Secrets in the lab!

Here is a very fascinating interview (via Bora):

JG: I read your paper from 1985 about sequencing the mummy remains. What was the genesis of that?

SP: I knew there were hundreds and thousands of mummies around in museums and that they found hundreds of new ones every year, and molecular cloning in bacteria was a rather new thing at the time, so I found in the literature that no one had tried to extract DNA from Egyptian mummies, or any old remains actually. So I started to do that as a hobby in late evenings and weekends, secretly from my thesis advisor.

JG: As a lowly graduate student, where do you find a piece of mummy to start this investigation?

SP: I had studied Egyptology, so the professor of Egyptology knew me quite well. He helped me to sample a mummy in the museum in Uppsala. He also had very good connections with a very large museum in Berlin, which was East Berlin at the time. Germany has a long, long tradition in Egyptology, going back to the 19^th century. After the British Museum and the Museum in Paris, the Berlin Museum has the biggest collection outside Egypt.

JG: So you went with your professor to the museum in East Berlin…

SP: He had convinced them of our idea in advance. We sampled, I think, 36 different mummies. Small samples, of course.

JG: Had people ever looked at mummy tissue before, at things like proteins?

SP: There had been some work on histology of mummies, and there had been some work on trying immunoreactivity of proteins extracted from it, with very mixed results. I don’t think there were any convincing results from Egyptian mummies.

JG: In what kind of state are the mummies? Are you wearing gloves or masks? What are you doing?

SP: We only worked with mummies that were already unwrapped and with things that were broken, so we were not destroying anything to get to the tissues. With a scalpel we removed a little piece. It was the first time this was done, so we had no big qualms about contamination. I had no idea this could be such a big issue.

JG: What did you do with these 36 scalpeled samples?

SP: We screened them with histology. We looked at both with traditional stainings—hematoxylin-and-eosin staining and staining with ethidium bromide—and under UV light to see if one could see any fluorescence from DNA. In the skin of a particular mummy, you could see that the cell nuclei lit up. So, there was DNA there and at the place you would expect it to be.

JG: Was your interest in this simply the challenge of getting DNA sequence out of it or was there a bigger idea?

SP: It was clearly the idea that if you could study the DNA of ancient Egyptians, you could elucidate aspects of Egyptian history that you couldn’t by traditional sources of archeology and the written records.

JG: Do you mean the relationships between people?

SP: Population history. Say, when Alexander the Great conquered Egypt, did that mean there were lots of people from Greece who actually came there and settled there? When the Assyrians came there, did that have an influence? Or was the population continuous? Political things that influenced the population.

Since then it has become clear that it is almost impossible to work with human remains because of contamination. It is very hard to exclude that the DNA you look at is not contaminated with modern humans.

JG: Then, how do we know that this sequence in the 1985 paper is in fact the sequence of a real Egyptian?

SP: In hindsight, we don’t know that. In 1985, I had no idea how hard this is [to retrieve uncontaminated ancient DNA sequences] and thus did not do the controls we now know are necessary. We’ve even published at a later point on this.

JG: But there have been no data to refute the sequence of this mummy.

SP: But nothing to prove it either! It could well have been contamination, and if that was the last that had ever been written on ancient DNA, that would have been a sad state of affairs and the end of the field.

Stories like these bring science the flavour of a thriller — don’t they? Take a look!

Tags: ancient DNA, Svante Paabo, Svante Paeaebo