Neanderthal Man (5 page)

This battle had been initiated by the out-of-Africa hypothesis, which Allan Wilson and his colleagues had proposed based largely on the patterns of present-day human mtDNA variation. Initially, the idea had been met with ridicule and hostility by the paleontological community. Almost all paleontologists at the time subscribed to the so-called multiregional model for the origin of modern humans—holding that modern humans evolved on several continents, more or less independently, from
Homo erectus.
They saw a deep history dividing current groups of humans: the ancestors of current Europeans, for instance, were thought to be the Neanderthals and perhaps earlier European hominins; the ancestors of current Asians were thought to be other archaic forms in Asia, going back to Peking Man. However, a growing number of respected paleontologists, foremost among them Chris Stringer at the Natural History Museum in London, now viewed the out-of-Africa model of modern human origins as the best fit to both the fossil record and the archaeological evidence. Chris had been invited by
Cell
to the press conference, where he announced that our retrieval of Neanderthal DNA was to paleontology what the lunar landing had been to space exploration. I was of course pleased, though not surprised, by his praise. I was even more pleased when the “other side,” the multiregionalists, had good things to say at least about the technical  aspects of our work—particularly when the most vociferous and pugnacious of them, Milford Wolpoff, of the University of Michigan, declared in a commentary in
Science
that “if anyone would be able to do this, it would be Svante.”

All in all, I was stunned by the attention our paper received. It was reported on the first page of many major newspapers and on radio and TV news shows worldwide. In the week after the paper appeared, I spent most of my time on the phone with journalists. I had worked on ancient DNA since 1984 and had gradually realized that it must in principle be possible to recover Neanderthal DNA. And nine months had now passed since Matthias called and awakened me to say he saw a DNA sequence that did not look human come out of one of our sequencing machines. So I’d had time to get used to the idea and, unlike most of the rest of the world, was not shaken by our achievement. Once the media frenzy had died down, though, I felt the need for some perspective. I wanted to reflect on the years that had led up to this discovery and to think about where I would go next.

___________________________________

It did not begin with Neanderthals, but with ancient Egyptian mummies. Ever since my mother took me to Egypt when I was thirteen, I had been fascinated with its ancient history. But when I started to pursue this study in earnest, at the University of Uppsala in my native Sweden, it became increasingly clear that my fascination with Pharaohs, pyramids, and mummies was the romantic dream of an adolescent. I did my homework; I memorized the hieroglyphs and the historical facts; I even worked two consecutive summers cataloging pottery shards and other artifacts at the Mediterranean Museum in Stockholm, which might well have become my future workplace, were I to become an Egyptologist in Sweden. I found that the same people did very much the same things the second summer as they had the first summer. Moreover, they went to lunch at the same time, to the same restaurant, ordered the same meals, discussed the same Egyptological puzzles and academic gossip. In essence, I came to realize that the discipline of Egyptology was moving too slowly for my tastes. It was not the kind of professional life I imagined for myself. I wanted more excitement, and more relevance to the world I saw around me.

This disenchantment threw me into a crisis of sorts. In response, and inspired by my father, who had been an MD and later became a biochemist, I decided to study medicine, with a view to doing basic research. I entered medical school at the University of Uppsala and after a few years surprised myself by how much I enjoyed seeing patients. It seemed to be one of the few professions in which you not only met all sorts of people but could also play a positive role in their lives. This ability to engage with people was an unexpected talent, and after four years of medical studies I had another mini-crisis: Should I become a clinician or move, as I had originally meant to do, into basic research? I opted for the latter, thinking that I could—and most likely would—come back to the hospital after my PhD. I joined the lab of one of the then-hottest scientists in Uppsala, Per Pettersson. Not long  before, his group had been the first to clone the genetic sequence of an important class of transplantation antigens, protein molecules that sit on the surface of immune cells and mediate their recognition of viral and bacterial proteins. Not only had Pettersson produced exciting biology insights with relevance to clinical practice, but his lab was one of the few in Uppsala that had mastered the then-novel methods of cloning and manipulating DNA by introducing it into bacteria.

