Should we genetically modify ourselves?
Introduction
According to the Cambridge dictionary genetic modification (GM) is “the process of changing the structure of the genes of a living thing in order to make it healthier, stronger, or more useful to humans”. Since 1973 when the first genetically modified organism (GMO) bacterium was created biotechnology has been used to manipulate a variety of organisms genes, and has been useful for medicine, scientific research and agriculture.
In 1994 the first GM crop was created to be less perishable, and since then GM has been used to make crops that are resistant to pathogens and herbicides and are better nutritionally. In 2016 26 countries planted biotech crops, and approximately 18 million farmers grew them, and benefitted due to the higher yields and lower costs associated with growing them. Golden Rice, made commercially available in 2004 after over 10 years of research was made to combat Vitamin A Deficiency (VAD). In a study published in the WHO Bulletin "Vitamin A deficiency and attributable mortality in under-5-year-olds" they found in 2005, 190 million children and 19 million pregnant women in 122 countries were affected by VAD which is responsible for 1-2 million deaths, 500,000 cases of irreversible blindness and millions of cases of xerophthalmia annually. According to the International Rice Research Institute (IRRI) Rice is the staple food for more than 3.5 billion people worldwide, around half of the world's population and it is especially important in Asia where 600 million people live in extreme poverty and rice is responsible for 30% to 70% of their calorie intake. Golden rice has potentially saved millions of people from turning blind, and while this isn’t an example of GM of humans it does show how genetic engineering has been useful for us in the past, even though people were sceptical of genetic engineering of crops due to its potential impact on humans and the environment. And there are many other examples of how GM has helped humans, like in the mass production of insulin which has been useful in controlling diabetes. Before GM, insulin had to be taken from the pancreas of slaughtered pigs and cattle which some patients were allergic to and had damaging side effects. GM ensured that insulin can be made quickly and cheaply so the 3% of the population that suffer from diabetes can have insulin readily available, that they won’t react badly to.
There is a debate which has split the scientific community over whether humans should genetically modify ourselves because of ethical issues, possible side effects and whether the potential benefits outweigh the potential disadvantages. Because of this debate, in April 2015, scientists called for a moratorium on germline gene engineering.
Gene therapy can be used as a treatment for cancer. One approach, known as CAR T-cell therapy has received approval from the U.S. Food and Drug Administration (FDA) “responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs”. Research in gene therapy for cancer is currently focused in multiple areas, including genetically engineered viruses that directly kill cancer cells, gene transfer to alter the abnormal functioning of cancer cells, and immunotherapy (including CAR T-cell therapy), which helps the immune system better find and kill tumours.
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy
Figure 1. A visual explanation for CAR T cell
A type of treatment in which a patient’s T cells (a type of lymphocyte) are taken, and changed by inserting a gene so they will bind to cancer cells and kill them. Blood from a vein in the patient’s arm flows through a tube to an apheresis machine, which removes the white blood cells, and sends the rest of the blood back to the patient. Then, the gene for a special receptor called a chimeric antigen receptor (CAR) is inserted into the T cells in the laboratory. Millions of the CAR T cells are grown in the laboratory and then given to the patient by infusion which are able to bind to an antigen on the cancer cells and kill them.
In conclusion genome therapy, which edits genes, has already been approved to be used in medicine to help people improve. Without this technology there might not be any other technology which can help cure people with problems like cancer, and if it wasn’t legal for them to use they may have died. If humans have the technology to help each other we should, so once we have perfected the technology for CRISPR/Cas9 and other forms of genetic engineeering to a level that is acceptable by regulatory agencies like the FDA with minimal side effects and a good survival rate we should.
