25 Interviews for the FNP’s 25th Anniversary. The Foundation for Polish Science (FNP) celebrates its 25th anniversary this year. To mark the occasion, we have invited 25 beneficiaries of our programmes to tell us about how they “practise” science. What fascinates them? What is so exciting, compelling and important in their particular field that they have decided to devote a major part of their lives to it? How does one achieve success?
The interviewees are researchers representing many very different fields, at different stages of their scientific careers, with diverse experience. But they have one thing in common: they practise science of the highest world standard, they have impressive achievements to their credit and different kinds of FNP support in their extensive CVs. We are launching the publication of our cycle; successive interviews will appear regularly on the FNP website.
DNA, Bones and Scientists
Martyna Molak-Tomsia, PhD, who studies ancient DNA, talks to Patrycja Dołowy.
PATRYCJA DOŁOWY: I like the fact that you have your own website and a Facebook fan page. It’s not common among scientists.
MARTYNA MOLAK-TOMSIA: I learned to do that working on my PhD in Australia. They made very sure we posted updated information on the website. Poland is only starting to think about this kind of science popularization. Until recently scientists stayed in their ivory tower, they had no contact with “living” people, they felt no need to tell society what they were working on. They didn’t even tell other researchers, apart from narrow specialists from their field whom they met at conferences and who read their papers in specialist periodicals. I think we scientists are responsible for explaining to taxpayers, in simple terms, what we do and what their money is being spent on. I post information in accessible form on my website.
And in the process you show how fascinating genetics can be. People associate this field mainly with GMO and are scared of it, unfortunately.
I don’t work with modified organisms, which cause the biggest, groundless fears in non-scientific circles. My segment of molecular biology is, to put it colloquially, sexy. This is research from where Indiana Jones meets Jurassic Park. I take old bones that an archaeologist has dug up and extract genetic information from them. I use the tools of molecular biology to solve problems put forward by archaeologists and historians. That’s a slightly different kind of biology. Thanks to genetics we can answer questions about how specific groups of people migrated, how they are related to one another. This is the borderline of science fiction, so people find it interesting. It’s just scary sometimes because of stories like the one about Jurassic Park. Some research on ancient DNA, though not the part I’m involved in, analyses genetic material from historical animals. In future it could be used for cloning long-extinct species, like mammoths; dinosaurs – not so much.
Why not dinosaurs?
DNA remains in the cells of living organism after they die, but it changes with time. It is eaten by microorganisms, decomposed by enzymes. Spontaneous physicochemical reactions occur as well, making the DNA fragments increasingly shorter and more difficult to analyse. The older the remains and the worse the conditions in which they were resting, the harder it is to recover DNA. You can study remains from as far back as several hundred thousand years as long as they were resting in a permafrost area or a cave, at a stable temperature. Dinosaurs, which died out 65 million years ago, are a tough one. There probably isn’t a single place on Earth where a relatively stable, low temperature would be maintained for tens of millions of years. This is such a long time that it’s unlikely to be possible to re-create dinosaurs from their ancient DNA. It’s true that just a few years ago it seemed impossible to go farther back than a few thousand years with DNA research, but in the case of dinosaurs the limitations are due to simple physicochemical causes.
But it works with mammoths?
The bodies of mammoths were preserved thanks to permafrost areas. When melting ice exposes them, they are in such good condition that Siberian dogs eat them. Maybe even people do, though I wouldn’t try it myself… Anyway, we have complete genetic information on mammoths. Their entire genome has been sequenced. We know exactly how a mammoth differs from its closest relative, the Indian elephant. We can (theoretically for now) modify an elephant’s genome so as to obtain a mammoth. It’s a long and expensive project, but not beyond our reach. Perhaps even within our lifetime we will get to see walking mammoths.
Incredible! But you don’t work with paleobiologists but with archaeologists, right?
