Welcome to my genome

HE IS a professor of genetics at Harvard Medical School, but George Church is also a vegan, cannot hold a tune, gave up driving due to narcolepsy and suffers headaches after running. Technology Quarterly did not discover these intimate details through surveillance, interrogation or going through his trash, but simply by browsing a website where Dr Church makes such particulars freely available, and much more besides. The Personal Genome Project (PGP), a medical study designed by Dr Church and for which he was the first subject, even allows visitors to download his entire genome and rummage through his DNA.

It is all part of a grand experiment to help researchers explore the interactions between genetics, environment, behaviour and disease, with the ultimate goal of developing customised therapies for individuals. The only way to do this, Dr Church believes, is with complete openness. “It really is hard to do good science on closed data sets,” he says. To compare, say, a study on autoimmunity in a group of people with a study on their general health could well prove impossible because of anonymity. But with open data, Dr Church and his colleagues have managed to conduct 25 different studies on the same group in just one month.

The idea is that linking genes to outcomes, whether deadly diseases or talents like singing, requires a huge array of raw data about people’s lives, diets and their surroundings; data that do not sit well with traditional notions of privacy. Dr Church is seeking volunteers willing to waive confidentiality and lay bare their genetic code, medical records and daily habits to the world. More than 3,500 people have done so. While the PGP expects to eventually enroll 100,000 subjects, Dr Church is already dreaming much bigger: “We’re constructing it a little like Wikipedia, which has beat out all the proprietary closed systems. If enough people see enough benefit from it, it could scale to a billion people.”

Such an undertaking would have been unimaginable, and unimaginably expensive, a decade ago. Dr Church has done much himself to make it possible. His 1984 Harvard PhD included the first method for direct genome sequencing: determining the exact order of nucleotides within DNA. These nucleotides contain four nucleobases (adenine, guanine, cytosine and thymine) that form base-pairs and give the DNA molecule its famous double-helical structure. He also came up with the idea of “multiplexing”, where many pieces of DNA are sequenced simultaneously rather than one by one.

In the late 1980s Dr Church helped organise the internationally funded Human Genome Project, whose aim was to sequence all 3.3 billion base-pairs within a human genome. Even before it started, he was not satisfied with the programme because the goal was one genome, and a very expensive genome at that. The sprawling effort eventually took 15 years, cost around $3 billion and delivered a genome that was a blend of different individuals and riddled with gaps.

Although it was an historic milestone, it had relatively little value in practical, personal or medical terms, says Dr Church. “What I really wanted was for everybody to have their genome and ideally everybody to share their genome, and for that we needed to bring the price way down.”

Genetics to go

In 1994 his automated technologies led to the first commercial genome sequence, that of a bacterium that causes stomach ulcers, and later to dramatic improvements in the accuracy and cost of sequencing human genomes, reducing the cost to around $1,000 today. Since 2007, Dr Church has co-founded 12 biotech companies and advised many more.

One of these, Genia, is commercialising a process called nanopore sequencing that Dr Church first devised in 1988. Distinct polymer tags are attached to each of the four nucleotides poised to contribute to a single molecule of replicating DNA. As they react, the tags are released near a protein layer full of tiny holes called nanopores. Each tag blocks the flow of electrical ions across the layer in a different way. Because it relies on electronics rather than optics, nanopore sequencing promises faster, cheaper sequencing. Dr Church holds up a fingernail-sized chip containing 128,000 nanopores that he reckons will bring the cost of sequencing down to $100. In June, Genia was acquired by Roche, a Swiss pharmaceuticals giant.

“Making new petroleum should be as simple and straightforward as brewing beer.”

Sequencing a genome is one thing, but interpreting it and understanding it is quite another. Dr Church’s endeavours in that field are equally impressive. In 2007 he co-founded Joule Unlimited, a biofuels company that hopes to use genetically engineered bacteria to convert waste carbon dioxide directly into fuels. As a lot of the problems with the bioreactor and the genetics have been solved, he says: “Making new petroleum should be as simple and straightforward as brewing beer.” But the margins are tight and it is unclear yet whether the process will be commercially competitive.

Another project that excites Dr Church is Revive and Restore, a controversial effort to bring back animals and plants from extinction. There are certain species, he believes, that are good for humanity and in order to keep them alive it is necessary to conserve the whole ecosystem they live in, too. To do that, he says, may well require reviving some species that are already extinct.

