Bio-hacking: Welcome to the future, engineering our own deaths!
Half a century ago, if I were to tell people that one day they would be able to choose and edit their own genes in the future — they would probably believe me. Genome engineering has been around for longer than we give it credit for.
In fact, DNA was first discovered in the late 19th century by Swiss physiological chemist Friedrich Miescher. 1869 was a landmark year in the field of genetic engineering. It established the much needed ground work for the evolution and understanding of human DNA.
Miescher revolutionized the field of genetics with his discovery of the material inside the nucleus of a white blood cell, which he called ‘nuclein’, which eventually got changed to nucleic acid, and eventually to Deoxyribionucleic acid, or as we know it DNA.
Miescher used the nuclei in white blood cells found on the bandages of his local surgical clinic to expand on his discovery of this mysterious new substance. After diving deeper, he encountered a substance that piqued his interest, with properties including high phosphorous content and a high resistance to protein digestion. Upon further research, Miescher realized that he had stumbled upon a prolific discovery that would go on to revolutionize the field of bioengineering, or as many like to call it, biohacking.
But Miescher was not the first to establish a vague idea of genetics or traits for that matter. In fact, this story begins in a monastery in the mid 19th-century with a monk turned mathematician, Gregor Mendel. Mendel was the first to establish a system of inheritance by conducting his famous pea pod experiment; in which he studied the traits of pea pods being passed down through the next generation. Darwin himself conducted several studies on inheritance.
Both Miescher and Mendel were instrumental in the discovery of DNA, but it was through the discovery of biologists James Watson, Francis Crick and Rosalind Franklin that we were able to further understand the chemical and physical properties of DNA, including the most notable of them all: the double helix.
But today, DNA is simply the canvas of our bigger picture, genome engineering. The first genetic engineering project was the production of a bacteria resistant to a common antibiotic Kanamycin. Eventually, within the span of a few years, scientists engineered the first animal (a mouse), and went on to engineer plants as well; something your parents might know about.
There was much controversy stirred about common vegetables like tomatoes and lettuce, being engineered to possess capabilities like longer shelf life and better taste. This eventually led to the fine distinction between organic and GMO foods.
The key to genetic engineering is our best friend, and likely the cause of our next world war is CRISPR. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, but I don’t think either of us have the time or willpower to understand what they mean ;).
In simple terms, CRISPR is a gene editing device that has almost limitless biological capabilities that allow it to find and change DNA in a cell. CRISPR is being used to splice and replace DNA that could potentially have lifesaving capabilities.
But our hipster-y Chuck Norris on his way to take over the world has trouble making detailed, specific changes to cellular DNA. CRISPR is ideal for broad and vague splicing of DNA. Recently, scientists have discovered a new method of gene editing, prime editing.
Don’t we all have that one sibling, relative or friend that we compare ourselves with that’s somehow superior in every aspect? That’s prime editing in a nutshell. Think of prime editing as the better looking brother, or sister for that matter (Rosalind Franklin?) of CRISPR.
This new method, prime editing, is perfect for detailed cellular DNA editing. Think of it like CRISPR on steroids. Prime editing uses the ‘search and replace’ technology that CRISPR pioneered in, just in much more detail. It has the ability to find and replace individual strands of DNA by using an RNA guide.
To understand how Prime Editing works, we must first understand CRISPR.
CRISPR has 2 main components.
- CAS-9 Enzyme
- Guide RNA
The CAS-9 enzyme essentially cuts the wanted part of DNA, like a pair of scissors! But how does the CAS-9 enzyme know where to make the big snip? This is where the guide RNA kicks in. The guide RNA consists of the navigator and the target sequence. The target sequence simply lays out the path for the RNA to follow (with the CAS-9), and the navigator leads the way!
Once they reach the target DNA, the CAS-9 enzyme, binds itself to the target sequence of the double strands (the RNA), and snips out the intended portion to insert either a mutation of the original, or a new sequence in itself.
Basically CRISPR is conducting a kindergarten cut-and-glue craft, inside of your DNA!
Prime editing on the other hand, instead of being regulated to snip both strands of our DNA, can edit one DNA strand alone. It is divided into 3 main components
- Our old friend the CAS-9 Enzyme
- The Reverse Transcriptase Enzyme
- CAS-9’s bestie, the Guide RNA
The CAS-9 enzyme continues to function as a molecular scissor , but in this case, it only cuts one strand of DNA as opposed to both.
The Reverse Transcriptase Enzyme reads the RNA and uses it as a template to create complimentary DNA to the particular RNA strand!
The third component of prime editing is PEG-RNA, or Prime Editing Guide RNA. The guide RNA acts like a navigator guiding the complex to the target DNA in the genome.
Next, the PEG-RNA forms a complex with the CAS-9 enzyme and the reverse transcriptase.
Once the PEG-RNA guides the newly-formed complex towards the target location, and snips a part of the DNA.
There are 2 distinct parts to the PEG-RNA. One of the pieces is the earlier-produced complimentary DNA that binds to the snipped DNA, and the second piece is the RNA sequence that codes for the new edit!
Our transcriptase then goes on to read the RNA sequence on the PEG-RNA, and then reverse transcribes the RNA to form the new DNA for the snipped target area using the nucleotides.
The same process is now repeated for the second strand, to achieve the desired outcome, it can be tweaked as needed, but now the first strand serves as a working template for the second.
