Ruey-Lin Chen, “Scientific exploration of causation in biomedical research”
Channel: CEFISES at UCLouvain
Date: 2023-08-08

Talk given at the Mechanisms and Ontic Causation in the Life Sciences conference, the second workshop of the MeCauLife group.

Abstract: The topic of causation is one of the hottest issues in both metaphysics and philosophy of science. To date, however, most work in the philosophy of science aims to provide a general theory of causation, focusing on connecting the precise understanding of the causation concept per se with scientific explanation and causal reasoning. Philosophers of science seemingly pay little attention to the establishment of causation criteria in scientific practice, especially that in biomedical research. The main purpose of biomedical scientists concerned with causation is to search for causes or factors of some effects of interests so that they can solve problems or eliminate undesirable effects (say, diseases) rather than explain those phenomena. How do they find a causal relationship between a specific cause and a specific effect? According to what criterion of causation do they derive a reliable claim that a specific factor is the real cause of an effect of interest? I call the general method or approach that biomedical scientists establish for their goal and practice “scientific exploration of causation.” This paper aims to explore the details of scientific exploration of causation and supply a case study of gene targeting on mouse embryonic stem (ES) cells to illustrate those details. 

The scientific exploration of causation is a compound method which integrates database searches, operational techniques, standardizing protocols, exploratory experiments, and confirmation of hypotheses and predictions. This method is best illustrated by using the gene targeting on mouse ES cells to produce gene knock-in and knockout mice to investigate functions or dysfunctions of specific genes. Biomedical scientists establish a reliable causal relationship between some specific expression and a specific gene by this kind of investigation. Why can a causal relationship be established reliably? The key is the method of gene targeting in knock-in and knockout. 

A gene knock-in refers to the method that involves inserting an exogenous gene (in general, a DNA sequence) to a targeted locus of a genome in an organism or substituting an original gene in the genetic locus with another new one. A gene knockout, contrary to gene knock-in, refers to the method according to which a targeted gene in an organism is deleted from or made inactive in the genome of the organism. The two methods offer sufficient evidence for judgments of causation, which biomedical scientists frequently appeal to Robert Koch's postulates of causality in order to justify. Koch's postulates of genetics include (1) observe an association between a gene or allele and an expression or disease; (2) isolate the gene from the individual that has the expression or disease and establish it in culture; (3) induce the expression or the disease by transferring the gene to a host organism. In this paper, I will also discuss the possible reconstruction of Koch's postulates in terms of the philosophical understanding of causation.