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Testes Yields Versatile Stem Cells - Jan 09

STEM CELLS

Volume 27 Issue 1, Pages 138 - 149

Published Online: 5 Jan 2009

Nina Kossack 1 2, Juanito Meneses 3, Shai Shefi 4 5, Ha Nam Nguyen 1, Shawn Chavez 1, Cory Nicholas 1, Joerg Gromoll 2, Paul J. Turek 4 *, Renee A. Reijo-Pera 1 *||
1Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Palo Alto, California, USA
2Center of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany
3Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA
4Department of Urology, University of California, San Francisco, San Francisco, California, USA
5Sheba Medical Center, Tel Hashomer, Israel

 

News Items:

San Francisco Chronicle Jan 13 2009          Testes found to yield versatile stem cells

STEM CELLS Journal Names Co-Editors

DURHAM, N.C., Nov. 15 /PRNewswire/ -- AlphaMed Press, publisher of the journal STEM CELLS(R), has named Donald G. Phinney and Miodrag Stojkovic as co-editors.

Curt I. Civin, current STEM CELLS Editor, retires after eight years of unprecedented growth in areas of the journal's most significant metrics: Impact Factor, number of pages published, and number of manuscripts submitted. During his tenure as editor-in-chief, Dr. Civin was assisted by three outgoing senior editors: Alan M. Gewirtz, Robert G. Hawley, and Margaret A. Goodell.

Successful Cloning of Human Embryo

DURHAM, N.C., January 17 - A California research team has become the first to report, and painstakingly document, the cloning of a human embryo using donated oocytes (egg cells) and DNA from the cells of an adult donor. The study was published online today by the journal "Stem Cells."

Mouse Adult Stem Cells Developed into Heart and Blood Cells

DURHAM, N.C., April 30 - Researchers have succeeded in inducing stem cells grown from mouse skin cells to differentiate into functioning cardiovascular and blood cells, according to a study publishing online tomorrow in the journal "Stem Cells."

"Induced Pluripotent stem (iPS) cells are reprogrammed cells obtained by genetic manipulation of normal adult cells that then express capabilities similar to embryonic stem cells," explains Dr. Miodrag Stojković, Co-Editor of "Stem Cells." "That is, iPS cells are theoretically able to differentiate into 220 different cell types. For the first time, scientists from UCLA were able to induce the Differentiation of mouse iPS cells into functional heart cells, smooth muscle cells, and blood cells."

3rd Annual Young Investigator Award Presented at International Stem Cell Symposium

Durham, NC & Seoul, Korea, June 20, 2008 – The journal STEM CELLS® announces that Lena Motoda, MD, PhD won the 3rd Annual STEM CELLS® Young InvestigatorAward.

additional excerpts - James Thomson

 

Additional excerpts from our interview with Dr. Thomson


Stem Cells Portal (SCP):

Work in the field of human embryonic stem cells 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 did this affect your work in 1998?

 

James Thomson (JT):

Prior to that it wasn't clear how this would be perceived in the public realm, so before initiating the work I talked with some very good ethicists on campus, discussing the implications. The work has been heavily scrutinized from the beginning, which on the whole is a positive thing.

However, the controversy has somewhat hindered the field because it has led to financial implications. NIH grants would not fund this at the beginning, and now only on a limited number of cell lines, which may have limited the number of people entering the field.

SCP:
What was the reaction of the public vs. the scientific community to your derivation of the first hESC lines?

 

JT:
The scientific community was generally positive. The public in Madison was positive, it's a very liberal place, but there were of course differences of opinion elsewhere.

SCP:
As somebody who stands on the frontier of hESC research today, how do you think this will affect the future of hESC research?

 

JT:
I think most of the controversy has gone away already with the exception of the current administration; both new candidates for president have indicated their support for this research. One thing that President Bush did do was let this research go forward, even in a restricted way, which has at least opened the door to this field, and that door cannot now be closed. Also, this was not as damaging to the basic research at the time. The existing cell lines were OK for this at the time, however as time has gone on that policy has become more damaging.

 

SCP:
Please comment about your feelings as to the importance of public discussions and lectures regarding ESC research.