Yes, I deal with people. They’re not as old. My research focuses on people from our era. I have studied medieval Slavs from eastern Poland, Indians from today’s Peru from the Inca period. Now we are studying a civilization from over 1,000 years ago that lived on Lake Titicaca. My associates are just back from Bolivia after collecting samples.
Dr Martyna Molak-Tomsia by Magdalena Wiśniewska
It really is like Indiana Jones!
We collect samples of bones of people from a given culture, extract genetic information, compare the people to one another. We are able to tell what their relationships are. In Peru we analysed graves in which several people were buried. We confirmed the hypothesis of ethnologists and historians that these were people from one male line with their wives. We also checked the kinship between the inhabitants of three Peruvian villages lying 30 kilometres from one another. We discovered that mainly women moved. Our conclusions fitted the hypothesis that marriages were contracted between villages and that the bride moved to her husband’s village. As you can see, we don’t really deal with biology, even though our tools are biological. But researchers who work with older remains answer questions posed by biology. For example, they recently discovered a relationship between modern humans and Neanderthals. For many years scientists were unable to confirm whether Neanderthals were our ancestors or our cousins. They assumed that in the period when Homo sapiens was already living in the Middle East and Europe simultaneously with Neanderthals, these groups did not mix. Thanks to studies of ancient DNA we now know that they did. All people from outside Africa – every descendant of that migration – has about 2-3% of the genome of Neanderthals in them.
So genetically this was not a different species?
It all depends on the definition. There are still great ongoing debates in the biology of species. Now, thanks to genetics, many old paradigms have had to be changed. One definition says that if individuals produce fertile progeny, they come from one species. According to this definition, contemporary humans and Neanderthals are the same species. A few years ago scientists studied DNA from one tiny bone from a phalanx – a piece of finger found in the Denisova Cave in Siberia. Earlier, an anthropologist looked at the bone and said: a humanoid species. After the DNA was analysed it turned out this was a completely separate Homo group. The development of ancient DNA genetics has enabled us to make incredible discoveries. We would never have expected that a completely different group of hominids lived next to us. Our evolutionary tree is much more complicated than we thought. Since we managed to find this particular separate group, maybe there were many more of them and we are in for more discoveries, and the human tree will turn out to be a complicated bush.
Tests have recently appeared enabling us to test our DNA and check where our ancestors came from. Of course it usually turns out that they came from different directions, that we are all mixed.
I myself took part in one such test, in the Genographic project by National Geographic. They send you a kit with a special stick; you swab the inside of your cheek, secure the sample and send it back. In this test they check many genetic markers scattered across the genome. We know millions of them right now. Their composition in a specific person can be compared to check which comparative groups that person is most similar to. For example, they send you a graph showing you are a Central European in 87% while some of your ancestors came from faraway Asia. They also check some other markers that provide less information but more unambiguous results. For example, based on mitochondrial DNA you can quite accurately tell where ancestors from the maternal line came from – your mother, grandmother, great-grandmother etc. Offspring inherit mitochondrial DNA from their mother in unchanged form (it does not cross over between parental molecules). On the other hand, sporadic mutations occur in it more often than in genomic DNA. This makes it possible to trace millennia after millennia with good accuracy. Y chromosome DNA is also traced, along the paternal line.
Can we determine the time when those ancestors migrated, when they met?
These methods are based on quite a few assumptions. There are a good many unknowns. My doctoral dissertation in fact involved refining one such method. We need to determine how quickly changes in a genome occur, and this is difficult. Ancient DNA comes to the rescue. We have a bone that we’ve been able to study and can radiocarbon date it, for example, to 30,000 years ago. The bone has its genetic type, which we compare to contemporary material. Thanks to this we know how many mutations appeared in the genome over 30,000 years. Of course to calculate how fast DNA mutates we have to have a lot of such data from different periods.
What is this research of yours like in practice? You get a bone from an archaeologist, and then what?
