CRISPR and gene editing / modification

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Introduction
CRISPR stands for clustered regularly interspaced short palindromic repeats[1]. It is a technique where a group of technologies is used to make precise edits to a DNA sequence, by making alterations to it. In other words, it is an attempt to “knockout” a gene and render it inactive or modify it. [2]. Two molecules, CAS9 protein and a short RNA molecule work together to allow the change in the DNA sequence. The RNA molecule will guide the CAS9 protein to the correct position on the DNA strand. CAS9 will then cut the DNA. The repair mechanism that regularly repairs DNA lesions then fixes the DNA strand, incorporating the required change to the structure. This repair mechanism is what allows us to make deletions, insertions, and modifications to the DNA. [3]

CRISPR Process[4]

Contents

What Came Before CRISPR

Meganucleases: The Original Editor

This is one of the most specific of the technologies and it can recognize 12-40 bp (base pairs) in a sequence, therefore, it can only handle minor variations at the recognition site. This is good because it means that off-target effects are low, on the downside, there is a limited range to choose from if we need to find the right site on the DNA to make a change. [5]

Zinc Finger Nucleases: Programmable Editing

Protein engineering is done to create a nuclease that will be programmed to target any site in the genome. Zinc finger motifs are arranged in an array to recognize longer DNA sequences, but this introduces design restriction due to the fact that an array can influence the specificity of neighbouring fingers.[6]

TALENS: Improved Resolution

Before CRISPR, TALENS (Transcription activator-like effector nucleases) was used. It consists of several TALE motifs in a combination to target a specific sequence, and compared to ZFNs, they are cheaper and produce faster results, also, they do not affect the binding of adjacent domains. However, TALENS are difficult to clone due to their large size. Scientists would have continued to use this technology if CRISPR had not been developed. In fact, CRISPR is more flexible, scalable, and more user-friendly than TALENS, hence the shift to it. Compared to previous technologies that required protein engineering, CRISPR only requires the reprogramming of the RNA molecule being used, and there is also less chance of error by using this technique. [7]

History

1987: At Osaka University, a Japanese team of scientists found a pattern of DNA sequences in a gene belonging to E. coli. It had five short repeating segments of DNA separated by short non-repeating 'spacer' DNA sequences, which are non-coding DNA sequences, it was later discovered that many microbe species had this specific sequence later in the 90’s [8]

2002: Researchers, Francisco Mojica and Ruud Jansen, were the first to refer to the sequences as CRISPR. The second set of sequences they dubbed 'Cas genes', an abbreviation for CRISPR-associated genes. The Cas genes appeared to code for enzymes that cut DNA. [9]

2005: Researchers discovered that viruses cannot infect spacer sequences in DNA, which suggested that these sequences play a role in the adaptive immune system in prokaryotes. This further led to the discovery that CRISPR-Cas systems function as a defense mechanism to prevent repeated infections by the same virus.[10]

2008: It was discovered that DNA, not RNA, is the target of the CRISPR-Cas system. [11]

2012: George Church, Jennifer Doudna, Emmanuelle Charpentier, and Feng Zhang discovered that by designing a guide RNA to target a specific region in the genome, “the CRISPR-Cas9 system can be used as a “cut-and-paste” tool to modify genomes.[12]

2013: Feng Zhang, who had previously worked on other genome editing systems such as TALENs, was the first one to successfully adapt CRISPR-Cas9 for genome editing in eukaryotic cells. Zhang and his team used Cas9 and demonstrated targeted genome cleaving in human and mouse cells. They also showed that the system could (i) be programmed to target multiple genomic loci, and (ii) could drive homology-directed repair.[13]

2016: CRISPR-CAS9 was used on human embryos for the first time by a Chinese scientist. This is discussed further on down below. [14]

2018: A landmark clinical trial using CRISPR-CAS9 gene editing successfully proved that CRISPR-CAS9 components could be infused into the bloodstream. In the trial, six people with a rare and fatal condition called transthyretin amyloidosis received a single treatment. All experienced a drop in the level of a misshapen protein associated with the disease, and those with two doses saw a drop of almost 86%. The downside is that the drug has to be taken routinely and isn’t permanent, which is something scientists are working on right now.[15]

