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Genetic Engineering and Genetic Alteration of humans

Discussion in 'Physical & Life Sciences' started by Victor Medvil, Apr 2, 2020.

  1. Osmotik

    Osmotik Member

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    I want to get in to the biomedical engineering/bioengineering field, and I struggle with ethical and spiritual topics on this subject. But since you guys have already said, most Christians aren't against medicine or eating healthy. Maybe this will just be a whole new test of faith and morals. I can't help but feel that genetic enhancements will cause a whole new complication of hierarchies, availability, classism, etc.
     
  2. Ophiolite

    Ophiolite Recalcitrant Procrastinating Ape

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    Taking that thought on board, isn't it important, from your viewpoint, to have Christians at the heart of the process to contribute their ethical concerns and help to shape practices acceptable to all?
     
  3. Osmotik

    Osmotik Member

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    I'm still learning as I am newly returned to the faith, but yes I would say so.
     
  4. stevevw

    stevevw inquisitive

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    I guess it's like all other medicine such as organ transplants, operations on the heart to replace bits to make it work better, fixing broken bones, giving medicines that help the body fight disease. It all manipulates human bodies to help them when they breakdown to work better. It all depends on how knowledge and tech are used. Whether we take we know and begin to play god. Knowing human nature people will play god and that is the worry. There are usually consequences when we overstep the line into unethical territory. Playing god and changing nature has already caused problems and though there are many benefits there is a fine line between using what we know for good or bad.
     
  5. FrumiousBandersnatch

    FrumiousBandersnatch Well-Known Member

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    What would you consider to be 'playing God', and what do you feel would constitute overstepping the line into unethical territory?
     
  6. stevevw

    stevevw inquisitive

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    For one designer babies, choosing babies based on what features and traits they have instead of taking them for who they are when born. There is a difference between screening for disorders and being picky about the type of traits you want. If a baby has a disorder do we start eliminating them and if we cant do we then abort them. There are already too many reasons why people abort babies now let aloe coming up with new ones.

    The area of genetics is going to bring up many ethical dilemmas as well. I think we have been playing God for some time as far as manipulating nature. The human genome is accumulating many mutations because we have interfered with the natural evolution of living things. The more we mess with nature the more repercussions we will have in the long run.
     
  7. Kaon

    Kaon Well-Known Member

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    Good luck letting another imperfect human tweak the GENES... wow. We are destined and desperate to repeat our shameful history - warnings be damned.
     
  8. FrumiousBandersnatch

    FrumiousBandersnatch Well-Known Member

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    There's a very fuzzy border (and some disagreement) between what are disorders and what is picking the traits you want - some would say that Down's syndrome is a disorder that would be better avoided, but others say they can make a positive and different contribution to human society. Humankind is extremely lacking in genetic diversity, and we must be wary of further reducing it, except where necessary to reduce suffering.

    What mutations do you think we have accumulated "because we have interfered with the natural evolution of living things"?

    How does our interference with the evolution of other living things cause mutations in us?

    If what you say is true, mutations in humans should show an increase over time that correlates with our interference in the natural evolution of living things. What is the evidence for this?
     
  9. stevevw

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    I think there is also something in being willing to accept life as it comes. To accept that life isn't perfect. If we go down the path of trying to create a world where there are no or very little imperfections then I think we lose something of our humanity.

    Natural selection is supposed to weed out the weak and dysfunctional caused by deleterious mutations. But because humans are always coming up with ways of keeping weak and sick people alive this is negating the power of selection and therefore as time goes by humans are collecting more deleterious mutations which are having and will have a negative effect on humans fitness.

    Mutation and Human Exceptionalism: Our Future Genetic Load

    What is exceptional about humans is the recent detachment from the challenges of the natural environment and the ability to modify phenotypic traits in ways that mitigate the fitness effects of mutations, e.g., precision and personalized medicine. This results in a relaxation of selection against mildly deleterious mutations, including those magnifying the mutation rate itself. The long-term consequence of such effects is an expected genetic deterioration in the baseline human condition, potentially measurable on the timescale of a few generations in westernized societies, and because the brain is a particularly large mutational target, this is of particular concern.
    Mutation and Human Exceptionalism: Our Future Genetic Load

    Not mutations in us but has an overall effect on nature, ecosystems, and biodiversity. There are direct and indirect effects because of human behavior and interference on the environment and nature. You could make a general argument that though we have created many good things overall we are having much more of a negative impact by living a selfish lifestyle that puts humans first above all else which is more or less playing god. So much so that scientists are saying we have entered a new stage the Anthropocene era where the effects of humans are being found everywhere on earth.

