Induced Pluripotent Stem Cells: An Emerging Technology Platform and the Gartner Hype Cycle

Figure 1. The hype cycle of innovation.

Adapted from [9].

Undoubtedly, the science of induced pluripotent stem (iPS) cells is moving forward at breakneck speed; however, with this new knowledge comes important responsibilities for the regenerative medicine community, not least the portrayal of hype and hope. This month‘s Regenerative Medicine features an interview with Andras Nagy (Samuel Lunenfeld Research Institute, Canada) [1] and an editorial by Timothy Nelson and Andre Terzic (Mayo Clinic, USA) [2], both of which demonstrate the need for pragmatism tempered with caution. The challenge is how to balance enthusiasm with reality for at least a decade whilst iPS cell research and translation hopefully progress through all the necessary steps in order to produce safe, effective and affordable therapies. The glamour of the research breakthroughs will immutably turn into the seemingly endless grind of product development and regulatory challenges. Therefore, appropriate public expectation for both iPS cell progress and inevitable setbacks will greatly help everyone, including scientists, regen companies, funders and most of all patients.

Hype or hope, where is iPS cell technology today? Not a single week seems to go by without reports of further breakthroughs on the iPS cell technology front. These reports are not just original papers in leading scientific journals but also articles in the regular media: web, television and press. Nor are the popular press alone in their enthusiasm; hallowed journals including Science have openly declared iPS cells as the “Breakthrough of the Year” [3]. Even President Obama flagged them at the signing of the recent Stem Cell Executive Order as, “…groundbreaking work to convert ordinary human cells into ones that resemble embryonic stem cells” [101]. Everyone wants to be in on the latest stem cell action and iPS cells are no exception. However, perhaps we should have a sense of déjà vu, after all, the regenerative medicine industry has been here before, albeit under the earlier guise of ‘tissue engineering‘ [4], where hype and hope quickly gave way to a disastrous collapse of the fledgling industry when inevitably reality set in [5]. To quote one of the pioneers and leading tissue engineer, Robert Nerem (Georgia Tech, GA, USA), “To date, tissue engineering has been over-promised and under-delivered” [6]. Failure to deliver per se was not the major cause of the downfall of tissue engineering. Indeed, a number of their products received US FDA approval and a couple have since been deployed to treat over a third of a million patients [102]. It was failure to deliver at the totally unrealistic level that was expected by the investors and the public that burst the bubble. A total mismatch between the achievable and the tsunami of hype. Tissue-engineered skin was undoubtedly a major achievement and yet at the time it was dwarfed by the promise of major organs including entire lab-grown hearts that appeared to be tantalizingly close [7]. Now is therefore the time to quickly learn from the past and manage the hype and unreasonable expectations that are beginning to surround the emerging technology of iPS cells before it is once again too late. This will require far greater public understanding rather than mere awareness plus a trusted industry voice [8]. However, successful preparation ideally requires an ability to be able to predict the future. Fortunately, new technologies very early in their lifecycle seem to follow similar trends with respect to their hype profile. Understand the likely future trend for iPS cells, and we just might be able to sensibly manage public expectation. The science is definitely very exciting; however, the public quite rightly want cures for patients – two events that are years, if not more likely decades, apart. Maintaining essential public support over this lengthy period, including ensuring continuous funding, is therefore crucial if the promise of iPS cells and other ground-breaking new regenerative medicine technologies are to be properly realized.

To be commercially successful, a basic discovery has to be translated into real products that are then embraced by the market. In the case of iPS cell technology, the public is already eagerly buying into the dream of future cures. The delivery timescale is clearly uncertain, however, hype and reality distort individual stakeholder perspectives quite often by many years. For example, the amazing level of confusion that exists over the word ‘translation‘, ranging from mouse model translation to mass manufacturing translation, is becoming legend. At every point along this route the public will have an opinion ranging from inflated enthusiasm, disillusionment and finally satisfaction. All are measures of the degree of hype. This hype cycle for emerging technology platforms has been demonstrated to follow a regular pattern described by Gartner (Stamford, CT, USA) [9]. The overall shape of the hype cycle remains fairly constant over a great many different emerging technology platforms, ranging from major innovations in biotech to information technology and e-commerce. However, depending upon the exact technology, the duration and degree of public visibility vary. Figure 1 is a graphical representation of the Gartner hype cycle [9]. Knowing where a particular technology is positioned on this curve is an invaluable planning aid and therefore could potentially manage unreasonable expectation.

The curve is based on an understanding of the maturity and evolution of a technology very early in its lifecycle – exactly where iPS cells are today and for that matter all of regenerative medicine, albeit at very different positions along the curve. The hype cycle characterizes the typical progression of an emerging technology from excessive and unjustified enthusiasm through a period of disillusionment followed by an eventual understanding of the technology‘s relevance and role to society [9]. The ‘Peak of Inflated Expectation‘ typically occurs when there is a frenzy of publicity, but because of the very early stage of the development cycle, the performance of the underlying platform technology is still poor. Hence, there can be no real benefits. Because the technology fails to live up to overinflated expectation it is rapidly discredited with negative publicity and spirals into the ‘Trough of Disillusionment‘ [9]. However, for a technology with proven science and a clear market if successful, the Trough of Disillusionment is merely an over-reaction just like the proceeding Peak of Inflated Expectation. All the while, the science is maturing and the underlying technology is moving forward, albeit at a pace that is far slower than the perceived rate that followed the initial ‘Technology Trigger‘. By mastering hype and hope levels, the depth and width of the Trough of Disillusionment are in our hands. A quick look back in time and examples rapidly spring to mind. Take the internet, the excessive hype of the dot-com boom and then bust, a period in the doldrums and then the emergence of today‘s highly successful and sustainable Web 2.0. Closer to home, tissue engineering and somatic cell therapy followed exactly the same pattern with both now starting to climb the ‘Slope of Enlightenment‘ having rapidly fallen into the Trough of Disillusionment during 2001–2002 [4].

The biggest challenge for the whole of biotechnology, including regen, is the fact that, “biotech stocks sell on the ‘story‘ of their promising science and the products that likely will evolve from it” [10]. Telling the story to retain private investors and public confidence (since the majority of the funding is from government or state) but not overselling is clearly an essential art.

Where is iPS cell technology today? The ‘Technology Trigger‘ was the initial discovery in 2006 by Shinya Yamanaka in mice and then reinforced a year later when Yamanaka and Jamie Thomson independently demonstrated the approach in man [11]. Clearly the technology is not yet sliding into the Trough of Disillusionment – there are far too many positive news stories and commercial activities, for example the formation of an iPS cell-dedicated biotech company iZumi Bio (Mountain View, CA, USA) by seasoned venture capitalists [12]. The technology is therefore either still on the rise (most likely) or at the peak. Indeed, there is real concern that iPS cells could fall victim to the same hype that plagued the early days of human embryonic stem cell research [12,13] but at least human embryonic stem cell technology is now firmly inching its way out of the Trough, including a successful FDA Investigational New Drug filing by Geron Corporation (Menlo Park, CA, USA) [14] and big Pharma actively starting to engage, for example Pfizer Regenerative Medicine and the UCL London Project to Cure Blindness [15].

The Gartner hype cycle is a simple but reliable tool for understanding the inevitable trend of excitement and disillusionment that surrounds all emerging technologies. Beware the Peak of Inflated Expectation as serious stakeholders will shy away in order not to get caught up in the surrounding hype and tidal wave of unrealistic expectation. However, once in the Trough of Disillusionment, the real opportunities will slowly start to emerge [9]. So, why should the iPS cell story be any different?

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.