Nina Nechama Gilshteyn, Class of 2021
Advancements in biotechnology along with sequencing the human genome have led to a cambrian explosion in the research of Gene's, genetics, and genomics. A current controversial topic pertains to the ideas of Russian geneticist Denis Rebrikov who is attempting to genetically engineer HIV resistant embryos by disabling the CCR5 gene which allows HIV to invade host cells, (3,8). Rebrikov also is attempting to test the efficiency of his genetic editing by implanting these modified embryos into HIV positive women, (3,8). Although there aren't any full proof ways to help an affected mother experience gestation without endangering her fetus, it may not be ethically sound to do this experiment at this time. Even though genetically modifying human embryos is possible, the lack of supporting evidence still endangers the fetus, therefore this experiment should be done on animal models or synthetic human tissue while affected mothers adopt or implant an embryo into a surrogate.
Human Immunodeficiency Virus (HIV) is a pathogen that can be spread through bodily fluids such as blood, saliva, and breast milk. HIV infects white blood cells such as cytotoxic T cells and macrophages with viral RNA that becomes integrated into the host genome with the help of some viral enzymes. When a significant amount of white blood cells die from this infection, the HIV is referred to acquired immunodeficiency syndrome. Some symptoms include decreased T cell count, and swollen lymph glands. There are certain drugs that improve symptoms but there is no cure (2). Infection can be prevented by using condoms, sterile needles, and surrogate mothers for planned pregnancy as blood is exchanged between the mother and fetus during pregnancy.
There usually is a fair likelihood for something to go wrong during experimentation. To minimize the risk of an unfavorable outcome, it would be better to confirm a high experimental success rate in a scientific model. Rebrikov is currently risking the chance that the genetic engineering would fail, leaving the embryo susceptible to acquiring the incurable disorder. Children typically don't have fully developed immune systems, so they acquire autoimmune deficiency syndrome more rapidly and severely, leading to a shorter life expectancy. Only 45% of the children who acquired HIV by birth in Rwanda during 1994 lived longer than 2 years (6). These children did not have access to the current treatment plans which would have resulted in a lifetime cost of $17,335 (4). If Rebrikov makes a mistake, a mother would have a sick child, emotional trauma, and a financial burden. A mother could avoid this entirely by using a surrogate and formula to birth and nurse her child, respectively. Although the genetically modified embryos are intended to protect that child, the treatment endangers the child due to uncertainty.
If a genetically modified child would be born without HIV despite developing in an affected mother, then genetically modified embryos could become more popular. This raises questions about the regulations that should be placed onto the embryonic modification industry. Should people be allowed to purchase modifications for certain features such as eye color? Surely the interactions between genes that complicate inheritance reduce the genetic malleability of such phenotypes, but this form of technology may be feasible in the near future. It might be interesting to also consider the possibility of creating a common form of genetic modification that can act as biomarkers for certain health issues. Psychiatric diseases are primarily diagnosed based on patient reported and clinician observed phenotypes, which may result in a delay of accurate diagnosis. Certain helpful biomarkers are being developed such as monitoring concentration of proteins in the CSF and looking for Gene's that are associated with a disorder, but these exams are costly and don't fully explain what is occurring in the transcriptome and/or proteome (5). It may be interesting to successful engineer embryos to express MRI or CT scan detectable neurotransmitters such as serotonin. MRI detectable serotonin could improve the accuracy of prescribing medications such as Sertraline, that increase serotonin levels in the brain (1) by comparing the relative abundance of serotonin between neurotypical individuals and psychiatric patients. Working towards embryonic genetic engineering could be used to both prevent and better diagnose diseases.
Although Rebrikov's experiment poses an unnecessary risk onto a family, certain affected mothers may want to safely experience pregnancy in their lifetime. This idea could potentially be tested on animal models until there's a 95-100% success rate. Current research for in utero HIV transmission uses mice as a model. This research relies on antibodies but it is not fully successful due to the evolving nature of HIV (7). Animals do share similarities with humans which make them a good stepping stone in research but not as a guarantee for what would happen to humans. In order to better determine the best medications for humans, researcher must past clinical trials. Stem cells and stem cell technology has been popular. It would be interesting to 3-D print a placenta and uterus using progenitor cells, and then place an experimental human lymphoid progenitor tissue within such a model. If the affermented tissue contained the same gene modification as the experimental embryo while successfully producing HIV immune lymphocytes, then Robrikov may convince regulatory committees to gain permission to experiment on humans. The use of synthesized human tissues has not yet been developed but it would be better to develop this form of testing for Robrikov, which could then lead to the development of embryos that have been genetically modified for biomarkers.