Overall, Prime editing holds worlds worth of potential to drastically change what we know as human evolution, and possibly even deter the course of us destroying ourselves as a species. Many view prime editing as the key to our future, as it holds promise to cure hereditary diseases and in the future, could also be used to contribute to human enhancements.
For example, China is spearheading the efforts to cure cancer using genetic engineering, because cancer, like many other terminal illnesses mutates based on the genetic and cell structure in each patient’s body, hence there is no as such ‘universal’ cure to it, rather, the gene editing therapy would be modified in such a way that it would mutate to serve each host patients cells.
In specific, I want to talk about how gene editing can pair with optogenetics. Optogenetics is an experimental medical treatment that uses a combination of optics (lights) and genetics. The idea, is that through genetically modified cells, we could, in theory activate these cells to conduct certain operations by a sequence of lights.
The field of optogenetics is known for enabling precise temporal and spatial control. Using genetically encoded tools, like microbial opsins, we can control cellular action through an advanced sequence of lights. We can combine CRISPR and optogenetic tools to create photo reactive cell structures. In theory, these tools would allow scientists to cue certain cellular actions through certain light sequences.
We can achieve such an end product using 2 experimental fusion proteins.
- The genomic anchor — an inactive, dead Cas9 protein (dCas9) fused to CIB1
- The activator — the CRY2 photolyase homology region (CRY2PHR) fused to a transcriptional activator domain (VP64 or p65)
Upon photoreactive patterns being induced upon the subject, dCas9-CIB1 fusion binds to the target DNA sequence as directed by the guide RNA (gRNA), while the CRY2PHR-activator fusion floats freely. The best performing combination was NLS-dCas9-trCIB1 and NLSx3-CRYPHR-p65 — it had the lowest background activity in the dark state and highest fold induction at 31X, hence saying that the particles reacted best to the given pattern.
By using a slit pattern during blue light exposure (470nm), the researchers showed that expression of the human ASCL1 gene could be spatially controlled in a reversible and repeatable manner. Hence proving our theory that genetics and optics can be combined, especially with the precise hand of prime editing guiding us.
Optogenetics and Prime editing is also being use to treat neural and spinal injuries. For example, optogenetics pioneered in that field, when scientists did an experiment on mice, realizing that they could activate certain neurons to treat the illness by light. Prime editing is being used to add a healing genome to these neurons or cells that can help treat the ailment faster.
There are several companies leading the way in the world of Prime Editing, and gene editing as well. I will just highlight 3 of the most interesting.
- Precision BioSciences is one of the best funded companies with bold goals in this field. They developed their own genetic editor with prime editing capabilities called ARCUS that has the gene editing enzyme, the homing endonuclease (rather than CAS-9 in a CRISPR machine). ARCUS is going to be used for precision treating chronic illnesses! They are the most promising because of their new ARCUS technology.
- Pairwise plants is also an extremely interesting company. Instead of focusing on human genome editing, they are working to genetically modifying fruits and vegetables from the seed itself to contain more vitamins, and be a healthier alternative to other options in the grocery store!
- Inscripta is perhaps the most interesting of them all. It recognizes itself as a digital genome editing platform, in which scientists can ethically experiment with genes, using their own assay, called the Inscripta Machine. They have developed their own cell nuclei called the MAD-7 nuclease which they are working to distribute worldwide for experimentation!
Overall, prime editing shows strong promise in the fields of human enhancement and evolution for the matter — but there are too many ethical concerns surrounding it.
For long, ethics has clouded the field of medicine, second guessing the pioneering works of medical researchers, but to put it simply, Prime editing is a whole new ball game. The science of genetics is expanding faster and faster, and according to many who pioneer in the field, designer babies are on the horizon.
One of the most notable names in the world of genome engineering is Dr. He Jiankui, who claims he created the first genetic engineered babies. Dr. Jiankui performed an HIV test on the embryos of twins, and found out they tested positive.
Without telling his peers, he went ahead to use CRISPR/Prime editing technology to snip the HIV gene out of the twins and reinsert a mutated sequence, hence the babies were born healthy.
Dr. Jiankui’s story is just one of many, of doctors’ around the globe who are working hard to cure the genetic issues that plague our world, but many say that it is unethical to ‘play god’. Many high-profile scientists at the International Summit of Human Genetics have spoken out against gene editing, claiming it would be similar to opening a ‘pandora’s box’ .
We have gotten as far as editing genes to cure diseases, and are working on many more, but the perennial question in genetic ethics is where do we draw the line? The boundaries are ever moving. Today, we are curing diseases with genetic engineering, what comes next? Scientists say designer babies, are not out of reach after all.
One day, the time will come when we cross the line into genetic enhancement, and design our own babies, cure them free of all diseases, but violating the system of nature placed before us since the dawn of time. Mortality rates would hit an all time low, with genetic engineering soon becoming something as a normal in the future, hopefully it can be affordable as well. Population will spike, and the rich will have the best of it.
The real question is not why we should cross the line into enhancement. No, we have already begun that journey, there is no turning back. The question is when?
When we, not only as individuals, but as a people, realize that once we cross this line, there is no going back, THEN only can we succeed. We as a people, not as individuals will have to deal with the consequences; or the discoveries of genome engineering. We must ask ourselves, is it worth the risk? Is our world going to be full of future captain America’s? Are we engineering our own demise? What the future holds in store for us, we don’t know, but as Caesar once said before crossing the rubicon, alea iacta est. The die is cast.
