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Category: genetics

This year marks the Eighth Review Conference (RevCon) of the Biological Toxins and Weapons Convention (BWC). At the same time, ongoing international efforts to further and more deeply investigate the brain’s complex neuronal circuitry are creating unprecedented capabilities to both understand and control neurological processes of thought, emotion, and behavior. These advances have tremendous promise for human health, but the potential for their misuse has also been noted, with most discussions centering on research and development of agents that are addressed by existing BWC and Chemical Weapons Convention (CWC) proscriptions. In this article, we discuss the dual-use possibilities fostered by employing emergent biotechnologic techniques and tools—specifically, novel gene editors like clustered regular interspaced short palindromic repeats (CRISPR)—to produce neuroweapons. Based on our analyses, we posit the strong likelihood that development of genetically modified or created neurotropic substances will advance apace with other gene-based therapeutics, and we assert that this represents a novel—and realizable—path to creating potential neuroweapons. In light of this, we propose that it will be important to re-address current categorizations of weaponizable tools and substances, so as to better inform and generate tractable policy to enable improved surveillance and governance of novel neuroweapons.

Keywords: : CRISPR, Gene editing, Neuroweapon, Neurotherapeutic pathways, Dual-use neuroscience, Biosecurity policy.

T his year marks the Eighth Review Conference (RevCon) of the Biological Toxins and Weapons Convention (BWC), the purpose of which is to ensure that the convened parties’ directives continue to be relevant to and viable for prohibiting the development, production, and stockpiling of biological weapons in the face of newly emerging scientific advancements and biotechnologies. Apropos of issues raised at previous RevCons and elsewhere, there are growing concerns about current and future weaponization of neurobiological agents and tools (ie, “neuroweapons”1–6).

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A, C57BL/6J mice were genetically engineered using CRISPR–Cas9 genomic editing to encode 288L and 330R in mDPP4 on one chromosome (heterozygous, 288/330+/−) or on both chromosomes (homozygous, 288/330+/+). b, Northern blot of mDPP4 mRNA expression. c, Immunohistochemistry (IHC) of mDPP4 protein in the lungs, brain and kidneys of individual C57BL/6J wild-type (WT), 288/330+/− and 288/330+/+ mice. d, Viral titres for MERS-CoV at 3 days post-infection from C57BL/6J WT, 288/330+/− and 288/330+/+ (all n = 4) mice infected with 5 × 105 plaque-forming units (p.f.u.) of the indicated viruses. Bar graphs show means + s.d.

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If you look up ‘scientific overachiever’ in the dictionary, you’re likely to find a two-word definition: George Church.

The American geneticist, molecular engineer, and chemist splits his time between roles as Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT. He’s also a member of the National Academy of Sciences, acts as an advisor to a plethora of cutting edge companies, and heads up synthetic biology at the Wyss Institute for Biologically Inspired Engineering, of which he’s a founding member.

Oh, and George is author to hundreds of published papers, 60 patents and a popular science book (also, theoretically, George Church may live in an alternate reality where there are more than 24 hours in a day).

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“Tim Crow must be proud to see his theory being tested at a complex level.” That’s how I tweeted the news on a recent Brain article by van den Heuvel et al (2019). Tim Crow’s theory on schizophrenia as a possible by-product of human brain evolution was quite inspiring and led to many fruitful discussions in our evolutionary psychiatry group when I was a junior trainee (which I wrote about a while ago: EPSIG Newsletter, June 2018). And here it was, the theory was tested by using novel methodology. Now I am pleased to say that the article did not disappoint, so I can enjoy the initial thrill and share my take with the Mental Elf World.

Tim Crow’s original question was intriguing: “Is schizophrenia the price that Homo sapiens pay for language?” (Crow, 1997). He argued that schizophrenia may be considered an extreme variation of brain systems which are relatively new in evolutionary timescale. Brain structures that are mostly implicated in schizophrenia were also unique to humans as mediators of language and higher cognitive functions. Those relatively new (in evolutionary timescale) brain systems may be more vulnerable to insults (e.g. stress, trauma, neurodevelopmental conditions) and manifest as dysfunctional brain circuits in schizophrenia.

The prevalence of schizophrenia is fairly constant across human populations (Jablensky et al. 1992), and the prevalence does not change despite low fecundity rates of people with schizophrenia. This can only be possible in the case of overall genetic predisposition across the population.

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Interesting research paper on a new nanobot technology. I’m watching for ways in which suitable substrates for mind uploading can be constructed, and DNA self-guided assembly has potential.

Here are some excerpts and a weblink to the paper:

“…Chemical approaches have opened synthetic routes to build dynamic materials from scratch using chemical reactions, ultimately allowing flexibility in design…”

… As a realization of this concept, we engineered a mechanism termed DASH—DNA-based Assembly and Synthesis of Hierarchical materials—providing a mesoscale approach to create dynamic materials from biomolecular building blocks using artificial metabolism. DASH was developed on the basis of nanotechnology that uses DNA as a generic material ranging from nanostructures to hydrogels, for enzymatic substrates, and as linkers between nanoparticles…”

“…Next, to illustrate the potential uses of self-generated materials, we created various hybrid functional materials from the DASH patterns. The DASH patterns served as a versatile mesoscale scaffold for a diverse range of functional nanomaterials beyond DNA, ranging from proteins to inorganic nanoparticles, such as avidin, quantum dots, and DNA-conjugated gold nanoparticles (AuNPs) (Fig. 4D, figs. S37 and S38, and Supplementary Text). The generated patterns were also rendered functional with catalytic activity when conjugated with enzymes (figs. S39 and S40 and Supplementary Text). We also showed that the DNA molecules within the DASH patterns retained the DNA’s genetic properties and that, in a cell-free fashion, the materials themselves successfully produced green fluorescent proteins (GFPs) by incorporating a reporter gene for sfGFP (Fig. 4E and figs. S9 and S41) (40). The protein production capability of the materials established the foundation for future cell-free production of proteins, including enzymes, in a spatiotemporally controlled manner.

