(Wikimedia)

How to create an auroch

To re-create a large brutish cow that isn't very tasty and probably doesn't like being milked, here's what you do


Beth Shapiro
May 24, 2015 7:59PM (UTC)
Excerpted from "How to Clone a Mammoth: The Science of De-Extinction"

So, mammoth cloning is not going to happen. No intact  genomes will have survived the 3,700 years since the last mammoth walked on Wrangel  Island. No mammoth chromosomes will  be found that  are sufficiently repairable to transform the  cells  in which they  are found into pluripotent stem cells. From my perspective, it doesn’t matter how many trips are made to deepest Siberia or how many tunnels are blasted into  the  permafrost. It’s  just  not  going to happen.

Should we just  give  up? Walk away dejectedly with our tails between our  legs?  Go  back to the rest tent and cry into our mosquito-laden rice soup?  Of course  not!  As it turns out, there are perfectly reasonable, perfectly feasible ways of bringing back a mammoth. Well, of bringing back kind of a mammoth. But let us not drown ourselves in the semantic argument just yet.  First, the science.

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There are two ways to bring an extinct species back to life that are feasible in the present day. One of these is so straightforward that  most people  probably have not thought of it in the context of de-extinction. The other is more magical, and by “magical,” I mean the most-incredible-scientific-advance-in-a-long-while kind of magical. Let’s begin with the more straightforward approach.

It is possible to bring an extinct species  back right now using technology that our species began to refine some twenty or thirty thousand years  ago. It is around this  time  that  we find the first genetic and archaeological evidence of domestication—changing the  course  of evolution to suit  our  needs  and  desires. The approach is not overly sophisticated and requires only a reasonable grasp of basic  evolutionary biology. Mainly, the idea  is to take advantage of three facts. First, the physical and behavioral characteristics that  define  an  individual—that  individual’s phenotype—are determined by  the  sequence of  the  individual’s genome—its genotype—and the interaction of that  genotype with the environment. Second, genotypes are passed down from parents to offspring. Third, natural selection can change the relative frequencies of different phenotypes within a population. In the wild, phenotypes that  are better  adapted to the environment in which the organism lives will become more common than phenotypes  that  are less well adapted to the same environment.

To bring a mammoth back,  we can simply take advantage of nature’s own process  of genetic engineering. All we have to do is find  the  hairiest, most  cold-tolerant elephants that  exist  and breed them with each other. After a few generations, we will have created, without calling upon  any DNA-sequencing technology at all, an elephant that can live in Siberia.

BACK-BREEDING

Henri Kerkdijk-Otten is a friend  of mine who lives  in the Netherlands and loves cows.  Specifically, he loves large  brutish cows that may  or may  not taste very  good and  probably don’t enjoy being milked. Henri loves aurochs. Unfortunately for Henri, aurochs have  been  extinct since  the middle of  the seventeenth century.

Henri,  however, has a plan.  He will bring his beloved aurochs back from extinction not by finding well-preserved fossils in European  forests and  not by nuclear transfer but  by the comparatively simpler process  of selective breeding. His hope is that he can create an auroch by carefully selecting and breeding animals that have  physical and behavioral traits reminiscent of the ancient  aurochs. After this process  of choosing which cow  gets  to mate with which bull  continues for many  generations, the aurochs  (or at least  a close rendition of the aurochs) will  be back. They will  be able  to roam  free in the  Dutch grasslands, where they will  presumably thrive on the ubiquitous tulips.

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Aurochs are  the  wild  ancestors of domestic cattle. Around 10,000 years ago, human populations in the Near East and South Asia  began farming and  taming wild  aurochs. Eventually, this gave rise to the two main variations of domestic cattle—humpless taurine cattle and humped zebu.  Today, taurine cattle are widely distributed across  the  globe and  belong to  familiar-sounding breeds  like  Holstein, Angus, and  Hereford. Zebu  tend  to  be farmed  in the tropics, thanks to adaptations that allow them  to survive better than taurine cattle in very warm climates. Because domestic cattle are descended from aurochs, much of the genetic diversity that was present  in wild aurochs is probably still present in living cattle. It may, however, be distributed among the various breeds. To reengineer an auroch, one simply has to concentrate into a single new lineage all of the auroch-like traits that  are present in living zebu and taurine cattle. The end product will not contain the genome sequence of a purebred auroch. It will, however, look like an auroch.

