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Author
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Topic: Darwin Turns to Design by Point Mutations
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Jed Macosko
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Member # 314
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posted 15. August 2002 18:05
[The following is part of chapter 1 from a book I hope to finish by 2009, in time for the 150th anniversary of Darwin's "Origin". If you have a copy of his original work, you can see that I have made small changes, or point mutations, to his manuscript. After many such mutations, the text says something completely new. This is similar to the claim that by small modifications, an organism can change into a utterly different species. However, my thesis is that these changes require intelligent foresight. Therefore, the process of converting Darwin's book from one supporting naturalistic evolution to one in favor of intelligent design becomes an illustration for my central thesis.]
On the Origin of Bioinformation
by Jed C. Macosko
La Sierra, Riverside, California,
October 1st, 2009.
On the Origin of Bioinformation by Means of Intelligent Forsight,
or the
Preservation of Promising Innovations in the History of Life.
By Jed C. Macosko
Chapter I
Man-made Complexity
Sources of Complexity – Effects of Accident – Correlation of Ideas – Intelligence – Character of Man-made Complexity – Similarity between Man-made and Biological Complexity – Origin of Man-made Complexity from prior Knowledge – Molecular Machines, their Complexity and Specificity – Principle of Foresight consistently applied, its Effects – Methodical and Accidental Foresight – Unknown Origin of Man-made Information – Importance of Foresight in Man-made Information.
When we look to the variety of functional features of a given set of plants or animals, one of the first points which strikes us, is, that they generally have much more complexity and specificity, than the useful components of even our most technologically advanced man-made machines. When we reflect on the vast diversity of tasks carried out by plants and animals, and which may have been even more complex during past geologic ages than presently, I think we are driven to conclude that the greater complexity in nature is simply due to plants and animals having been produced by a force at least as creative as, and perhaps somewhat more ingenious than, that creative drive which has spurred the development of man-made technology. There is, also, I think, some probability in the view propounded by Charles Darwin, that this greater complexity in nature may be partly connected with an excess of time. It seems pretty clear that innovations, biological or otherwise, can accumulate over time, thus it may be several iterations of invention before the creative force causes any appreciable amount of improvement; and that when the entity has once been caused to improve, it could continue to be improved over many iterations. No case is on record of an invention ceasing to be improvable under man’s creative influence. Our oldest technologies, such as agriculture, still often yield new innovations: our oldest forms of art, music and storytelling, are still subject to our improvements and modifications.
It has been disputed from where the sources of man-made complexity, whatever they may be, generally derive; whether from his brain or from his mind, or gathered entirely from the pool of ideas around him. Richard Dawkins and his followers have proposed that something similar to our genes exist in the realm of ideas; and that there is no truly novel innovation but only a rehashing of older inventions, supplemented by an individual’s genetically-derived instincts. But I am strongly inclined to suspect that the most frequent cause of man-made complexity may be attributed to the mind of an individual, having been stimulated by prior experience, using experience to create a pool of possible, and novel, outcomes, and then choosing one of those outcomes. Several reasons make me believe in this; but the chief one is the remarkable differences that exists in the types of complexity originating from different minds; the mind appearing to be far more variable than any other part of a man, with respect to his ability create different kinds of complexity. Nothing is simpler than to give a class of students precisely the same reading material and homework, and few things more different than the completed assignments, even when a teacher desires uniformity. How many classroom there are in which students excel by such a variety of means, though instructed by the same lectures given by the same professor! This is generally attributed to different upbringing or genetic disposition; but how many siblings are raised in identical ways, and yet produce vastly different creative works! In some few such cases it has been found out that very trifling changes in pedagogy, such as the use of a little more or less analogy at some point in a lecture, will determine whether or not a student demonstrates learning a particular subject. I cannot here enter on the copious details which I have collected on this curious subject through my years of teaching; but to show how unique the laws are which determine the diverse creativity of students subjected to similar conditions, I may just mention that my general chemistry pupils one particular spring, even though I had a set of identical twins, formulated innovative solutions to my ‘chemical puzzlers’ in vastly different ways; whereas, my physical chemistry student from the same spring (two Asian males, one Hispanic female and one African-American female) had nearly identical answers for all of their problems sets and even some of their laboratory reports. Many bright students have quite obtuse final projects, the same exact condition as the projects of those who never attended class. When, on the one hand, we see younger men and women, though often not instructed in a given subject, yet solving difficult problems in that subject quite freely; and when, on the other hand, we see individuals, though trained for years in a particular field, perfectly informed, well-versed, and intelligent (of which I could give numerous instances), yet failing to work their way around a mental roadblock, we need not be surprised at this mental activity, when it originates from different people, appearing not quite predictable, and producing creative works not perfectly like their closest relatives or neighbors.
