Semisynthetic organisms and synthetic biology

Unintended Consequences of Expanding the Genetic Alphabet

Conclusion:

…phototoxicity results presented herein using a human skin cancer cell line are intended to create awareness to the scientific community of the potential unintended consequences of expanding the genetic alphabet with unnatural nucleosides like those used in this work.

Reported as:  Unintended consequences of creating the world’s first semisynthetic organism

Excerpt:

…the artificial base pair makes living cells more susceptible to damage from low doses of sunlight and standard fluorescent light bulbs, leading to a significant decrease in cell survival and growth.

My comment: This discovery shows how little is known about the energy-dependent fine-tuning of links from angstroms to ecosystems. For example, biophysically constrained viral latency occurs in the context of hydrogen-atom transfer in DNA base pairs in solution. That’s how hydrogen-atom transfer links the epigenetic landscape to the physical landscape of supercoiled DNA.  It’s also how the innate immune system and the de novo creation of genes are linked to healthy longevity and increasing organismal complexity.

Until now, synthetic/unnatural nucleosides have not been fully considered in the context of energy-dependent ecological adaptation.  For example, all organisms must adapt to ecological variation via energy-dependent hydrogen-atom transfer in DNA base pairs in solution. Ecological adaptation links the speed of light on contact with water to cell-type differentiation in all living genera via the physiology of reproduction and supercoiled DNA.

See, for instance: Hydrogen-atom transfer in DNA base pairs (6)

My comment: Researchers who thought they could create ecologically adapted organisms via unnatural nucleosides may be among the theorists who will continue to dismiss Einstein’s claims about molecular machines; Schrodinger’s claims about the anti-entropic energy of sunlight; and claims about amino acid substitutions, which Dobzhansky (1973) indirectly linked to all energy-dependent biodiversity via Darwin’s ‘conditions of life.’ Darwin’s ‘conditions of life’ were removed by population geneticists based on their assumptions about how de Vries (1902) definition of mutation could lead to the creation of one species from another species.  Natural selection for energy-dependent codon optimality was replaced with natural selection of beneficial mutations long before experimental evidence of biologically-based cause and effect confirmed that cause and effect were energy-dependent.

See also: Study results advance ‘transposon theory of aging’

My comment: There is a model of nutrient energy-dependent viral latency, which protects organized genomes from virus-driven entropy via RNA methylation linked to learning and memory. There are models of RNA-directed DNA methylation that link energy-dependent changes in the microRNA/messenger RNA balance from RNA-mediated amino acid substitutions to cell type differentiation in all living genera.  But this is the first I have heard about a “transposon theory of aging.” I do not welcome the addition of theories that do not address the energy-dependent modification of chromatin, which these authors place into the context of gene-centric neo-Darwinian pseudoscientific nonsense.

See: Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila

Abstract conclusion: (with my emphasis)

Together, these data support the retrotransposon theory of aging, which hypothesizes that epigenetically silenced TEs become deleteriously activated as cellular defense and surveillance mechanisms break down with age. Furthermore, interventions that maintain repressive heterochromatin and preserve TE silencing may prove key to preventing damage caused by TE activation and extending healthy life span.

My comment: The difference between the retrotransposon theory of aging and the transposon theory of aging can be compared in the context of a model that links nutrient-dependent pheromone-controlled RNA-mediated cell type differentiation to healthy longevity and virus-driven energy theft to all pathology, which includes that pathology of aging.

Retrotransposon (also called transposons via RNA intermediates)

A retrovirus can be transformed into an LTR retrotransposon through inactivation or deletion of the domains that enable extracellular mobility.

See also: The Darwin Code by Greg Bear

As a fiction writer, however, I was in heaven–ancient viruses in our genes! And hardly anyone had heard of them.

My comment: Current claims about transposable element activation can be placed into the context of well established claims about energy-dependent healthy longevity and a model of human endogenous retrovirus-driven energy theft that links energy-dependent changes angstroms to ecosystems in all living genera, which is what Greg Bear did in two novels.

See the reviews in Nature:

1) Evolution rising from the grave

Bear goes a little further in suggesting that such change can occur over about a generation, an idea that might be a little too radical at the moment. However, he does mention data suggesting that fruitflies can adapt to a new environment in just a few generations of selection.

