On the eve of the U.S. National Academies of Sciences and Medicine International Summit on Human Gene Editing, Center for Genetics and Society and Friends of the Earth released a new report today, Extreme Genetic Engineering and the Human Future: Reclaiming Emerging Biotechnologies for the Common Good.
With the breakneck speed of recent developments in genetic engineering and synthetic biology that could be used to alter human DNA, the report examines health, regulatory, social and ethical questions.
The Center for Genetics and Society also released an open letter today, signed by more than 130 advocates and scholars, calling for a ban on heritable genetic modification of human beings.
“Genetic modification of children was recently the stuff of science fiction,” said lead author Pete Shanks, consulting researcher with the Center for Genetics and Society and author of "Human Genetic Engineering: A Guide for Activists, Skeptics, and the Very Perplexed." “But now, with new technology, the fantasy could become reality. Once the process begins, there will be no going back. This is a line we must not cross.”
Dana Perls, report co-author and food and technology campaigner with Friends of the Earth explains, “History has shown us that rushing new technologies to market before we understand their impacts on people, our society and our environment can result in negative unintended consequences. We have seen this with the first generation of genetically engineered crops—and the stakes are infinitely higher when it comes to the question of genetically engineering our children.”
Recent research in genetic engineering and synthetic biology has enabled scientists to artificially redesign life—everything from microbes to people. Powerful new techniques for gene editing bring the prospect of redesigning humans much closer. In April 2015, researchers from Sun Yat-sen University in China reported they had used gene editing techniques to alter human embryos for the first time in history. Those embryos were “nonviable” and could not have been used to initiate a pregnancy, but the attempt itself is a historically significant moment.
“The controversy about germline gene editing often downplays important points, including that we have other ways to avoid transmitting serious genetic diseases to future generations,” said Center for Genetics and Society Executive Director Marcy Darnovsky, PhD, who will present at the National Academies summit. “This technology will alter both human biology and human society. The scientists developing it cannot be the only ones making decisions that are so important for all of us. We need to invite discussion from thought leaders on ethics, disability rights, reproductive justice and other points of view, to inform best practices toward regulatory oversight.”
Stuart Newman, PhD, professor of cell biology and anatomy at New York Medical College, is a developmental biologist who previously filed a preemptive U.S. patent application to prevent the construction and commercialization of human-nonhuman chimeras. He shares these concerns: “Producing genetically modified human embryos is a first step toward making quasi-humans for spare parts. This will be followed by attempts to produce disease-free and other made-to-order children, with inevitable experimental errors. This is a technological move that will benefit the health of no living person, will harm some future ones and should be avoided at all cost.”
“These proposed applications raise social justice questions and put us at risk of reviving eugenics—controlled breeding to increase the occurrence of 'desirable' heritable characteristics,” said Emily Smith Beitiks, PhD, associate director of the Paul K. Longmore Institute on Disability at San Francisco State University. “Who gets to decide what diversity looks like and who is valued?”
“It is critical to not breach our scientific and moral integrity in the face of these rapid developments. Historically, research projects thought of as exciting research with no consideration for ethical or moral implications, were in fact egregious mistakes with unintended harmful consequences,” said Milton Reynolds, board chair of Literacy for Environmental Justice. “Only after the harm had been committed—witness the Tuskegee experiments on African American men and syphilis experiments on Guatemalans—was it clear to those researchers that scientific and moral integrity had been breached resulting in tragic consequences.”
The report puts human gene editing into the context of broader developments in synthetic biology. It examines the systemic and commercial incentives to rush newly discovered biotechnologies to market, regardless of their social utility and ahead of appropriate, transparent assessment and oversight.
The report calls for:
- National and international prohibitions on the use of gene editing and synthetic biology to alter human embryos or gametes for reproductive purposes. This call is especially relevant in those countries, like the U.S., that have not already enacted such a prohibition.
- Explicit and expansive public engagement on the human applications of synthetic biology, including and going beyond safety thresholds and addressing the social and ethical concerns.
- An ongoing, transparent, democratic process with which to evaluate and appropriately regulate new, emerging and proposed human applications of synthetic biology.
- Increased investment in more socially just and less risky solutions to environmental, health and social problems.
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By Ana Maldonado-Contreras
- Your gut is home to trillions of bacteria that are vital for keeping you healthy.
- Some of these microbes help to regulate the immune system.
- New research, which has not yet been peer-reviewed, shows the presence of certain bacteria in the gut may reveal which people are more vulnerable to a more severe case of COVID-19.
You may not know it, but you have an army of microbes living inside of you that are essential for fighting off threats, including the virus that causes COVID-19.
