杏吧原创

BOB MURPHY has had some close shaves. He once found a deadly viper slithering into his sleeping bag in a Southeast Asian jungle. He was in a four-wheel drive that rolled over on a dirt trail in the Australian desert. He nearly plummeted to his death when a cliff he was standing on in Vietnam collapsed. And last year, he found himself in the middle of a war zone in Armenia. 鈥淚鈥檓 like a cat with nine lives,鈥� he says.

Murphy is a 鈥渉unter-gatherer鈥� 鈥� a biologist charged with cataloguing Earth鈥檚 rich array of plants and animals. For decades, he has plunged into the farthest-flung corners of the globe to find and collect new species. 鈥淚t鈥檚 not for everyone,鈥� he says. 鈥淧eople can end up with broken bones or malaria or puff up with insect bites, and the days are long and tough.鈥� Indeed, the dangers can be life threatening. In 2001, Murphy鈥檚 friend and fellow collector Joe Slowinski died after being bitten by a venomous snake he had caught in Myanmar.

Despite the risks, hunter-gatherers will soon be in high demand as an audacious scheme gets under way. This biological 鈥渕oonshot鈥�, known as the Earth BioGenome Project, is scheduled to launch in June. Its mission is to sequence the genomes of all known species of flora and fauna on Earth. Nature鈥檚 recipe books could hold clues to making far superior medicines, materials, biofuels and crops, unravelling our evolutionary past and help us to be better custodians of our planet. The first challenge, however, will be collecting specimens from the wild. Then comes the sequencing itself, which will require Herculean amounts of human labour and computing power. Can it be done?

The Human Genome Project seemed equally far-fetched when it was proposed in the late 1980s. 鈥淭here were many people who told us, 鈥楾his is a waste of money, it鈥檚 way too costly鈥�,鈥� says David Haussler at the University of California, Santa Cruz. 鈥� or about $4.8 billion at today鈥檚 prices 鈥� and took over a decade to complete, but the treasure trove of information it unlocked has wildly exceeded expectations. Not only did it give birth to the personalised medicine revolution, it also propelled advances in diverse fields including forensics, archaeology and bioinformatics. Not to mention, every $1 of public money invested has since generated . 鈥淚t鈥檚 paid for itself many times over,鈥� says Haussler.

鈥淭he plan is to decode the genomes of 1.5 million species in just 10 years鈥�

It was this success that inspired at the University of California, Davis, to start pondering an Earth-scale genome project three years ago. 鈥淓verybody鈥檚 first expression is like, 鈥楬e鈥檚 gone insane鈥�,鈥� he chuckles. But his initial rough calculations suggested it was doable. 鈥淚 saw that with today鈥檚 technology, the time and cost would basically be the same as for the Human Genome Project,鈥� he says. 鈥淭he insights we鈥檝e gained from just one genome have been incredible, so imagine what could be revealed by sequencing the rest of life?鈥�

At the time, Lewin was a member of 鈥� a scheme launched in 2009 with the goal of sequencing 10,000 vertebrate genomes. Similar projects soon popped up aiming to sequence 10,000 bird genomes (), 5000 insect genomes (), 10,000 dog genomes (), 7000 marine invertebrate genomes () and 1000 plant genomes (). 鈥淚t just seemed like the logical next step to sequence everything,鈥� he says.

In November 2015, at a meeting of 23 biologists at the Smithsonian Institution in Washington DC, Lewin floated his idea: to sequence, over a 10-year period, every eukaryote known to exist on Earth. These are organisms with cell nuclei, including animals, plants and fungi 鈥� of which there are about 1.5 million. 鈥淭here were some very sober people there, but by the end of the meeting, enough were convinced,鈥� he says. A framework for the Earth BioGenome project was teased out over several follow-up meetings, and with research powerhouses including the Smithsonian Institution, the Wellcome Sanger Institute in the UK, BGI in China, and the S茫o Paulo Research Foundation (FAPESP) in Brazil.

鈥淚ndigenous people may be hired to help find specimens of rare plants鈥�

Just 2500 eukaryotes have been sequenced to date, so it will be a gargantuan endeavour. The goal for the first three years is to produce a high-quality genome for one member of each of the 9000 eukaryotic families. Then, over the following three years, a draft genome for one member of each of the 150,000 genera 鈥� the taxonomic group below families 鈥� will be assembled. And the last four years will be spent compiling drafts for the remaining species, which can be refined later on.

These lofty targets mean sequencing eight high-quality genomes per day during the first phase, more than 100 drafts daily in the second, and in excess of 1000 every day in the third. With current technology, a high-quality genome takes about a week to sequence and costs between $1000 and $30,000, depending on its size. A draft takes a few hours and cost about $800. But costs and sequencing times are likely to fall as technology improves, says Lewin. And, despite the enormity of the task, Guojie Zhang, a biologist at BGI, thinks it can be done. 鈥淲ith the sequencing power we can access now, it would actually be possible to finish the sequencing for all 1.5 million eukaryotic species within a year,鈥� he says.

In fact, the main difficulties will be in logistics, including getting permission from governments to sequence native species, and collecting and preparing samples. Some specimens will come from museum collections, but they are only suitable for draft genomes because high-quality sequences require fresh tissue from multiple organs 鈥� hence the need for hunter-gatherers like Murphy, who is based at the University of Toronto in Canada and collects specimens for Genome 10K. Finding rare species 鈥� particularly in difficult-to-access areas like the deep sea or dense forest 鈥� will be challenging. Murphy鈥檚 speciality is frogs and snakes. Sometimes he travels by plane or boat to reach remote places, but mostly he treks on foot into the wilderness with local porters or elephants carrying his supplies. The investment of time and effort can be huge. 鈥淲e expect one of the legless lizards we want for Genome 10K may take six months of fieldwork to find, if we鈥檙e lucky,鈥� he says.

