Alternate facts and Australian stem cell research

02 February 2017
By Martin Pera
Former Program Leader of Stem Cells Australia

In The Australian of 30 January, Angela Shanahan did her part to welcome in the Trump era with a tirade replete with a bizarre collection of “alternate facts” regarding stem cell research.  The piece was ostensibly a reply to media criticism of the public relations campaign in support of the award of Australian of the Year to stem cell researcher Alan Mackay-Sim. However, Shanahan’s article swiftly morphed into an incompetent rehash of tired old arguments concerning the use of human embryos in stem cell research.  The suppositions and conclusions in the article are at best ill-informed and out of date, and at worst complete misrepresentations of reality. They invite refutation.

Research conducted by Professor Alan Trounson and his associates (full disclosure-I was one of those associates) was at the forefront of the human embryonic stem cell field, and Australian scientists played a key role in the establishment and dissemination of this important technology internationally.  

Today, as an outgrowth of these pioneering discoveries, there are clinical trials progressing all over the world based on products derived from human embryonic stem cells, for conditions ranging from macular degeneration (a common form of blindness in the aging population), Type I diabetes, spinal cord injury, myocardial infarction, to Parkinson’s disease, with more studies rolling out on a regular basis.  Appropriately, these are early stage investigations.  As with the development of any new drug, medical device or surgical procedure, some of these stem cell interventions will fail in their first iteration, and will require much further study and refinement before they become the standard of care for any condition.

Importantly though, all of this work is based on science that has stood up to peer review and extensive scrutiny by regulatory authorities, and the clinical trials are being conducted in a rigorous fashion with full ethical oversight.  This stands in striking contrast to many so-called stem cell treatments currently on offer here and elsewhere outside of any regulatory oversight using products derived from adult tissues like fat. We do know that at least thus far, these embryonic stem cell products appear to be safe in man. 

Equally significant but less visible is the quiet revolution in research empowered by the use of pluripotent stem cell derivatives in human genetics, disease modelling and drug development. The effects of genes predisposing to Alzheimer’s disease are currently modelled in human brain organoids developed in a petri dish from pluripotent stem cells. Heart muscle cells made from embryonic stem cells are now employed in the pharmaceutical industry to assess potential toxic effects of drugs on cardiac rhythm. Nervous system progenitors made from pluripotent stem cells are providing critical insight into the effects of the Zika virus on the developing human brain. The application of embryonic stem cells in neuroscience and cardiovascular medicine can be traced directly back to discoveries made by Australian stem cell researchers and their collaborators. 

The knowledge base acquired through basic research on the biology of human embryonic stem cells since the late 1990s has had another very important consequence.  It is now possible to develop pluripotent stem cells directly from adult tissues, through the process of cell reprogramming. This seminal discovery of induced pluripotent stem cells won Shinya Yamanaka the Nobel Prize for Physiology or Medicine in 2012.

Though embryonic stem cells remain a critical platform for ongoing clinical studies, and as a gold standard for benchmarking research, it is gradually becoming apparent that induced pluripotent stem cells derived from adult tissues are probably bioequivalent to the embryo-derived cells.  It is likely that these induced pluripotent stem cells will come to dominate the field in the future.  This approach offers a genuine alternative to the use of embryonic stem cells, but as Professor Yamanaka acknowledged in his Nobel lecture, the advances could not have been achieved without essential background studies on stem cells derived from human embryos. 

Shanahan’s piece is also disingenuous in its representation of the Australian funding and regulatory environment in stem cell research.  Embryonic stem cell studies represented only a portion of the research portfolio of the Australian Stem Cell Centre, which supported successful research into adult stem cells in brain, bone marrow, lung, and other tissues.  The continued support from the Australian Research Council of research in this field, via the Australian Stem Cell Centre and more latterly Stem Cells Australia, has enabled a number of very significant advances in basic and applied research with both adult and embryonic cells. 

Some recent examples include Professor Bob Graham’s discovery of the ability of the adult heart to undergo regeneration, Professor Lars Nielsen’s development of a cell culture platform to produce white blood cells for treatment of cancer patients, Professor Melissa Little’s striking demonstration of how to grow a human kidney from pluripotent stem cells in the laboratory, and the report from the team of Dr. Elizabeth Ng and Professors Ed Stanley and Andrew Elefanty describing the generation of blood stem cells from human pluripotent stem cells. These are all seminal observations published in internationally recognised, high impact, peer-reviewed journals, all with profound implications for the understanding and treatment of human disease, and all supported over many years through the vision of the Australian Research Council. 

Shanahan discusses the Australian stem cell legislation as though it was an ill-considered and morally bankrupt set of edicts forced overnight onto a gullible public by manipulative and self-serving scientists. On the contrary, our Australian stem cell legislation was the product of extended discussion and debate engaging a very broad spectrum of public opinion, followed up by a thorough independent review in 2005 and revision by amendment in 2006. 

Far from allowing unrestricted experimentation, our laws demand that any research involving human embryos be subject to stringent ethical oversight on a local and national level, and that the researchers demonstrate that the aims of their study absolutely require the use of human embryos to achieve their goals.

As research using pluripotent stem cells (derived from embryos or adult tissues) advances, new and challenging ethical questions will continue to arise. To cite a few examples, we as a society will face important decisions ahead concerning the use of pluripotent stem cells for the production and use of human sperm and eggs in the laboratory, the modelling of human embryo development in a culture dish, and the incorporation of stem cells into human-animal chimeras. 

The scientific community will continue to play a responsible role in communicating openly and accurately the potential benefits of such research, as well as its limitations and ethical implications. However, we do so in the face of a political environment that increasingly encourages the public to reject sound scientific enquiry and to instead embrace disinformation.  As responsible scientists, we will continue to hold the media to account when it steers public discourse towards the whirlpool of ignorance.