In 1982, a young CU chemist named Tom Cech was the first to show that RNA does more than carry the information of DNA. RNA itself can initiate and regulate chemical reactions – it is both genetic material and an effector of cellular processes. RNA might, in fact, spontaneously replicate itself, perhaps offering hints to the origin of life on Earth. For this discovery, Cech earned the 1989 Nobel Prize in Chemistry. Since then, Cech, his lab, and the BioFrontiers Institute he directs have consistently pushed the field of biochemistry, constantly incorporating new technologies and new techniques. Here C3 talks with Cech, this perpetual futurist, about the direction of cancer research.
C3: Where do you see the field of cancer research heading?
Cech: That’s an awfully broad question! I’ll pick one area, but if you ask me again tomorrow, I might pick a different one. For the next 10–20 years, I think precision medicine is a huge opportunity. In spite of all the sequencing of human tumor samples that is so popular right now, only in a small fraction of cases does the genomic information give guidance on therapeutic direction. In the future, we’ll do a lot better. This whole field is in its infancy and there’s a lot of hard work to be done to gain all of the power from the human genome.
C3: Is that because we still lack data or because we lack the ability to understand the data we already have?
Cech: Both. The two things go hand in hand – the ability to generate data and the ability to understand it. We’re still inventing technologies that will allow us to collect better data. But the biggest challenge is in computational biology, to train a generation of biomedical scientists who can look at biology through the lens of this data.
C3: How do you see this impacting patients, now or in the future?
Cech: Two things. First is with clinical trials. I can say this with great certainty because it’s already happening. We know now that, for example, breast cancer is not one disease but really perhaps ten major diseases and a bunch of minor ones that are only grossly lumped together with the term “breast cancer.” For clinical trials, you might have a drug that’s highly effective against one of the ten subtypes, so when you test it on all breast cancer patients, it’s only 10 percent efficacious. But if you could identify the responders ahead of time, and treat only that subgroup, the same drug would be highly effective. Now we’re starting to figure out ahead of time who is most likely to be helped by any drug and we are enriching our clinical trials for these people.
C3: And the other way precision medicine will affect patients?
Cech: The other thing concerns treating the patients themselves. In the future, if you have cancer or diabetes or heart disease or obesity or pulmonary disease, your doctor will be accompanied by a new breed of genetic counselor. Instead of saying, “you’ve got obesity and should go on a diet,” they’ll say, “We’ve looked at your genome and your RNA and your proteins and your metabolism and we don’t think most of these diets are going to do you any good, but we have some more precise advice for you.”
C3: You seem to be constantly incorporating new technologies in your lab, for example taking advantage of the gene editing strategy called CRISPR. What other new technologies do you think will speed cancer research?
Cech: One biggie is in imaging – to image individual biological molecules with ever-increasing precision. For example, cryo-electron microscopy is allowing pictures to be taken of complex biomolecules at the level where you can almost see the individual atoms. Both Anschutz and Boulder have recently upgraded our electron microscopes to take advantage of this capability. You can see the surface of a biomolecule that a drug will need to bind to. Or you can actually see a drug candidate bound to the biomolecule and say, “Oh wow, if we made this drug a little bigger on the left side, it would fit in this little pocket and it would bind even better.”
Cech: We do what’s called fundamental science – to try to understand the basic biology behind some of these questions of health and disease. We do this with the knowledge that there is usually a big time gap between uncovering the basic knowledge and actually making an impact on people. But many of today’s breakthroughs – take immuno-oncology – are based on basic science discoveries that happened 30 years ago. The work we’re doing today will be of medical value in the future. It’s an ongoing process. If scientists were to stop discovering new aspects of human biology today, there would be no immediate difference at all, but 20 or 30 years from now we would have lost out on a big opportunity.