Mark Your Calendars — The Future is Here.
Since the beginning of time, innovation through new technologies has propelled our society to completely different eras. Furthermore, change within our society has made ideas that were once seen as impossible, finally possible. If you refer back to around 100 years ago and ask any significant physicist about atomic energy, I’m positive they would assert my answer; that it is impossible. With the discovery of the neutron, these theories were immediately disproven. The point I’m trying to display is how one form of innovation in society can push us towards more revolutionary technologies.
Since the discoveries of significant technologies, many enthusiasts and those who share an interest have dreamed of the future of these technologies. For glasses, many are excited about lenses capable of directing us around and giving us notifications. For genetics, however, it’s cloning and Genetically Modified Humans. For those who don’t understand what exactly that is, a quick analogy can solve that — Have you ever bought vegetables and saw two options, organic or GMO? The latter option refers to Genetically Modified Organism, or in laymen, an organism like a vegetable that had it’s DNA edited. And before you ask why they would sell such a vegetable, it actually makes a lot more sense than you would think. From the standpoint of a farmer, imagine attempting to grow a crop with factors like the temperature, condensation, humidity, bugs, soil, and more. As humans, we are unable to control most of these naturally, but we can genetically. Although many GMOs include non-generic genetics, they significantly help our agriculture industry. With the power of genetically modifying plants, we can prevent them from dying, and this concept is somewhat interchangeable with humans.
The ABCs of DNA
Our human genome (set of chromosomes) is comprised up of a long strand of DNA or Deoxyribonucleic Acid. Our DNA is basically our code for how we process nutrients, grow, and look and is around 10 Billion Miles long.
Most of us who are not geneticists will return to their 8th-grade science class whenever they think about DNA. And as most of you will recall, DNA is fundamental to any form of life. Every living organism has a DNA sequence, whether you observe plants or animals, you will immediately discover similarities. Our DNA is comprised of two strands, these strands contain two base pairs, these base pairs are composed of two nucleotides, which are made from five-carbon sugars, a nitrogenous base and a phosphate group.
The individual base pairs are comprised of two different nucleotides that must partner up. These pairings are A + C, T +G or Adenine + Thymine, Cytosine and Guanine. These base pairs are crucial for any type of genome editing or DNA splicing as they assist in replacing DNA strands.
Our DNA is crucial for assisting in our everyday functions as it provides a way for the body to remember specific things. Each day, our hair grows, on average, at 0.44mm, and our body needs to ensure that our hair matches our previous hair, which is why our hair cells are replicated with the same DNA. In fact, every cell in our body contains the same DNA, just different portions depending on their function. Our DNA acts as a map, and this map may sometimes have errors, and this is where genome editing comes in.
Protein Please.
Proteins are a fundamental aspect of human health for numerous reasons. Most see it at the tip of the iceberg for muscle building, but that couldn’t be more wrong. Proteins or ribosomes can also assist as enzymes, carriers, hormones, or even genome editing. Our bodies actually specialize in creating protein through the means of the Central Dogma of Genetics or Biology, which uses half of a DNA strand (referred to as RNA) to program proteins for different functions. Although our bodies create thousands of types of proteins, the only one that can physically cut DNA is labelled Cas-9. This Cas-9 protein comes from a family of over 45 different proteins that have relative functions but don’t compare to the strength of the Cas-9. Within Genome editing, geneticists will use this Cas-9 gene to actually cut off a portion of your DNA and allow it to properly heal. This process can be labelled as CRISPR.
CRISPR? Never heard of it.
CRISPR was discovered in the late 1980s by Yoshizumi Ishino and a research partner in Osaka, Japan. The discovery showed a DNA sequence containing five individual like strands with random sequences in between. The discovery was seen within bacteria, and the partners weren’t even aware of its revolutionary aspect. Instead, Yoshizumi Ishino decided to write a paper on it, that discusses the Cas-9 protein and how it assists in defending the immune system.
Over time, studies of random bacteria continued to display these results of the five like sequences and eventually got its name CRISPR or Clustered Regularly Inter-Spaced Short Palindromic Repeats. After numerous findings, scientists began realizing its real significance, the capability of cutting DNA. But this finding wasn’t immediate, and instead was as a result of numerous observations of the body’s immune system.
Once a virus enters our bodies, the immediate response is to send nearby white blood cells and enzymes to attempt to kill the virus. The Innate Immunity system utilizes barrier tissues, cells and molecules to defend against any pathogens. Commonly this system is ultimately defeated, and the virus lives on. But on the chance that they beat the virus, we will see the adaptive immunity or antibodies. These enzymes will try to clear up the ‘battleground’ and will cut up the viruses’ DNA. The enzymes will then take the viruses’ DNA and place it inside the gaps in our own DNA, which allows for Adaptive immunity to function.
