Additional excerpts from our interview with Dr. Bongso
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Stem Cells Portal (SCP):
Please explain how you first became interested in hESCs.Â
Ariff Bongso (AB):
My training was in Mammalian Reproductive Biology from the Ontario Veterinary College of the University of Guelph, Canada. More specifically, I acquired a wide spectrum of knowledge and skills in the area of ‘Embryo transfer’ and ‘In Vitro Fertilization’ in domestic animals and later went on to apply this to the human in the field of clinical embryology. Although I was trained as a veterinarian with a PhD in ‘comparative reproduction’ I was very keen to apply my skills and knowledge to the human and came to Singapore to take up a faculty position and be attached to Singapore’s first IVF program in the Department of Obstetrics and Gynaecology of the National University of Singapore in 1987.
SCP:
Work in the field of hESCs involves the use of surplus and donated human embryos. This has always been a somewhat controversial issue in the public realm, and thus this research has always had to undergo evaluation, regulation, and even approval by people who are not scientists. How has this affected your work?Â
AB:
Thanks to the Singapore government the controversies surrounding hESC research have not been a problem because the regulatory framework was very elegantly developed. The government through the Bioethical Advisory Committee (BAC) comprising of individuals of all walks of life deliberated with the public for over one year to get their feedback on hESC research. Several awareness meetings, discussions and talks were given to the public through various forms of media by stem cell scientists and embryologists about the actual details of the science of stem cell biology. Religious and inter-faith organizations were also involved. The concept and definition of the ‘beginning of life’ was discussed at length between scientists and religious groups and scholars in Singapore and the views presented in the press and other media. Singapore is a multi racial, multi-religious society and it would be difficult to accommodate the views of all groups and so the government through the BAC made their recommendations based on consensus. The larger majority of the public supported hESC research with the only major concern towards reproductive cloning. The guidelines have been finally formulated for stem cell scientists as to what can and what cannot be done with the right checks, balances and penalties. Thus, my research has not been affected because I know where my boundaries lie.
SCP:
What do you see as the nearest practical application of hESC research?
AB:
To me the biggest challenge facing hESC scientists is the elimination of teratoma formation through hESC-derived tissue therapy. I see little interest in this important area as safety is fundamental to taking this science to the clinic. It has been claimed that even a few rogue undifferentiated hESCs in the hESC-derived tissue population can induce teratomas in immunodeficient mice. This thus is a very worrying problem. Once this issue is resolved I believe that the nearest application of hESC research should be for liver diseases (cirrhosis and liver failure). This is because the liver is the only organ that undergoes spontaneous regeneration and is therefore the ‘Holy Grail’ for regenerative medicine. It has its own stem cells, is not a complicated organ like the brain or heart. Injecting just a few hESC-derived hepatocytes may help to trigger of the intrinsic regeneration process in patients with cirrhosis still having a part of intact liver. We can also learn a lot from the regenerative machinery of this organ.
SCP:
Where do you see the potential of hESC and iPS cells to treat human infertility?
AB:
If one is referring to the production of germ cells (male and female gametes) from iPSCs or hESC, I think this is a long shot. Although nice in vitro systems that can help promote differentiation of hESC or iPSCs towards a germ cell lineage have been developed, there would be obstacles at the point of meiosis to produce complete functional gametes for the purpose of human infertility. The molecular mechanisms involved during and after meiosis in vitro, are very complex and would require very complex in vitro environments. In the studies that have demonstrated ’gamete-like’ structures after hESC differentiation in vitro, I am not sure from a functional point of view whether they can be used for reprogramming or generate embryos with normal embryogenesis.
SCP:
Are there ways in which you feel we should be educating and including the public in this important work?Â
AB:
I believe this is very important. I have been personally involved with the Singapore public, giving talks, seminars and discussions using powerpoint slide presentations. These were also delivered to religious organizations. I realized that many religious scholars and members of the public are not familiar with the facts of the science and even presume that hESCs are derived from mature concepti where all organ systems are fully developed. The timing of the beginning of life has also got to be discussed openly from a multi-religious point of view. We did this in a very cordial and harmonious way in Singapore through our inter-faith organization. This helped our national Bioethical Advisory Committee to smoothly make their recommendations and guidelines for hESC research and application through consensus of opinion. The majority of the Singapore public was in favor of hESC research and application. The BAC used the Day-14 rule (beginning of primitive streak formation) where human embryos after Day-14 could not be manipulated and reproductive cloning was disallowed. Given our own experience in Singapore I believe that educating the public on stem cell research is important and extremely useful.
The ways we should be going about this is to make stem cell scientists provide talks together with dialogue sessions on TV and in the Newspapers. A hotline for public feedback is also useful. Involvement of the inter-faith religious organizations is extremely useful as they would be the conduits between stem cell scientists and the public.
SCP:
What are some of the biggest challenges you faced as a student and new investigator, and what strategies did you use to meet these challenges?Â
AB:
As a student my biggest barrier was to write a proper scientific article by myself that would be accepted in a journal. I had trouble in writing in scientific English and not knowing where to start and where to end. My initial manuscripts went into pages most of which were redundant. I think the acceptance of my first paper written all by myself made me realize that there were three fundamental questions one had to seek answers to when structuring a manuscript. They are ‘Where are you going’, ‘How are you going’ and ‘Have you got there’. This basically is putting forward a hypothesis and attempting to prove or disprove it. ‘Where are you going’ is clearly seen as the objectives in the ‘Introduction’ section of a manuscript, ‘How are you going’ is the Materials and Methods’ and ‘Have you got there’ is the ‘Results and Discussion’ sections.
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