My comment: In 1999, Bear linked ecological adaptation from fruitflies to the transgenerational epigenetic inheritance of Zika virus damage that is manifested in craniofacial morphology and brain development.

2) Living with the Neanderthals

Bear does an admirable job of trying to square religious beliefs and scientific reason when functional magnetic resonance imaging is used to see what a revelation looks like. And he never takes us quite to the brink of a miracle, stating emphatically in an epilogue that he isn’t advocating special creation or God-directed evolution. In short, he reminds us that the mystic experiences that people have are neurological events as real as any other perception, and suggests that they might just be manifestations of a higher organic (as opposed to spiritual) existence.

My comment: Bear took us beyond the brink of the miracle of creation by linking the energy-dependent de novo creation of olfactory receptor genes to cell type differentiation in all living genera with an example of how viral latency must have been biophysically constrained in the new human subspecies. He probably was not trying to square religious beliefs and scientific reason. But there is no question among serious scientists that he addressed the miracle of smell and taste via the de novo creation of G protein-coupled receptors.

See: The Miracles of Smell and Taste

See for comparison: Epigenetics and Genetics of Viral Latency

  … viral latency is responsible for life-long pathogenesis and mortality risk…

My comment: Unconstrained viral latency is responsible for life-long pathogenesis and mortality risk because the de novo creation of receptors in all tissue types is biophysically constrained. Virus-driven energy theft is linked from constraint-breaking mutations to all pathology in all cell type of all living genera, which links it to mortality risk in humans.

See also for comparison: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man.

My comment: Greg Bear linked claims about energy-dependent RNA-mediated cell type differentiation from the nutrient-dependent pheromone-controlled physiology of reproduction in bacteria to the nutrient-dependent pheromone-controlled physiology of human reproduction.

A relative who is suffering from insomnia and high blood pressure recently told me he would refuse to listen to anything I said about epigenetics, viruses, or amino acid substitutions.  I was explaining what the latest research had showed to others who helped another relative with her first honey harvest.

See also: Could quality of sleep have to do with sex differences?

Excerpt:

Could there be a link between the body clock that regulates sleep and being a female or a male? Yes, according to an original study…

See also our section on molecular epigenetics and RNA-mediated sex differences in cell types, which we now know link all energy-dependent cell type differentiation in all living genera from the innate immune system to supercoiled DNA in organisms and individuals with different sleep patterns.

From Fertilization to Adult Sexual Behavior

Excerpt:

Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

The similar proteins across species that link alternative splicings of otherwise identical genes to cell type differentiation in all living genera can now be placed into the context of a special edition on science fiction. 

Greg Bear’s science fiction did not link human endogenous retroviruses to sex differences in RNA-mediated cell types, but he linked the content of our 1996 Hormones and Behavior review to every other aspect of energy-dependent cell type differentiation in all living genera. Simply put, Greg Bear started to get it right in 1985 with publication of Blood Music, and he has never stopped getting it right.

See also: Actor Steven Kearney reads excerpts from Greg Bear’s 1985 novel Blood Music. Bear was one of the first sci-fi authors to delve deep into the possibilities of synthetic biology. In this section, a biologist named Michael Bernard is infected with a killer virus that has wiped out most of North America. The virus is made up of tiny biological computers called “noocytes,” where were intended to improve the human body — giving it routine maintenance and maximizing human potential. Instead, it wiped out most of North America.

The current issue of Nature includes this review: Getting it right

Introduction: Science fiction is a difficult genre. In its most orthodox hard-SF form the writer has to get both the science and the fiction right, and very often the science bit proves tricky. So when scientists start writing, at least that is taken care of. Many researchers are keen on speculative fiction…

Science fiction novelist, Greg Bear consistently confirms that he has the facts before he puts them into the context of speculative fiction. His speculation linked viral latency to the energy-dependent ecological adaptation of a new human subspecies. But he also linked virus-driven energy theft to all pathology in Quantico.

See: Jon Stewart interviews Greg Bear

As always, Greg Bear gets it right! That’s scary, but nothing can scare away the laughter. Fortunately, at least no one is claiming that Greg Bear got it wrong.

See also: Light energy-induced base pair changes (2)

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