Year: 2011
Type: editorial
Abstract: In this issue, we explore what is for BioEssays a new medium for scientific debate: the formal Point<>Counterpoint. Ana Soto and Carlos Sonnenschein ask critical questions of the somatic mutation theory (SMT) of cancer, long the widely accepted model for carcinogenesis. Specifically they make the case that the SMT not only fails to provide an explanation for observable phenomena in cancer biology, but that, arguably, it is - with current technologies - essentially untestable 1. Citing gathering evidence they assert that, in contrast, the cellular context is critical to carcinogenesis, a concept about which the fundamental form of the SMT is silent. The two Tufts University scientists suggest that the default state of cells is proliferation, and that malignant transformation of cells may be initiated by loss of contextual constraints on that default state. They propose an alternative model to the SMT, in which the role of the tissue microenvironment is dominant: the tissue organisation field theory (TOFT). Soto and Sonnenschein are not alone. For example, in a recent issue of BioEssays, Harry Rubin reviewed the critical role of non-cell autonomous changes in carcinogenesis, a process he refers to as "field cancerization"2. Soto and Sonnenschein provocatively suggest that the SMT has lulled us into a sense of complacency, which is detrimental to creative scientific progress. If science were the law, then Soto and Sonnenschein have generated a powerful case for the prosecution of the SMT. A fundamental principle of the law is the right to a fair defense. It is clear that the SMT is founded on almost a century of observations. Though (admittedly) subject to much incremental adjustment, it remains a workhorse for most researchers who study cancer. In a counterpoint to the article by Soto and Sonnenschein, David Vaux, from La Trobe University, Melbourne, provides a carefully-argued case for acquittal 3. He reminds us of the accumulated evidence for driver genetic changes within cancers from animal and other models. He also draws our attention to the translation of the principle of oncogene addiction into clinical practice in the effective use of targeted therapeutics in cancers in which the target carries mutations. Confronted with the "normalisation" of cancer cells following transplantation to new environments, Vaux suggests that epigenetic factors may account for the reprogramming of the cancer genome. These articles deliberately challenge the reader. It would have been possible for us to commission a completely different piece presenting a "balance" between these theories. With further incremental adjustments, a compromise between the SMT and the TOFT can be (and has been) achieved that would leave both theories with their shibboleths intact. Soto and Sonnenschein believe that such equivocation compromises creativity, and ultimately, scientific progress. The gatekeeper in Shakespeare's Macbeth tells us that, like alcohol, equivocation adds to the desire but takes away from the performance. The format of the Point<>Counterpoint invites the reader to act, to participate in the debate, and to judge who is right, to which extent, and how to synthesise two extreme positions. In effect, and extending the metaphor of the law, if Soto and Sonnenschein represent the prosecution, and Vaux the defense, then readers are the judge and jury. The Point<>Counterpoint format is an interesting one, well suited to the remit of BioEssays. It also presents technical challenges. These begin with the prosecution and defense teams. It takes courage to resist the temptation to corrupt the core elements of extreme positions by endless, individually trivial, compromises. Extreme positions force us clearly to identify the key elements of important theories, which is essential for their experimental testing. Theories that can be bent to fit all phenomena are arguably less testable than purer contentions of principle. And testability – or more precisely, the ability to be subjected to the test of disproof – is the measure of scientific value, as Karl Popper argued. It can be uncomfortable to take extreme positions, because it might suggest that the adversary is ignorant of evidence for other models. Soto, Sonnenschein and Vaux have boldly articulated their respective positions, under explicit instructions not to qualify or compromise their cases – that is the reader's job. It is important to create a "safe" space in which to hold such a debate – just as in a court of law. Neither side was provided with anything other than the abstract of the other's article. It is necessary to ensure that the pieces are congruent, for there must be points of contact between the cases for the reader to generate a meaningful synthesis. At the same time they do not intricately dissect and rebut each other's content in the first instance. However, we recognise that both sets of authors need a right of reply, and we have provided for a follow-up letter from each in order to ensure that the opportunity exists to address specific points in a later issue of BioEssays. Nothing is new under the sun! It is worth noting that this dialectic assumes that science consists of (and advances by) underlying Platonic truths (models) for which facts only represent a manifestation, rather than via the Aristotelian accumulation of uninterpreted facts. Is this rhetoric? Consider that we are in an era of massively parallel sequencing, where the difference between the datum and the reality from which it is derived is becoming critical. The bioinformatician is increasingly important in turning information into knowledge, and ultimately validates models such as those we are contrasting here. The Manichaean polarisation of extreme views ("good" versus "bad") is visible in many parts of life, from politics to religion, where the practical consequences are obvious to all. The problem with extremes lies in the failure of synthesis, not in the articulation of extreme positions. Socratic method depends on a dialectic between such positions, the resolution of which leads to a better truth. We call on the scientific community to play that role, with this Point<>Counterpoint as the stimulus. David Thomas Editorial Board Member Andrew Moore Editor-in-Chief
Source: BioEssays
Authors: David Thomas, Andrew Moore
Institution: Peter MacCallum Cancer Centre
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2131309676