NY Magazine: What It’s Like to ‘Wake Up’ From Autism After Magnetic Stimulation
... Though he wasn’t diagnosed with autism until he was 40, John Elder Robison felt isolated and disconnected throughout his entire youth and early adulthood. But in 2008, at 50, he took part in what became a three-year research project looking at brain function in individuals with autism spectrum disorders and exploring the use of transcranial magnetic stimulation (TMS) to help them.
TMS is a noninvasive procedure that uses magnetic pulses to stimulate nerve cells in the brain. During treatment, a coil is placed against the patient’s scalp and the TMS energy passes through the skull into the outermost layer of the brain. ...
The treatment left Robison momentarily crippled by the weight of other people’s feelings, and he spoke with Science of Us about his experience, which he also discusses in his recently released book, Switched On: A Memoir of Brain Change and Emotional Awakening. ...
Do you understand now what was happening?
TMS modified my emotional response to what you might call ordinary situations. I often put it this way: You might be crossing the street and you fall and you skin your knee. I’d say, “Come on, get up!” The very best advice I could give is come on, get going, this car could run you over. People would see my practical response as cold and emotionless. After TMS, I’d look at you and wince at your skinned knee. I never did that before. And I now realize that wincing at your skinned knee is the response most people have. I still have the autistic response, but I’m also aware of what you might now call the “empathetic response from personal experience.” People can tell you about something a million times, and it won’t mean anything to you until you experience it. That said, it’s important to understand that I always had the ability to feel your pain. Like, if you were my girlfriend and you got sick I’d be more worried about you than your own mother. I was always that way. But no matter how much I cared about you, if we were crossing the street, you fell down and skinned your knee, I would see your skinned knee and I would say “Come on, we gotta get going,” or I would say, “Here, I’ll get you a Band-Aid.” I would have a practical response. The way I responded is no reflection on how much I cared for you. I could care for you with all the love in the world and still I’d respond practically.
So you don’t feel you’d really lacked empathy before?
No. In fact, studies have shown that autistic people feel things more deeply, not less at all. It’s true that autism is described as a condition with communication impairment. And so, to be diagnosed with autism, you must have an impaired ability to speak, to understand speech, or to understand or convey unspoken cues.
So what exactly happened when you first stated noticing emotional cues?
It hit me all at once with an intensity that was absolutely scary. As I lay in bed, trying to fall asleep, the world started revolving. I became afraid I was having a stroke. I’d close my eyes and the world would spin like I was drunk, about to throw up. I don’t drink or do drugs. So for me to have the world spinning like that made me think there was something terribly wrong. And not only was the world spinning, I would close my eyes and I would have these really vivid, half-awake, half-asleep dreams that were a collage of things from the past and things that had just happened that day and they were just so real. The experience was so unsettling that I woke up and wrote a 1,500-word missive to the scientists describing what had happened. Then, finally, I was able to fall asleep.
The next day at work I looked at one of my colleagues and I thought to myself: He has the most beautiful brown eyes. That’s the type of thought I simply do not have. I don’t usually have any comment on your eyes because I don’t look in anyone’s eyes. For me to look in your eyes and say that they are beautiful is totally out of character. When I got to work I walked into the waiting room, as I usually do, and I looked at everyone and there was this flood of emotion. I could see it all: They were scared and anxious and eager, and never in my life had I seen something like that. I had to step out of the room because I didn’t know how to cope. It felt like ESP. Maybe in the past I used the logical part of my brain to look at people around me and carefully analyze. I figured out situations using logic. So I had that powerful ability but now the screen of emotion was turned on, too. ...
Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general populationFrom the paper
Nature Genetics (2016) doi:10.1038/ng.3529
Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of this risk are unclear in people not ascertained for neuropsychiatric symptoms. Using several large ASD consortium and population-based resources (total n > 38,000), we find genome-wide genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both LD score correlation and de novo variant analysis, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in diagnosis with an ASD or other neuropsychiatric disorder. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology.
... Consistent with traditional approaches to psychiatric phenotypes, most genetic studies of ASDs compare cases to controls to identify risk-associated variation. This approach has been highly productive— recent studies have linked common polygenic as well as de novo and inherited rare variation to ASD risk1,2. Common genotyped SNPs are estimated to account for at least 20% of ASD liability1,3,4. Contributing de novo variants are found in 10–20% of cases, but de novo mutations collectively explain less than 5% of overall ASD liability1,5,6.
