Kevin Mitchell: Wired that way – genes do shape behaviours but it’s complicated

Many of our psychological traits are innate in origin. There is overwhelming evidence from twin, family and general population studies that all manner of personality traits, as well as things such as intelligence, sexuality and risk of psychiatric disorders, are highly heritable. Put concretely, this means that a sizeable fraction of the population spread of values such as IQ scores or personality measures is attributable to genetic differences between people. The story of our lives most definitively does not start with a blank page.

But exactly how does our genetic heritage influence our psychological traits? Are there direct links from molecules to minds? Are there dedicated genetic and neural modules underlying various cognitive functions? What does it mean to say we have found ‘genes for intelligence’, or extraversion, or schizophrenia? This commonly used ‘gene for X’ construction is unfortunate in suggesting that such genes have a dedicated function: that it is their purpose to cause X. This is not the case at all. Interestingly, the confusion arises from a conflation of two very different meanings of the word ‘gene’.

From the perspective of molecular biology, a gene is a stretch of DNA that codes for a specific protein. So there is a gene for the protein haemoglobin, which carries oxygen around in the blood, and a gene for insulin, which regulates our blood sugar, and genes for metabolic enzymes and neurotransmitter receptors and antibodies, and so on; we have a total of about 20,000 genes defined in this way. It is right to think of the purpose of these genes as encoding those proteins with those cellular or physiological functions.

But from the point of view of heredity, a gene is some physical unit that can be passed from parent to offspring that is associated with some trait or condition. There is a gene for sickle-cell anaemia, for example, that explains how the disease runs in families. The key idea linking these two different concepts of the gene is variation: the ‘gene’ for sickle-cell anaemia is really just a mutation or change in sequence in the stretch of DNA that codes for haemoglobin. That mutation does not have a purpose – it only has an effect.

So, when we talk about genes for intelligence, say, what we really mean is genetic variants that cause differences in intelligence. These might be having their effects in highly indirect ways. Though we all share a human genome, with a common plan for making a human body and a human brain, wired so as to confer our general human nature, genetic variation in that plan arises inevitably, as errors creep in each time DNA is copied to make new sperm and egg cells. The accumulated genetic variation leads to variation in how our brains develop and function, and ultimately to variation in our individual natures.

This is not metaphorical. We can directly see the effects of genetic variation on our brains. Neuroimaging technologies reveal extensive individual differences in the size of various parts of the brain, including functionally defined areas of the cerebral cortex. They reveal how these areas are laid out and interconnected, and the pathways by which they are activated and communicate with each other under different conditions. All these parameters are at least partly heritable – some highly so.

That said, the relationship between these kinds of neural properties and psychological traits is far from simple. There is a long history of searching for correlations between isolated parameters of brain structure – or function – and specific behavioural traits, and certainly no shortage of apparently positive associations in the published literature. But for the most part, these have not held up to further scrutiny.

It turns out that the brain is simply not so modular: even quite specific cognitive functions rely not on isolated areas but on interconnected brain subsystems. And the high-level properties that we recognise as stable psychological traits cannot even be linked to the functioning of specific subsystems, but emerge instead from the interplay between them.

Intelligence, for example, is not linked to any localised brain parameter. It correlates instead with overall brain size and with global parameters of white matter connectivity and the efficiency of brain networks. There is no one bit of the brain that you do your thinking with. Rather than being tied to the function of one component, intelligence seems to reflect instead the interactions between many different components – more like the way we think of the overall performance of a car than, say, horsepower or braking efficiency.

This lack of discrete modularity is also true at the genetic level. A large number of genetic variants that are common in the population have now been associated with intelligence. Each of these by itself has only a tiny effect, but collectively they account for about 10 per cent of the variance in intelligence across the studied population. Remarkably, many of the genes affected by these genetic variants encode proteins with functions in brain development. This didn’t have to be the case – it might have turned out that intelligence was linked to some specific neurotransmitter pathway, or to the metabolic efficiency of neurons or some other direct molecular parameter. Instead, it appears to reflect much more generally how well the brain is put together.

The effects of genetic variation on other cognitive and behavioural traits are similarly indirect and emergent. They are also, typically, not very specific. The vast majority of the genes that direct the processes of neural development are multitaskers: they are involved in diverse cellular processes in many different brain regions. In addition, because cellular systems are all highly interdependent, any given cellular process will also be affected indirectly by genetic variation affecting many other proteins with diverse functions. The effects of any individual genetic variant are thus rarely restricted to just one part of the brain or one cognitive function or one psychological trait.

What all this means is that we should not expect the discovery of genetic variants affecting a given psychological trait to directly highlight the hypothetical molecular underpinnings of the affected cognitive functions. In fact, it is an error to think of cognitive functions or mental states as having molecular underpinnings – they have neural underpinnings.

