Neanderthal Man (35 page)

The second protein on Martin’s list that carried two changes had no known function—a reflection of our woefully inadequate knowledge of what genes do. A third one was involved in the synthesis of molecules necessary to produce proteins in the cells. I had no clue what that might mean, and wondered whether the gene actually had additional functions that were unknown to us—not at all an unlikely possibility given our limited knowledge about the function of genes. But the two remaining proteins with two amino-acid changes were both present in skin—one was involved in how cells attach to one another, particularly while wounds are healing, and the other was present in the upper layers of the skin, in certain sweat glands, and in hair roots. This suggested that something in the  skin had changed during the course of recent human evolution. Perhaps future work will show that the former protein has something to do with the tendency for wounds to heal faster in apes than in humans, and that the latter has something to do with our lack of fur. But for the time being it is just not possible to tell. We are simply too ignorant about how genes affect the ways our bodies work.

A future version of Martin’s and Janet’s catalog, based on a complete version of the Neanderthal genome and more knowledge about genetic variation in people today, will contain positions in the human genome that changed between perhaps 400,000 years ago, when our ancestors parted ways with Neanderthals and then spread to become present in all humans, and about 50,000 years ago, when the “replacement crowd” fanned out across the globe, on the other. After that time, no further changes could be established in
all
humans simply because humans were spread out across continents. Based on the numbers we obtained using the parts of the Neanderthal genome we had, we estimated that the total number of DNA sequence positions at which the Neanderthals differed from all humans today will be on the order of 100,000. This will represent an essentially complete answer to the question of what makes modern humans “modern,” at least from a genetic perspective. If in an imaginary experiment one were to change each of these 100,000 nucleotides back to their ancestral state in a modern human, the result would be an individual who, in a genetic sense, was similar to the common ancestor of Neanderthals and modern humans. In the future, one of the most important research objectives in anthropology will be to study this catalog in order to identify those genetic changes that are of relevance for how modern humans think and behave.

________________________________

In science, very few results are definitive. In fact, soon after arriving at an insight, often after great effort, one can generally foresee imminent developments that will improve upon it. Yet at some point, it is necessary to draw a line and say that the time has come to publish. In the fall of 2009, I felt that we had reached that point.

The paper that we were going to write would be a milestone in several ways. Above all else, it was the first genome sequenced from an extinct form of humans. True, Eske Willerslev’s group in Copenhagen, Denmark, had published a genome from a lock of Eskimo hair that spring. But the lock of hair was just 4,000 years old and had been preserved in the permafrost, and 80 percent of its DNA was human. The title of their paper said that they had sequenced an “extinct Palaeo-Eskimo,” although I wondered what present-day Eskimos thought about the contention that they were extinct. The Neanderthals were truly old, truly extinct, a different form of humans, and of crucial evolutionary importance as the closest relative of all present-day humans, no matter where they live on the planet. I also felt that we had set the technical stage for much future work; unlike carcasses preserved in permafrost, the bones we had used hadn’t been preserved in extraordinary ways. They were similar to thousands of human and animal bones found in caves in many parts of the world. I hoped that the techniques we had developed could now be used to recover whole genomes from many such remains. The finding most likely to create controversy was that Neanderthals had contributed parts of their genome to present-day people in Eurasia. But since we had come to this conclusion three times using three different approaches, I felt that we had definitively laid this question to rest. Future work would surely clarify the details of when, where, and how it had happened, but we had definitively shown that it
had
happened. The time had come for us to present our results to the world.

My ambition was to write a paper that would be as understandable as possible to a wide audience since not only geneticists would be interested in what we had done, but also archaeologists, paleontologists, and others. In fact, I was getting pressure from various directions to publish our findings. The
Science
editor was asking me when the paper would be submitted, and journalists kept calling not only me but other members of the team to ask when we would publish. I was starting to feel increasingly embarrassed about giving scientific talks that were focused more on technical issues than on what the genome told us, even though everybody realized that by now we must have interesting results to report. Despite the pressure, I felt that it was crucial to keep our main findings secret until publication. I worried that one of the fifty or so people in the know would tell a journalist that we had found evidence of Neanderthal gene flow in present-day people. If that happened, the news would quickly be all over the media.

An additional recurring worry was that another group would publish Neanderthal sequences before we did. This second worry was of course focused on one particular person: our previous partner and current competitor, Eddy Rubin at Berkeley, whom we knew had access to Neanderthal bones and the resources necessary to work on them. I thought about all the efforts expended by everyone involved in this project over the past four years and imagined what it would feel like to wake up to newspaper headlines saying that Neanderthals had contributed genes to people today, based on perhaps ten times less data than we had, analyzed in haste. Quite uncharacteristically, I even found myself fretting about this as I tried to fall asleep at night.

It was impossible to hide my worries during our weekly phone meetings. I started to reiterate that no one was allowed to say anything about any aspect of our results to the press, however pushy a journalist might be. That not a single consortium member ever did so is testimony to the loyalty of the entire team. I also started to pressure everyone in the consortium to deliver descriptions of what they had done. This was less easy for them to achieve. Some scientists are so driven by intellectual curiosity that once they’ve found the solution to a problem, they will be remiss in going through the tedium of writing it up and publishing it. This, of course, is very bad. Not only does the public, which has ultimately funded the research, have a right to learn about the results, but other scientists also need to know the details of how results were achieved so that they can improve and build on them. In fact, this is the main reason why, when scientists are being considered for appointments and promotions, they’re judged not on  how many interesting projects they have started but, instead, on how many projects they have finished and published. Some members of the consortium delivered their texts quickly, some slowly and in a preliminary form, and some not at all. I thought about how to pressure even distinguished colleagues to deliver their write-ups and finally came up with an idea: I needed to take advantage of their vanity.

