Human Augmentation: CRISPR

From New Media Business Blog

Jump to: navigation, search

Contents

Introduction

What is CRISPR

Genome Editing with CRISPR-Cas9 by McGovern Institute for Brain Research at MIT

CRISPR is a unique family of DNA sequences in bacteria. Snippets of DNA are contained in the sequences from viruses that have attacked the bacterium. These snippets are used to detect and destroy DNA from further attacks by similar viruses and play a key role in the bacterial defence system. This forms the basis of a technology known as CRISPR/Cas9 that effectively and specifically changes genes within organisms[1].


CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. CRISPR/Cas9, a simpler version of the CRISPR/Cas system, has been modified to edit genomes. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added[2].


In 1987, Osaka University research Yoshizumi Ishino discover clustered DNA repeats in bacteria. He discovered Cas-9 proteins to be part of the bacterial defense system of E.Coli. This mechanism was able to specifically seek and destroy future viruses. In 1993, Fransico Mojica was the first scientist to identify what is now called a CRISPR locus. He hypothesized that CRISPR is an adaptive immune system. This discovery got the ball rolling for researchers after him to further investigate the topic[3]. In 2013, Feng Zhang, who had previously worked on other genome editing systems such as TALENs, was first to successfully adapt CRISPR-Cas9 for genome editing in eukaryotic cells[4].

How CRISPR Works

The CRISPR immune system works to protect bacteria from repeated viral attack via three basic steps[5]:

  1. Adaptation – DNA from an invading virus is processed into short segments that are inserted into the CRISPR sequence as new spacers.
  2. Production of CRISPR RNA – CRISPR repeats and spacers in the bacterial DNA undergo transcription, the process of copying DNA into RNA (ribonucleic acid). Unlike the double-chain helix structure of DNA, the resulting RNA is a single-chain molecule. This RNA chain is cut into short pieces called CRISPR RNAs.
  3. Targeting – CRISPR RNAs guide bacterial molecular machinery to destroy the viral material. Because CRISPR RNA sequences are copied from the viral DNA sequences acquired during adaptation, they are exact matches to the viral genome and thus serve as excellent guides.

For a more in-depth explanation with visualization, refer to the video on the right that MIT has made depicting the CRISPR/Cas9 editing in action.

Healthcare

CRISPR applications in Healthcare hold the possibility of eradicating infectious diseases, eliminating genetic disease inheritance, and editing human life to design the baby of your choice. The technology is still new, however, it's estimated that breakthroughs in these fields are five years away or less.

Gene Drive

CRISPR applications in Healthcare hold the possibility of eradicating infectious diseases, eliminating genetic disease inheritance, and editing human life to design the baby of your choice. The technology is still new, however, it's estimated that breakthroughs in these fields are five years away or less.


Gene Drive Infographic

What is a Gene Drive? It’s a process in which scientists add an altered gene with a desired trait into a population – usually animals – to ensure that the population inherits this desired trait. Through natural reproduction alone, offspring normally have a fifty percent chance of inheriting a gene. This rate of inheritance decreases over time as some genes may disappear completely.[6]. However, with the gene drive and the application of CRISPR, the effectiveness of inheritance increases to close to one hundred percent. CRISPR aids scientists in targeting genes with desired traits more effectively, in addition to accelerating the transmission of the trait across the population.[7]

Applications to Infectious Diseases - Malaria

Genetic Engineering and Diseases – Gene Drive & Malaria

Almost half of the population of the human race resides within areas that contain high malaria incidents, and at present, over one million people are killed each year from it.[1] Malaria is an infectious disease carried by mosquitoes with the Plasmodium parasite. The disease is released in humans and animals upon being bitten by an infected mosquito. Malaria can be treated through antibiotics, however, in the parts of the world where malaria is most prominent, the antibiotics are too expensive for those that need them. In addition, parasites are starting to become resistant to some of the medications prescribed. With the application of CRISPR, scientists could edit the malaria carrying genes of mosquitos. This would then pass down through the population thus possibly eliminating malaria for good. Already, a team of researchers at the University of California have been successful creating these modified mosquitos. [2] However, further testing must be completed before they release them into the wild. One of the consequences as a result could be the extinction of this strain of mosquitos. [3] Research is also underway on other infectious diseases that CRISPR could potentially eradicate. These include: Dengue Fever, Zika, Lyme Disease, sleeping sickness, and the plague.[4] The technology is still new, so further research must be done before it can be fully applied to to an entire species. There’s also the implications of the effects the gene drive edited species has on the animal ecosystem as a whole. Suppose bats - which like eating mosquitos - consumes CRISPR edited mosquitos, the effects of this are entirely unknown. Nothing at all could happen, or a chain reaction could be caused and wipe out this bat population. The technology has the potential to be powerful enough to revive extinct species, as scientists are currently attempting with the wooly mammoth. [5] It’s also powerful enough to make species go extinct. Another concern is that while scientists might focus on editing one particular portion of the gene drive, another may inadvertently be triggered. They might think they’ve eliminated the malaria carrying gene, however, instead this gene has only grown stronger. The technology must still be refined before it can be completely relied on. From the security perspective, as the technology becomes more simplistic and accessibility greater, this raises the possibility that nations or groups might use the technology and develop malicious gene drives in the form of bioweapons that could spread farther and faster. As with all CRISPR discussions, the ethical debates have only just begun.[6]