Nobel Peace Prize in Chemistry

On October 7, 2020, Emmanuelle Charpentier and Jennifer Doudna were awarded the Nobel Peace Prize in Chemistry for the development of a method for genome editing. They developed the “molecular scissors” in genome editing, which results in precisely edited genes. They hope to one day use this to cure inherited diseases.[16]

CRISPR Companies

There are several notable firms that are researching and developing CRISPR technologies. Here we will be discussing four companies that are focused on medical solutions, but keep in mind there are plenty of other industries looking to use CRISPR to their benefit. We will discuss some of these in the later sections.

CRISPR Therapeutics

CRISPR Therapeutics Logo


One of the co-founders of CRISPR Therapeutics is Dr. Emmanuelle Charpentier, who is also a co-inventor of CRISPR. This company is working to develop CRISPR medicines and products to fight against serious diseases. In particular, the company is focusing on Sickle Cell Disease and Beta Thalassemia, which both involve blood cells. They are also working on treatments for blood cancers such as Multiple Myeloma.[17] Currently, several of their research projects are in the clinical trial phase.[18] Clinical trials are studies done to learn more about the treatment for diseases or conditions. The results of these clinical trials will then be used to determine how safe and effective the treatment is which is a big step for CRISPR’s future.



Intellia

Intellia Logo


Intellia, a leading genome editing company, was co-founded by the other co-inventor of CRISPR, Jennifer Doudna. This company is also researching how CRISPR can treat diseases. One project Intellia is pursuing is the use of CRISPR to select and edit the genes of patient immune cells to identify and attack cancer cells in hopes of improving the treatment of tumour and immune related diseases. Intellia further categorizes their therapies into In Vivo and Ex Vivo which simply mean whether CRISPR is directly used on the patient versus extracting cells and editing them before re-infusing the cells back into the patient’s body.[19] One of their current ex vivo therapies aims to treat acute myeloid leukemia, a cancer affecting the bone marrow and blood.[20]



Mammoth Biosciences

Mammoth Biosciences Logo


Mammoth Biosciences is another company co-founded by Jennifer Doudna. Mammoth biosciences continues to discover more Cas protein variations (aka tools) that can improve the existing CRISPR tool kit.[21] They also focus on diagnostics and using CRISPR to find gene sequences.[22] Their most notable project currently is their DETECTR platform. DETECTR can potentially detect whether or not a disease is present. Essentially, it’s a biological search engine. This has great potential in helping patients since CRISPR could be used to detect and address symptoms early on to mitigate and/or eliminate the effects of diseases.[23] A noteworthy application of this is how Mammoth Biosciences was able to use their technology to combat Covid-19. They received an emergency use authorization for DETECTR to assist with COVID-19 testing from the Food and Drug Administration last summer [24]. In addition, from an article by Forbes, it was highlighted that they obtained a contract with the Department of Defense to develop technologies to detect future emerging biological threats. [25]


Moderna & Metagenomi Partnership

Moderna & Metagenomi Logos


Moderna, a well known COVID-19 vaccine provider, recently signed a research partnership with CRISPR company Metagenomi. The companies will be focussing on in vivo therapies for genetic diseases with each company offering their own research expertise. Among Metagenomi’s CRISPR technologies is a discovery platform that can find new samples to be used alongside other gene editing tools. [26]





Agriculture

With agriculture, we will be looking at CRISPR as a solution to food sustainability. To explain one aspect of this problem, try to imagine a world without chocolate. This is probably difficult to think about, but it’s very likely that without innovation we could lose the cacao plant. Currently, cacao is susceptible to pathogens making it at risk of disappearing. This, among many other problems, is what CRISPR studies are looking to solve.

