- Email: [email protected]
How not to clone a mammoth
Perspectives
Book How not to clone a mammoth The first line of the US mule-training manual is said to read: “First gain the animal’s attention by striking it smartly between the ears with a stout stick”. For authors, their book’s title does the same job. I got some odd glances on the tube a while ago when I was reading a work provocatively labelled (in sixty-point capitals) The Wisdom of Whores which, despite the empty seats that opened up on both sides of me, is in fact an enthralling account of the epidemiology of HIV/AIDS. The most recent Diagram Prize for Oddest Book Title of the Year at the Frankfurt Book Fair was won by Strangers Have the Best Candy, which should also guarantee a seat on a crowded train. How to Clone a Mammoth, too, might be a contestant for the titular crown. However, this is a book that waves a stout stick but never really gets round to using it. It is full of attention-grabbing speculations about the potential scientific process of “de-extinction”, but its ultimate response to its own front cover is that “You won’t be able to” and, yes, there it is, in the author’s own words on page 99: “Mammoth cloning is not going to happen”. The elephant in the room is not, it seems, a mammoth. The four letters of the genetic code too often mutate from A, G, C, and T to H, Y, P, and E and evolutionary biologist Beth Shapiro is happy to admit that her book is laced with that invaluable lubricant. She uses it to ease down the bitter pills of jargon that now infest biology, with techniques of potentially astonishing power such as CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats; a means of using a bacterial defence against phages to target mammalian DNA) and TALENS (Transcription Activator-like Effector Nucleases; enzymes that can delete or add sequences to a genome). Remarkable as these methods are, www.thelancet.com Vol 386 July 11, 2015
they are far from effective. Earlier this year, a Chinese group reported an attempt to correct a thalassaemia deletion in a human embryo using CRISPR. The rather synthetic uproar about ethics that greeted this work rather obscured the unfortunate fact that the method did not succeed most of the time, and when it did often targeted the wrong genes.
“The four letters of the genetic code too often mutate from A, G, C, and T to H, Y, P, and E and evolutionary biologist Beth Shapiro is happy to admit that her book is laced with that invaluable lubricant.” And that was with living cells, using a complete gene sequence. With ancient DNA things are much, much, harder. First, the stuff is hard to find. That once did not seem to be a problem until experiments with amber recovered just as much insect DNA from pieces without a preserved fly as from those with one. Methods are now more rigorous and ancient DNA has told us a lot about the past, the fact that the human gene for red hair may have come from hybridisation with Neanderthals included. However, the stuff is invariably broken into tiny pieces, and recreating the sequence is a task for computer science rather than biochemistry. There’s not much hope of inserting the mammoth genes for thick hair and cold-resistant haemoglobin into a modern elephant. Another idea, Shapiro explains, is to cut and paste your pachyderm; to compare the most mammoth-like sections of a number of elephant genomes and then to assemble a simulacrum of the extinct proboscid that is really an elephant in disguise. Rather more rational (albeit needing several lifetimes’ work) is the idea of breeding from hairy elephants with
dumpy legs until an individual emerges hirsute and squat enough to withstand the arctic cold. Other schemes include the possibility of finding frozen sperm in a mammoth carcase and fertilising an elephant with it, but that idea is fantastical indeed. If the spurious Mammoth ever does appear the creatures could move to Pleistocene Park in Siberia, a recent attempt to simulate what the tundra looked like in the days when it was grazed by their extinct relatives. The mammoth steppe was the largest single block of habitat ever seen, far larger than the tropical rainforest, and those great beasts were what ecologists call a “keystone species”: a creature whose activities determine the fate of many others. Wolves are the same: when they were introduced into the USA’s Yellowstone National Park 15 years ago, they reduced elk numbers by half, so that ground cover increased, sheltering voles that were eaten by hawks, and so on and on. A Russian enthusiast has already fenced off a section of Siberian tundra and filled it with wild horses, bison, and deer. Shapiro describes how the effect has been dramatic; a great increase in rich grassland as the animals trample the soil and recycle nutriments and, less predictably, less snow cover in winter as their hooves sweep it away. That, in turn, means that the permafrost gets colder than before, and—an unexpected bonus—releases less carbon dioxide. A new behemoth might then play a part in keeping the whole planet cool. Another approach to populating Pleistocene Park is simpler: why not get the conservationists of the world to knit great woolly suits for the animals to keep them warm and comfortable in wintry Siberia?
