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My Clone Sleeps Alone

“As you must have guessed by now,” the man took over, “I am, we are, clones of a single individual. Some two hundred and fifty years ago, my name was Kahn. Now it is Man…I am over ten billion individuals but only one consciousness…No other humans are quickened, since I am the perfect pattern.” Joe Haldeman – The Forever War

In nature, some plants and single-celled organisms produce genetically identical offspring through a process called asexual reproduction. In asexual reproduction, a new individual is generated from a copy of a single cell from the parent organism. For example, water hyacinth produces multiple copies of genetically-identical plants through a process known as apomixis, or asexual seed formation.

Archaea, bacteria, and protists reproduce asexually by binary fission, where a cell divides giving rise to two cells, each having the potential to grow to the size of the original cell. Finally, some plants, invertebrates (such as water fleas, aphids, stick insects, some ants, bees and parasitic wasps), and vertebrates (such as some reptiles, amphibians, fish, and few birds) reproduce using parthenogenesis, a form of asexual reproduction where an unfertilized egg develops into a new individual in the absence of the male gamete.

Natural clones, also known as identical twins, occur in humans and other mammals. Natural clones are produced when a fertilized egg splits, creating two or more embryos that carry almost identical DNA. Identical twins have nearly the same genetic makeup as each other.

But when most people think about cloning, they think about scientists cloning animals, especially Dolly the cloned sheep. Few people understand that scientists have been working on cloning for over 100 years.

History

The first cloned animals were created by Hans Driesch, a philosopher and biologist who cloned a sea urchin in 1891. He took a two-cell sea urchin embryo, shook it apart, and showed that each cell developed into a complete individual, refuting the then prevalent idea that if the cells from a two-cell embryo were separated, each could create only half a creature. Then in 1902, embryologist Hans Spemann used a hair from his infant son as a noose to constrict the egg of a salamander into a dumb-bell shape, with the nucleus in one half and only cytoplasm and other cellular material in the other, pioneering the process of nuclear transfer. In this process, the nucleus is removed from an egg, and replaced with the nucleus of an older donor cell. A new clone – a genetic copy of the donor – forms when the egg starts to divide.

In 1951, a team of scientists in Philadelphia working at the lab of Robert Briggs cloned a frog embryo, taking the nucleus out of a frog embryo cell and used it to replace the nucleus of an unfertilized frog egg cell. Despite claims in 1977 by German development biologist Karl Illmensee that he had cloned three mice (never independently replicated), and the claims of author David Rorvik in his 1978 book “In His Image: The Cloning of a Man” that the world’s first human clone had been born (a claim later admitted by the publisher – but not Rorvik – to be a hoax), no progress was made until 1986, when two teams, working independently but using nearly the same method, announced that they had cloned a mammal. One team was led by Steen Willadsen in England>, which cloned a sheep’s embryo. The other, led by Neal First in America, cloned a cow’s embryo.

On July 5, 1996, Dolly, a Finn Dorset lamb, was born at the Roslin Institute in Edinburgh, Scotland, cloned from a frozen mammary cell from another adult sheep. The team that created her, led by Scotsman Ian Wilmut, hoped to create an animal whose cells were genetically young again, rather than prematurely adult. When Dolly was euthanized nearly six years after her birth, concern was raised that her progressive lung disease was caused because her cells were already old; she also had premature arthritis. Over the course of her life, Dolly gave birth to four lambs, proving clones can reproduce.

In 1997, Teruhiko Wakayama and Ryuzo Yanagimachi of the University of Hawaii created Cumulina the cloned mouse. She was cloned from cumulus cells (cells which surround developing egg cells) using traditional nuclear transfer, a technique now known as the Honolulu Technique. The nucleus was taken from the cumulus cell and implanted in an egg cell from another mouse. The new cell was then treated with a chemical to make it grow and divide. The scientists repeated the process for three generations, yielding over fifty mice that were virtually identical by the end of July, 1998, with a success rate of 50:1, compared to the Roslin Institute’s technique (used to create Dolly) which had a success rate of 277:1.

Cloning Today

Cloned animals have showed up in a variety of places in the past few years. In 2007, South Korean scientists produced drug-detecting dogs that are clones of a prized security dog named Chase. Because only 30 percent of natural-born sniffer dogs can normally pass the required training, researchers hoped cloned dogs would significantly improve this rated. In 2011, it was reported that all of Chase’s clones passed the required training.

