Ancient DNA and the New Science of the Human Past
When Matthias Meyer began studying the ancient DNA in the 400,000 year old fossils he also found in the Sima de los Huesos, or Pit of Bones cave, deep beneath the Atapuerca mountains in Spain, he was pretty sure he knew what he’d find. The bones looked like they belonged to an ancestor of the Neanderthals, who roamed Europe from at least 250,000 to 30,000 years ago. Right place, right time, right bones ought to mean right genetic material too.
But as he examined the genome he and his collaborators had painstakingly put together, Meyer couldn’t find the matches he expected with the Neanderthal genome. This was another pre-human group altogether—the Denisovans, who were around until about 41,000 years ago. There was just one problem with that: the Denisovans, as far we know, were never near Spain. The only traces we have of them place them some 6,000 miles (9,700 km) away, in Siberia, not a distance easily traversed in the Pleistocene.
The story of whose ancestor is in the Pit of Bones and how the remains got there could shed new light on the evolutionary relationships among early humans. And the techniques used to probe the question, detailed in this week’s Nature, could open up new vistas in the exploration of human ancestry.
(MORE: Neanderthals Cleaned Their Caves—Why Can’t You Clean Your Room?)
The DNA used in the study is some of the oldest ever to be sequenced. Meyer, a molecular geneticist at the Max Planck Institute of Evolutionary Biology, and colleagues, including paleogeneticist Svante Paabo, are experts at this kind of genetic sleuthing, and part of the group that released a draft Neanderthal genome in 2010, as well as a Denisovan genome in 2012. But working with DNA this ancient was a new challenge. The Neanderthal and Denisovan fossils used for sequencing are all less than 100,000 years old. The DNA from the Pit of Bones is four times as ancient—and that’s a problem.
DNA falls apart as it ages, disintegrating into fragments like a rusty tin can. The older it is, the tinier the pieces that are left, and the tinier the pieces, the harder to get a sequence. Heat makes DNA fall apart faster. Meyer says, “previous ancient sequencing studies were made easier because the DNA was deposited during a cold period.”
“But if you go back then a few hundred thousand years further,” he says, “some of these times you had warmer temperatures than now.” Some DNA from that era has also been sequenced from rare samples preserved in permafrost. But the fossils in the Pit of Bones had been exposed to warmer temperatures.
(MORE: Tutankhamen Died on His Knees—Then His Body Spontaneously Combusted)
The Genomic Ancient DNA Revolution
To make their study work, the team thus focused on sequencing DNA from the mitochondria of the cell, rather DNA from the nucleus of the cell. While each cell has just one set of nuclear DNA, it also has at least several hundred copies of the mitochondrial version, so there would be more of it left after all this time. While nuclear DNA has many repetitive sections that make it difficult to sequence from small fragments—you can never tell if what you have is the next piece in the puzzle or just a duplicate lying around—mitochondrial DNA does not.
The researchers next sieved out DNA fragments from two grams of fossil femur, collecting fragments that tended to consist of clumps of single-stranded DNA, rather than the long double strands that sequencing usually works best for. Still, with some creative tweaking, Meyer and his colleagues were able to get the sequencer to detect the samples.
Along the way, they also had to deal with contamination from modern human DNA— from excavators and even the researchers themselves, despite their efforts to keep their work field sterile—a problem that plagues every study of ancient genetic material. Even with all that meticulous processing, in the end, Meyer estimates, “there’s less than a 10th of the DNA of an ancient cell inside two grams of material.”
But it was enough to get a reading—to reveal that what seemed to be the wrong bones were in the wrong place. So how did they get there? The researchers lay out several possible explanations, none of them particularly tidy or airtight. The fossil could come from an ancestor of the Denisovans — but that would imply that the Denisovans and Neanderthals lived in the same areas, at least for a while, while remaining genetically distinct. It could be from a group, separate from the other two, that gave the Denisovans their mitochondrial DNA—but the bones look a little too Neanderthal-like to be totally distinct. Narrowing down these and other possibilities will require a sequence of nuclear DNA, a task that will require further refinements of sample-production technique and a much larger amount of fossil bone.
(MORE: Rethinking Your Ancestors—the Fossilized Ones)
Still, the fact that a mitochondrial genome could be reconstructed in this way has important ramifications, says Beth Shapiro, a professor of ecology and evolutionary biology at University of California, Santa Cruz, who specializes in paleogenomics. “It means that there are likely to be many more samples out there that contain recoverable amounts of DNA — samples that we otherwise might have glossed over or given up on, thinking they were too old, or from a climate that was too warm, for DNA to be preserved,” she wrote in an email.
One thing at least is clear: We have hardly written the last chapter on either genetic science or our human ancestry. As either one advances it will carry the other along with it—a nice case of cooperative evolution if ever there was one.
A Survivor’s Quest To Unearth Ancient Patterns Of Cancer
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Kathryn Hunt
I earned a MSc in Palaeopathology from Durham University in 2013 concentrating on the identification, standardization and collective coordination of data concerning the archaeological evidence of cancer in human skeletal and mummified remains. My interest in this aspect of bioarchaology peaked when I was diagnosed with ovarian cancer in 2009.
