Surely you’re joking, mr Ernberg!

Have we really solved the riddle of cancer? Yes, says Ingemar Ernberg, the venerable professor who has written the foreword to ”Prostatacancer”, hot off the presses of the Karolinska University Press.

I was somewhat surprised by his argument, which runs something like this: If there ever were a riddle of cancer, we have solved it by showing how the cell’s actions are controlled by gene regulatory networks. With ceaseless environmental perturbations of these networks, coupled with the powerful organizing principle of evolution, nothing mysterious remains.

Certainly, the advances in tumor biology have been tremendous over the past decades. And it is no coincidence that much of what we have learned about genetics and cell signaling has been discovered in the context of cancer. But can we really say that we understand these processes because we have identified the constituent parts and some of their connections?

If this were true, the riddle of consciousness was really solved in the 1800:s, when Golgi invented the silver staining that for the first time enabled us to see how neurons connect with axons and dendrites.

What professor Ernberg does not consider is the complexity that arises through the dynamic information transfer of the network. On this higher-order level, in cells just as in the nervous system, behavior emerges that cannot meaningfully be accounted for by cataloging the interactions of the component parts.

If this is not immediately obvious, consider the following. Certain genes, when upregulated, cause cells to proliferate a lot. An example is the c-myc gene. This gene can be accidentally moved to the place for the immunoglobulin gene in certain lymphocytes when they are infected with the Epstein-Barr virus. As a result, the lymphocytes proliferate enormously, and we have leukemia. Other genes, which sometimes cause cells to proliferate a lot, can also sometimes cause them to die a lot. An example is th JNK gene. There has been much controversy over whether JNK is pro- or antiproliferative. Now, it is generally accepted that it is both.

In total, we humans have around 20 000 genes. Even if each gene only interacts with 10% of the other genes, and the interaction is always linear, a model to explain the cell’s behaviour would be totally intractable even with enormous computing power. When many of the interactions are non-linear, it becomes clear that a successful description of this system, with the power to predict what it will do, must consider a higher level of organisation. Analogies abound; reading the Pickwick papers by Charles Dickens letter by letter vs. by the meaning of phrases and their conjunctions (D. Hofstadter, in Gödel, Escher, Bach), or understanding a city by copying the telephone directory vs. actually finding out where people are going every day and why (Sidney Brenner).

The riddle of cancer remains. The most important discovery we have made so far is that the riddle of cancer is identical the to riddle of Life itself; namely how the genes and proteins that are the basic units of biological information, as well as the basic operators on this information, together determine the fate of the cells which are the smallest units of life as we know it.

(I am indebted to professor Ernberg for having created much of the intellectual arena where I have encountered several of the more groundbreaking recent advances of thought in tumor biology, and I argue against him safe in the knowledge that he will only be pleased that his ideas are debated.)


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