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He said it: John Sanford gene gun inventor, on the rarity of beneficial mutations

John Sanford

Cornell plant geneticist John Sanford writes in Genetic Entropy & the Mystery of the Genome:

Bergman (2004) has studied the topic of beneficial mutations. Among other things, he did a simple literature search via Biological Abstracts and Medline. He found 453,732 ‘mutation’ hits, but among these only 186 mentioned the word ‘beneficial’ (about 4 in 10,000). When those 186 references were reviewed, almost all the presumed ‘beneficial mutations’ were only beneficial in a very narrow sense–but each mutation consistently involved loss of function changes–hence loss of information.

While it is almost universally accepted that beneficial (information creating) mutations must occur, this belief seems to be based upon uncritical acceptance of RM/NS, rather than upon any actual evidence. I do not doubt there are beneficial mutations as evidenced by rapid adaptation yet I contest the fact that they build meaningful information in the genome instead of degrade preexisting information in the genome.” (pp.26-27)

See also: Darwin’s beneficial mutations do not benefit each other

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Eocene, No one is saying that John Sanford cannot do science or that his work is not helpful. What we are saying is that his discoveries help show that evolution could not have happened as Darwin and the neo-Darwinists claim. Here is the article I referred to above with links to various scientific papers verifying this: "In Darwinian evolution, variations must add new information to produce innovations. Neo-Darwinism ascribes those variations to genetic mutations. In 2005, geneticist John Sanford (Cornell) argued that the accumulation of mutations always decreases fitness in a process he called “genetic entropy.”1 The downhill trend is amplified by a number of factors, including selection interference and epistasis (interactions between mutations).2 Now, genetic entropy from epistasis has received support by two new papers in Science. For mutations under epistasis to produce innovation, there must be a way for them to work together (synergistic epistasis). This is often assumed but has not been observed. Most experiments have shown beneficial mutations working against each other (antagonistic epistasis; see 12/14/2006), or causing even less fitness than if they acted alone (decompensatory epistasis; see 10/19/2004). In a new paper in Science,3 Khan et al, working with Richard Lenski [Michigan State], leader of the longest-running experiment on evolution of E. coli, found a law of diminishing returns with beneficial mutations due to negative epistasis. The abstract said: Epistatic interactions between mutations play a prominent role in evolutionary theories. Many studies have found that epistasis is widespread, but they have rarely considered beneficial mutations. We analyzed the effects of epistasis on fitness for the first five mutations to fix in an experimental population of Escherichia coli. Epistasis depended on the effects of the combined mutations—the larger the expected benefit, the more negative the epistatic effect. Epistasis thus tended to produce diminishing returns with genotype fitness, although interactions involving one particular mutation had the opposite effect. These data support models in which negative epistasis contributes to declining rates of adaptation over time. Within the paper, they said, “We observed an overall negative relation, indicating that epistatic effects became more negative as the expected fitness rose....” Near the conclusion, they confirmed witnessing a type of genetic entropy: “A conspicuous feature of the mean-fitness trajectory for this population—and indeed for most experimental populations evolving in a constant environment—is that the rate of adaptation declined over time.” The reason they gave was that “epistatic interactions contribute greatly to this deceleration by reducing the effect-size of the remaining beneficial mutations as a population approaches a fitness peak. In other words, epistasis acts as a drag that reduces the contribution of later beneficial mutations.” No increases in adaptation or fitness were observed, and no explanation was offered for how neo-Darwinism could overcome the downward trend in fitness. Another paper in the same issue of Science found similar bad news. A group of researchers in Massachusetts put “diminishing returns” in the title of their paper.4 They introduced beneficial mutations into bacteria, but found them decelerating adaptation. Their abstract said, “These