Abstract
No to Genetic Determinism
I first met Irv Gottesman in the late 1970s during one of his visits to London and when I was in the process of applying for a U.K. Medical Research Council (MRC) fellowship to train as a psychiatric geneticist. At that time psychiatric genetics had become very unfashionable in the United Kingdom, and following the recent death of Irv’s long-standing collaborator James (Jerry) Shields, there were no longer any established research-active experts in the United Kingdom in the areas that interested me, the genetics of adult psychiatric disorders. Although I had been encouraged to apply to the MRC by the Institute of Psychiatry’s most senior professor, Sir Denis Hill, I had picked up hints of disapproval from others among my teachers. Why, I asked Irv, was there suspicion and sometimes downright antipathy to genetics, especially among psychiatric researchers, especially those focusing on social correlates of common disorders? Irv’s view was that there were two widespread misconceptions among “environmentalist” researchers. The first was that most geneticists were out to prove that disorders such as schizophrenia are determined by genes. The second was the fear that the geneticists might be right!
Of course anyone who had actually read Gottesman and Shields’s classic twin study of schizophrenia would know that their finding that over 40% of their Maudsley identical twins were discordant for the disorder provided sufficient evidence that genes did not explain everything. Part of the problem may also have been that what little genetics had been taught to psychiatric researchers of that era when they were at medical school would have focused on Mendelian traits and disorders where the correspondence between genotype and phenotype is somewhat clear-cut. However even here, Irv pointed out, it is only somewhat clear-cut. Even before he had embarked on his Maudsley Twin study Gottesman was among the first to import into behavioral genetics the concept of a reaction norm, or as he preferred to call it a reaction range (Gottesman, 1963). The idea of a reaction norm was first introduced by an early pioneer, Wolterek, working mainly on water flea genetics. Irv’s insight was that what was good for the water flea was good for humans too. What a genotype confers is not the certainty of a trait or a disease but rather a range of phenotypes so that what is observed is the result of a dynamic interplay between the gene or genes and relevant environmental factors.
Subsequently Gottesman and Shields introduced to psychiatric genetics another major concept about how genes could act in a probabilistic rather than deterministic fashion in their article (Gottesman & Shields, 1967) applying a polygenic liability-threshold model to schizophrenia. This was, in a historical context, a particularly bold move since, at the time they wrote the article, Irv and Jerry were working at the MRC Psychiatric Genetics Unit at the Institute of Psychiatry, under Eliot Slater, whose widely accepted incompletely penetrant single gene model they directly challenged. Both Slater and Shields died before molecular psychiatric genetics really came to the fore, but happily Irv lived to see the polygenic theory of schizophrenia finally proven beyond doubt by recent very large-scale genome-wide association studies.
I was eventually awarded my MRC training fellowship in 1979, and in early 1981 the MRC sent me to the United States to study at Washington University in St. Louis with Irv and that other doyen of polygenic threshold models Theodore (Ted) Reich. Irv and I became close friends and continued to collaborate almost until the time of his death. One of our more unusual collaborations was not actually on research but on a court case that gave us 15 minutes of front-page fame in Hong Kong and Irv another chance to demolish determinism.
The Hong Kong Case
In 2000 the Hong Kong Equal Opportunities Commission (EOC) fought a court action against the Hong Kong government on behalf of three unrelated young men who had been denied employment respectively as a fireman, an ambulance driver, and a customs officer because each of them had a parent who had been diagnosed as schizophrenic. Irv and I were called as expert witnesses by the EOC. The details of the case have been nicely reported in an article coauthored by the eminent Hong Kong psychiatrist Felice Lieh-Mak, who was also called as an expert witness (Wong & Lieh-Mak, 2001).The gist was as follows: The government’s side argued, following reports from their occupational health doctors who had examined the young men, that all three were at high risk of developing schizophrenia and that schizophrenia in turn is associated with a tendency to commit violent acts, rendering the young men unsuitable for responsible government jobs.
In their reports the government doctors had quoted extensively from Irv’s writings including the empirical risk figure of 13% for the offspring of a schizophrenic themselves developing the disorder. In their defense therefore the government’s side argued that in the interest of public safety they were justified in denying the three plaintiffs their jobs. The three young men were examined by Felice Lieh-Mak, who found no evidence of psychosis or of any prodromal symptoms. She also examined in detail the medical records of the affected parents, agreeing that two of them were undoubtedly schizophrenic but suggesting that the late onset illness of the third was more likely to have been delusional disorder. Irv and I offered individualized calculations taking into account the plaintiffs’ current age, their healthy survival through part of the age of risk, and the fact that there were no other affected relatives. By our estimates the risk of schizophrenia in the two men with schizophrenic parents was under 5% and even lower for the man whose parent’s diagnosis was in question. This evidence together with figures on the low probability of someone with a diagnosis of schizophrenia actually committing a seriously violent act convinced the court that the public safety defense did not hold water. The three men were each awarded sizeable damages in the region of HK$1 million plus costs.
Irv and I came away both delighted with the verdict and impressed by the intellect and numeracy of the judge who had probed and scrutinized our statistical arguments. This was, we thought, a triumph of reason over determinism. What we had not realized, for it could not be mentioned by either side in court, was that shortly before the case there had been a notorious and tragic event in Hong Kong. A police officer had suddenly shot dead a man in his custody under the delusion that the arrested was a malevolent ghost. The police officer was subsequently diagnosed by a court appointed psychiatrist as schizophrenic and, it turned out, the officer’s brother had been diagnosed with the same disorder. It was therefore commendable indeed that the Hong Kong court had not been deterred by the possibility of public outcry in deciding that rare events and deterministic thinking should not override cool reason.
Perhaps our Hong Kong case should have received more widespread publicity beyond the former British colony and now Special Territory of the People’s Republic of China, for it surely has wider implications concerning the troublesome close relative of genetic determinism, genetic discrimination. We should perhaps be particularly wary in the current postgenomic era. Now, in sharp contrast with the 1970s, genetic “explanations” of both normal and abnormal behavior are all too fashionable and “it’s in his/her/their DNA” has become a glib phrase used, particularly by the media, about all sorts of traits, habits, and even customs. In these circumstances we should all be prepared to be Gottesman-like and loudly respond “No it isn’t.”
Footnotes
Declaration of Conflicting Interests
The author declared no conflicts of interest with respect to the authorship or the publication of this article.