|Year : 2021 | Volume
| Issue : 1 | Page : 4-11
Microbes: Friends or foe? An overview on the impact of COVID-19 pandemic on human health and modern eugenics for recurrence prevention
Divyanu Jain1, Abha Sood2, Hiroyuki Takenaka3, Mitsuaki Sano4, Shuhei So5, Isao Tomita6, Naohiro Kanayama7, Ajay K Jain8
1 Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; Department of Obstetrics and Gynecology, IVF Center, Jaipur Golden Hospital, New Delhi, India
2 Department of Obstetrics and Gynecology, IVF Center, Jaipur Golden Hospital, New Delhi, India
3 Micro Algae Corporation Gifu Research Institute, Gifu, Japan
4 Tea Science Center, University of Shizuoka, Hamamatsu, Shizuoka, Japan
5 Department of Reproductive and Perinatal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
6 School of Pharmaceutical Science, University of Shizuoka; Japan Institute for the Control of Aging, Japan Zeil.Co.Ltd., Hamamatsu, Shizuoka, Japan
7 Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine; Shizuoka College of Medicalcare Science, Hamamatsu, Shizuoka, Japan
8 Department of Obstetrics and Gynecology, IVF Center, Jaipur Golden Hospital, New Delhi; IVF Center, Muzaffarnagar Medical College, Muzaffarnagar, Uttar Pradesh, India
|Date of Submission||13-Aug-2020|
|Date of Decision||01-Mar-2021|
|Date of Acceptance||11-Mar-2021|
|Date of Web Publication||30-Mar-2021|
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-Ku, Hamamatsu, Shizuoka 431-3192
Source of Support: None, Conflict of Interest: None
Microbes are an essential component of our ecosystem which have coexisted with humans and all other life forms for millions of years. These microbes have proven beneficial in our everyday life in many ways, but the recognized pathogenic forms have also proven to be dangerous to human life. The recent pandemic caused by the severe acute respiratory syndrome coronavirus 2 is evidence for the significant impact of negative human interference with the natural ecosystem which might include but is not limited to rapid urbanization, pollution, agricultural change, food consumption, and global warming. In this context, the principle of “eugenics” proposed by Sir Galton has been discussed in the current perspective. The aim of this review is to discuss the application of ethical scientific practices to promote healthy human evolution without disturbing the ecological balance. We reviewed literature relevant to the impact of microbial systems on public health including the recent COVID-19 pandemic. We suggest that the concept of “modern eugenics” should be reconsidered in ethical scientific terms by focusing on the beneficial gene(s) and eliminating harmful gene(s) of pathogenic organisms. This might contribute to the human genetic enhancement and facilitate a safe symbiotic ecosystem. In the past, scientists have successfully developed simple and safe bioassays for the identification of mutagens and carcinogens using pathogenic microorganisms. Similarly, recently developed gene therapies using viral vectors are excellent examples of the ethical and scientific application of modern eugenics for healthy human evolution. Therefore, it is necessary to establish an “International Society for Positive Science” comprising of individuals from all fields to critically analyze the positive and ethical use of science to promote and strengthen the cohabitation of all species and prevent the recurrence of future pandemics.