results provide the first evidence that patterns of epistasis may differ for within- and between-gene interactions during adaptation and that diminishing returns epistasis contributes to the consistent observation of decelerating fitness gains during adaptation.” Aware of the study by Khan et al, they claimed that “across these two distinct model systems 7 of 10 alleles consistently showed antagonism, whereas only 2 exhibited synergy.” A look in both papers, however, showed no clear examples of evolutionary progress in the experiments, and certainly no new species arising. In fact, the experiments were more a test of artificial selection—studying which mutants adapted to contrived laboratory conditions. In addition, fitness gains were measured by reproduction rates which, in some cases of adaptation, might have deleterious trade-offs, such as metabolic cost. Commenting on these papers in Science,5 three authors from University of Pennsylvania noted that, “In Evolution, the Sum Is Less than Its Parts.” The figure caption explained, “The mutations conferred smaller marginal benefits in combination than they did individually. This antagonistic epistasis causes progressively slower rates of adaptation over time.” Khryazhrimsky, Draghi and Plotkin referred to some microbe experiments that showed initial gains due to beneficial mutations (in isolated lab populations) that slowed to a crawl due to epistasis, or then “discover rare phenotypic innovations,” then diverge into populations that either coexist or compete. More work will be needed, they said, to quantify these effects in the wild with different organisms, population sizes and natural ecologies. Though hopeful that evolution can march onward in spite of these genetic brakes, they admitted that “the prevalence of antagonistic epistasis measured by the two groups ensures a predictable tempo of adaptation characterized by diminishing marginal returns.” They pulled victory from the jaws of defeat, claiming that these experiments “represent resounding achievement for the reductionist approach to studying biology.” A pro-evolution article in Science Daily summarized the work of the first paper thorough the eyes of Tim Cooper [U of Houston], one of the participants. “The more mutations the researchers added, the more they interfered with each other,” was one of the “surprising” results. “It was as if the mutations got in each other's way as they all tried to accomplish the same thing.” Hopefully readers will pardon Cooper for the anthropomorphism. “The effect of their interactions depended on the presence of other mutations, which turned out to be overwhelmingly negative.” What does this mean for evolutionary progress? “These results point us toward expecting to see the rate of a population’s fitness declining over time even with the continual addition of new beneficial mutations,” Cooper said. In contrast to the depressing news in Science, three authors in Nature claimed hopeful news with mutations under epistasis.6 “Cryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme” was the optimistic title of their paper, but a close look at their experiment shows it was a case of artificial selection on RNA ribozymes only. It did not involve a real cell culture, and the gains from “cryptic variation” only showed adaptations to contrived conditions in the lab. They explained the adaptation as a case of “pre-adaptation” or “exaptation” with mutations hiding out till an opportunity arrived for them to show some adaptation in the scientists’ contrived environments. Their simplified model substituted for real evidence, because “this facilitating role for cryptic variation has not been proven, partly because most pertinent work focuses on complex phenotypes of whole organisms whose genetic basis is incompletely understood.” Nevertheless, they claimed by extrapolation that “Our results highlight the positive role that robustness and epistasis can have in adaptive evolution.” This paper came out in print a day before the pessimistic papers in Science. Speaking of mutations, researchers at USC discovered “a chromosomal mutation responsible for a very rare condition in which people grow excess hair all over their bodies” (see Medical Xpress). While the benefit of such a condition might only count in the arctic, it shows that some mutations can have drastic effects. Even if a hairy female could survive the cold, though, what male would want to marry her? Such mutations would probably not become fixed in a population or else Eskimos would all have it. Most mutations are nearly neutral and invisible to natural selection, as Sanford explained in detail in his book. Because they are not eliminated by purifying selection, they therefore accumulate in the genome, dragging it into genetic entropy. Mutations are not good material for natural selection." 