How Do Resident Bacteria Keep You Healthy?<p>Our immune defense is part of a complex biological response against harmful pathogens, such as viruses or bacteria. However, because our bodies are inhabited by trillions of mostly beneficial bacteria, virus and fungi, activation of our immune response is tightly regulated to distinguish between harmful and helpful microbes.</p><p>Our bacteria are spectacular companions diligently helping prime our immune system defenses to combat infections. A seminal study found that mice treated with antibiotics that eliminate bacteria in the gut exhibited an impaired immune response. These animals had low counts of virus-fighting white blood cells, weak antibody responses and poor production of a protein that is vital for <a href="https://doi.org/10.1073/pnas.1019378108" target="_blank">combating viral infection and modulating the immune response</a>.</p><p><a href="https://doi.org/10.1371/journal.pone.0184976" target="_blank" rel="noopener noreferrer">In another study</a>, mice were fed <em>Lactobacillus</em> bacteria, commonly used as probiotic in fermented food. These microbes reduced the severity of influenza infection. The <em>Lactobacillus</em>-treated mice did not lose weight and had only mild lung damage compared with untreated mice. Similarly, others have found that treatment of mice with <em>Lactobacillus</em> protects against different <a href="https://doi.org/10.1038/srep04638" target="_blank" rel="noopener noreferrer">subtypes of</a> <a href="https://doi.org/10.1038/s41598-017-17487-8" target="_blank" rel="noopener noreferrer">influenza</a> <a href="https://doi.org/10.1371/journal.ppat.1008072" target="_blank" rel="noopener noreferrer">virus</a> and human respiratory syncytial virus – the <a href="https://doi.org/10.1038/s41598-019-39602-7" target="_blank" rel="noopener noreferrer">major cause of viral bronchiolitis and pneumonia in children</a>.</p>
Chronic Disease and Microbes<p>Patients with chronic illnesses including Type 2 diabetes, obesity and cardiovascular disease exhibit a hyperactive immune system that fails to recognize a harmless stimulus and is linked to an altered gut microbiome.</p><p>In these chronic diseases, the gut microbiome lacks bacteria that activate <a href="https://doi.org/10.1126/science.1198469" target="_blank" rel="noopener noreferrer">immune cells</a> that block the response against harmless bacteria in our guts. Such alteration of the gut microbiome is also observed in <a href="https://doi.org/10.1073/pnas.1002601107" target="_blank" rel="noopener noreferrer">babies delivered by cesarean section</a>, individuals consuming a poor <a href="https://doi.org/10.1038/nature12820" target="_blank" rel="noopener noreferrer">diet</a> and the <a href="https://doi.org/10.1038/nature11053" target="_blank" rel="noopener noreferrer">elderly</a>.</p><p>In the U.S., 117 million individuals – about half the adult population – <a href="https://health.gov/our-work/food-nutrition/2015-2020-dietary-guidelines/guidelines/" target="_blank" rel="noopener noreferrer">suffer from Type 2 diabetes, obesity, cardiovascular disease or a combination of them</a>. That suggests that half of American adults carry a faulty microbiome army.</p><p>Research in my laboratory focuses on identifying gut bacteria that are critical for creating a balanced immune system, which fights life-threatening bacterial and viral infections, while tolerating the beneficial bacteria in and on us.</p><p>Given that diet affects the diversity of bacteria in the gut, <a href="https://www.umassmed.edu/nutrition/melody-trial-info/" target="_blank" rel="noopener noreferrer">my lab studies show how diet can be used</a> as a therapy for chronic diseases. Using different foods, people can shift their gut microbiome to one that boosts a healthy immune response.</p><p>A fraction of patients infected with SARS-CoV-2, the virus that causes COVID-19 disease, develop severe complications that require hospitalization in intensive care units. What do many of those patients have in common? <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm" target="_blank" rel="noopener noreferrer">Old age</a> and chronic diet-related diseases like obesity, Type 2 diabetes and cardiovascular disease.</p><p><a href="http://doi.org/10.1016/j.jada.2008.12.019" target="_blank" rel="noopener noreferrer">Black and Latinx people are disproportionately affected by obesity, Type 2 diabetes and cardiovascular disease</a>, all of which are linked to poor nutrition. Thus, it is not a coincidence that <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6933e1.htm" target="_blank" rel="noopener noreferrer">these groups have suffered more deaths from COVID-19</a> compared with whites. This is the case not only in the U.S. but also <a href="https://www.washingtonpost.com/world/europe/blacks-in-britain-are-four-times-as-likely-to-die-of-coronavirus-as-whites-data-show/2020/05/07/2dc76710-9067-11ea-9322-a29e75effc93_story.html" target="_blank" rel="noopener noreferrer">in Britain</a>.</p>