Keywords: COVID-19, eugenics, pandemic, pathogenic microbes, pneumonia
|How to cite this article:|
Jain D, Sood A, Takenaka H, Sano M, So S, Tomita I, Kanayama N, Jain AK. Microbes: Friends or foe? An overview on the impact of COVID-19 pandemic on human health and modern eugenics for recurrence prevention. Environ Dis 2021;6:4-11
|How to cite this URL:|
Jain D, Sood A, Takenaka H, Sano M, So S, Tomita I, Kanayama N, Jain AK. Microbes: Friends or foe? An overview on the impact of COVID-19 pandemic on human health and modern eugenics for recurrence prevention. Environ Dis [serial online] 2021 [cited 2022 Jun 25];6:4-11. Available from: http://www.environmentmed.org/text.asp?2021/6/1/4/312680
| Introduction|| |
Life originating from single-celled to multicellular life forms is a complex product of specific nucleotide sequences that determine the functionality of every organism. To date, viruses, bacteria, alga, multicellular plants, and animals have flourished mutually and maintained the ecosystem on this planet. These microbes are also an important component of the human microbiome. However, the unfortunate loss of this balance has revealed that even the smallest component of this ecosystem such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause unprecedented destruction and affect all life forms. The latest advancements in genome sequencing, bioinformatics, and high-throughput technologies have enabled rapid and exhaustive investigation of microorganisms and study their impact on human health. These technologies allow early identification of pathogens and enhance our understanding of the microbial-host interactions that further help in preventing infectious diseases and protect human health. The ethical use of these scientific advancements has significantly contributed to public health by increasing our knowledge on virulence, antibiotic resistance, transmission, mutation, and evolution., Therefore, this article aims to briefly review the sustained mutual relationship among the diverse living biota and emphasize the importance of ethical scientific practices to prevent the imbalance in this relationship for preventing the recurrence of another global health crisis like the recent COVID-19 pandemic.
| Methods|| |
A literature search performed for the present study included three databases – PubMed, EMBASE, and Google Scholar using the terms, “microbes,” “eugenics,” “pandemic,” “coronavirus,” and “public health.” The inclusion criteria were as follows: articles in the English language, all types of articles, and relevance to the topic. Articles were excluded that were not in the English language or unrelated to the research topic. Additional references were retrieved manually from the cited references.
| Viruses|| |
The genetic material of viruses can enter animals including humans and can be transferred to subsequent generations. This process of gene flow from viruses to animals highlights the significance of germline integration.
Viruses involved in human evolution
It is estimated that that in the entire human genome, sequences of human endogenous retroviruses (HERV) amount to approximately 8% of its total size,, and it is speculated that these sequences are derived from at least 504 phylogenetically different sources. In 2015, Masson and Rowe suggested that HERV infection of the germ line has played a major role in human evolution and consequently in human fertility. HERVs have been associated with the “syncytin” proteins involved in pregnancy-related processes. Bjerregaard et al. first demonstrated the presence of syncytin 1 and its receptor SLC1A5 in human gametes. Syncytin 2 has been found to have an immunosuppressive domain, which may protect the fetus against the maternal immune system. During embryo development, a number of HERVs are transcribed when the genome is first activated and some of these endogenous retroviral elements are expressed in normal tissues, as well as diseased states in later stages of development.,, Pertaining to these physiological roles, syncytin genes have been subjected to a positive selection during the course of evolution. It is observed that in conditions such as pre-eclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), intrauterine growth retardation, and gestational diabetes mellitus; the expression of placental syncytin 1 and 2 is altered.,,
Recently, a direct link between syncytin 1 and impaired response to H1N1pdm09 influenza was found in pregnant women which occurs due to suppressed maternal immunity. This may be true with other pathogens that pregnant women may be susceptible to and provide a very important diagnostic and therapeutic approach for pregnant patients during pandemics including the present COVID-19 pandemic. These studies show that viral components have remained an integral component of the living biota for billions of years and are responsible for the evolution of the human genome. Therefore, even advanced genetic engineering and gene therapy require human-friendly viral elements for appropriate scientific use.
| Bacteria|| |
Probiotics are living bacterial strains that benefit human health upon ingestion in sufficient concentrations. Species belonging to the genera Lactobacillus and Bifidobacterium provide major health benefits by boosting the immune system, improving the gastrointestinal microflora, maintaining serum cholesterol, cancer prevention, treatment of bowel diseases, and antihypertensive effect., A study reported downregulation of TNF-α and COX-2, and upregulation of potent anti-inflammatory cytokines such as interleukin-4 (IL-4), IL-6, and IL-10 in a mouse model of colitis fed with Lactobacillus plantarum 91. Numerous ongoing in vitro and in vivo studies are focused on exploring the beneficial effects of probiotics for human use.