The first  genetic-engineering experiments performed by humans  involved genetic manipulation of wolves, probably gray wolves that  lived in Europe  as long as 30,000  years  ago.  It is at this  time  that  we  find  the  first  probable evidence of domestic dogs: bones found in archaeological sites that look similar to but distinct from the bones of gray wolves. These early stages of dog domestication were, of course,  not hardcore genetic-engineering experiments. Instead, wolves that  were more tolerant of humans and  humans who  were  more tolerant of wolves both benefited from a closer association. Just like my own dogs, these first dogs benefited from access  to table  scraps. The people  living in proximity to these early dogs benefited from early warnings of approaching danger, much the same way  I benefit from  knowing that  the mail  has  arrived. Once  the symbiosis was  established, humans put  genetic engineering to  work.  Today we have  big dogs, small  dogs, strong dogs, fluffy  dogs, dogs with short  legs, dogs with long ears, hunting dogs, herding dogs, dogs that  can find people  buried in avalanches, dogs that  provide life support for  people  with disabilities, and  dogs that  can  be  carried in leopard-spotted purses  on trips  to the grocery store.

Henri  and his colleagues plan to reverse-engineer the domestication process  in cattle. Instead of breeding for traits that we tend to associate with domestic animals—tameness and manageability, for example—they want to re-create the wild  ancestor of the domestic cow. Beginning with the more “primitive” breeds— including Maremmana, Moronesa, and two Dutch  breeds, Limia and  Sayaguesa—they have  developed a selective breeding program  designed to capture the physical and behavioral characteristics  of aurochs and,  in doing so, create  a new cattle breed.  The process  is known as back-breeding, which is a name that  highlights the goal: to breed back traits that used to exist and hopefully still exist  somewhere in the gene pool of living individuals.

Today’s effort  is not  the  first  attempt to back-breed the  auroch.  In  the  1920s and  ’30s,  the  German brothers Heinz and Lutz Heck,  who  happened to be directors of the  Hellabrunn Zoological Gardens in Munich and the Berlin Zoological Gardens,  respectively, were instructed to re-create the auroch. This directive is said  to have  come from  Hermann Göring, who,  as an avid  hunter, wished to re-create the folkloric prey of Roman hunters. (Although it is unappealing to attribute the first back- breeding experiments to the Nazis, one cannot ignore the timing  of this work  in  interpreting its  motivation.) The Heck brothers had  the same  goal but performed their experiments separately. They each  selected different cattle breeds  and  used these  breeds  in different crosses. At the  time,  no scientific re- constructions of  the  auroch were  available, and  so  neither brother had  a particularly good sense  of what an auroch  actually  looked  like.

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In 1932, Heinz Heck declared his back-breeding experiment a success. A bull  was  born  that  he felt  looked  similar enough to what he believed an auroch should look  like that  his new  bull could  be called  an auroch. According to Heinz’s records  (which he stopped keeping after  the birth of this  bull), the bull  was  75 percent Corsican cattle, 17.5 percent Gray  cattle, and the remaining  17.5 percent was  a mix  between Scottish Highland, Podolic Gray,  Angeln, and Black Pied Lowland cattle. Selective breeding continued after  the  birth of this  bull,  eventually giving rise to what is today known as Heck cattle. Around two thousand Heck cattle are alive today, living in zoos and roaming pastures, mostly in Europe.

Are Heck cattle aurochs? Heck cattle certainly look primitive, particularly to someone  who (like  the Heck brothers) might not have  access  to accurate reconstructions of  real  wild  aurochs. Heck  cattle have  dark  coats  and  long, curved horns,  which are two  characteristics that  were  definitely found in wild  aurochs. Heck cattle are also more cold tolerant than many other domestic breeds  and  can survive under  relatively poor forage conditions, much as their wild  ancestors must have done during Pleistocene glacial cycles. That, however, is about where the similarity ends. Heck  cattle are large  for domestic cattle, but  not as large  as the average auroch bull would have been. A Heck bull stands around 1.4 meters  high at the shoulder and weigh up to 600 kilograms. An auroch  bull,  with a shoulder height around 2 meters,  would have been taller  than the average European man. Also, while  the coat color of Heck bulls  is similar to what we believe was characteristic of auroch  bulls, Heck cows  are lighter and more variable in color than  auroch  cows were. The overall body  shape of Heck cattle is also  different from  that  of aurochs, mainly in that  it is smaller and, like all domestic taurine cattle, lacks the prominent neck musculature of the wild  ancestors. Finally, while  the horns of Heck cattle are long, relative to those of domestic cattle breeds, their  shape  and  curvature are somewhat different from  an  auroch’s:  they  curve  slightly too close to the head and point a little bit too far outward.