Work Cited
Human Immunodeficiency Virus (HIV) is a pathogen that can be spread through bodily fluids such as blood, saliva, and breast milk. HIV infects white blood cells such as cytotoxic T cells and macrophages with viral RNA that becomes integrated into the host genome with the help of some viral enzymes. When a significant amount of white blood cells die from this infection, the HIV is referred to acquired immunodeficiency syndrome. Some symptoms include decreased T cell count, and swollen lymph glands. There are certain drugs that improve symptoms but there is no cure (2). Infection can be prevented by using condoms, sterile needles, and surrogate mothers for planned pregnancy as blood is exchanged between the mother and fetus during pregnancy.
There usually is a fair likelihood for something to go wrong during experimentation. To minimize the risk of an unfavorable outcome, it would be better to confirm a high experimental success rate in a scientific model. Rebrikov is currently risking the chance that the genetic engineering would fail, leaving the embryo susceptible to acquiring the incurable disorder. Children typically don't have fully developed immune systems, so they acquire autoimmune deficiency syndrome more rapidly and severely, leading to a shorter life expectancy. Only 45% of the children who acquired HIV by birth in Rwanda during 1994 lived longer than 2 years (6). These children did not have access to the current treatment plans which would have resulted in a lifetime cost of $17,335 (4). If Rebrikov makes a mistake, a mother would have a sick child, emotional trauma, and a financial burden. A mother could avoid this entirely by using a surrogate and formula to birth and nurse her child, respectively. Although the genetically modified embryos are intended to protect that child, the treatment endangers the child due to uncertainty.
If a genetically modified child would be born without HIV despite developing in an affected mother, then genetically modified embryos could become more popular. This raises questions about the regulations that should be placed onto the embryonic modification industry. Should people be allowed to purchase modifications for certain features such as eye color? Surely the interactions between genes that complicate inheritance reduce the genetic malleability of such phenotypes, but this form of technology may be feasible in the near future. It might be interesting to also consider the possibility of creating a common form of genetic modification that can act as biomarkers for certain health issues. Psychiatric diseases are primarily diagnosed based on patient reported and clinician observed phenotypes, which may result in a delay of accurate diagnosis. Certain helpful biomarkers are being developed such as monitoring concentration of proteins in the CSF and looking for Gene's that are associated with a disorder, but these exams are costly and don't fully explain what is occurring in the transcriptome and/or proteome (5). It may be interesting to successful engineer embryos to express MRI or CT scan detectable neurotransmitters such as serotonin. MRI detectable serotonin could improve the accuracy of prescribing medications such as Sertraline, that increase serotonin levels in the brain (1) by comparing the relative abundance of serotonin between neurotypical individuals and psychiatric patients. Working towards embryonic genetic engineering could be used to both prevent and better diagnose diseases.
Although Rebrikov's experiment poses an unnecessary risk onto a family, certain affected mothers may want to safely experience pregnancy in their lifetime. This idea could potentially be tested on animal models until there's a 95-100% success rate. Current research for in utero HIV transmission uses mice as a model. This research relies on antibodies but it is not fully successful due to the evolving nature of HIV (7). Animals do share similarities with humans which make them a good stepping stone in research but not as a guarantee for what would happen to humans. In order to better determine the best medications for humans, researcher must past clinical trials. Stem cells and stem cell technology has been popular. It would be interesting to 3-D print a placenta and uterus using progenitor cells, and then place an experimental human lymphoid progenitor tissue within such a model. If the affermented tissue contained the same gene modification as the experimental embryo while successfully producing HIV immune lymphocytes, then Robrikov may convince regulatory committees to gain permission to experiment on humans. The use of synthesized human tissues has not yet been developed but it would be better to develop this form of testing for Robrikov, which could then lead to the development of embryos that have been genetically modified for biomarkers.
Work Cited
- Bethesda (MD), "LiverTox: Clinical and Research Information on Drug-Induced Liver Injury," National Institute of Diabetes and Digestive and Kidney Diseases. 2013.
- Center for Substance Abuse Treatment. Substance Abuse Treatment for Persons with HIV/AIDS. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2000. (Treatment Improvement Protocol (TIP) Series, No. 37.) Chapter 1-- Introduction to HIV/AIDS.
- Cyeanoski D., "Russian biologist plans more CRISPR-edited babies," Nature. 2019; 570: 145-146.
- Collins et. al, "Cost-Effectiveness of Early Infant HIV Diagnosis of HIV-Exposed Infants and Immediate Antiretroviral Therapy in HIV-Infected Children under 24 Months in Thailand," PLoS ONE. 2014; 9(3): e91004.
- Lakhan et al, "Biomarkers in psychiatry: drawbacks and potential for misuse," BioMed Central. 2010; 3:1.
- Marston et al.,"Estimating the Net Effect of HIV on Child Mortality in African Populations Affected by Generalized HIV Epidemics," JAIDS. 2005; 38(2):219-227.
- Ordonhez et al., "Maternal LAMP/p55gagHIV-1 DNA Immunization Induces In Utero Priming and a Long-Lasting Immune Response in Vaccinated Neonates" PLoS One. 2012; 7(2): e31608
- Stein, "A Russian Biologist Wants To Create More Gene-Edited Babies," NPR. 2019.
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