    Climate Change Is Already Altering the World’s Gene Pool
    Climate Change Is Already Altering the World’s Gene Pool

    Human impact has pushed Earth into the Anthropocene, scientists say
    Human impact has pushed Earth into the Anthropocene, scientists say

    Impacts of Genetic Engineering on Biodiversity
    Impacts of Genetic Engineering on Biodiversity

    It has from what I have posted above.
     
  10. FrumiousBandersnatch

    FrumiousBandersnatch Well-Known Member

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    That paper appears to be a prospective evaluation of the possible reduction of fitness, estimated to be ~1%, from a "complete relaxation of selection" on mildly deleterious mutations. It doesn't say what has happened (although it hints that there may have been changes), but what might happen "...which will likely be realized in only the most technologically advanced of populations." Given the global travel and mixing of populations in the current century (pandemics apart!), any such effect is likely to be significantly diluted.

    You said, "The human genome is accumulating many mutations because we have interfered with the natural evolution of living things." Now you seem to be saying you meant that we're degrading the biosphere, which is something entirely different...

    What you posted above is not what you originally claimed.
     
  11. ZNP

    ZNP Well-Known Member

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    None of this matters. Unless you can tell North Korea and Iran and Russia what they can and cannot do it doesn't matter what you think is ethical. Any and all things will be done. People will abort babies based on genetics (already done to millions of babies, in China people were aborting babies because they were girls). People will try to create a master race (again, already done). People with the best intentions will cause the greatest calamity.
     
  12. Ophiolite

    Ophiolite Recalcitrant Procrastinating Ape

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    Your view is incomplete, or distorted. I struggle to find the right word. Wrong is too strong.

    Natural selection tends to do certain things. The key word there is tends. Chance can intervene, saving or sacrificing in individual cases.

    Natural selection does not weed out the "weak and dysfunctional" it tends to weed out those unfit for a specific set of environmental conditions. An inability to speak is not significant limitation in a technically modern society. If the affected individual has a brilliant mind they are likely fitter than many who are as voluble as a babbling brook.
    Put another way the specifications of fitness for a species change over time in response to environmental changes.
     
  13. stevevw

    stevevw inquisitive

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    Yet the paper says that in only a few generations there could be a deterioration in the human condition especially the brain. I think we are already seeing that with the high mental illness and suicide levels and the number of mental disorders and other brain conditions. Plus many other physical conditions.

    The point is most of these mutations have accumulated in the last few thousand years and even they have probably happened in the last 1000 years or even less. Rather than the rate slowing because of the world becoming more connected I think it will speed up the rate as most of the parts of the world who are connecting are like western industrialized nations and even more so.

    Most Mutations in the Human Genome are Recent and Probably Harmful

    Most Mutations in the Human Genome are Recent and Probably Harmful

    That is not counting things like the virus which seems to be the result of diseases that are mutating. The same with how antibiotics are causing superbugs. Though antibiotics were a way of fighting bacterial infections at the same time the saturation of artificial antibiotics is allowing bacteria to evolve into strains that become more deadly and harder to combat.

    I think the biggest impact comes room epigenetic changes which are more related to lifestyle impacts on prenatal development. So as life has become more stressful and there are more pathogens around this will affect how genes are expressed and they are usually negative outcomes.
    Epigenetics between the generations: We inherit more than just genes
    Epigenetics between the generations: We inherit more than just genes
    The Impact of Traditional Food and Lifestyle Behavior on Epigenetic Burden of Chronic Disease
    Error - Cookies Turned Off

    Humans don't live in a bubble. All life is connected and when we harm the biosphere it also affects humans.
     
  14. stevevw

    stevevw inquisitive

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    Yeah, I agree that it is subject to the environment. But what I was meaning by weak and dysfunctional can usually be seen as non-viable for humans. We need a certain level of function and strength to survive and just like some animals, those weakling offsprings are left to die or even killed as they know they cannot survive on their own. But what happens in modern society is that we have created a situation where we are saving everyone and dragging the weak and dysfunctional along. That can have an accumulating effect.