In 1971, Ames developed a very simple cost-effective bioassay using the pathogenic microbes, Escherichia More Details coli, and Salmonella More Details typhimurium to identify the mutagenic and carcinogenic potential of environmental pollutants., Later, Kada et al. also developed a simple Rec assay to identify the mutagens and DNA damaging agents using Bacillus subtilis., Ames and Rec assays have been recognized by the scientific communities of many countries as initial screening tests to determine the mutagenic potential of new chemicals and drugs owing to their high predictive value for mutagenicity, carcinogenicity, and genotoxicity. Recently, genetically engineered S. typhimurium has been used for the detection of microscopic solid tumor masses. Bacteria such as Escherichia coli have also been used for designing diagnostics for inflammatory diseases as they can detect tetrathionate produced during inflammation. Therefore, these applications show that even highly pathogenic bacteria which are otherwise harmful can be utilized for constructive and safe scientific purposes which can benefit humans.
Several bacteria have been engineered for the targeted delivery of therapeutics in the human body. The advantage of drug delivery through bacteria is that rapid degradation of the drug can be prevented as in oral or parental route, systemic drug exposure is minimized and these bacteria can reach difficult sites such as the colon and some tumors. These bacterial therapeutics have been found useful for diseases such as inflammatory bowel disease, diabetes mellitus, human immunodeficiency virus (HIV), and cancer immunotherapy. S. typhimurium strain has been engineered for tumor suppression using toll-like receptor 5 host reaction in the tumor microenvironment upon bacterial colonization. Similarly, recombinant Listeria monocytogenes strains have been found enormously effective as tumor therapeutics.
| Algae|| |
Algae originated billions of years ago and have been existing since then. These organisms have been both harmful and useful for human beings. Several bioactive compounds such as polysaccharides, carotenoids, omega-3 polyunsaturated fatty acids, and polyphenols have been isolated and purified from microalgae. Additionally, Nostoc, Nostochopsis, Aphanothecae, Chlorella, Arthrospira (formerly Spirulina), Dunaliella, Haematococcus, and Euglena are being used as a supplement and food color. Pharmacological compounds such as immune modulators, antidiabetic, antioxidant, anti-inflammatory, anticancer, antibacterial, antivirals, and antihypercholesterolemia drugs have been isolated from microalga. However, microalgae such as Cyanobacteria, diatoms, and dinoflagellates have been found to produce hepatotoxins (microcystin and nodularin), neurotoxins (saxitoxin, anatoxin, and ß-N-methylamino-L-alanine, cytotoxins (cylindrospermopsin), and dermatoxins (aplysiatoxin and lyngbyatoxin) that may have a serious effect on human health.,
| Severe Acute Respiratory Syndrome Coronavirus 2 and the COVID-19 Pandemic|| |
Coronaviruses are not new microorganisms. They have been already classified as family Coronaviridae; subfamily Coronavirinae and order Nidovirales. The pathogenic impact of these viruses was realized in 2002 when a SARS outbreak caused by SARS-CoV, occurred in Guangdong, China. A decade later, another pathogenic coronavirus, known as the Middle East respiratory syndrome coronavirus (MERS-CoV) caused an endemic in the Middle Eastern countries. In December 2019, the Chinese city Wuhan suffered from the outbreak of another coronavirus which caused many casualties. The causal pathogen was reported to be a member of the beta group of coronaviruses. This novel virus was named Wuhan coronavirus or 2019 novel coronavirus.