Almost all genetic risk factors for ASDs can be found in unaffected individuals. For example, most people who carry a 16p11.2 deletion, the most common large mutational risk factor for ASDs, do not meet the criteria for an ASD diagnosis7. Across healthy populations, there is also substantial variability in capacity for social interaction and social communication8. Although such phenotypic variation is well established, the genetic relationship between neuropsychiatric disorders and typical social and behavioral variation remains unclear. From the first published descriptions of ASDs, clinical and epidemiological reports have commonly noted subthreshold traits of autism in the family members of many diagnosed individuals9,10. Twin and family studies have suggested that these similarities are at least in part inherited and also suggest that traits and diagnosis are correlated genetically11–13, but the correlation has yet to be estimated using measured genetic data.
... These data strongly suggest that genetic influences on ASD risk—both inherited and de novo—influence typical variation in the population in social and communication ability. They also link clinically significant problems to impairments that are less likely to be ascertained. The results have major implications for genetic models of neuropsychiatric disorder risk. It is likely that inherited liability for ASDs is reflected in the behavioral traits of some family members of affected individuals. This links genetic and phenotypic burden in an intuitively consistent fashion with complex, continuously distributed polygenic disease risk. For traits such as height, it is simple to conceptualize a model in which tall parents (for example, those with a height 2 s.d. above the mean) are more likely to have a child who is very tall (for example, one with a height 3 s.d. above the mean). Historically, this concept has been more complicated in neuropsychiatric disorders. Despite extensive evi- dence, some have even questioned the role of inheritance given that the parents of individuals with ASDs or schizophrenia rarely carry a diagnosis themselves. These results suggest that familiality should be studied in a manner beyond a count of categorically affected family members and that trait variation in controls can provide insight into the underlying etiology of severe neurodevelopmental and psychiatric disorders. The behavioral influence of de novo and inherited genetic risk for ASDs can be quantified, and studies assessing continuous trait variation are likely better equipped to examine the phenotypic correlates of neuropsychiatric disease risk.
Nature News: The laboratory monkeys run obsessively in circles, largely ignore their peers and grunt anxiously when stared at. Engineered to have a gene that is related to autism spectrum disorder in people, the monkeys are the most realistic animal model of the condition yet, say their creators. Researchers hope that the animals will open up new ways to test treatments and investigate the biology of autism. But the jury is still out on how well the monkeys’ condition matches that of people with autism.
Autism has a vast array of symptoms and types, but researchers think that at least 100 genes play a part. The scientists who led the latest work, which is published on 25 January in Nature (Z. Liu et al. Nature http://dx.doi.org/10.1038/nature16533; 2016), turned to the autism-related gene MECP2: both people who have extra copies of the gene (MECP2-duplication syndrome) and people who have certain mutations in this gene (Rett’s syndrome) share many of the symptoms of autism. Previously researchers have engineered monkeys to have autism-related genes (H. Liu et al. Cell Stem Cell 14, 323–328; 2014), but this is the first published demonstration of a link between those genes and the animals’ behaviour.
... Qiu, meanwhile, is excited by the prospect of using the model to identify exactly where in the brain the MECP2 overexpression causes trouble. His team is already using brain-imaging technology on the monkeys to pinpoint such areas. Next, the researchers plan to use the CRISPR gene-editing technique to knock out the extra MECP2 copies in cells in those regions and then check whether the autisim-like symptoms stop.Here's the paper:
Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2
Nature (2016) doi:10.1038/nature16533
Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing1, 2, 3, 4. Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes5. Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders6. Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression7, 8. Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep-sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test9. The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F1 progeny. Moreover, F1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.
Neuroscience News: Quantitative study identifies 239 genes whose ‘vulnerability’ to devastating de novo mutation makes them priority research targets.Here is the paper at PNAS:
... devastating “ultra-rare” mutations of genes that they classify as “vulnerable” play a causal role in roughly half of all ASD cases. The vulnerable genes to which they refer harbor what they call an LGD, or likely gene-disruption. These LGD mutations can occur “spontaneously” between generations, and when that happens they are found in the affected child but not found in either parent.
Although LGDs can impair the function of key genes, and in this way have a deleterious impact on health, this is not always the case. The study, whose first author is the quantitative biologist Ivan Iossifov, a CSHL assistant professor and on faculty at the New York Genome Center, finds that “autism genes” – i.e., those that, when mutated, may contribute to an ASD diagnosis – tend to have fewer mutations than most genes in the human gene pool.
