Why Are We Celebrating the Reprogramming of Adult Cells?

by Theresa A. Deisher, Ave Maria Biotechnology Company, Research and Development Director

The recent publications about the ability to reprogram adult skin cells to become virtually identical to embryonic stem cells has been hailed by pro-life groups as a ‘Moral Victory’.  Initially, I believed the work to be ‘Moral’, while at the same time I found the term ‘Victory’ perplexing.

I stated publicly on ‘Conversations with Fr. Bob’, a Seattle, WA talk radio show taped December 3, 2007, that I saw “no moral issues with the technique” of adult cell reprogramming.  Unfortunately, I learned later that the published works cannot be considered ‘Moral’.  The ability to transform adult cells into embryonic stem cells could be moral, however, a close inspection of the two published papers revealed that cells from an electively aborted fetus were used in the work, and therefore it cannot be considered moral.

In order to transform adult cells into embryonic cells, the researchers introduced four genes essential for ‘embryonic stem cell character’ into the adult cells.  First, the researchers had to make the genes and virus materials needed to transform the adult cells.  Both researchers used versions of the HEK 293 cell to do this.  This is a cell, the Human Embryonic Kidney 293 cell, used commonly in biomedical research for DNA (gene) and virus production.  I was informed quite recently that the 293 cells were produced from an electively aborted fetus.  I was able to verify that easily.  The term embryonic in the name is misleading.

The genes and virus material used to transform the adult cells could have readily been produced by any number of other cell lines available for this purpose, such as HeLa, COS or CHO cells, none of which come from electively aborted fetuses.

For too many years, scientists like me have not questioned the source of cell lines used commonly in biomedical research and drug development.  Silence is acquiescence, and acquiescence leads to further abuse.  Today, the widespread use of fresh aborted fetal tissue in biomedical research and drug discovery may be the result of those years of silence.

Why have we been silent when there are alternatives to cells such as the HEK 293, made from an aborted fetus?  Blockbuster drugs were developed, biomedical research made huge strides, and health care was transformed in the 21st century without the use of morally unacceptable cell lines and tissues.  Within the past decade, the use of aborted fetal cell lines and tissues in drug discovery has become pervasive.  Interestingly, Biotech Industry News recently published the fact that the lowest number of annual new drug approvals ever occurred in 2006. “The number of real innovations for diseases that never had a treatment before or drugs that are really better, there is just not much there. There just are not a lot of innovations lately” (Jordan, Newark Star-Ledger, 1/4/08).  Obviously, scientific abrogation of morals has not yielded greater medical advances for humanity.

As we have discussed, if the genes and virus needed to transform the adult cells were made using a morally licit cell line, which could easily be done, then this breakthrough adult reprogramming would be ‘Moral’.  However, what is the ‘Victory’ here?

The reprogramming has been described by Robert Lanza of Advanced Cell Technology, an embryonic stem cell company with a history of making and then retracting research claims, as “It’s a bit like learning how to turn lead into gold.”  One does not need to be an alchemist to know that it is not possible to turn lead into gold.  In this case, the description might more aptly be that these scientists have found a way to turn bread into garbage.

Embryonic stem cells were first isolated from mice in 1980.  Since that time there have been no diseases treated, no people helped by these cells, despite the hundreds of millions of dollars that have been poured into this area of research.  In contrast, adult stem cells were first identified in mice in the late 1990s, and already, in 2008, many different diseases have been treated and thousands of people have been helped.  Embryonic stem cells have not been able to treat disease or help people because they form fatal tumors when given to adults.  The very essence of being embryonic stem cells is what causes the fatal tumor formation.  We can say this because fatal tumor formation (teratoma formation) is the gold standard used to determine whether a cell is truly an embryonic stem cell or not.  Reprogrammed adult cells display this embryonic characteristic: they form fatal tumors in adults.

