18AR23-18

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AR 23:18 - On the brink of yet another reproduction revolution

In this issue:

GENETICS - immortality by way of "an optimized human genome that can be stored indefinitely and grown later"

+ the "boutique business of designing new synthetic lifeforms"

+ how using artificial eggs and Crispr, anyone might become a biological parent to the healthiest possible baby

Apologia Report 23:18 (1,384)

June 6, 2018

GENETICS

"The Next Best Version of Me: How to Live Forever" by David Ewing Duncan -- intro: "Researchers want to synthesize an optimized human genome that can be stored indefinitely and grown decades from now."

Begins with a profile of George Church: "The 63-year-old geneticist presides over one of the largest and best-funded academic biology labs in the world, headquartered on the second floor of the massive glass and steel New Research Building at Harvard Medical School. ...

"Church is one of the leaders of an initiative called the Genome Project-Write, or GP-Write.... The group <www.bit.ly/2M2NGwe> is still debating how far to go in synthesizing human DNA, but Church - standing in his office in a rumpled sport coat, behind the slender lectern he uses as a desk - says his lab has already made its own decision on the matter: 'We want to synthesize modified versions of all the genes in the human genome in the next few years.' ...

"'What we're planning to do is far beyond Crispr,' <www.bit.ly/2JeSrRl> Church says. "It's the difference between editing a book and writing one." ...

"Church envisions being able to make cells resistant to viruses. 'Like HIV and hepatitis B,' he says.

"Church and others who are working to synthesize human DNA have created their own effort within GP-Write - the Human Genome Project-Write, or HGP-Write - and its prospects for success have biologists abuzz over the potential....

"Theoretically, scientists could one day manufacture genomes, human or otherwise, almost as easily as writing code on a computer, transforming digital DNA on someone's laptop into living cells of, say, Homo sapiens. Mindful of the controversy, Church and his HGP-Write colleagues insist that minting people is not their goal, though the sheer audacity of making genome-scale changes to human DNA is enough to cause controversy."

Stanford bioethicist and legal scholar Henry Greely says what many are thinking: "Now we're talking about a thorough rewriting of life? Hairs will stand on end. Hackles will be raised."

Duncan notes that Synthetic Biology is "a field dedicated to understanding and reengineering the basic building blocks of life. ...

"In 2010, a team at the J. Craig Venter Institute created the first synthetic, self-replicating bacterial cell. But nothing so far has approached the ambitions of GP-Write or HGP-Write, which take their names from the original Human Genome Project, the massive endeavor that sequenced the 3 billion pairs of letters making up a human genome at a cost of $2.7 billion to US taxpayers. (A second, private effort led by geneticist Craig Venter was completed for significantly less money.) 'We are looking at HGP-Write as the bookend' to the Human Genome Project, says geneticist Andrew Hessel, one of the founders of GP-Write and HGP-Write and a former researcher in the life-science unit of software giant Autodesk."

Church and his camp "have a ready answer to the question posed by Francis Collins and others about synthesizing human genomes - why do it? Hessel, Church, and company talk about the potential for large, genome-wide changes that could be used to develop viral-resistant cells, synthetic organs, and new drugs. They draw the line, however, at the prospect of activating a synthetic genome in germ-line cells that could alter the genes we pass down to our kids. ...

"The GP-Write movement had its latest big breakthrough last year, when [prominent synthetic biologist, New York University’s Jeff] Boeke's lab ... announced it had fully synthesized six of the 16 chromosomes that make up the genome of baker's yeast. Boeke plans to finish all 16 chromosomes by the end of this year. 'We're setting out to untangle, streamline, and reorganize yeast's genetic blueprint,' he says. 'Once we've synthesized all 16 chromosomes, we plan to create a functioning yeast cell.'

"That will be a remarkable accomplishment, but given that yeast has only about one-quarter as many genes as people do, it's still not anything close to the complexity of synthesizing all or even part of a human genome." (And that suggests why the intro speaks of the project taking decades.) WIRED, Apr '18, pp87-91. <www.bit.ly/2xCBajO>

"Live forever," eh? Imagine the attraction this holds for someone who suddenly discovers themself in prison <www.goo.gl/DkCOzL> for life and no chance of parole.

"Gene Machines" (no byline) -- begins by introducing the London DNA Foundry <www.bit.ly/2JgHl2F> which rests "in the basement of Imperial College [and] is an example of a wider movement. Similar biofoundries are being set up around the world. ... Instead of biotechnology companies buying and operating their own laboratories, foundries will do it for them."