    When you consider the specific conditions apart from the obvious which may also be a disorder or disease of some sort that modern tech and medicine are allowing to stay within the gene pool we are accumulating a lot of what would be classed as mutations not conducive for the optimum state for human survival especially when seen as a whole and not just individual mutations. Add to this the Negative Epistasis effects of accumulating mutations and this can compound things by accelerating harmful mutations.
     
  15. FrumiousBandersnatch

    FrumiousBandersnatch Well-Known Member

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    What you think may have occurred with regard to health conditions means nothing unless you have some solid evidence. Consider also that improvements in the diagnosis of such health conditions has inflated the figures over the timescale you mentioned.

    If you read that article it is simply saying that a rapidly expanding population with a normal rate of mutation results in an accumulation of mutations quicker than natural selection can winnow them out. No surprises there, nothing to indicate an increased rate of mutation.

    So? Disease-causing organisms evolve - that's nothing new.

    It's possible that epigenetic changes may affect our resilience - the paper you linked treats this as hypothetical.

    Agreed... so?
     
  16. stevevw

    stevevw inquisitive

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    The paper I posted has the evidence. It is more than just talking about improvements in diagnosis or any natural level of mutation. The paper is talking about how humans are more prone to exposing themselves to harmful mutations through lifestyle such as with pollution from industrialization which has increased over the last 100 years.

    This is compounded by the more we introduce technology and medical advances that help people survive with those deleterious mutations the more we keep them floating around the gene pool. This is accelerating out demise and the paper is talking about deteriorations within generations if we keep going the way we are. These factors are a direct link to the way we live, and the negative effects increase as time goes by.

    First, few other species willingly expose themselves to environmental mutagens to the extent that humans do. Presumably, there is some room for reducing the human mutation rate by minimizing negative environmental effects, e.g., through reductions in exposure to smoke from tobacco and other sources, harmful food additives, radon gas, UV irradiation, etc.

    Second, owing to the remarkable advances in living conditions and medicine over the past century, and many more likely to come, humans uniquely modify the environment in ways that minimize the consequences of acquired genetic afflictions. Today’s ethical imperative for maximizing individual reproductive potential and longevity independent of genetic background raises significant questions about the future of the human gene pool.

    It is now known that sublethal levels of antibiotics indirectly increase the mutation rate in target bacteria by inducing the stress response (Kohanski et al. 2010; Andersson and Hughes 2014)

    But on the other hand, because of the vast majority of heritable mutations have very minor effects (below), and because we are all born with large numbers of them, they are for the most part recalcitrant to identification for their individual effects. This means that the myriad of clinical procedures for mitigating the consequences of bad genes (e.g., surgical procedures, pharmaceuticals, nutritional supplements, and physical and psychiatric therapies) can only result in the relaxation of natural selection against a broad class of deleterious mutations.


    The paper is saying this has a compounding effect which increases the rate of harmful mutations while at the same time reducing the ability for natural selection to weed out mutations. On top of this, the effects on the brain may be more acute as it is dependent on many genes and if more sensitive to harmful mutations. The paper is saying that this maybe why we are seeing an increase in mental disorders. The fact is we are seeing an increase in mental illness not because of better diagnosing and many of these are being linked back to pre and post-natal conditions such as lifestyle and pathogens.

    However, with all such alleles behaving in the same way across a large number of loci, the net effect will be a decline in fitness equal to the product of the genome-wide mutation rate and the average (now hidden) effect of mutations.
    This situation might increase in severity over time in a sort of positive feedback loop.

    And because of our enormous current effective population size (109), all replication/repair loci in the human population must already harbor defective alleles at low frequencies, so this feedback process need not await the arrival of new mutator alleles. Furthermore, as noted above, any relaxation of selection on the consequences of somatic mutations is likely to simultaneously relax selection on the germline mutation rate. It is therefore plausible that the human mutation rate is destined to slowly increase toward exceptional levels.


    Thus, without any compelling counterarguments at this time, it remains difficult to escape the conclusion that numerous physical and psychological attributes are likely to slowly deteriorate in technologically advanced societies, with notable changes in average preintervention phenotypes expected on a timescale of a few generations, i.e., 100 years, in societies where medical care is widely applied.

