Senior Vice Provost, Dean for the Social Sciences and University Professor, New York University, Adjunct Professor of Community Medicine, Mount Sinai School of Medicine, New York, NY, Research Associate at the National Bureau of Economic Research (NB
Breaking the Wall of Nature and Nurture. How Genes and Environment Combine to Affect Our Life Course
When the wall came down in the fall of 1989, I didn’t hear anything about it, because my grandfather had just been struck down in an accident in Miami Beach. I was spending day and night supporting my grandmother.
Good morning. Thank you Sebastian and everybody else for coming to hear me speak. I have a little pet theory; this is not my own research just my hobby, but all academics are studying themselves in some way. So, I imagine that Tania started looking at emotional compassion, because she is an identical twin. I started looking at nature and nurture, I think, because of my own childhood, which I want to start with. A childhood natural experiment, I call it. (Sorry about these slides) This on my left is the neighbourhood where I grew up in. It was a low-income neighbourhood, what we call a ghetto of Puerto Rican and African American families- except for my sister and I, who you can see in the picture. You can guess which one is me, I think. As we grew up there, the children of artists, we ended up, not understandably perhaps, with very different outcomes from our neighbours. So, here I am standing before you, having the great honour of giving this lecture. That is me playing the clarinet very badly in the 7th grade, and there was my best friend from the yearbook, who shortly after that photo was taken, was shot in the neck and paralysed from waste down for the rest of his life. I think that is what motivated me in my own research to ask: why did we have these different outcomes? Little did I know, I was getting into one of the great debates in the last 150 years, which is “Nature versus Nurture”.
On the one hand, we have the mass that represent the behaviouralists, who think that any behaviour, personality, any aspect of our lives, can be socialised, can be taught, famously, as argued by Watson. Then we have the other Watson: Watson and Crick, who discovered DNA that led to an argument- that most of what we do, say, believe, our personality, is innate, is part of the genes. I want to argue today, show you some evidence, that that is a false dichotomy.
Sociologists are fond of saying, “Yes, yes, how genes matter depend on your environment.” If you have a gene for aggression, lets say, and you are born in the ghetto like me, you end up in jail. But, if you have that same gene for aggression, and you are born into a very wealthy family, you end up as CEO or executive. (Laughter in audience) But how do we do we get from that simple proverb to a real empirical strategy to understand gene environment or interactions? In fact, I want to make a broader claim that actually the genes of those around you are part of your actual social environment.
But, let me tell you a little story of how I got here. As a sociologist, we can’t really run experiments to answer our questions very well; because I can’t randomly assign half of this room to become married, and the other half to get divorced, and then follow you. So, my ideal experiment would be to take two twins like this and take them at birth, or even before birth, separate them, and raise them in randomly assigned households. Then I would have to be a stalker, hide in bushes for about 35 years or 40 years, watching them and taking detailed notes to know how they turn out. Then I will know the effects of nurture- as separate from nature.
Of course, I cannot do that, but there is some new promise with the rise in molecular genetics, the sequencing of the genome, and the identification of polymorphisms: markers that are distinct within the human population that vary from person to person. I want to talk about one in particular today, but I have to explain a little of what I mean. There are two main types or variations of polymorphisms. One is what is called a SNP: a substitution at a single point of one base for another, in this case T to A. There is another kind, there are multiple kinds, but the second is a Microsatellite, or Variable Number Tandem Repeat. Imagine if you had to copy the same sentence over and over again, you would probably make a mistake of how many times you wrote it. It is a very common error in replication to have repeats like this of different numbers and different people. That is the kind that I want to talk about today, in particular I am going to talk about the serotonin transporter.
How many of you are on Prozac or some other... no you don’t have to answer that. (Laughter in audience) Serotonin transporter is that protein on the right that allows the serotonin to be reuptaked back into the presynaptic neuron and therefore be used again. The SSRIs or the Prozac slows that process down and leaves more serotonin in a synapse. There are two major alleles in the human population of the promoter region, which is not the shape of the protein itself, but the regulatory reach- how much of this protein are you going to produce, how many of these transporters are you going to have? There is the long allele and the short allele. The long allele, think of it as a helicopter landing pad; it is a bigger promoter, therefore it is easier for it to be transcribed, and you get more of the transporters. The short allele gives you fewer.