Most scientists, like most people, want recognition for a job well done. They thrive on how often their papers are cited in other publications and how many invitations they get to deliver lectures. Apportioning the credit in our case would be difficult. Several groups and more than fifty scientists had contributed to our project and would appear as authors on the paper, and it would be hard to attribute credit to individuals for each of the different, often very creative and laborious analyses that had been done. In spite of this, everybody had worked selflessly toward the common goal, but it seemed only fair to apportion some individual credit. The question I faced was how to do that, and in the process also stimulate people to write quicker and well.

As is typical of many large scientific papers, most results presented in our paper would be presented as so-called supplementary material that wouldn’t be included in the print journal but would instead be published electronically on the journal’s website. The bulk of this considerable pile of material would be the technical minutiae interesting only to the experts. Normally, the authors of the supplementary material are the same and appear in the same order as on the paper. I decided to change that. I suggested that each section of this supplementary material would have separate authors and include a corresponding author to whom any interested readers would be referred in case they had questions. This system would make much clearer who had done which experiments and analyses. It would also make each person personally responsible for the quality of the section, as any glory—or any blame—would be directed at least partly to him or her. To further improve the quality, we assigned one member of the consortium not involved in that particular aspect of the work to carefully read such supplementary sections in order to find errors and faults in the presentation. This all helped. People actually delivered their supplementary sections, which eventually swelled to 19 chapters and 174 pages. My task became to modify these sections and write the main text that would be printed in the journal. In this, the ever energetic David Reich was a great help. There was much e-mailing about changes to the text of the main paper but finally, in the first days of February 2010, Ed Green  submitted everything to
Science.

On the first of March we received comments from three reviewers, and almost three weeks later we received comments from a fourth reviewer. It isn’t unusual for reviewers to find many things to complain about in a manuscript. In this case, however, they didn’t have much to say: the two years we spent trying to find flaws in each other’s work had allowed us to find most of the weak points ourselves. Nevertheless, there was quite a lot of back and forth about the text with the editor. In the end, the paper appeared on May 7, 2010, complete with its 174 pages of supplementary material.
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The paper was “more like a book than a scientific paper,” as one paleontologist put it.

On the day the paper appeared, the two major institutions in the world that provide the scientific community with access to genome sequences, the European Bioinformatics Institute in Cambridge, England, and the Genome Browser maintained by the University of California at Santa Cruz in the United States, made the Neanderthal genome freely available to all. In addition, we made available in a public database all of the DNA fragments we had sequenced from the Neanderthal bones, including those that we had judged to be of bacterial origin. I wanted everyone to be able to check every detail of what we had done. And I wanted them to do a better job if they could.

With the appearance of the paper came the anticipated media frenzy. However, my previous dealings with journalists had left me somewhat jaded so I left Ed, David, Johannes, and the others in the consortium to deal with the press. In fact, the day our paper was published, I was scheduled to give a big lecture at Vanderbilt University in Nashville, Tennessee. That trip, which had been planned for a long time, was a convenient way for me to avoid the hype. But the excitement did rub off on my very friendly hosts in Nashville. When they learned that someone who sounded rather odd had called asking for me at my hotel, they worried about my safety, thinking of Christian fundamentalists who might be opposed to an evolutionary origin of humans. They had the police trace the phone call. It had come from the university campus; for some reason, this made them even more nervous so they had two police officers in civilian clothes follow me around everywhere I went on campus. This was the first time I have had bodyguards when giving a talk. I appreciated the concern for my safety, and the attention made me feel important. But those two huge men, in their dark suits and earpieces, eyeing everyone who approached me with suspicion, made  the after-lecture mingling with faculty and students slightly awkward.

As it happened, the Neanderthal paper appeared the week before the 2010 Cold Spring Harbor Genome Meeting, so I went straight from Nashville to Long Island. I very much enjoyed presenting our main findings in the same auditorium where, four years earlier, I had announced our intention to do the project. I ended my talk by saying that I hoped the Neanderthal genome would prove a useful resource for scientists in the future. As it happened, the future came only five minutes after I had stepped down from the stage.

The speaker who followed me was Corey McLean, a graduate student from Stanford University. As I sat down, I vaguely thought to myself that I didn’t envy him; following a talk that attracted a lot of attention was never easy. Very quickly I came to regret this condescending attitude. Corey gave a brilliant presentation. He had analyzed the genomes of humans and apes and identified a total of 583 large chunks of DNA lost in humans but present in the apes. He had then looked at what genes were in those regions and identified several interesting genes that had been lost in humans. One of these encoded a protein expressed in penile spines, which are structures on the penises of apes that cause males to ejaculate very quickly. These spines are not present in humans, which enables us to enjoy prolonged intercourse. The gene Corey had found to be lost might well be the reason for that. Another chunk that humans had lost encoded a protein that might limit the extent to which neurons divide and might have something to do with how the brain got larger in humans. This was fascinating! But what was most satisfying to me was that, in just the few days the Neanderthal genome had been publicly available, Corey had already checked the Neanderthal genome to see which of the deletions present-day humans share with Neanderthals. This was precisely how I had hoped our work would be applied, as a tool that would allow others to extend their own research by timing when changes had happened during human evolution. Corey had found that the Neanderthals did indeed have the penile spine deletion, so we immediately learned something about the intimate anatomy of Neanderthals that the fossil record couldn’t tell us. The deletion involved in brain size was also shared with Neanderthals, a finding that we would have anticipated given our knowledge from fossils that their brains were as large as ours. But some of the other chunks that he hadn’t yet investigated were not deleted in Neanderthals. Future work would show whether they truly were absent in all humans today and, if so, whether they had some likely consequences for how present-day humans differed from Neanderthals.