This seems paradoxical, but only on the surface. Iossifov explains that genes with devastating de novo LGD mutations, when they occur in a child and give rise to autism, usually don’t remain in the gene pool for more than one generation before they are, in evolutionary terms, purged. This is because those born with severe autism rarely reproduce.
The team’s data helps the research community prioritize which genes with LGDs are most likely to play a causal role in ASD. The team pares down a list of about 500 likely causal genes to slightly more than 200 best “candidate” autism genes.
The current study also sheds new light on the transmission to children of LGDs that are carried by parents who harbor them but whose health is nevertheless not severely affected. Such transmission events were observed and documented in the families used in the study, comprising the Simons Simplex Collection (SSC). When parents carry potentially devastating LGD mutations, these are more frequently found in the ASD-affected children than in their unaffected children, and most often come from the mother.
This result supports a theory first published in 2007 by senior author Michael Wigler, a CSHL professor, and Dr. Kenny Ye, a statistician at Albert Einstein College of Medicine. They predicted that unaffected mothers are “carriers” of devastating mutations that are preferentially transmitted to children affected with severe ASD. Females have an as yet unexplained factor that protects them from mutations which, when they occur in males, will be significantly more likely to cause ASD. It is well known that at least four times as many males as females have ASD.
Wigler’s 2007 “unified theory” of sporadic autism causation predicted precisely this effect. “Devastating de novo mutations in autism genes should be under strong negative selection pressure,” he explains. “And that is among the findings of the paper we’re publishing today. Our analysis also revealed that a surprising proportion of rare devastating mutations transmitted by parents occurs in genes expressed in the embryonic brain.” This finding tends to support theories suggesting that at least some of the gene mutations with the power to cause ASD occur in genes that are indispensable for normal brain development.
Low load for disruptive mutations in autism genes and their biased transmission
We previously computed that genes with de novo (DN) likely gene-disruptive (LGD) mutations in children with autism spectrum disorders (ASD) have high vulnerability: disruptive mutations in many of these genes, the vulnerable autism genes, will have a high likelihood of resulting in ASD. Because individuals with ASD have lower fecundity, such mutations in autism genes would be under strong negative selection pressure. An immediate prediction is that these genes will have a lower LGD load than typical genes in the human gene pool. We confirm this hypothesis in an explicit test by measuring the load of disruptive mutations in whole-exome sequence databases from two cohorts. We use information about mutational load to show that lower and higher intelligence quotients (IQ) affected individuals can be distinguished by the mutational load in their respective gene targets, as well as to help prioritize gene targets by their likelihood of being autism genes. Moreover, we demonstrate that transmission of rare disruptions in genes with a lower LGD load occurs more often to affected offspring; we show transmission originates most often from the mother, and transmission of such variants is seen more often in offspring with lower IQ. A surprising proportion of transmission of these rare events comes from genes expressed in the embryonic brain that show sharply reduced expression shortly after birth.
The contribution of de novo coding mutations to autism spectrum disorder
(doi:10.1038/nature13908)
Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females.
Predicting the diagnosis of autism spectrum disorder using gene pathway analysis (Nature Molecular Psychiatry)From my comments:
Abstract
Autism spectrum disorder (ASD) depends on a clinical interview with no biomarkers to aid diagnosis. The current investigation interrogated single-nucleotide polymorphisms (SNPs) of individuals with ASD from the Autism Genetic Resource Exchange (AGRE) database. SNPs were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived pathways to identify affected cellular processes and develop a diagnostic test. This test was then applied to two independent samples from the Simons Foundation Autism Research Initiative (SFARI) and Wellcome Trust 1958 normal birth cohort (WTBC) for validation. Using AGRE SNP data from a Central European (CEU) cohort, we created a genetic diagnostic classifier consisting of 237 SNPs in 146 genes that correctly predicted ASD diagnosis in 85.6% of CEU cases. This classifier also predicted 84.3% of cases in an ethnically related Tuscan cohort; however, prediction was less accurate (56.4%) in a genetically dissimilar Han Chinese cohort (HAN). Eight SNPs in three genes (KCNMB4, GNAO1, GRM5) had the largest effect in the classifier with some acting as vulnerability SNPs, whereas others were protective. Prediction accuracy diminished as the number of SNPs analyzed in the model was decreased. Our diagnostic classifier correctly predicted ASD diagnosis with an accuracy of 71.7% in CEU individuals from the SFARI (ASD) and WTBC (controls) validation data sets. In conclusion, we have developed an accurate diagnostic test for a genetically homogeneous group to aid in early detection of ASD. While SNPs differ across ethnic groups, our pathway approach identified cellular processes common to ASD across ethnicities. Our results have wide implications for detection, intervention and prevention of ASD.