Genetic differences from other coronaviruses
SARS-CoV-2 shares fewer genetic similarities to SARS-CoV (about 79%) and MERS-CoV (about 50%). The arrangement of nucleocapsid protein, envelope protein, and membrane protein among beta coronaviruses is different. Remarkable variations in SARS-CoV and SARS-CoV-2 have been reported, such as the absence of 8a protein and fluctuation in the number of amino acids in 8b and 3c protein in SARS-CoV-2. The spike glycoprotein of SARS-CoV-2 is the mixture of bat SARS-CoV and an unknown Beta-CoV. However, it has been confirmed that the SARS-CoV-2 also uses the same angiotensin-converting enzyme 2 (ACE2) cell receptor and mechanism for entry into the host cell which was being used by the earlier SARS-CoV., The single N501T mutation in SARS-CoV-2's Spike protein has further significantly enhanced its binding affinity for ACE2. To facilitate the complete entry of the pathogen into the cell following this initial process, the spike protein has to be primed by an enzyme called a protease. Similar to SARS-CoV, SARS-CoV-2 uses a protease called TMPRSS2 to complete this process., After the virus enters the host cell and uncoats, the genome is transcribed and then translated.
Modes of transmission
In addition to aerosol transmission, the virus has also been detected in the stool, gastrointestinal tract, saliva, and urine samples. Evidence supports the presence of SARS-CoV-2 even in the semen of patients who had recovered from the infection. Considering the evidence from these studies, there is a high possibility that the transmission of the SARS-CoV-2 may occur through other modes which have not been investigated yet, and the recovered patients might act as silent carriers of the pathogen or even propagate the mutated forms of this virus.
Factors affecting the severity of severe acute respiratory syndrome coronavirus 2
SARS-CoV-2 disease outcomes were observed to be more lethal in the presence of preexisting comorbidities such as hypertension and diabetes,, as well as factors such as smoking, obesity, and prolonged waiting time to hospital admission. In the majority of the severe cases, lymphopenia and sustained inflammation have been reported. Notably, these observations in COVID-19 patients were similar to those patients who suffered from SARS during the 2003 epidemic suggesting a biological mechanism behind the regional epidemiological variability.
| Potential Risk Of Pneumonia From Other Pathogens|| |
A number of pathogens including viruses, bacteria, and fungi have been identified which severely affect the human respiratory system [Figure 1]. Even after successful identification of these pathogens, outbreaks have occurred globally affecting a large portion of the human population.
|Figure 1: Infectious pathogens affecting the human respiratory system and causing global outbreaks|
Click here to view
Apart from coronavirus, there are several known bacteria and fungi that have the potential of causing severe respiratory illnesses. Extensive studies on pathogenic bacteria have indicated that Streptococcus pneumonia, Legionella pneumophila, Mycoplasma pneumonia, Chlamydophila pneumonia, Coxiella burnetii, Haemophilus influenza, and Pseudomonas aeruginosa can cause pneumonia-like symptoms in humans. Pneumocystis pneumonia has been reported in patients infected with the HIV and in patients on chronic immunosuppressive medication. The clinical symptoms of Pneumocystis pneumonia include fever, cough, subtle to acute onset of progressive dyspnea, with pleuritic chest pain which are strikingly similar to other types of pneumonia. Considering the impact of the COVID-19 pandemic, the possibility of outbreaks with these other “known” pathogenic microorganisms cannot be denied, but timely interventions might help in preventing these disasters.
| Discussion|| |
It is undeniable that different pathogens (viruses, bacteria, and fungi) may cause similar clinical manifestations of a disease with variable severity that can be partly attributed to their common genetic makeup. This is evident by the fact that SARS-CoV, MERS-CoV, and SARS-CoV-2 are all members of the same family and have evolved due to modifications in their common/original genotype resulting in these pathogenic forms. One common manifestation of these three viruses is the dormant incubation period of 4–20 days without showing any appearance of clinical symptoms in the infected patient. However, the quality of this dormant incubation period in SARS-CoV-2 is very much similar to that of HIV. This shows that a simple pathogen might have transformed into a highly infectious form by mutations or genetic recombination which is evident from the genesis of SARS-CoV-2 that caused a global pandemic. Hence, it is high time to initiate extensive collaborative studies to study these microbes and identify mechanisms that have enabled them to become infectious to this extent. The global climate and environmental conditions are variable throughout the year. The human genome is also highly diverse and every individual may not be susceptible to the same pathogen at the same time. It cannot be denied that there may be several possible mutant strains of SARS-CoV-2 that could propagate in different environmental conditions and infect the world's genetically diverse population at different periods.