1. John Sanford, Genetic Entropy and the Mystery of the Genome (Ivan Press, 2005). 2. Ibid., pp. 109-111. 3. Khan et al., Negative Epistasis Between Beneficial Mutations in an Evolving Bacterial Population, Science, 3 June 2011: Vol. 332 no. 6034 pp. 1193-1196. DOI: 10.1126/science.1203801. 4. Chou et al., Diminishing Returns Epistasis Among Beneficial Mutations Decelerates Adaptation, Science, 3 June 2011: Vol. 332 no. 6034 pp. 1190-1192, DOI: 10.1126/science.1203799. 5. Khryazhrimsky, Draghi and Plotkin, In Evolution, the Sum Is Less than Its Parts, Science, 3 June 2011: Vol. 332 no. 6034 pp. 1160-1161, DOI: 10.1126/science.1208072. 6. Hayden, Ferrada and Wagner, Cryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme, Nature, 474 (02 June 2011), pages 92–95, doi:10.1038/nature10083. Here is the link one more time: http://crev.info/content/110605-genetic_entropy_confirmed tjguy
"John Sanford Gene Gun Inventor" http://www.dailyyonder.com/letter-langdon-shot-and-stacked/2009/08/03/2270 Article Quote: "More recently the gene gun, invented and patented by John C. Sanford, has introduced "improvements" to rural America, changing food production, crops, and access to basic farm inputs like seeds. Sanford’s invention involved a Crossman air gun used to “shoot” plant cells with alien gene implants. In the case of corn and soybeans, his gene implants were mostly bacterial. The idea that a gene from an animal could exist inside a plant and bestow certain traits of the animal to the plant seemed other-worldly. But the gene gun has become a regular tool of plant breeders who’ve used it to give plants immunity to chemical herbicides or lethal defenses against certain insects. Gene implantation is more chance than science. It’s a big casino. Because there is no accurate way to control implants, it takes a number of attempts to generate a single success. Newly implanted cells are grown in Petri dishes, and resistance to antibiotics or other chemicals is the gauge of that success. Any cells that survive treatment with those chemicals are replicated to see exactly what the creation will become and if it has value. The main difference between Bell’s telephone and Sanford’s gene gun isn’t originality; both used existing technology to create new totally different applications. But while Bell’s telephone never generated other new patentable creations, Sanford’s invention has created plants for large seed companies, companies that have now convinced courts that their ‘hit or miss creations’ should be protected by patent laws." ----- Here is a paper outlining some of the historical background of the GMO industry and Dr John C Sanford's unfortunate contribution to this profit obsessed FrankenFood industry. http://www.capewineacademy.co.za/dissertations/Genetically%20Modified%20Organisms%20in%20the%20Wine%20Industry%20v.corrected.pdf Paper quote of Dr John C Sanford's contribution: Biolistics or Particle Bombardment "In 1987, John C. Sanford (Cornell University) and his co-worker Theodore M. Klein constructed a DNA particle gun that used tungsten particles to bombard cells, with a .22 calibre blank cartridge as the motive force. Researchers at Agracetus in Middleton, Wisconsin have developed a similar gun using gold particles propelled by the vaporization of a water droplet. Today, the mechanism of particle bombardment often involves the acceleration of gold or tungsten particles through a partial vacuum under the pressure of helium gas (Fig. 2.1). Particles of 1-2 microns in diameter are first coated with purified plasmid DNA and then accelerated through the walls of intact cells. The DNA is then randomly integrated into the organism’s genome. Because small holes in cell walls and membranes rapidly close by themselves, the punctures are temporary and do not irreversibly compromise the integrity of the cells. Although the particles remain in the cytoplasm, they are too small to interfere with any cellular functions." ************** There are a few lines out of the Jurassic Park film by the fictional character Dr Ian Malcolm which fit in perfectly with the disasterous field of GMO technologies. Dr Ian Malcolm: "Don’t you see the danger, John[John C Sanford], inherent in what you’re doing here? Genetic power is the most awesome force the planet’s ever witnessed, yet you wield it like a kid that’s found his dad’s gun.[In this case - Gene Gun] Dr Ian Malcolm: “it didnt require any discipline to attain it” “what you call discovery, I call rape of the natural world” Dr. Ian Malcolm: “Yeah, but your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should.” ----- Eocene