The approach taken here first selects 775 SNPs of interest based on pathway information (not considered in standard GWAS) and then only requires 5E-03 significance. A linear predictor is formed from the 237 SNPs that pass this threshold. The ultimate test is, of course, whether the predictor actually works on (independent) validation samples. Once you have a statistically valid predictor, it doesn't matter how you arrived at it.This recent letter to the editor of Molecular Psychiatry claims that the predictive power came from the fact that the case and control groups had slightly different ancestral origin (via neuroskeptic):
... cases have more diverse ancestral origins within Europe than controls. The putative risk alleles are more common in the Northeastern than in the Northwestern Europe, whereas the putative protective alleles reflect the opposite trend.But I don't understand how this explains the moderate success of the classifier in the Chinese cohort -- I'll have to look more carefully. Here are the title and abstract of the new paper.
Population structure confounds autism genetic classifier
T G Belgard, I Jankovic, J K Lowe and D H Geschwind
Abstract
A classifier was recently reported to predict with 70% accuracy if an individual has an autism spectrum disorder using 237 single-nucleotide polymorphisms (SNPs).1 Biomarkers, genetic or otherwise, that would facilitate earlier autism spectrum disorder diagnosis are crucial; therefore, these results warrant careful scrutiny. One potential confounder of such genetic studies is bias when cases and controls have different ancestral origins.
CONFIDENTIAL
November 4, 1943
Professor R. T. Birge
Chairman, Department of Physics
University of California
Berkeley, California
Dear Professor Birge:
In these war times it is not always easy to think constructively about the peace that is to follow, even in such relatively small things as the welfare of our department. I would like to make one suggestion to you which concerns that, and about which I have myself a very sure and strong conviction.
As you know, we have quite a number of physicists here, and I have run into a few who are young and whose qualities I had not known before. Of these there is one who is in every way so outstanding and so clearly recognized as such, that I think it appropriate to call his name to your attention, with the urgent request that you consider him for a position in the department at the earliest time that that is possible. You may remember the name because he once applied for a fellowship in Berkeley: it is Richard Feynman. He is by all odds the most brilliant young physicist here, and everyone knows this. He is a man of thoroughly engaging character and personality, extremely clear, extremely normal in all respects, and an excellent teacher with a warm feeling for physics in all its aspects. He has the best possible relations both with the theoretical people of whom he is one, and with the experimental people with whom he works in very close harmony.
The reason for telling you about him now is that his excellence is so well known, both at Princeton where he worked before he came here, and to a not inconsiderable number of "big shots" on this project, that he has already been offered a position for the post war period, and will most certainly be offered others. I feel that he would be a great strength for our department, tending to tie together its teaching, its research and its experimental and theoretical aspects. I may give you two quotations from men with whom he has worked. Bethe has said that he would rather lose any two other men than Feyman from this present job, and Wigner said, "He is a second Dirac, only this time human."
Of course, there are several people here whose recommendation you might want; in the first instance Professors Brode and McMillan. I hope you will not mind my calling this matter to your attention, but I feel that if we can follow the suggestion I have made, all of us will be very happy and proud about it in the future. I cannot too strongly emphasize Feynman's remarkable personal qualities which have been generally recognized by officers, scientists and laity in this community.
With every good wish,
Robert Oppenheimer
CALIFORNIA INSTITUTE OF TECHNOLOGY
CHARLES C. LAURITSEN LABORATORY OF HIGH ENERGY PHYSICS
October 14, 1985
Dr. Stephen Wolfram
School of Natural Sciences
The Institute for Advanced Study
Princeton, NJ 08540
Dear Wolfram:
1. It is not my opinion that the present organizational structure of science inhibits "complexity research" - I do not believe such an institution is necessary.
2. You say you want to create your own environment - but you will not be doing that: you will create (perhaps!) an environment that you might like to work in - but you will not be working in this environment - you will be administering it - and the administration environment is not what you seek - is it? You won't enjoy administrating people because you won’t succeed in it.
You don’t understand "ordinary people." To you they are "stupid fools" - so you will not tolerate them or treat their foibles with tolerance or patience - but will drive yourself wild (or they will drive you wild) trying to deal with them in an effective way.
Find a way to do your research with as little contact with non-technical people as possible, with one exception, fall madly in love! That is my advice, my friend.