“Modern eugenics,” a sustainable strategy for preventing future pandemics
In the context of the present COVID-19 pandemic, the concept of “eugenics” proposed by Francis Galton in 1883 should be reconsidered in a positive aspect. The basis of this theory is the “selection of desired heritable characteristics to improve the future generation.” In the early 19th century, this concept was exploited and involved unethical practices such as forced sterilizations, enforcing restrictions on immigration based on ethnicity, and even euthanasia for improving human heredity. In present circumstances, the basic concept of eugenics with an ethical scientific approach might be useful in avoiding future biological disasters that can be worse than the present COVID-19 pandemic. In 2003, Epstein proposed reforms in the intrinsic concept and advocated “modern eugenics” for the appropriate use of genetics and science. To be ethically permissible and scientifically effective, the modification of this concept must be limited to the identification and scientific application of useful gene(s), and elimination of harmful genes in pathogenic microorganisms with the help of advanced scientific techniques such as genetic engineering and gene therapy.
The term “eugenics” is often associated with antiethical practices targeting specific races, religions, sex, and ethnic groups. The original idea of promoting “good genes” has been confused with the term “better babies” or a means for getting rid of unwanted hereditary traits. On the contrary, if we think scientifically in terms of public health, eugenics may be considered as an infection control technique aimed at eradication of disease and promotion of good health for future generations. Eugenics might include current health measures such as quarantine/self-isolation and vaccinations, implemented for the safety of all individuals irrespective of race, sex, citizenship, or religion. These measures have helped in minimizing the spread of the deadly coronavirus and in promoting good health among susceptible/uninfected individuals. These overlapping concepts of eugenics and public health might also include some broad preventive health measures such as public and personal hygiene, diet, exercise, and lifestyle modification.
An excellent example of modern eugenics is the recent approval of the first “oncolytic virus” developed from the human herpes simplex virus 1 using intensive genetic engineering for melanoma immunotherapy. Compelling evidence is available in the form of successful clinical trials involving adeno-associated virus serotype 8 vector for the treatment of patients with severe hemophilia B., Similar examples include S. typhimurium, E. coli, and B. subtilis that are pathogenic bacteria, but scientists made them useful for humans by developing very simple and safe bioassays for the detection of mutagens and carcinogens., Another scientific application of modern eugenics may involve diagnosing and treating diseases at the gamete and embryo levels; this might be particularly helpful for families with hereditary diseases that affect the quality of life. These scientific applications of modern eugenics are ethical and unbiased, contributing to healthy human evolution. It is well evident that microbes are an integral and indispensable part of human life; they are indeed useful in various ways but simultaneously may also be harmful. It depends on our scientific aims and purposes, and how the scientific communities utilize them. Therefore, improvement of population health involves a deeper understanding of genetics and environmental interaction among different species that is necessary to enact policies related to the development and application of appropriate genetic technologies.
