The history is not finished… There are some questions. It is not he who applies the science of medicine to developing medical innovations. If the possible phenotypic variance of replicability is high (kmax >> kmin) replicators tend to reduce their enzymatic activity in favour of their replication rate, to the extent allowed by the trade-off between replicability and catalytic activities (which is represented by g in Eq 7 and illustrated on Fig 5). If the vaccinated group is told to lock down for a certain period and the placebo group is thrown in the fire, it would not be an effective/accurate study (just an example). The system controls parasitic damage due to the negative density dependence of the parasitic subpopulation: local metabolic efficiency decreases with the number of parasites increasing, and finally local metabolism may collapse due to the exclusion of any one of the required catalytic activities which renders the metabolic neighbourhood incomplete, the parasite thus killing local metabolism and thereby committing suicide. Egg cultures, the more common way of producing vaccines, can provoke allergic reactions; the in vitro production of RNA avoids this possibility. When the COVID protein is displayed on a cell surface, is there any danger the immune system will attack and kill that cell ? I am a master’s student (MSc. The MCRS can keep different replicator species together due to their mandatory metabolic cooperation and limited mobility on mineral surfaces, catalysing reaction steps of a coherent reaction network that produces their own monomers from externally supplied compounds. Im actually going to participate in the phase 3 trial of this vaccine tomorrow and I’m scared to death. Nat Biotech (2012) 30(12):1210-1216 A structural problem of the MCRS is even more pressing, however: maintaining a working metabolism may need many more different catalytic activities than the surface-bound metabolic system can maintain against the assortment load (the number of copies lost by selection in metabolically incomplete neighbourhoods) [42]. Thank you. Fiscal Note: Modest – between $1,000 – $5,000 Received: 10/23/20″ With the considerable progress in DNA sequencing, it has become relatively easy to determine the genome sequence of pathogens. You left a lot of strawmen in your path…, Not sure where you “fact checked” Olivias statement about gates claiming to reduce the population with vaccines. The replication/catalytic activity trade-off parameter was g = 1 in every case. its all a scam, total EVIL influence. How many cells need to take up and produce the COVID protein in order for the vaccine to be effective ? Ridiculous comment, did you even read the article? [4] Review about RNA vaccines- Schlake et al. The dynamical importance of catalytic promiscuity lies in the opportunity to increase the number of catalysed metabolic reactions without increasing the number of replicator types involved [24]. The surfaces delimit the section of the trait space that replicators can occupy in case of A = 2. SARS-CoV-2, when it develops into COVID-19 is rarely fatal in under 80’s without comorbidities. The MCRS does not survive in a mean-field (well-mixed) setting, but it has been shown to be robustly coexistent both in the ecological and the evolutionary sense in spatial (e.g., surface-bound) models [20,33,34,37]: it resists competitive exclusion within the community, as well as the invasion of parasitic sequences produced by frequent mutations. The evolved activity patterns depend on the six key parameters (system size A, catalytic trade-off b, catalytic/replicability trade-off g, replicator mobility D, metabolite diffusibility Nmet, and replicability range kmax) of the model. b, kmax and D are specified on the top and right sides of the panels, other parameters: A = 3, Nmet = 5, g = 1.0. While injection of simple RNA can elicit an immune response, RNAs in this form are prone to a rapid degradation. with e.g. Conceptualization, Its everchanging. And the possible role of mRNA vaccines in future disease prophylaxis is remarkable. Are you aware that viruses enter cells and produce their proteins by making mRNA? However, producing vaccines is a long and complex process, and it has been difficult to implement vaccines against certain pathogens. Surely some of the expired mRNA switches off its own production in some way? https://doi.org/10.1371/journal.pcbi.1008634.g004. Wikipedia has bias moderators who impose their idologies no matter hiw correct or incorrect. How do I trust such a people? This video gives a nice summary. The eco-evolutionary dynamics of the model are critically dependent on 6 of its 13 parameters (see Table 1): i) the trade-off among different enzymatic activities (b), ii) the trade-off between enzymatic activities and replicability (g) iii) replicator mobility (D), iv) the size of the metabolic neighbourhood (Nmet), v) system size (A) and vi) the attainable maximum of replicability (kmax). Fig 5). What would that outcome look like? This allows for evolving a more complex metabolic network without a prohibitively high assortment load on the MCRS. Fig 7). Whereas, The original studies published in The Lancet and The New England Journal of 32 Medicine(NEJM) initially citing harm due to hydroxychloroquine and chloroquine use were 33 retracted by said journals due to dubious research methodology and incorrect conclusions34 (7, 8, 9); and35 36 Strong catalytic trade-off (small b) also favours specialization, especially at higher replicator mobilities, because two different specialists are more efficient catalysts than two promiscuous ribozymes each with the same two activities that are strongly traded off. Simulations with the same parameter settings were