There are many possible positives for genetic engineering. Germline Gene editing can be used as a shortcut to evolution; so we can adapt faster to problems like global warming which might otherwise take thousands of years to adapt to. Scientists have already started looking into this idea for cows, as some cows are better suited to hotter weather, cows with a lighter colour, last longer. Scientists have taken the thinking a step further for coral and have genetically engineered coral using CRISPR/Cas9 to make them better suited to the rising temperatures, which is very important after heatwaves wiped out almost a third of the Great Barrier Reefs corals in 2016. The results, published in Proceedings of the National Academy of Sciences detail that because of how coral reproduce this form of genetic engineering is hard. As corals breed only once or twice a year and they eject huge quantities of eggs and sperm into the ocean, which mix freely and fertilise each other, so it is hard to collect the embryo at the correct time for gene editing to occur when the egg and sperm have just met, but before the newly formed embryos start dividing, however it is possible. This is a positive as otherwise in More Economically Developed Countries (MEDCs) evolution will no longer occur, this is because according to Charles Darwin’s survival of the fittest theory of natural selection the fittest people in each generation survive long enough to pass on their genes to the next generation, but with medicine improving and being readily available to most people in MEDCs everyone has the opportunity to pass on their genes so there is no purge of faulty genes. This way we can become genetically more suited for the environment
Having the technology to create genetically superior humans by using human germline engineering makes it more likely children in the next generation will be genetically superior, so not only will we pass on genes to make us healthier and better suited to the environment so we can have a better quality of life; we can pass on genes that can make the next generation smarter and faster and age slower so they live longer. As is common with most scientific research tests were done on animals before being performed on humans as there genes work in the same way, but there are fewer ethical issues associated with it as we hold different standard for tests on animals and humans
Figure 2. The skin on the soles of the GM marmosets glows green under ultraviolet light. Some of the monkeys passed on the trait to their offspring. Photograph: Nature
https://www.theguardian.com/science/2009/may/27/genetically-modified-gm-monkeys-germline
Erika Sasaki and her team at the Central Institute for Experimental Animals in Kawasaki, Japan performed a study on marmoset monkeys (figure 2) where they genetically modified monkeys to glow in ultraviolet light to see if they would pass onto the next generation., added a gene to marmoset embryos that made them glow green under ultraviolet light. The embryos were transferred into surrogate females, which led to five live births.
All of the newborn monkeys carried the green gene somewhere in their bodies, and two were able to pass the gene on to their own offspring. A male GM marmoset was born using sperm from one of the monkeys and two more glowing marmosets have been born since. All the monkeys are otherwise healthy.
However, marmoset monkeys are very different to humans even though the marmoset brain is compact, too at 8 grams, making it easy to analyse. Even though the frontal lobe is more developed in marmosets and more like the human version than the frontal lobes of other animals with similarly small brains ass with all animal research we cannot be sure the same thing will happen in humans, as they are very different organisms.
This study by Erika Sasaki eat al shows that when the technology improves to when it can be used on humans it is very likely the new genes will be passed onto the next generation, potentially getting rid of diseases and creating a stronger, smarter generation.
Genetically engineering embryos may result in fewer abortions, which may have a positive psychological effect on the parents, especially the mother. A lot of research has been done to see if there is a correlation between mental health of a potential mother and whether she goes through with the pregnancy including by Priscilla Coleman (2011) of Bowling Green State University, the author of the meta-analyses published in the British Journal of Psychiatry who found women who have had an abortion have an 81% higher risk of subsequent mental health problems compared to women who have not had an abortion, and 138% higher risk of mental health problems compared to women who give birth. Coleman also found a link between women having abortions and higher rates of “anxiety, alcohol use/misuse, marijuana use, and suicidal behaviour”. This is important as with Huntington’s there is a 50% chance your child has it if you carry the defective gene, it is not morally right to tell people with the disease not to have children, and if the mother has an abortion it might affect her negatively. This way people with the disease can have healthy children, and the disease can be wiped out of our population and the population will be healthier and have a better quality of life.
Figure 3. Different Restrictions on genetic engineering of humans.