It has been observed in animal studies that those for the shorter allele, or this gene knocked out, end up with a phenotype of social defeat: depression, anxiety. They can measure all this in mice, and they find these very depressed mice. So, when it was discovered in animal models that this had this important outcome, people started looking at it in humans. At first, it was thought that the short allele was bad; it lead to this depression, to this negative phenotype. But, then that left us with a mystery story. It is a mystery that takes place over 40 million years or so, because we share this variation of short and long with our relatives- as you can see: all the simians and prosimians. In fact, what makes the mystery even more interesting is the fact that the promoter has got shorter and shorter over evolutionary history. In other words, the bad allele has been getting more frequent as we have “evolved”. So, humans have the highest rate of the short “bad allele”.
That led some people to say, “Well, maybe it is not bad; maybe we are conceptualising it the wrong way?” They started this debate or this concept of the orchid versus the dandelion. An orchid is a beautiful flower, but you need to take very good care of it, like (? 50:14 petit pois) in a jar, perfect temperature, everything. If you do that, if you give it the perfect environment, then you get this beautiful flower. But, a dandelion, I like to think of it as: (Laughter) because we are Germany, make fun of the French. In humans, the idea is that it is an emotionally reactive, emotionally sensitive allele. So, that is why maybe it stuck around. It gives you sensitivity to other people’s moods and emotions; it makes you reactive. But, if you are a dandelion, as no drama Obama probably is, that you are cool and calm and you do not react. But, you don’t look as beautiful- I don’t know if Barack is more beautiful than Nicolas or not, but you can survive like in a dandelion and you look the same, and it its across all environments. Like- Dandelions can live in many environments.
So, that concept got very popular in the psychological literature to explain, to make it more complicated, the story of the fact that there are these two alleles, and it is not just negative to have the short one. This parallels literature in evolution and biology, which is called phenotypic capacitances. Is this serotonin transporter a phenotypic capacitor? This comes from writings fifty years ago by Waddington that argued that there are certain genes that mask variation. When they are released, when they are compromised, you get a radiation of different phenotypes as an evolutionary strategy to survive. So, in other words, you uncork the genie bottle, and these different creatures come out. And at least in a challenging environment, hopefully one of them will survive.
I looked at twins. I don’t think Tania was in my study, but twins we could separate out into those who share their genome completely and only have differences in their environment, and twins who have both differences in environment but also differences in the genome, i.e. fraternal twins that are the same sex. But when we do that, we find that, indeed, those with the short allele end up more different in their depression- not the average level, but the difference between the two siblings is greater when you have the orchid allele than when you have the dandelion allele. When we separate that out to genetically identical monozygotic twins and dizygotic twins, we see the same pattern.
So that explains that maybe there is something to this allele orchid, dandelion hypothesis. However, that doesn’t really answer the mystery of why has this remained imbalanced? Why don’t we all have the short allele? Why is it that some level of group selection do we need both in the population?
There you turn to another theory of evolution, which is called frequency dependent selection, or balancing selection. We can think of many examples of this in nature. One is apostatic selection. I show you these multi-coloured fish, because evolution actually preserves the range of variety in their morphology and colour, because it increases the search cost for their predators. If the fish are all the same colour, it is easier for a predator fish to hone in on them; but when they have different colours it is more confusing.
Likewise, on the right is an image of the major histocompatability complex protein, and we have a lot of variation in that. The idea is that, at least some us, if there is a major plague, at least some of us will have the right one to survive and repopulate the earth. So maybe this happening on a behavioural level as well, I asked. Maybe there is balancing selection going on for these particular alleles.
You could think of a game theory, like the games that were described by Tania. Maybe it is actually good to be the grumpy, demanding, Sarkosy-baby if you are going to get a lot of attention, and your siblings don’t have that allele. They are calm; you are screaming all the time, and you get more investment from your parents that way. Or maybe it works the other way. Maybe when you are the bad kid, or the demanding, screaming, loud, sensitive kid, then your parents shun you, and you end up worse off. But the key to this theory is that your genotype alone does not matter. Your genotype only matters in the context of your family’s genotype, particularly your siblings that you are in competition in the nest, if you will, with.
So, again, I looked at twins, and I looked at in this case, not identical twins, but only fraternal twins. What did I find? I found that, indeed, if you have the long alleles, and you have no short alleles, it doesn’t really matter what your siblings are, in terms of their alleles. If you have the short, sensitive, reactive alleles, then it does matter what your siblings do. In fact, if you are all a bunch of whining difficult babies, then you are fine; you are all whining. But if you are the only one, then you get less parental investment, and you end up worse off in your mental health and your psychology as you age. Our environment is not just our uterus that we were gestated in; it is not just the toys, books, and our colleagues around us; it is the very genes around us, and therefore there is no wall between nature and nurture. Thank you.