The advancements in molecular biology have enabled the identification of the genetic sequences of any organism, and accordingly, the same can be used or misused. If the present pathogenic harmful gene of SARS-CoV-2 could be replaced by a productive gene, e.g., hemophilia/thalassemia and is used as a carrier in a patient who is deficient in these genes, then it may act as an excellent tool for gene therapy [Figure 2]. On the other hand, if SARS-CoV-2 is hybridized with the HIV, then it might become more disastrous than its present form. To sustain life on this planet, scientists should not wait for another organism to become pathogenic and then struggle to find its cure; rather prevent the organism from becoming pathogenic for humans and make use of its beneficial properties. Scientists investigating RNA viruses particularly coronavirus have emphasized the importance of large collaborative studies for the expansion of datasets and classification of diseases in terms of severity and contagiousness. Public health policies must aim to provide guidance to the general public regarding safe and scientific applications of advanced genetic techniques. The shared scientific knowledge will not only improve health outcomes but also prevent the spread of misinformation and will create an opportunity to integrate ethical genetic services in public health policies. Identification of genetic risk factors for various infectious and noninfectious diseases and early interventions with gene therapy might help in reducing the disease burden on our community. These ethical scientific applications of modern eugenics might be possible by the establishment of an “International Society for Positive Science” with intellectuals from all fields who can bring together productive ideas for the development of diagnostics and therapeutics that facilitate human evolution and prevent future biological disasters.
|Figure 2: Modern eugenics for human genetic enhancement and prevention of future pandemics|
Click here to view
| Conclusion|| |
Evolution on this planet is evidence that positive developments take many years and destruction happens in no time. A crucial lesson from the COVID-19 pandemic is that it is time to protect modern civilization with the ethical use of science and recognize the importance of coexistence between humans and other life forms. Our aim is not only to prevent future biological disasters but also to facilitate the process of evolution without disturbing the ecological balance between species.
CRediT author statement
DJ: Conceptualization, Methodology, Writing-Original draft preparation; AS: Visualization, Writing-Original draft preparation; HT, MS, SS: Writing-Reviewing and Editing; IT, NK, and AKJ: Supervision, Writing-Reviewing, and Editing.
Financial support and sponsorship
The authors did not receive any private or public funding for the writing or publication of this manuscript.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Miller RR, Montoya V, Gardy JL, Patrick DM, Tang P. Metagenomics for pathogen detection in public health. Genome Med 2013;5:81.
Sariola S, Gilbert SF. Toward a symbiotic perspective on public health: Recognizing the ambivalence of microbes in the anthropocene. Microorganisms 2020;8:746.
Katzourakis A, Gifford RJ. Endogenous viral elements in animal genomes. PLoS Genet 2010;6:e1001191.
Belshaw R, Pereira V, Katzourakis A, Talbot G, Paces J, Burt A, et al
. Long-term reinfection of the human genome by endogenous retroviruses. Proc Natl Acad Sci U S A 2004;101:4894-9.
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al
. Initial sequencing and analysis of the human genome. Nature 2001;409:860-921.
Garazha A, Ivanova A, Suntsova M, Malakhova G, Roumiantsev S, Zhavoronkov A, et al
. New bioinformatic tool for quick identification of functionally relevant endogenous retroviral inserts in human genome. Cell Cycle 2015;14:1476-84.
Robbez-Masson L, Rowe HM. Retrotransposons shape species-specific embryonic stem cell gene expression. Retrovirology 2015;12:45.
Grandi N, Tramontano E. HERV envelope proteins: Physiological role and pathogenic potential in cancer and autoimmunity. Front Microbiol 2018;9:462.
Bjerregaard B, Lemmen JG, Petersen MR, Østrup E, Iversen LH, Almstrup K, et al
. Syncytin-1 and its receptor is present in human gametes. J Assist Reprod Genet 2014;31:533-9.
Mangeney M, Renard M, Schlecht-Louf G, Bouallaga I, Heidmann O, Letzelter C, et al
. Placental syncytins: Genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins. Proc Natl Acad Sci U S A 2007;104:20534-9.
Rawn SM, Cross JC. The evolution, regulation, and function of placenta-specific genes. Annu Rev Cell Dev Biol 2008;24:159-81.
Grow EJ, Flynn RA, Chavez SL, Bayless NL, Wossidlo M, Wesche DJ, et al
. Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells. Nature 2015;522:221-5.
Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, et al
. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 2000;403:785-9.
Menendez L, Benigno BB, McDonald JF. L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas. Mol Cancer 2004;3:12.