Germline Gene Editing is banned by 40 countries. One of the main problems associated with genetic engineering of humans is eugenics, there is a strong belief that people will go too far with designer babies. Once genetic engineering on embryos is allowed there is a possibility that people who have a lot of money will be able to choose what their child looks like and possible characteristics. Once a gene is found to be associated with characteristics like sports ability or IQ, parents will be able to make the ‘perfect’ child. This is often seen as a benefit of genetic engineering but as only rich people would be able to genetically engineer their children richer people having more desirable assets which would result in a very different hierarchy. Genetically engineered people would be smarter or traditionally better looking and so would be at the top of the hierarchy, and would also be richer. Eventually it could eventually lead to speciation as well as to a smaller gene pool as all parents genetically engineer their children to be the same. For example in China if the technology was available to choose the gender of your child most children would be male, which would have a huge impact on their ability to have children. In addition to that there are social trends in history for what is traditionally beautiful, in Germany in the 1930s all children would be born blonde with blue hair. This shows genetic engineering can be another tool to separate different classes of people, so genetic engineering shouldn’t happen because it could potentially worsen how some people are treated.
In addition to that it may be used for medical reasons only, but some things have been kept in our gene pool for a reason, like Asperger’s syndrome. But the parent of someone who is genetically more likely to have it may not want their child to have it for social reason, so even though they could make great discoveries the child won’t have the intellect and so it may decrease the rate at which we better ourselves as a society. Also science and medicine have previously been used against people due to prejudice in society, for example for homosexuality aversion therapy was used because it was said to be scientific. There have been articles like Beliefs about the Etiology of Homosexuality and about the Ramifications of Discovering Its Possible Genetic Origin that talk about a gene responsible for sexuality, in the future this could potentially be informed and used against people, so they are seen as abnormal and scorned more by society as we try to purge them out by the next generation.
We have disease for a reason, without illnesses and death the world would become overpopulated. This could worsen environmental issues, silently aggravating the forces behind global warming, environmental pollution, habitat loss, intensive farming practices and the consumption of finite natural resources.
There are many potential benefits for genetically engineering humans including for medical reasons, for example in China in April 2015 a team of scientists led by Junjui Huang, a gene-functioning researcher at Sun Yat-Sen University in Guangzhou published an article ""CRISPR /Cas9-mediated Gene Editing in Human Tripronuclear Zygotes" . The research published in the online journal Protein and Cell (after they were rejected by both Nature and Science due to ethical objections) details how they created the first genetically modified human embryos. Junjui Huang et al. describe how they used 86 non-viable triponuclear zygotes (where two sperms fertilise a single egg, which will start dividing like normal embryos do, but will stop growing due to the abnormal genes). Using the gene editing technique Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), specifically CRISPR associated protein-9 (Cas9) which was discovered by scientists at MIT in the 1980s as described in there paper “Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product”.
Figure 4. Process of CRISPR/Cas9
https://weekly.biotechprimer.com/the-science-of-crisprcas9/
The researchers were studying E.coli and noticed that bacteria had small blocks of palilndromic DNA repeated, with non repeated spacers of DNA between them (CRISPR) which match with pieces of DNA from viral invadors that they or their ancestors had faced. When needed the SNA contained in the spacer is converted to RNA, an enzyme and a second piece of RNA latch on, forming a structure that will bind to strands that match the spacers available. Researchers use synthetic RNA sequences to control the cutting of any DNA they choose. The cell will repair the cut, but if not done correctly it can disable the gene. This adaptive immunity found in select bacteria can be used for GM as just as the bacteria can take a piece of the pathogen and store it before the protein Cas9 makes the cut after being guided by RNA the bacteria can do the same with unwanted, and harmful DNA in human cells.
71 of the 86 zygotes survived 48 hours, to its 8 cell stage, which is long enough for the CRISPR/Cas9 and molecules to replace DNA. 54 had been genetically tested and only 28 embryos had the HBB blood gene that causes beta-thalassaemia spliced, and few of these contained the replacement genetic material.
