We welcome Coffman's comments on our article. He makes two main points: on the one hand, he recognizes that reductionistic tendencies have gone too far in explaining development at large and carcinogenesis, in particular. On the other hand, he cleverly raises doubts about the validity of the criticisms leveled against such reductionistic views.
As others have done, he resorts to the technique of discrediting arguments over the value of a theory by using terms like ''reactionary'' instead of ''progressive'' and ''holistic'' as opposed to ''reductionistic''. In this fashion, something is unworthy not on its merits but on the connotation that it has in the contemporaneous zeitgeist. More specifically, who can be against '' . . . seek(ing) explanations that integrate multiple levels of biological organization?'' For sure, we are not against this commendable goal. In both our book (1) and in the BioEssays article that he both lauds and criticizes, we addressed the need for a hierarchical approach to carcinogenesis.
We found Dr. Coffman's arguments against our organicist, hierarchical view of cancer somewhat vague. In the first place, central to our theory is the nature of the default state. Dr. Coffman mentions that there are ''epistemological problems inherent in the concept of a biological 'default state''' but intriguingly he does not reveal what those problems are for the readership to evaluate. He also claims that we have misrepresented Boveri. We based the statement quoted by Dr. Coffman on the following passage from THE ORIGIN OF MALIGNANT TUMORS, the seminal Boveri book, '' . . . With the significance that I ascribe to chromosomes, we cannot avoid the assumption that the difference between cells of different tissues are caused by certain diversities in the chromatin-complex. These diversities are not to be thought of as if the kinds of chromosomes in one tissue were different from those in another, for we know that the number of chromosomes is the same in different tissues at least in single cases. Rather the differences in question must have their cause in that in every tissue, certain parts of chromosomes grow especially strong while, in another tissue, they fall into the background or disappear entirely.'' (2) This was precisely the point that we wanted to make, namely, that in this 1914 view a difference in phenotypes necessitates differences at the genetic level. Parenthetically, Boveri has provided in his book multiple, sometimes conflicting, explanations about the nature of cancer. It is not uncommon to fall into the temptation to read these explanations on a present-day contextual frame rather than on the context of knowledge in the early twentieth century based on each of his diverse and alternative explanations. Recent publications have done so, claiming for instance that