Abstract
The emergence of gene therapy as a scientific discipline in the 1990s stimulated a lot of public hype, a spike in investor speculation, and, ultimately, a number of clinical trials that were largely unsuccessful. In retrospect, we learned that these first-generation technologies were inadequate and the clinical targets were not well thought out (Wilson, 2009). However, the “promise” of this emerging new therapeutic platform captured the imagination of many stakeholders, which drove support. A confluence of events occurred in the late 1990s that contributed to a crescendo of investment in the field that was followed by an equally spectacular and precipitous decline. A litany of scientific milestones was achieved in preclinical models, which together with the initiation of clinical trials, fueled hope for imminent and broad-based success. This coincided with a surge in investment in technology-based companies, led by those focused on internet businesses; not far behind, however, was interest in biotechnology companies, including those working on cell and gene therapies. This all crashed at the turn of the century. It became clear that the technical challenges of successful cell and gene therapy were much more daunting than originally envisioned: preclinical success did not translate to clinical success and several tragic and highly publicized adverse events occurred in clinical trials (Hacein-Bey-Abina et al., 2008; Raper et al., 2003). The bottom line was that the enthusiasm and hype exceeded what the science could support. Simultaneously, we witnessed a dramatic withdrawal of investment in internet and biotechnology-based businesses in what has been called the bursting of the dot.com bubble. A bubble of this nature is defined as a self-perpetuating increase in share prices of an industry beyond its actual value followed by an eventual and often acute drop in value. Yale economist Robert Shiller refers to the psychology of a stock market bubble as “irrational exuberance” (Shiller, 2005). While there are admittedly some superficial similarities to the frothy atmosphere that existed in the mid- to late 1990s in this space, I contend that the current state of affairs in cell and gene therapy is very different from what was in place when the bubble burst in 2000.
During the last decade, research in the basic science of gene therapy continued at a modest pace through mostly government and private foundation investments. This resulted in new and substantially improved technology platforms for transferring cells and genes into humans (Grieger and Samulski, 2012; Segura et al., 2013). The community also became smarter in selecting clinical targets for early demonstration of success. Renewed interest of the biopharmaceutical industry in orphan diseases has helped, since many of these diseases are ripe for early demonstration of clinical success. With this as a foundation, indisputable success in the clinic was finally achieved (Maguire et al., 2008; Nathwani et al., 2011; Grupp et al., 2013), including the first commercial approval for a gene therapy product in the West (Bryant et al., 2013), leading to recognition by even the naysayers that “gene therapy is back.” Large-scale capital investments, however, did not immediately follow these critical clinical successes due, in part, to the recession which began in 2008 and to lingering doubts in the minds of investors burned by the previous bubble collapse. However, once the markets started to improve and positive clinical results continued to be reported by many different groups, investments in gene and cell therapies picked up and have not turned back. Many still believe that we have simply entered into a new bubble cycle, although it is anyone's guess as to how long it will last. One key difference between the current environment and the dot.com bubble is that the scientific foundation of the field is much more solid in 2013 than it was in the year 2000. This bodes well for the long-term viability of gene therapy even if the currently high levels of exuberance begin to wane over time.
What does this mean for stakeholders in the cell and gene therapy communities? Well, for a start, these much-needed investments will jump-start clinical development programs that are ready for prime time. The chances are good that successful commercial products will emerge. One urgent question is, who will actually do all the work? The reduced financial and moral support for gene therapy since the dot.com bubble collapse drove senior scientists away and, most troubling, discouraged young scientists from entering the field. The need for talent was evident at the last annual meeting of the American Society of Gene and Cell Therapy, where biopharmaceutical recruiters were scouring the hallways of the conference center. Most importantly, we need to recognize that this is a new beginning rather than the end game in order to move beyond some of the missteps of the past and stay focused on progressing toward safe and effective cell and gene therapies.
Footnotes
Author Disclosure Statement
J. Wilson is a founder of, consultant to, and grant recipient of several gene therapy biotechnology companies including ReGenX Biosciences. He is an inventor on a number of gene therapy patents.