by Pbo, Svante
Reflecting on such questions, I came to realize that this was unlikely to be the case. The most reasonable scenario is that all humans today, regardless of whether we live inside or outside of Africa, are part of the replacement crowd. And although many paleontologists and geneticists, including myself, had thought that the replacement crowd spread around the world without mixing with the other human groups that they encountered, after its having happened once was ascertained, there was reason to think it may have happened more times. Since we have no ancient genomes from other parts of the world, we are effectively blind to possible contributions from other archaic humans. This is particularly the case in Africa, where genetic variation is larger than elsewhere, so a contribution from some archaic group would be hard to detect. Nevertheless, when the replacement crowd spread across Africa, they could well have mixed with archaic humans there and incorporated their DNA into their gene pool. I decided to point this out to journalists and in talks to make it clear that there was little reason to believe that Africans had no archaic DNA in their genomes. Probably all humans do, and indeed, some more recent analyses of present-day people in Africa have suggested that this is the case.
One evening, when I was especially tired after a long day at work followed by some particularly rambunctious behavior by our now five-year-old son, a crazy question came to me just after he had fallen asleep: If all people today carry 1 to 4 percent of the Neanderthal genome, could one imagine that by pure chance, as a freak result of the random assortment of DNA segments during the production and fusion of sperm and eggs, a child could be born who is entirely or almost entirely Neanderthal? Could the many Neanderthal DNA fragments that exist in people today have happened to come together in my sperm cell and Linda’s egg cell that ended up developing into our rambunctious son? Just how Neanderthal could he—or I—be?
I decided to do a simple calculation. The segments that Rasmus had identified were about 100,000 nucleotides long, and on average perhaps 5 percent of people outside Africa carried any one of them. If all Neanderthal fragments were of this length and if, together, they made up the entire Neanderthal genome, there would be about 30,000 fragments in existence. Many Neanderthal DNA fragments were in fact both shorter in length and less frequent than 5 percent, and perhaps they wouldn’t add up to the whole genome, but I wanted to deliberately bias my calculations to see if it could at all be possible that my son was of completely Neanderthal descent. Under these assumptions, his chance of having a particular Neanderthal DNA fragment was like drawing a ticket in a lottery where 5 percent of tickets were winners. His chance of carrying the Neanderthal fragment on both of a pair of his chromosomes was like drawing a winning ticket in this lottery twice. This was 5 percent of 5 percent or 0.25 percent. To be entirely Neanderthal for the genome he had gotten from Linda and the genome he had gotten from me, he would have to have drawn winning tickets twice for each of the 30,000 segments, or 60,000 times in row! The chance of this was of course infinitesimally small (in fact, a zero and a decimal point followed by 76,000 zeros and then some number). So not only was my son very unlikely to be wholly Neanderthal, even among all 8 billion people on earth there was no chance that a Neanderthal child would be born. So I had to dismiss the idea that my son was to any appreciable degree Neanderthal. Thankfully, I could also write off the risk that any latter-day Neanderthal would walk into our lab one day and offer me a blood sample, making our entire effort to sequence a Neanderthal genome from ancient bones unnecessary.
Nevertheless, clearly identifying which DNA segments in our genomes come from Neanderthals and finding out if all parts of the Neanderthal genome exist scattered among people today are both important research goals. The size and number of these segments would say something about how many cases of actual mixed children were behind the contribution of Neanderthal DNA to the replacement crowd and when this contribution occurred. Also, any parts that might be missing could be very interesting, because they may contain the genetic essence of the crucial difference between the modern human replacement crowd and Neanderthals.
At this point in my musings, I realized after making the calculations about my son that others would also be interested in finding out what parts of their genomes were of Neanderthal origin. People wrote to me every year suggesting that they (or their loved ones) were part Neanderthal. Often they included photos, which tended to show slightly stocky individuals, and quite often they volunteered to contribute a blood sample for our research. Now that we actually had a Neanderthal genome, I could imagine comparing our Neanderthal DNA sequences to DNA sequences of any person today and identifying the segments in the person’s genome that were close enough to the Neanderthals to have been inherited from them. After all, there were already many companies that offered this kind of analysis with respect to ancestry from different parts of the world. For example, people in the United States are often interested in finding out how much of their ancestry comes from Africa, Europe, Asia, or from Native Americans. In the future, this could be done for Neanderthal ancestry. I was intrigued, but again, I was also worried. There might be a stigma associated with being “Neanderthal.” Would people feel bad if they knew that some part of their genome that carried genes involved in how brain cells work came from Neanderthals? Would future arguments between spouses include arguments such as “You never take out the trash because such-and-such brain gene of yours is Neanderthal”? Could this stigma be applied to entire groups of people if some population happened to have a high frequency of a Neanderthal variant of a gene?