The relationship between our genotypes and our psychological traits, while substantial, is highly indirect and emergent. It involves the interplay of the effects of thousands of genetic variants, realised through the complex processes of development, ultimately giving rise to variation in many parameters of brain structure and function, which, collectively, impinge on the high-level cognitive and behavioural functions that underpin individual differences in our psychology.

And that’s just the way things are. Nature is under no obligation to make things simple for us. When we open the lid of the black box, we should not expect to see lots of neatly separated smaller black boxes inside – it’s a mess in there.

Innate: How the Wiring of our Brains Shapes Who We Are by Kevin Mitchell is published via Princeton University Press.Aeon counter – do not remove

This article was originally published at Aeon and has been republished under Creative Commons.

Remembering Luigi Cavalli-Sforza, pioneer in population genetics

Luigi Cavalli-Sforza, a pioneer in using genetic information to help trace human evolution, history and patterns of migration, passed away on August 31 at the age of 96. Hailed as a breakthrough in the understanding of human evolution, his book, The History and Geography of Human Genes offers the first full-scale reconstruction of where human populations originated and the paths by which they spread throughout the world. It remains among the most influential of all PUP publications; American Journal of Human Biology called it “A crowning achievement, a compendium of a career’s work, and a sourcebook for years to come. . . . a landmark publication, a standard by which work in this field must be judged in the future.”

From the New York Times:

Millions of people in recent years have sent off samples of their saliva to DNA-testing companies like 23andMe and Ancestry.com hoping to find out where their forebears came from and whether they have mystery relatives in some distant land, or even around the corner.

The trend itself can be traced to an Italian physician and geneticist, Luigi Luca Cavalli-Sforza, who died on Aug. 31 at his home in Belluno, Italy, at 96. He laid the foundation for such testing, having honed his skills more than 60 years ago using blood types and 300 years of church records to study heredity in the villagers of his own country.

Dr. Cavalli-Sforza was a pioneer in using genetic information to help trace human evolution, history and patterns of migration. The founder of a field that he called genetic geography, he was renowned for synthesizing information from diverse disciplines — genetics, archaeology, linguistics, anthropology and statistics — to explain how human populations fanned out over the earth from their original home in Africa.

Stanford Medicine News Center chronicles Cavalli-Sforza’s work creating the field of genetic geography, which, according to Jarad Diamond, “demolish[ed] scientists’ attempts to classify human populations into races in the same way that they classify birds and other species into races.”

He is survived by his sons Matteo, Francesco and Luca Tommaso Cavalli-Sforza, and by his daughter Violetta Cavalli-Sforza.

Browse our 2018 History of Science & History of Knowledge Catalog

We are pleased to announce our new History of Science & History of Knowledge catalog for 2018! Among the exciting new titles are an annotated edition of Albert Einstein’s travel diaries, a new look at the history of heredity, eugenics, and the asylum, and the latest volume of The Collected Papers of Albert Einstein.

 

The Travel Diaries of Albert Einstein makes available the complete journal that Einstein kept on his momentous 1922 journey to the Far East and Middle East.

The telegraphic-style diary entries—quirky, succinct, and at times irreverent—record Einstein’s musings on science, philosophy, art, and politics, as well as his immediate impressions and broader thoughts on particular events and encounters. Entries also contain passages that reveal Einstein’s stereotyping of members of various nations and raise questions about his attitudes on race. This beautiful edition features stunning facsimiles of the diary’s pages, accompanied by an English translation, an extensive historical introduction, numerous illustrations, and annotations.

This volume offers an initial, intimate glimpse into a brilliant mind encountering the great, wide world.

In the early 1800s, a century before there was any concept of the gene, physicians in insane asylums began to record causes of madness in their admission books. Almost from the beginning, they pointed to heredity as the most important of these causes. Genetics in the Madhouse is the untold story of how the collection and sorting of hereditary data in mental hospitals, schools for “feebleminded” children, and prisons gave rise to a new science of human heredity.

In this compelling book, Theodore Porter draws on untapped archival evidence from across Europe and North America to bring to light the hidden history behind modern genetics. Porter argues that asylum doctors developed many of the ideologies and methods of what would come to be known as eugenics, and deepens our appreciation of the moral issues at stake in data work conducted on the border of subjectivity and science.

A bold rethinking of the asylum, Genetics in the Madhouse shows how heredity was a human science as well as a medical and biological one.

Volume 15 of The Collected Papers of Albert Einstein covers one of the most thrilling two-year periods in twentieth-century physics. The almost one hundred writings by Einstein, of which a third have never been published, and the more than thirteen hundred letters show Einstein’s immense productivity and hectic pace of life.

Between June 1925 and May 1927, Einstein quickly grasps the conceptual peculiarities involved in the new quantum mechanics and investigates the problem of motion in general relativity, hoping for a hint at a new avenue to unified field theory. He also falls victim to scientific fraud and experiences rekindled love for an old sweetheart. He participates in the League of Nations’ International Committee on Intellectual Cooperation and remains intensely committed to the shaping of the Hebrew University in Jerusalem, although his enthusiasm for this cause is sorely tested.