    In the United States, the incidences of a variety of afflictions including autism, male infertility, asthma, immune-system disorders, diabetes, etc., already exhibit increases exceeding the expected rate. Much of this change is almost certainly due to alterations in environmental factors. However, mitigating these effects by modifications in behavior and/or medical intervention will also simply exacerbate the issues noted above by relaxing selection on any underlying genetic factors.

    This observational work may substantially underestimate the mutational vulnerability of the world’s most complex organ, the human brain. Because human brain function is governed by the expression of thousands of genes, the germline mutation rate to psychological disorders may be unusually high.

    Unlike global environmental change, there is no obvious technological fix for the uniquely human goal of intentionally ameliorating the effects of mutation, nor is there a simple ethical imperative for doing otherwise, short of refocusing our ethical goals on future descendants. Unless some altered course is taken, as improved biomedical procedures continue to minimize the cumulative consequences of our genetic (and/or environmentally induced) afflictions, and the associated biomedical industries reap the financial rewards, this will come at a progressively increasing cost for individuals with the resources and/or desires to apply such solutions.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788123/

    The many disorders and diseases we are seeing now are most likely the result of increased mutations and relaxed selection which is having a negative effect on human genomes. Any attempts to elevate this through medical interventions are likely to make matters worse by relaxing selection even more. It is almost as though modern life is slowly making us go mad and killing us.

    Epigenetics seems to be implicated more and more in how new disorders and diseases are introduced.
    You said that I was first making claims about disorders and diseases existing within the human genome and that I was now making a broader claim about the deterioration of ecosystems etc. I was merely saying that they are all connected so deteriorations in ecosystems are connected to deteriorations in humans.
     
  17. FrumiousBandersnatch

    FrumiousBandersnatch Well-Known Member

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    As I said, there is no evidence there of a greater rate of mutation, only reasonable speculation that minor deleterious mutations may be accumulating faster that natural selection windows them out. This is nothing new.

    Again: You said, "The human genome is accumulating many mutations because we have interfered with the natural evolution of living things."

    I'm waiting for you to supply some evidence of this specific claim.
     
  18. stevevw

    stevevw inquisitive

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    Therefore would not that lead to an overall increase in mutations and therefore have some detrimental effect. Also what about this

    It is now known that sublethal levels of antibiotics indirectly increase the mutation rate in target bacteria by inducing the stress response (Kohanski et al. 2010; Andersson and Hughes 2014)

    Isn't this saying that the mutation rate has increased in bacteria targeted by antibiotics? If so cant this happen elsewhere by other tech and medical advances or introductions of human-made interventions that introduce mutation increases ie chemicals radiations, pathogens, etc.

    But still, this is not the point as to whether the rate of mutations is the same or not. The point is that modern lifestyle is causing the accumulation of harmful mutations. It is a lifestyle cause the same as negative effects from climate change, pollution, and genetic engineering. They are human-caused negative effects.
    This sounds a bit like a climate denier. There is an increase in temperature, increased carbon emissions cause temperature increases, humans have caused increases in carbon emissions but there is no evidence humans have caused climate change. There is an increase in mental disorders and diseases for humans, humans have increased pathogens and contagions that cause disorders and diseases but there is no evidence that it is human-caused.

    You don't have to be a scientist to know that humans have caused detrimental harm to the environment in many different ways. That we have had an increase in mental disorders and diseases. That all changes in humans/living things and the environment have effects at the genetic level. Many scientists call this the Anthropocene era a period of changes many harmful caused by humans. Do you really think none of this has changed the natural course of things and effected things at the genetic level.

    One of the greatest areas of new research and discovery is epigenetics and despite you saying there is not much evidence to the contrary there is significant support for how lifestyle and environmental influences such as pathogens and stresses or diet can change how genes are expressed. Some of this can affect germline cells which can be passed down to the next generation. It is these changes that are most relevant to how human genomes are being more and more affected by human activity.
     
