Paradigm shifts and unexpected catalysts
Over the past 40 years I’ve witnessed at least three major paradigm shifts in public awareness regarding the impact of biological research, all driven by unexpected catalysts, and all creating new business opportunities.
When I was in graduate school during the early 1980s we witnessed the emergence of the biotechnology industry, enabled by advances in recombinant DNA technology and the ability to study and manipulate biology at the molecular level. When I started graduate school in 1979 we actually knew very little about the molecular mechanisms underlying cancer. I remember being amazed at the pace of advances in our understanding of oncology during the 1980s, virtually all based on new techniques in molecular biological research. Although there is still much we do not understand about how cancer begins and progresses, or how to stop it, by 1985 the biological research community had advanced from having almost no understanding of cancer to possessing an incredible wealth of new knowledge, opening up many new avenues for investigation that might lead to effective interventions. That knowledge, and the technologies that were used to develop it, fueled the emergence of the biotech industry.
During the prior decade there had been significant public concern about the potential for misuse of recombinant DNA technology. The Asilomar Conference in 1975 established guidelines for safe research involving recombinant DNA. In 1977, Cambridge, MA became the first city in the world to regulate the manipulation of genetic material. In the midst of all this public debate and concern, venture and private equity investors began to recognize the potential positive impact of this new “bio technology”. Investors started pouring huge sums into new companies based primarily on ideas coming from brilliant scientists who agreed to get personally involved in the research that would lead to development of life changing new products.
Genentech’s IPO in 1980 was a landmark event covered in the Wall Street Journal, and over the subsequent 5-10 years we’d see many prominent biology professors get involved with biotechnology companies. I recall having a conversation with David Botstein at the time, as I was puzzled as to why some of the most respected biologists in the world were leaving tenured academic positions to work at new biotech companies, or staying in academics but engaging in corporate funded research in spite of raising concerns over possible conflict of interest. In the field of biology, work in industry had previously been viewed with disdain among those committed to the pursuit of knowledge. David’s explanation was quite simple: these new companies were offering to provide an order of magnitude more money to be spent on a project than could be obtained through NIH grants. This unprecedented level of financial support provided an opportunity to make critical scientific advances rapidly, and to see these discoveries have a meaningful impact on people’s lives.
This impact would play out right before our eyes, in a very visible manner. In 1982 the FDA approved the first consumer GMO product developed through genetic engineering: human insulin to treat diabetes. Between 1980 and 1990 I personally witnessed the transformation of the Kendall Square and Lechmere area in Cambridge, MA from a wasteland of old abandoned red brick factories, previously used for manufacturing goods ranging from textiles to candy, to an oasis of modern buildings and a nexus for new biotechnology companies and Pharma research that continues to grow today. Just as envisioned by the industry’s pioneers, new drugs, diagnostic tests, plant variants, and other products of biotechnology were being developed to change people’s lives for the better. There were still skeptics, people fundamentally opposed to genetically modified organisms (GMO), and some concerned that all of the money flowing into molecular biology research would detract from the pursuit on non-molecular biological research. Nonetheless, during that time the general public’s appreciation for technologies used in recombinant DNA research, and biotechnology broadly speaking, underwent a major paradigm shift. A new industry had come into being, and new opportunities seemed endless.
My second experience with an unexpected catalyst came roughly a decade later. In the late 1980s to early 1990s I had the opportunity to lead the PCR business for Perkin-Elmer and Applied Biosystems, who were early pioneers in developing and commercializing systems for performing PCR and applications thereof. Although we had a big impact in the world of biological research very quickly, during those early years the general public had no idea what the acronym “PCR” stood for. People I met in the street would shy away from conversations whenever I mentioned that I worked in the field of DNA analysis. That all changed in 1994 with the highly publicized trial of OJ Simpson who had been charged with the murders of his ex-wife Nicole Brown Simpson and her friend Ron Goldman.