In the scenario, that the virus reappears and attacks the immune system, specific antibodies coded with the viruses RNA will begin searching for it. They will scan almost every cell to determine whether it is carrying or inhibits the infected RNA. On arrival of the infected RNA, the antibodies will use the specific Cas-9 protein to cut it up and destroy it.
This discovery lead scientists to ask the question, what if we change their target?
How does CRISPR help?
After the discovery of CRISPR, geneticists began testing and researching how they can retarget these antibodies to specific areas of the human DNA that may be mutated or infected. After some time, scientists developed the base editing system. This system, which is later explained, was the primary form of CRISPR genome editing, which is still seen today.
Compared to other genome editing techniques, CRISPR is inexpensive, universal, and reliable. CRISPR is also universal as it works with every single organism without defeat. And is much more accessible due to its reasonable price of around $70, compared to other methods that may range in the thousands of dollars.
CRISPR allows geneticists to remove a possibly dangerous or infected portion of our DNA and permits the DNA to heal with a healthier strand. This process of removal can enable humans to bypass significant diseases and infections that may typically be fatal or create long term effects. A few examples of illnesses that CRISPR can cure are cancer, AIDS, blood disorders, muscular dystrophy, and Huntington’s disease.
The Amazon Prime Of Genetics
CRISPR has been used for over 18 years, and within that period, there have been many issues that have arisen. In many scenarios, CRISPR will attempt to replace an infected sequence of DNA and rely upon the body’s processes to mutate and heal. However, this process is incredibly unreliable and, in many scenarios, fails. So geneticists soon began developing a tool that has much more precision and accuracy, a device that only splices half of the DNA. This tool is known as Prime Editing or a Precision Cutter as it allows for the cutting of half the strand, which solves issues with healing that commonly arise.
This tool’s precision allows CRISPR to treat genetic diseases that arise from natural mutated genetics or sequences. This revolutionary discovery has permitted the CRISPR process to be much more precise and much more effective.
The primary tool used in CRISPR is base editing. This tool, while somewhat useful, wouldn’t correctly allow for the treatment of multi-letter genetic diseases and, instead, assist in treating the single-letter genetic disorders.
The Bio-Ethics of CRISPR and Prime Editing
The future of CRISPR and genome editing is insightful and something to look forward to, but at what point is genome editing unethical? In many scenarios, genome editing works with the consent of the organism involved (other than test animals). This consent is crucial as the rearrangement of DNA can affect a human much more than you can imagine. Although it provides the health benefit of removing a genetic disease, it may affect your future children, as your genes are passed on in miosis.
Although consent is quite easy to achieve with a living human, it is impossible to have a fetus, or as people describe them, ‘designer babies.’ These test-tube embryos cannot possibly consent to have their DNA changed for their gender, hair/eye colour, behaviour, etc. Through miosis, these genes will be passed down for generations, possibly disrupting human evolution.
Although these topics may seem unethical, clinical trials have gone forward without repercussions from society. For example, China has conducted a study of 78 embryos that have been modified using the CRISPR Cas-9 method, in which only 28 of them achieved proper modification. Out of these 28 embryos, zero of them were successfully birthed. While it may seem wrong to disrupt the work of thousands of years of Darwinism, this disruption has already occurred. As many would argue that In-Vitro Fertilisation, or better known as IVF, is unethical and extraordinarily unnatural, but I’m sure you know somebody or know of somebody who was a ‘Test-tube baby.’
An issue that may arise is the fact parents may feel obligated to genetically modify their babies using CRISPR, despite financial costs. An example of this can be seen in Iceland when a group of Icelandic people was found to carry a specific gene sequence that decreased their chances of developing Alzheimer’s. This gene was exclusive to a particular group of people, which soon increased the desire to hold it. Due to this increased desire, doctors will be forced to place a price tag on this luxury. And as many parents may not be in the financial situation to provide their child with this benefit, many would feel guilty as they couldn’t live up to their obligation as a parent.
Over time CRISPR will continue to develop, and with Prime editing, the possibilities of CRISPR have reached new and improved levels. As a young student, I’m excited to see the future of genome editing and what the future holds.
If you are interested in further developing your knowledge of this topic, I’ve provided a few reliable papers that go over some more difficult concepts about how the Cas-9 protein functions and how CRISPR works.
Development and Applications of CRISPR-Cas9 for Genome Engineering
A simple guide to CRISPR, one of the biggest science stories of the decade
Antibodies Part 1: CRISPR | Radiolab | WNYC Studios
Search-and-replace genome editing without double-strand breaks or donor DNA