I felt that we should try to control such applications of our work. The only way to do this that I could think of was to patent the use of the Neanderthal genome for such ancestry testing. If we did so, anyone who wanted to earn money by testing people would need to obtain a license from us. That would allow us to impose conditions on how information was given to the customers. We could also charge a fee for such licenses so that our lab and the Max Planck Society might get back some of the money invested in the Neanderthal project. I talked about this to Christian Kilger, a former graduate student who was now an attorney specializing in biotech patents in Berlin. Together we discussed how one could share putative patent revenues among the research groups in the consortium.
Thinking this plan might be slightly controversial, I presented it to the group in one of our Friday meetings. I soon found out that I had totally misjudged the situation. Some people were passionately against the idea of a patent. In particular, Martin Kircher and Udo Stenzel, whose professional abilities I much respected, were against patenting the use of something that occurred naturally, such as the Neanderthal genome. Overall, this was a minority view in the group but it was upheld with almost religious fervor. Others held the exact opposite viewpoint. Ed Green, for example, had even visited the largest commercial ancestry company, 23andMe, in California and seemed open to working with it in the future. The debate raged in our meetings, in the cafeteria, in the labs, and at our desks. I invited Christian Kilger and a patent attorney from the Max Planck Society to explain what patents were and how they functioned. They went to great lengths to explain that a patent would put limitations only on the commercial use of the Neanderthal genome—and even then, only for the particular purpose of ancestry testing—and that it would in no way limit any scientific applications. This did nothing to change any opinions or end the emotional tone of our debate.
I didn’t want a long divisive fight about this issue in the group. I wanted even less to push through a decision against the will of a dedicated minority. We were still far from submitting our paper and needed cohesion in the group. So, two weeks after raising the issue, I announced during a Friday meeting that I had decided to drop the patent idea. I received an e-mail from Christian that ended with “What a chance missed.” I shared his sentiment. It had been an opportunity to both fund future research and positively influence how commercial companies could use our results. In fact, as I write this, 23andMe has started offering Neandert
hal ancestry testing. Other companies are sure to follow. But group cohesion was what drove our project forward. It was too valuable an asset to risk destroying.
Chapter 20
Human Essence?
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Our institute in Leipzig is a fascinating place. In one way or another, almost every researcher there studies what it means to be human, but they all approach this rather fuzzy-sounding question from a fact-oriented, experimental perspective. One particularly interesting line of research is that of Mike Tomasello, the director of the department for comparative and developmental psychology. His group is interested in differences in cognitive development between humans and the great apes.
To measure those differences, Mike’s group administers the same “intelligence” tests to both. Of special interest is how well apes and human children cooperate with their peers to achieve goals such as figuring out how to get an intricate contraption to release a toy or candy. One insight that has come from Mike’s work is that, until about ten months of age, there are hardly any detectable cognitive differences between young humans and young apes. However, at around one year of age, humans start doing something that the ape youngsters don’t: they start to draw others’ attention to objects of interest by pointing at them. What’s more, from that age on, most human children find pointing at things intrinsically interesting. They will point to a lamp, a flower, or a cat, not because they want the lamp, the flower, or the cat, but for the sole purpose of directing the attention of their moms, dads, or others to it. It is the very act of directing the attention of another person that is fascinating to them. It seems that by about one year of age, they have begun both to discover that other people have a worldview and interests not so dissimilar from their own and to take steps toward being able to direct the attention of others.
Mike has suggested that this compulsion to direct the attention of others is one of the first cognitive traits that emerge during childhood development that is truly unique to humans.{58} It is certainly one of the first signs that the children have started to develop what psychologists call a theory of mind, an appreciation that others have different perceptions than one’s own. It is easy to imagine that the enormous human capacity for social activities, for manipulating others, for politics, and for concerted action of the sort that result in large and complex societies arise out of this ability to put oneself in another’s shoes and manipulate that person’s attention and interest. I believe that Mike and his group have pointed to something that is fundamental for what set humans on a historic trajectory so different from that of the apes and the many extinct forms of humans, such as Neanderthals.
Mike has also pointed out another potentially very important propensity that sets human children apart from ape youngsters: human children, much more than apes, tend to imitate what their parents and other humans do. In other words, human children “ape” whereas apes do not “ape.” And reciprocally, human parents and other adults correct and modify behaviors in their children to a much greater extent than ape parents do. In many societies, humans have even formalized this activity—it is what we know as teaching. In fact, a very large part of all activities that humans do with their children is teaching, in either an implicit or explicit form. Often it is institutionalized in the form of school and universities. In contrast, there has been almost no teaching observed in apes. It is fascinating to me that the human propensity to readily learn from others may emanate from the shared attention that first manifests itself in the toddler who points to the lamp just to get her dad to look at it.