Pettersson asked me to join his group’s efforts to study a protein encoded by an adenovirus, a virus that causes diarrhea, cold-like symptoms, and other unpleasant features of our lives. It was thought that this viral protein became bound by the transplantation antigens inside the cell, so that, once transported to the cell surface, it could be recognized by immune-­system cells, which would then become active and kill other infected cells in the body. Over the next three years, I and the others working on this protein came to realize that this idea of what the protein did was utterly wrong. We found that rather than becoming a hapless target of the immune system, the viral protein seeks out the transplantation antigens inside the cell, binds to them, and blocks their transport out to the cell surface. Since the infected cell thus ends up having no transplantation antigens on its surface, the immune system cannot recognize that it is infected. This protein camouflages the adenovirus, so to speak. In fact, it leads to the creation of a cell within which the adenovirus can probably survive for a long time, perhaps even as long as the infected person lives. That viruses could foil the immune system of their hosts in this way was a revelation, and our work resulted in a number of high-profile papers in the best journals. Indeed, it turns out that other viruses, too, use similar mechanisms to evade the immune system.

This was my first taste of cutting-edge science, and it was fascinating. It was also the first (but not the last) time I saw that progress in science often entails a painful process of realizing that your ideas and those of your peers are wrong, and an even longer struggle to persuade your closest associates and then the world at large to consider a new idea.

But somehow, in the midst of all the biological excitement, I could not quite shake off my romantic fascination with ancient Egypt. Whenever I had time, I went to lectures at the Institute of Egyptology, and I continued to take classes in Coptic, the language of pharaonic Egypt as spoken during the Christian era. I befriended Rostislav Holthoer, a jovial Finnish Egyptologist with an immense capacity for friendships across social, political, and cultural boundaries. During long dinners and evenings at Rosti’s home  in Uppsala in the late 1970s and early ’80s, I often complained that I loved Egyptology but saw little future in it, while I also loved molecular biology, with its apparently boundless promise of advances in the welfare of humankind. I was torn between two equally alluring career paths—a conundrum no less painful because it was doubtless viewed without much sympathy as the fretting of a young man faced with nothing but good choices.

But Rosti was patient with me. He listened when I explained how scientists could now take DNA from any organism (be it a fungus, a virus, a plant, an animal, or a human), join it to a plasmid (a carrier molecule made of DNA from a bacterial virus), and introduce the plasmid into bacteria, where it would replicate along with its host, making hundreds or thousands of copies of the foreign DNA. I explained how we could then determine the sequence of the foreign DNA’s four nucleotides and find differences in the sequences between the DNAs of two individuals or two species. The more similar two sequences were—that is, the fewer the number of differences between them—the more closely related they were. In fact, from the number of shared mutations we could infer not only how the particular sequences had evolved from common ancestral DNA sequences over thousands and millions of years but also approximately when those ancestral DNA sequences had existed. For example, in a 1981 study the British molecular biologist Alec Jeffreys analyzed the DNA sequence of a gene that encodes a protein in the red pigment in the blood of both humans and apes and deduced when the genes began evolving independently in humans and apes. This, I explained, could soon be done for many genes, from many individuals of any species. In this way, scientists would be able to determine how different species were related to one another in the past, as well as when they began their separate histories, with much greater accuracy than was possible from the study of morphology or fossils.

As I explained all this to Rosti, a question gradually arose in my mind. Would this kind of investigation necessarily be restricted to DNA from blood samples or tissues from humans and animals that live today? What about those Egyptian mummies? Could DNA molecules have survived in them—and could they, too, be joined to plasmids and made to replicate in bacteria? Could it be possible to study ancient DNA sequences and thereby clarify how ancient Egyptians were related to one another and to people today? If that could be done, then we could answer questions that no one could answer by the conventional means of Egyptology. For example, how are present-day Egyptians related to Egyptians who lived when the Pharaohs ruled, some 2,000 to 5,000 years ago? Did great political and cultural  changes, such as the conquest by Alexander the Great in the fourth century BCE, or by the Arabs in the seventh century AD, result in replacement of a large part of the Egyptian population? Alternatively, were these just military and political events that caused the native population to adopt new languages, new religions, and new ways of life? In essence, were the people who lived in Egypt today the same as those who built the pyramids, or had their ancestors mixed so much with invaders that modern Egyptians were now completely different from their country’s ancient population? Such questions were breathtaking. Surely they must have already occurred to someone else.

