There are more things in heaven and earth, Horatio,Than are dreamt of in your philosophy. - Hamlet
Bacteria for obvious reasons don’t like that.
It is akin to the Hepatitis virus infecting the human liver cell and using it
for its own propagation to the detriment of the host cell, causing inflammation
of the liver as a whole and sometime death of the infected individual; Infect a
cell, multiply within (CCCs) and then infect more cells and the parade goes on
until the immune system kicks in and the fight leads to the hepatic inflammation.
Okay, so the bacteriophage (virus) has attached itself to
the bacterium surface and injected its DNA within it. The Bacterium also
happens to have its own piece of coded DNA in place and within it is this nifty
fragment called the CRISPR (clustered regularly interspaced short palindromic
repeats). These repeats are so called “Spacers” (25-30 nucleotides) and sandwiched
within these repeated palindromic segments of nucleic acids are cleaved
portions of the infecting virus’s selected DNA fragment. There are many such
repeats and bottled in between two CRISPRs is a unique fragment of the viral
DNA. Multiple fragments from the same virus or one or two from many different
viruses reside here.
One can look at it as a “Guest House” All guests visiting
the Great House must live in there. Each guest has a bodyguard on duty, where,
if they are noted to have mischief in their DNA will be handled swiftly by the bodyguards
and delivered to the police (in this case Cas9 protein) without harming the
owners of the great house beyond.
As I was saying, the CRISPR holds these
fragments in check and when a similar virus happens to stroll along that has
previously caused mischief by injecting its DNA to cause harm, the CRISPR goes
into full throttle, slashing and killing the deadly DNA.
Funny you should ask about CRISPR. It is the most talked
about latest technology to hit the media. In fact the two ladies; Jennifer
Doudna and Emmanuelle Charpentier were nominated for a potential Nobel Prize in
Chemistry. So that brings us to the question, what’s the buzz about?
It is a big as in B I G buzzy development! Let us look at
where this CRISPR came from first and then address how it might help us down the stretch.
Bacteria and viruses happen to have survived on this planet
much longer than humans. Those two microbes have developed a relationship with
each other. Since no one wants to be vanquished by another, the bacteria have
developed a strategy to prevent the viruses from using its cellular interior from
being used as a factory for producing more viruses and then discarding it to
the “file cabinet.” You see, viruses that infect bacteria are called
bacteriophages and in so doing, they insert their DNA into the bacteria to
circumvent the bacterial machinery so they can produce more of their own
progeny. Kind of like your in-laws visiting your home, staying in it for a long
time and eventually by proxy taking over the ownership.
Okay, so the bacteriophage (virus) has attached itself to
the bacterium surface and injected its DNA within it. The Bacterium also
happens to have its own piece of coded DNA in place and within it is this nifty
fragment called the CRISPR (clustered regularly interspaced short palindromic
repeats). These repeats are so called “Spacers” (25-30 nucleotides) and sandwiched
within these repeated palindromic segments of nucleic acids are cleaved
portions of the infecting virus’s selected DNA fragment. There are many such
repeats and bottled in between two CRISPRs is a unique fragment of the viral
DNA. Multiple fragments from the same virus or one or two from many different
viruses reside here.
The CRISPR segment creates a messenger RNA that merges with
the single strand of the DNA of the double-stranded virus (guide RNA or gRNA) and
then is rapidly segmented further by being cleaved containing multiple smaller
strands each containing a viral DNA fragment and the CRISPR spacer called the
crRNA. These fragments attach to the transactivated RNA or tracrRNA and that helps
bind to the Cas9 protein and then the orgy begins.
The Cas9 protein cleaves (cuts) away all the crRNA that are
attached to the viral DNA in exactly the spots where they are attached thus
fragmenting the viral DNA and rendering it useless from further replication!
Imagine the simple ingenuity of the Bacterium. But here is the kicker, the
viruses don’t sit back and take this kind of bullying within the CRISPR Guest
House either. They perform Single Nucleotide Polymorphisms (SNP) or colloquially,
single point mutations and thus try to hoodwink the bacterium from recognizing
the DNA strand. That single SNP is enough to throw the whole game asunder. And
it does. But the slow-poke bacterium compared to the Ferrari driven viruses
adapt albeit slowly and incorporate the new segment within and thus the battle
for survival and supremacy proceeds anew. When the bacterium divides the latest
CRISPR information also goes with it to the daughter cells to help protect them.
And the species survives!
And you might ask, how does this help us?
And rightly you ask the most daunting of questions. The
answer is simpler than you think. If we can use the nuclease enzyme to cut out
a bad portion or multiple bad portions of the human DNA and insert the healthy
version into the stem cell, Voila, we have a healthy being! But before you go
drinking and smoking hoping for the CRISPR to save your DNA mutations, consider
this, we are a long way away from using this technology in humans. The
unintended consequences in tinkering with a single gene insertion for a single
gene = single disease paradigm might be low but inserting mRNAs that enhance or
suppress gene functions and placing them as lords over the genome might have
serious pitfalls. You might cure the cancer and kill the patient with some other
evil. Happens! As you are aware that “the
hip bone is connected to the leg bone…”and so on, a change here might make a
big change there. If you are into the butterfly effect the analogy fits well
here. Reminds me also of the Lorentz strange attractor, but we will leave that
for another day.
We certainly can keep this wonderful technology in the
laboratory and mess around till we have more data to configure the monster of
Lamarckian twists that lurk within this technology. Many hundreds if not
thousands of experiments are needed to evaluate the hypothesis in a controlled
environment and after validation, with trepidation move ever so slowly in the
human sphere. But those in love with the “Disruption” fall madly in love and
leave caution to the wind. And the wind can be destructive. There are pernicious consequences in the split between what is and what could be. So careful out
there, girls and boys!
In cancer for instance, one might snip away a mutated oncogene
or have a RNAi sitting adjacent to and enhancing a tumor suppressor gene to
shut down the cancer process. The possibilities are endless. Similarly
Infectious Diseases could be rendered moot by vaccinating individuals at risk
with a CRISPR Cas9 system to destroy the invading bacteria.
Speaking of vaccinations, this is nature’s way of
vaccinating against an invader. Plug in the coordinates and destroy the target.
Mission Possible!
The mechanism and the understanding are not as daunting as
one might think, but using them without safeguards is akin to future genetic
disasters. Just sayin!
We have infectious diseases, cancers, chronic illnesses, hereditary
genetic misfortunes to consider in alleviating the burdens on humans but we
have time and some hard work ahead.
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