Current Issues

Selective Breeding vs Genetic Modification[27]

The global population is expected to reach 10 billion by 2050.[28] Along with that, global temperatures are expected to rise 2 degrees Celsius by 2050.[29] These factors together will both impact our world’s food supply. With more people, there will be more mouths to feed and climate change will reduce the available land for farming. An example of climate change’s effects is that temperatures will be warmer which thereby affects the moisture levels of land and potentially increasing the life cycles of natural pests. Many plants require specific conditions to grow and these changes will therefore impact various crops. They are also at risk of pathogens or diseases as well as natural pests. In addition, food waste is also a problem our society faces. There's a lot of produce that is discarded simply because they have imperfections from slight bruising during transport to being off colour. Methods to avoid these imperfections could then be used to reduce our food waste

How CRISPR Can Help

CRISPR definitely appears to be something amazingly innovative when it comes to agriculture, however gene editing with crops is something humans have done for thousands of years. Selective breeding is the process of selecting two parent plants with desirable traits and breeding them in order to achieve offspring plants that have those traits.[30] For example, cabbage, broccoli, cauliflower, brussel sprouts, and kale are all variations that came from a plant known as the wild cabbage.


Selective breeding takes a long time and this is where CRISPR can come in. CRISPR is basically a quicker and easier way to selectively breed. Often with selective breeding, you first have to find a plant with the trait you’re looking for. This requires luck and can be both time consuming and difficult. Rather than going through the trouble of the entire selective breeding process, all that needs to be done with CRISPR is to edit the plant directly which saves time and is more efficient compared to the traditional process. In addition, CRISPR can be used to edit plant genes in order for them to have better nutrients, higher yield, better resistance against pests, and could even potentially edit out allergenic genes. Not everyone’s going to be a fan of this but, there are also CRISPR studies being conducted to reduce the amount of caffeine in coffee beans.

Genetic Modification vs Gene Editing

One common misconception in regards to gene editing is that it’s the same as GMOs. People tend to have a negative bias associated with GMO’s because they’re ‘not natural’ and that same bias carries onto gene editing. However, GMOs and Gene Editing aren’t exactly the same. They are similar in that they both result in the alteration of an organism, but there are some notable differences.
GMO vs Gene Editing[31]

The main difference between these two methods is that Genetic modification is broader and includes the alteration that people are often wary of, that is introducing foreign genes, whether it is created synthetically or taken from a different species, and infusing it into an organism. Comparatively, CRISPR processes are used to alter or cut DNA within the organism. CRISPR alterations are also changes that could have occurred in nature. [32] Sanushka Naidoo, an associate professor in the Department of Biochemistry, Genetics and Microbiology at the University of Pretoria, describes some of her research in a Ted Talk how when looking at the effects of pathogens on pine trees, some species are more resilient against disease because there is a specific gene activated in their genome.[33] In simplistic terms, CRISPR editing could be taking the nonresilient pine tree and editing their gene so that the specific gene that can protect them from pathogens is turned “on”. Meanwhile, since GMOs can involve synthetic genes, these types of alterations would not be naturally occurring.

List of Potential CRISPR Crops

Below is an incomplete list that captures some of the crops that are being studied for CRISPR editing. Since there are so many crops to discuss, our group chose to talk about four of them: the tomato, cacao, wheat, and canola plants.
List of CRISPR Crops[34]

Tomato

As of October 2021, the tomato became the first crispr edited food released for sale.[35] The Sicilian Rouge High GABA tomato was released in Japan The gene-edited seeds were manufactured by Sanatech Seed and distributed to the public by the company. Over 4,200 farmers purchased these seeds to grow as well. Without going too deep into the biology, the tomatoes were genetically edited to potentially have a calming effect on the body, and could reduce high blood pressure.

Cacao

Cacao plants are weak to pathogens which results in significant losses for farmers. Scientists are looking to use CRISPR to target a gene that suppresses the defense response and to edit this gene so the cacao plant can respond.[36] According to a 2018 study, the edited cacao tissue had increased resistance against a pathogen that cacao can encounter.[37]

Wheat

Studies are being conducted to reduce the amount of gluten content in the grains. Researchers from a dutch university in particular are looking to remove parts within gluten that the immune system reacts to.[38] Another group is looking at editing wheat so that it’s safe for people with gluten allergies to consume but still retain some gluten-like quality so that the wheat can still be used in baking.[39] I also want to note that for a plant, wheat is very complex so it might be a while before we see any results.