GinoB, If an organism experiences a number of "neutral" mutations, what makes any of them any more likely to be beneficial in changed environment than the state of its genome before the neutral mutations? It adds up to a belief that as long as there are mutations there will be benefit. What example do you have of a neutral mutation that proved beneficial in a changed environment? Maybe there are some. It's not so far-fetched. But it still doesn't solve the problem of combining several neutral mutations to arrive at a "solution" that requires all of them to be beneficial rather than neutral. Why is that a problem? For the same reason that having, say, a remote control and two batteries doesn't accomplish anything unless one can abstractly visualize the remote, with both batteries correctly inserted, able to function, and then plan the steps of removing the cover and inserting new batteries. Some things just don't happen without planning, intent, and foresight. What is the barrier, you will ask again? The barrier is that what improvements can occasionally occur from a single modified gene may do so. Those that require the coordination of several interrelated modifications - say improved sense of light, a modification to the nervous system to process it, and an behavioral change in response to light - those are like putting the remote and the batteries in the dryer and spinning them, waiting for them to fall into place, and then not fall apart again. And that's being generous. ScottAndrews2
as to 'neutral WRT reproductive fitness – over 98% by some estimates': I guess you didn't count this following study in your survey of evidence:
Unexpectedly small effects of mutations in bacteria bring new perspectives – November 2010 Excerpt: Most mutations in the genes of the Salmonella bacterium have a surprisingly small negative impact on bacterial fitness. And this is the case regardless whether they lead to changes in the bacterial proteins or not.,,, using extremely sensitive growth measurements, doctoral candidate Peter Lind showed that most mutations reduced the rate of growth of bacteria by only 0.500 percent. No mutations completely disabled the function of the proteins, and very few had no impact at all. Even more surprising was the fact that mutations that do not change the protein sequence had negative effects similar to those of mutations that led to substitution of amino acids. A possible explanation is that most mutations may have their negative effect by altering mRNA structure, not proteins, as is commonly assumed. http://www.physorg.com/news/2010-11-unexpectedly-small-effects-mutations-bacteria.html
Ginob, Isn't this a fascinating study? Will you honestly revise your 'neutrality' estimate? bornagain77
The flip side is: the large percentage of mutations in any given environment are neutral WRT reproductive fitness – over 98% by some estimates.
And what is the estimate on the % of detrimental mutations? It seems, by your math, we will be covering more than 100% of all genetic changes.
This huge reserve pool of neutral mutations virtually guaranteed that when the environment changes some of the previously neutral mutations will become beneficial.
Yup, it's still relative.
Such beneficial effects of previously neutral mutations, especially when they combine with new mutations, are a well known phenomenon in evolutionary theory.
You mean a well known phenomenon in biological organisms. But one that still hasn't been known to produce new, useful multi-part systems. See also: Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution The point being is your position boils down to nothing but sheer dumb luck, meaning it does not belong in a science classroom. Joseph
Yes. Here is another article referring to Sanford and his work as well as the mutation problem. http://crev.info/content/110605-genetic_entropy_confirmed Enjoy! tjguy
The take home point from both Dr. Behe's work and Dr. Sanford's work is not so much the point that information increasing mutations NEVER occur for parent species, (which, though it in all likelihood is a true point, is, none-the-less, a VERY difficult position to defend scientifically), but the much more modest scientific claim from Drs. Behe and Sanford is that the rate of detrimental mutations to beneficial mutations is so overwhelmingly detrimental that any rare beneficial 'information increasing' mutations will be completely swamped by the detrimental 'information decreasing' mutations. Dr. Sanford has dubbed this principle 'Genetic Entropy' notes:
