The biggest impact of reading the newly published book The Drug Hunters, in which pharmaceutical industry consultant Donald Kirsch writes about the histories of medicines like aspirin, penicillin, and insulin, is how it messes with your confidence about the future of health care.
Take the story of scurvy, which isn't a disease you've likely thought twice about. Just eat a little citrus, you'll be fine. But up until the mid-1930s, we didn't even know vitamin C existed. For generations, scurvy was treated with sulfuric acid, which is like treating stomach cancer with a punch to the gut. It wasn't until the mid-18th century, when a Scottish physician named James Lind made a lucky guess, that anybody even considered the idea that eating the occasional orange might be a way to make your gums stop bleeding.
Put that in a modern context. A disease like cancer seems impossibly complicated and scary. But maybe, like with scurvy, there's some obvious piece of the puzzle we've been missing, something right under our noses that we walk past every day and don't think twice about. Maybe in 100 years, everybody will be saying, "Can you believe people used to get cancer all the time? They didn't even know that eating lawn grass would have fixed everything!"
All it takes is one person willing to try something stupid—the 2017 equivalent of feeding oranges to sailors—to save millions of lives. Are you willing to count on that happening?
We called Kirsch to talk about big cures, lucky guesses, and the medical Mad Libs of his profession.
I haven't decided if your book is encouraging or terrifying. The big lesson seems to be, the fact that we have any medicine at all is really just dumb luck.
I would say it's more like smart luck. What's that famous old quote from (19th century French chemist) Louis Pasteur? "Chance favors the prepared mind." That may be true, but no matter how smart you are and how much you know, it's still luck.
Given the infinite number of compound possibilities, and the improbability of ever finding the right combination, is it remarkable that we've cured anything at all?
If you look at it by the numbers, it is remarkable. I once had a businessperson come to me, who was investing in finding cures, and he said, "Why don't you just screen every possible compound that could be a drug in one shot?" He thought this would save a lot of time.
Did you tell him he was full of shit?
I always try to be respectful, so I said, "Okay, I'll come up with a plan for you." There was a real nice study from (Swiss pharmaceutical company) Ciba-Geigy in the mid-90s, a sort of theoretical study that calculated the total number of possible drug compounds. It's 3 x 1062.
I don't even know what that number is.
It's an unfathomably large number. So I said to this guy, "Here's what I need. A purchase order for all 3 x 1062 compound possibilities, which I'm sure you'll have no problem funding because it was your idea. The second thing is, I'll need a place to store them."
So you were a smartass?
[Laughs.] A little, yeah. I told him, "If I take one molecule of each, and I pack them together at the same density of water, I'm going to need a compound room that would extend from the center of the sun out to the asteroid belt. So, why don't we start with those two things?" Is it safe to assume he took his investment elsewhere?
Yep. Is that part of the excitement of being a drug hunter? All the odds are stacked against you, and there's no rational expectation that you'll ever discover anything that helps anybody. You have to be naively optimistic.
I prefer to think of it as an optimistic dreamer. My wife criticizes me for being too much of a dreamer, but I think that's just in my DNA.
You think you were born for this line of work?
I once had an old boss who used to say, "What do you want on your tombstone? That you went on a luxury cruise, or that you cured a disease?" I think that impulse is what drives everybody. We all want to do something meaningful, something that lasts long after we've gone. For me, I want to help sick people.
When we're young, everybody has big dreams. Unpublished authors think they're going to write the next Great American Novel. Actors think they'll become the next Marlon Brando. Do drug hunters have something similar?
Do we want to be famous? Maybe not famous, but when you were young and ambitious, did you think, "I'll be the one who finds the cure for cancer!"
Everybody has different reasons. Maybe their grandfather died from a certain disease and they want to be the one to cure it. But for me, and a lot of drug hunters, we try not to be too grandiose. "Oh, I'm going to improve the human condition, I'm going to make America great again." You can't do that. I mean, it would be amazing to find the cure for cancer.
You'd get universities named after you.