…” Our implementation of the concept, DASH, successfully demonstrated various applications of the material. We succeeded in constructing machines from this novel dynamic biomaterial with emergent regeneration, locomotion, and racing behaviors by programming them as a series of FSAs. Bottom-up design based on bioengineering foundations without restrictions of life fundamentally allowed these active and programmable behaviors. It is not difficult to envision that the material could be integrated as a locomotive ele-ment in biomolecular machines and robots. The DASH patterns could be easily recognized by naked eyes or smartphones, which may lead to better detection technologies that are more feasible in point-of-care settings. DASH may also be used as a template for other materials, for example, to create dynamic waves of protein expression or nanoparticle assemblies. In addition, we envision that further expansion of artificial metabolism may be used for self-sustaining structural components and self-adapting substrates for chemical production pathways. Ultimately, our material may allow the construction of self-reproducing machines through the production of enzymes from generated materials that, in turn, reproduce the material. Our biomaterial powered by artificial metabolism is an important step toward the creation of “artificial” biological systems with dynamic, life-like capabilities.”…

Metabolism is a key process that makes life alive—the combination of anabolism and catabolism sustains life by a continuous flux of matter and energy. In other words, the materials comprising life are synthesized, assembled, dissipated, and decomposed autonomously in a controlled, hierarchical manner using biological processes. Although some biological approaches for creating dynamic materials have been reported, the construction of such materials by mimicking metabolism from scratch based on bioengineering has not yet been achieved. Various chemical approaches, especially dissipative assemblies, allow the construction of dynamic materials in a synthetic fashion, analogous to part of metabolism. Inspired by these approaches, here, we report a bottom-up construction of dynamic biomaterials powered by artificial metabolism, representing a combination of irreversible biosynthesis and dissipative assembly processes. An emergent locomotion behavior resembling a slime mold was programmed with this material by using an abstract design model similar to mechanical systems. Dynamic properties, such as autonomous pattern generation and continuous polarized regeneration, enabled locomotion along the designated tracks against a constant flow. Furthermore, an emergent racing behavior of two locomotive bodies was achieved by expanding the program. Other applications, including pathogen detection and hybrid nanomaterials, illustrated further potential use of this material. Dynamic biomaterials powered by artificial metabolism could provide a previously unexplored route to realize “artificial” biological systems with regenerating and self-sustaining characteristics.

Characteristic properties of life, such as dynamic self-generation of organisms, are sustained by metabolism. Using a flux of matter and energy, molecules are irreversibly synthesized from ingredients and then further dynamically assembled into macromolecules and beyond by series of biological reactions, resulting in the structural hierarchy of life’s materials (2–4). Mimicking metabolism as a material generation system may lead to the engineering of novel dynamic biomaterials with characteristic properties of life. Although various approaches have been reported to bioengineer such dynamic materials, mimicking metabolism from the ground up is still under development. For instance, engineered living materials allow material generation by life (5, 6). However, this approach relies on external living systems, such as cells, to generate the material. Similarly, other dynamic biomaterials, such as active cytoskeletons, directly use already-existing metabolism designed by life (7–10).

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https://www.youtube.com/watch?v=7N1P8qLMajM&t=1s

Scientists at Rutgers University-Newark have discovered that when a key protein needed to generate new brain cells during prenatal and early childhood development is missing, part of the brain goes haywire—causing an imbalance in its circuitry that can lead to long-term cognitive and movement behaviors characteristic of autism spectrum disorder.

“During , there is a coordinated series of events that have to occur at the right time and the right place in order to establish the appropriate number of cells with the right connections,” said Juan Pablo Zanin, Rutgers-Newark research associate and lead author on a paper published in the Journal of Neuroscience.” Each of these steps is carefully regulated and if any of these steps are not regulated correctly, this can impact behavior.”

Zanin has been working with Wilma Friedman, professor of cellular neurobiology in the Department of Biological Sciences, studying the p75NTR —needed to regulate —to determine its exact function in brain development, gain a better understanding of how this genetic mutation could cause to die off and discover whether there is a genetic link to autism or like Alzheimer’s.

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Findings from a recent research project, conducted by a Marshall University scientist and assistant professor in the Marshall University College of Science, with researchers in Texas, was recently published in the December issue of the prestigious online journal, Nature Communications.

Dr. Eugene Shakirov is studying the connection between ribosomes and telomeres in plants. Telomeres are the physical ends of chromosomes and they shorten with age in most cells. Accelerated shortening of telomeres is linked to age-related diseases and overly long telomeres are often linked to cancer.

Telomere length varies between individuals at birth and is known to predetermine cellular lifespan, but the genes establishing length variations are largely unknown. The research being done by Shakirov, along with collaborators at the University of Texas at Austin, Texas A&M University, HudsonAlpha Institute for Biology and the Kazan Federal University in Russia focused on the study of the genetic and epigenetic causes of natural telomere length variation in Arabidopsis thaliana, a small flowering plant.

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