Maliniemi P, Vincendeau M, Mayer J, Frank O, Hahtola S, Karenko L, et al
. Expression of human endogenous retrovirus-w including syncytin-1 in cutaneous T-cell lymphoma. PLoS One 2013;8:e76281.
Mo H, Ouyang D, Xu L, Gao Q, He X. Human endogenous retroviral syncytin exerts inhibitory effect on invasive phenotype of B16F10 melanoma cells. Chin J Cancer Res 2013;25:556-64.
Esnault C, Cornelis G, Heidmann O, Heidmann T. Differential evolutionary fate of an ancestral primate endogenous retrovirus envelope gene, the EnvV syncytin, captured for a function in placentation. PLoS Genet 2013;9:e1003400.
Langbein M, Strick R, Strissel PL, Vogt N, Parsch H, Beckmann MW, et al
. Impaired cytotrophoblast cell-cell fusion is associated with reduced syncytin and increased apoptosis in patients with placental dysfunction. Mol Reprod Dev 2008;75:175-83.
Lokossou AG, Toudic C, Barbeau B. Implication of human endogenous retrovirus envelope proteins in placental functions. Viruses 2014;6:4609-27.
Soygur B, Sati L, Demir R. Altered expression of human endogenous retroviruses syncytin-1, syncytin-2 and their receptors in human normal and gestational diabetic placenta. Histol Histopathol 2016;31:1037-47.
Tolosa JM, Parsons KS, Hansbro PM, Smith R, Wark PA. The placental protein syncytin-1 impairs antiviral responses and exaggerates inflammatory responses to influenza. PLoS One 2015;10:e0118629.
Saarela M, Mogensen G, Fondén R, Mättö J, Mattila-Sandholm T. Probiotic bacteria: Safety, functional and technological properties. J Biotechnol 2000;84:197-215.
Nagpal R, Kumar A, Kumar M, Behare PV, Jain S, Yadav H. Probiotics, their health benefits and applications for developing healthier foods: A review. FEMS Microbiol Lett 2012;334:1-5.
Duary RK, Bhausaheb MA, Batish VK, Grover S. Anti-inflammatory and immunomodulatory efficacy of indigenous probiotic Lactobacillus plantarum
Lp91 in colitis mouse model. Mol Biol Rep 2012;39:4765-75.
Ames BN. The detection of chemical mutagens with enteric bacteria. In “Chemical Mutagens: Principles and Methods for Their Detection” (A. Hollaender, ed.), Plenum, New York; 1971;1:267-82.
Ames BN, Mccann J, Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res 1975;31:347-63.
Kada T. Mutagenicity and carcinogenicity screening of food additives by the rec assay and reversion procedures. IARC (International Agency Res Cancer) Sci Publ 1976;12:105-15.
Kada T, Moriya M, Shirasu Y. Screening of pesticides for DNA interactions by “rec-assay” and mutagenesis testing, and frameshift mutagens detected. Mutat Res 1974;26:243-8.
Panteli JT, Forkus BA, Van Dessel N, Forbes NS. Genetically modified bacteria as a tool to detect microscopic solid tumor masses with triggered release of a recombinant biomarker. Integr Biol (Camb) 2015;7:423-34.
Riglar DT, Giessen TW, Baym M, Kerns SJ, Niederhuber MJ, Bronson RT, et al
. Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation. Nat Biotechnol 2017;35:653-8.
Riglar DT, Silver PA. Engineering bacteria for diagnostic and therapeutic applications. Nat Rev Microbiol 2018;16:214-25.
Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, et al
. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin Gastroenterol Hepatol 2006;4:754-9.
Duan FF, Liu JH, March JC. Engineered commensal bacteria reprogram intestinal cells into glucose-responsive insulin-secreting cells for the treatment of diabetes. Diabetes 2015;64:1794-803.