For example, Dr Church thinks that woolly mammoths could help prevent the Arctic permafrost from melting. Their grazing would invigorate the flora growing on the surface, which would provide more protection from the sun. His laboratory is developing a robotic system called multiplex automated genome engineering (MAGE) that can perform up to 50 different genome alterations at nearly the same time, creating billions of variants in a matter of hours. MAGE would allow scientists to start with an intact genome of a living Asian elephant and change it wholesale into one that is comparable to an extinct mammoth, using information pieced together from frozen fragments of mammoths. Passenger pigeons, dodos, giant auroch cattle and even Neanderthals might follow.

But de-extinction is not ambitious enough for Dr Church. Synthetic genomics has the potential to change the course of evolution, “with the difference that [it] will be under our own conscious deliberation and control,” he writes in his book “Regenesis”. Ultimately, he thinks that will mean altering humanity itself.

A project that interests him would be engineering human cells to resist all known viruses. He suggests two ways of doing this. The first would involve creating “mirror” humans—recoding a person’s DNA to switch the chirality, or handedness, of their entire body at the molecular level. It would render that person immune to viruses, but at the cost of them being unable to digest most normal foods or interact with the natural microbiome that helps to keep their gut healthy.

Slightly less drastic might be using a tool like MAGE to make hundreds of changes to a person’s genetic code, which converts genetic information into useful proteins. Altering enough of the right nucleotides at once could eliminate the specific sequences that viruses need to reproduce, but still produce the necessary proteins required for that person’s well-being. “This process is probably easier than changing ourselves into mirror people,” says Dr Church.

But would anyone want to go to such an extreme? In the future Dr Church sees a world in which individuals tinker with their DNA to eliminate diseases, give their offspring extra abilities or simply to look more attractive. Very few people currently try to obtain information about their propensity to carry diseases, which Dr Church reckons is one of the best ways of controlling disease. “But we are willing to fix things that aren’t broken, for example with cosmetic surgery.” This is why Dr Church thinks there will be a desire for people to change themselves substantially. “We already are radically different from our ancient ancestors, augmented with cellphones, computers, cars and jets. To draw a sharp line between physics and biology doesn’t make any sense.”

To boldly go

To travel beyond the Earth, astronauts could also have their bodies altered to give them a better chance of surviving the journey. They could be genetically engineered to resist radiation and osteoporosis, a weakening of the bones which would result from prolonged weightlessness. Those that remain on Earth could be altered to reduce their carbon footprint. “All the discussion is about how to make buildings bigger rather than people smaller,” he told a conference at the Massachusetts Institute of Technology earlier this year. “We’re well beyond Darwinian limitations to evolution. Evolution right now is in the marketplace,” he now says.

Even objects could be revolutionised by genomics. DNA is a good way of storing information. It is possible to use it to store data for 700,000 years at a million times the density of today’s disc drives, says Dr Church. In 2012, he encoded “Regenesis” into DNA and made 70 billion copies of it. Dr Church is beginning discussions with data-storage companies about commercialising the technology.

The fantastical possibilities of genomics and the rapid democratisation of its technologies raise the spectre of bioterrorism. Synthetic biology is potentially more dangerous than chemical or nuclear weaponry since organisms can self-replicate and spread rapidly, says Dr Church. “There has to be industry-wide surveillance, licensing and rigorous testing. But it’s futile to try to keep things out of the scientific literature. Even if you could stop the dissemination of results, it would mean that only the bad guys would do research and none of the good guys could see what’s going on.”

Now entering his seventh decade, Dr Church has no plans to retire. “Reversal of ageing is high on my list of things to do, and not just because I’m getting old,” he says. The tools are now available to make rapid progress. “We’ve taken my 60-year-old fibroblast [connective tissue] cells, changed them into a different form and then back to fibroblasts and they’re young again, most of the time. Turning that into a whole body therapy is another leap but my point is that we can do it.”

If his body fails before the science is ready, Dr Church has a backup plan, literally. He was one of the scientists behind the BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies), a $3 billion, decade-long project announced by President Obama in 2013 to map the human brain. Innovation in biotechnology is proceeding rapidly enough to consider copying a brain. “If we can come up with a way of backing up my brain into another that I have in my back-pack, we’ll do it,” he says with a smile. “People talk themselves out of things very easily. Things that they think are a million years away or never, are actually four years away.”