Sure, of course. But what if I focused on a smaller disease, one that effects maybe 10,000 people across the world, and I find a cure for that? Well, that's not bad. I'd like to have that on my tombstone. "He helped 10,000 sick people get better." That's still pretty good. You wrote in your book that a drug hunter "never ends up with the same drug you started out stalking." How do you mean? You start looking for one cure but stumble onto another?
Look at something like ether. For years it was used to treat things like headaches, vertigo, epilepsy, palsy, hysteria, and rheumatism. It was worthless for all that. But then one day this dentist William Morton says, "I'm going to see if I can use this put people to sleep so they can have surgery." That was the trick. This was in the mid-1840s. Why couldn't somebody have discovered ether's effectiveness as an anesthetic in the 1740s? No reason at all. Just nobody had the idea. Those kinds of revelations happen even today. A drug meant for Alzheimer's has just been found to regrow human teeth. That's insane.
Remember when Minoxidil was used solely to treat high blood pressure? It wasn't a home run, but it did a decent job. But now it's used to grow hair. You rub it on your scalp. That was just a chance clinical observation. Somebody looked at a patient on Minoxidil and thought, "His hair seems a little thicker." Not all of the great drug discoveries were happy accidents. Sometimes it was thanks to some curious chemists acting like Keith Richards.
[Laughs.] Ah yes. There's a story in your book about Scottish physicians huffing a bunch of compounds just to see what happened.
And it worked! They discovered chloroform. That's also how people end up killing themselves.
That's what we call screening today. You behave like teenagers doing whippets behind a 7-11?
[Laughs.] No, no, no. We don't use our own bodies as guinea pigs anymore, but it's the same theory. You can rely too much on common sense. You just have to try everything and anything and hope for the best. It sounds like to be a drug hunter, you have to be a little bit insane.
You have to be a lot insane. It's not a career that makes sense on paper. You spend a decade of studying, going after your PhD, and when you finally get out and land a big job, well, let's just say there aren't a lot of financial rewards. The pay stinks?
Drug hunters don't get paid like physicians or lawyers. Not even close. That makes no sense. If you're talking about an economy based on supply and demand, what's in more demand than new drugs that cure diseases?
I'm not an economist, but I've found that when a career is especially exciting and fun and fulfilling, the pay usually goes down. Drug hunting is a very creative business, and it's about following your passions when there's no guarantee what you're chasing after will lead to any payoff. You take a pay cut when you're in that line of work.
The greed of big pharma has to be responsible somehow, right? They only pay out for the golden tickets, and the little guys always get screwed.
Yeah, that's what everybody believes. I was just listening to Trump's news conference last week, when he took a good swipe at the pharmaceutical industry.
He said pharmaceutical companies are "getting away with murder."
Right, right. Well actually, I don't think I agree. Big pharma isn't perfect, but it's also paradoxical. How so?
Look, we're dealing with people's survival, health, life and death. They're trying to make money from it. Tell me it's not going to be tricky. Sure, but the fear is these companies are more interested in getting customers hooked on medicine rather than finding a cure.
I wouldn't say "hooked." That's kind of harsh. But think about it: In any other business, it's all about sales. Just last summer, (biopharmaceutical company) Gilead was heavily criticized for a developing a Hepatitis C drug and then selling it for a profit.
But it was an insane profit, right? Something like $75,000 for a full course of treatment.
Which, admittedly, is a lot of money. But this is a drug that cures the disease, so they have to find a way to make a buck on it. That's a lot of bucks though.
I've heard arguments from public health groups, who basically said that if you're living with Hepatitis C, they have to do all sorts of supportive treatments to keep you alive. Even at Gilead's huge price point, it's still cheaper than nursing a sick person along for years and years and years. Plus, this is an infectious disease. You catch it from somebody. Because of this drug, we'll have fewer people walking around with the disease, and that means there's less chance of other people catching it. Overall, this cure, even at an outrageous price point, it's probably good for society. I still hate them.
[Laughs.] That's okay. I think they're used to it.