Sincerely,
(Signed, 'Richard P. Feynman')
Richard P. Feynman
I’m O.K., You’re a Psychopath (NYTimes): ... For Baron-Cohen, psychopaths are just one population lacking in empathy. ... Baron-Cohen calls these ... groups “Zero-Negative” because there is “nothing positive to recommend them” and they are “unequivocally bad for the sufferer and those around them.” He provides a thoughtful discussion of the usual sad tangle of bad genes and bad environments that lead to the creation of these Zero-Negative individuals.
People with autism and Asperger’s syndrome, Baron-Cohen argues, are also empathy-deficient, though he calls them “Zero-Positive.” They differ from psychopaths and the like because they possess a special gift for systemizing; they can “set aside the temporal dimension in order to see — in stark relief — the eternal repeating patterns in nature.” This capacity, he says, can lead to special abilities in domains like music, science and art. More controversially, he suggests, this systemizing impulse provides an alternative route for the development of a moral code — a strong desire to follow the rules and ensure they are applied fairly. Such individuals can thereby be moral without empathy, “through brute logic alone.”
Wikipedia: ... Most individuals with Williams syndrome are highly verbal and overly sociable, having what has been described as a "cocktail party" type personality, and exhibit a remarkable blend of cognitive strengths and weaknesses.[3] Individuals with WS hyperfocus on the eyes of others in social engagements.
... While patients with Williams syndrome often have abnormal proficiency in verbal skills, they do not perform better on verbal tasks than average. This syndrome is characterized more by a deficiency in other areas of processing. [Glib, but often mildly retarded.]
In this provocative study of behavioral economics, Cowen (Discover Your Inner Economist) reveals that autistic tendencies toward classification, categorization and specialization can be used as a vehicle for understanding how people use information. Cowen spends a great deal of time dispelling autism's societal stigma, arguing that mainstream society is reaping benefits from mimicking autistic cognitive strengths. As stimulating as is the premise, the book often feels like its own long exercise in categorization, with each chapter an analysis of the human mania for classification (e.g., the obsession with ranking achievements and endeavors). According to Cowen, human brains are constantly absorbing bits of information that get smaller and are delivered faster as technology advances. The more information people receive, the more they crave—this shorter attention span is far from a flaw to the author, but a liberating mechanism that allows humans time to contemplate more ambitious, long-range pursuits. ...
How should the collapse of the world financial system affect economics? Part II
- Mad, bad, and dangerous to know
Steve Keen
- A financial crisis on top of the ecological crisis: Ending the monopoly of neoclassical economics
Peter Söderbaum
- Toward a new sustainable economy
Robert Costanza
- After the bust: The outlook for macroeconomics and macroeconomic policy
Thomas I. Palley
- A non-formal look at the non-formal economy
Sean Mallin
Human decision-making deviates in one way or another from the standard assumptions of the rationalistic paradigm in economics. If such deviations from rationality and self-interest were small and purely idiosyncratic, they would on average cancel out, and economic theory would not be too wide off the mark when predicting outcomes for large aggregates of agents. Following the lead of Vernon Smith, early studies of alternative market mechanisms by experimental economists can be viewed as tests of the hypothesis of idiosyncratic deviations from standard economic theory. If deviations from rationality and self-interest were systematic, however, this would call for a revision of economic theory itself.
...now Nobel Laureate Vernon Smith has decided to speak openly about what he calls the deficiencies and the selective advantages of Asperger's.
“I can switch out and go into a concentrated mode and the world is completely shut out,” he said in a recent interview. “If I'm writing something, nothing else exists.”
Smith says his capacity for deep concentration contributed to his ability to win the Nobel Prize.
“Perhaps even more importantly, I don't have any trouble thinking outside the box,” he said. “I don't feel any social pressure to do things the way other people are doing them, professionally. And so I have been more open to different ways of looking at a lot of the problems in economics."
CNBC: Did you feel like you seemed strange in the eyes of other people?
SMITH: Oh, yes.
CNBC: How so?
SMITH: Sometimes I'm described as "not there" in a social situation. You know, a social situation that lasts for a couple of hours I find it to be a tremendous amount of strain, so I've been known just to go to bed and read.
...neither I, nor my parents, or anyone in my family, or any neighbor or friend, had any idea how to go about choosing a college. So, I went to the city library, found a book on choosing a college, and learned among other things that the 'best' college in the United States was Caltech. Being naïve and impetuous I decided that I should prepare myself to enter Caltech, as, without preparation, my 'C' average in High School would not even qualify me to take the entrance exam. A serious Quaker College, Friend's University, was located near my home in West Wichita. I enrolled in physics, chemistry, calculus, astronomy and literature courses for one year, earned top grades, and sat for the entrance exams for Caltech.