It is safe to conclude that  the Heck brothers did not quite  hit the mark. This failure, however, does not spell doom for the present back-breeding project. Today, we know  much more than  the Heck  brothers knew  in the early  twentieth century about what traits defined  aurochs. We have better descriptions of the various breed  phenotypes and  a better understanding of the  temperaments  of these breeds. We have abundant genetic data  that  help to determine which breeds are the most primitive. We even have ancient DNA data  from actual aurochs. Using all of these  data, there is little doubt that we will make different and more scientifically  justified choices about what animals to  use  in  the  back- breeding project, which will  eventually lead  to the birth of animals that  better  resemble  wild  aurochs.

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Of course,  these  animals will  not actually be aurochs. Not  exactly, anyway. Selective breeding is a process  by which individuals that  display the desired  phenotype are bred together to try to replicate that  phenotype in the next generation. The phenotype, however, is a consequence of the interaction between genotype and  environment. Genetically, the  gradual  concentration of genes  that  code for auroch-like traits has to happen by chance. When the gametes—the sperm or egg cells that  will  go on to become the next generation—are formed, each one contains a shuffled version of that organism’s parents’ genomes. This shuffling of genetic material, called  recombination, is an important source  of genetic variation within populations. Recombination shuffles genes or parts  of genes from mom’s chromosome onto dad’s chromosome and vice versa. When the sperm or eggs are formed, they  will  contain some  DNA  from  mom  and  some  DNA  from dad. If a phenotype that  we want to select is coded for by a gene that  came from mom, but the egg that  is fertilized contains dad’s version of that  gene,  then  the offspring, despite our best  intentions,  will  not display that  phenotype.

We can guide the process  of concentrating specific  traits into a single lineage by selective breeding, but  we cannot selectively choose  which gametes go  on to become  that  next  generation. Some  offspring will  get  the right genes  and  display the desired phenotype, and others  will not. This does not mean that  the process will  never work.  It will,  however, be slow. Selecting for multiple traits simultaneously will be particularly challenging, as the genes for each trait need to wind up, by chance,  in the same fertilized egg. Despite this,  selective breeding is and has been a powerful tool  in  our  species’ history, as attested by  the  variety of forms  of domestic plants and  animals that  we encounter every day.  There is no reason  why, with sufficient time,  resources, and patience, we cannot recover  at least  some traits of the wild  auroch using the selective breeding approach.

As the auroch back-breeding experiment proceeds, I anticipate that the animals will  gradually become  more and  more auroch-like in their  physique and  behavior. Some auroch traits may, however, never be recoverable from living cattle breeds. The DNA  sequence that  coded  for a particular trait  may  have  been lost, for example, or the trait  may have been the product of a genetic  interaction with an  environment that   no  longer exists. Some  people  (myself included) would argue that  this  does not matter—that by filling the niche of the auroch, even partially, the experiment is  a  success. De-extinction purists will,   however, never  be satisfied with a back-breeding product, because the result will always be something new, not something old. Auroch 2.0 will  not be an auroch. Not precisely, anyway.

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IS  SIMPLER  NECESSARILY  BETTER?

One advantage to back-breeding as a means  of de-extinction is that  it  relies  so  little on  molecular biology technologies. Genomes don’t have to be sequenced, genes don’t have to be identified, and genetic variants don’t have to be linked to specific  traits. The gradual transition from one form to another happens without embryonic stem cells and long hours  spent  in a lab. And the results of the experiments are validated qualitatively: does it or does it not look more like an auroch?

The simplicity of back-breeding, however, may  also be its downfall. While  traits such  as dark coat color, long forward-facing horns,  or strongly expressed neck and shoulder musculature may emerge in the population after  some generations of selective breeding, the genes that  code  for  these  traits once  the traits reemerge may be different genes  from those  that  coded for the same traits in the extinct species.