Lack of new ideas has been said to be the bane of established companies; but on this view we attribute a vibrant pool of inventions to the same cause that produces a dearth thereof: the human mind; and invention is the source of all the fantastic technologies of our day. I may add, that as some companies’ inventors will depend on ideas stimulated by the interesting technologies already present in their firms, and their inventions vary only slightly from previous ideas—demonstrating a close dependence on prior thought; so will some innovations spring up most freely under the most unfavorable conditions (for instance, George Washington Carver working with the lowly peanut), showing that inventors’ minds are not been thus affected by working on seemingly simple ideas.
A long list could easily be given of 'midnight inventions;' by this term I mean an idea, which suddenly pops into one’s head and is new and sometimes very different in character from that of any idea which precedes it. Such inventions can be reduced to practice by long hours in the laboratory, workshop, &c., but sometimes are so simple that they are immediately implemented. These ideas are extremely rare in the average person’s mind, but far from rare for those whom the world would describe as a ‘genius’ in a specific area; and in this case we see that the differences in the mind of an individual affect how ideas are generated. Moreover, it is the opinion of most psychologist that there is an essential difference between the mind or soul of an individual and the synapse in that person’s brain; so that, in fact, ‘midnight inventions’ would be more than simply the result of abnormal brain chemistry and would therefore support my view, that invention may be largely attributed to the mind or spirit, or to both, using its power of imagination to conceive many possible innovations. These cases anyhow show that innovation is not necessarily connected, as some authors have supposed, with the ideas that precede it.
Inventions from the same mind, and the creative works of the same person, sometimes differ considerably from each other, though both the genetics and the environment of the creator have obviously been exactly the same; and this shows how unimportant the direct effects of the conditions of life are in comparison with the laws that govern the mind’s innate ability to create, and to innovate, and to invent; for had the action of the conditions been direct, if an individual invented anything, all their inventions would probably have looked similar. To judge how much, in the case of any innovation, we should attribute to the direct action of genetics, environment, upbringing, prior stimulation, &c., is most difficult: my impression is, that within a single human mind such agencies have produced very little direct effect, though apparently more in the case of corporations and large think-tanks. Under this point of view, Dr. Todd Griffin’s recent work on “the discovery machine” (www.discoverymachine.com) seems extremely valuable. When individuals or small groups of inventors followed the discovery machine’s invention protocol in the same way, the innovations that they generated at first appear to be directly due to the protocol; but in some cases it can be shown that following quite opposite protocols produces similar types of inventions. Nevertheless some slight amount of inventing may, I think, be attributed to the direct action of the procedure followed during the course of creating--as, in some cases, the blending of two technologies from a protocol that first identifies various amenable methodologies, the use of new materials from a protocol that starts from tractable resources, and perhaps the cooption of physical phenomenon by a protocol that seeks to review all relevant laws and properties.
Accident also has a deciding influence, as in the serendipitous invention of 3M’s Post-it™ notes. In drug discovery it has a more marked effect; for instance, I find that a certain fragment of the influenza virus has the property of aggregating artificial cells, in acidic environments; and I presume that this phenomenon may be safely attributed to the same property observed in whole flu virus with living cells. The serendipity lies in accidentally neutralizing the acid solution of clustered artificial cells and observing a clear, non-aggregated suspension. I conclude that while the intact virus irreversibly aggregates cells, the fragments cluster cells reversibly, and therefore the mechanism of clustering is driven by a tiny patch of amino acid residues. This patch of residues is then the target of anti-influenza drugs. In this way, accident seems to play a role in the formation of man-made technologies.
