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Professor Peter Rathjen was interviewed in 2001 for the Interviews with Australian scientists series. By viewing the interviews in this series, or reading the transcripts and extracts, your students can begin to appreciate Australia's contribution to the growth of scientific knowledge.
The following summary of Rathjen's career sets the context for the extract chosen for these teachers notes. The extract covers how he began to investigate embryonic stem cells in mammals and the work he was doing at the time of the interview. Use the focus questions that accompany the extract to promote discussion among your students.
Peter Rathjen was born in 1964, in Cambridge, England. He grew up in Adelaide, South Australia. As an undergraduate he studied in the Department of Biochemistry at Adelaide University, working in part as a member of the team that discovered RNA self-processing in viroids. He received a BSc (Hons) from the university in 1984 for studies on the avocado sunblotch viroid.
As the 1985 Rhodes Scholar for South Australia he undertook a DPhil at Oxford University from 1985 to 1988, studying mobile genetic elements in yeast and mammals. He began work on the molecular regulation of embryonic stem (ES) cell differentiation during a two-year postdoctoral position with Dr J K Heath, also at Oxford.
Rathjen returned to the Department of Biochemistry at Adelaide University in 1990 as a lecturer. In 1995 he was promoted to Chair of the department, and in 2000 to Head of the new Department of Molecular Biosciences. His research interests include the molecular basis of mammalian development, the differentiation of ES cells, and the use of genetic and ES cell technologies for human therapy. This work has proven to be commercially valuable and forms a basis for the cell reprogramming division of BresaGen Ltd, an Adelaide-based biotechnology company for which he has acted as a scientific director. He is also a team leader at the Australian Research Council Special Research Centre for the Molecular Genetics of Development.
In 2000 Rathjen received a Young Tall Poppy Award from the Australian Institute of Political Science in recognition of his outstanding scholarship and his research achievements of national and international standing.
Tell us about that postdoctoral work.
Embryonic stem cells are really quite fascinating. Perhaps the best way to describe them is to put them in their true biological context.
We start life as a single cell, a fertilised egg. And nothing much happens for a little while. Yet our bodies consist of several trillion cells, of several hundred different kinds, and all of those cells are organised into a structure that looks human. Where they came from in the first place is a very small group of about 10 to 20 cells called embryonic stem cells, which existed in the embryo at about the time it implanted into the mother’s uterus. The whole story of embryogenesis is of how those 10 cells turned into trillions of cells, how that one kind of cell turned into several hundred kinds of cells. The beauty of embryonic stem cells is that they are the true founder cells of the entire mammal. Those cells can turn into any other kind of cell.
When I was in Oxford we were working on how we might stop that, how we might keep them as embryonic stem cells and stop them from differentiating, from turning into any other kind of cell.
After those postdoc years in Oxford, you had a number of options. What made you choose to return and take up a lectureship at the University of Adelaide?
The reasons were entirely personal. My family was in Adelaide but I had never ever expected to be able to return there. I have always had a very deep sense of being an Australian, though, and never intended at all to stay overseas for any protracted period. Returning to try and do something of importance in Australia for Australia has always been a deep philosophy of mine. Probably, I spent about 2 years longer in Oxford than I would have by choice; by 3 years I had had about enough and could have gone somewhere else with profit.
Actually, careerwise I doubt that it was the right thing to return at that stage. I would have been better off staying overseas and working as a postdoc for another 2 to 3 years, building scientific networks and building a track record before I undertook the very pressurised job of starting off as a young lecturer. But the opportunity to work in a university, which had always attracted me, and to come back to Australia – in particular, to come back to a really strong department – was just overwhelmingly attractive to me.
You mentioned that since Oxford you have continued with embryonic stem cells. What specifically are you working on now?
When we came back here I decided to start working on how to control the differentiation of those cells. What signals – and they are usually protein signals – do you have to give to the cells to instruct them to become a new kind of cell? How do you tell them to become blood, or skin, or bone?
We undertook that work for the specific reason that no-one knows just how the embryo itself does that. We know that this one kind of cell turns into several hundred kinds of cells, but not really why or how it does so, or even why, for example, the cells in one part of your body become brain cells and the cells elsewhere in your body don’t. What controls it all? We wanted to understand that basic science.
We reasoned that if we could take our embryonic stem cells and tell them to become newer cells, we would probably be copying what goes on in the embryo. And our first 10 years’ work suggests that that is the case. We are starting to learn very valuable things about how the embryo itself came into being.
Secondly, we recognised very early on that if we could learn to produce particular kinds of cells there might be commercial opportunities – and more importantly, I suspect, therapeutic opportunities. If you can make cells, you can transplant them into people who need them for some reason. For example, a stroke results in death of neural cells, and there is already evidence to suggest that if you could transplant replacement neural cells, you could alleviate stroke. Again, many diseases result in damage of bone marrow. If you could learn how to produce bone marrow in the laboratory by differentiating these stem cells, perhaps that could give you a therapeutic intervention for treatment of bone marrow disease.
The particular advantage of using these stem cells is that they are immortal. You can quite easily grow as many of them as you like, and you can also differentiate them into as many cells as you like, producing an unlimited number of any kind of cell to transplant. In addition, it turns out to be possible to modify the genes in embryonic stem cells better than in just about any other kind of cell we know. So you can start with an embryonic stem cell population and, through knowing what you are doing, turn it into any kind of cell, in any kind of number, with any kind of gene in it. What a formidable opportunity to then start trying to correct disease!
Where does your group stand internationally in this research?
I think we are up with the game. It has been an interesting time for us, because for the first 6 or 7 years we were almost the only group thinking along these lines. Our world changed almost overnight when America reported the isolation of human embryonic stem cells, which suddenly made people aware that experiments in the mouse might be transferable to the human. That prompted enormous worldwide interest: what are these cells, how do you grow them, how do you control their differentiation? I would say that intellectually we had got a long way ahead of the rest of the world during those years when other people weren’t thinking much about these things, but in the last few years the rest of the world has substantially caught up.
And that of course is the problem we always deal with in Australia. We are quite good at taking the early steps in research, but when the Americans and the Europeans really start to build the huge teams and move fast, when they throw in the big funding schemes, we struggle to compete.
Select activities that are most appropriate for your lesson plan or add your own. You can also encourage students to identify key issues in the preceding extract and devise their own questions or topics for discussion.
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