Canola

Yield 10 Bioscience is a company that worked on creating CRISPR edited versions of canola plants. They edited this trait known as C3007 and the edit is designed to increase the oil content in canola .[40] The company is also looking into editing these plants to increase their seed yield.

Meet Dolly the Sheep

Dolly the Sheep

Dolly was part of a series of experiments at The Roslin Institute. The research team consisted of scientists, embryologists, surgeons, vets and farm staff, all of whom were Led by Sir Ian Wilmut. The goal was to develop a method for producing genetically modified livestock, and to see Whether a specialized cell, such as skin or brain cell, could be used to make a whole new animal.

Dolly was cloned from the mammary gland of a 6-year-old Finn Dorset sheep and an egg cell taken from a Scottish Blackface sheep. Her white face showed she was a clone, because if she had been genetically related to her surrogate mother, she would have had a black face. She was important because even though other sheep had been cloned before her, she was the first mammal made from an adult cell, which no one thought was possible. Fun fact: she was named after country singer Dolly Parton [41]

Dolly’s Life

February 5, 1996 – Dolly was born

February 22, 1997 - Her existence was announced to the world at the same time as the release of the scientific papers

1997 – Her telomeres were discovered to be shorter than a normal sheep of that age. It was later found that since her DNA was from that of an adult sheep, the telomeres might not have been renewed at development. (Telomeres are at the end of DNA molecules and protect it from damage; they become shorter as a being ages) There were also no signs of premature or accelerated aging.

April 1998 – She gave birth to Bonnie

1999 – She gave birth to twins: Sally and Rosie

2000 – She gave birth to triplets Darcy, Cotton, and lucy - She was infected with a virus called JSRV (Jaagsiekte Sheep Retrovirus) along with the other sheep at the Roslin Institute - She later recovered

2001 – Dolly developed arthritis but fully recovered; no explanation was found on how she recovered, despite extensive experimenting and research

2003 – She developed a cough, which showed to be tumours growing in her lungs. She was euthanized at the age of 6

The Roslin Institute donated her body to the National Museum of Scotland, where she is one of the most popular exhibits.[42]

Risks

There are several factors that pose a risk to further adoption of CRISPR agricultural technologies. First, existing strict regulation will continue to be a barrier to develop and test CRISPR related crops. However, as we will discuss later, eastern countries such as Russia and China already have more relaxed regulations to promote more innovation within gene editing. This is also demonstrated by the tomato that Japan allowed for release. Although regulation is still strict in western countries, recently the UK government has decided to relax its regulation in regards to gene edited crops by potentially eliminating the need for a license to run testing trials.[43] They also plan on separating Gene edited regulations versus GMO regulations which are known to be stricter. Adoption of CRISPR edited plants also remains a risk since it is difficult to advocate for these crops since public opinion regards gene editing as an unnatural process.[44] Further societal factors will need to be considered until we see more CRISPR foods in the market. Lastly, with gene editing there is always the risk of unknown mutations occurring. Until this notable risk is dealt with, uncertainty will continue to follow CRISPR.

Health Care

The possibilities are endless with CRISPR in the healthcare industry. It can eradicate diseases such as mosquito-borne diseases and incurable cancer. This could potentially save humans from long-term suffering and prevent certain human conditions. However, the use of CRISPR can be controversial like the experiment with the baby twins’ embryos that a Chinese researcher attempted to prevent HIV. [45] We will discuss some real-life examples that have occurred with the CRISPR technologies and some potential issues.

