Edward J. Steele - Robyn A. Lindley - Robert V. Blanden
Lamarck's Signature : How Retrogenes Are Changing Darwin's Natural Selection Paradigm

"The main purpose of this book is to convey how the new molecular genetics is gradually eroding the edifices constructed in the past by neo-Darwinists to support the concept of natural selection acting on random genetic variations as the only mechanistic agent of evolutionary change. In the process, we are witnessing the birth of a new paradigm in evolutionary theory in the immune system based on a combination of Darwinian and Lamarckian concepts of evolution." -- p. 11
Lamarck's Signature begins with a bold preface and 'pre-chapter' entitled "Dogma" which are presumably intended to whip up controversy and garner quick attention from the scientific community. The authors then settle into a much less provocative explanation of various topics like molecular biology and the immune system for about half a dozen chapters before launching into a tirade for a final chapter and Epilogue. A more subtle approach--especially near the end of the book--would have been more warranted, but I suppose Steele is beginning to tire to the lack of response to his twenty year old theory. To stir the pot a bit more vigorously, he has chosen to conclude this work in a more combative style.

The first three chapters are excellent. I have read numerous explanations of DNA, RNA, enzymes, protein, etc. and their interactions with each other, but this was the best one I have encountered to date. A general audience interested in the subject will be able to understand the processes without it being overly watered down to the point where little or nothing is learned. The evolution of RNA and the immune system are also fascinating aspects of life's wonder. The authors' exploration of this area is well done.

After the first three chapters things become a bit more difficult for an average reader to understand. Unfortunately, this is the same area where the authors are really trying to build their case. They certainly show that the immune system is capable of changing its makeup (DNA structure) within a person's lifetime. I wasn't convinced that these changes were passed on to the reproductive cells though. I'd expect that immunities (for instance--to chickenpox) would be passed on to children if their theory was watertight.

It wasn't until page 153 that I realized that the "Ted Steele" frequently referred to was actually the same person as the author--Edward J. Steele. Apparently Steele has been published using a variety of names. The ones I noticed from the references provided in this book alone were E.J., Edward J., E., Edward, and Ted. This strange changing of published names can be confusing if the reader isn't made aware--especially since "Ted" isn't normally a shortened form of Edward.

Throughout the book the authors' position appeared to me to be one very similar to that of neo-Darwinists (believers in the theory that natural selection combined with genetic principles account for life's diversity). The one exception being that a bit of neo-Lamarckism (theory that somatic modifications in a multicellular organism can be passed on to the germline and hence on to progeny) is believed by them to be occurring with respect to a specific aspect of the immune system (the V(D)J DNA sequence). For instance, on page 47 they state

"So at the molecular level, simple Darwinian selection of the fittest sequences can be imagined. Some of the most cogent proofs of the natural selection schema have been provided by mutant selection studies in molecular genetics."
Indeed, the foundation of their theory is that Darwinian selection works on the immune system within individual organisms. This Darwinian selection is subsequently written back into the DNA at a molecular level via reverse transcription. (The Darwinian selection aspect is similar to other processes in the body like the pruning of neurons in children and William Calvin's theory on how the mind works.) The Lamarckian aspect doesn't come into play unless they can prove that this new DNA is then transferred from the somatic cells to the germ cells (which are the cells used for reproduction).

They echo this sentiment from the outset by stating on page 3 in Chapter 1 that "we wish to emphasise here that so far our analysis and explanations [i.e. the neo-Lamarckian portion of their theory that goes beyond neo-Darwinism] are limited to the immune system of animals with backbones, the vertebrates." However, beginning in Chapter 7, entitled "Beyond the Immune System?" the authors delve into wild speculations that far exceed their original emphasis. Without any empirical evidence to support these later suppositions, they begin to attack neo-Darwinists (notably Richard Dawkins and Daniel C. Dennett).

Despite their early innuendoes about the foolishness of believing in an 'intelligent designer' they suddenly jump on the bandwagon of creationists like David Berlinski and Michael Denton. Berlinski's now famous essay is hardly 'brilliant'. It is littered with falsehoods and ignores a wealth of information in order to make an incorrect point. His misuse of Dawkins' biomorph analogy is repeated by Steele and company. Dawkins doesn't set himself up as the 'intelligent designer' in the analogy as he doesn't know what he is creating. Rather, Dawkins' role is that of natural selection--changing the conditions without forethought and unable to perfectly duplicate previously created biomorphs.

Denton is lauded for pointing out all the 'negative evidence' relevant to the fossil record. A lack of evidence isn't hard to find, however, when one doesn't look for it. Such is the case with Denton's book which relied on dated material and omitted many of the material archaeological finds of the 20th Century.

Comparing Richard Dawkins to the Church (p. 221), as both oppose new ideas in the authors' view, is a huge overstatement. As Dawkins states in (at least the first edition of) The Extended Phenotype, he may offer to eat his hat with regard to his opinion on neo-Lamarckism when sufficient evidence presents itself. That is a typical scientific view. It will be interesting to see if Dawkins has changed his tune with regard to neo-Lamarckism in his revised and republished version of The Extended Phenotype.

I recommend Lamarck's Signature for it is thought provoking and generally well written (for the first few chapters at least). The jury is still out on whether neo-Lamarckian 'dogma' can be truthfully incorporated into our reality.

