In a paper published in Science in 1994, Dieter Ebert showed, using laboratory experiments on a horizontally-transmitted disease in Daphnia, that spore production and infection was lower when the geographic distance between parasite and wild-caught Daphnia host origins were greater. Ebert’s findings suggested that parasites were locally adapted and contradicted the hypothesis that co-evolved parasites were less virulent than novel ones. Twenty-four years after the paper was published I asked Dieter Ebert about his motivation to do this study, his daily routine during these experiments, and what we have learnt since about host-parasite co-evolution in this system.
Citation: Ebert, D. (1994). Virulence and local adaptation of a horizontally transmitted parasite. Science, 265(5175), 1084-1086.
Date of interview: Questions sent by email on 7th December 2017; responses received by email on 25th June 2018.
Hari Sridhar: Correct me if I’m wrong, but this paper seems to have come out of work you did during your second post-doc. Could you trace the motivation for this piece of work in relation to what you did during your PhD and your first post-doc.?
Dieter Ebert: This is correct. This work resulted from my second postdoc, which I did in the Zoology Department at Oxford University with W.D. (Bill) Hamilton. Before this, I did a PhD at Basel University and a postdoc at the Smithsonian Tropical Research Institute in Panama. The project of my second postdoc was entirely unrelated to my earlier studies. My second postdoc was on the evolution of host – parasite interactions. After my PhD I was looking for a new topic, an emerging field within the area of evolutionary biology. The evolution and ecology of host – parasite interactions was an emerging field and in particular there was a need to work experimentally. There was plenty of theory and many open questions, but a lack of good experimental systems to answer them. I knew Daphnia very well from my PhD work, so I decided that I will try to develop this system for work on host – parasite interactions. After having worked out how to run experiments with host and parasites, I decided to test ideas about local adaptation of hosts and parasites and how they relate to the evolution of virulence. This is how this paper come about.
HS: Stepping back a little, how did you get interested in Daphnia and the topic of host-parasite evolution? Do you continue to work on Daphnia magna and Pleistophora intestinalis today? If not, when was the last time you worked on it and why did you move away from this system?
DE: I did already my Master thesis (it was called “diploma” at this time) on Daphnia. This was just by chance, as I wanted to do population genetics and there was only one option in Munich at this time. With my Master and also my PhD using the Daphnia system I decided to move away from it for my first postdoc (on social spiders), but came back to Daphnia, as it is a very convenient system. Pleistophora instestinalis (today called Glugoides intestinalis) was the first parasite I got in culture. But it is not the easiest of the parasites I encountered. It grows slowly, is hardly virulent and parasite fitness is difficult to quantify. Later I moved to other parasites, mainly the bacterium Pasteuria ramosa and the microsporidia of the genus Hamiltosporidium. We still have Glugoides intestinalis in culture in the laboratory, but we hardly work with it.
HS: If you don’t mind my asking, how come your post-doc. supervisor, W.D. Hamilton, was not an author on this paper? Could you tell us a little about what it was like working with him?
DE: W.D. (Bill) Hamilton had the rule that he would only be part of a paper if he substantially contributed to it. I had offered him to be co-author, but he declined. We published later on a paper together (Ebert & Hamilton, TREE, 1996) that had more of the conceptual underpinnings of the topic.
I enjoyed being in Bill’s group. I did not see him too much, as he was travelling a lot. But we would meet from time to time over a cup of tea and talk about everything we had in mind.
HS: This paper reports on the findings of a “laboratory transplant experiment”. Could you tell us a little more about this laboratory – who did it belong to, what has happened to it now etc.?
DE: The Zoology Department at Oxford University was a packed full place. We had very little space to work in. I had a quarter of a room, which was desk and lab at the same time and three small incubators in the basement. Most of my desk work I did at home, as I had not enough space in my office. People where very friendly and we shared equipment across groups and even departments. For example, the algae I needed to feed the Daphnia was produced by a group in genetics department.
Lately, I learned that the building of the Zoology Department at Oxford University is about to be destroyed because of problems with asbestos.
HS: What is the story behind the locations from which samples were collected (Table 1), i.e. why these particular locations (four near Oxford, one from Kew Garden, two from North Germany, one from south Germany and one from Moscow)? Do you continue to sample from these sites even today? When was the last time you visited them?
DE: When I arrived in Oxford I went by bicycle and car all over the country side to look for ponds where I could find Daphnia. The ponds in the UK listed in Table 1 are the results of these excursions. The ponds in Germany and Russia are field sites of other Daphnia researchers, who sent me material to the UK. As we continue to work with Daphnia from different localities, we have now a large collection of animals in the laboratory (from > 200 populations).
HS: In footnote 8 of the paper you describe the experimental protocol you followed. Could you reflect on this and tell us a little more about what a typical day was like for you during this work, did you work alone or did you have people to help you, what was your work routine etc.