 

JT:
I have done a lot of this over the years, mostly early on, not as much now due to time pressures. What I've learned is that the press is a medium that informs the public but does not educate them. In the first 6 months of the Bush presidency it was clearly a hot topic news story, with new stories every day, but in polls it seemed that the public still really had no idea what these cells were or where they came from. I don't know how to change that. The science reporters who get the initial story usually do a very good job, but there is still a problem getting it out to the public. With public lectures, it really only gets out to a small audience
.

 

SCP:
Please comment on the problems you feel are associated with:

a) suboptimal in vitro growth conditions

 

JT:
This isn't such a problem anymore, they grow well, the medium has improved a lot over the last 10 years.

 

SCP:
b) genetic manipulation of hESCs

 

JT:
They are actually as efficient as mouse cells as things like homologous recombination, just their doubling time is different, so experiments in humans take longer.

SCP:
c) our understanding of epigenetic mechanisms and targeted differentiation of hESCs

 

JT:
It's almost certain that there are epigenetic changes, the question is, how significant are these changes? There are many labs looking into this, but how critically important these mechanisms are is not clear yet. The genetic changes probably are a big deal when considering transplants (re: changes in genes over time in tissue culture). Making sure these transplants are safe will probably take years to work out.

SCP:
Do you believe that ultimately iPS cells will be most useful as a model to study human disease, or are they likely to provide patient-specific cell therapies?

 

JT:
They will likely be most useful as model systems. Immunorejection was never the major limiting factor that has kept stem cells from being used in therapies. It's getting them to functionally integrate in a way that repairs the tissues But the ability to control genetic background should help our ability to research drug development.

 

SCP:
The development of new technologies and the protection of these technologies is am important topic for consideration. Unfortunately, we have as yet no world-wide policy or strategy regarding the patenting of hESC work.

What direction do you think scientists and policy makers should be taking on this issue?

 

JT:
I really don't know. It seems that the original reason for patents in Britain was that they allowed information to get into the public domain, in return for a limited amount of time to develop it, which I think is a very good use for patents. But in academics that model doesn't make sense because you are already motivated to get things out into the public domain. So it really hinges on whether having these patents facilitates commercialization of the product, which is a good thing, but it's hard to say how much it really benefits us since we don't have a parallel universe where these things don't exist.

 

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?

 

JT:
I took such a back door approach, it was unusual. I found a way to keep myself employable without having to live from RO1 to RO1 like most people do. The work with primates was also very difficult to get funding for. So always look at alternatives that aren't in the normal track, because the percentage of PhDs who get jobs in academics these days is pretty low.

SCP:
What advice would you give to young scientists in the field today who are trying to balance the demands of work and family/personal life i
n this increasingly demanding and competitive field?

 

JT:
I don't have great advice for this because I got married very late! I now protect my time with my family in a way that if I was just starting out I really couldn't because the demands in the lab are so high. That's a very difficult issue.

 

SCP:
What do you feel is one of the most important experiences or defining moments in your education, career, or life that has contributed to your success as a researcher?

 

JT:
I think everyone has some sort of a mentor, teacher, etc. that has at some point inspired them in some way. For me it was a biologist when I was an undergraduate. I don't know why this guy had such an influence on my, but I changed from a mainly math and physics major to biology because of him. It takes a unique individual who is there at the right time and actually cares about you as an individual.

additional excerpts - Rudolf Jaenisch

Additional excerpts from our interview with Dr. Jaenisch

 

Stem Cells Portal (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?

Rudolf Jaenisch (RJ):

Well the work with mESCs has of course been untouched by this controversy.  For hESCs, it has affected me because work with non-presidential human ES cells is cumbersome in this country.  If you want to work on your own non-presidential hESC lines, you have to go through the hassles of separating your laboratory and this work from all of the other federally funded research in this area in your lab and your institute.  And it is difficult to raise money or to write a grant for this work, so these are all hurdles, which I think are substantial.

SCP:
As somebody who stands on the frontier of hESC research today, how do you think this will affect the future of hESC research?

RJ:
I think it will be less and less.  The policy in this country (USA) has been so extreme that it only can become better with whoever forms the next administration here.  There are certainly other countries, like Germany, that are extreme, and they are facing even worse problems than we in the US.

SCP:
There are many confusing data that Oct4 has been detected in adult stem cells and tissues. In your opinion, how important is Oct 4 for somatic cell self renewal?