The U.S. Food and Drug Administration ruled in 2008 that meat from cloned animals is safe to eat. Currently, two U.S. companies, Trans Ova Genetics and ViaGen, offer cloning services to cattle breeders.

In 2007, two clones (Show Me and Shawnee) from the mare Sage, awarded “best playing polo pony” at the 1997 International Gold Cup, were born. Earlier this December, polo superstar Adolfo Cambiaso rode Show Me in the championship match of the Argentine National Open, which his team La Dolfina won. Polo horses are hard to find and extremely expensive. Each world-class rider may have dozens, the best of which may cost more than $200,000 each. Cambiaso teamed up with Alan Meeker of Crestview Genetics, a Texan firm, to clone eight of his mounts. Although polo’s various governing bodies approved clones for competition, no clone had yet been tested in a match prior to this, since polo horses seldom compete until they are five years old. In June 2012, the Fédération Equestre Internationale lifted a ban on cloned horses, making them eligible for the 2016 Summer Olympic Games. Cloned racehorses aren’t popular because the U.S. Jockey Club, with which horses must register to race in North America, bans cloned horses.

Finally, there is a growing interest in cloning extinct species. In 2003, a team of Spanish and French scientists used frozen skin to clone a bucardo, or Pyrenean ibex, a subspecies of Spanish ibex that went extinct in 2000. Unfortunately, the clone died minutes after birth. Researchers will make another attempt using the 14-year-old preserved cells from the last animal, which was named Celia. Celia’s cells have been frozen during the last 14 years in liquid nitrogen, and if the cells prove to be intact, an attempt to clone embryos and implant them in female goats

In Australia, the genome of an extinct Australian frog has been revived and reactivated by a team of scientists by implanting a “dead” cell nucleus into a fresh egg from another frog species, although none of the embryos survived beyond a few days.

One of the questions being raised about such cloning is whether such cloning techniques “bring back” an extinct species, or just create a new one that looks exactly like the old one. At a TEDx conference in Washington DC sponsored by National Geographic, scientists and conservationists met to discuss the so called ‘de-extinction’ of a number of species, as well as the ethical, moral and technical questions of doing so. According to one of the conference organisers “That remains to be seen. It is one reason to do the research: is the genome the species? The answer will vary from species to species. De-extincted plants should flourish as if they’d never left, if suitable pollinators are still around. But if California condors had gone extinct, it’s unclear if they could be brought back fully, because the young rely on parental training.”

References

Broad, William J. Court Affirms: Boy Clone Saga Is a Hoax.” Science, Vol. 213, July 3 1981, p.118-119.

Broad, William J. Publisher Settles Suit, Says Clone Book Is a Fake. Science, Vol. 216. April 23, 1982. p.391.

Cloned Horses Allowed in Olympics. ABC News. Posted Jul 12, 2012 7:39am. http://abcnews.go.com/blogs/headlines/2012/07/cloned-horses-allowed-in-olympics/. Retrieved 12/14/2013.

Culliton, Barbara J. Scientists Dispute Book’s Claim That Human Clone Has Been Born. Science, Vol. 199. March 24, 1978. p.1314-1316.

Gurdon, J.B., & Byrne, J.A. (2003) The first half-century of nuclear transplantation. Proc. Natl. Acad. Sci. USA100, 8048-8052.

Room Needed on the Ark

Startling StoriesImagine in the not-so-distant future an asteroid is on a direct course to hit the Earth. It’s large enough to destroy most life as we know it. NASA, the European Space Agency and China’s National Space Administration are scrambling to launch teams that will attempt to deflect the asteroid, but there is no guarantee that they will be successful.

Meanwhile a team of scrappy and resourceful aerospace engineers and biologists put into motion a plan meant to rescue at least a few species – including humans – from extinction. A spacecraft that will carry genetic material, along with live plants and animals, is readied for launch.

The hope is that after escaping the cataclysmic effects of the asteroid strike, the space ark would travel long enough for the Earth’s dust to settle (literally) so that the ship could return and restore life on our planet. Or perhaps the ship would continue on to a distant solar system, and the life it carries would be used to start a new settlement on a habitable planet.