repeated at least 5 times, each with different random seeds, and their results were averaged. An experimental study on ribozymes [25] suggests weak trade-offs between different catalytic activities of the same RNA sequence, which supports the idea that catalytic promiscuity may have played a role in maintaining prebiotic RNA communities, because weak catalytic trade-offs (larger b values in case of our model) help the spread of generalist replicators. One risk is, could another, 3rd virus use the cell penetration mechanism and combine with it to produce a new virus that is self replicating and makes the antigen for the 2nd? Molecular Biology and Biotechnology) from Makerere University- Uganda. Antigens are pieces of the virus you want to stop, not the RNA virus/vaccine. that 80 % of our genome are made of unknown non-coding sequences, especially made up of transoposon (LTR etc ..). Making a Flu Vaccine Without the Virus – http://news.sciencemag.org/2012/11/making-flu-vaccine-without-virus RNA replicators may disappear from their habitat for several reasons in a prebiotic environment (e.g. Neither your comment nor the the one you respond to have supporting information. Am concerned that the vaccine will protect against Covid-19 but injure the immune system making one–especially elderly–more vulnerable to other diseases such as cancer. In the past , Gates said if we make the vaccines right, we can reduce the population. This is the result of allowing unlimited campaign dollars. For such complete promiscuity to emerge the catalytic trade-off must be weak (b > 1), and the mobility of both the replicators and the metabolites may be very small–the promiscuous system is not particularly sensitive to decreasing D and Nmet. Each grid site can be empty or occupied by a single replicator. Any one of the enzymatic activities missing from the metabolic neighbourhood implies zero local metabolic help, and thus no replication. The information is now ready-to-use by the chef, who can add the ingredients in the order specified by the recipe and create a cake (the protein). What’s to prevent the mRNA from entering germline cells? membrane) connecting the previous two to the external world while providing them with individual existence. The model is a two-dimensional cellular automaton with 90 000 grid sites on a 300x300 square lattice representing prebiotic mineral surfaces to which replicators are attached. Software, Supervision, Published results with the influenza vaccine [9] showed promising protection in mice. [6] Review about the CureVac vaccine – Kallen et al., Human Vaccines and Immunotherapeutics (2013) 9(10):2263-2276 After 7 days passed the 2nd injection there were 20 “serious cases” of covid 19 – 2 in the vaccinated group; 18 in the placebo group. But is it all broken down and acetylated? That said, there have been studies to investigate adverse events following vaccination, and these indicate that genetic predisposition might play an important role. The coexistence of different sequences (physically independent but functionally connected genes/ribozymes) is a feasible solution to Eigen`s paradox [15,19–21], but without a strict functional dependence between the replicators it leads inevitably to the problem of competitive exclusion: different species of RNA molecules cannot coexist on a single common resource (the common nucleotide pool) for long. It is its initial purpose, being a transcript of the DNA, much smaller, able to each the protein making part in the cytoplasm, while being able to exit the nucleus because of its much smaller size than the DNA. Without a clear knowledge of genetıcs, being against emergency mass vaccination may cause a tragıc future. Once your paper is ready, we will email it to you. For your information, my brother was treated with chloroquine and zinc and he is currently virus free. THANK YOU. This is a goldengoose for profit when we have actual drugs or elements that remove the symptoms that are deadly. What, why, how, & possibly when (timing of vaccine) does this happen? The animal trials for coronavirus vaccine, if they didn’t die from the wild virus from disease enhancement from pathogenic priming, Some of the people who died from covid died because of the immune systems over reaction. It seems risky to rush into human trials. A potentially dynamically important but mostly neglected feature of RNA enzymes (ribozymes) is their capacity to catalyse more than a single reaction. Whereas, A proposed regimen to treat COVID-19 for Stage 1, includes 10 days of 27 hydroxychloroquine, Azithromycin, zinc, and on occasion Vitamin D (6); and 28 29 ama-assn.org Notify me of follow-up comments by email. 5. No, Is the Subject Area "Metabolites" applicable to this article? The trade-off surface for replicability k is scaled between a minimum (kmin) and a maximum (kmax) value, so that Why would we not simply boost our immune system by providing building-block nutrient minerals, viruses, bacteria, and fungus DESIGNED to protect us. The selective pressure for increasing the efficiency of a second active centre on the same sequence probably reduces the efficiency and the structural complexity of a resident catalytic site. Nature is trying to do us a favour. Fast replicating sequences are unable to outgrow and exclude slower members of the community because the fast species need the presence of the slow ones locally [20]. Writing – review & editing, Affiliations Even in such an apocalyptic scenario we’d still probably want to limit vaccination in some respects to try to ensure its safety before injecting the entire population of a country, let alone the planet. In this case, system size is A = 3 (number of catalytic activities needed for the metabolism). The