Small, Yet Mighty: Lessons from CRISPR
Updated: Oct 8, 2019
A common theme in biology is that no matter how smart we think we are, or how ingenious one of our artificial experimental or therapeutic techniques are, nature is ALWAYS smarter and more efficient.
For years, researchers were faced with a problem in genetic engineering: The distinct lack of proper tools. Bio-engineered genes could be constructed with relative ease, but nobody could accurately insert their creation into the DNA of a cell. Not until the precise DNA cutting abilities of CRISPR/Cas9, a novel and unique antiviral countermeasure discovered in bacteria, were demonstrated.
The easiest way to imagine CRISPR/Cas9 is as a two-part pair of enzymatic "scissors" that are designed to cut through DNA at very specific points. Half DNA-slicing-enzyme, and half RNA-guide, this ingenious little guy is usually deployed by a bacteria to slice and dice foreign virus DNA when bacteria are invaded by a virus. However, in early 2013, researchers demonstrated by slicing genes in both human and mouse cells, this system could be configured for any gene sequence out there.
This humble scientific experiment gripped the world with two visions: one of an enticing Utopian future free of disease and the other of a dystopia resembling that of the film Gattaca. It rightfully ignited heated ethics debating how we should use this newfound power.
Thankfully, the majority of the world agreed that restraint was in the best interest of our species and that human experimentation should be cautiously approached, as while the new tech was truly revolutionary, it was still a long shot from being a viable instrument of genetic therapy.
Yet this caused a question to haunt the back of scientists' minds for years. This could be used to create engineered humans! What would that mean?
We didn’t have to wait very long to find out.
In November of last year, He Jiankui of Southern University of Science and Technology in China announced to the world that he had created the world’s first genetically engineered babies. Twin girls, named Lulu and Nana, had been altered using the CRISPR/ Cas9 system to target gene CCR5 in an effort to cause a mutation that would grant them protection against HIV.
Welcome to the brave new world.
The news froze scientists across the globe and brought forward a startling realization: There is far more at stake here than the technological progress of mankind.
The He Jiankui incident revealed to the world the danger of our rapid pace of scientific discovery. Unbridled scientific progress is, to apply a botanical simile, like a magnificently tall tree devoured from the inside by termites. Without a strong core, without guiding principles, ethics, and most importantly, purpose, such a tree can fall prey to even a relatively mild storm.
This becomes a serious issue when one lives in the shadow of such a tree.
Science conducted for the sole purpose of, “can we do it?” is very dangerous.
To quote the fictional Dr. Ian Malcom from the novel Jurassic Park, “Your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should.”
As human beings, we have a ontological responsibility to consider the purpose behind our actions. One clear purpose of CRISPR/Cas9 could be the eradication of terrible diseases, such as Huntington’s and Tay-Sachs. However, the same genome slicing tech could be used to wipe entire species from the face of the planet by those with more nefarious purposes, to say nothing of those simply in error.
The mosquito Anopheles gambiae, endemic to sub-Saharan Africa and a vector for malaria, causes over a million deaths annually. To combat this health crisis, researchers began to consider the best way to stop malaria from spreading would be to stop the mosquitoes from spreading. And we’re not talking about netting here. They mean permanently. By using gene drives, scientists could effectively carry out a mosquito genocide at the level of the creatures' DNA.
Here's how it works...
Remember, CRISPR/Cas9 is essentially a pair of highly specific genetic scissors. These scissors, researchers discovered, may be joined to a bio-engineered gene and then introduced into a population. Once introduced, the engineered gene spreads through that population at an exponentially higher rate than would otherwise be possible by more conventional processes. This takes place through a process called Homology which, while too technical to explain here in detail, allows damaged (or sliced) DNA to repair itself using similar nearby material (a nearby genetically modified gene, for example).
This is simultaneously exciting and terrifying--and it's almost here.
A team of researchers at Imperial College in London recently identified three genes in the malaria carrying mosquito, A. gambiae, that when mutated render the females of the species infertile. In highly contained laboratory experiments, this team demonstrated that 75% of a population of mosquitoes could be rendered infertile by their gene drive. Not quite 100% species eradication yet, but close enough to merit the question:
Should we do it?
What happens when we erase a major component of an ecological food-web? What fills that niche? And will the results of these actions create a better world?
It's smaller than a speck of dust, but CRISPR/Cas9 has the power to change the entire planet.
This incredible power, as unbelievable as it might seem, is yet another product that points to the importance of seriously considering our responsibility as individuals. There is something to be said, and not in a small way, for taking ourselves seriously. It was human beings that unraveled the mystery and might of CRISPR/Cas9; and now it is human beings that must decide how to use such power ethically.
There is a temptation, perhaps, to view this as a sort of dilemma we will never face. Yet in reality, humanity is every bit as interconnected as the genes within a strand of DNA. Our actions have ripple effects, consequences that stretch out across time and space. So consider, as you go about your daily life, what small decisions you might make that could slice through the tragedy of another person's life and infuse it with hope and a vision for the future.
We are all, in the end, small.
Small, yet mighty.
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