RJ:
I think it was very attractive to think that Oct4, being the key gene that is important for self renewal of ESCs, might also have a role in adult stem cells.  Indeed, there were hundreds of papers that said they found Oct4 expression in adult stem cells, in the gut, blood, skin, etc., but not in the progenitor cells, which are not immortal.  The evidence was either staining for protein, or PCR.  When I looked at most of those data I was really worried, because the controls were not good and the PCR seems to have been really stretched to its limit, and was unconvincing.  So we looked at this very carefully in mice.  We took a mouse and deleted the Oct4 gene in the adult tissues, and asked if it made any difference to the tissue homeostasis in various tissues.  And there was absolutely no difference – we found that the tissue didn’t need Oct4 in the adults.  And then we stressed these mice.  For instance, we irradiated them, to slough off the intestinal epithelium and found that the mice without Oct4 could regenerate their intestinal epithelium as well as the controls. The same results with the blood and the skin – there was no difference in regeneration even when you stressed the system – the Oct4 deficient stem cells renewed the tissues.  Then we asked the question, could we see Oct4 expression in these cells.  By staining we couldn’t see it.  But by PCR, we detected a low signal (10,000 times less than ESC cells).  However, the signal was there regardless of whether or not the gene was there!  We saw the same signal in mice in which we had deleted the gene as in mice which had the gene.  So obviously this was at the limit of PCR detection and the signal was an artifact.  So basically from our studies, and I stress they were in mice, there is no functional role of Oct4.  Hopefully this will put to rest some of this controversy. 

There is also another interesting argument for this.  We also know that Oct4 is a powerful oncogene. If you express Oct4 ectopically in the mouse, they immediately develop tumors. It’s as powerful an oncogene as c-myc.  So if Oct4 was expressed normally as part of the normal adult stem cell renewal, it should show up as an oncogene all over the place, in many tumors, but it never does.  What that says to me is that this gene is so well silenced that it doesn’t get activated, and has no role in adult development.  Putting this together makes me very much doubt the evidence from people who claim it has some role in normal adult stem cells.  This does not mean that in tissue culture cells, under certain circumstances, this gene could not get reactivated.

SCP:
We know many things about the epigenetic background and profile of animal embryos, but not human embryos. There are some studies which claim that intracytoplasmic sperm injection (ICSI) and assisted reproduction can result in humans in Beckwith-Wiedemann (B-W) syndrome. Do you believe it is assisted reproduction itself, or some specific part of these medical treatments, for instance, suboptimal in vitro culture conditions, that is causing this condition?

RJ:
There are several studies indicating that the incidence of B-W does go up several fold, but the number of patients with B-W is still very low.  I think it is a very interesting finding and a concern.  We know from mouse that when you culture embryos in the petri dish, that you do lose imprints of some of the very sensitive genes, and one of the genes is IGF2, which is actually involved in B-W.  It depends on the media composition.  In the mouse, it’s the NaCl concentration that’s important.  And they even see imprinting defects after implantation.  So it is concerning that you might find this in humans.  The issue is that when the embryo is out of the mother and in culture for a couple days under certain medium conditions, you have to worry that you may lose some imprinting on very sensitive genes.  We would like to understand how to avoid this, but you can’t experiment with human embryos. Any study to do this would be very difficult and challenging.  But the incidence of this disease is very low.  You can look at the problem in mice but the results do not necessarily translate to humans.

SCP:
Please comment about your feelings as to the importance of public discussions and lectures regarding ESC research.  Are there ways in which you feel we should be educating and including the public in this important work? 

RJ:
This discussion is very important , as there is so much misconception in the public.  I think good science writers have an enormously important role here.  And not just with the public but also with legislators.  It’s amazing how much misinformation there is even among the  legislators. I’ve seen how these issues are discussed and misunderstood.  It’s a very important task for scientists working in this field to be available to inform the public and the legislature about the science and the facts.  And to get the facts out independently of ideology and other considerations.  
We have to take this obligation very seriously.

SCP:
How detrimental, in your opinion, is the fact that the policies on stem cell research are different in so many countries?    

