Jonathon Hricko, “The causal reality of entities: The gene knock-in and knockout cases”
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: This paper explores the possibility of the causal reality of entities. By “the causal reality of entities,” we mean the following two theses: (1) An entity that is taken as being a cause of some effect or phenomenon in some causal hypothesis or inference exists; and (2) the causation between the entity and the effect is real rather than a mere cognitive connection. We argue that the causal reality of entities in some scientific cases is accessible, for example, the gene knock-in and knockout cases. We don't attempt to claim that all posited entities playing causal roles in a variety of hypotheses can be demonstrated to exist, nor that all instances of causation that scientists accept regarding such entities are real. Our argument is local, only applicable to the cases in this paper and other similar ones. 

In genetic engineering, 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. The goal of the knock-in method is to observe whether or not a new phenotype would be expressed. 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 goal of the knockout method is to investigate the expression of the genome in an organism when losing a targeted gene by comparing the phenotypic difference between the knockout organism and normal individuals.

To achieve the goal of this paper, we show that experiments using the methods of gene knock-in and knockout (1) can demonstrate the existence of a particular gene that is taken as being responsible for some phenotypic feature; and (2) can demonstrate that the particular gene is a real cause of that phenotypic feature, which the method of the classical genetics cannot do. 

One distinctive feature of this paper is that we are providing an argument combining the reality of an entity and the reality of causation between the entity and its supposed effect. On the case of the gene knock-in, we first invoke experimental individuation as a reality criterion of entities to warrant the existence of a knock-in gene (Chen 2016, Chen and Hricko 2021). We then use the existence of the entity to warrant the reality of the causation between the gene and the phenotype. Regarding this point, our argument is different from the causal argument for the reality of entities proposed by Cartwright (1983), Clarke (2001), and Egg (2016), and we compare and discern the difference between our individuation argument and their causal argument. On the case of the gene knockout, we first invoke the interventionist account of causality to warrant the causation between the intervened object and the effect (Woodward 2003). We then argue that the intervened object is an existing entity by comparing the knockout organism and normal individuals. Combining the two reasons, we warrant belief in the causal reality of the knockout gene. In doing so, we don't intend to argue for a general thesis about the reality of causation. We emphasize again that our argument is local, only for the causal reality in the cases in this paper and other similar cases. Besides the locality of the claim, we also contrast our argument with Hacking's (1983) manipulation argument for the reality of entities.