Remember George Orwell’s society, subdued by Big Brother’s complete control of thought and feeling? 1984 came and went, and nothing happened; we dodged the bullet. Or did we?

Memories…

“I cannot but remember such things were,

That were most precious to me”

-Macbeth, William Shakespeare.

One of the fondest memories of my youth is dancing a tango called “Memories” (I’m giving away my age) in a sidewalk café on the Mediterranean coast on a warm summer evening. Strange what our brain chooses to retain forever. Even stranger is what experiences most of us forget, while others remember forever. I am talking about Post Traumatic Stress Disorder or PTSD, which many of us participating in the horrors of war easily forgot while others are doomed to re-live them again and again. Why?

 

What long-term memories are made of

It has been generally accepted that long-term memories are maintained in the brain by structural changes in the synaptic connections between neurons. You can actually see them in a microscope; the neuronal connections that contain the information of a particular memory become thickened as a result of protein synthesis, and once formed, it is very hard to get rid of them. In other words, they are “long-term” As it commonly turns out in biology, this is not the whole story.

As always, behind every successful feat of biology, there is an enzyme. It’s true of memory, as well. It has been known for a while that the enzyme PKMξ (which for us, mortals, is Phosphokinase M zeta) and other similar enzymes are required for the early stages of memory formation. But it was always thought that once the thickened connections are formed, nothing else is needed to retain those memories. Now comes an international team of neuroscientists from the U.S. and Israel (Science, vol. 317, pp. 951-953, 2007) and reports that PKM zeta is essential to the maintenance of long-term memory. They fed rats with a saccharin solution, which rats simply hate (can you blame them?). They followed up 40 minutes later with nausea-inducing lithium, just to make sure. They, then, injected into the cerebral cortexes of half the group with a compound called ZIP, which inhibits PKM zeta, and the other half with a placebo. As long as the experiment lasted (25 days), the group injected with ZIP, the PKM zeta inhibitor, had no memory of the bad experience and drank again and again from the nauseating elixir. The placebo group avoided it like the plague.

“Remember thee?

Ay, thy poor ghost, whiles memory holds a seat

In this distracted globe. Remember thee?

Yea, from the table of my memory

I’ll wipe away all trivial fond records.”

Here is Hamlet, tormented by the memory of the assassination of his beloved father, trying to selectively wipe out fond memories so as to accentuate the pain and seek revenge. Great poetic drama, but is it possible?

The implications of the report in Science are literally mind-boggling. It is quite simple to inhibit all long-term memory formation by inhibiting the formation of the thickened connections between neurons through the use of protein synthesis inhibitors. But this is tantamount to killing a mosquito with a hydrogen bomb; you, and your memories, will be wiped out.

Now that we have an enzyme as a potential target, it is only a question of time before specific enhancers and inhibitors will be synthesized. Now, we are talking “smart bombs” rather than nukes. How wonderful would it have been if instead of memorizing Hamlet and Macbeth in high school, I could just pop a pill enhancing PKM zeta’s activity? Or, wouldn’t it be great if we could cure all our traumatized war veterans with a simple drug inhibiting the enzyme, something like ZIP?

 

It’s not so simple

On the neurobiological level, we still don’t know that we can be selective. We don’t know if we can wipe out unwanted memories and retain the rest. But this is eminently susceptible to testing, and I am sure it will be done in short order. Sorry Hamlet, you have been waiting for 400 years; wait for a few more.

But a deeper question, and less prone to unequivocal answers, is the psychological, ethical, and moral question: Do we want it? On the one hand, we witness the torment of our Vietnam and Iraq veterans suffering from PTSD, and we reflexively answer: Of course! But ask Eli Wiesel if he would want to forget the Holocaust. Who would be a witness today to the horrors of yesteryear? Or would Primo Levi write his masterpiece If This be a Man or Survival in Auschwitz if he simply wiped out his horrible memories? Oh, yes; Primo Levi finally succumbed to the recurring torment of his private hell and committed suicide. Would he have preferred to forget it all?

And on a political level, do you trust governments to resist the temptation of suppressing “inconvenient truths” with an easily administered pill? The Russian government reverted to the Soviet practice of interning investigative journalists in psychiatric wards. What if they wanted to wipe out any memories of inconvenient revelations by the courageous journalists? What if our soldiers were ordered to take the pill after every brutal engagement?

These are tough questions. Science is neither good or bad; it is neutral. What we do with it is fraught with bright promise and dark danger. What shall we choose?