The use of DNA evidence was a much discussed aspect of this case, as Simpson’s DNA was clearly at the crime scene. However, Simpson’s all-star team of attorneys cast doubt on whether the LA Police Department had properly handled and analyzed the samples. In 1995 a jury ultimately found Simpson not guilty for reasons that have now been covered in books and movies, and most likely had to do with systemic racism in the LAPD and a jury willing to find reasonable doubt in spite of the DNA evidence. Nonetheless, after that horrible double murder and ensuing trial, watched on television by more people worldwide than any prior trial, yet another paradigm shift had occurred in the general public’s appreciation for biology. The acronyms PCR and DNA had now become part of the common lexicon, and virtually everyone felt they knew something about DNA analysis. Over the following 25 years these technologies have been presented in countless books (fiction and non-fiction), television series and movies, all reflecting the fascination of the general public with the power of DNA analysis. During this same period the biotechnology industry flourished, with life science research and commercial applications growing to become a major sector of commerce worldwide.
My third experience with unexpected catalysts is happening right now. In 2021, following a year of living with the COVID19 pandemic, we are witnessing yet another period where powerful technology developed originally for use in molecular biology research has captured the attention of the general public. Just as was the case with recombinant DNA in the 1980s, and PCR in the 1990s, over the past 20 years the revolution in DNA sequencing and genome analysis has transformed biological research as well as R&D in fields ranging from pharmaceuticals, agriculture, food processing, environmental testing, and forensic analysis - but was still relatively unrecognized by the general public. During this period the cost and time involved in generating sequence information have dropped by orders of magnitude, and applications of this information have grown exponentially. Nonetheless, the pace of commercialization was held up by regulatory processes that, for example, made the typical time to develop a new drug roughly a decade. Our collective need to move rapidly in the face of the COVID19 pandemic changed all that - at least with respect to infectious disease research and efforts to detect and treat infection with SARS-CoV-2. As a result, there is now a great appreciation for the molecular biology of viruses, and the impact of genome sequencing technology in understanding the SARS-CoV-2 virus, and developing effective therapies for COVID19. What’s more, the general public is now aware and widely supportive of the expanded use of this technology to address other infectious diseases.
This impact of genome sequencing is discussed in an excellent article that was published in the New York Times (https://www.nytimes.com/interactive/2021/03/25/magazine/genome-sequencing-covid-variants.html). Quoting from that story:
“And unexpectedly, Covid-19 has proved to be the catalyst. “What the pandemic has done is accelerate the adoption of genomics into infectious disease by several years,” says deSouza, the Illumina chief executive. He also told me he believes that the pandemic has accelerated the adoption of genomics into society more broadly — suggesting that quietly, in the midst of chaos and a global catastrophe, the age of cheap, rapid sequencing has arrived.”
In parallel with this paradigm shift in public awareness of the power of genome analysis, another important factor has come into play. The stock market is once again going through a period of irrational exuberance, with sky high valuations for companies in spite of a pandemic that has taken over half a million American lives as of this writing, and created the worst economic disaster of my lifetime. Given the recent accumulation of capital by wealthy individuals and companies that were not negatively impacted by the pandemic, enormous amounts of money are now being invested in new companies that are applying the tools of molecular biology and genome analysis, particularly in healthcare, and notably in fighting infectious diseases and cancer. As a result, in spite of the sadness and depression that grips most of our country today, I expect that over the coming decade we will see substantial value creation as these investments bear fruit, along with new jobs, and a host of new therapies that will enable many of us to live healthier and happier lives. Unlike a year ago, nearly every person walking down the street now has some sense of what a virus is, and the topic of vaccines and antiviral drugs is in the news daily. What’s more, the general public appreciates the positive impact genome analysis and biotechnology can have, and as a result, sees a light at the end of this dark tunnel. Yet another paradigm shift has taken hold.
Of all of the new opportunities being pursued as a consequence of the COVID19 pandemic, there are a few that are quite obviously compelling, and which will likely be expedited. These include development and deployment of a global infectious disease surveillance system based on rapid genome analysis, and new antiviral drugs to enable early effective response to future pandemics. Think tanks have been formed at places such as the CDC, the White House Office of Science Technology and Policy, and privately led groups such as the Center for Strategic Risks, and the Rockefeller Foundation. There is broad support for implementing these capabilities in government and industry, and the general public recognizes the value of these tools for preventing future pandemics. So even as we still witness thousands of new infections every day, and breakthrough “escape” variants that lead to hot spots of infection, there is reason to be optimistic about our ability to end the current pandemic, and prevent a similar impact from bio threats that will emerge in the future. And once again, the influx of funding from governments, philanthropies and the private sector is likely to lead to a next wave of new products and services based on a better understanding of genome structure and function at the molecular level.
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