Cross of Gold?

Now I'm going to show how Linus Pauling got into trouble. It's a complicated subject but I'll try to keep it reasonably simple. The process for discovering and evaluating potential disease treatments or preventive measures begins with basic research. What are the mechanisms of disease? That is called the etiology, the process that produces the undesirable state of health. 

Our ability to experiment on humans to explore such questions is obviously very limited. We can observe people with a condition, certainly, and in the 20th Century our ability to do that expanded immensely with X rays and then more sophisticated imaging techniques; and the ability to do things like count the various kinds of blood cells, measure hormone levels, and do many other sorts of tests. But establishing causation is difficult without experimentation. No, it isn't always impossible, contrary to some people's claims, but randomized controlled trials are usually the best and most compelling way to do it. That's why they're called the "Gold Standard" for clinical research, hence the title of this post. But as the title implies, maybe that's too limiting. We'll see.

If we're studying the etiology of disease, that usually means we have to experiment on non-human animals, since we can't ethically expose humans to our suspected causal agent. Generally, this has to mean mammals, because they're the only creatures who are enough like us that we can draw inferences about humans with some confidence. Even so, what we observe in rats and guinea pigs and even chimpanzees often turns out not to apply to H. sapiens. 

But at least it's a start. Once we think we have a good idea of the etiology of a disease, we can develop some biologically plausible ideas about how we might prevent or treat it. Unfortunately, as I have emphasized, chemistry cannot predict biology. We may think we understand the biochemical mechanism of disease, and come up with an idea of how introducing a new chemical (i.e. a drug or medication) might interfere with that mechanism, but I can tell you with complete confidence, based on the long and bitter experience of biomedical research, that idea will either be wrong, or the adverse effects of the intervention aren't worth the benefits.

So, given that our brilliant ideas are likely to fail, and even harm people, how can we ethically proceed? First, we need an "animal model" of our human disease. We have to believe that our disease maps onto something in rats or monkeys, and have a way of giving the animals the disease (unless we're lucky enough to find some who have it naturally, which is highly unlikely), and then try the treatment on them. PETA is not at all happy, obviously, but right now I'm not discussing the ethics of experimenting on animals, just describing the process of developing treatments.

Anyhow, let's say the treatment looks promising in the animal models and any adverse effects seem tolerable. But we can't know if that will be true in humans until we try it. The first thing we need to do is establish enough confidence in the safety of the treatment that we can proceed without committing a felony. That's what's called a Phase One trial. So we'll start there next time.