"Designer Babies"

Genetic Engineering Will Change Everything Forever – CRISPR

Imagine that you’re at a point in your lives where you’re choosing to have children, except instead of leaving things to chance you decide you want your child to have Brown Hair, Blue Eyes, be at least 6 feet tall, have a high metabolism, stronger bones, be immune from disease, have no genetic challenges, and be highly intelligent - welcome to a world where you can design your own baby!

IVF infographic

Although the concept of designer babies sounds like a new scientific breakthrough, the science has already been in effect for close to thirty years. Presently the technique known as Pre-implantation genetic diagnosis is used by doctors for in vitro fertilization (IVF).[1] Parents that suffer from infertility issues usually look to IVF in the hopes of having children. This infographic summarizes the of process of IVF. Doctors take eggs and sperm and place them together in a lab allowing for fertilization of the eggs. The resulting embryos then undergo pre-implantation genetic diagnosis (PGD), whereby doctors determine whether any of the embryos contain certain genetic defects. The eggs that pass through this quality control check are then placed inside the uterus and await a pregnancy diagnosis.[2] Potential parents have had success with PGD screening for a variety of inherited genetic disorders including down syndrome, hemophilia, and cystic fibrosis. There are hundreds of different gene disorders that can be tested for, however, there is no guarantee that the embroyos chosen will be completely flawless. Another concern with IVF and PGD is the cost - estimated at close to $13,000[3] for the process alone, not including the additional costs of DNA sequencing, which are currently also a few thousand dollars. The parents that could truly benefit from this are unlikely to be able to afford it. Although this treatment has mostly been used towards genetic disorders, some parents have also used it to select the gender of their child. Although PGD has been extremely useful in observing and finding which embroyos are likely to contain genetic disorders, beyond choosing these embroyos and hoping pregnancy takes hold, there’s still a strong chance that a disorder may be present. The doctors perform no actual modifications to the genes, they simply discard the defective ones.


"Build-A-Baby"

With the advances of DNA sequencing and the applications of CRISPR, custom designing your own children could be a possibility in 5 to 10 years. Currently the company Illumina has a machine that can sequence an individuals DNA for $1000, and they’re actively working on creating another machine to lower this cost down to $100. At a cost that low, the average person may afford to sequence their genome and become aware of the likelihood of inheriting genetic traits from their parents or learning which traits they may pass to their children.[4] In 2015, researchers in China were the first to successfully edit the human genome. They used CRISPR to correct embryos containing a rare blood disease known as beta thalassemia.[5] Beyond China, scientists in other parts of the world are still studying the effects of genetically editing embryos using CRISPR. As the graphic shows, there are many parts of the world where genetically editing human embryos is outright banned, along with simply performing research on it. As the technology becomes better understood and more applications are realised, those nations that restrict its use may be at a disadvantage. Suppose the non regulated nations permit CRISPR editing for their future population allowing for strong effects on their economies, militaries, and perhaps even extending life.