RJ:
I think it very much depends on the country.  In Germany it’s a very contentious issue, and due to their history they have made strict embryo protection laws, which I think are very bad.  In the US there is no law at all.  But there is a ban on federal funding for this research.  I think this has shaped the public opinion.  But there are also some interesting cases with some very conservative senators who are anti-abortionists, but are also staunch supporters of embryonic stem cell research and therapeutic cloning.  I think it is because they see in their families or their friends the potential of this type of research for medicine.  And it immediately changes how they look at this.  So the opinion people have is very personally colored.

SCP:
What do you feel is one of the most important experiences or defining moments in your education, career, or life that has contributed to your success as a researcher?

RJ:
I think when I was a visiting fellow in Beatrice Mintz’s lab that was a most decisive experience for me. I was a postoc in Arnold Levine’s laboratory at the time and he was a very generous advisor.  He taught me how to work with SV-40 and taught me molecular biology, and when I went to Mintz’s lab for 9 months, I learned to think the way she was thinking about development and embryos, and began to combine it with the molecular biology I had learned in Arnold Levine’s lab.   This likely was the most important experience for my subsequent career.  When we injected the DNA into the embryos and made the first transgenic mice, and then when I saw the first mice being born I was blown away.  And they were all normal and we didn’t know what to do with them.  We couldn’t believe it that they might carry the injected DNA.  Importantly I had to figure out how to find the DNA if it was present. Southern blotting or PCR had not been invented yet, so I had to learn techniques such as Nick translation and cot curves to detect DNA sequences, and it took a long time to actually prove that these animals were indeed transgenic.

additional excerpts - Alan Trounson

 

Additional Excerpts from our Interview with Dr. Alan Trounson

Stem Cells Portal (SCP):
Work in the field of human embryonic stem cells 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?


Alan Trounson (AT):
I had been subject to a lot of public interest and publicity with the development of IVF in Australia in the late 1970s and 1980s, and there were several issues that we had to deal with in a very public way, such as presenting the arguments in favour of having IVF available to couples, then moving on to genetic diagnosis, and so on.  There were some strong conservative views against these developments, so I have actually been through the publicity associated with this type of research before, and in many ways the arguments for stem cells are very much the same, such as the issue of embryos being discarded or used for research.  I don’t particularly like this process with all the publicity, but scientists have to contribute.  In the case of stem cells, patient advocates also have a very important role, but scientists also play a crucial role in educating the community. 

Because we were very successful in the early days of IVF, we also inherited some very draconian laws with respect to human embryo research, which impeded a lot of our research capacity in the 1980s and early 1990s.  The laws in Victoria, Australia, were intended to prevent the ‘slippery slope” to unethical procedures from happening; they were the first laws anywhere in the world and were very difficult to operate within.  Much of our work them was done in collaboration with people overseas or interstate, by necessity, because it wasn’t possible to do some of the experimental work in Victoria. hESCs are not attracting the same degree of critique, although nuclear transfer (SCNT) has been impeded in some instances.  Whether that has adversely affected outcomes I’m not sure, because SCNT still hasn’t been successful in humans.  Without these problems, would the work have been easier, had a bigger impact, taken the field further forward?  I’m not sure.  The impact of the American President coming out against new hESC derivation certainly impeded the work in the US, until the California (CIRM) and other initiatives got going.  There were some hold ups in research because there was the feeling from some members of the scientific community that this was an area that they shouldn’t work in because career opportunities might be very limited.  Adverse regulations may have kept some of the best scientists from becoming involved hESCs. The advent of programs like the one in California (CIRM) has really changed all that.

SCP:
Please comment about your feelings as to the importance of public discussions and lectures regarding ESC research.

AT:
I think it is very much the role of scientists to be involved in education.  I think the public wants to be educated and to have an opinion based on fact.  The internet is a very effective way of providing information, but public presentations and debates are also all part of what science is nowadays, no matter what field you’re in, whether its genetic engineering, new energy sources, etc.  The public wants to know what the thrust of the research is and what the outcomes are likely to be.  And the only people that can really address that in any serious way are the scientists.  It’s a very important role that we have.  We also have to be able to talk in a way that is understood by the public, comprehensible and useful, it’s a language which has to be modified form our own internal scientific language, and teaching people to do that has always been an important role of senior researchers.   

