11 minute read
CRISPR: Could it Change Evolution?
- Tom D., Alexandre R., Chi-Yu H., Ines V.
Recently, there has been a lot of debate surrounding the rise of genetically modified organisms and their possible implications. Genetic modification using the CRISPR-Cas9 protein can greatly advance our medical care as it has the potential to cure genetic diseases such as cystic fibrosis and cancer. However, genetic engineering faces many challenges that must be addressed before it can reach its full implementation.
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Very few women have gotten a Nobel Prize in chemistry since its invention, only 5 actually, out of 183 winners. The fact that two women have gotten the Nobel for their work and are recognised for it, as sometimes men took all the credit for them, shows a leap towards a more gender-equal scientific community. The two women who discovered CRISPR have different nationalities: Emanuelle Charpentier is French and Jennifer Doudna is American. Furthermore, since they have won the Nobel Prize together with different nationalities, it promotes the idea of a growing international scientific community. Our era is defined by globalization and this award reflects that very well. Their scientific discovery unleashed a whole new world of possibilities for genetics.
Firstly, let’s define what a gene is. The smallest unit of life is a cell, and within these cells, they are DNA molecules (or deoxyribonucleic acid). DNA has a double helix structure with the following base pairs A, C, T, and G: A pairs with T, and C with G. A specific sequence of base pairs codes for a gene that defines a certain characteristic (red hair, big eyes, etc). The idea of CRISPR came from microbiology. A common belief is that bacteria and viruses are bad for people, but few people know that there is a type of virus that infects bacteria called bacteriophages. By injecting its genome into the bacteria, the bacteriophage uses the microbe to reproduce, killing it in the process.
In 1987, a Japanese molecular biologist called Yoshizumi Ishino discovered CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats while studying E. coli from the large intestine. While studying them, he found a strange phenomenon (now known as CRISPR): repeating arrangements of base pairs in their DNA. The reason why this is unusual is that the same arrangements define the same characteristics, thus it seemed like a wasted space on the genome. It turns out that this phenomenon is also present in other bacteria and people didn’t know why until 2005. That is when a French scientist, Rodolphe Barrangou, devised an experiment where he put fresh bacteria up against bacteriophages. Unsurprisingly, most of the bacteria died, but the scientist studied the few that survived and found that repeating patterns occurred again. After more research, he came up with the conclusion that these repeating patterns called CRISPR were actually caused by the bacteriophages.
How are bacteriophages and CRISPR related? Well, bacteria have a defense mechanism: when one survives a bacteriophage attack, it will snip a strand of
DNA is short for deoxyribonucleic acid how a bacteriphage infects a becterium
(wikimedia.commons.com)
DNA from the virus. It then inserts that strand of DNA into its own DNA. This is where CRISPR comes into play. In order to distinguish the bacterium’s original DNA from the bacteriophage’s DNA that has been inserted, the bacterium will add a specific arrangement of base pairs called CRISPR that sandwiches the bacteriophage’s DNA. These base pairs (or CRISPR) essentially signal: “whatever is in between us is the DNA that we snipped from bacteriophages.” In the future, when the bacteriophage attacks again, the bacteria will produce guide RNAs that identify the bacteriophage. When the RNAs successfully identify the virus, they will command the production of a protein called Cas9 which acts like a scalpel that cuts a strand of the virus, thus altering it.
Cas9 is the magic potion here. With it, scientists will be able to do genetic operations. To start with, they’ll need to know about the gene they want to insert, which they can get from a database of some sort. Then they can make a guide RNA and its Cas9. Finally, they will be able to inject the RNA and Cas9 into a person. The RNA repeats the process of identifying the DNA, and the Cas9 will be able to snip the desired (or undesired) strand of the DNA. This is how genetic operation theoretically works with CRISPR/Cas9, and while it is not yet viable in humans, researchers are currently working to perfect it.
A specific genetic scissor called CRISPR-Cas9 is easier to operate and gives quicker and better results than the prevailing technology in genetic modification. Many companies specialised in pharmaceutical and agricultural industries want the license in order to utilise it because not only will research take less time and cost less, but it also opens new horizons to products yet to be created.
The medical innovations that are currently being researched with this apparatus are mesmerizing. The genetic scissors are being employed in many investigations in the subjects of immuno-oncology (cancer), regenerative medicine, and numerous genetic diseases. For example, in regenerative medicine, CRISPR is being combined with stem cells (cells that haven't been differentiated yet, and could, for example, become blood, nerve or liver cells) in order to find a treatment for diabetes. A group of scientists at Washington University discovered a way to transform stem cells into pancreatic B cells. The latter releases insulin into the blood and allows sugar levels to decrease. The Wolfram syndrome is when the gene WFS1 causes the apoptosis (death) of the pancreatic B cells. With the use of CRISPR scissors, the scientists modified the WFS1 gene and found after six months, mice had regular blood sugar levels. Curing diabetes would be a major step forward in medicine considering that in 2018, about 10% of the American population had diabetes, and in 2017, the total cost of treating diabetes was about $327 billion. A cure would not only improve livelihoods but also help the economy.
3d model of the cas9 protein
Genetically modified crops, also called GMOs, are being increasingly used all around the world. In the US, 94% of all soybean crops are genetically modified. GMOs have been amply criticized in the recent years. Despite the scientific consensus and the many regulations they face, many people still believe these foods can harm them. Others argue that the plants’ increased photosynthesis gives them an advantage over natural variants and could cause damage to the environment. Despite this downside, GMOs have many positive effects. They have increased nutritional benefits, increased yields and resistance to weeds and insects. The reduced use of pesticides has many ecological benefits since excessive usage of it has led to the poisoning of water sources. GMOs can prove to be very beneficial for developing countries that are still largely dependent on agriculture. Due to their benefits, more and more GMOs are grown in developing countries.