DE: Reading this protocol now (after 25 years), I was smiling, as the methods are rather similar to what we still do today. A typical day would start with preparing the food for the animals. Then I would check survival of the animals, transfer them to new jars, count the number of babies released since last check and feed all animals. This would take between 3 and 6 hours a day. The biggest work was to quantify parasite growth inside the host. The transmission stages of the parasite are tiny (about 2 microns in length) and one needs to take care not to overlook them. I spent many days on the microscope. But I still like to work on the microscope today.
HS: You acknowledge a number of people at the end of your paper. Could you tell us a little more about how you knew them and their contribution to this paper:
- S. Young
- W. Lampert
- M. Teschner
- E. von Krosigk
- L.Y. Yampolsky
- W.D. Hamilton
- K. Mangin
- R.M. May
- S. Gupta
- M. Lipsitch
- D. Clayton
- J. Lawton
- H. Stirnadel
- M. Cook
- J Wearing-Wide
- E.A. Herre
DE: 1. to 5. are people who helped me to get the Daphnia from different populations. With W. Lampert and L. Yampolsky I am still in contact. Most of the others were members of the Zoology Department at Oxford. I met them regularly during tea time and we talked a lot about host – parasite (co-)evolution. This was a great source of inspiration and I love to think back to these discussions.
HS: How long did the writing of this paper take? When and where did you do most of the writing?
DE: Analysis and writing was about 2-3 months. I wrote mostly at home, where I had my first little computer.
HS Did this paper have a relatively smooth ride through peer-review? Was Science the first place this was submitted to?
DE: Yes, Science was the first place where I submitted it. The review process was rather smooth, but I still remember that the reviews were about as long as the paper itself and my reply to the reviewers was even 50% longer than the manuscript.
HS: What kind of attention did this paper receive when it was published?
DE: I received very good feedback. I had numerous interviews with radio stations and journals. I got invitations to talk at other institutes. I think the questions I addressed in this paper hit the Zeitgeist very well. What was also of interest for the community was the new system I introduced. At a time when hardly anybody was able to do experimental work with hosts and parasites, such a new system was very much welcomed. Today there are about 15 research groups using this system.
HS: What kind of impact did this paper have on your career and the future course of your research?
DE: A single author paper in Science certainly opens doors. I was rather amazed to experience this. I guess it contributed to helping me getting my next positions and grants.
HS: Today, 24 years after it was published, would you say that the main conclusion still holds true, more-or-less: “This finding indicates local adaptation of the parasite, but contradicts the hypothesis that long-standing co-evolved parasites are less virulent than novel parasites”
DE: Yes, no doubt.
HS: If you were to redo this study today, would you do anything differently?
DE: I would try to have a better sampling of populations. I had to use what I had at the time. Today, I would do a more balanced design and also would use more parasites isolates.
HS: This paper has been cited close to 500 times. At the time of the study, did you anticipate at all that it would have this impact? Would you know what is it mostly cited for?
DE: No, I did not anticipate this. It is indeed cited mostly for the two aspects which I feel are most important in the study: virulence and local adaptation.
HS: In your study you assume that geographic distance is a good estimate of genetic distance. Has future work found support for this assumption?
DE: This assumption has been supported by other studies (e.g. Fields et al. Molecular Ecology, 2015). However, the correlation between geographic and genetic distance is not very strong.
HS: In the concluding lines of your paper you suggest that the well-known examples of “virulent, introduced pathogens” might be exceptions. Has subsequent research found support for this suggestion?
DE: Generally yes, but not in every single case. It is hard to do research on exceptions.
HS: In Footnote 9 you refer to unpublished results by Ebert &Yampolsky. Was this published later? Similarly, was unpublished results by Ebert in Footnote 13 published later?
DE: The unpublished results by Ebert &Yampolsky were never published. But other people studying biogeography of other Daphnia magna populations across Europe confirmed this.
HS: Have you ever read this paper after it was published? If yes, in what context?
DE: I had several time questions by readers and in this context I read all or part of the paper. Once I was invited for a journal club where the paper was discussed and I re-read the paper for this occasion.
HS: Would you count this paper as a favorite, among all the papers you have written?
DE: The link of this paper to my personal development in the field is very strong. This makes me feeling strongly attached to it. So yes, it is one of my favorites.
HS: What would you say to a student who is about to read this paper today? What should he or she take away from this paper written 24 years ago? Would you add any caveats?
DE: I think the paper stands as it is. There is nothing I regret or where I think the results are not right. Work with other parasites of Daphnia done in my group are largely consistent with the first results. Studies in other systems also largely confirmed that the overall conclusion is sound. However, we know now that in some systems the story is much more complex. Maybe I was lucky that in my system the outcome was rather clear cut.