First we have to clean the bone or tooth from the outside, because it has been touched by lots of people: it lay somewhere, it was moved, there’s a lot of DNA on it from the air, from skin. The DNA inside a bone is very old, damaged. Any, even the smallest signal from “fresh” DNA will be stronger than from ancient DNA. To clean a sample, we use various solutions that eliminate DNA. You can also (and we usually do) physically scrape off the surface layer. This involves drills and grinders. A very large part of my work is taken up by a hand-held multi-grinder. Once the tooth is clean, we have to get at the DNA that’s inside, between the mineral structure of the bone. We use different chemicals and solutions that digest the proteins surrounding the DNA. We get rid of the mineral layer. For this to be effective, we need to increase the tooth surface that’s in contact with the solutions. This is where the drill comes in again. We have to grind the tooth into the smallest possible pieces. We also have special mills for pulverizing teeth or bones. The chemical solutions we add to this powder release pure DNA. The aim is to separate DNA from proteins and other substances. We take advantage of the fact that DNA dissolves under different conditions than proteins and other substances and that it is electrically charged. We end up with a test tube and the hope that it holds our ancient DNA. To minimize the danger that a different DNA could fly in during these procedures, they are all performed in clean rooms separated from the rest of the world.
Like in the film Outbreak?
We have such a room at the Museum and Institute of Zoology of the Polish Academy of Sciences in Warsaw. You enter it through a lock that blows air. It’s a metal tin into which only air purified by a set of filters flows. Before going inside I put on a disposable suit, mask, two pairs of gloves, protectors. Like a spaceman. It’s all so as not to contaminate the samples of DNA, of which we have very little and it’s in very poor condition. Once we have isolated pure DNA, we use different methods to extract information from it. Fortunately there has been a giant leap in DNA analysis in recent years. High-capacity, large-scale DNA sequencing methods have been developed. DNA extract is placed in a machine that captures individual DNA fragments. It produces information in the form of gigabytes of data. You have to separate impurities from what is of interest to us. That’s how it is done today. Bioinformatics is the biggest challenge for molecular biologists. Today it is practically the most important part of analyses.
So you don’t have to reconstruct fragments that are missing?
Methods exist for physically joining broken threads, and we use them. But thanks to bioinformatics, short DNA fragments are joined together into larger fragments on a computer. We can read practically all the information in this way. It’s a paradox: 30 years ago, when our field emerged, the fact that DNA was very damaged was a nightmare for researchers. Today, with the new methods, it is very typical for fragments of ancient DNA to be chemically damaged, so by looking at the readings of a sequencing machine we can distinguish ancient DNA from DNA that comes from contemporary contamination immediately and with high probability.
You received a stipend from the Foundation for Polish Science.
Under the START programme, I received the Barbara Skarga Stipend for scientists who cross the boundaries between various fields of science, and later another grant. This is a unique way of helping researchers. Most research grants are targeted at specific projects. FNP stipends are for people. The Foundation takes into account who we are, what we do and whether we are worth investing in. This support gives us mental peace, enabling us to focus on research. Without it most researchers have to make extra money moonlighting. That distracts them from their main research work. We don’t have that problem. We have just finished a study on Slavs from the early Middle Ages living in the Podlasie region. We had a few burial grounds from the area. We were able to determine that the people there mixed (military hordes came and went in the area), but there was no displacement or replacement involved. Actually, we are genetically similar to those people. Unfortunately the samples we studied, though not very old – just a thousand years, were very poorly preserved. It was hard to extract information from them. We have warm summers and cold winters here; DNA freezes, thaws, little of it remains. Burial in the ground is not something that allows DNA to survive well, either. The information we have comes mainly from mitochondrial DNA, which keeps much better in ancient material because every cell contains up to a few thousand copies of this DNA. We were able to discover a region within Podlasie that was slightly different genetically. Data from historical sources suggest that an ethnically different group could in fact have lived there. Now comes the difficult stage of integrating my purely biological results with archaeological and historical information.
