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Mon 1 Jan 2007 03:11 PM

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The Hard Cell

Once relegated to the depths of clinical journals, embryonic stem cell research has become a permanent fixture on the nation’s front pages. Ahead of his lecture at Arab Health 2007, Dr David T. Scadden, co-director of the Harvard Stem Cell Initiative and a leading authority on stem cell research, spoke to HME about the debate.

To reference the title of your upcoming lecture, will stem cells revolutionise medicine?

Stem cells have the capacity to change the way in which we deal with a number of degenerative diseases, although the way in which it will happen may not be exactly as people envisage.

The cells certainly have the capacity to regenerate tissue, but viewing them simply as the way to generate replacement parts is too narrow and perhaps too ambitious a view.

We know that a number of adult tissues have endogenous stem cells and that those adult stem cells may also be an important aspect of using stem cells more effectively in medicine. We tend to use adult stems only in the setting of a replacement for bone marrow function; however, the potential to be able to target these cells with drugs is something that is becoming more apparent.

Tissues like the brain, the intestine, all have stem cells, and being able to modify the activity of those cells with medications (with regard) to their ability to repair offers a real opportunity to change the approach to diseases involving those tissues. Such a therapy might not just forestall the progression of disability but potentially restore ability. If that is the case, than it may be possible to have drug-based therapy that will be an important component and derivative of stem cell biology.

I think stem cells will also change the way we deal with cancer. There has been a hypothesis that is long standing, that cancer may have an organisation somewhat similar to normal tissues. Within cancer there is a broad range of cells, but only a very small number compose the regenerating pool of cells that allow for persistence and metastasis of cancer. Those are stem-like cells for cancer.

This concept has been validated through the work of John Dick and others, and has now been shown to be true in at least seven different human cancers. If it is true very broadly, it would change cancer drug development.

We might now target the stem cells and change the molecular targets that have been prioritised for new therapies, perhaps changing how we monitor response to therapy. This would be a direct result of stem cell biology with a near time effect in our treatment of cancer.

(A further approach) is the ability to potentially create disease models using disease-specific embryonic stem cells. Such cells would enable studies on the basis of, and potential drug therapies to interrupt, disease. These areas all have very different time lines in terms of an effect transferred into the clinic. Each offers real potential and we need to pursue them in parallel.

Embryonic stem cell research, even in the medical community, is often accused of being less therapeutically relevant than somatic (adult) stem cell research, which receives less attention.

It’s a commonly stated opinion, but my impression from being in the field is very different. The idea that umbilical cord blood stem cells are somehow being under-explored is absolutely not the case in my opinion.

These are being very vigorously pursued. There is also the misimpression that umbilical cord stem cells are somehow the equivalent of embryonic stem cells, and that is absolutely not the case.

There are very rare scattered reports of embryonic cell-like properties of a subset of these cells, but there is no question that the embryonic stem cell is an entirely different entity in terms of what it can do in a laboratory compared to an umbilical cord blood cell. More research on adult stem cells is important, but not as a substitute for studying embryonic stem cells.

I assure you that the scientific community is very anxious to get itself out of the target sights of people who are opposed to the work on embryonic cells. If we could accomplish the same with adult stem cells as we can with embryonic, we would do so without hesitation.

Unfortunately, we are just not there yet. To be able to use only adult stem cells we need to study them and contrast them to embryonic stem cells. Studying both is necessary now if we are ever to get to the point of just being able to use adult cells.

Federal funding for stem cell research in the US is strictly limited. What impact have these cost limitations had on your, and future, research?

There are two major issues. One is that if we are to do work in this area, we need to spend time raising the funds but also it requires a duplication in materials and equipment that is strikingly inefficient. We have laboratories where we have to rebuy pieces of equipment that are half a million dollars each, in order to avoid the charge of misusing federal funds.

The other important issue, which is non-quantifiable, is that of young people. For talented young people who are thinking about how they are going to invest their careers, the idea that they may be entering into a field where the possibility of being able to do their work is still ambiguous can be daunting.

If they were deciding between say, stem cell science and neuroscience, they would likely choose the other field. This impacts on our ability to have the best and brightest move the field forward. Indirectly, it inhibits our ability to test the promise that many of us feel is so inherent in this field.

Embryonic stem cell research is a notoriously controversial issue. Can we move on from this position of ethics versus science?

I take objection with the notion that it is ethics versus science. I think many people who work in this field do so out of a sense that they are doing something of deep moral value.

Certainly as a physician, I think the idea that we would put cells in the incinerator rather than potentially developing a therapy for people whose diseases remain unmitigated, is frankly an ethically unacceptable choice from my perspective. It is important that people recognise that there are two ethically defensible positions.

One is that people may regard the potential life in the freezer of an in vitro fertilisation clinic as something that is equivalent to a whole person. The other is that a product that will be discarded has the potential to provide the life enhancing, if not life preserving, activity of new medicine. Each of these stands on ethical grounds.

For those who object to stem cell research on ethical grounds, I am sympathetic to their view, but I don’t share it. I am committed to relieving suffering of the living and stem cell research offers that potential.

It is also important to note that stem cell research started back in the 1950s, with adult stem cells. But it didn’t achieve clinical practice until 25 years later.

Those early days of research were fraught with comparable types of ethical debates and concerns about scientific validity. Yet this has moved forward into life-saving medical procedures, and it has had a phenomenal impact.

We are very early in our understanding of embryonic stem cells. It is not realistic to expect that we will immediately have new therapies. But ultimately, this is a science that if we turn our back on it now, we potentially turn our back on diseases for which we currently have no treatment.

Do you feel the incident with Dr Hwang Woo-Suk damaged the public’s perception of the field? (Dr Hwang claimed to have created several human embryonic stem cell lines from unfertilised human oocytes. The lines were later shown to be fabricated.)

Yes, I do. I think, certainly within the scientific community, the imperfections and foibles of us all are not something that is a great surprise. We do try to have ethical codes in place and the scientific process, certainly, means that this kind of activity will be discovered in a relatively short period of time.

But we are a field that attracts a particular interest, and scrutiny by the public, and appropriately so, and that is highly dependent on the public’s trust. And when someone who has claimed so much, so overtly defrauded all of us, then it really taints the deal. It brings everything into question.

Where do you expect embryonic stem cell research to be in ten years?

I expect we will move from very limited understanding of how these cells work to a more in-depth understanding that will enable us to guide them to become particular types of cells, and that we will understand ways to incorporate these cells into complex tissues.

I’d also hope that we will have a whole number of arrows in the quiver that represent drugs targeting the endogenous stem cells in the body. I hope that we will have a fundamentally different outlook on chronic diseases. That instead of trying to simply forestall inevitable decline, we can use stem cell biology to return people to function and improve the quality of their lives.

Despite the difficulties, could you see yourself working in another field?

Quite honestly, I can’t. This is an area of just such tremendous potential. Think about it; what are the areas of ongoing biological research where you can have an impact on a wide range of diseases that could really affect people’s lives, and also change people’s outlook towards illness? To me, this is it.


David T. Scadden is a professor of medicine at Harvard University and serves as co-director of the Harvard Stem Cell Initiative. Dr Scadden will be speaking at Advances in Healthcare, a conference held as part of Arab Health 2007. For more information, please visit
www.hmsdc.hms.harvard.edu

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