    Last edited: Apr 7, 2020
  19. FrumiousBandersnatch

    FrumiousBandersnatch Well-Known Member

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    You have to be careful with the language here. Firstly, there would not be an increase in the rate of mutations (as I said before). It is plausible that mutations that would otherwise be mildly detrimental could accumulate - however, they will only accumulate if their detrimental effects are compensated for by medical intervention and/or better nutrition, standard of living, etc.; IOW if they are no longer significantly detrimental with regard to reproductive fitness because the environment has changed.

    It's true that bacteria are rapidly reproducing organisms that gain significant benefit from boosting their mutation rates under stress (by switching to less efficient DNA repair mechanisms IIRC). So, yes - if we cause stress to bacteria their mutation rates will probably increase - so we should try not to do that. But how is that relevant to mutations in humans?

    Firstly, that depends how you define 'harmful' - in evolutionary terms they are not significantly detrimental or they wouldn't accumulate.

    Secondly, the paper you quoted says that those mutations accumulate because they are no longer subject to the same selection pressures, not because the rate of mutation has increased. You have yet to give any evidence that modern lifestyle has significantly affected the mutation rate.

    Don't be silly. I'm asking you for evidence to support your claim. While you're at it, I'd like to see the evidence of a significant increase in human disorders, diseases, pathogens and contagions (allowing for better diagnostics). Last I heard, human disorders, diseases, pathogens and contagions had declined to the point that we are now suffering from novel disorders due to a lack of immune stimulation during development.

    I'm asking for evidence of an increase in mental disorders and diseases (allowing for better diagnostics).

    That's overstating it. Not all changes have effects at the genetic level.

    Sure, there is evidence of some genetic changes in living things due to human activities - I'm asking you to provide evidence that it is significantly deleterious to the human genome.

    I haven't said there isn't much evidence, I'm saying you haven't provided any, so I'm asking you to provide evidence that any such effects are significantly detrimental to the human genome, as you claimed.

    I'm asking you to support your claim with evidence because I want to see the evidence; if what you say is true, I'm surprised I haven't heard about it, and I'd like to know more.
     
  20. stevevw

    stevevw inquisitive

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    I think you will find that I wasn’t talking about the increase in mutation rate but an increase in the accumulation of mutations.
    I don’t think it is as black and white as that. Not all mutations are weeded out as a result of improved medical interventions. That was the point of the paper I linked that not all disease disorders are completely cured or eradicated and modern medicine allows more sick and disordered people to live to allow more harmful mutations to hang around. The mutations are too small for natural selection to weed out. IE

    as improved biomedical procedures continue to minimize the cumulative consequences of our genetic (and/or environmentally induced) afflictions


    Also, modern ways of life invite diseases and disorders too fast for selection to weed out.

    Furthermore, as noted above, any relaxation of selection on the consequences of somatic mutations is likely to simultaneously relax selection on the germline mutation rate.

    This is supported by the fact that disorders are increasing

    In the United States, the incidences of a variety of afflictions including autism, male infertility, asthma, immune-system disorders, diabetes, etc., already exhibit increases exceeding the expected rate.

    It's true that bacteria are rapidly reproducing organisms that gain significant benefit from boosting their mutation rates under stress (by switching to less efficient DNA repair mechanisms IIRC). So, yes - if we cause stress to bacteria their mutation rates will probably increase - so we should try not to do that. But how is that relevant to mutations in humans? [/quote] My point is not just about genetic disorders in humans, but generally, human activity is causing more infections, diseases, and disorders in humans some of which are related to being genetically modified.

    Now a recent study published in the Annals of Internal Medicine suggests far more people than previously thought are carrying variants of rare genetic diseases and could force us to redefine what is considered a healthy genome.
    Far More People Than Thought Are Carrying Rare Genetic Diseases - ExtremeTech
    Estimating Mutation Load in Human Genomes
    Millions of new variants have been discovered in human genomic datasets. Many of these, especially rare variants, have been annotated as deleterious
    Moreover a large number of deleterious mutations may also exist in the non-coding portion of the genome75, meaning that studies focusing on exomes have only studied a small portion of the mutational load that may exist in the human genome37.
    Estimating Mutation Load in Human Genomes

    Firstly, that depends on how you define 'harmful' - in evolutionary terms, they are not significantly detrimental or they wouldn't accumulate.[/quote] That is what some of the papers are saying that the mutations are only slight and not picked up by selection. But they accumulate over time and this can have a harmful effect as the more get into the gene pool.
    Secondly, the paper you quoted says that those mutations accumulate because they are no longer subject to the same selection pressures, not because the rate of mutation has increased. You have yet to give any evidence that modern lifestyle has significantly affected the mutation rate.[/quote] As mentioned above I think I was pointing out that mutations have been accumulating and therefore increasing but not increasing in the rate of speed.

