The ID Report

By Robert Deyes
ARN Correspondent

Put intuition aside for a moment and imagine a scenario where E.coli knockout strains that have been deleted for conditionally essential genes are rescued by proteins taken from a protein library composed of >10exp6 de novo designed sequences. The prevailing assumption- that functional proteins are constrained to a very small subset of possible sequences- would lead us to infer that finding them by a random search through sequence space would be tantamount to impossible. But a PLOS One paper published in early 2011 appears on the surface to have given us much room for thought. Scientists from Princeton's Department of Chemistry and Molecular Biology used a combinatorial library of 102-residue long proteins to rescue non-viable E.coli knockouts. The functional losses in the knockout strains affected serine, glutamate and isoleucine biosynthesis and disabled the cells' natural capacity for iron acquisition in iron-limited environments.

The E.coli knockouts were auxotrophic meaning that they exhibited a failure to grow on minimal (M9-glucose) media even after several weeks of incubation. But following transformation with the combinatorial library, several cases of successful colony growth were documented suggesting that the certain genes contained therein had successfully complemented the deletions. Sequence comparisons through formal BLAST searches showed that the rescue proteins involved, eighteen in all, were unlike any protein found in nature.

Truth be told these rescue proteins were not entirely random. Their sequences had been engineered to ensure that they would fold into a stable 3-D structure. And not just any structure. Molecular biologists are well aware that canonical sequence rules exist that must be adhered to if they are to maximize the chances of proteins folding correctly. In an alpha-helical fold, for example, polar and non-polar residues must be carefully ordered to make certain that the hydrophilic ('water-loving') and hydrophobic ('water-hating') faces of the fold emerge. The Princeton group adopted a binary code strategy of polar and non-polar residues to get 1.5x10exp6 four-helix bundles. In this singularly fundamental aspect they were designed.

What was the molecular basis that allowed rescue? From their own experiments the Princeton group ruled out the likely hood that novel pathways that bypass the adverse effects of the knockout genes had arisen since E.coli mutants that were deficient in other steps of the naturally occurring biosynthetic pathways could not be rescued. Also dismissed was the interpretation that "global alterations in metabolism had been induced by the mere expression of foreign genes" (a stress response of some kind) since none of the eighteen rescue proteins appeared to have been unfolded- a tell-tale symptom of such a global response. Mutations that minimally disrupted their structure abolished their rescue capabilities.

The evidence seemed compelling. These de novo sequences were exerting specific fonctional effects that served to avert an otherwise fatal outcome for their bacterial hosts. Still the 'design' point-of-departure raised above was without question central to this particular success story. In his book Signature In The Cell Stephen Meyer has noted how it is sequence specificity that ensures that amino acid chains fold into "useful shapes or conformations" (Ref 1). Without a library tailored for the formation of four-helix bundles, the Princeton study is unlikely to have yielded anything that would come close to salvaging the debilitated bacteria. To make matters worse, this study failed to consider in detail the cooperativity that so evidently characterizes the organismic molecular scheme. What we see here is akin to taking one piece out of a jigsaw puzzle and finding another to put in its place albeit with some considerable force of fit. Those who espouse blind evolution are still left reeling over how to explain the origin of the entire puzzle.

Importantly cells transformed with rescue proteins exhibited growth that was "significantly slower than those expressing the natural protein" (the non-knockout strains). Exponential growth occurred 24-144 hours later and reached culture densities that in some cases were as low as 12-15% of wild-type. The authors readily admit that the library proteins may "function by different mechanisms than the natural proteins they replace". Indeed assays designed to test for the deleted functions failed to show that the de novo sequences exhibited comparable enzymatic activities. The evolutionary inference given by the authors- that billions of years of evolution have driven optimal activities for faster growth- therefore appears to be nothing more than a rehash of a positively stale Darwinian fairytale. After all, if the proteins function by different mechanisms, one cannot allege that they are in any sense on the way to becoming the more efficient naturally occurring protein entities we observe in E.coli today.

For the full PLOS One article see:
Michael A. Fisher, Kara L. McKinley, Luke H. Bradley, Sara R. Viola, Michael H. Hecht (2011) De Novo Designed Proteins from a Library of Artificial Sequences Function in Escherichia Coli and Enable Cell Growth, See http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015364

Further Reading
1. Stephen Meyer (2009) Signature In The Cell: DNA And The Evidence For Intelligent Design, Harper Collins Publishers, New York, p.99

by Denyse O'Leary
ARN correspondent

Yes, the abandonment was recounted in "E.O. Wilson's Theory of Altruism Shakes Up Understanding of Evolution" by Pamela Weintraub. Harvard biologist E. O. Wilson's 1975 Sociobiology was thought to give evolutionary psychology some respectability. Wilson, who learned his trade studying social insects, promoted the idea of kin selection - that people are genetically programmed ("bred into their bones") to behave in socially constructive ways in order to help the genes they share with others get passed on. For example, a woman looks after her sister's children to help the genes she shares with her sister get passed on. And she looks after her new neighbour from Rangoon's children to help ... hey, ... wait a minute.