Evolution Vs Genetic Entropy - Andy McIntosh - video http://www.metacafe.com/watch/4028086
It is very interesting to note that the principle of Genetic Entropy, contrary to evolutionary models, lends itself very well to mathematical analysis by computer simulation:
"No human investigation can be called true science without passing through mathematical tests." Leonardo Da Vinci Using Computer Simulation to Understand Mutation Accumulation Dynamics and Genetic Load: Excerpt: We apply a biologically realistic forward-time population genetics program to study human mutation accumulation under a wide-range of circumstances.,, Our numerical simulations consistently show that deleterious mutations accumulate linearly across a large portion of the relevant parameter space. http://bioinformatics.cau.edu.cn/lecture/chinaproof.pdf MENDEL’S ACCOUNTANT: J. SANFORD†, J. BAUMGARDNER‡, W. BREWER§, P. GIBSON¶, AND W. REMINE http://mendelsaccount.sourceforge.net http://www.scpe.org/vols/vol08/no2/SCPE_8_2_02.pdf
Whereas the following study by Dr. Behe surveys four decades of experimental work, and solidly backs up the conclusion that there has never been an observed violation of the principle of genetic entropy:
“The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain - Michael Behe - December 2010 Excerpt: In its most recent issue The Quarterly Review of Biology has published a review by myself of laboratory evolution experiments of microbes going back four decades.,,, The gist of the paper is that so far the overwhelming number of adaptive (that is, helpful) mutations seen in laboratory evolution experiments are either loss or modification of function. Of course we had already known that the great majority of mutations that have a visible effect on an organism are deleterious. Now, surprisingly, it seems that even the great majority of helpful mutations degrade the genome to a greater or lesser extent.,,, I dub it “The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain.(that is a net 'fitness gain' within a 'stressed' environment i.e. remove the stress from the environment and the parent strain is always more 'fit') http://behe.uncommondescent.com/2010/12/the-first-rule-of-adaptive-evolution/
Michael Behe talks about the preceding paper on this podcast:
Michael Behe: Challenging Darwin, One Peer-Reviewed Paper at a Time - December 2010 http://intelligentdesign.podomatic.com/player/web/2010-12-23T11_53_46-08_00
A few more notes:
Where's the substantiating evidence for neo-Darwinism? https://docs.google.com/document/d/1q-PBeQELzT4pkgxB2ZOxGxwv6ynOixfzqzsFlCJ9jrw/edit "Is there a real connection between entropy in physics and the entropy of information? ....The equations of information theory and the second law are the same, suggesting that the idea of entropy is something fundamental..." Tom Siegfried, Dallas Morning News, 5/14/90 - Quotes attributed to Robert W. Lucky, Ex. Director of Research, AT&T, Bell Laboratories & John A. Wheeler, of Princeton & Univ. of TX, Austin in the article
Verse and music:
Romans 8:18-21 I consider that our present sufferings are not worth comparing with the glory that will be revealed in us. The creation waits in eager expectation for the sons of God to be revealed. For the creation was subjected to frustration, not by its own choice, but by the will of the one who subjected it, in hope that the creation itself will be liberated from its bondage to decay and brought into the glorious freedom of the children of God. Mandy Moore - Only Hope http://www.youtube.com/v/0ofeDruIwTM&fs=1&source=uds&autoplay=1
One issue is that “beneficial” is a relative word, meaning what is beneficial for one generation in one environment is not necessarily beneficial for another environment nor some other generation.
The flip side is: the large percentage of mutations in any given environment are neutral WRT reproductive fitness - over 98% by some estimates. This huge reserve pool of neutral mutations virtually guaranteed that when the environment changes some of the previously neutral mutations will become beneficial. Such beneficial effects of previously neutral mutations, especially when they combine with new mutations, are a well known phenomenon in evolutionary theory. GinoB
So someone other than Behe has done a review like this, then. Who all else knows about this little problem regarding the elusive benifitial mutation, but just hasn't bothered to tell anyone, or is afraid to? M. Holcumbrink
One issue is that "beneficial" is a relative word, meaning what is beneficial for one generation in one environment is not necessarily beneficial for another environment nor some other generation. Joseph

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