flip side of intense mixing (high D) is the advantage it gives to parasites which in turn may destroy the system eventually, as explained in the next section. Yes If a neuron produced antigens on its surface, it would be killed by the immune system. Yes They are 2 different things for a political purpose. Your email address will not be published. Prebiotic ribozymes may have been of very low efficiency and specificity, but they might have had more than a single activity [25,43]. However, RNA vaccines have some distinct advantages. For example, an E2 specialist may be combined with an E1/E3 double generalist to provide a metabolically sufficient system at any location where they co-occur (see the time course of simulations on Fig 6). The third, classical generalist-dominated system (Fig 8C) consists mainly of replicators providing all the three activities with nearly the same activity level and frequencies (reddish squares in Fig 7). The scientific method is a set of procedures that scientists follow in order to gain knowledge about the world. “He litterally says with the use of new vaccines and reproductive care we could reduce the population by 10 or 15%” https://youtu.be/JaF-fq2Zn7I. High replicability is a direct fitness advantage, the most obvious feature on which efficient selection can operate [15,28]. System size (number of enzymatic activity types in the system) is A = 3 (top) and A = 5 (bottom). RNA vaccines rely on a different way to mimic infection. System size and relative catalytic promiscuity: At larger system sizes (with A = 5) the functional complementary pattern of the system becomes more complicated and it may also change more dynamically in order to maintain the metabolic complementation at all times in any persistent system. They are a combination of attenuated (weakened ) or parts of inactivated viruses mixed with an adjuvant. Moreover, these tailored, on-demand vaccines are practical – the company BioNTech claims that it could be manufactured in 5 months [12]). How are the trials setup and monitored? This may be due to the implicit constraint set by the catalytic trade-off parameter (b) on the system, even without considering the–probably rather strict–direct structural constraints of replicator length and folding. Meaning the article lays it all out as if it is predicted. 4. Ask the Brain: Why Do We Crave Sugar When We’re Stressed? science, is not a thing to believe in. Development of nucleotide vaccines based on DNA, and the related molecule RNA, is another promising area of progress in the field [4]. Based on enzymatic activities and replicability we classify different types of replicators (Fig 4): a∈(1,…A). Evolutionary Systems Research Group, ELKH Centre for Ecological Research, Tihany, Hungary, Figure 2: Disease prevention. I am in my final year (Doing research) and I would like to be trained in this field (RNA vaccine development technology) so that Uganda can also participate in this new technology. Being that this is not a natural route of things, and GMOing is kinda like a chainsaw to do a paper cut out, the process on much of this is actually quite sloppy at the micro level. Simulations demonstrate that surface-bound replicators may coexist by adopting different promiscuity patterns for a wide range of the model parameters (Fig 6). Why is that? Whereas, AMA policy H-120.988, “Patient Access to Treatments Prescribed by Their 37 Physicians,” supports a physician’s autonomy to prescribe medications the physician believes to 38 be in the patient’s best interest, where the benefits outweigh risk and the patient consents; and 39 40 The question that needs closer empirical scrutiny is how constraining these constraints really are. The danger is in how that happens. The metabolic neighbourhood of a replicator is the local area centered on its position on the surface within which all the mandatory catalytic activities have to be present so that the focal replicator be supplied by monomers for its own reproduction. So the method is not affecting the DNA but is on the side of our immune system. Coloured regions represent parts of the phenotypic trait-space which replicators are permitted to occupy by the trade-off constraints. All these observations in animals point to a potential use in humans. ELKH-ELTE Theoretical Biology and Evolutionary Research Group, Eötvös Loránd University, Budapest, Hungary, Stephen p, you said google. 41, No. No one can. The urgent technology is not a DNA vaccine. Reading articles like this and others (from the Rockefeller Foundation for example) from the past couple decades makes it clear that there was a plan in place to bring about a pandemic, with carefully laid-out “solutions” to the pandemic. RESOLVED, That our AMA rescind its joint statement with the American Pharmacists 12 Association and American Society of Health System Pharmacists, and update it with a joint 13 statement notifying patients that further studies are ongoing to clarify any potential benefit of 14 hydroxychloroquine and combination therapies for the treatment of COVID-19 (Directive to Take 15 Action); and be it further16 17 Thank you Kamul. Later, when the real pathogen is present (bottom), those cells recognize the same antigen and react rapidly and strongly against the infectious agent (secondary response). In fact there were other mRNA vaccines under development, yet none are approved? Its self inflicted chosen ignorance backed by apathy of justice when put against ego. A is the number of enzymatic activities necessary for the metabolic function (A = 3 or 5 in the simulations), and Nmet is the number of cells within the metabolic neighbourhood of replicator i. AMA-ASSN.ORG For instance, they can change the sequence of RNA to