We have to record our results in a way enabling an archaeologist or historian to draw conclusions from them. That’s a challenge in itself. But there are others. A thousand years ago Christianity came to these lands. In the 12th century, pagans and Christians lived next to each other. We wanted to compare them, to check if one group had displaced the other, for example, or if the descendants of the pagans actually willingly converted to Christianity. The problem is, the pagans cremated their dead so the remains are so poorly preserved that we managed to determine very little from them.
It’s still incredible that you study ordinary people. I thought only crypts had good conditions for DNA.
Despite what you might think, a lot is left of us, and we can learn something even from such old bones taken from the ground. DNA analysis methods are developing very well. But there are also projects focusing on specific historical figures. There’s one spectacular example from a few years ago. Remains were found in Britain, in a car park in Leicester, that were suspected to be those of King Richard III. They had been buried without honours, but there were clues indicating that this could be the body of the king who was killed in the Battle of Bosworth in 1485. First of all, researchers determined that where the car park is today, there used to be a Franciscan church where Richard III had been buried, according to historical reports. Secondly, a burial without honours – the body was only wrapped in a shroud – was confirmed in historical materials: Henry VII Tudor, Richard III’s successor, didn’t respect his predecessor. An archaeological and anthropological analysis was performed on the remains (the bones had marks left by blows sustained in battle), and then a genetic analysis. Comparing the DNA from the bones with the DNA of living descendants was very easy because every British ruler has a very detailed genealogy. Relatives were found. They were tested and the DNA was compared. It was Richard III. The family tree was verified in the process: there had been marital infidelity, some of the children had different fathers…
A few years ago our Institute worked on identifying the remains of Nicolas Copernicus. The accuracy of those studies was rather limited at the time, unfortunately. Today they could have been performed with much greater certainty.
Dr Martyna Molak-Tomsia by Magdalena Wiśniewska
Egyptian mummies probably have the best-preserved DNA, right?
Not at all! Mummies were treated with various chemicals that preserved the shape of the body but degraded the DNA. All research conducted on ancient Egyptian remains so far has been questioned by the scientific community. Perhaps reliable genetic data can be obtained soon from those regions, which are extremely important for civilization. Pharaoh mummies lie in very good conditions, they have very deep crypts, a cool and stable temperature, but the body embalming process in Egypt was drastic for DNA. Actually, it’s also hard to obtain anything from museum exhibits kept in formaldehyde, for the same reason.
What is the oldest ancient DNA?
The oldest remains from which DNA has been extracted are those of a horse in today’s Canada. They are about 700,000 years old. That’s a lot. The oldest human remains with analysed DNA are about 400,000 years old.
That’s also a very long time!
They come from a cave in Spain. The thing about caves is that the temperature inside is low and stable. A stable temperature is important, because every change in temperature causes microscale kinetic changes and leads to the disintegration of a long DNA molecule.
Can analyses of ancient DNA help solve crimes from decades ago?
From a scientific viewpoint, bones from 50 years ago from a criminal investigation are the same type of genetic material as we study during archaeological excavations. As far as procedures are concerned, the material obtained in criminal cases is forensic DNA. That’s a different group of researchers, who have their own DNA analysis methods. Of course many of the methods are the same as ours, but they have to remember that their DNA will serve as evidence in court.
Your plans for the near future?
I’m having a baby soon. I’ll be away from science for a time, but the Foundation is not stopping my stipend. It continues to support me at this breakthrough moment of my life, appreciating what I’ve accomplished so far and giving me the peace of mind thanks to which I’ll be able to return to research later on. It is investing in me and my future scientific research.
MARTYNA MOLAK-TOMSIA, PhD, works at the Museum and Institute of Zoology of the Polish Academy of Sciences in Warsaw. She is a two-times beneficiary of the START programme (2015 and 2016), and in 2015 under this programme received the Barbara Skarga Stipend for scientists whose research is distinguished by boldly crossing the boundaries between various fields of science, opening up new research perspectives and creating new values in science.