How to Clone a Mammoth: The Science of De-Extinction Beth Shapiro. Princeton University Press, 2015. £16·95 ISBN 9780691157054
Steve Jones [email protected]
125
Book How not to clone a mammoth The first line of the US mule-training manual is said to read: “First gain the animal’s attention by striking it smartly between the ears with a stout stick”. For authors, their book’s title does the same job. I got some odd glances on the tube a while ago when I was reading a work provocatively labelled (in sixty-point capitals) The Wisdom of Whores which, despite the empty seats that opened up on both sides of me, is in fact an enthralling account of the epidemiology of HIV/AIDS. The most recent Diagram Prize for Oddest Book Title of the Year at the Frankfurt Book Fair was won by Strangers Have the Best Candy, which should also guarantee a seat on a crowded train. How to Clone a Mammoth, too, might be a contestant for the titular crown. However, this is a book that waves a stout stick but never really gets round to using it. It is full of attention-grabbing speculations about the potential scientific process of “de-extinction”, but its ultimate response to its own front cover is that “You won’t be able to” and, yes, there it is, in the author’s own words on page 99: “Mammoth cloning is not going to happen”. The elephant in the room is not, it seems, a mammoth. The four letters of the genetic code too often mutate from A, G, C, and T to H, Y, P, and E and evolutionary biologist Beth Shapiro is happy to admit that her book is laced with that invaluable lubricant. She uses it to ease down the bitter pills of jargon that now infest biology, with techniques of potentially astonishing power such as CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats; a means of using a bacterial defence against phages to target mammalian DNA) and TALENS (Transcription Activator-like Effector Nucleases; enzymes that can delete or add sequences to a genome). Remarkable as these methods are, www.thelancet.com Vol 386 July 11, 2015
they are far from effective. Earlier this year, a Chinese group reported an attempt to correct a thalassaemia deletion in a human embryo using CRISPR. The rather synthetic uproar about ethics that greeted this work rather obscured the unfortunate fact that the method did not succeed most of the time, and when it did often targeted the wrong genes.
“The four letters of the genetic code too often mutate from A, G, C, and T to H, Y, P, and E and evolutionary biologist Beth Shapiro is happy to admit that her book is laced with that invaluable lubricant.” And that was with living cells, using a complete gene sequence. With ancient DNA things are much, much, harder. First, the stuff is hard to find. That once did not seem to be a problem until experiments with amber recovered just as much insect DNA from pieces without a preserved fly as from those with one. Methods are now more rigorous and ancient DNA has told us a lot about the past, the fact that the human gene for red hair may have come from hybridisation with Neanderthals included. However, the stuff is invariably broken into tiny pieces, and recreating the sequence is a task for computer science rather than biochemistry. There’s not much hope of inserting the mammoth genes for thick hair and cold-resistant haemoglobin into a modern elephant. Another idea, Shapiro explains, is to cut and paste your pachyderm; to compare the most mammoth-like sections of a number of elephant genomes and then to assemble a simulacrum of the extinct proboscid that is really an elephant in disguise. Rather more rational (albeit needing several lifetimes’ work) is the idea of breeding from hairy elephants with
dumpy legs until an individual emerges hirsute and squat enough to withstand the arctic cold. Other schemes include the possibility of finding frozen sperm in a mammoth carcase and fertilising an elephant with it, but that idea is fantastical indeed. If the spurious Mammoth ever does appear the creatures could move to Pleistocene Park in Siberia, a recent attempt to simulate what the tundra looked like in the days when it was grazed by their extinct relatives. The mammoth steppe was the largest single block of habitat ever seen, far larger than the tropical rainforest, and those great beasts were what ecologists call a “keystone species”: a creature whose activities determine the fate of many others. Wolves are the same: when they were introduced into the USA’s Yellowstone National Park 15 years ago, they reduced elk numbers by half, so that ground cover increased, sheltering voles that were eaten by hawks, and so on and on. A Russian enthusiast has already fenced off a section of Siberian tundra and filled it with wild horses, bison, and deer. Shapiro describes how the effect has been dramatic; a great increase in rich grassland as the animals trample the soil and recycle nutriments and, less predictably, less snow cover in winter as their hooves sweep it away. That, in turn, means that the permafrost gets colder than before, and—an unexpected bonus—releases less carbon dioxide. A new behemoth might then play a part in keeping the whole planet cool. Another approach to populating Pleistocene Park is simpler: why not get the conservationists of the world to knit great woolly suits for the animals to keep them warm and comfortable in wintry Siberia?
How to Clone a Mammoth: The Science of De-Extinction Beth Shapiro. Princeton University Press, 2015. £16·95 ISBN 9780691157054
Steve Jones [email protected]
125