make it much easier to store. Interestingly, because of the versatility of RNA vaccines, they could be tailored to fit the antigen repertoire of each patient tumor. And ? b is a continuous parameter, b = 1 representing a linear trade-off, b > 1 standing for weak and b < 1 for strong trade-off (Fig 4). The anchoring of macromolecular replicators (as well as the temporary attachment of metabolites and monomers) to the mineral surface is the central assumption of the “prebiotic pizza” hypothesis [10,38]. [5] Introductory video about synthesis of proteins from DNA and RNA http://www.pbs.org/wgbh/nova/body/cellular-factory.html You do know it’s useless against Covid right? A feasible assumption would be that RNA replication was catalysed by other RNA molecules, and recent experimental work [9,14,41] points to the possibility of the imminent discovery of an RNA molecule capable of copying sequences at least as long as themselves with a sufficient accuracy, but we are not quite there yet. Compared to previous vaccines, this method is more robust, more versatile, and yet, equally efficient. I’ll wait to get covid and do it the natural way. mRNA are chains of nucleotides – are artificial mRNA nucleotides any different to naturally occurring ones? Its one of the most traditionally facists like mussi described it you can get. Lot of people were predicting that the body will explode or any other kind of stupidities, based on the poor technical knowledge and frusration not beeing the inventor of these new technolgies !!! I was wondering how long the mRNA persists in the cells, and continues to produce the antigen protein? My question is for how long is this mRNA produced? These variables (Ea and k) represent the phenotypes of the replicators. What would happen if the mRNA vaccine entered the nucleus of the cell and altered DNA? I agree that humans do not have immunity for the malaria however, Anopheles mosquitoes have been genetically engineered to resist Plasmodium infection which then offers protection to humans. Parasites (P) use monomers supplied by metabolism in their replication, but they do not contribute to monomer production. Well, quite not an old technology. One way that the immune system is kept in check is by co-stimulatory molecules — these are proteins on the surface of antigen presenting cells (but NOT on other cells, like cancer cells) that are required to fully activate an immune cell (more specifically, I’m referring to T cells here). Generalists with two activities (Fig 8B) occur in all the three possible activity combinations, also at high and similar densities, surrounded by a cloud of mutants, typically at average (neutral) catalytic trade-off (b) and moderate replicator (D) and metabolite mobility (Nmet). Any cooperative system may suffer from parasites–so does the MCRS. It is the ego that conflicts or causes blindspots, deadends of thought trains for the convenience of the thinker. Yippy and other non-bias search engines are out propagated and never reach much public. Funding: This research was funded by the National Research, Development and Innovation Office (NKFIH) under grant numbers K124438, K119347 (BK and TC), PD120799 (BK) and GINOP 2.3.2-15-2016-00057 (TC). Data Availability: All relevant data are within the paper and at github.com/danithered/mcrs_promisc. Think of scientists as ppl who want to replace blocks with an new color of block for purposes we need not get into. Ä°t is not the natural way for the non broken RNA to re enter into the nucleus, where cell DNA functıons.The feedback mechanısms to stop any synthesıed product, are medited by hormones,neural stımulus and product concentratıons.The cell chemistry is astonıshıngly precise.Durıng transportatıon and preservatıon, the vaccine is at very cold temperatures, but it is stored at normal frıdge temps for a few days before ınjectıon,like other vaccines and drugs.To maintain the intracellular chemical reactıons, temp must be normal body tempreture.The questıon may be: Does somethıng we artıfıcıally make provoke any faults.But, the methods, and trıals on volunteers and many control mechanisms are to observe anythıng wrong in vitro or in vivo. The physico-chemical reason for this is that for an enzyme to be an efficient catalyst it has to be a relatively long sequence folded into a compact 3D structure. Formal analysis, Obviously, fixing all replicators to the surface with extremely limited movement (i.e., assuming D = 0) is detrimental for a system consisting of specialized, single-activity ribozymes, because it produces homogeneous, unviable patches of specialists lacking metabolic complementation (see the difference in the yellow area between D = 0 and D = 5 on Fig 7). That could cause oncogenesis? A natural virus it is only produced during infection. Ooops, story is repeting iteself once again. But the features of prebiotic enzymes should not be derived from today`s extremely specialized enzymes. When the Gate’s foundation produces a “miracle” treatment of cure through the efforts of a for profit institution, the profits accrue to the foundation, which uses them to further its. Is that right? Enzymatic activities (Ea) and replicability (k) are also traded off. People should be researching treatment more then anything. What are their risks? This would be an example of convergent evolution in covid-19 and HIV, where a different evolutionary pathway is taken towards the same result. Some of these mega-billionaires are actually interested in solving world problems – but if we want to have more influence over them, we need to change the tax system to recover, or divert the tax-exempt dollars that are flowing to them… https://nonprofitquarterly.org/is-the-gates-foundation-out-of-control/.