There are many laws regulating invention, some few of which can be dimly seen, and will be hereafter briefly mentioned. I will here only allude to what may be called correlation of ideas. Any clever idea in the planning stage or in a design prototype will almost certainly entail innovations in the finished product. In start-up companies, the correlations between quite distinct phases of product development are very curious; and many instances are given in XXXXX’s intriguing work on this subject. Engineers believe that technologies for manufacturing can almost always be co-opted in a simplified form for consumers. Some instances of correlation are quite whimsical; thus composers of poetic ditties are invariably good at organizing; bridge playing and musical aptitude go together, of which many remarkable cases could be given amongst both modern and historical virtuosos. From the facts collected by XXXXX, it appears that chess masters and other board game experts are much more likely to invent efficient ways to do laundry and various household tasks. Architects think up more puns; painters and sculptors are apt to plan, as is asserted, more romantic dates; detectives design atypical meals; dancers and figure skaters are incessant doodlers, and authors are frequently prone to scheming elaborate practical jokes. Hence, if an intelligent person goes on inventing and innovating, in all his various expressions, he will almost certainly consciously or unconsciously invent other, unrelated creations, owing to the mysterious laws of the correlation of ideas.
The result of the various, quite unknown, or dimly seen outworking of intelligence is infinitely complex and diversified. It is well worth while carefully to study the several treatises published on artificial intelligence systems, as on the expert systems, computation, even Deep Blue, Deeper Blue, &c.; and it is really surprising to note the endless points in structure and design in which the systems and sub-systems differ from each other. For example, in the Deeper Blue chess program, the whole organisation seems to have become plastic, and tends to respond to it opponents moves like a true intelligence.
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Frances
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Member # 169
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posted 16. August 2002 01:11
An interesting approach but I would like to get to the crux of the matter. You seem to suggest that change requires some foresight. Based on what evidence have you reached this conclusion? And what about evidence that suggests that lack of foresight is no necessary impediment to evolution perse?
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Art
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Member # 179
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posted 16. August 2002 23:42
Hi Jed,
Assuming that your “word play” is intended to make points similar to those you were stressing at the recent virtual Summer Workshop, I think it’s helpful to contrast the exercise with the things that proteins can really do.
For example: quote:
1: Nat Biotechnol 1999 Jan;17(1):58-61
Comment in:
Nat Biotechnol. 1999 Jan;17(1):21.
Nat Biotechnol. 1999 Mar;17(3):210.
Evolutionary molecular engineering by random elongation mutagenesis.
Matsuura T, Miyai K, Trakulnaleamsai S, Yomo T, Shima Y, Miki S, Yamamoto K, Urabe I.
Department of Biotechnology, Graduate School of Engineering, Osaka University,
Yamadaoka, Suita, Japan.
We describe a new method of random mutagenesis that employs the addition of peptide tails with random sequences to the C-terminal of enzyme molecules. A mutant population of catalase I from Bacillus stearothermophilus prepared by this method has a diversity in thermostability and enzyme activity equal to that obtained after random point mutagenesis. When a triple mutant of catalase I (I108T/D130N/1222T)-the thermostability of which is much lower than that of the wild type-was subjected to random elongation mutagenesis, we generated a mutant population containing only mutants with higher thermostability than the triple mutant. Some had an even higher stability than the wild-type enzyme, whose thermostability is considered to be optimized. These results indicate that peptide addition expands the protein sequence space resulting in a new fitness landscape. The enzyme can then move along the routes of the new landscape until it reaches a new optimum. The combination of random elongation mutagenesis with random point mutagenesis should be a useful approach to the in vitro evolution of proteins with new properties.
