we couldn't all be cowboys, so some of us are clowns

So, last week, I bored a bunch of you to tears by talking about antisense technology as a therapeutic approach to treating cancer. ads, being ads, jumped in with the idea of siRNAs and shRNAs. I dwelled in nerdy bliss for a few days over this. And then, today, I discovered that a paper was just published that proves that siRNAs and shRNAs can suppress the activity of two flaviviruses (and one of them is the often-discussed in California West-Nile Virus) in mice. Granted, this was proven in mice. And yes, the molecules had to be injected directly into each mouse's brain. But it worked.

That last paragraph might seem like a bunch of gibberish, but the take away is this: there has not been developed a cure for West-Nile Virus by any means. But a step has been taken. And that is how it always goes in research. You take one step forward, and it can seem monumental. And sometimes it is monumental. But it is one step. And there are many steps before you discover whether you are on a path to a major breakthrough or you are just barreling into a brick wall.

Research, then, seems to require some specific characteristics in people. First, it requires that making a single step feels purposeful enough. Of course, it really is purposeful. Even if that winds up being a step on a dead-end path, you have to make the map, or the next person is doomed to stumble around just as blindly. Still, that is easy to write, and hard to believe when you have spent five years trying to elucidate the structure of one molecule, for example. Secondly, it demands a single-mindedness that keeps you from second-guessing yourself. You need to be smart enough to know you might be wrong, but have the cojones to say, f*ck it, b*tches, and take that next step anyway. More often than not, this also means you need a doggedness that tells you to strive for victory where others have failed. With most discoveries, it is not that the explorer was the first to think of it. It's that they were the first to not talk themselves out of it. And that is quite a tightrope to walk, between brilliance and madness.

The favorite example I have seen play out of this is Judah Folkman. When I was an undergraduate, my professors used to all sniff upon mention of Folkman, and elude to him being slightly off-kilter and very much arrogant. For decades, he had been advancing his firm belief that cancer tumors were angiogenesis-dependent. What is angiogenesis? It is the act of growing new blood vessels. The idea here is that tumors, in order to continue to feed their out-of-control growth, need to spring their own blood vessels to keep wreaking havoc. For a long time, Folkman was fairly alone on the pulpit preaching about angiogenesis.

His work has since been thoroughly validated. In fact, one of the bigger breakthroughs in oncology therapy in the last five years has been the emergence of anti-angiogenesic therapy. Shut off a tumor's blood supply, and it cannot grow anymore. It is not a cure, but it is extending patients' survival.

But here's the thing: Folkman has been saying it since 1971, and it was not until 2003 that the tree truly bore fruit. That is a long wait. How did he know that he was onto something real and true in 1971? How did he know that it was worth shouting out from the rooftops? How did he stay so determined to prove he was right through decades of rolled eyes? And was any of it conscious at all? I always wonder in these situations- is this just how he saw the world? In his world, in his head, it made sense. And he just wasn't cut from the kind of fabric that would doubt his own mind.

I do not know. But I remain in awe, while deeply aware of my own shortcomings in this area. Forget about research. I can't even trust my own mind on the day-to-day drudgeries of existence.