    I think we have eradicated many diseases, but these have mostly been because of a lack of tech and medical abilities which are not so much about human-induced diseases and disorders. What I am talking about are human-induced diseases and disorders that come from lifestyle and there are many examples.

    The most obvious are heart disease, diabetes and obesity
    The number of American children with chronic illnesses has roughly quadrupled in the past 50 years, including an almost fourfold increase in childhood obesity in the past three decades and twice the asthma rates since the 1980s. People are more sedentary and less physically active than before, and fast food is more available. type I diabetes, "a childhood form of diabetes almost unheard of at the turn of the 20th century, is up from one in 5,000 or 10,000 to one in 250 in some regions
    Why Are Humans Always So Sick? | Live Science

    There are many more Multiple sclerosis, metabolic syndrome, malfunctions of the immune system, etc.
    Chronic and degenerative illnesses are largely new to mankind. In fact, diseases such as cancer, diabetes, fibromyalgia, and multiple sclerosis have been termed modern or man-made diseases because they were relatively rare until three hundred years or so ago.
    Modern Disease and the Rise of the Allopathic Model | Chelsea Green Publishing

    But it is also the many chronic diseases that the above diseases bring as well like cancers, liver, lung kidney-pancreas diseases, disorders associated with metabolic syndrome which can be many such as atherosclerosis and musculoskeletal diseases. Too many to name but all mostly associated with lifestyle.

    2.1 The global burden of chronic

    The burden of chronic diseases is rapidly increasing worldwide. It has been calculated that, in 2001, chronic diseases contributed approximately 60% of the 56.5 million total reported deaths in the world and approximately 46% of the global burden of disease (1). The proportion of the burden of NCDs is expected to increase to 57% by 2020. Almost half of the total chronic disease deaths are attributable to cardiovascular diseases; obesity and diabetes are also showing worrying trends, not only because they already affect a large proportion of the population, but also because they have started to appear earlier in life.
    WHO | 2. Background


    Then there are the psychological and mental disorders associated with the brain which are increasing every day.
    Mental health issues increased significantly in young adults over the last decade
    Mental health issues increased significantly in young adults over last decade: Shift may be due in part to rise of digital media, study suggests
    And developmental disorders in children that are increasing.
    Increase in Developmental Disabilities Among Children in the United States
    Increase in Developmental Disabilities Among Children in the US

    Why if the phenotypes of all living things are a representation of our genotypes and this is closely connected to the environment and what happens to it then this is going to have an effect on our bodies and minds and thus our genetic state sooner or later. As mentioned this is especially true with epigenetics. So if our environments are polluted or there are many pathogens or we are living under stress because of modern life or we destroy other species and ecosystems which deplete the overall variety of life and the health of biodiversity this will affect our genetic expression and makeup and this can be passed to future generations.

    So I have mentioned this above with epigenetics and here is some evidence.

    Epigenetics and Human Disease
    Genetic causes for human disorders are being discovered at an unprecedented pace. A growing subclass of disease-causing mutations involves changes in the epigenome or in the abundance and activity of proteins that regulate chromatin structure. This article focuses on research that has uncovered human diseases that stem from such epigenetic deregulation.

    The Barker or thrifty phenotype hypothesis, which has evolved into the fetal origins hypothesis of adult disease posits that reduced fetal nutrition is associated with an increased risk of adult disorders including coronary heart disease, stroke, diabetes, and hypertension (Guilloteau et al. 2009; Calkins and Devaskar 2011; Dyer and Rosenfeld 2011).
    Epigenetics and Human Disease

    Epigenetic influences and human diseases

    The findings from various studies clearly suggest that aberrations in the epigenome are critical factors in the initiation and progression of many diseases.
    Epigenetics of human diseases and scope in future therapeutics - ScienceDirect

    Epigenetic Inheritance of Disease and Disease Risk
    Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations.
    Epigenetic Inheritance of Disease and Disease Risk
     
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