Discovering Microbes That Predict COVID-19 Severity<p>The COVID-19 pandemic has inspired me to shift my research and explore the role of the gut microbiome in the overly aggressive immune response against SARS-CoV-2 infection.</p><p>My colleagues and I have hypothesized that critically ill SARS-CoV-2 patients with conditions like obesity, Type 2 diabetes and cardiovascular disease exhibit an altered gut microbiome that aggravates <a href="https://theconversation.com/exercise-may-help-reduce-risk-of-deadly-covid-19-complication-ards-136922" target="_blank" rel="noopener noreferrer">acute respiratory distress syndrome</a>.</p><p>Acute respiratory distress syndrome, a life-threatening lung injury, in SARS-CoV-2 patients is thought to develop from a <a href="http://doi.org/10.1016/j.cytogfr.2020.05.003" target="_blank" rel="noopener noreferrer">fatal overreaction of the immune response</a> called a <a href="https://theconversation.com/blocking-the-deadly-cytokine-storm-is-a-vital-weapon-for-treating-covid-19-137690" target="_blank" rel="noopener noreferrer">cytokine storm</a> <a href="http://doi.org/10.1016/S2213-2600(20)30216-2" target="_blank" rel="noopener noreferrer">that causes an uncontrolled flood</a> <a href="http://doi.org/10.1016/S2213-2600(20)30216-2" target="_blank" rel="noopener noreferrer">of immune cells into the lungs</a>. In these patients, their own uncontrolled inflammatory immune response, rather than the virus itself, causes the <a href="http://doi.org/10.1007/s00134-020-05991-x" target="_blank" rel="noopener noreferrer">severe lung injury and multiorgan failures</a> that lead to death.</p><p>Several studies <a href="https://doi.org/10.1016/j.trsl.2020.08.004" target="_blank" rel="noopener noreferrer">described in one recent review</a> have identified an altered gut microbiome in patients with COVID-19. However, identification of specific bacteria within the microbiome that could predict COVID-19 severity is lacking.</p><p>To address this question, my colleagues and I recruited COVID-19 hospitalized patients with severe and moderate symptoms. We collected stool and saliva samples to determine whether bacteria within the gut and oral microbiome could predict COVID-19 severity. The identification of microbiome markers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment.</p><p><a href="https://doi.org/10.1101/2021.01.05.20249061" target="_blank" rel="noopener noreferrer">We demonstrated</a>, in a paper which has not yet been peer reviewed, that the composition of the gut microbiome is the strongest predictor of COVID-19 severity compared to patient's clinical characteristics commonly used to do so. Specifically, we identified that the presence of a bacterium in the stool – called <em>Enterococcus faecalis</em>– was a robust predictor of COVID-19 severity. Not surprisingly, <em>Enterococcus faecalis</em> has been associated with <a href="https://doi.org/10.1053/j.gastro.2011.05.035" target="_blank" rel="noopener noreferrer">chronic</a> <a href="https://doi.org/10.1016/S0002-9440(10)61172-8" target="_blank" rel="noopener noreferrer">inflammation</a>.</p><p><em>Enterococcus faecalis</em> collected from feces can be grown outside of the body in clinical laboratories. Thus, an <em>E. faecalis</em> test might be a cost-effective, rapid and relatively easy way to identify patients who are likely to require more supportive care and therapeutic interventions to improve their chances of survival.</p><p>But it is not yet clear from our research what is the contribution of the altered microbiome in the immune response to SARS-CoV-2 infection. A recent study has shown that <a href="https://doi.org/10.1101/2020.12.11.416180" target="_blank" rel="noopener noreferrer">SARS-CoV-2 infection triggers an imbalance in immune cells</a> called <a href="https://doi.org/10.1111/imr.12170" target="_blank" rel="noopener noreferrer">T regulatory cells that are critical to immune balance</a>.</p><p>Bacteria from the gut microbiome are responsible for the <a href="https://doi.org/10.7554/eLife.30916.001" target="_blank" rel="noopener noreferrer">proper activation</a> <a href="https://doi.org/10.1126/science.1198469" target="_blank" rel="noopener noreferrer">of those T-regulatory</a> <a href="https://doi.org/10.1038/nri.2016.36" target="_blank" rel="noopener noreferrer">cells</a>. Thus, researchers like me need to take repeated patient stool, saliva and blood samples over a longer time frame to learn how the altered microbiome observed in COVID-19 patients can modulate COVID-19 disease severity, perhaps by altering the development of the T-regulatory cells.</p><p>As a Latina scientist investigating interactions between diet, microbiome and immunity, I must stress the importance of better policies to improve access to healthy foods, which lead to a healthier microbiome. It is also important to design culturally sensitive dietary interventions for Black and Latinx communities. While a good-quality diet might not prevent SARS-CoV-2 infection, it can treat the underlying conditions related to its severity.</p><p><em><a href="https://theconversation.com/profiles/ana-maldonado-contreras-1152969" target="_blank">Ana Maldonado-Contreras</a> is an assistant professor of Microbiology and Physiological Systems at the University of Massachusetts Medical School.</em></p><p><em>Disclosure statement: Ana Maldonado-Contreras receives funding from The Helmsley Charitable Trust and her work has been supported by the American Gastroenterological Association. She received The Charles A. King Trust Postdoctoral Research Fellowship. She is also member of the Diversity Committee of the American Gastroenterological Association.</em></p><p><em style="">Reposted with permission from <a href="https://theconversation.com/a-healthy-microbiome-builds-a-strong-immune-system-that-could-help-defeat-covid-19-145668" target="_blank" rel="noopener noreferrer" style="">The Conversation</a>. </em></p>
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