Mosquito-borne Diseases

Mosquito-borne diseases like Malaria and Dengue are transmitted to humans through infected mosquitoes that carry parasites. Malaria is the biggest mosquito-borne disease with over 229 million cases worldwide according to the World’s Health Organization in 2019, and 97% of these cases are found in Africa.[46] Dengue fever saw an 800% increase in cases over the last two decades from 2000 to 2019.[47]

How Gene Drive Works [48]

Not all mosquitoes can carry diseases - only three specific types are disease-transmitting:[49]

  • Aedes aegypti - spreads Zika, yellow fever, and dengue fever; originated in Africa
  • Aedes albopictus - spreads yellow fever and dengue fever and West Nile virus; originated in Southeast Asia
  • Anopheles gambiae - the species is one of the most efficient transmitters for the spread of malaria and dengue.

Additionally, only females are capable of transmitting these diseases due to the fact that they need to feed on human blood to produce eggs.[49]

Researchers are genetically modifying mosquitoes using CRISPR by adding a protein in male mosquitoes to kill off female mosquitoes before they reach a biting age. [50]Another method is to alter the female's mouth so they resemble the males, prohibiting them from being able to extract blood from humans.[51] Lastly, some researchers are using CRISPR to knock out the FREP1 protein that allows parasites to reside (and survive) inside the female mosquitoes. [52]The only issue is that modified traits typically pass on to only half of the offspring and start to dilute. Researchers are using “gene drive” to ensure that all offspring and its offsprings will inherit the modifications. [53]As more and more mosquitoes inherit these modifications, females will become sterile as they die before they mature or cannot produce eggs as they cannot bite for blood.

These disease-spreading mosquitoes mainly live in tropical and subtropical regions. With global warming, a lot of regions are warmer than usual which means these species are spreading further. It is estimated that Aedes aegypti mosquitoes are invading the southern United States at a rate of 37 miles (59.5km) per year.[54] In 2020, the US Environmental Protection Agency (EPA) approved the release of up to 750 million of these insects in Florida by a British biotechnology company, Oxitec. In May 2021, 12000 genetically engineered male Aedes aegypti mosquito eggs, known as the OX5034, were released. Oxitec focuses on altering the male mosquitoes “to carry a gene that makes their female progeny depend on the antibiotic tetracycline-and thus fated to die in the wild… [F]emale numbers [will be] depleted, and the population is suppressed”.[54] Oxitec has already done trials in Brazil, Cayman Island, Malaysia and Panama where they saw over 90% reduction in the Aedes aegypti population.[54] From 2009 and 2010, they released 3 million of these modified mosquitoes in Cayman Island and saw a 96% population reduction.[55] This technology will ultimately eradicate these transmissions by limiting the disease-transmitting species.

Despite eradicating diseases sound like a good thing - Florida citizens were not happy to be treated as guinea pigs. They held a petition on change.org to oppose the genetically modified mosquitoes as they believe it affects the ecosystem. [56] Oxitect argues that they only target 1 out of 3000 species and will not cause any environmental impact.[54] However, there is not enough data to demonstrate whether these genetically modified species have any mutation impact on the species that consume them.

Cancer

Cancer is known to be aggressive and cancerous cells can invade multiple organs by multiplying at a rapid rate. With the new CRISPR technology, researchers are finding new ways to make cancer treatments more effective. Immunotherapy aims to boost the body’s natural immune system so they recognize and attack cancerous cells. Whereas, gene therapy focuses on replacing the faulty genes that are functioning abnormally.[57] CAR-T immunotherapy focuses on genetically engineering t-cells which are white blood cells covered in receptors that recognize whether a cell is safe or dangerous. If a cell is dangerous, the receptor would tell the t-cell to attack. The process is fairly simple. The patient’s blood would be extracted and their t-cells would be genetically modified to be able to detect tumors and act as “super-killers”. These cells would be multiplied then infused back into the patient's body.[58]

Overview of Immunotherapy Process [59]

In 2016, China was the first to conduct a human trial.[60] They had a group of patients with advanced lung cancer and injected PD-1 edited T cells to help attack their cancerous cells as regular radiation and chemotherapy was not helping. The PD1 protein tells the T-cell to destroy or not destroy a specific cell; researchers found that cancerous cells were able to bypass this so the T-cells leave them alone. CRISPR was used to modify that gene so the cancerous cells cannot evade the T-cells. Their main goal at that time was to test whether using CRISPR for immunotherapy was safe or not rather than to eradicate the disease. They found that this technology was safe and does not induce a strong immune reaction. They also found a low frequency of mutations. [60] The tumor of one of its patients, a 55-year-old woman, shrank and was stable for 75 weeks before progressing. [60]