Junjui et al reported “of target effects” and “mosaicism” where editing sometimes occurred at the wrong place in the DNA. The off target effects reported could possibly create a new disease, and a cell from a mosaic embryo could make doctors not be able to fully understand what is going on inside of the embryo. The researchers also reported that there could have been more damage than documented as they did not examine the entire genetics of the embryo.
These results show us that eliminating diseases by editing the DNA of embryos won’t happen in the near future, but there are so many genetic disorders that we could potentially stop like haemophilia, sickle-cell anemia and cystic fibrosis where we can improve the quality of life for so many. As the technology improves, and if we use viable embryos we may see very different results.
However Rudolf Jaenisch, a biology professor at MIT known for his development of the first transgenic animal, makes a valid point. Why would anyone want to edit the genes of human embryos to prevent diseases. Even in the most severe cases like Huntingtons, editing poses ethical problems because of the way genes are distributed in the embryo, only half of the embryo will inherit it. In the editing of the genes of embryos the process has to start before you know if the faulty gene was passed on, so half of the time healthy embryos will be edited and have altered DNA for no reason. So many people; like Dr Jaenisch, believe genetic engineering humans will always be wrong because “it is unacceptable to mutate normal embryos,”
As with many things o do with advancing technology there is a stigma associated with genetic engineering because of fear of the unknown, many of the people who disagree with genetic engineering of humans disagree because of the potential impacts on society. But as the technology improves stringent laws will be put into place worldwide so there are guidelines for what the technology can be used for so designer babies wont be made if that is what is agreed upon, and it will be used for medical reasons.
In conclusion I believe when we are certain that there will be very few side effects from GM of humans we should do it; this is because I believe we should do anything to make people’s quality of life easier. I agree with both the Hippocratic oath, which says “I will use treatment to help the sick according to my ability and judgment, but never with a view to injury and wrong-doing” and the Pillars of medical ethics, beneficence and non-maleficence which refers to “the idea of having the best outcome for the patient in mind at all times, particularly when all the options available have been considered” and “do no harm“ respectively. There are so many diseases with no solution, GM can help, and I believe the possible benefits outweigh the side effects once the technology has advanced further, but bans would have to be lifted first so more research can be done into it and less of a stigma is associated with GM.
References.
https://dictionary.cambridge.org/dictionary/english/genetic-modification
https://gmoanswers.com/improving-nutrition-developing-world
Humphrey, J.H.; West, K.P. Jr; Sommer, A. (1992). "Vitamin A deficiency and attributable mortality in under-5-year-olds" (PDF). WHO Bulletin
http://irri.org/our-work/research
Priscilla K. Coleman. “Abortion and mental health: quantitative synthesis and analysis of research published 1995–2009” (2011)
Y Ishino, H Shinagawa, K Makino, M Amemura, A Nakata “Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product.” Journal of Bacteriology (1987)
Ushma S. Neill “A conversation with Rudolf Jaenisch” (2015)
Liang, P., Xu, Y., Zhang, X., Ding, C., Huang, R., Zhang, Z., Lv, J., Xie, X., Chen, Y., Li, Y., Sun, Y., Bai, Y., Songyang, Z., Ma, W., Zhou, C., … Huang, J. (2015). CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & cell, 6(5), 363-372.
CRISPR/Cas9-mediated genome editing in a reef-building coral
Phillip A. Cleves, Marie E. Strader, Line K. Bay, John R. Pringle, and Mikhail V. Matz
PNAS May 15, 2018 115 (20) 5235-5240
Beliefs about the Etiology of Homosexuality and about the Ramifications of Discovering Its Possible Genetic Origin. Jane P. Sheldon, PhD, Associate Professor of Psychology, Carla A. Pfeffer, MSW, currently a graduate student, […], and Elizabeth M. Petty, MD, Associate Professor
https://www.smithsonianmag.com/smart-news/can-genetically-engineered-cows-fight-climate-change-180955821/
https://www.fda.gov/aboutfda/whatwedo/default.htm
http://www.everythingconnects.org/overpopulation-effects.html
Date Accessed – 26/10/2018 for all websites