This focus on teaching and learning probably has fundamental consequences for human societies. Whereas apes must learn every skill they eventually acquire through trial-and-error and without a parent or other group member actively teaching them, humans can much more effectively build on the accumulated knowledge of previous generations. As a result, when an engineer improves a car, she need not invent it from scratch. She will build on the inventions of previous generations all the way back to the invention of the combustion engine in the twentieth century and of the wheel in antiquity. To this accumulated wisdom of her ancestors she will merely add some modifications to the design that later generations of engineers will in turn take for granted and continue to build upon. Mike calls this the “ratchet effect.” It is clearly a key to the enormous cultural and technological success of humans.
My fascination with Mike’s work stems from my conviction that there are genetic underpinnings to our propensity for shared attention and the ability to learn complex things from others. In fact, there is ample evidence to suggest that genetic traits are a necessary foundation to these human behaviors. In the past, people sometimes did what we now consider to be unethical experiments in which they raised newborn apes together with their own children in their home. Although apes learned how to do many human-like things—they could construct simple two-word sentences, manipulate household appliances, use bicycles, and smoke cigarettes—they did not learn truly complex skills and they did not engage in communication on the scale that humans do. In essence, they did not become cognitively human. So it’s clear that there is a biological substrate necessary for fully acquiring human culture.
This is not to say that genes alone are sufficient for acquiring human culture, only that they are a necessary substrate. In the imaginary experiment where a human child is raised in the absence of any contact with other human beings, it is very likely that the child would never develop most of the cognitive traits that we associate with humans, including awareness of the interests of others. That unfortunate child would probably also not develop the most sophisticated of cultural traits that emanates from our tendency to share attention with others: language. So I am convinced that social input is necessary for the development of human cognition. However, no matter how early in life and how intensively they are integrated into human society and no matter how much teaching they are subject to, apes do not develop more than rudimentary cultural skills. Social training alone is not enough. A genetic readiness to acquire human culture is necessary. Similarly, I am convinced that a newborn human raised by chimpanzees would fail to become cognitively chimpanzee. There is surely also a genetic substrate necessary to becoming fully chimpanzee that humans lack. But since we are humans, we are more interested in what makes humans human than in what makes chimpanzees chimpanzee. We should not be ashamed of being “humancentric” in our interests. In fact, there is an objective reason to be so parochial. The reason is that humans, and not chimpanzees, have come to dominate much of the planet and the biosphere. We have done so because of the power of our culture and technology; these have allowed us to increase our numbers vastly, to colonize areas of the planet that otherwise would not have been habitable for us, and to have an impact on and even threaten aspects of the biosphere. Understanding what caused this unique development is one of the most fascinating, perhaps even one of the most pressing, problems that scientists face today. One key to the genetic underpinnings of this development may well be found through comparing the genomes of present-day humans with Neanderthals. Indeed, it is this feeling that kept me going during years of struggling with the technical minutiae of retrieving the Neanderthal genome.
According to the fossil record, Neanderthals appeared between 300,000 and 400,000 years ago and existed until about 30,000 years ago. Throughout their entire existence their technology did not change much. They continued to produce much the same technology throughout their history, a history that was three or four times longer than what modern humans have experienced. Only at the very end of their history, when they may have had contact with modern humans, does their technology change in some regions. Over the millennia, they expanded and retracted with the changing climates in the areas they lived in Europe and western Asia, but they didn’t expand across open water to other uninhabited parts of the world. They spread pretty much as other large mammals had done before them. In that, they were similar to other extinct forms of h
umans that had existed in Africa for the past 6 million years and in Asia and Europe for about 2 million years.
All of this changed abruptly when fully modern humans appeared in Africa and spread around the world in the form of the replacement crowd. In the 50,000 years that followed—a time four to eight times shorter than the entire length of time the Neanderthals existed—the replacement crowd not only settled on almost every habitable speck of land on the planet, they developed technology that allowed them to go to the moon and beyond. If there is a genetic underpinning to this cultural and technological explosion, as I’m sure there is, then scientists should eventually be able to understand this by comparing the genomes of Neanderthals to the genomes of people living today.
Fueled by this dream, I was itching to start looking for crucial differences between Neanderthals and present-day humans once Udo had finally mapped all the Neanderthal fragments in the summer of 2009. But I also realized that I needed to be realistic about what those differences would tell us. The dirty little secret of genomics is that we still know next to nothing about how a genome translates into the particularities of a living and breathing individual. If I sequenced my own genome and showed it to a geneticist, she would be able to say approximately where on the planet I or my ancestors came from by matching variants in my genome with the geographic patterns of variants across the globe. She would not, however, be able to tell whether I was smart or dumb, tall or short, or almost anything else that matters with respect to how I function as a human being. Indeed, despite the fact that most efforts to understand the genome have sprung from efforts to combat disease, for the vast majority of diseases, such as Alzheimer’s, cancer, diabetes, or heart disease, our current understanding allows us only to assign vague probabilities to the likelihood that an individual will develop them. So in my realistic moments, I realized that we would not be able to directly identify the genetic underpinnings of the differences between Neanderthals and modern humans. There would be no smoking gun to be found.
