A handful of headlines joined in to herald this “breakthrough”:
US researchers create schizophrenic mice
Scientists Engineer World's First Schizophrenic Mice
Most of the articles qualified their headline’s claims and explained that this was the “first” genetically engineered schizophrenic mouse and that other mouse models of schizophrenia were chemically (or behaviorally) induced.
In fact, there have been very many (always unfruitful) claims that mice and rats dosed with amphetamine, amphetamine-like drugs, LSD, DMT, mescaline, PCP, or exposed to startling stimuli or raised in social isolation are useful models of schizophrenia. (see “Animal Models of Psychiatric Disorders.” Mark A. Geyer and Athina Markou in Psychopharmacology - The Fourth Generation of Progress. American College of Neuropsychopharmacology.)
It is a near certainty that each and every one of the scientists involved in those studies made claims about the implications of their research that uniformly proved to be false. Not one of those studies resulted in benefit to human sufferers of schizophrenia – not one. Not one. Weigh zero, nada, none, against the suffering of the mice and rats. There was benefit of course, it can be measured in the dollars and cents that went into the vivisectors’ bank accounts.
The report that led to the headlines was “Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans.” (Hikida et al. PNAS. 2007.) The senior author was Akira Sawa.
DISC1 (“Disrupted-In-Schizophrenia 1”) is a gene that was discovered and named in 2000.
DISC1 was discovered by Scottish geneticists studying a Scottish family with a high incidence of schizophrenia. DISC1 was subsequently shown to be associated with a variety of major mental illnesses.
In 2005, Sawa autopsied 60 brains from humans with major mental disorders. “Human postmortem orbital cortices … from normal controls as well as patients with [schizophrenia], bipolar disorder, and [major depression] were obtained … Each group had 15 subjects.” The researchers found an association between these conditions and DISC1 in these human brains.
It wasn’t long after the discovery and naming of DISC1 that Sawa and others began inserting the gene into mice and rats. There was, apparently, a sort of race to do this and claim credit for creating a new model. While reading about this “breakthrough,” I happened upon an article on about.com, written by a high-functioning idiot, that led me to read about Dr. Jacqueline Crawley.
According to an NIMH web page, “Dr. Crawley is chief of the Laboratory of Behavioral Neuroscience of the Intramural Research Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH) in Bethesda, Maryland.”
I almost titled this essay, “The Miracle Worker,” because Crawley’s lab has solved just about every medical problem facing society today. According to NIMH, her lab has characterized mutant mouse models for “behavioral phenotypes with conceptual analogies to human symptoms” of: autism, Alzheimer's, cognitive decline, anxiety, depression, schizophrenia, attention deficit hyperactivity disorder, Tay-Sachs, Sandhoff’s, Lowe syndrome, Smith-Lemli-Opitz syndrome, Fragile X syndrome, ataxia telangiectasia, epilepsy, and obesity. Wow. Wow!!! I wonder what’s holding up all the cures? Maybe those “conceptual analogies” are a little too conceptual?
To discover genes underlying autism, mouse behavioral assays with face validity to the diagnostic symptoms of autism are being developed, including social approach, reciprocal social interaction, juvenile play, auditory and olfactory communication, motor stereotypies, repetitive and perseverative behaviors, and resistance to change in routine. Applying this approach, an obscure inbred strain of mice, BTBR T+tf/J, was discovered to display social deficits, communication abnormalities, and repetitive self-grooming, relevant to the three core symptoms of autism.Wow!
Mark A. Geyer and Athina Markou (in “Animal Models of Psychiatric Disorders”) have this to say about “face validity”:
Face validity refers to the phenomenological similarity between the behavior (i.e., dependent variable) exhibited by the animal model and the specific symptoms of the human condition. Although face validity appears to be a desirable and is certainly an intuitively appealing criterion with which to validate models, such a criterion is actually not necessary, can be misleading, and is difficult to defend rigorously. Because the majority of models involve a species other than the one whose condition one tries to mimic, it is unrealistic to expect the two species to exhibit similar symptoms or phenomenology, even in cases where the etiology of the condition is known. In contrast, finding similarities between certain aspects of the behavior or physiology of animals and humans does not necessarily implicate similar etiology. Moreover, establishing the face validity of a model objectively is impossible, because claims for face validity of a model almost invariably involve subjective arbitrary arguments that are not necessarily accepted by all investigators in the field. While face validity can provide a heuristic starting point for the development of an animal model, it cannot be used to establish the validity of the model. In summary, the face validity of most models of human psychopathology is difficult to establish objectively and is irrelevant to the potential usefulness of the model in understanding the disease. It should be understood that face validity refers to the superficial similarity in symptomatology between the model and the disorder (e.g. changes in appetite or activity levels which are dependent variables) and can be distinguished from construct validity, which relies on similarities in underlying processes or mechanisms (e.g. hypothetical constructs specifying the mechanisms that lead to changes in appetite or activity levels). Thus, while face validity does not detract from an animal model, it simply does not provide scientific support for a model.This new trend -- inserting genes associated with disease in humans into animals -- is burdened with insurmountable problems. No gene operates in isolation from other genes. Genes associated with mental illness in humans exist naturally in a milieu of human genes that respond to and interact with those genes. When such a gene is inserted into a different organism, it interacts with and influences the action of a new constellation of genes. Expectations that drugs that block the expression or influence of such a gene in a mouse will act similarly in a different species are based on a false understanding of the dynamics of complex systems.
Meanwhile, we should be counseling persons who are carriers of DISC1 of the risks of procreating.