So the scientific world quaked last August when Wilson renounced the theory that he had made famous. He and two Harvard colleagues, Martin Nowak and Corina Tarnita, reported in Nature that the mathematical construct on which inclusive fitness was based crumbles under closer scrutiny. The new work indicates that self-sacrifice to protect a relation’s genes does not drive evolution. In human terms, family is not so important after all; altruism emerges to protect social groups whether they are kin or not.

Wilson has been a familiar face in the Darwin racket for nearly four decades, touted in legacy media as an eminent, impressive scholar who made evolutionary psychology into a real science - when his theory was so obviously out of touch that the simplest experience of non-Harvard life confutes it. For one thing, as agnostic philosopher David Stove points out, in human terms (as opposed to insect terms), altruism is not what needs explaining, but the lack thereof. The recent Toronto subway shutdown (a minor event, to be sure), here and here, provides a useful multicultural snapshot of what Stove means: It was the boor, the unsocial person who was "out of it", not the social person. Everyone seemed to recognize the danger of an out-of-control crowd. (We've all heard the cautionary tales, many of them true.) And the only genetics involved was the fact that we were all humans, endowed with the intelligence to see that danger and remember the tales.

Evolutionary psychology is never going to be a science because it is a discipline without a subject: Its tailless ape, who behavior requires an explanation that does not take into account conscious human awareness in real time - but looks everywhere else for an explanation instead - does not exist.

Denyse O'Leary is co-author of The Spiritual Brain.

By Robert Deyes
ARN Correspondent

In his 1987 seminal work entitled Impossibility In Medicine the American psychiatrist Jean Goodwin presented to the world the following acutely insightful vista of the brain:

"Despite many assertions to the contrary, the brain is not "like a computer". Yes, the brain has many electrical connections, just like a computer. But at each point in a computer only a binary decision can be made- yes or no, on or off, 0 or 1. Each point in the brain, each brain cell, contains all the genetic information necessary to reproduce the entire organism. A brain cell is not a switch. It has a memory; it can be subtle. Each brain cell is like a computer. The brain is like a hundred billion computers all connected together. It is impossible to understand because it is too complex. As Emerson Pugh wrote, "If the human brain was so simple that we could understand it, we would be so simple that we couldn't."" (1)

In so doing he hinted at an aspect of the brain that tied in well with a philosophical thought-chain expounded by ID philosopher Bill Dembski in his book No Free Lunch:

"Humans have designed all sorts of engineering marvels, everything from Cray supercomputers to Gothic cathedrals. But that means, if we are to believe Melvin Kooner, that a blind evolutionary process...cobbled together human neuro-anatomy which in turn gave rise to human consciousness, which in turn produces artifacts like supercomputers which in turn are not cobbled together at all but instead are carefully designed. Out pop purpose, intelligence, and design from a process that started with no purpose, intelligence, or design. This is magic" (2)

In my most recent essay Lessons From A Broken Brain I provide a high-level overview of key medical moments that helped define the hundred-billion-computer organ housed atop our bodies. The design inference shines through in the brief details I present.

On a somewhat related note there is a fascinating clip on the work of Dutch kinetic sculptor Theo Jansen who has created his own brand of beach creatures. With over twenty years of arduous work under his belt, Jansen started by pulling his 'offspring creatures' up into the wind, then gave them propellers and wings/sails to increase their running power. The commentator on this clip notes that: "through hours of experimenting and trial and error, Theo's designs are becoming more and more independent".

Jansen's own conclusion?

"What I have found about this experience of making new forms of life is that you discover all the problems that the real creator must have had creating this world"

And these are not even thinking, autonomous, reproducing beings! See Beach Creatures

Further Reading

1. No Way: The Nature of the Impossible, edited by Philip Davis and David Park. Cited in Inside The Mind Of God- Images And Words Of Inner Space, edited by Michael Reagan, Templeton Foundation Press, New York, p.61
2. William Dembski (2002) No Free Lunch: Why Specified Complexity Cannot Be Purchased Without Intelligence, Rowman & Littlefield Publishers, Inc, Lanham, Maryland, p.369