 In practice it's not sufficient to merely have a target and decide how small molecules are going to bind to it. Drug design or drug discovery is a far greater problem in general. So let me draw a patient here, Professor X. So Professor X is somewhat overweight, knows, we need a mouth, foreign eyes, and Professor X has a very small brain. If Professor X is now ill and wants to take a drug here, what happens? Well, let's say that this is a drug related to something in the brain. So this is really where we want things to act. That's the target molecule. First, we need to bind to the target. But second, we need to make sure that we're not binding elsewhere. It should not bind there, it should not bind there, it should certainly not bind there, it should not bind there. There are quite a few organs in our bodies. Many places where we don't want things to bind. And this means that first we need to eat the drug, right? Then this drug needs to go through the stomach. That's where everything we eat ends up. Then it should go out in the blood system and then it should go up to the brain and then in the brain it should magically reach the receptor. Then we need, after that we also need to somehow get it to work reasonably well there and then we need to get out of the body. We don't want this to accumulate in the body. This leads to a number of steps here that I'm going to go through. First, we have something called administration or absorption or administration. That is literally how we get the drug into the body. The problem here is that the stomach is a pretty nasty place. You might have pH 1 or 2 there. You have proteases. It can't be a protein. So we're going to need a very solid drug to get them there. And we also don't want the drug that is active in reasonably small concentrations because you don't want to eat 10 kilos of drugs per day. Then I need to be lucky. This needs to get to the target. And of course, luck is not going to count in practice. We have what we call the distribution in our bodies, that is. So the distribution here means that it has to be soluble enough to get out in the bloodstream and then it has to go through the bloodstream. Then it has to be small enough to get across the barrier between the blood and the brain because the blood is not freely exchanging with the brain. And then, by into this small receptor, that's going to be difficult. That's going to be really difficult. Then I need to make sure that once it's had this role, things are working fine. At some point, it's going to metabolize, i.e., be broken down. Metabolism. And we need to make sure that nothing bad happens here. In some cases, we can accept a few side effects. You might have noticed that there are several painkillers where they warn you against drinking alcohol if you've taken them. That's precisely because when they're being broken down, the pathways and the liver that are then used, they interfere with the pathways you normally have for alcohol. And if you mix the two, bad things can happen. Then, at some point, we need to go to the bathroom. Excretion. Well, I'm not so much thinking about what you do in the back room, but what happens in the liver and kidney, right? At some point, we need to get this cleanse of the body from this. We need to get it out from our bloodstream. You don't want a drug that keeps on building up in the body week after week after week because eventually the concentration will be so high that there are side effects. It's also a good idea if it's not toxic. Toxic is sitting. Well, everything is on a sliding scale. Even water is toxic if you drink enough of it. So we want something that is not too toxic, at least in the concentrations we need here. This process is frequently summed up as ADME and TOX. So when you see people in the pharma industry talk about ADME TOX, they often write it this way. ADME TOX is frequently the main problem in drug design. It's a much greater problem, any idiot almost, including me, can design a small molecule that binds to something. Solving all these problems on the other hand, this is where the vast majority of drugs fail. Because sure, you might have a great drug to treat, say, headaches. But if that drug doesn't survive in the stomach, it will have to be injected. How many patients do you think are going to accept having to go to the doctor and get an injection every time they have a headache? Nobody. That will never make it to the market. By far the best drugs are drugs that you can deliver in a slow and steady concentration, like with a patch on your skin or something. Unfortunately, that doesn't work for most drugs. We have people, even in my team here, trying to develop better formulation for that so that we can design drugs to do it. But hey, if we can't do that, at least make something that you can eat in small tablets and then gradually have it released. You would also like to be able to predict, say, the metabolism. Because you don't want to do human trials here, right? We would like to predict this already in the test tube. I'll tell you why in a second. So both the metabolism and excretion get super complicated because now we have a ton of very biological processes in the liver and kidneys or so to predict them. And same thing there. We would like to predict that it's not too toxic early on. These are side effects that would otherwise show up when you're testing things with a million patients. And that's where drug design companies cry and fail because it's very costly to fail that late.