PMID: 9920270 [PubMed - indexed for MEDLINE]
This is somewhat akin to ripping out the middle of TOOS, letting a monkey type random pages of gibberish and sticking it on the end of the book, and - voila - ending up with a coherent package that reads as well, or better than, the original. Go figure ![[Smile]](smile.gif) .
What does this mean? For me, it reinforces the suggestion that proteins are low-information moieties - this is why the “high-information” analogy of TOOS fails to apply in the case of catalase I.
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Jed Macosko
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Member # 314
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posted 08. September 2002 00:57
Dear Frances and Walt,
I'm sorry that it has taken so long to get back to you. I've been delaying my response until I could get a hold of the article Walt mentioned. Thank you, Walt, for pointing that paper out to me. It is extremely relevant to Doug Axe's work and my earlier virtual Summer Workshop conversation that you mentioned.
In answer to your question, Frances, about the evidence that has helped me reach my conclusion that foresight is necessary to real biological question, I would like to use the a quote from the final paragraph of the paper Walt mentioned. The quote is:
"... random substitution and random elongation involve different concepts of random mutagenesis. ... Alternating use of these two different types of random mutagenesis may represent the sequence followed in Nature for the evolution of proteins."
What Doug Axe showed in his 1999 JMB paper (if you don't have a copy I can send you the .pdf) was that random substitutions are not enough to take one protein to a very similar (50% sequence identity, 75% sequence parity) protein, through functional intermediates, on any reasonable time scale. Another paper, also from JMB in '99, written by Francisco Blanco et al. attempts the more ambitious goal of going from one protein to a completely different protein via folded intermediates. They partially succeed, though only the intermediates one step away from either the start or the end were properly folded. Moreover, the reason they succeed in filling the space between the second and penultimate intermediates with somewhat folded proteins is because they use foresight. Indeed, if Nature (with a capital "N") uses random substitutions to achieve the evolution of proteins, studies like those done by Blanco et al. convince me that Nature also uses foresight.
As far as your point, Walt, about the Urabe paper indicating that proteins are low-information moieties, I would agree with you whole-heartedly, if Urabe and coworkers did what you described. However, after reading their article, I do not believe they did the biological equivalent of, "ripping out the middle of TOOS, letting a monkey type random pages of gibberish and sticking it on the end of the book, and - voila - ending up with a coherent package that reads as well, or better than, the original." Instead, what they did was more like copying a few pages out of an instruction manual, randomly replacing words with their synonyms, then tacking the new pages onto the back of the manual and seeing if customers can more clearly follow the instructions. I'll bet if you tried that on some household appliances, you might find that after making 10,240,000,000,000 different versions (like was done in Urabe's study) of the pages tacked to the back of the original manual, one or two might help customers figure out how to operate their appliance more easily. The reason this works is because the function (understanding an appliance) is still contained in the unaltered front part of the mutant manuals. The last few pages contain information that has been altered slightly and may, by chance, complement the original instructions.
To summarize the differences in our analogies:
1) The pages were not ripped out, but copied and tacked to the back after slight modification.
2) The modified ending was not gibberish but readable sentences where words had been replaced by their synonyms.
3) The final version of the new book doesn't necessarily "read better" than the original, but instead performs a function, in my case aid the proper use of an appliance, slightly better than the original book.
These differences may seem inconsequential, but they highlight the different ways you and I see the information content of proteins. Therefore, I regard this article to only reinforce my thesis, that evolution of novelty requires foresight. And the analogy of "Darwin by point mutation" still holds, since I am changing the function of TOOS from one that proposes a naturalistic theory of the origin of biodiversity, to one that sets forth an intelligence-based theory. Whereas it is possible, by the same strategy used by Urabe et al., to make a simple improvement to a function by trying 10,240,000,000,000 different "decorations", it is fundamentally impossible to get a new function without resorting to intelligent foresight.
Thank you for perusing the beginnings of TOOB. I hope that I will have time to finish it by 2009. Your comments have certainly spurred me onward!
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