Human Immunodeficiency Viruses

The most controversial news regarding CRISPR is the twin embryos that were modified by a Chinese researcher in an attempt to prevent HIV in 2018. He Jiankui, a Chinese researcher and ex-professor at Southern University of Science and Technology in Shenzhen created the first germline-edited babies, Lulu and Nana.[61] He claimed to have disabled a gene called the CCR5 which involves helping HIV enter into healthy genes.[62] By disabling this gene, the babies become immune to HIV. This violated the government's ban on gene-editing on human embryos and he was fined 3 years in prison and 3 million yuan (approx. $604,000 CAD).[63] Researchers dug deeper into his research and found he failed to do proper testing and documentation. They realized that the CCR5 genes carried by these twin babies are entirely new as they were not edited uniformly. “Nana has accidentally had a single extra-base pair added to one, and four deleted from the other. Meanwhile, Lulu has inherited a copy with 15 base pairs inadvertently deleted, as well as an entirely unaltered version”.[62] This indicates that they are probably not immune to HIV and these changes could be passed on to their children. These new alters could lead to mutations that we are unaware of. Since their identities are completely hidden from the Chinese government, there are no new updates on these babies and how their current lives are.

Notable Mentions

Sickle Cell Disease is a genetic blood disorder where the red blood cells are deformed. Researchers are using CRISPR to genome-edit stem cells to increase the level of fetal hemoglobin which is only produced during the fetal stage. The fetal hemoglobin will fix the mutated gene that is causing the deformed red blood cells. The first patient went through the experiment in 2019 and it was a proven success.[64]

CRISPR can also be used for eye diseases like Leber Congenital Amaurosis (LCA) or Retinitis Pigmentosa (RP). Some people have deformed photoreceptor cells which can cause colour blindness or blindness. CRISPR is used to create a healthy copy of the deformed gene so it can produce the proper “protein that converts light to an electrical signal in the retina to restore patient’s vision loss”.[65] In 2017, the U.S. Food and Drug Administration approved Luxturna, a new gene therapy for blindness, treating both children and adult patients.[65] In 2020, Canada approved Luxturna. [66]

Lastly, eGenesis is a biotech company that is genetically editing pigs’ genes using CRISPR so that its organs can be transplanted safely into humans. They are making multiple modifications to prevent rejection and to deactivate any potential pig viruses.[67] This would be a huge breakthrough to increase supply in organ transplants, saving lives.

Risks

If CRISPR was used properly (and ethically), it can save lives and improve the quality of healthcare. It could modify specific genes or cells to make them function properly and eradicate humans suffering from diseases. However, there are three potential risks to point out.
Environmental impact includes how these genetically engineered species can impact the food chain. For example, if a frog continues to consume genetically engineered mosquitoes; what impact will it cause the frogs internally? And what happens when the birds eat the frogs? Since this technology is fairly new with limited data, there could be huge mutations happening. It messes with the nature of things - of how the ecosystem is supposed to be. Next, there could be political risks like power struggles between countries trying to use this technology to their own benefit. This could be modifying genes to enhance the abilities of their armies or creating an army of super-killer babies. The technology could be used for the wrong purpose. As for social impact, as CRISPR technology can help improve or eradicate diseases, this leads to prolonging the lifespan of individuals who are “supposed” to die. This could lead to overpopulation. Additionally, there could be long-term effects from modifying and cutting out genes. What if it makes us healthier as time goes on and natural death is not an option anymore? With the limitless possibilities of CRISPR technology, it also comes with huge risks.