While the technology is still in its infancy, the ethical debate has almost overshadowed it. Some of the key issues concern governance of the technology, and the potential societal impacts of it. Most governments have little or no regulation in place regarding human reproduction. However, as shown above some nations currently have a ban on human embroyo editing. The underlying question then is should we be allowed to genetically edit our children the way we want to? This is not a simple question to answer, and the possibilities are endless. If CRISPR was allowed and the current gene sequencing costs stay as they are, wealthier people may be the only ones able to afford to edit their children. This would continue to widen the class structure in place within society. In addition, it may stigmatize the non-CRISPR children. On the other hand, if the procedures were affordable and allowed, many children would be the same and we as people could lose that unique undefined sense of what makes us “us”. These ethical discussions are ongoing and far from over.
CRISPR Regulations by Countries

Genetic Diseases

There are thousands of genetics diseases that are a result of a single error within DNA. CRISPR may potentially eradicate all of these. [6] Researchers in China have already effectively injected CRISPR to a patient with terminal lung cancer. They used some of the their existing cells, made modifications and then injected them back into the patient. The goal is for the edited cells to attack and kill the cancer cells. This application is still new, so the effects are still being monitored. The scientists anticipate further injections being administered.[7]

A major concern to applying CRISPR to humans with genetic diseases is that it will travel throughout the body and could potentially get into other cells that you're not targeting. Although the genetic disease symptoms may pass, new ailments may be created as a result. In effect, this could lead to an immune system attack. Researchers must determine how to apply it only to the intended areas without affecting anything else. Another concern is that CRISPR’s effects are only experienced by the individual, their offspring will receive no benefit.[8]

Drug Discovery and Development

CRISPR is revolutionizing drug discovery and development, actively redefining what’s possible in both disease and pharmaceuticals research and development. CRISPR is emerging as a "key tool in drug discovery for its applications in target identification and validation to preclinical testing".[9]

One of the keys to successful drug development is the availability of suitable models to make important early drug development decisions. Since the 1970s, the emergence of gene editing methodologies – one of the most significant barriers to extensive editing capabilities - has been the inability to produce efficient, scalable and applicable physiologically-accurate models.[10]

"Using CRISPR to Alter Fertilized Eggs"

One application of CRISPR is in creating disease models that more closely resemble humans. This application has helped to drastically reduce the drug development timeframe from years to weeks and at a fraction of the cost. The use of CRISPR greatly shortens the time and reduces the cost associated with generating new disease models. For example, without the use of CRISPR, creating a mouse or rat model with multiple mutations can take many months and/or years, with each mutation costing approximately $20,000.00. [11]

CRISPRs main benefit to drug discovery and development comes from its speed, ease of use, control (being programmable in nature) and efficacy – these advantages are overcoming certain limitations of gene editing precursors, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALEN) [12]

Another notable advantage to using CRISPR is its ability to alter multiple genes at once. This is significant because most human diseases and disorders are not monogenic in nature – meaning that there is the possibility of many different types of mutations across multiple genes. [13]

As CRISPR paves a new course in drug discovery and development, notable biotech and pharma companies are jumping at the opportunity to incorporate this technology in a fast growing market with high adoption rates of this technology. In fact, gene editing market is forecast to grow at 14% CAGR and exceed USD $8.1B by 2025. [14]

Gene Therapy Treatment

Gene therapy, which involves adding additional genes to cells, dates back to the 1990s. [15] Still to this day, gene therapy is predominately used in treating rare genetic disorders such as Duchenne Muscular Dystrophy, Huntington's disease, cystic fibrosis (CF), sickle cell disease among many others. One of the advantages of using CRISPR and its gene editing capabilities to alter existing cells is the treatment of a much wider range of conditions, including but not limited to HIV to high blood pressure. [16] CRISPR technology offers the potential to treat hundreds of diseases, both rare and common by targeting the underlying cause(s) of the disease, with the possibility to treat and cure diseases by being able to modify the genome. Essentially, CRISPR can be used as an “off switch” to turn off the mutated disease-causing genes and or repair defective genes or sequences of genes. [17]

"Gene Therapy Administration - Ex Vivo vs. In Vivo"

CRISPR is helping to usher in the era of ‘Regenerative Medicine’. For example, CRISPR is changing the way physicians treat certain blood disorders including leukemia. The standard treatment today involves regular blood transfusions, with the only cure being a bone-marrow transplant from a donor. This treatment carries both high risk of morbidity and mortality. CRISPR offers a safe, more effective and efficient treatment for leukemia by taking stem cells from a patient, editing the stem cells to correct the defect/mutation in the genes. The edited cells are then re-administered to the patient. [18]

Some of the areas of concern surrounding CRISPR's use in drug discovery and development and gene therapy treatment circle around our genetic understanding, the efficacy of the drugs and therapy treatment as well as the delivery of the actual treatment. While CRISPR is programmable, there is a potential for CRISPR to make unintended changes to other parts of the genome – known as off-target effects. There are also barriers and unknowns to overcome when it comes to delivering CRISPR-edited genes into a living patient, known as in-vivo treatment as CRISPR is generally delivered to a living patient via a virus. [19] The virus in which CRISPR-edited genes are administered are theoretically harmless, but there are questions raised about the long-term effects of administering such treatment through the use of viruses.

