Response to a complaint about the Earth BioGenome project
Keith Robison posted some complaints about the earth biogenome project on his blog, titling the post Ill-concieved MegaProject Du Jour: I've been on the working group as a minor member, and here is my response, which is here in one piece, (it is in three parts in the comments on his blog due to character limits on comments). My main hope is that biologists can think big about the studying life on earth in the 21st century. Here is the response.
Dear Dr. Robison, thanks for noticing and commenting on the Earth BioGenome project announcement. I am a member of the working group, and whilst I do not presume to speak for everyone or anyone involved, I would like to suggest a more optimistic outlook is not only warranted, but can be easily supported. A full response merits a detailed white paper, which is being drafted, but for now I would like to briefly respond to these comments.
First, I must thank you and note our compete agreement with the comment: “I have no doubt that having sequences for all eukaryotes would reveal fascinating biological insights.” I would add that these insights will fundamentally invigorate biological sciences, greatly enhancing our understanding of the life on earth, most of which remains to be discovered and will provide the inspiration and impulse for future generations. There is no doubt that genome reference sequences will be the foundation for the study of life on planet earth in the 21st century. And it is almost impossible to overstate the value of cataloguing all of life on earth and how it evolved, especially in the context of intense ongoing efforts to find possible microbial life on Mars and various moons in the solar system. Life on Mars will never compare with the majesty of for example the amazon rain forest, sequoias of Redwood National Park, and the marine life of the barrier reefs around the world. The latest discovery of potentially habitable planets in the Trappist-1 system 39 light years (~230 trillion miles) from earth only underscores the rarity and importance of the life around us.
To focus on a few of your comments that address details of the proposed initiative that were not included in Elizabeth Pennisi’s excellent meeting review.
Infrastructure for ALL Biologists. Perhaps most fundamentally, I and others on the working group disagree most with the implicit premise that only medically defined goals such as drug discovery are important. The current scientific grant system is very good at funding the most obviously useful endeavors, but it is hubris to say we know what the most important species on the planet are today and will be in the future. For example, discovering and describing all of the life on planet earth will allow comprehensive searches for molecules of pharmacological importance and will provide understanding of their evolutionary and biological context. From there, materials scientists will search for structural biomolecules, plant biochemists will describe secondary metabolic pathways, molecular geneticists will use new and as yet undiscovered tools similar to crispr and RNAi for theoretical and applied research, quantitative geneticists, agronomists will immediately use the knowledge to improve our agricultural ecosystems, biomedical specialists will rapidly incorporate insights on pathogens and symbionts related with individual health, and evolutionary biologists will look back in time to understand the evolution of life on earth.
Perhaps most elegantly we would have the ability to identify and study the relationships among all species on earth, changing our understanding of our planet agricultural ecosystems. Finally the time to generate this infrastructure is now, as the ongoing human driven extinction event continues. This project cannot save the species on the planet, but we hope it will bring awareness to the grandeur of life on earth, and the need to set aside ecosystems for conservation of this inheritance.
Cost: For Planet Earth it is Small Potatoes.
This would be, first and foremost, an international initiative because biodiversity on earth is international. For the sake of argument, that the US were to provide (Make America Great Again!) 25% of the cost, and the EU, and China also contributed 25% each and the rest were shared by other countries around the world. Consider also that for many countries their major contribution would be access to and assistance with the collection of samples. As currently envisioned, a 10 year project might only require a direct US contribution of $100M a year. Whilst for any individual this is a lot of money, for governments this investment in biology, and the acceleration of biological research.
How Realistic is The Proposed Cost? There are somewhere between 8-15 million species on the planet, although some estimates suggest that sequencing of environmental samples would greatly increase this estimate. However only ~1.5 million eukaryotic species have been described, and it is reasonable to estimate costs based on the sequencing of 2 million species. Crucially, we are assuming that only about half of our costs will be actual genome sequencing (at around $500 per species), and as you recognize, that may not be the hardest part. Most agree that the collection, processing, archiving, and describing the samples will be the most difficult logistical and legal challenges.
Proposed Reference Quality. We know – from hard experience how we know – the technical challenges of achieving reference quality genomes. But we are confident that technology advances from companies such as Oxford Nanopore and Pacific Biosciences will continue to decrease costs while increasing sequence quality and genome contiguity. Standards being established by the genomics community are establishing efficient combined approaches that permit new standards of genome quality including 1Mb contig N50s and 10Mb scaffold N50s.
A defense of Complete Genomics against our ingrained scientific skepticism. This announcement was the result of information provided during a small sequencing technology session of the BioGenomics conference un-related to the announcement of the Earth BioGenome project, so I do not presume to speak for them. But I would like to stick up for them, against the ingrained pessimism we often grow as the people who have to work with the technology today, often forgetting that our annoyances of today are the miracles of only yesterday. In my opinion, their rolling circle nano-ball DNA template technology has always had theoretical and practical advantages for template density and signal to noise technique over the more diffuse bridge PCR technique. Together with the sequencing by synthesis that replaced their previous ligation sequencing, and the support of international partners such as BGI as both partner and large scale user there is no reason to doubt that their goals are achievable.
From presentation at the meeting it is clear that sequencing and analytical steps are becoming more efficient and inexpensive, driven in part by a very competitive landscape with several companies and technologies racing to drop prices by an order of magnitude. For humans, the $100-$200 genome may be here far sooner than we think.
Scientific Collaboration and Friendship. Although my response has been long, I want to finish by echoing the words of BGI president Huanming Yang. As many know, the BGI has helped lead and fund most of the genome 10K and other large taxon-based sequencing projects with a broader vision than was possible within the constrained missions of US funding agencies. Professor Huanming expressed in an impassioned talk that the collaboration and friendship generated by these international projects is potentially more important than the actual science. As he expressed at the meeting in an impassioned talk (I paraphrase): In a hundred years, when we will all be long gone I hope that we will have made every effort to save the species we can on this planet. That vision might involve “frozen zoos” of cells from as many species as possible, and that genome sequences for everything in databases is simply taken for granted as part of the furniture by future researchers.
As your comments make clear, the best path can be hard to find, but we hope that such a resource would be just a small part in bring the world closer together and suggest that now is not too soon to start.