...Caltech was a meat grinder like I could never have imagined. I studied night, day, weekends and survived hundreds of problems, but what a joy to take freshman chemistry from Linus Pauling, hear physics lectures by J. Robert Oppenheimer on his frequent visits to Caltech, attend a visiting lecture by Bertrand Russell, and regularly see von Karman, Anderson, Zwicky, Tolman, Millikan and other legendary figures of that time, on campus.
I was majoring in physics, but switched to electrical engineering, which was in the same division (Mathematics, Physics and EE) as a senior. In this way I did not have to take the dreaded "Smyth's course," required for physics majors, but not EE, and received my BS on schedule in 1949. At the time I relished the unbending facts and mathematics of physics/engineering. Then, as a senior, I took an economics course and found it very intriguing - you could actually learn something about the economic principles underlying the claims of socialism, capitalism and other such 'isms.' Curious about advanced economics, I went to the Caltech library, stumbled upon two books, Samuelson's Foundations, and von Mises' Human Action. From the former, it was clear that economics could be done like physics, but from the latter there seemed to be much in the way of reasoning that was not like physics. I also subscribed to the Quarterly Journal of Economics, and one of the first issues had a paper by Hollis Chenery on Engineering Production Functions. So, economics was also like engineering! I had not a hint then as to how much those first impressions would be changed in my thinking over the decades to follow. ...
For micro I supplemented with courses Samuelson taught down the Charles River at MIT. After Caltech, Harvard seemed easy, and I got virtually straight A's. ...Graduate school is an endurance test, but was not that demanding for me after having survived the undergraduate meat grinder.
The first thing to which one has to adapt is the fact that no matter how high people might sample in the right tail of the distribution for "intelligence," ... that sample is still normally distributed in performing on the materials in the Caltech curriculum. The second thing you learn, if you were reared with my naive background, is the incredible arrogance that develops in conjunction with the acquisition of what you ultimately come to realize is a really very, very small bit of knowledge compared with our vast human ignorance. ... the difference between Harvard and Caltech: "At Harvard they believe they are the best in the world; at Caltech they know they are the best in the world."
Before leaving Bok’s temporary office in Loeb House, mindful of the Summers fiasco, I remarked to Derek that the time was not far off when academia would have no choice but to hand political correctness back to the politicians. Since 1978, when a pail of water had been dumped over E. O. Wilson for saying that genes influence the behavior of humans as well as of other animals, the assault against behavioral science by wishful thinking has remained vigorous. But as science is able to prove its hypotheses ever more indisputably, such irrationality must recede or betray itself as such. In showing that human genes do matter, behavioral biologists will no longer be limited to comparisons of fraternal and identical twins. Soon the cost of sequencing the As, Ts, Gs, and Cs of individual DNA molecules will drop to a thousandth of what it has been, thereby transposing our studies of behavioral differences to the much more revealing molecular level. DNA messages extracted from, say, many hundreds of psychopaths can then be compared to equivalent numbers of DNA messages from individuals prevented by their consciences from habitually lying, stealing, or killing. Specific DNA sequences consistently occurring only in psychopaths will allow us to pinpoint the genes likely malfunctioning to produce psychopathy. The thought that some people might be born to grow up wicked is inherently upsetting. But if we find such behavior to be innate, the integrity of science, no less than that of ethics, demands that we let the truth be known.
The relative extents to which genetic factors determine human intellectual abilities will also soon become much better known. At the etiological heart of much of schizophrenia and autism are learning defects resulting from the failure of key brain cells to link up properly to each other. As we find the human genes whose malfunctioning gives rise to such devastating developmental failures, we may well discover that sequence differences within many of them also lead to much of the observable variation in human IQs. A priori, there is no firm reason to anticipate that the intellectual capacities of peoples geographically separated in their evolution should prove to have evolved identically. Our desire to reserve equal powers of reason as some universal heritage of humanity will not be enough to make it so.
Rather than face up to facts that will likely change the way we look at ourselves, many persons of good will may see only harm in our looking too closely at individual genetic essences. So I was not surprised when Derek, who had spent most of our meeting listening, asked apprehensively how many years would pass before the key genes affecting differences in human intelligence would be found. My back-of-the-envelope answer of “15 years” meant that Summers’ then undetermined successor would not necessarily need to handle this very hot potato.
Upon returning to the Yard, however, I wondered if even 10 years would pass.