Lagenaur LA, Sanders-Beer BE, Brichacek B, Pal R, Liu X, Liu Y, et al
. Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus
. Mucosal Immunol 2011;4:648-57.
Zheng JH, Nguyen VH, Jiang SN, Park SH, Tan W, Hong SH, et al
. Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium
secreting heterologous flagellin. Sci Transl Med 2017;9:eaak9537.
Gunn GR, Zubair A, Peters C, Pan ZK, Wu TC, Paterson Y. Two Listeria monocytogenes
vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16. J Immunol 2001;167:6471-9.
Barkia I, Saari N, Manning SR. Microalgae for high-value products towards human health and nutrition. Mar Drugs 2019;17:304.
Woodhouse JN, Rapadas M and Neilan BA, in In Cyanobacteria: An Economic Perspective, ed. N. K. Sharma A. K. Rai and L. J. Stal, John Wiley & Sons, Ltd, Chichester, UK, 1 edn, 2013. p. 257-68.
Roy-Lachapelle A, Solliec M, Bouchard MF, Sauvé S. Detection of cyanotoxins in algae dietary supplements. Toxins (Basel) 2017;9:76.
Zhong NS, Zheng BJ, Li YM, Poon LLM, Xie ZH, Chan KH, et al
. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003. Lancet 2003;362:1353-8.
Mohd HA, Al-Tawfiq JA, Memish ZA. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir. Virol J 2016;13:87.
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al
. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020;395:565-74.
Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 ,314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323:1239-42.
Li B, Si HR, Zhu Y, Yang XL, Anderson DE, Shi ZL, Wang LF, Zhou P. Discovery of bat coronaviruses through surveillance and probe capture-based next-generation sequencing. mSphere 2020;5:e00807-19.
Gralinski LE, Menachery VD. Return of the coronavirus: 2019-nCoV. Viruses 2020;12:135.
Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al
. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci 2020;63:457-60.
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. J Virol 2020;94:e00127-20.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al
. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.e8.
Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, et al
. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – An update on the status. Mil Med Res 2020;7:11.
Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Netw Open 2020;3:e208292.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al
. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.
Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, et al
. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev 2020;36:e3319.
Hu L, Chen S, Fu Y, Gao Z, Long H, Ren HW, et al
. Risk factors associated with clinical outcomes in 323 coronavirus disease 2019 (COVID-19) hospitalized patients in Wuhan, China. Clin Infect Dis 2020;71:2089-98.
Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J, Duhamel A, et al
. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity 2020;28:1195-9.
Feng Z, Yu Q, Yao S. et al
. Early prediction of disease progression in COVID-19 pneumonia patients with chest CT and clinical characteristics. Nat Commun 2020;11:4968.
Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, et al
. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent Sci 2020;6:315-31.
Cillóniz C, Cardozo C, García-Vidal C. Epidemiology, pathophysiology, and microbiology of community-acquired pneumonia. Ann Res Hosp 2018;2:1-1.
Sepkowitz KA. Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome. Clin Infect Dis 2002;34:1098-107.
Epstein CJ. Is modern genetics the new eugenics? Genet Med 2003;5:469-75.
Pernick MS. Eugenics and public health in American history. Am J Public Health 1997;87:1767-72.
Pol J, Kroemer G, Galluzzi L. First oncolytic virus approved for melanoma immunotherapy. Oncoimmunology 2016;5:e1115641.
Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, et al
. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 2014;371:1994-2004.
George LA, Sullivan SK, Giermasz A, Rasko JE, Samelson-Jones BJ, Ducore J, et al
. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med 2017;377:2215-27.
Jain D, Jain AK. Diagnosis and treatment of genome at the gamete and embryo levels: the probable future of major diseases. Curr Sci 2020;119:1402-3.
Husev M, Rovenchak A. On the Verge of Life: Distribution of Nucleotide Sequences in Viral RNAs. Biosemiotics 2021:1-17.
[Figure 1], [Figure 2]