Somatic vs Germline

There are two different categories of gene therapies: germline therapy and somatic therapy. Germline therapy are modifications done to reproductive cells like sperm and eggs. They are made early in the embryo so the gene can be copied into every cell. The changes to DNA made are passed down from generation to generation, which is the major downside of germline. There is a fear that untold consequences of mutations will happen down the line in future generations. Somatic therapies on the other hand target non-reproductive cells. The gene that is edited for example blood cells does not affect any other cells. The big upside of somatic therapy is that the edited genes are not passed on to individuals’ offspring. As gene-editing is in its infancy we are still very unsure how editing a specific gene may affect humans as time passes, making somatic more desirable currently. For example, editing a certain gene may lead to individual offspring having a certain cancer becoming common in their bloodline due to this one edit. [68].

Somatic vs Germline Differences [69].

Ethics

The West’s Outlook

The US has a congressional ban on germline editing and allows research only on somatic editing. The use of genetically engineered embryos for pregnancy is banned in most of Europe and the US. The EU has said tampering with the gene pool would be a crime against humanity and a lot of the basis around this is caution. If the field is rushed or a single case of failure occurs it could kill or put massive roadblocks on the whole concept of genetic modification. The US does support somatic gene-edited babies but has said under safe and strict oversight [70]. Germany does have the ability to make great strides in this field with a great biotech industry, but however is highly reluctant due to its past. Nazi scientists did eugenics campaigns on prisoners of war and in the holocaust to try and create better humans and push the human body to the limit. In doing so Germany fears not to have any correlation with its past or face any public outcry. [71]. Another major reason behind this is an embryo edited through germline would have those genes inherited by future generations and affect the whole gene pool carrying over to future generations. So the west has taken a slow and steady approach.

China

China on the other hand has a more relaxed policy. China is against germline editing in law, but in reality, you can do whatever you like. This is what one doctor did in 2017 in creating the first genome-edited twins and editing a third baby after. The doctor’s goal was to give these babies protection against HIV. The doctor forged documents, misled the parents, and failed any safety testing. In doing so he created children with genes that have never been seen before and scientists are not sure if they have HIV protection. The genes are inherited from the parents but they weren’t uniformly edited. The question remains how these children's lives and children may be. The doctor in question is facing extensive prison time for violating China’s ban on germline and messing up as well as a fine of $430,000. China also has a track record of losing track of patients with cancer that is it doing experimental gene-editing on[72].
Chinese Soldiers in a Parade[73].

Russia

Russia has no official rules or regulations but does supposedly quote on quote support the WHO’s policies on genetic engineering and safety regulations. That’s all for show since a Russian doctor is trying to cure not only HIV but also deafness to one-up the Chinese. The Russian doctor Denis Rebrikov is targeting the same gene as the Chinese doctor. He wants to cure women who have HIV and are drug-resistant to therapies to have healthy children. Denis has said himself I quote” far as I know, we don't have direct restriction of such type of experiments, but usually, Russia agrees with international rules. I know that transmission of germline-edited embryos into women is prohibited in most countries in Europe. In Russian law, we don't have such language.” The Russian ministry of health has said it will investigate each step beforehand but Russia struggles with oversight. Hospitals have little authority and independent say on medical procedures, basically whatever the Kremlin says goes even if it has little factual backing[74].
Russian Doctor Denis Rebrikov [75]

Militarization

The UK recently announced it would spend $1.3 billion on an advanced research and invention agency. It is based on a similar US defense project to help genome editing. Since the UK has one of the best research centers for gene editing it strongly believes it will impact the military[76]. The US Military is investing millions into genetic extinction technology to kill invasive species. The UN has reported however that this same technology could be used in warfare to kill enemy soldiers and maybe a multipurpose mission. China is the only one that has done gene-editing experimentation on its soldiers. It is not clear how successful the experiments were but US intelligence has confirmed they have been ongoing for years [77]

Religion

15 percent of religious Americans think gene editing is morally acceptable. That means the vast majority of Americans that are religious do not think gene editing is justifiable at this point. Many religions believe touching an embryo violates God’s will and his creation. It is common in religion that a child is a gift from God that should not be altered or touched in anyway until they are born. Majority of Americans would only want gene-editing for medical reasons. They believe designer babies are pushing the natural limits of the world and should not be allowed in society.[78].