Does it actually matter? If we want long forward-facing horns, and the bull  has long forward-facing horns,  does it really  matter what specific genes  are making it happen? It might matter. Genes don’t always, or even often,  have  just  one function. A gene that makes curved horns might have other  consequences on the resulting cattle phenotype that  we don’t want. It might make their skull  slightly differently shaped, for example, or somehow influence  the shape  or texture of their hooves. In  addition, genes don’t act in isolation but instead act in concert with other genes that  are also expressed in the cell.

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An example of an interaction between genes that  is used  in introductory biology classes is the way  that  coat  color in horses is determined. Horses have a single gene that determines whether their  coat  will  be red or black. The dominant allele  produces a black  coat  and  the recessive allele  produces a red coat. If  this gene acted alone, individuals that carried either two copies of the dominant allele  or one dominant and one recessive allele  would have black coats and  individuals that  carried two  copies  of the recessive would have  red coats. However, there are many  different types  of red or reddish horses.  This comes about because of yet another gene—the cream dilution gene—that modifies the expression of the red alleles. A horse that  has two  copies  of the recessive red  allele  can  be chestnut colored, palomino, or even white or cream  colored, depending on how  many  copies  of the cream dilution allele it carries.

While not all interactions among genes  are known, and  very few are well understood, this does not mean that  selective breeding for specific  traits is impossible. Through multiple generations of back-breeding, using different crosses involving different individuals or different breeds, the right combination of genes, or at least  combinations of genes  that  provide the right phenotypes, may eventually be discovered. How  long it will  take depends on several factors, including how  many  traits are  being selected, how  easy  the animals are to breed,  and  how  long it takes  to go from one generation to the next.

TOO  SLOW  FOR  SUCCESS?

The generation time of cattle is short  compared to many  species. Female  cattle can breed for the first time when  they  are between one and two years old, and gestation takes around nine months. A selectively bred individual can be born, develop into an adult, get pregnant, and give birth to the next generation all within two to three years. While not a breakneck pace, one can imagine how a selective breeding program could  progress reasonably quickly in cattle.

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Progress would be much,  much  slower for some of the other candidate species for de-extinction. For example, male elephants begin making sperm between ten and fifteen years  old,  and  female elephants in the wild will become pregnant for the first time around age twelve. Gestation time in elephants is between twenty and twenty-two months. That means  there would be a fourteen-year wait  between when the first selectively bred offspring is born and when that offspring can produce the next generation. At that pace,  only  five generations could  be produced in a human lifetime. There must  be a better  way.

Of course  there is. An easy way  to minimize the time it takes to selectively breed a trait into a lineage is to make sure that every individual in the next generation contains the target trait. This is not possible with back-breeding, where the offspring of two parents  may  or may  not  inherit the target trait  or traits. However, new technologies—specifically, the genome engineering technologies  that are behind the second presently feasible (and the more magical) pathway to de-extinction—make it possible to edit  the genome directly. By manipulating the DNA  sequence in a cell and then using that cell to create living individuals, we can be certain that  the target trait is present in the next  generation. We can make the entire process  of resurrecting extinct traits in living species  move along much more quickly and efficiently.

For example, we know  that  mammoth hemoglobin—the protein in red blood cells that takes up oxygen in the lungs and then distributes it via the circulatory system to the rest of the body— differs  from  elephant hemoglobin by  exactly four mutations.

These four differences modify the performance of the hemoglobin by making the mammoth version more efficient than  the elephant version at delivering oxygen when the temperature in the body  is very low (think mammoth feet standing in the snow).

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We will  not find a living elephant that has the mammoth version of these hemoglobin genes. The common ancestor of mammoths  and living elephants lived  in the tropics, and adaptations to life in the cold  would have  evolved in mammoths only  after the mammoth lineage diverged from the Asian elephant lineage. Since  all mammoths are extinct, there are precisely no individuals alive who have these particular genes. In order  to create an elephant that  makes  mammoth hemoglobin, we  will  have  to make the mammoth version of those genes from scratch and then somehow insert that version of the gene into an elephant cell. We can do that.

Excerpted from "How to Clone a Mammoth: The Science of De-Extinction" by Beth Shapiro (2015), courtesy of Princeton University Press. 


Beth Shapiro

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