Combatting Antibiotic Resistance

We live in a world where there exists an ever growing number of bacteria resistant to healthcare’s most effective antibiotics. According to the World Health Organization (WHO), ‘antibiotic resistance is one of the biggest threats to global health, food security and development today’. [20] Antibiotics used today don’t explicitly target only harmful bacteria, instead they attack both good and bad bacteria, giving rise to infectious diseases that are immune to current antibiotics, furthering the antibiotic resistance cycle. [21]

Startups armed with the scientists are developing antimicrobial treatments with the use of CRISPR technology, targeting the resistant and harmful genes and deactivating them. Scientists are currently working on a CRISPR carrying-pill that directs harmful bacteria to dismantle their own genes, effectively leaving only good bacteria intact. Once optimized, this theoretical CRISPR pill could have the potential to '‘precisely target single strains of harmful bacteria, while leaving other types – including beneficial gut bacteria – intact.’' [22]

Scientists are hopeful that such a treatment can help in the race against antibiotic resistance, however they are barriers to implementing such a treatment. One of the barriers in combatting antibiotic resistance with CRISPR technology revolves around precision. In order for CRISPR to dismantle the harmful bacteria, scientists need to be able to accurately locate a suitable bacteriophage (a virus that infects bacteria) and intervene on the microbiome (a community of microorganisms that inhabit a certain environment). [23] This proves difficult because each type of bacteria generally will only infect specific bacteria, requiring scientists to successfully and with precision manufacture phages that carry similar DNA.[24]

Performance Enhancement

Can We Make Super Athletes By Modifying Genes?

Human performance enhancement using CRISPR/Cas9 technology will be with us in the very near future, if it's not already being done. It can range from changing the performance of future children via designer baby to adjusting minute details on athletes via gene doping. With either end of the spectrum, the immediate testing and use of the technology on humans are likely only hindered by ethical concerns. This section focuses on enhancing skeletal muscle development.

Myostatin Inhibition

Myostatin gene location in human

Myostatin inhibition will likely be one of the fastest applications of CRISPR for performance enhancement for the following reasons. The location of genes to disable are already known as shown on the left[1]. Myostatin has a singular role for muscle development/stagnation unlike hormones such as testosterone or human growth hormone, which have vital functions outside of skeletal muscle development[2]. The side effects for myostatin deficiency in mammals are seemingly low[3] and it carries huge implications for rehabilitating muscle injuries.


Myostatin (muscle inhibiting hormone) in mammals suppress skeletal muscle development and growth to ensure that muscles do not grow too large[4]. Reduction in myostatin expression via mutation leads to overgrowth of muscle tissue and increase in muscle density, but otherwise is not known to cause medical problems [5]. The fact that myostatin only governs skeletal muscle growth means that its deficiency does not cause smooth (intestines) or cardiac (heart) muscle growth; a problem commonly found in using IGF-1 (Insulin-like Growth Factor 1) for muscle growth[6].


Without genetic mutation that causes deficiency, myostatin in human act through two major pathways:

  • Preventing myoblasts from becoming skeletal muscle
  • Inhibiting an enzyme called Akt that can cause muscle hypertrophy


Belgian Blue

Myoblasts are precursors to muscle fibres that become muscle cells through myogenesis [7] and Akt are proteins that get activated via growth factors or insulin to play a role in cell growth and metabolism[8]. Without genetic mutation, muscle development takes place through hypertrophy: the strengthening and enlargement of preexisting muscle fibres[9]. This implies a genetic upper bound for muscle development without the use of performance enhancing drugs like anabolic steroids. However, anabolic steroids cannot increase the number of fibres. Their main effect in muscle building are through hypertrophy (semi-permanent)[10] and intramuscular water retention (temporary)[11].

Myostatin inhibition causes hyperplasia (increase in the number of muscle fibres), essentially increasing the ceiling for muscle development. Myostatin inhibition as a condition is already inheritable without enabling gene drive through CRISPR/Cas9 [12]. This simplifies the process of editing myostatin alleles for the purpose of human augmentation. Belgian Blue is a breed that takes advantage of the mutation[13].

In a paper published in Nature, CRISPR/Cas9 mediated genes were used to reduce myostatin expression in fish[14]. The study found that the Japanese rice fish that were edited had significantly higher body length and weight, with unimpaired ability to reproduce and pass down the edited genes. Although hypertrophy from reduced myostatin was shown in subsequent generations, they also showed higher chance of spinal deformity.

