The bright researchers at MIT & Harvard deserve widespread recognition for their breakthrough CRISPR application research. The write-up, which you can read here dives into some of the promising applications of their findings. Since most of the world knows very little about the topic and the underlying basics of genetics, this article is intended to help bring some simplicity to the topic and hopefully some excitement about this discovery.
I've found it useful and effective to explain genetics using an analogy to syntax and grammar. Read on to follow me on a simplified explanation of the world of genetics. You can, of course, skip to ahead here, but I hope you enjoy the lesson.
First, let's convert some basic genetic terms into syntax. The Genome is the entire collection of our DNA, like a complete encyclopedia (or Wikipedia for the younger generation), offering instructions on how to make a human being. The Exome represents all of the books which contain instructions which we call, the coding regions. The rest of the Genome, that's not the coding region consists of indexes, references tables, *annotations, and other essential parts which do not provide instructions. Genes would be each volume containing very specific instructions. Those instructions are Exons in the forms of say paragraphs or steps needed to carry out a specific action. Introns can be viewed as pertinent spaces, indentations, bullets, etc., which could influence the exons. Think about if you placed too many spaces and how tha t woul d read. SNPs (pronounced "snips") might be best described as nomenclatures which don't necessarily change the meaning of instructions but could provide an understanding of the traits of the writer. Like writing "cannot" instead of "can not." A variant is any spelling or grammatical change. That change can range from being simple and having no effect to being simple or complex with definitive effect. A complex change could be an omission, a shifting of an entire paragraph, or an entire duplication of a chapter. The reason those are complex is that they're harder to identify. Think of it this way: would spell check catch that I've repeated this question? Think of it this way: would spell check catch that I've repeated this question?
RNA is uniquely different from DNA, and scientists are interested in understanding how RNA is "expressed." To best conceptualize what is meant by RNA expression, try pretending that cells are blind. They cannot read the DNA instructions and rather must hear them. Therefore the text is transcribed into audio instructions, and this is known as RNA transcription.
If you're still with me, follow me further on this imaginative journey. Imagine that this is an instruction found within our DNA:
" If you encounter a bare while hiking, stop and back away slowly, in the direction you came. Walk, don't run, and keep your eye on the bare so you see how it reacts. "
I want you to read the above sentence out loud. When you do, is the meaning of that sentence altered by the fact that I misspelled bear as bare? It is not. This would be an “ineffective” missense mutation arising from a point mutation where a nucleotide (a single letter) was swapped. Where swapping the letter “a” and “e” of bear to bare does not change that it’s still a four-letter word, nor does it change the total effect of the sentence. In the same way, most gene variations are just as harmless when it comes to affecting the way the instructions are carried out. Your cells do their job perfectly fine. So then, finding gene variations is not the goal. Uncovering their effect matters most. What if I swapped the "a" out for another "e?" If you encountered beer in the woods, you may have found a very cool campground.
To exemplify how other types of variations can actually change the instruction entirely let's think of an Indel. An Indel is short for "insertion or deletion." Now, imagine deleting the “Walk, don’t…” part of the instruction above, and the instruction began with “Run.” That might be bad, and it is certainly an “effective” variation.
Finally, I arrive at CRISPR.
Before, I asterisked the word "annotations" and that's because I wanted to return to this and highlight a relatively new discovery about genetics. It turns out that DNA can keep a record of its changes and experiences. In a way that's similar to annotations in a document, you might share at work. It was that discovery that led to the hypothesis of using CRISPR's to edit genes. By leveraging DNA's natural ability to annotate itself, we might be able to make changes. It turns out, the hypothesis is right, and now while there's a whole other email to be written here, I'll keep it simple and in line with the analogy. CRISPR is a manual audio spell check.
So what did guys at MIT and Harvard do? Right now, most researchers are using CRISPR to edit out "bad" DNA in organisms in order to stop the spread of disease. That, in and of itself has massive implications with many calls for concern. In the MIT discovery, they demonstrated that CRISPR could be used further "up the stack," by catching and stopping the spread of disease without changing the molecular biology of the organism itself. Instead of changing the "bad" genetic code, we can catch the "bad" the effect instead. Thus keeping the molecular integrity which makes each organism unique Whereby otherwise, the concern is that if a DNA edit is made to one organism, would then also change the genes that the organism passes on to its future generations. From bacteria to human scale, the future implications to any organism's lineage has unforeseen and "God-like" impact. They proved that instead, one could apply a barrier to stop the harm that organism might unintentionally do to us, our crops, our water, and so forth instead of changing the organism. A matter of intent versus effect, nature versus nurture, and breed versus stigma.
It's also a matter of us versus nature, as we are the only ones with the consciousness to have contention with life at this scale; as far as we know.
Back to the point. What's the difference? Allow me to compare the current plan or an idea to end Malaria with CRISPR edited mosquitoes with an alternative solution using my imagination of what's now clearly possible as a result of what MIT-Harvard proved. Instead of changing the genes within the mosquitoes to stop them from carrying Malaria, we could create a bug spray for our skin. Whereby the spray would detect the Malaria carrying code the moment the mosquito plunged it straw-like mouth into our skin immediately rendering the disease impotent from infecting us.
Effectively, they've created the foundation for products to be powered with gene-alteration detection which can deploy an autocorrect type of feature AND an emergency brake to stop any potential harm that may be inflicted. This would attenuate the moral and ethical concerns and debates about our inability to predict the consequences of altering life itself. Their work has profound potential for drug delivery, screening, and diagnostic tools. The range of use cases is vast, which could span from mechanical medical equipment (tubes, filters, screening tools, etc.), to digital software, and from ointments to oral medications or vaccinations.
We could be better prepared to more quickly respond and defend against future epidemics, pandemics, or from intentional malicious biological attacks of war!
Congratulations to you all.
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