From Designer Babies To Changed Destinies — The Ins & Outs Of Gene Editing
Close your eyes and think about the way you breathe, your heartbeat, and the black void that pops up in your head. Think about your past, how you grew up, your thoughts and ideas, and your body. What’s unique about this is that your body, and the way you perceive it, is very different than how another person does. Every human in the world is different, and that all comes from our genes. Genes are found in each of the 37 TRILLION (yes, that's right TRILLION) cells that make up our body and are what truly makes us who we are.
You may have heard of the expression “you are a product of your surroundings” and though this may be true socially, it is not biologically. You are actually a product of your parents, and their genes — passed down through chromosomes.
Chromosomes are entire chains of DNA grouped with some proteins that are present in each of our cells. One of their biggest roles is to determine our gender. We have twenty-three pairs of chromosomes, twenty-two of them being called “autosomes” The one chromosome that remains is a “sex chromosome”, which determines the sex of a human. Each pair of chromosomes contain one from the father and one from the mother — the mother always being an X and the father being either an X or Y. The father’s sperm decides the gender of the human, if the sperm is an X for the “sex chromosome” the human will be a female, and if it is a Y chromosome it will be a male. Females have an XX configuration of chromosomes, while males have XY configurations.
Chromosomes are more than just these strands of DNA that decide your biological gender. Chromosomes are also mediums in which genes are passed down from generation to generation.
So Yogya, what are Genes?
Well, to answer this we must step back just a little bit. As mentioned earlier, our body has well over 30 trillion cells, each being vital in the development of our bodies, but it’s what's inside these cells that make them so important. In each cell, there is a nucleus, which contains 23 pairs of chromosomes. In each of these chromosomes, a copy of DNA is present. DNA is just a long strand of genes, configured in a double helix (as seen below), comprised of four different bases. The four different bases are adenine (A), cytosine (C), guanine (G), and thymine (T). The two strands are held together by a hydrogen bond — where A pairs with T, and C pairs with G.
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You may be thinking, why does this matter? Why should I care about these things that are already pre-set in my body?
Well, the simple answer is that they aren’t necessarily pre-set. With our constantly advancing technology, we have found many different ways to alter or change our genome (the collection of all our genes), which has led to many revolutionary advancements.
You see, many of the diseases we are facing today result from genetic mutations in our genes. Cystic fibrosis, Sickle Cell Anemia, Tay-Sachs disease, Phenylketonuria and Colour-Blindness are all examples of conditions that some of our faulty genes can produce.
Genetic mutations occur most often during the process of cell replication, where the DNA in a cell replicates itself. During this process, specific parts of a gene can be deleted, duplicated, or replaced — sometimes leading to harm.
ATG TTA CCG CAG … Normal Genetic Sequence
ATG TTT CCG CAG … Point Mutation| Leads To Cystic Fibrosis
Simple genetic mutations, such as the one shown above where only one of the bases is changed can lead to massive consequences. For example, this exact genetic mutation leads to Cystic Fibrosis, a disease that causes constant genetic degradation of the lungs, as well as one of the most common genetic diseases.
So what?
Most of these diseases were discovered at a time where much couldn’t be done about them. Cystic Fibrosis was discovered in 1938, where it killed thousands. Since it is a genetic disease there is no medicine you can take, no quick fix. But, that could all change with the discovery of CRISPR.
Wait, Wait, Wait — What Is Gene Editing?
Before I talk about CRISPR and its implications, it’s important for you to understand what Gene Editing actually is.
Out of the 3 billion base pairs in our body, a small portion of them go wrong at some point in our life. Most times, this “mutation” is harmless, being repaired by our body naturally, or sustaining no real damage. But, sometimes this mutation causes a drastic change in what the gene communicates — what it makes the cell do. You see, even the slightest change in our genes can lead to physical changes — such as different eye colours or body type. These changes, if unintentional can lead to major consequences.
Gene Editing is the process of editing, deleting, and altering DNA. It helps us correct mistakes in our genes which allow our bodies to continue to function properly.
There are many different approaches and technologies that have been used for Gene Editing, the most effective being CRISPR.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats Repetitive)
I’d be surprised if you haven't heard about CRISPR — founded in 2009, it is the biggest breakthrough in Gene Editing. Before CRISPR, we still were able to edit our genes, but with far more equipment, cost, and time.
