Prominent scientist explains a move from Germany
Singapore has invested heavily in science in the last decade and has attracted scientists from around the globe to its biomedical research enterprise. The Lion City's science funding includes more than US$20 million for stem cell research, and scientists there face fewer hurdles to working with stem cell lines than those in some other nations1. In 2008, developmental stem cell biologists Davor Solter and his wife Barbara Knowles moved to steamy Singapore to join the Institute of Medical Biology housed in the new Biopolis complex. Reporter Amber Dance visited him in his new labs.
What attracted you to Singapore?
I retired in Germany. I wasn't planning to do anything. But both [my wife and I] had contact with Singapore before. I came before as a scientific advisor for the Genome Institute. Several of our friends came here and they were happy. It became apparent that we actually could do something that would be useful for Singapore. Singapore had perfectly fine science, but some of the organizational elements were not quite clear. This, combined with the fact that we realized that we could start some totally new projects, was quite attractive.
If you just walk through the lab, you won't notice any difference whatsoever. If you don't know how hot it is outside, you'd think, “That's Frankfurt or Cincinnati or Chicago.” It's a little bit more goal-oriented. Singapore was always a goal-oriented society — being relatively small and having to live on the basis of nothing, no natural resources. That's why Singapore is really impressive. From '65 to now, from basically being one of the poorest countries in the world to one of the richest, all through work — impressive.
A couple of years ago, The New York Times called Singapore an “emerging hotbed” for stem cell research2. Do you find that the regulations of what you can and can't do with stem cells are different here?
I think that very likely iPS cells will become a moment in scientific development that will be forgotten.
I think any basic question dealing with stem cells could have been answered in any country. All these rules, all these laws are being more or less overtaken by the research. With transdifferentiation and iPS [induced pluripotent stem] cells — ES [embryonic stem] cells, embryos, all this [controversy over eggs and embryos] is going to disappear. We don't need it; forget it; it will never happen again. And totally new ethical questions are going to come up.
Singapore is probably among the most liberal. They use the same system as England and that is considered rather liberal. Though I actually think the United States is the most liberal because there is no law; you can do whatever you want as long as you can pay for it. [Singapore's policies] might make it easier to attract people from countries that have stricter regulations, like Germany. If you want to work very simply on stem cells, then this would be a good place.
What is the funding situation?
We in the institute do not have a [defined] budget. So far it hasn't happened that our director said, “OK, that was enough.” I talk with people in the States who are struggling with money and writing grants all the time. Someone in my position would probably spend 50%–70% of their active time writing grants. So that's an enormous plus. [But] science here is pretty expensive. Buying mice is very expensive because we don't have a Charles River production facility next door. They are all imported.
How about the teaching and mentoring situation?
Our main goal in coming here was not to develop our own careers — I don't care, it can stay exactly as it is — but actually to [train young scientists who will someday] replace us. We were really happy with the quality of people we managed to attract. There is this pool of people who cannot escape, the A*STAR [Agency for Science Technology and Research] scholars. They have to come here and be postdocs for four years. And so the selection is really, really good.
When you look at the institutes, at least the principal investigators, you see the number of [those] Singapore-raised or Singapore-trained is very low. My idea is that any A*STAR scholar who deserves it should become a PI [principle investigator]. For example, we have a career development committee. We discuss every postdoc: how is this person doing? What do we need to tell this person to do more? What should we tell their mentor to watch over? And so on.
Are there any downsides to being here?
Barbara said, “Just say it is paradise on Earth.” It's actually very difficult to think of something even inconvenient. We complained in the beginning that it took a relatively long time to purchase things. But you soon get used to it. When I started my scientific career in Yugoslavia, you had to think six months to a year ahead. So if you have to wait two weeks here, it's probably rather fast.
Could US and European science enterprises learn anything from the way science is done here?
I don't think we could learn much. There are small differences in emphasis. You have this feeling that whoever started this [Singapore's investment in science] is very serious. In the United States, this firm commitment of government to continuous biomedical research is a little bit missing. The European Union is still operating on the idea that science is like agriculture: how many metric tons of wheat you are going to produce, and how much it will cost? [In Singapore], it doesn't look like somebody is going to come tomorrow and say, “Well, we spent all this money. And where is the bacon? When is [the payoff] going to come?” People realize that in biomedical sciences, the payoffs are a little bit slow. There seems to be patience.
What research questions are you addressing?
The basic question is: how come the oocyte can reprogram? Oocyte and sperm are completely terminally differentiated cells. They come together and, suddenly, they completely change their program. What are the molecules, and what are the processes, that make it possible for [an] oocyte to take a sperm cell and reprogram it? Or take a somatic cell nucleus and reprogram it into a totipotent cell?
With the derivation of iPS cells, the question is now, are the processes in any way the same? Or are we totally bypassing those controls, and therefore the product is, in a way, totally wrong? That's a problem because we are planning to use iPS cells or ES cells, eventually, to somebody's good. Their derivatives are going to be injected into somebody. These cells are going to be there and they are going to stay. So one has to be pretty sure that nothing bad will be found 10 years later. I think it's very important to understand exactly how this programming works and how it is different from the reprogramming that we know is not dangerous, the reprogramming that happens to sperm and egg.
What excites you about the field of stem cell research today?
If there is going to be cell and tissue replacement therapy, it will be based on stimulation of [a] person's own stem cells or on transdifferentiation. And I'm actually thinking that transdifferentiation is very likely to work. If a person needs a certain cell replacement — let's say something really simple, like a cornea — now, we would take a fibroblast and put all these factors in to turn it into iPS cells. And then we would redifferentiate these iPS cells first into ectoderm, then into some kind of epithelium, then into corneal epithelium. Now, why cannot we just take a fibroblast and put in three or four factors and make them into cornea? It might be safer. I think that very likely iPS cells will become a moment in scientific development that will be forgotten.
Colman, A. Stem cell research in Singapore. Cell 132, 519–521 (2008).
Arnold, W. Singapore acts as haven for stem cell research. The New York Times 17 August 2006. Article
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Dance, A. Davor Solter: non-retiring with stem cells in Singapore. Nat Rep Stem Cells (2009). https://doi.org/10.1038/stemcells.2009.124