In mammals, sheep zygotes were successfully edited using CRISPR/Cas9 to produce myostatin deficient lambs [15]. 53 blastocysts were produced with CRISPR/Cas9 content injection. Once transferred, 19 ewes became pregrnant and 22 lambs were born. Of the 22 lambs, 10 showed myostatin mutation with heavier bodyweight than control [16]. The study suggests that that CRISPR/Cas9 edited mammals are already able to be mass (re)produced.

The first tested human case was in 2004 where a boy was born with an unusual muscular development in Germany. While he experienced stimulus-induced myoclonus (twitches from loud sound, lights, and/or movements) shortly after birth, it gradually subsided after two months[17]. Outside of the initial myoclonus, he developed without health problems and continued to have increased muscle bulk and strength. His mother was a former professional athlete who was identified with one of two myostatin genes deactivated, where as the boy had both deactivated[18].

US Department of Defense

Captain America: The First Avenger (2011); classic super soldier transformation as envisioned by Marvel

The US military has reasons to be interested in inducing myostatin deficiency beyond the obvious applications for performance enhancement. Just in terms of musculoskeletal abilities and injuries, 15-30% of military personnel are considered Medically Not Ready (MNR) to deploy, which translates to $6 Billion in salary annually[19]. In addition, Veterans Affairs's payout for musculoskeletal injuries account for $5.5 Billion out of $21 Billion annually[20]. The greatest concern for the people with such injuries is that substantial recoveries are unlikely for those with major injuries as muscle cells do not regenerate. The use of CRISPR/Cas9 may allow better rehabilitation through myostatin deficiency induced hyperplasia to regrow new muscle fibres.

Creating Captain America might not be too far off in the future. Pentagon has started a project with Louisiana State University to test the effect of a stable level of testosterone during prolonged combat and severe caloric deficit[21]. Dubbed as “Optimizing Performance in Soldiers Study”, the team is to research how regular testosterone boost (weekly injection) can mitigate the physical and mental performance degradation experienced by combatants from prolonged battle accompanied by caloric deficit. Using anabolic steroids like testosterone can potentially enhance physical and mental performance in these situations, but they are not without downsides.

Some of the major side effects of using external testosterone include [22]:

  • Shutting down the natural production of testosterone, potentially requiring months or years to recover after ceasing usage
  • Needing regular injections for steady levels and aromatase inhibitors to combat increased level of estradiol (a form of estrogen that increase with increased level of external testosterone)
  • Having to monitor 10+ bio-markers that are affected by testosterone to ensure they are not negatively affected, and if they are, having to use appropriate treatments
  • Potentially self injecting in unsanitary conditions if the users are not back in base in time for injection, which may be the case for longer missions,


If CRISPR/Cas9 can be used to increase the natural testosterone production indefinitely and endogenously, the side effects above will be mitigated. Myostatin inhibition can be used to solely boost the physical performance of combatants instead, which reduces the number of parameters that can damage the users. However, using CRISPR to induce myostatin inhibition or boost testosterone production are not as well researched and may be permanent in comparison to injections.

World Anti-Doping Agency

As of Dec. 2, 2017, 25 Russian Olympians were disqualified from Sochi due to doping[23]

World Anti-Doping Agency (WADA), which conducts anti-doping tests for the Olympics, has already banned the use of “agents modifying myostatin function(s)” in 2008[24]. WADA has also prohibited gene doping, including "the use of normal or genetically modified cells" for the purpose of performance enhancement[25]. These regulations preclude the use of CRISPR/Cas9 for myostatin inhibition definitively.

The problem may be that WADA is already ineffective with detecting non-CRISPR methods of performance enhancing. Grigory Rodchenkov, the former head of WADA lab in Russia, blew the whistle on Russia for organizing a state-sponsored doping program in preparation for the 2014 Sochi Olympics[26]. As of Dec. 2, 2017, 25 Russian Olympians were disqualified from Sochi due to doping and International Olympic Committee (IOC) is deciding whether they will allow the Russian Federation to participate in the 2018 Pyeongchang Olympics by Dec. 5, 2017[27] (Russia has now been banned from the 2018 Olympics[28]). The IOC and WADA have only started the investigation due to Rodchenkov's report. The use of performance enhancing drugs by the Russian athletes would not have been detected without the whistle-blower, despite having the methods to perform them. WADA is developing tests for gene doping with substances like EPO[29], but the list of detectable substances is not exhaustive. Given how cost efficient and easy gene editing became with CRISPR/Cas9, WADA will likely have a difficult time detecting athletes who enhance their performance through gene doping and editing.