I went to the university library and searched in journals and books but found no report of any isolation of DNA in ancient materials. No one seemed even to have tried to isolate ancient DNA. Or if they had, they had not succeeded, because if so, surely they would have published their findings. I talked to the more experienced graduate students and postdocs in Pettersson’s lab. Given how sensitive DNA is, they argued, why would you expect it to last for thousands of years? The conversations were discouraging, but I didn’t give up hope. In my forays into the literature, I had found articles whose authors claimed to have detected proteins in hundred-­year-old animal hides in museums—proteins that could still be detected by antibodies. I had also found studies claiming to have detected, under the microscope, the outlines of cells in ancient Egyptian mummies. So
something
did seem to survive, at least sometimes. I decided to do a few experiments.

The first question seemed to be whether DNA could survive for long in tissues after death. I speculated that if the tissue became desiccated, as was the case when a mummy was prepared by the embalmers in ancient Egypt, then DNA might well survive for a long period since the enzymes that degrade DNA need water to be active. This would be the first thing to test. So in the summer of 1981, when not too many people were around in the lab, I went to the supermarket and bought a piece of calf liver. I glued the receipt from the store onto the first page of a new lab book that I would use to record these experiments. I labeled the book with my name but nothing else, since I had decided to keep my experiments as secret as possible. Pettersson might forbid me to pursue them, if they struck him as an unnecessary distraction from the intensely competitive study of the molecular workings of the immune system that I was supposed to be working on. And, in any case, I wanted to keep all this under wraps to spare myself the ridicule of my lab colleagues in the likely event of failure.

To somewhat imitate ancient Egyptian mummification, I decided to artificially mummify the calf liver by sequestering it in an oven in the lab heated to 50°C. The first effect of this was that the secrecy of my project was compromised. By the second day, the repugnant smell elicited considerable comment, and I had to reveal my project before someone found the liver and disposed of it. Fortunately, the smell decreased as the desiccation progressed, and neither the smell nor word of what was putrefying in the lab made it to my professor.

After a few days, the liver had become hard, blackish-brown, and dry—just like an Egyptian mummy. I proceeded to extract DNA from it, with immediate success. The DNA was in small pieces of a few hundred nucleotide pairs instead of the many thousands of nucleotide pairs typical of DNA extracted from fresh tissue, but there was still lots of it. I felt vindicated. It was not totally ridiculous to think that DNA could survive in a dead tissue—at least for some days or weeks. But what about thousands of years? The obvious next step was to try performing the same stunt with an Egyptian mummy. Now my friendship with Rosti came in handy.

Rosti had been primed by my fretting about Egyptology and molecular biology and was happy to abet my attempt to take Egyptology into the molecular age. The small university museum of which he was the curator had some mummies, and he consented to my request to sample them. He was, of course, not about to let me cut them open and remove their livers. But if a mummy was already unwrapped and its limbs had broken off, Rosti allowed me to remove small pieces of skin or muscle tissue from the area where the mummy had already been broken to try my DNA extraction. Three such mummies were available. As soon as I put the scalpel to what had once been the skin and muscles of a person who existed some 3,000 years ago, I realized that the texture of the tissue was different from that of the calf liver I had baked in the oven. The liver had been hard and a bit tough to slice up, whereas the mummies were brittle and their tissues tended to crumble to brown powder when cut. Undeterred, I submitted them to the same extraction procedure I had performed on the liver. The mummy extracts differed from the liver extract in that they were as brown as the mummies themselves, whereas the liver extract had been as clear as water. And when I looked for DNA in the mummy extracts by letting them migrate in a gel in an electric field and staining them with a dye that would fluoresce pink in ultraviolet light if it had bound to DNA, I saw nothing except the brown stuff, which indeed fluoresced in the ultraviolet light, but blue instead of pink, not what was expected if it was DNA. I repeated this  process on the two other mummies. Again, there was no DNA; nothing but an undetermined brown substance had ended up in the extracts that I had hoped would contain DNA. My lab colleagues seemed to be right: How could the fragile DNA molecules survive for thousands of years, when even inside a cell it needed constant repair in order not to decompose?