Since then, I have dedicated myself to uncovering ancient cultural concepts and biological features of this ancient disease for the benefit of modern understanding and research. In 2012, a few colleagues with mutual interest in the antiquity of cancer and myself formed the Palaeo-oncological Research Organization (PRO). We aim to increase interest and research into the subject while standardizing the field and publicizing this important, yet ignored, aspect of cancer research.
Kathryn Hunt was studying archaeology in college and doing digs of ancient burial sites in Egypt when, at 22, her studies were interrupted by the diagnosis of a Nerf ball-sized malignant tumor in her ovaries and immediate, aggressive treatment.
Today, she’s a bona fide survivor–and her passion for the field has taken a personal turn. A master’s degree now in hand, she’s embarking on a major project to uncover the ancient history of cancer, a disease that’s often assumed to be triggered by modern ills (even being called “purely man-made” by a few researchers).
“The impressive advancement of modern cancer research has been based on limited knowledge of cancer over several decades,” she says. “However, cancer was also active in humans for hundreds of thousands of years before that.”
The field of “paleo-oncology” is not entirely new, but it is very small and scattered. For example, the researchers who concluded that cancer was a man-made disease did this on the basis of studying Egyptian mummies. While it may be true that cancer rates, in today’s time of smoking, toxic chemicals, and longer life expectancy, may be higher than the past, cancer is actually a very old disease, says Hunt. Hippocrates, ancient Greece’s father of medicine, first named the disease. The possible earliest documented case in a human ancestor was 1.5 million year in Africa, and scientists have even found it in dinosaur fossils.
Hunt is now launching an organization, the Paleo-oncological Research Organization, that is working to compile and code for evidence of cancer in an online, open-source database that spans societies and eras. The long-term work aims to answer unwieldy questions about how cancer has evolved, both culturally and biologically, over key historical periods. She wonders how cancer changed when humans became farmers, rather than hunters and gatherers, or once the Industrial Revolution truly got going.
“I realized that the reason why no one has done this work extensively is because there’s never been a foundation. There’s never been a jumping off point,” she says. She’ll be raising the profile of the discussion at a conference of archeologists this spring. Recent advances in DNA analysis will likely help her work along with researchers’ knowledge about all kinds of diseases in the ancient past, such as tuberculosis.
A recently named TED Fellow for 2014, Hunt is in full remission and plans to make this work her life’s contribution to combating a disease she wishes no one else would have to battle, especially at such a young age. “If we can get a better understanding of why cancer manifests the way it does, because of genetic, environmental, and cultural factors…. that behavior might lead us to better treatment, better prevention, and better quality of life for those going through cancer,” she says.
“The year I was diagnosed with ovarian cancer–which is now in remission–I’d just gotten back from an expedition to Egypt, where I was looking at bones. There were quite a few individuals who had evidence of a sort of bone disease, but because of my diagnosis, I started to think about it on another level. There are all of these subtle references to cancer in ancient literature. Why aren’t we seeing it in the bones?
“There wasn’t a lot of evidence because people didn’t know what to look for. It lit my fire. A few years ago, a few colleagues and I put together the Paleo-oncology Research Organization, and I’ve collected more than 230 cases of evidence of cancer in ancient societies. Now we’re making an open-source database with interactive maps and forums where researchers can discuss and share information. In April, we brought 10 of them together for the first time to strategize.
“Our next step will be getting funding to look at individuals who might have had cancer–doing a radiological analysis and potentially a DNA analysis. If we can trace the global history of cancer, we might be able to identify patterns. Patterns don’t necessarily tell you facts, but they do indicate areas to focus on.”
Hunt was born in Alaska. She studied anthropology and classical studies at the Pacific Lutheran University (PLU), graduating in 2011. She then obtained a master’s degree in paleopathology from Durham University. In 2009, aged 22, Hunt was diagnosed with ovarian cancer. She later entered remission. This experience moved Hunt towards researching cancer in antiquity.
Since beginning her studies, Hunt has documented 230 cases of ancient cancer. By researching ancient texts, Hunt has found sources of interest such as references to cancer as an illness by ancient Egyptians and even records of ancient cancer treatments such as surgery, cauterization and fasting. Aside from her achievements within the field, Hunt has been a vocal advocate for the expansion of the field itself, also generating both awareness and interest for the fairly new subject of paleo-oncology.
Part of Hunt’s purpose for studying ancient cancer is to help the scientific community to better understand the various forms of the disease, including potentially unknown causes and treatments. Hunt has conducted studies all around the world, including the time she spent having been invited to do fieldwork in Egypt’s Valley of Kings as an undergrad. One of Hunt’s ultimate goals is to find the definitive earliest appearance of cancer in humans. After bringing together multiple colleagues to form an interactive, open source database, Hunt was awarded a TED fellowship.
Kathryn Hunt founded the Paleo-Oncologist Research Organization on April 11th, 2013. The organization is a multidisciplinary institution that is part of the relatively new field known as paleo-oncology, the study of ancient diseases in humans and animals. The field has been consistently growing and requires the contributions of historians and scientists alike to further the world’s understanding of ancient diseases.