Future of Competition

If and when designer babies become common, it would be unfair to ban individuals from competing in sports for the decisions made by their parents. Sporting events in the future may be separated into genetically natural and genetically enhanced categories, not dissimilar to parasports and non-parasports. They could also be unified into a single category with any and all enhancements (physical or genetic) allowed. Gene doping mentioned in the video at the beginning of section may allow a level playing field between genetically (or physically) natural and enhanced athletes.

Some questions that can be asked looking forward are whether the criteria for fairness will change in sports due to genetic editing. It could be argued that every athlete having the best (and presumably the same) set of genes for a particular sport is more fair than the athletes being limited to what they were born with. A counter argument would be that more developed nations with better research infrastructures will likely produce better athletes barring training methods and the athletes' effort. Would sports become less entertaining with every athlete potentially having the same ability or would the suprahuman aspect of professional sports make them more interesting? How would this affect amateur and young adult leagues? Would athletes advance to professional leagues based on their work ethics, the ability to read a play, creativity? Or can these all be improved through gene editing in the future? Regardless of how these questions will be answered, the landscape of athletic competition will become volatile once performance enhancement through gene editing is in full force.

Agriculture

Applications in Agriculture The most immediate applications of CRISPR technology are happening in the agriculture segment. Companies like Du Pont and Exxon Mobil are already experimenting with CRISPR to bring to market gene edited products as soon as 2022. [30] The concept of augmenting food has been around for about 10,000 when our ancestors started to domesticate crops and began noticing desirable traits within the food. [31]

Enhancing Desired Traits

CRISPR is a new technology for enhancing crops, but Selective Breeding has been around since early prehistory. Secondly, GMO’s have been experimented with as early as the 1970’s. GMO’s are highly controversial within the scientific community and the media due to their perception of being unnatural. Genome editing is a more efficient and precise technique of manipulating genes than the conventional breeding methods. [32]

Selective Breeding

Selective breeding (also called artificial selection) is the process by which humans use animal breeding and plant breeding to selectively develop particular phenotypic traits (characteristics) by choosing which typically animal or plant males and females will sexually reproduce and have offspring together. [33] Selective breeding makes use of existing, naturally present gene variants in a species and the natural process of breeding, similar to CRISPR gene editing in that no foreign DNA is introduced. [34] However, the notable difference here is that with selective breeding the newly produced offspring is where the the benefits of the selection will be seen, while with CRISPR gene editing an already living organism can have its DNA selectively edited. An agricultural example of selective breeding is grocery store produce. Almost all the fruits and vegetables available for purchase have been selectively bred to be bigger, juicier, tastier and to last longer.

Genetically Modified Organisms

A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques (i.e., a genetically engineered organism). [35] The key distinction with GMO’s are that foreign DNA is introduced into the organism to enhance the value of the organism, by adding desired traits. For example, tomatoes have been developed that resist frost and freezing temperatures with antifreeze genes from a cold-water fish, the winter flounder (Pseudopleuronectes americanus). Even more bizarre is that geneticists have bred GMO pigs that glow in the dark by inserting into their DNA a gene for bioluminescence from a jellyfish. [36] CRISPR is a relatively new and rapidly growing technique that has yet to be fully understood or defined. It is the author's belief that CRISPR gene editing will develop its own concrete definition that has similarities to selective breeding and GMO’s. In 2015, Sweden decided to classify CRISPR edited plants to not be GMO’s unless there is foreign DNA being introduced. In November 2015, Sweden became the first country within the EU to deliver a legislative ruling on whether CRISPR-Cas9-editted plants fall within the definition of GMOs, and would subsequently be subject to the same restrictions as GMOs. The Swedish Board of Agriculture ruled that some plants edited using CRISPR-Cas9 technology do and others do not fall within the GMO definition. The distinction is based on the presence or absence of foreign DNA: plants with foreign DNA introduced through any means (CRISPR-Cas9 or otherwise) were ruled to be GMOs, while plants edited with CRISPR-Cas9 but lacking foreign DNA were ruled not to be. [37]