The London DNA Foundry "can mix, in the precise concentrations required, 150,000 samples of DNA in a morning" from a library with "snippets of genetic code from which different genetic 'circuits' can be assembled. A circuit, in biotech speak, is a collection of genes that work together towards a common goal.... The genes comprising a potential circuit are then assembled into circular DNA molecules called plasmids. ...

"Once the mixture is correct, the test plats are whisked into a machine which multiplies the number of plasmids in each well using a process called a polymerase chain reaction (PCR). And then, when the PCR has done its work, the plasmids are introduced into living cells - either bacterial or yeast. After that, the cells are incubated, and the result is tested to see which, if any, of the circuits performed as expected.

"Such is the London DNA Foundry's scale that it can build and test about 15,000 different genetic designs in a day. ... Some other biofoundries, however, offer a wider range of services. For example Transcriptic, a firm <www.bit.ly/2sIzUpx> in Silicon Valley, will also allow customers to store entire cell lines that may be tested later, or to grow tissues from them for testing.

"One of Transcriptic's particular specialties is preclinical drug screening. ...

"Paul Freemont, a director of the London DNA Foundry, hopes that once it is clear what processes are of most interest to customers, the sorts of industrial standards which are commonplace in other industries will start to emerge among biofoundries. That will make it easier for the process of designing new synthetic lifeforms to be scaled up from the bespoke boutique business it is now to something more like a global industry. That day is not yet here. But if there is demand, then biofoundries will surely play their part in the next phase of the Industrial Revolution." The Economist, Mar 3 '18, p71. [1]

"Science Is Getting Us Closer to the End of Infertility: In an era of artificial eggs and Crispr, anyone could become a biological parent to the healthiest baby" by Jason Pontin -- "About 40 years ago, Louise Brown, the first human created using in vitro fertilization, was conceived in a petri dish. Not long after her birth, Leon Kass, a prominent biologist and ethicist at the University of Chicago, wrung his hands about the then-revolutionary technology of joining sperm and egg outside the body. The mere existence of the baby girl, he wrote in an article, called into question 'the idea of the humanness of our human life and the meaning of our embodiment, our sexual being, and our relation to ancestors and descendants.' The editors of Nova magazine suggested in vitro fertilization was 'the biggest threat since the atom bomb.' The American Medical Association wanted to halt research altogether."

[Now, jump to the present without asking questions about botched embryos.] "Millions of babies were conceived using IVF. They were born healthy and perfectly normal babies, and they grew to become healthy and perfectly normal adults. ...

"We are now on the brink of another revolution in reproduction, one that could make IVF look quaint. Through an emerging technology called in vitro gametogenesis (or IVG), scientists are learning how to convert adult human cells - taken perhaps from the inside of a cheek or from a piece of skin on the arm - into artificial gametes, lab-made eggs and sperm, that could be combined to create an embryo and then be implanted in a womb. For the infertile or people having trouble conceiving, it would be a huge breakthrough. Even adults with no sperm or eggs could conceivably become biological parents.

"In the future, new kinds of families might become possible: a child could have a single biological parent because an individual could theoretically make both their own eggs and sperm; a same-sex couple could have a child who is biologically related to both of them; or a grieving widow might use fresh hair follicles from a dead spouse's brush to have a child her late husband didn't live to see.

"At the same time, modern gene-editing technologies such as Crispr-Cas9 would make it relatively easy to repair, add, or remove genes during the IVG process, eliminating diseases or conferring advantages that would ripple through a child's genome."

Pontin reviews how we started down the road to artificial gametes. "How soon before humans have children using IVG?" Postin suggests it is too soon to tell. One scientist "guesses it will take five years to produce egg-like cells from other human cells, with another 10 to 20 years of testing before doctors and regulators feel the process is safe enough to use in a clinic. ...

"Once scientists and regulators are confident they have minimized the potential risks of IVG, we could easily make heritable changes to germ cells like eggs, sperm, or early-stage embryos, and with those changes, we'd be altering the germ line, our shared human inheritance. ...

"Then there is genetic disease. ... A doctor might say, 'Your child will have a higher chance of developing X. Would you like us to fix that for you?'

"Proving that IVG and gene editing are broadly safe and reliable will be necessary before regulatory agencies around the world relax the laws that currently preclude creating a human being from synthetic gametes or tinkering with the human germ line. ... Because IVG and gene editing are so strange, there may be popular and expert demand for their oversight. But in what form?"

Postin briefly considers "other ethical quandaries." However, his conclusion suggests that science will simply continue as it has ever since IVF gave us so many happy babies. WIRED, Apr '18, pp14-19. <www.bit.ly/2JsOpbK>

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