Short-Term Implications

The ability to create designer babies is far in the future and not a current focus of the majority of countries and research firms. The current focus is to eliminate hereditary diseases and have healthier human beings. Designer babies and a dual-society are far in the future, National Academy of Sciences has recommended that CRISPR only be used to cure and prevent serious diseases and not to enhance babies.

Future of CRISPR

Human Cloning

When Dolly the Sheep was cloned in the 90s, the question many asked is when will humans be cloned. Would billionaires and powerful people of society clone themselves? Over 40 countries banned human cloning shortly after Dolly the Sheep was created including Russia, U.K. and Canada but still allow it for medical research. Researchers have since discovered that it is highly difficult to clone human embryos and keep them alive. The human embryos in question were being cloned for stem cell research that may allow for the creation of human organs and tissue. It was not until 2013 that the Mitalipov group successful cloned two human embryos. The embryos were never placed in a woman and so far no one has done so. With the introduction of CRISPR cloning has taken a step back, but the question remains when will a gene-edited clone become reality? We are still a long way off from this, but with even the same gene makeup as the original human a clone will never have the same personality. In the movie Boys From Brazil, Hitler clones himself creating a young boy who is compassionate and nothing like him. The reason for this are the life experiences we all go through are distinctly different and shape all of us in different ways. No two clones as a result will ever be the same in personality, mindset or ambitions [79].

Designer babies

Designer babies are a term coined for children that can be created anyway of a parent's choosing. Same as a car or any other customizable thing these days you would be able to do the same to your child. Rather than leaving anything to chance by nature or God your child would be designed to the closest specifications you choose. Not only would hereditary diseases be eliminated but you could choose anything from the eye color of a child all the way to the height and lungs abilities. In theory, the perfect human could be created physically to be the best athlete, the smartest person in the class, and have the best looks to top it off. Any part of the child could be changed to match what the parent desires, want a blue-eyed, blonde-haired child done, want to make your child the greatest pianist give him 12 fingers. Parents could sit with a doctor in the planning phase to do all this. A group of highly intelligent humans could be easily designed in the not-so-distant future and be future world leaders and scientists. [80]

A Potential Designer Baby of the Future [81].

Dual-Class Society

In the use of designer babies there are a few snags that come along the way one being a dual-class society. Society could be very easily divided amongst those that are gene edited and those that are not. Human history has for centuries had class systems and divides be it on race, religion or wealth and gene-editing could very easily be the next step in that. Gene edited individuals will likely get the best jobs and positions with anyone unedited falling well below them and not even being in contention. They may be given menial tasks and seen as lesser. The other issue is that gene editing is quite expensive and may only be done by wealthy individuals or select nations. This will harm society if only the wealthy can make their children far superior than the rest of the general population and help them stay powerful. Poorer nations may be left behind and considered as lesser if they have the inability to edit their children to the same pedigree and standard as the rest of the world. Discrimination would now be on if you were gene edited and how well it was done to determine your life and skill level [82].

Conclusion

From agricultural advancements and resolving the diminishing global food supply to curing medical illnesses and eliminating deadly diseases, CRISPR can mitigate several problems our world is currently facing.With big companies such as Moderna entering the CRISPR industry, we can expect more firms looking towards CRISPR as viable investment option to create solutions. In addition, with time, existing risks and biases will hopefully be overcome which will further elevate CRISPR technology into the mainstream. A dystopian era is still far off in the future, and hopefully it stays that way as we see more regulation adapted to suit CRISPR technologies while still being lenient enough for development to continue.

Authors

Kristina Wu Harleen Birak Zinnia Chen Harman Shergill
Beedie School of Business
Simon Fraser University
Burnaby, BC, Canada
kristina_wu@sfu.ca
Beedie School of Business
Simon Fraser University
Burnaby, BC, Canada
hkb21@sfu.ca
Beedie School of Business
Simon Fraser University
Burnaby, BC, Canada
zinniac@sfu.ca
Beedie School of Business
Simon Fraser University
Burnaby, BC, Canada
hss28@sfu.ca

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