THE COLLECTED PAPERS OF ALBERT EINSTEIN is one of the most ambitious publishing ventures ever undertaken in the documentation of the history of science.  Selected from among more than 40,000 documents contained in the personal collection of Albert Einstein (1879-1955), and 20,000 Einstein and Einstein-related documents discovered by the editors since the beginning of the Einstein Papers Project, The Collected Papers provides the first complete picture of a massive written legacy that ranges from Einstein’s first work on the special and general theories of relativity and the origins of quantum theory, to expressions of his profound concern with international cooperation and reconciliation, civil liberties, education, Zionism, pacifism, and disarmament. The open access digital edition of the first 14 volumes of the Collected Papers is available online at einsteinpapers.press.princeton.edu.

Dalton Conley & Jason Fletcher on how genomics is transforming the social sciences

GenomeSocial sciences have long been leery of genetics, but in the past decade, a small but intrepid group of economists, political scientists, and sociologists have harnessed the genomics revolution to paint a more complete picture of human social life. The Genome Factor shows how genomics is transforming the social sciences—and how social scientists are integrating both nature and nurture into a unified, comprehensive understanding of human behavior at both the individual and society-wide levels. The book raises pertinent questions: Can and should we target policies based on genotype? What evidence demonstrates how genes and environments work together to produce socioeconomic outcomes? Recently, The Genome Factor‘s authors, Dalton Conley and Jason Fletcher, answered some questions about their work.

What inspired you to write The Genome Factor?

JF: Our book discusses how findings and theories in genetics and biological sciences have shaped social science inquiry—the theories, methodologies, and interpretations of findings used in economics, sociology, political science, and related disciplines —both historically and in the newer era of molecular genetics. We have witnessed, and participated in, a period of rapid change and cross-pollination between the social and biological sciences. Our book draws out some of the major implications of this cross-pollination—we particularly focus on how new findings in genetics has overturned ideas and theories in the social sciences. We also use a critical eye to evaluate what social scientists and the broader public should believe about the overwhelming number of new findings produced in genetics.

What insights did you learn in writing the book?

JF: Genetics, the human genome project in particular, has been quite successful and influential in the past two decades, but has also experienced major setbacks and is still reeling from years of disappointments and a paradigm shift. There has been a major re-evaluation and resetting of expectations the clarity and power of genetic effects. Only 15 years ago, a main model was on the so-called OGOD model—one gene, one disease. While there are a few important examples where this model works, it has mostly failed. This failure has had wide implications on how genetic analysis is conducted as well as a rethinking of previous results; many of which are now thought to false findings. Now, much analysis is conducted using data 10s or 100s of thousands of people because the thinking is that most disease is caused by tens, hundreds, or even thousands of genes that each have a tiny effect. This shift has major implications for social science as well. It means genetic effects are diffuse and subtle, which makes it challenging to combine genetic and social science research. Genetics has also shifted from a science of mechanistic understanding to a large scale data mining enterprises. As social scientists, this approach is in opposition to our norms of producing evidence. This is something we will need to struggle through in the future.

How did you select the topics for the book chapters?

JF: We wanted to tackle big topics across multiple disciplines. We discuss some of the recent history of combining genetics and social science, before the molecular revolution when “genetics” were inferred from family relationships rather than measured directly. We then pivot to provide examples of cutting edge research in economics and sociology that has incorporated genetics to push social science inquiry forward. One example is the use of population genetic changes as a determinant of levels of economic development across the world. We also focus our attention to the near future and discuss how policy decisions may be affected by the inclusion of genetic data into social science and policy analysis. Can and should we target policies based on genotype? What evidence do we have that demonstrates how genes and environments work together to produce socioeconomic outcomes?

What impact do you hope The Genome Factor will have?

JF: We hope that readers see the promise as well as the perils of combining genetic and social science analysis. We provide a lot of examples of ongoing work, but also want to show the reader how we think about the larger issues that will remain as genetics progresses. We seek to show the reader how to look through a social science lens when thinking about genetic discoveries. This is a rapidly advancing field, so the particular examples we discuss will be out of date soon, but we want our broader ideas and lens to have longer staying power. As an example, advances in gene editing (CRISPR) have the potential to fundamentally transform genetic analysis. We discuss these gene editing discoveries in the context of some of their likely social impacts.

Dalton Conley is the Henry Putnam University Professor of Sociology at Princeton University. His many books include Parentology: Everything You Wanted to Know about the Science of Raising Children but Were Too Exhausted to Ask. He lives in New York City. Jason Fletcher is Professor of Public Affairs, Sociology, Agricultural and Applied Economics, and Population Health Sciences at the University of Wisconsin–Madison. He lives in Madison. They are the authors of The Genome Factor: What the Social Genomics Revolution Reveals about Ourselves, Our History, and the Future.