I’m curious. Are you?

April 5, 2009 by Kevin Graham

Over the past decade there has been increasing pressure put on biomedical researchers to justify their projects by establishing short term timelines to produce technological or clinical applications. The drive for applicable or “translational” research is in many ways perfectly reasonable. For publically funded research there are limited amounts of tax dollars to go around, and the public is looking for a return on their investment. Also, new technological developments are an economic advantage for the country or region that discovers and brings them to market, so there is a huge financial incentive.
The desire for research that is directly applicable in the short term is also driven by researchers themselves. Translational research is no doubt extremely satisfying, seeing an idea progress from the lab bench to a patient or market place is a very tangible way of evaluating your success. Another contributing factor is that in order to highlight the importance of research to society research is almost always framed in terms of the human health issues that it might solve. As stem cell researchers we are certainly guilty of this. Why study neural stem cells? To use these cells to repair brain injury of course. Why study pancreatic stem cells? To combat diabetes of course.

Although in both of these examples the rationale behind the research, treatment of human disease, is certainly true, the constant demand to justify research projects in terms of their directly applicable endpoints has become a very real threat to basic biomedical research. For decades, if not centuries, we have relied on basic scientific curiosity, a desire to understand the fundamentals of the world around us and of life itself, to provide the inspiration for research projects. Over this time we have come to realize that great medical and technological achievements springboard off of years of basic research, research that is often done with no awareness or indication of the payoff that will follow in the years to come.

Despite the well established link between basic and eventual translational research there has been a creeping negativity and even contempt towards researchers who engage in the most basic of biomedical research studies. The term “academic research” (commonly defined as research done without a practical purpose or intention) has become a term of derision.

Perhaps then we need a reminder of the great importance of so-called “academic research”. I found this one publication from the Journal of Biological Chemistry published in 1962. The title is: “Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal.” Why did the researchers do this project? Were they investigating tooth development in the hope of one day being able to regenerate adult teeth after facial trauma or tooth decay? Perhaps. But perhaps their reasoning was simply that they were just curious about what this protein was and what it did. I wonder if during the 1960’s people would have made the argument that the tight economic times necessitated that projects like this would have to be cancelled. After all it seems somewhat pointless or “academic” don’t you think?

Turns out this protein was subjected to further scrutiny over the years, eventually being named epidermal growth factor (EGF). EGF was one of the first growth factors to be isolated, one of a family of factors later found to be involved in processes such as cell division, cell survival and cell movement. This work set the foundation for the subsequent discovery that many forms of cancer showed extremely high levels of the receptor for EGF, making them dependent on its activity. By the early 1990’s compounds that inhibit the EGF pathway were being discovered and put through the clinical trials process. In 2003 the first compound was approved by the FDA for therapeutic use against a specific form of lung cancer, and since this time compounds targeting EGF or similar pathways have entered clinical trials and are now used in the treatment of many different types of cancer.

This example is one of many similar stories, in truth the development of nearly every medical treatment can be traced back to basic research that was undertaken for a completely unrelated purpose, or perhaps for no purpose other than pure scientific curiosity.

As a stem cell researcher in a lab which is actively investigating the function of both normal neural stem cells and brain tumor stem cells, I have generally framed the purpose for my research in terms of the search for a novel cancer treatment. In our lab we have projects that could be classified as basic fundamental research; where are neural stem cells located, how many are there, how can we distinguish them, how do they decide when to divide and when to stop? We also have projects that would fit under the term “translational research”, such screening projects to look for new compounds and new pathways to target brain tumor stem cells.

My personal project involves normal neural stem cells, an attempt to discover how in one division they can produce two progeny cells with vastly different identities. I initially approached this question with the idea of applying this knowledge to brain tumor stem cells. Perhaps being armed with an understanding of how normal neural stem cells make these decisions we could find new avenues to attack and if not kill the brain tumor stem cells, at least influence their decisions to produce a more benign cell type.

Although the motivation for my research remains in the context of finding a novel treatment for brain cancer, in light of the historical twists and turns of research discoveries I have to admit that I don’t really know how the knowledge that I acquire will eventually get used. Likely the knowledge gained from my work will add to what others find over the next 5-10 years, clarifying the pathways and processes that neural stem cells use to produce new neurons in the brain. This knowledge might be applied to cancer research but it is equally likely that it will instead be used to design a treatment for Parkinson’s or to repair areas of the brain damaged after a stroke. Or someone might draw a connection between what I find in neural stem cells and what they find in cardiac stem cells and the research may take off in an entirely new direction. Or as in the example above, perhaps the eventual application of this research is so distinct from my original quest that I can’t even envision what it might be right now.

So in light of this uncertainty, when asked about why I do the research I do, maybe I should cease to describe my research in terms of cancer treatment. In support of the principles and historical success of basic research I should be proud to simply say “because I’m curious”.

Written by Kevin Graham · Filed Under Home Blog 1, Point of View, Research

Comments

One Response to “I’m curious. Are you?”

Alexey on April 21st, 2009 10:32 pm

Hi Kevin,
thank you for posting this,
I was inspired by your post and cited you and express some of my thoughts here -
http://bit.ly/V8bwn

Got something to say?

By using this site you agree to the Connecting for Kids terms of use. Click here to review the Terms of Use guidelines for this site.

Rett Syndrome and induced Pluripotent Stem cells goes “Green”

June 17, 2009 by Aaron Cheung

Stem cell researchers at The Hospital for Sick Children have now devised a method, reported in the scientific journal Nature Methods, that will facilitate the generation of induced Pluripotent Stem (iPS) cells. I have previously blogged about the promise of iPS cells (see related articles). iPS cells are cells which have been reprogrammed from a differentiated somatic cell (such as your skin cells) to a pluripotent stem cell (like an embryonic stem cell, only that you don’t need to use embryos!). The generation of iPS cells is inherently very rare which occurs at a frequency of about 0.01% meaning you can generate about one iPS cell line out of hundred thousand cells. Out of which, many lines fail to satisfy the different rigorous tests necessary to be given the prestigious name of “iPS cell”.

A group led by Dr. James Ellis, and lead author Dr. Akitsu Hotta, at The Hospital for Sick Children has generated a reporter, named EOS, that will facilitate the generation of iPS cells for both mouse and human. The reporter has DNA elements (called promoters) that will drive the expression of a fluorescent protein (GFP) and an antibiotic resistance gene (puromycin) that will only turn on in pluripotent stem cells, but remain off in differentiated cells. Therefore, scientists can now generate iPS cells from different sources and the iPS cells will literally “light up with a green colour” once reprogramming has been achieved. Furthermore, by adding puromycin to your culture, it will keep the iPS cells in a pluripotent state as iPS cells will normally spontaneously differentiate.

To demonstrate the applicability of EOS, Ellis also derived iPS cells from patients who have a neurodevelopmental disorder called Rett Syndrome. Rett Syndrome is an Autism Spectrum Disorder which affects almost exclusively females at an incidence of 1 in 10,000 and is one of the leading causes of mental retardation in girls. These Rett Syndrome iPS cells were green when placed under a fluorescent microscope and Ellis demonstrated that neurons can be generated from these Rett Syndrome iPS cells, the cell type affected in Rett Syndrome.

In conclusion, the EOS reporter will facilitate the generation of iPS and will be particularly useful for new labs going into this rapidly developing field. Furthermore, Rett Syndrome iPS cells that were also generated in this study will be invaluable for future drug screens that may be beneficial to those with Rett Syndrome.

Article:
Hotta, A. et al. Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nature Methods 6, 370–376 (2009).

RSS |