Oscillator

Last week's issue of Nature focused on the progress (or lack thereof) in genomics and related fields since the Human Genome Project (HGP) was completed ten years ago. In many ways, the era of genomics has yet to fulfill many of the promises made twenty years ago, but the investment in science and technology has at the same time made a valuable impact on many fields in basic science. Understanding this recent history of the genomics bubble is crucial to how we approach current science and technology investments in areas such as personal genomics and importantly, synthetic biology.

In a fascinating paper reviewed by Philip Ball in one of the issue's columns, researchers from Swiss business schools analyze the interactions and investments between the public and private interests involved in the push to sequence the human genome in the late 1980's and early 1990's. They hypothesize that the HGP constitutes a "social bubble":

According to the social bubble hypothesis, the social interactions between enthusiastic supporters weave a network of reinforcing feedbacks that lead to widespread endorsement and extraordinary commitment by those involved in the project. The term "bubble" is borrowed from the financial economic literature, in which a bubble is defined as a transient appreciation of prices above fundamental value, resulting from excessive expectations of future capital gain.

This "exuberant over-optimism," they argue, is what allowed such a risky project to be funded at such a large scale in the first place. Private interests typically do not invest in projects where the proposed benefits will come decades down the line, as with the HGP (and likely still decades from now). The competition between private interests, which sought to commercialize and capitalize what was fundamentally a basic research project, and government funded researchers drove much of the development of sequencing technology but also complicated what people saw as the motivations for large-scale scientific projects and furthered the hype surrounding genomic technology. This privatizing and commercializing of scientific knowledge and parts of our bodies is still hugely important. Myriad Genetics Inc. was founded in 1991 at the start of the HGP to develop cancer therapies and diagnostics based on genomic science. Just last week, Myriad's patents on the sequences of genes involved in a certain form of familial breast cancer were invalidated after a long court battle.

Despite widespread patenting of genes and some tangible breakthroughs in diagnostics and personally tailored medicines, the Human Genome Project has largely failed to produce the real changes to medicine it originally promised. Instead of simply collecting more data that could neatly be fit into the boxes set out for it by past research, much of genomics instead has opened up a new and unprecedented understanding (or at least acknowledgment) of complexity in biological systems. For me, this complexity is what makes biology exciting and an interesting and important field to study. I was taking AP Biology just as the HGP bubble was beginning to burst, and finishing my undergraduate degree in molecular biology as departments in Systems Biology were being founded.

Indeed, systems and synthetic biology are the heirs of the genome projects begun twenty years ago. Synthetic biology really began in its current form around 2000, just as the human genome was being published. Synthetic biologists take sequence information from these large-scale bioinformatics projects and turn them back into things: molecules that are replicated and controlled, sequences that are read by living cells, translated into protein molecules and observable cellular behaviors. Synthetic biology has taken on some of the goals of the original HGP, particularly the goal to create a repository of cloned gene sequences, and has re-grounded some of the information-focused technology back into real biology.

However, synthetic biology can also be described by a social bubble, with outsized expectations and promises of what synthetic biology can deliver on investor time-scales. Some of the players of the public/private competition and hype machine are even the same. Craig Venter was a driver of the race to sequence the genome, founding a non-profit research institute (the Institute for Genomic Research) as well as a for-profit company (Celera Genomics) that aimed to commercialize products, patent genes, and sell information to researchers. Today, Venter runs the J. Craig Venter Institute, a non-profit entity that sequences and synthesizes billions of base pairs of DNA for research in synthetic biology and genomics, as well as the for-profit Synthetic Genomics. His programs consistently drive significant technological development in DNA sequencing and synthesis, while at the same time overhyping the potential pay-offs of such technology as well as creating many conflicts of interest between the basic research community and private interests.

Conflict, or at least tension, between private and public interests has been at the heart of synthetic biology since the beginning. The goals of synthetic biology are less amenable to a race mentality, however--which may partly explain why "synthetic life" is taking longer than expected (although it's also hard, so leave Craig alone!). There is no single final product of synthetic biology, even a fully synthesized genome is but one of many hundreds of proposed products of varying value to commercial, medical, research, and public interests. Current synthetic biology pioneers like Jay Keasling are using this diversity as a clue to how to manage public and private interests. Basic synthetic gene sequences involved that are generally usable in basic research are released into the public domain by his lab, but parts and synthetic genetic networks that are used to make valuable chemicals such as medicines and fuels are patented by his company, Amyris Biotechnologies. Others are pushing an entirely open-source model for synthetic biology, others entirely closed. The diversity of biological systems is translated into a diversity of dealing with and "standardizing" biological systems in synthetic biology.

Can we manage this diversity and these tensions and promote research and technology development without resorting to making unreasonable promises of outcomes on short time-scales? Can we continue to fund research as well as keep its findings accessible to all? Can we learn from the mistakes as well as the successes of the Human Genome Project to build a stronger, better synthetic biology? We must be able to properly manage the hype surrounding synthetic biology if we are to not fall into the same traps, to not follow the fads while being blind to important issues in front of us, to not focus on just one aspect of life to the detriment of others.