CIRM has many different activities to reach out to the public, such as spotlights on various diseases or conditions, and where we stand today in term of regenerative medicine.  These are generally held at the same time as our board meetings, which are public.  We also work hard on our websites to get information to the public; we have our scientists go out to give talks and we encourage all of the scientists that we fund to talk to the community about what they are doing and why.  It’s very common now to see young people at forums, rotary clubs, interest groups, and so on, talking to other young people about these issues.  At CIRM we have a very comprehensive education program, which we work very hard on, but this is also happening, in many other countries such as Australia, UK, and Sweden.

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?

AT:
The most challenging thing was learning new techniques, such as micromanipulation, molecular biology, etc. The way that I dealt with it was to collaborate with others who had those skills and I could learn from them.  I am also much more the type of scientist who is interested in practical outcomes, so I focused on this.

SCP:
What advice would you give to young scientists in the field today who are trying to balance the demands of work and family/personal life in this increasingly demanding and competitive field?

AT:
My advice would be to reach for the stars!  Try to see something that hasn’t been considered before, take an observation and question why that happened in that case, is this really possible.  Reach out and go beyond the edge and do that work.  It’s exciting and very fulfilling.  It does take a lot of time in the lab, and we are not normally employed to reach out into these areas by the public or private institutions that provide you with the money.  In Australia, we call it skunk time – the time which is not in your normal working hours, when you do some of the really odd experiments that you are interested in yourself – this time can lead to some of the most creative thoughts and exciting observations.  These were unconventional, innovative and creative explorations.  This was one of the most exiting and invigorating times in the lab for me, and very rewarding.

additional excerpts - Christine Mummery

Additional Questions from our Interview with Dr. Christine Mummery

Stem Cells Portal (SCP):
Please describe what fascinates you about hESCs.

Christine Mummery (CM):
I guess maybe the idea that you can control what they do if only you can find the right cues. Our developmental biology research has fed into this extremely well and has provided many of the clues on how to make hESC form cardiomyocytes even better. Also sharing the challenges they have presented (just keeping them undifferentiated and able to form cardiomyocytes in the early years) with like minded colleagues.

SCP:
Please comment about your feelings as to the importance of public discussions and lectures regarding ESC research.

CM:
These are very important, particularly to patient groups to ensure expectations and hope are not turned into hype and clinical trials are not initiated through pressure from the  desperate. The ISSCR is developing guidelines on this. Public lectures are really important in forming the political climate for science and I think as many people as possible should be aware of developments rather than fear of abstract and incorrect ideas of what scientists do with stem cells. I give quite a lot –science cafes, opening of debates, feminist issues on embryo donation, schools.

SCP:
Are there other ways in which you feel we should be educating and including the public in this important work?

CM:
Going into schools is certainly a way of reaching the public young, not only to educate about stem cells but about science in general. Two colleagues and I actually wrote a popular book in Dutch on stem cells which sold extraordinarily well for such a specialist subject. We find it in libraries and schools and many medics in training seem to find it a quick way to get at the basics. In the Netherlands, public debates are often part of developing new laws and these were also a prelude to the Embryo Law here.

SCP:
Do you believe iPS cells will ultimately be most useful as a model to study human disease, or are they likely to provide patient-specific cell therapies?

CM:
I think for studying human disease they could be great but we still need to see phenotypes. I think that is what people are rushing to do right now to be able to answer that question. Patient specific therapies would seem to me to be likely too expensive. Banking of specific HLA types however, may be easier than with hESC. The viral transfer of pluripotency genes still has to be solved of course but I guess that will not take too long.

SCP:
Do you know if some pharmaceutical companies are already using cardiac-differentiated hESCs to test new drugs?

CM:
Interest has grown now that many societies have moved a little on ethical objections and questions of standardization of culture and differentiation are moving along.  GSK has invested heavily in this type of research in the Harvard Stem Cell Institute recently so may be more will follow. Stem Cell for Safer Medicine (SC4SM) in the UK has likewise set up a programme to develop hESC for liver and cardiac drug screening in which Pharma is involved or at least consulted so I think that before long a great deal will be happening. Off target testing is of particular interest as high throughput as well as replacement of animals.

additional excerpts - Ariff Bongso

Additional excerpts from our interview with Dr. Bongso

 

Stem Cells Portal (SCP):

Please explain how you first became interested in hESCs. 

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? 

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? 

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? 

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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