A friend (with a BS in Molecular Biology and Master's Degree in Biomedical Science) who I lent the book to for a more expert opinion writes:
Thanks for letting me borrow Lamarck's Signature. I think the authors have an interesting hypothesis but I found their evidence very soft. Some specific comments:

The primary observation behind their argument is that highly non-random mutation patterns (Wu-Kabat structures) are found in immunoglobulin variable genes that are rearranged and expressed only in B cells of the immune system (figure 5.3). On page 166, they prepare to introduce their central hypothesis: "Given that 'Wu-Kabat structures' can only be fashioned during evolution at the level of antigen-binding by functional protein heterodimers, how is it possible for non-expressed germline V-gene segments to show highly detailed evidence of antigen-binding selection? Providing a rational answer to this question is the driving force behind our current research program." From the authors' perspective, this is explained by their soma-to-germline hypothesis: somatic hypermutation generates variability (true); mutants with greater affinity for the antigen are selected and expanded in a germinal center (true) while mutations in framework sequences are selected against, thereby generating Wu-Kabat structures (true); and finally, retroviruses randomly pick up some of these hypermutated genes and transmit them to the germline where they are incorporated into the chromosomal DNA (maybe). But there is a conventional explanation for non-random mutation patterns in germline genes, including the Wu-Kabat structures of immunoglobulins: germline mutations appear randomly; mutations that fall within the three complementary determining regions regions (CDRs) are allowed to accumulate because their changes are neutral or advantageous when expressed as antibodies in B cells; mutations in framework sequences are selected against since they produce non-functional antibodies; and with time Wu-Kabat structures appear in the germline without soma-to-germline feedback.

The strong approach to show that soma-to-germline transmission occurs in addition to conventional germline mutation/selection is by experiment. The authors do not describe any successful experiments (as opposed to uninterpretable or irrelevant experiments)--instead they search for more observations which are consistent with their hypothesis. That, I would say, is a weak approach. In figure 6.1 they outline a paternal transmission experiment performed by Steele in the late 1970's but that gave inconsistent results. Furthermore, these experiments examined young mice for TOLERANCE to transplantation antigens to which their male parents had been exposed. Since tolerance is generated by NEGATIVE selection of antibodies and T cell receptors (TCRs) that recognize "self" transplantation antigens, this experiment is irrelevant to their model which rests on positive selection. Indeed, if it were shown that acquired tolerence could be "retro-coded" into the germline, they would have to invent an entirely new mechanism involving the deletion of specific germline V genes. So this one experiment isn't even relevant to their model.

One argument that could be made against Darwinian explanations for immune system evolution is that "random germline mutation followed by natural selection would be an extremely slow way to build a repritoire (page 184)." Perhaps soma-to-germline transmission is faster and therefore a superior explanation? How much faster? Later (page 188) they quote the "wise advise" of a past Lamarckist:

"Those who have resorted to direct experiment have, for the most part, failed to realize the dominating influence of time in all the processes of natural evolution. Save in the production of freaks, sports or mutations, nature appears to work extremely slowly in bringing about permanent modifications in living things.... [T]he first note of caution [is] that there is every reason to believe that, if acquired characters are inherited, their incorporation into the hereditable make-up of an animal is likely to be a slow process and...we would hardly look to see it accomplished in the necessarily short time available to laboratory experiment."
This quotation, and their subsequent comments (including some regret for even trying to show soma-to-germline transmission experimentally) leave me wondering how much faster their mechanism could really be.

They also try to dismiss the Darwinian explanation because "it would favor single chain antibodies and no DNA rearrangement," rather than the two-chain, somatically rearranging structure observed in modern immunoglobluin genes (page 255). However, in chapter 4 they make it very clear that two-chain, fragmented, somatically rearranging genes are required for the immune system to produce an adequate antibody repritoire without overrunning the entire genome with different immunoglobulin genes. So, in the face of pressure favoring single chains and no rearrangement, the fragmented structure of antibody-producing genes would have to be conserved (through opposing selective pressure) in order to continue generating diversity. I think the Darwinian explanation remains convincing.

Chapter seven, "Beyond the Immune System?" is embarassingly unconvincing. They dismiss Darwinian explanations and favor soma-to-germline transmission with glaring bias. On one hand I have to admit that I am intrigued by the possibilities of their hypothesis for the evolution of the immune system. (It seems to be the ideal system in which to look for soma-to-germline transmission because of unique features like somatic hypermutation, clonal selection, intimate interaction with retroviruses, etc., and because the genes involved in antibody production are already well understood.) But it is hard to imagine--and chapter seven certainly didn't help me to imagine--that the retrogenes of their hypothesis could really be a factor in the evolution of other systems.

They could still be correct that there is some soma-to-germline transmission in vertebrate immune systems, but I think it needs to be shown through direct genetic experiments and not by merely hunting high and low for more observations that are consistent with a neo-Lamarckian mechanism. It would really be something if they could show, for example, that a specified V gene from transplanted B cells had inserted itself into the germline of a host mouse that does not already carry that sequence. This could be feasable using an immunodeficient mouse strain, transgenic B cell donors, and PCR (unless, of course, retrogenes are too rare of an event for controlled experimentation to detect....) Surely such a finding would finally vindicate the Lamarckist crusaders. As it stands, I think their observations are still consistent with neo-Darwinian selection.

Dr. Steele responds to the above.

from the publisher:
What if Lamarck, whose theory of the inheritance of acquired characteristics was blown apart by Charles Darwin over a century ago, was partly right after all? In this daring book, Steele and company reveal their ground-breaking research that has uncovered strong molecular genetic evidence that aspects of acquired immunities developed by parents in their own lifetime can be passed on to their offspring. The book gives new life and scientific credibility to the Lamarckian heresy-­the notion of the inheritance of acquired characteristics.

Edward J. Steele is Associate Professor of Biological Sciences at the University of Wollongong, New South Wales. Robyn A. Lindley is Director of the Technology Innovation Research Centre at the University of Wollongong. Robert V. Blanden is in the Division of Immunization and Cell Biology at the John Curtin School of Medical Research in Canberra, Australia.