You may have been reading this article thinking, this is all too good to be true. You are unfortunately right. CRISPR does come with a handful of fallbacks and possibilities that, in the wrong hands, could be devastating. The first one is that research has shown that in the parts of the genome where CRISPR is not acting, mutations may occur. These mutations can have serious repercussions that scientists can’t necessarily anticipate. A tested mouse had only one of its base pairs changed in its genome, and it presented more than 1500 mutations. The scientific team of CRISPR later said: “None of these DNA mutations were predicted by the computer algorithms mainly used by researchers to look for any unintended effects” . Another negative aspect of CRISPR is that it could be used not only in wrong ways but also in unethical ways. That’s exactly what a Chinese scientist did with the embryos of two twins in wanting to give them genetic resistance to HIV. This man, He Jiankui, was sentenced to three years of prison and a 430,000$ fine. This is just one example of how CRISPR could be used for unethical purposes. Adding on to that, we know that just changing 1 in 1 000 000 000 base pairs in the genome creates hundreds of unwanted mutations. People should exercise precaution when using CRISPR on humans. Imagine CRISPR being used for eugenics, for a dictator's wish to create a “perfect human”, whether it be arian or godlike. Some scientists have created what some may call “super-animals”, such as anti-malaria mosquitoes in Africa, or cows that only give birth to male calves which give more meat. These applications of CRISPR are extremely interesting but introducing a novel animal into an environment could have devastating consequences. What if it has mutations that make it inedible to its predator? It could disrupt a whole food chain and maybe even cause the extinction of multiple species. The uncertainty of the consequences linked to CRISPR are something to be carefully studied before using it, for who knows what the result will be.
To conclude, the CRISPR/Cas9 genetic scissor is as revolutionary for the scientific community and genetics as it is dangerous. The potential power of this tool is enormous: it can not only change organisms, but maybe even mankind in its entirety. The business potential that comes with CRISPR also is incredible. Could CRISPR eventually cure genetic and autoimmune diseases as well? Only time will tell.
Enola Holmes - An Amateur’s Review
- Melody Z.
Released on September 23rd, 2020, Enola Holmes immediately received massive viewership, becoming Netflix’s most watched movie during the first week following its release. Enola Holmes was directed by Harry Bradbeer (Killing Eve, Fleabag) and features a star-studded cast including Millie Bobby Brown, Helena Bonham Carter and Henry Cavill.
But who is Enola Holmes, you ask? Well, the character was created by Nancy Springer in her Young Adult series of detective novels: The Enola Holmes Mysteries. The movie is actually based on one of these books, The Case of the Missing Marquess. Enola is Sherlock and Mycroft Holmes' younger sister. She lives with her mother, Eudoria, who brought her up to be everything a Victorian lady should not be (independent, stubborn and clever).
When her mother disappears on her sixteenth birthday, Enola calls upon her renowned brothers to help. They unfortunately, prove virtually useless as Mycroft is hellbent on sending her to boarding school so she may learn to be a proper lady, while Sherlock is busy working on another case. Enola therefore decides to take matters into her own hands and escapes to London, disguising herself as a boy.
Now for the review. I’ll be honest, having watched and loved both Robert Downey Jr. and Benedict Cumberbatch’s performances as Sherlock Holmes, I was a little disappointed by Enola Holmes. I think of Sherlock Holmes and picture a quirky yet lovable sociopath against a backdrop of thrilling mystery, cinematic innovation and captivating soundtracks. Whether it’s the whole production or simply the characters, there is something intrinsically different about the Sherlock Holmes movies and the show Sherlock that I thought was lacking in Enola Holmes. Perhaps the intention was to detach Enola from that legacy, to create a separate character with her own story and attract new fans, in which case it has definitely succeeded.
(Spoilers ahead! In the next 2 paragraphs)
Throughout Enola’s adventures, we discover that her mother is a suffragette on a mission to pressure the government to allow women to vote. Through various characters, we learn about suffrage, feminism movements and women’s rights at the time, through the ingrained and omnipresent misogyny of Victorian England. Enola eventually gets sent to a ladies’ college by her brother Mycroft where she’s meant to learn the ways of ladyhood to become a good wife, mother and homemaker. The conditions in which Enola and the other boarders live are quite shocking—though there is obviously something to be said about the dramatic aspect—the girls are in uniform, marching around the school grounds like soldiers and punished as such, all to be taught such arts as standing up straight, eating properly and embroidery. Their future is clearly and tragically laid out in front of them.
I’ll note that the focus of the movie doesn’t seem to be the mystery but rather Enola’s journey and it’s fairly easy to forget about her initial goal. I also found the movie long—2 hours—which is usually manageable, but Enola Holmes felt like it dragged on a little too much before the final, determining plottwist. I did, however, appreciate that the supposed love story didn’t overshadow the plot and Enola’s adventure. I won’t say Enola Holmes is a bad movie because it isn’t, and it wouldn’t have had as much success if it were. Overall, I consider it more of a coming-of-age story bathed in action and comedy than the detective story I was expecting. Though I was disappointed because I based my opinion on what I had already seen in other Sherlock Holmes spinoffs, I highly recommend you watch it and form your own opinion on the movie.
