What if the Human Genome Project was paywalled?
In 1999 a Perkin-Elmer CEO envisioned a pay-for-access genome scheme that would have smothered two decades innovation in biotechnology and genomic medicine.
Today (April 25) is DNA Day, in recognition of Watson and Crick’s transformative 1953 paper describing the double helical structure of DNA. DNA Day also recognizes the completion of the first Human Genome Project fifty years later. And yesterday the Genetics Department at Washington University in St. Louis celebrated its 50th anniversary. One of the keynote speakers was Bob Waterston, our former department head who played a critical role in making the Human Genome Project happen. In his talk, Waterston recounted a chilling anecdote that illustrates what might have happened if the Human Genome Project turned out differently. Here’s a version of the anecdote from his recent memoir:
At one meeting in December 1999, called to explore possible collaboration [between the publicly-funded Human Genome Project and the private genomics company Celera], Tony White, the CEO of Perkin-Elmer, insisted that any combined genome-sequence product would only be available through the Celera website for years to come, and Celera would be the only source for any analyses, including annotations, that might come from joint efforts.
Many readers will remember that Craig Venter’s Celera was competing with the publicly-funded, international project to sequence the human genome. If you don’t work in biology, you may not appreciate just how disastrous it would have been if the CEO of Perkin-Elmer had gotten his way. Just about every aspect of biology has been transformed by genome sequencing–an analogy might be the impact that quantum mechanics has had on physics. Virtually no part of the broader field is untouched by the transformation. A key part of the genomic transformation of biology has to do with new tools that depend on access to reference genomes. Gene editing to cure disease, mRNA vaccines, ancient DNA studies, gut microbiome analysis, brain changes in autism, ecological studies–all of these depend on technologies that would either not exist or have been delayed for years if a private company had owned the human genome sequence.
Why? Because the technologies and computational methods that are so central to medical and biological research today depend heavily on aligning new DNA sequencing data to a reference genome sequence. These technologies aren’t only about ‘reading’ a DNA sequence–many of them use sequencing to measure critical molecular events, quantify the state of a cell, and to design new sequences that can be used in lab research and therapies. The Human Genome Project generated one of the first and most critical reference sequences. If every lab around the world had to pay Celera for access to that reference genome, much of the innovation that drives biology today would never have gotten off the ground.
This isn’t just speculation. We can make the direct comparison. Parts of the genome that were sequenced first by Celera locked up as its IP until the public project resequenced a freely available version. Comparing the Celera-first versus public-first parts of the genome, 2010 analysis found that “Celera's IP led to reductions in subsequent scientific research and product development on the order of 20 to 30 percent.”
Yesterday at our department’s 50th anniversary symposium, Bob Waterston told of how he and others pushed hard for open genome access at a now-famous 1996 meeting held at the Princess Hotel in Bermuda. At the time, the genome sequence of the nematode C. elegans was nearing completion and large-scale sequencing of the human genome was about to begin. What emerged are known as the Bermuda Principles, a central part of which was that new sequencing data would be shared immediately. Sequencing centers would upload their new sequencing data to an open database every day, thereby putting this data in the public domain. As one history of the Bermuda Principles puts it,
the Bermuda Principles addressed concerns about gene patents impeding scientific advancement, and were aspirational and flexible in implementation and justification. They endured as an archetype for how rapid data sharing could be realized and rationalized, and permitted adaptation to the needs of various scientific communities.
Biomedical science and the biotechnology industry would not be what they are today if those principles had not prevailed. Because they did prevail, patents on human genes and gene variants were already on their way to a natural death by the time the U.S. Supreme Court killed them for good in 2013.
Scientific knowledge is one of the most critical of what economists call public goods. Public goods are “non-rivalrous” and “non-excludable”. Non-rivalrous means one person’s use of a public good doesn’t diminish anyone’s ability to use it, and while non-excludable means it’s difficult to keep others from using it. Because of those features, private incentives to produce scientific knowledge are low, and economies then under-produce them, to everyone’s detriment. The Human Genome Project is a clear example of scientific knowledge as a public good. Public domain reference genomes can be freely used and reused by academic and industry labs to advance knowledge and invent new technologies and therapies. A 2013 report found that every $1 invested by the US government in the Human Genome Project led to a $141 addition to the US economy. Had Celera succeeded in paywalling the reference genome, it would have increased research costs and stifled innovation. But it also would have been difficult and time-consuming for Celera to enforce its monopoly, since bootleg sequence data could easily be shared and labs could (inefficiently and redundantly) resequence parts of the genome they cared about.
Publicly-funded work like this is the foundation on which nearly all of today’s technological innovation is built. It’s why we can now cure some fatal genetic diseases, treat cancer more effectively with better diagnoses, have a successful drug against obesity, shop at well-stocked grocery stores, text friends, stream movies, and fly to visit family on holidays. Had the human reference genome been locked up behind a paywall, our society would have been sicker and poorer for it.
For those interested in the early history of the technologies that made the Human Genome Project possible, I’ve transcribed a talk given by another former Genetics Department Head, Mark Johnston, who had a front row seat and made some critical contributions of his own. Click the link for the video and annotated transcript.