per cell and the random deletion and insertion of nucleotides at the joining sites. This process is duplicated on the second (light) chain of the immunoglobulin gene. The combined diversity generated by recombination which is limited by the number of gene segments and by nucleotide exchanges, which are unlimited, produces a potential repertoire of about 1011 different receptor specificities. This process occurs during transcription of the DNA and involves a set of coordinated enzymatic reactions. The total number of available receptor specificities is limited by the number of B and T lymphocytes.

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Adaptive Immunity: Chance or Necessity?

[Editor’s Note: Earlier this year, in a series of posts on the BioLogos website (“Adaptive Immunity: How Randomness Comes to the Rescue” and “Evolution and Immunity: Same Story“), Kathryn Applegate argued that the “random” processes of the vertebrate adaptive immune system serve as an example of how Darwinian mechanisms can generate biological complexity. Today, Discovery Institute presents part one of a response to Dr. Applegate from Donald L. Ewert, a research immunologist/virologist who spent much of his career studying the molecular and cell biology of the immune system, as well as theories about its evolution. Dr. Ewert received his Ph.D. from the University of Georgia in 1976. As a microbiologist, he operated a research laboratory at the Wistar Institute in Philadelphia for almost twenty years. The Wistar Institute is one of the world’s leading centers for biomedical research. His research, supported by National Institute of Health, National Science Foundation, and Department of Agriculture grants, has involved the immune system, viruses, and cellular biology.]

Introduction

In her articles on the BioLogos website, Kathryn Applegate attempts to show how the mechanisms used by the adaptive immune system to generate a diversity of antigen receptors are an example of Darwinian evolution. She focuses on aspects of these mechanisms that she characterizes as “blind” and “random,” stating, “Antibody production and evolution both involve mutation and selection.” She further claims that “the adaptive immune system harnesses the power of randomness to protect the body from assaults it has never seen before” and antibody “production requires randomness at multiple levels.” Applegate, however, frames her argument in theological terms, arguing that if “God uses natural processes — indeed, even a ‘blind’ system for generating massive amounts of diversity,” why could he not use the same mechanisms to “create life over long periods of time”?

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“Intelligent Design” in Hebrew?

In the Hebrew version of Wikipedia, the page on intelligent design translates ID with the phrase “tichnun tivoni,” which means something like “intelligent planning.” And so it’s translated regularly too in Ha’aretz and other Israeli news sources. The Wiki page is well supplied with the usual distortions that you’d expect from Wikipedia in any language, but never mind that. The question of how to translate “intelligent design” into the language of the Bible is an interesting one. Is there an actual Biblical phrase that captures the idea?

In the journal Azure, published by the Shalem Center in Jerusalem, an essay on the “Secret of the Sabbath” indirectly suggests an answer. Rabbi Yosef Yitzhak Lifshitz reflects on the passage from the book of Exodus about the construction of the Tabernacle in the desert. Following the Exodus from Egypt, the Israelites were in the wilderness on their way to the land of Israel. Rather than having them construct a permanent Temple to worship in, God directed Moses to oversee the construction of a large movable tent for the same purpose. To carry out the work of designing the structure, God chose Betzalel and endowed him with “wisdom, understanding and knowledge…to perform all manner of workmanship” (35:31, 33).

The phrase given above as “workmanship,” melechet machshevet, really means purposive creativity — or, if you will, intelligent design. A helpful insight in the debate with theistic evolution advocates emerges from this observation.

As Rabbi Lifshitz explains, drawing on a long line of earlier commentators back to the Talmud and Midrash, the connection with the Sabbath goes as follows. When God gave the Sabbath to the Israelites, in the form of the Fourth Commandment, he was exceedingly sparing on the details of what actually constitutes the “work” (melachah) from which they were henceforth to rest on the Sabbath.

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Swamidass-1
Photo: Joshua Swamidass, by J. Nathan Matias, via Flickr (cropped).

Darwin, Racism, and Eugenics in Detroit

Last week I participated in a stimulating panel discussion on Darwin, scientific racism, and eugenics at the Charles Wright Museum of African American History in Detroit. Other participants included distinguished evolutionary biologist Morris Goodman of Wayne State University, historian Damon Salesa of the University of Michigan, and biology professor Jerry Bergman of Northwest State College in Ohio. The moderator was author and broadcast journalist Edward Foxworth. The Charles Wright Museum is the world’s largest institution devoted to the subject of African American history, and it’s well worth a visit.

The museum’s presentation of the African American experience is outstanding; its galleries place you in the very midst of history, including a slave ship, plantation life, and early twentieth century Detroit.

The evening’s event was serious, thoughtful—and civil.

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Meet Pakicetus, the Terrestrial Mammal BioLogos Calls a “Whale”

In a previous post, we noted some fish-related problems with BioLogos’s page discussing the fossil record. But these aren’t the only marine mistakes on the page. BioLogos says regarding the evolution of whales: Recently, a 52-million-year-old whale fossil, Pakicetus, was found in Pakistan. It was clearly a small, wolf-sized whale, but it did not have the characteristic fat-pad, a structure that allows the whale’s jaw vibrations to be used for hearing. Also, its teeth were much like those of the terrestrial animals already thought to be related to whales. Aside from the fact that Pakicetus was discovered in 1983 (not exactly “recently”), there’s quite a bit more that should be said about this fossil. The claim that Pakicetus is a Read More ›

Something’s Fishy With BioLogos’s Description of Fish Fossil Record

In a prior post, I discussed how BioLogos’s website has a page titled “What does the fossil record show?” which is conspicuously missing any mention of the Cambrian explosion, or any other explosions in the history of life. The page also has other errors and omissions. In a section titled “Evidence of Gradual Change,” it states: “At 500 million years ago, ancient fish without jawbones surface.” Actually, the first known fossils of fish are from the lower Cambrian, meaning that their date is probably closer to 530 m.y.a., near the beginning of the Cambrian period. A Nature paper reporting this find was titled “Lower Cambrian vertebrates from south China.” It noted: “These finds imply that the first agnathans may have Read More ›

BioLogos’s Fossil Record Page Conspicuously Missing the Cambrian Explosion

The BioLogos website has a static page titled “What does the fossil record show?,” which would naturally lead one to expect that if you read the page, then you’ll learn what the fossil record shows. What’s odd about the page is that the page makes no mention whatsoever of the Cambrian explosion. This is despite the fact that Robert L. Carroll calls the Cambrian explosion “[t]he most conspicuous event in metazoan evolution”: The most conspicuous event in metazoan evolution was the dramatic origin of major new structures and body plans documented by the Cambrian explosion. Until 530 million years ago, multicellular animals consisted primarily of simple, soft-bodied forms, most of which have been identified from the fossil record as cnidarians Read More ›

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