DuPont Pioneer

In 2016, Iowa-based DuPont announced its first CRISPR-modified crop, which was waxy corn engineered to produce more yield. [38] It is important to note that agriculture will be the first commercial application of CRISPR technology and currently DuPont Pioneer is on track to be the first company to sell CRISPR edited products. According to DuPont, CRISPR-Cas has numerous potential agricultural applications including improvements to yield, disease resistance, and drought tolerance, as well as improvements beneficial to the end user such as output characteristics and nutritional content. [39] The waxy corn that is being produced, will have edited genes to make it more cost efficient in comparison to their current system for producing the same type of corn. “Using CRISPR-Cas advanced plant breeding, the waxy gene can be deleted entirely and directly in most current elite inbreds. This direct deployment of the waxy characteristic reduces the time necessary to create waxy hybrids and is expected to eliminate the yield drag associated with the introgression of the characteristic through conventional breeding.” Corn products and byproducts are heavily intertwined with the products we consume in our daily lives, so producing corn for cheaper is a huge opportunity for DuPont to improve their profit margins in their agriculture business.


BioFuels

A biofuel is a fuel that is produced through contemporary biological processes, such as agriculture and anaerobic digestion, rather than a fuel produced by geological processes such as those involved in the formation of fossil fuels, such as coal and petroleum, from prehistoric biological matter. [40] Another important application of CRISPR in agriculture is within the biofuels industry. Exon Mobil is on the forefront of this segment where they have created an oil-rich strain of algae that represents a major research advance toward commercializing algae-based biofuels. [41] They have managed to double the lipid content in edible ocean algae, using CRISPR, which can be refined into fuel to be used like diesel. This breakthrough will have huge implications in how the company sells their biofuels on the market. Currently in the United States, require most refiners, importers, and non-oxygenate blenders of gasoline to displace 10.21% of their gasoline with renewable fuels such as ethanol. This according to the 2009 Renewable Fuel Standard. [42]

Conclusion

CRISPR enables the editing and compiling of the code for life. While this power to change lives may be controlled within each nation, enforcing international governance structure will be impossible. The greatest concern is the inability to predict how the edited genes would affect their environment; possibly as long as life exists. Change in genetic structures have always occurred alongside evolution, but the gene drive can make natural selection obsolete. Once it reaches a critical mass, the only way for a gene drive enabled allele to be nullified without human intervention is through extinction. Gene drive will have little regards for what features of the organism allow higher probabilites of survival and propagation. It will simply spread.

But the excitement that CRISPR brings is wholly justified. It has the potential to eradicate numerous diseases that rely on vectors and mutations. It can empower couples that decided against having children in the fear of passing down hereditary conditions. These children could have superhuman intelligence and strength while being more creative than ever before. With the application and advancements in agriculture, world hunger could realistically be solved. CRISPR will change life at its core. To what extent, and whether it will create a positive outcome for life on Earth need to be asked each step of the way.

Authors

Howard Kim Daniel Hoyles Jalen Sekhon Christine Weber
hgkim@sfu.ca dhoyles@sfu.ca jalens@sfu.ca clweber@sfu.ca
Beedie School of Business
Simon Fraser University
Burnaby, BC, Canada
Beedie School of Business
Simon Fraser University
Burnaby, BC, Canada
Beedie School of Business
Simon Fraser University
Burnaby, BC, Canada
Beedie School of Business
Simon Fraser University
Burnaby, BC, Canada