A recent publication in ScienceExpress on February 14, 2008 by Yamanaka’s group in Japan has been widely touted as a demonstration that reprogrammed adult cells, iPS, do not necessarily form tumors.  Unfortunately, that claim has been made without a careful reading of this recent paper.  The ScienceExpress paper confirms the pluripotency of their iPS cells by demonstrating the tumor forming nature of their cells.  Tumors formed in 100% of adult mice who had the iPS injected into their flanks:

“We then tranplanted iPS-Hep and iPS-Stm cells (1 x 106 cells) subcutaneously into the hind flanks of nude mice (table S1). Four weeks after transplantation, all mice developed tumors (emphasis added) containing various tissues of the three germ lines, including neural tissues, muscle, cartilage, and gut-like epithelial tissues (fig. S3). This demonstrated that the iPSHep and iPS-Stm cells are pluripotent.”

The authors then went on to create chimeric mice by injecting the iPS cells into a blastocyst,  the stage of development after the fertilized zygote.  The chimeric blastocysts were then implanted into a receptive female mouse and pups were born.  When the iPS cells contributed to the germ line, offspring of these germ line transmitters were monitored for spontaneous tumor formation.

The authors report the absence of tumor formation in these chimeric mice.  The public should beware!  This is not a model for tumor formation of iPS injected into adults, which is how these cells would be used therapeutically.  The model for tumor formation in adults is quoted above, and ALL of the mice injected with iPS cells formed tumors.  Tumors such as the ones observed in the adult mice would be fatal in if they formed in your heart, brain, liver, lungs, kidneys, pancreas or other vital organs.

In essence, we are now able to take a perfectly good skin cell, or hepatocyte, or stomach cell and turn it into a fatal tumor-forming cell.  Is this really a ‘Victory’?

When I evaluate new therapies I apply four criteria: is the therapy 1) safe, 2) effective, 3) affordable and 4) ethical.  Neither embryonic stem cells nor adult reprogrammed cells meet all those criteria.  These cells are not safe; they form fatal tumors in adults.  Additionally, adult reprogrammed cells require transformation with viruses, another safety hazard.  One need only read the clinical history of gene therapy, and the deaths associated with it, to hesitate before lauding an advance that requires 4 gene therapies.  While adult reprogrammed cells could be ethical, as discussed earlier, this won’t be cheap, so it doesn’t meet the affordability criteria.  In distinct contrast, adult stem cell therapies, particularly those based on bone marrow stem cells, are safe, effective, affordable and ethical.

So why then this seeming U.S. obsession with embryonic stem cell attributes?  We all must ask ourselves this question.  What is the goal with stem cell research?  To treat human disease?  Then we should all be obsessed with adult stem cells, which are delivering on this promise.  Is it possible that the allure of embryonic stem cell attributes lies beyond treating human disease?  Subconsciously, could we as a society be drawn to embryonic properties like we are to ‘staying young’, to ‘living longer’?  Embryonic stem cell attributes are not the fountain of youth we might long for.  They are fatal tumor forming cells that no one would wish for a loved one with a grievous illness.

Dr. Deisher is a co-founder of and Research and Development Director for Ave Maria Biotechnology Company, dedicated to the discovery, development, and commercialization of safe, effective, affordable, and ethical human therapeutics.  Dr. Deisher, an internationally renowned expert in the field of adult stem cell therapies and regenerative medicine, has over 17 years of experience in scientific and corporate leadership positions involving research, discovery, production and commercialization of human therapeutics.  Dr. Deisher’s penchant for groundbreaking scientific discovery and her distinguished scientific research has resulted in 23 patents issued in her name.  She has published numerous scientific manuscripts and is a frequent invited lecturer and guest speaker in the area of stem cell technology and regenerative medicine.

Throughout her career, Dr. Deisher has been recruited by some of the country’s top biotechnology companies, including Genentech, Repligen, ZymoGenetics, Immunex and Amgen.  She has managed and mentored undergraduate honors students, post-doctoral fellows, scientific executives and over 20 research assistants/scientists at all levels of responsibility. Dr. Deisher graduated with honors and distinction from Stanford University, and obtained her Ph.D. in Molecular and Cellular Physiology from the Department of Molecular and Cellular Physiology, Stanford University.

Dr. Deisher was the first person to identify and patent stem cells from the adult heart, including what are now called ‘very small embryonic-like stem cells’.  Within the field of regenerative medicine, Dr. Deisher is also a patented inventor of the most potent mesenchymal growth factor identified and of the use of cytokines to mobilize adult embryoid-like cells.

Dr Deisher can be reached at: