If you’re like most people, you will have chosen the last face, which is actually a composite of the other 5 faces (source).
Each individual face has its flaw(s). Spock ears, mildly everted lips, incongruous eyebrows, etc. No face is ideal. But when combined, these flaws are evened out.
Same thing with siRNAs. Each individual siRNA has its own ugly off-target signature. But combined in a high-complexity siPool, the off-target warts are removed, and you’re left with a beautiful on-target phenotype.
And not all facial averages are equal. Perrett et al. found that a composite face created from faces pre-selected as being more attractive was preferred over a composite created from all available faces.
Likewise, siPools are composed of the best available individual siRNAs.
Being selective about what goes into a siPool is important, as we will discuss more in future posts.
This amusing anectdote from the autobiography of Francis Galton is à propos. (Galton pioneered composite facial analysis, in addition to finger print analysis, as discussed previously)
I could not make good composites of lunatics ;
their features are apt to be so irregular in different
ways that it was impossible to blend them. I took a
photographer with me to Hanwell, where it was
arranged that the patients should sit two at a time on
a bench. One of them was to be led forward and
posted in front of the camera, while his place on the
bench was filled by the second patient moving up
into it, whose previous place was to be occupied by a
third patient It happened that the second of the
pair who were the first to occupy the bench considered
himself to be a very mighty man, I forget whom, but
let us say Alexander the Great. He boiled with
internal fury at not being given precedence, and when
the photographer had his head well under the velvet
cloth, with his body bent, in the familiar attitude of
photographers while focusing, Alexander the Great
slid swiftly to his rear and administered a really good
bite to the unprotected hinder end of the poor
photographer, whose scared face emerging from
under the velvet cloth rises vividly in my memory as
I write this. The photographer guarded his rear
afterwards by posting himself in a corner of the
room.
Memories of My Life, pp 262-263