Lewin hopes that the demand for specimens to sequence will drive technological innovation. Drones or underwater vehicles could potentially roam remote areas and automatically sample different species, provided they were minimally invasive, he says. Indigenous people could also be hired to help find rare plants and use newly available handheld DNA sequencers to obtain rough sequences of specimens in the field. These devices, which cost as little as $1000, are already being used in the jungle and the Arctic.

Another challenge is how to store the whopping amounts of data. It is estimated that the project will generate several thousand petabytes per year 鈥� more than . Again, this could be a spur for innovation, this time in bioinformatics. One option may be to store DNA data in鈥� DNA. The code鈥檚 letters A, T, C and G can be used like the 0s and 1s in regular computing, and researchers at Columbia University recently showed that a gram of DNA can .

Finally, the project鈥檚 founders want to make sure it benefits all involved fairly. To do this, they have signed up Peruvian entrepreneur Juan Carlos Castilla-Rubio to build the . This open-access database will record the genomic sequence, appearance, location and associated indigenous knowledge for each species. The data will go on a blockchain 鈥� a type of ledger used in cryptocurrency 鈥� that traces where and how the information is used. Any commercial benefits can then be shared appropriately with all contributors, including local people who provide traditional know-how.

Castilla-Rubio came up with the idea when he was looking for ways to shift the Amazon鈥檚 economy away from destructive industries like farming, logging and mining towards more knowledge-based enterprises that preserve the environment. He recognised the huge economic potential of the genomic information tied up in the Amazon 鈥� which is home to 15 per cent of Earth鈥檚 land biodiversity 鈥� but also the problem of exploitation. In the past, large corporations have tapped the region鈥檚 natural resources and indigenous knowledge without paying their dues, for example, when a blood-pressure medication was developed from snake venom traditionally . The blockchain approach should prevent this type of biopiracy and ensure that the Earth BioGenome Project sticks to the 鈥� an international agreement made in 2010 to recognise the rights of countries over their genetic resources and traditional knowledge.

Of course, all this must be paid for 鈥� the total cost is estimated at $4.7 billion. As yet, the project has no dedicated funding, although publicity at this year鈥檚 World Economic Forum in Davos, Switzerland, has sparked enthusiasm. 鈥淢any individual countries are now expressing interest or are close to making large commitments, and we鈥檙e talking to some prominent people,鈥� says Lewin. But existing sequencing drives such as Genome 10K do have funding, and when the project is officially launched in June, it will begin by building on these. Lewin and fellow project leaders Gene Robinson at the University of Illinois and John Kress at the Smithsonian Institution plan to start by coordinating the activities of the various schemes to make sure enough genomes are sequenced each year to meet overall targets.

Given all the expense and effort, what pay-off can we expect? Lewin is confident that the open nature of the Earth Bank of Codes will lead to discoveries and innovations all around the world. One area with huge potential is pharmaceuticals. Already, 鈥� including aspirin and Botox 鈥� and we have only just scratched the surface. Genome sequencing can inspire new medicines by revealing how plants and animals have evolved their sophisticated defences against predators and disease. Guilherme Oliveira at the Vale Institute of Technology in Brazil, for example, is sequencing the Amazon鈥檚 jaborandi tree, which produces pilocarpine, a drug used to treat the eye disease glaucoma. Once his team has done this, they will be able to work out the pathway that produces the valuable chemical. It may be possible to replicate this process synthetically or tweak it to make even more potent medicines.

鈥淧otential applications range from engineering and renewable energy to AI鈥�

Another major beneficiary will be conservation, says Haussler. He believes sequencing endangered species will give us clues about which are most vulnerable to climate change and need the most attention. This knowledge will help caretakers manage remaining populations too. For example, when researchers sequenced the genome of the critically endangered , they found a recessive gene that was causing fatal skeletal abnormalities in some of the 400 remaining birds. Breeders are now using this information to selectively match up individuals without this gene to improve the health of the population.

Sequencing all life will also let us retrace evolution and see where each species sits in the family tree, says Susan Brown, a biologist at Kansas State University. This will answer long-standing questions such as whether vocal learning evolved once or multiple times in birds. Already, DNA sequencing has revealed unexpected relationships in our family tree. For instance, we have discovered that the . 鈥淚n the same way that the periodic table shows you how the different elements are related, the tree of life reveals relationships between different species,鈥� says Brown.

Lewin believes the potential benefits of the project go far beyond biology. The wealth of genomic information is likely to find applications in all sorts of fields from renewable energy and engineering to agriculture and artificial intelligence, he says. There could also be benefits we can鈥檛 even conceive of yet. In the same way we couldn鈥檛 predict all the innovations that came out of the Human Genome Project, 鈥渨e don鈥檛 know what we don鈥檛 know鈥�, he says.

Such enthusiasm is what keeps Lewin criss-crossing the globe to promote the Earth BioGenome Project. He is well aware there are vast challenges ahead, but he is also certain they will be worth it. 鈥淪ometimes, you just have to go for these things,鈥� he says. 鈥淲e鈥檝e got the technology, we鈥檝e got the expertise, now we just need the will.鈥�

This article appeared in print under the headline 鈥淩eading the book of life鈥