This would obviously be a technically complex operation that would require substantial advance planning. One of the big tasks for the biologists on the team would be to decide how the genetic material and live travelers on the space ark would be selected and collected.

An obvious source of genetic material would be gene banks that collect and store samples of a wide range of genetic material. Such repositories exist today. The Millenium Seed Bank Partnership, for example, is an international project meant to save seeds from wild plants around the world. There are a number of other more agriculture-focused gene banks around the world that preserve seeds from a variety of crops.

Animal genetic material is a bit more difficult to archive than plant seeds. Projects like the US Department of Agriculture’s national Animal Germplasm Program primarily focuses on collecting and storing semen and eggs, not embryos.

There is also a current push to sequence the genomes of as many different species as possible. Perhaps in the future will have the technology to start from a raw DNA sequence to create a living breathing animal. There have been recent proposals to use DNA sequences along with reproductive cloning technology to restore wild animal populations on the verge of extinction.

But whether an “archived” animal is grown from germ plasm or from a synthesized DNA sequence, there still must be at least one female for the fetuses to grow in. Not a simple proposition.

But it would not be enough for our space ark to carry a male and female of each species. There must be a minimum number of genetically distinct individuals to allow a population to survive and thrive.  Conservation biologists estimate that such a “minimum viable population” would require anywhere from a hundred to several thousand members to survive at least a century. The lower estimates usually assume that there would be minimal environmental changes and human intervention to keep the population going.

Even with human intervention a lack of genetic diversity in a population puts it at serious risk for being completely destroyed by disease or unexpected environmental changes. That’s already a problem today. Disease outbreaks have put agricultural “monocultures” of some crops (like the Cavendish banana) at risk of extinction.

If samples from many individuals of a species are required for genetic diversity, our hypothetical space ark might not have enough space to carry every known species. So how would a biologist decide which critters are most important to save? That turns out to be a complicated question.

Restoring – or creating – a stable ecosystem needs to have a wide variety of different species from microbes to large vertebrates and algae to trees. The exact needs would depend on the local climate, soil and atmospheric conditions, among other factors. So far, we humans haven’t been very successful in creating an ecosystem from scratch. And the less that’s known about the environment where the ecosystem is going to be established, the longer the list of potentially necessary species.

So for the space ark scenario to work, it would not only need to carry a variety of species, but a variety of individuals in each species. And that is, of course, in addition to the humans – not just an Adam and Eve, but a large mixed group of people with enough genetic variation to start a healthy human colony. Throw in the complex social and political considerations in selecting who gets rescued and the population would probably have to number in the thousands.

Our hypothetical space ark would have to be huge to carry them all!

The space ark scenario is admittedly pretty implausible, at least with present-day technology. Even so, I think it’s worth seriously considering how it might be done. That’s not just because catastrophe is always a possibility, but because I’d like to think that some day self-sufficient extraterrestrial colonies will be a reality. We need to start thinking about how we might do that now so that the genetic material can be saved and reproductive technologies can be developed before they become a necessity.

But there are many questions that need to be considered:

If we are going to collect and archive seeds and animal germ plasm and genomic DNA sequences should the focus be on agricultural species? or should we cast our species net as far and wide as possible?

Should we seriously consider setting up a gene bank on the Moon, just in case something terrible happens to the Earth? or would it be better to have our archives closer at hand so that they can be more easily maintained and added to? How much redundancy should there be between different seed and germ plasm repositories?

Or should we focus more of our resources on developing synthetic biology techniques, in the hope that they will eventually become advanced enough so that collections of physical specimens will become unnecessary?

And if Earthly life is destroyed, would it be worth trying to restore Earth’s ecosystems or better to start over elsewhere among the stars?

What do you all think?

Technical Reading 

Blackburn HD “Genebank development for the conservation of livestock genetic resources in the United States of America” Livestock Science 120:196-203 (2009) (pdf)

Holt WV et al “Wildlife conservation and reproductive cloning” Reproduction 127:317-324 (2004) (text)

Traill LW et al “Minimum viable population size” a meta-analysis of 30 years of published estimates” Biological Conservation 139:159-166 (2007) (pdf)

Shaffer ML “Minimum Population Sizes for species Conservation” BioScience 31(2):131-134 (1981) (pdf)

Zhu et al “Genetic diversity and disease control in rice” Nature 406:718-722 (2000) doi:10.1038/35021046 (text)