CRISPR leverages an enzyme called CAS and was inspired by how bacteria face viruses in our own bodies. You can think of it as a mug shot of sorts. CRISPR works by finding a specific part of your DNA, using a type of RNA called a gRNA (Guide RNA) to match it, then cut it out.
Guide RNA’s take the CAS enzyme to the specificied section of DNA by creating a supplement to its nucleotide/base sequence. Coming back to the pairs of bases, we know that A pairs with T and C pairs with G — these pairs or “opposites” are used to create the gRNA. Looking at the targetted sequence, and modelling the base that can pair with original base is what gRNA’s do. Since gRNA’s are essentially opposites of the targetted sequence, it is able to find it and deliver the CAS enzyme.
For Example:
If the targetted sequence is AACTGAA,
Then the gRNA created would be TTGACTT (the other base of the pair)
Going into the specifics of this process:
- Preconditioned gRNA’s are made to match the bases of the specific part of DNA it would like to alter (the other base of the pair), and are guided to the specific DNA section.
- The RNA from the gRNA bind with the DNA by locking on to the double helix of the DNA and unzipping it
- CAS-9 cuts this section, along with the gRNA
Boom! The faulty section of the DNA is taken out — but what now? Well, from here, two things can occur.
- Homology Directed Repair: The missing section is replaced with a template of gRNA or Cas-9. For this to occur smoothly, it must also extend past just the section you will replace, but also its surrounding bases, so it can connect back to the DNA.
- Non-Homologous End Joining: This is when the cell itself tries to use proteins to create a DNA pair-end complex, which aligns with the bases of the cut DNA.
As you can probably tell CRISPR is amazing. But, what makes it better than the other forms of Gene Editing that existed before it?
The revolution of CRISPR is better in the sense that it:
1) Targets DNA in a more simple manner
Since the target relies on the ribonucleotide (base) itself, and not the protein/DNA as a whole, gRNA’s are easily designable, ready, and cheap. They are able to target any sequence in the genome accurately.
2) Is much more efficient
The use of CAS-9 makes it so that the long and tedious lab processes are kept to a minimum, with the construct of the RNA’s.
3) Is much more powerful
CRISPR is able to edit multiple genes at the same time by injecting them with multiple gRNAs. Dr. Haoyi Wang, from the Rudolf Jaenisch’s group at the Whitehead Institute was able to introduce mutations in five different genes (in a mouse) simultaneously. Pretty sick!
Although this may seem like rainbows and unicorns, it is important to remember that CRISPR is still an evolving technology. There are many things we don't fully understand, and many risks involved with the process.
WOAH! What are scientists using CRISPR for now?
Well, that is a great question! Aside from the obvious medical-related applications of CRISPR such as treating genetic diseases and studying genetic growth, there are some recent, and cool applications of this technology.
- De-Extinction
Scientists at Harvard University have been working on using CRISPR to bring back extinct species of animals. Using CRISPR technology, researchers plan to introduce genes from the Mammoth to their modern-day relatives. Over several generations of breeding, this will be feasible. But, this is still a ways away.
In the year 2022, scientists are planning to do conduct this exact process on the band tail pigeon, introducing the genes of the extinct passenger pigeon. The first generation of these hybrid pigeons is expected to hatch by 2022.
2) Eradicating Pests
Pests have always been a big problem in our society — specifically pests such as mosquitos, which carry many diseases such as Malaria. What if I told you, with the help of CRISPR, transition through pests like mosquitos could be stopped?
Though this could occur, should it? There are many ethical questions surrounding ideas like these, which change the natural order of things and impact our future irreversibly. Questions surrounding the use of human embryos for research, the disparities Gene Editing could create (between different financial hierarchies), as well as the safety of Gene Editing are all things to be considered. What do you think?
3) DNA “Tape Recorders”
Researchers at Harvard University used CRISPR to make a molecular tool, called CAMERA. It stands for CRISPR-mediated analogue multi-event recording apparatus. When implemented the tool acts as a recorder of events during the lifetime of a cell. Events such as exposure to radiation, nutrients, viruses, and antibiotics. Cool, huh?
Implementing this could really help scientists understand how different environmental factors affect our cells at a molecular level.
Clearly, CRISPR is crazy, and there is still a long way to go before the technology is perfected. Who knows what will happen by then? Close your eyes and imagine the countless possibilities, and how this technology will quite literally change our world.
Thanks for reading! My name is Yogya, and I am on a mission to learn, grow, and impact our world. You can connect with me through my LinkedIn, and make sure to visit my page for more content soon!
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