The last episode of Elementary (S1 E17, Possibility Tw0) inspired me to concoct the perfect murder.
In this episode, the murderer secretly develops a new drug to give someone a disease called "Cerebral Amyloid Angiopathy" or CAA. Whilst we are assured by the fictional geneticists portrayed in this episode that "It's plausible, given unlimited resources", I decided not to take their word for it. I decided to try to figure out how I would do it myself, assuming that I had unlimited resources.
So first, I needed to understand the disease that I'm trying to cause. CAA is caused by the build up of a protein called Beta Amyloid in the capillaries within the brain, and eventually block them off. This prevents oxygen and other vital nutrients getting to these parts of the brain, leading cells dying off. The sufferer loses their cognitive functions, and experience dementia. If we want to trigger this disease in our victim, we need to figure out why Beta amyloid builds up in their brains.
One possible culprit is a fault in how the gene that encodes this protein, known as APP is controlled by the cell. When a gene that in the nucleus of a cell needs to be turned into protein, it has to find some way to deliver it's genetic information into other parts of the cell where protein is actually made. To to this, mRNA copies of the genes are made, which are sent out from the nucleus to the cell's protein factories. But the mRNA has a few hurdles to overcome before it delivers its message. The cell doesn't always want all of the information to be transcribed. The cells have their own internal editing staff which can chop off bits of mRNA, and alter the ways proteins are expressed. These fussy little editors are known as MicroRNA's. They can recognise specific sequences on an mRNA strand that they don't like, and splice them out of the finished molecule. One microRNA in particular, called MiR-124 acts on the APP gene.
This is important to us, because there is one part of the APP gene which is associated with an increased build up of Beta Amyloid when the APP gene is turned into protein (Amyloid precursor protein to be exact). Under normal circumstances, MiR-124 splices out the dangerous segment of the protein, and prevent the build up of Beta Amyloid. So if our assumptions on MiR-124 are correct, blocking it can cause CAA.
How do we go about doing that ? We can use a gene therapy to disrupt the function of this microRNA. There are tiny MicroRNA-like drugs called morpholinos, which we can design to block MiR-124. If we give enough of these to our unsuspecting victim, we can get the levels of Beta amlyoid to build up in their brain until they have CAA. Unfortunately we don't know how many days this will take, which is a pretty big problem when we take into account pricing. Through a convoluted set of calculations that I don't want to go into here, I found that it would cost $189,000 for each daily dose.
This murder method is further complicated by the fact that this drug can only be given by intravenous injection. So you'd have to find some way of covertly injecting someone daily with this drug until they started showing symptoms of the disease.
The murderer in Elementary solves this by putting the drug into the I/V lines of patients whilst they were recuperating in his hospital. So why did the murderer go to all this trouble and expense to kill people with CAA ?
It turns out the most crazy thing about this episode was the murderer's motive. The murderer wanted to get more funding to find a cure for CAA. The murderer did this by using the "unlimited resources" that the fictional geneticists mentioned earlier to cause CAA. This get's even more insane if we assume the murderer is using our method of causing CAA. You see, with a small edit, we can use a morpholino to mimic the MiR-124 microRNA. In a person suffering from CAA, MiR-124 has been shown to be lower. If we assume that this is the cause of the disease, then we can use this to actually treat CAA.
Now , I should be clear that the connection between MiR-124 levels and CAA have not really been proven, and all of this is just informed speculation. So why did I tell you about it ?
I wanted to make the point that if we do end up finding a way to edit our genomes to the point where we can maliciously cause diseases, we will also be at the point where we can edit the genome to cure them.
It's not often I am forced to re-consider my perspective on the future of medical technology, and even rarer that it's caused by a procedural drama like Elementary. But as Sherlock Holmes himself puts it at the end of the episode :
"A good detective knows that every task, every interaction no matter how seemingly banal, has the potential to contain multitudes. I live my life alert to this possibility."
I have a much longer (illustrated and fully referenced) version of this article can be found on my other blog:- http://defectivebrain.fieldofscience.com/2013/03/elemen…