References

  1. http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000138379;r=2:190055697-190062729;t=ENST00000260950 Accessed: Dec. 1, 2017
  2. https://www.nih.gov/news-events/nih-research-matters/understanding-how-testosterone-affects-men Accessed: Dec. 1, 2017
  3. https://ghr.nlm.nih.gov/gene/MSTN#conditions Accessed: October 20, 2017
  4. https://ghr.nlm.nih.gov/gene/MSTN#conditions Accessed: October 20, 2017
  5. https://ghr.nlm.nih.gov/gene/MSTN#conditions Accessed: October 20,2017
  6. Julie R. McMullen et al. "The Insulin-like Growth Factor 1 Receptor Induces Physiological Heart Growth via the Phosphoinositide 3-Kinase(p110α) Pathway" http://www.jbc.org/content/279/6/4782.full.html Accessed: Dec. 1, 2017
  7. https://meshb.nlm.nih.gov/record/ui?name=Myocytes Accessed: Dec. 1, 2017
  8. https://meshb.nlm.nih.gov/record/ui?ui=D051057 Accessed: Dec. 1, 2017
  9. https://www.unm.edu/~lkravitz/Article%20folder/hypertrophy.html Accessed: Dec. 1, 2017
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160183 Accessed: Dec. 1, 2017/
  11. https://www.ncbi.nlm.nih.gov/pubmed/6789809 Accessed: Dec. 1, 2017
  12. https://ghr.nlm.nih.gov/condition/myostatin-related-muscle-hypertrophy#inheritance Accessed: Oct. 20, 2017
  13. https://www.ncbi.nlm.nih.gov/pubmed/9314496 Accessed: Dec. 1, 2017
  14. Yeh, Ying-Chun, et al. “Using CRISPR/Cas9-Mediated gene editing to further explore growth and trade-off effects in myostatin-Mutated F4 medaka (Oryzias latipes).” Scientific Reports, vol. 7, no. 1, 12 Oct. 2017, doi:10.1038/s41598-017-09966-9.
  15. Efficient Generation of Myostatin Knock-Out Sheep Using CRISPR/Cas9 Technology and Microinjection into Zygotes http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136690#ack Accessed: Dec. 1, 2017
  16. Efficient Generation of Myostatin Knock-Out Sheep Using CRISPR/Cas9 Technology and Microinjection into Zygotes http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136690#ack Accessed: Dec. 1, 2017
  17. http://www.nejm.org/doi/full/10.1056/NEJMoa040933#t=article Accessed: Oct. 20, 2017
  18. http://www.nejm.org/doi/full/10.1056/NEJMoa040933#t=article Accessed: Oct. 20, 2017
  19. http://herl.pitt.edu/symposia/fitness-health/presentations/Nindl-SotS-20160330.pdf Accessed: Oct. 20, 2017
  20. http://herl.pitt.edu/symposia/fitness-health/presentations/Nindl-SotS-20160330.pdf Accessed: Oct. 20, 2017
  21. https://sites01.lsu.edu/wp/discover/2016/09/26/lsus-pennington-biomedical-conducts-optimizing-performance-study-for-soldiers/ Accessed: Oct. 20, 2017
  22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5182219/ Accessed: Oct. 20, 2017
  23. https://www.nytimes.com/2017/12/02/sports/olympics/russian-doping.html Accessed: Dec. 2, 2017
  24. https://www.wada-ama.org/en/prohibited-list/prohibited-at-all-times/hormone-and-metabolic-modulators Accessed: Oct. 1, 2017
  25. https://www.wada-ama.org/en/prohibited-list/prohibited-at-all-times/gene-doping Accessed: Oct. 1, 2017
  26. https://www.bloomberg.com/news/articles/2017-11-24/russia-loses-sochi-olympic-crown-as-doping-scandal-claims-medals Accessed: Dec. 2, 2017
  27. https://www.nytimes.com/2017/12/02/sports/olympics/russian-doping.html Accessed: Dec. 2, 2017
  28. https://www.nytimes.com/2017/12/05/sports/olympics/ioc-russia-winter-olympics.html Accessed: Dec. 5, 2017
  29. https://www.wada-ama.org/en/resources/research/epo-gene-doping-test-ongoing-improvement-and-implementation-in-wada-accredited Accessed: Dec. 1, 2017
  30. https://cen.acs.org/articles/95/i24/CRISPR-new-toolbox-better-crops.html
  31. http://www.labmanager.com/insights/2017/05/putting-crispr-to-work-in-agriculture#.WiDshrT82Hq
  32. http://www.labmanager.com/insights/2017/05/putting-crispr-to-work-in-agriculture#.WiDshrT82Hq
  33. https://en.wikipedia.org/wiki/Selective_breeding
  34. https://www.yourgenome.org/facts/what-is-selective-breeding
  35. https://en.wikipedia.org/wiki/Genetically_modified_organism
  36. https://www.livescience.com/40895-gmo-facts.html
  37. http://www.fcrn.org.uk/fcrn-blogs/jessica-finch/genome-editing-technique-crispr-cas9-and-its-role-agriculture
  38. https://cen.acs.org/articles/95/i24/CRISPR-new-toolbox-better-crops.html
  39. https://www.pioneer.com/home/site/us/agronomy/library/crispr-cas/
  40. https://en.wikipedia.org/wiki/Biofuel
  41. https://geneticliteracyproject.org/2017/06/21/crispr-edited-algae-high-biofuel-yield-created-exxonmobil-craig-venters-synthetic-genomics/
  42. https://en.wikipedia.org/wiki/Biofuel_in_the_United_States#Renewable_Fuel_Standard_.28RFS1.29
Personal tools