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article imageReverse aging? Eliminate disease? Bring back the Neanderthal? Special

By Les Horvitz     Oct 24, 2016 in Science
New York - Why wait for evolution to act if genetic technology can accelerate the process, especially if it can give us longer and healthier lives? That’s the message the eminent Harvard geneticist George Church wants to get out.
“We have to be cautious about being cautious,” Church told attendees at the recent TechFest in New York sponsored by The New Yorker Magazine. Church maintains that people are so wary about advances in genetic technology because they fail to understand it or appreciate all the good that can come from it. Cautious is one thing that no one has ever accused Church of being. Rather than shy away from controversy, Church seems to welcome vigorous debate. He’s one of the rare scientists – the astrophysicist Neil deGrasse Tyson is another – who takes every opportunity to present his views out in public. He recently appeared on The Late Show with Stephen Colbert to talk about the practicality of reversing the effects of old age and resurrecting extinct species like the woolly mammoth, both of which he believes may be possible to achieve in his lifetime (he’s now 62). No one has accused Church of lacking ambition, either.
Church has cultivated the image of an iconoclast with a theatrical flair, consuming nutrient broth intended to nourish cell lines for months at a time – he’s a vegan -- and wearing blinders in his lab as a reminder to his students not to succumb to tunnel vision.
Currently, Church is spearheading an initiative to synthesize a complete human genome. Put another way, the scientists involved in this effort, which is expected to take a decade, are hoping to build, from scratch, all the genes that make humans human. In 2005, he launched the Personal Genome Project, recruiting volunteers to undergo genetic testing, and then making the results available to the public. “Public sharing of genetic data is an explicit goal,” the project’s website says. By giving scientists more access to this data the project hopes to encourage them to make important discoveries.
A deeper understanding of the genome could give researchers the ability to identify and target disease-causing genetic mutations. Church believes that genetic technology offers the potential of ending disease once and for all.
Although wiping out disease may take several decades if it happens at all, Church’s lab is also involved in work that stands a good chance of reaping more immediate benefits. His team is making use of a new genetic editing technique called CRISPR to manipulate pig genes so their organs can be safely transplanted into humans. It’s long been known that pig organs were compatible for transplant into humans, Church says, but they carried retroviruses that made them risky for immunocompromised people. That impediment stalled progress — until CRISPR. Given the critical need for organ transplants and the paucity of donors, scientists eagerly seized on CRISPR to make pig organs safe for humans by deleting the viruses. And they did it fast, too — removing 62 viruses in just two weeks. They’re currently producing cloned virus-free pig embryos and running tests to transplant their organs into primates. Clinical tests on humans may begin within a year.
“CIRSPR was originally a natural bacterial defense system,” Church said, calling it “a valuable addition to our genetic tool box.” No one suspected how useful it would turn out to be until very recently. “You often don’t know what you’re missing until it arrives.” All that said, he holds out the hope of finding an even more precise genetic editing tool. Yet, for now, CRISPR has given scientists the ability to change T-cells, a vital part of the body’s immune system which is vulnerable to HIV so that the virus can no longer infect them. In a more controversial experiment, Chinese scientists used CRISPR to tinker with the DNA of nonviable human embryos, opening up the possibility of curing genetic disorders in the womb. But the experiment also raised a more ominous possibility by demonstrating the practicality of creating designer babies. The ensuing uproar put a halt to genetic manipulation of embryos, even those that had no chance of ever developing into fetuses. But as history has repeatedly shown, it’s almost impossible to put the genie back in the bottle once it’s been let out.
It’s not clear that Church would even want to though he emphasizes the need to proceed carefully.
To a large extent, the outcry against genetic engineering has focused on altering DNA in eggs, sperm or embryos, which can produce new traits that could be passed down from one generation to the next. But Church thinks that the fears of ethicists are overblown especially when weighed against the potential of curing inherited diseases like Huntington’s or Alzheimer’s, stopping them dead in their tracks so that people carrying these inimical genetic mutations won’t pass them along to future generations. Ignorance – and fear – can make life difficult for scientists like Church to make people understand what geneticists actually do and why their work is so important. There’s a big difference between transgenic experiments – taking genes from one species and inserting them into another — and genetic manipulation within a species. The latter type doesn’t arouse nearly as much controversy as the former. There’s considerably more resistance to genetically modified food, for example, but almost none to genetically modified microbes, Church observed. If you took a poll of residents of Martha’s Vineyard and Nantucket, both popular summer getaways for the wealthy and well-connected, you’d probably find that the majority of them are against GM food. But ask them about populating the islands with white-footed mice that are genetically modified so that they can’t transmit Lyme disease and you’ll be hard pressed to find anyone who’d object. Yet sometimes, if it wasn’t for GM food there wouldn’t be any food at all. “Without GM there wouldn’t be any papayas left in Hawaii,” Church says. That’s because the state’s papaya crop was in danger of being wiped out by a virus until scientists intervened in 1998, creating genetically modified papayas that were resistant to the disease.
Church applauds the wildly ambitious plan announced by Facebook founder Mark Zuckerberg’s plan to eliminate all diseases by the end of this century. Smallpox has been vanquished, polio is sporadic and Guinea Worm has almost been made extinct. Malaria, however, remains a much more serious challenge; 500,000 people worldwide are now resistant to antimalarial drugs. Nonetheless, developing nations have different types of diseases – mostly infectious -- which are easier for geneticists to target than those of the developed world, which are increasingly diseases like cancer and disorders like dementia that are associated with aging. That has led Church to take an interest in age reversal. The first thing to do is to identify biomarkers of aging to understand why people deteriorate as they grow older. This isn’t as quixotic a goal as you might imagine; blood factors from young mice have been shown to invigorate muscles, skeletal structure, and nerve tissue in older mice.
It’s one thing to keep people alive and healthier longer. It’s quite another to resurrect the dead. But Church hasn’t shied away from an effort to see whether he and his colleagues can’t sequence a large portion of the mammoth genome from a sample of mammoth hair with an eye to resurrecting the extinct mammal. His team replaced several genes in an elephant cell line with mammoth ones, including those that code for a cold-climate hemoglobin (the protein in red blood cells responsible for transporting oxygen) as well as long hair, small ears, and subdermal fat storage. His lab is using techniques similar to those they employed on pigs to make them suitable for organ transplant. But elephants are trickier to work with than pigs. “Like all kids, I was fascinated by large extinct creatures,” he told The New York Times, “and I tended to like the furry ones better.” He has even speculated that it might one day be possible to reconstruct a Neanderthal with a combination of the extinct hominid’s DNA and modified cells from living humans.
DNA has another advantage, too. It turns out that it is an exceptionally good way of storing information — not just genetic information, either. “We can fit the Internet into (a sample of) DNA that could fit in the palm of your hand and make backup copies cheaply,” Church says. Songs and movies have already been encoded in DNA. And unlike other media – think floppy drives or paperback books – DNA doesn’t deteriorate. Church even decided to use DNA to store and copy his 2014 book Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves in DNA, which he co-authored with Ed Regis. He then made 70 billion copies of his book, which is a record that not even J.K. Rowling or Stephen King could hope to match. In fact, it’s more than three times the total number of copies of the 200 most popular books in the world combined. And yet, Church noted wryly, all those billions of copies of his book could fit into a speck of dust.
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