Will humans ever recreate extinct species?

This essay was written for a high school biology project several years ago. Some of the science may therefore be slightly outdated.

Introduction

"Species, once lost, do not reappear."
- Charles Darwin

In 1991, Michael Crichton published his novel Jurassic Park, in which an eccentric millionaire uses the latest biotechnology to recreate dinosaurs on a remote tropical island. Two years later, the book was turned into a spectacular Steven Spielberg film, widely publicising the notion that extinction may not be forever. All of the instructions for making a life form (whether it is an animal, a plant, or a micro-organism) are contained in its DNA - a huge chain molecule stored inside each of the creature's cells. In theory, if you have a complete strand of DNA from an extinct animal (such as a dinosaur), you can use it to recreate the animal.

Unfortunately, the only parts of the dinosaur that we normally have today are its fossilised bones, and time and geological transformation have all but eliminated their DNA. (Whether they contain any recoverable DNA at all is currently a matter of great controversy, but you certainly can't extract a complete, perfect DNA sequence from a fossil bone.) However, in 1977 the science fiction writer Charles Pellegrino identified a possible source of well-preserved dinosaur cells. Amber - fossilised tree resin - sometimes contains insects in a state of near-perfect preservation. Some of these insects date back to the age of the dinosaurs, and if an insect's last meal consisted of dinosaur blood then the dinosaur's blood cells - and the DNA that they contained - might be preserved. This was the great idea that inspired Crichton to write Jurassic Park.

After the Spielberg movie brought Jurassic Park to massive audiences world-wide, scientists were quick to condemn it as being unrealistic science fiction. Michael Crichton has admitted in interviews that he had intended to put across a clear anti-science message when he wrote the book; however, the public were reassured by nearly all respectable biologists that the resurrection of dinosaurs was not even remotely feasible.

If Jurassic Park had been published today, I think that the public would have taken it a little more seriously. This is because of a scientific breakthrough that was achieved two years ago, in a small institute near Edinburgh, a breakthrough that shook the world and brought the re-creation of dinosaurs a small step closer to reality. That event was the birth of Dolly the sheep, the first large animal to be cloned using the genes of an adult cell.

There might not seem an obvious connection between duplicating a farm animal and bringing the dinosaurs back to life. However, the dinosaurs in Jurassic Park were actually cloned (although they are not normally thought of as such), albeit in an unusual way. The ability to clone an adult animal not only brought Jurassic Park closer to reality, but raised serious ethical questions about the potential applications of biotechnology.

Even if it is impossible to extract dinosaur DNA from the limited fossil material available, there are still many extinct animals that died out much more recently. The preserved skins and organs of these animals are still residing in our museums, and the extraction of DNA from these would present no major technical challenge. Even if we can't bring dinosaurs back to life, there is always the dodo.

Dolly the sheep was a nightmare of science fiction, one that many scientists insisted could never be brought to life. In this way, is she really that different from the monsters of Jurassic Park? And if it is possible to clone, perhaps the resurrection of extinct animals may be feasible after all.


Relics from the past

Is it possible to re-create extinct animals by selectively breeding living ones?

The evolutionary story of the perissodactyls - the odd-toed hoofed mammals - is a sad one of continual tragedy and extinction. Once representing a diversity of grazing mammals ranging from rabbit-sized forms to elephantine giants, this order is now reduced to only three small families: the horses, the rhinos, and the tapirs. On 12 August 1883, the quagga - a form of zebra, which was brown and was un-striped on the back portion of its body - became the latest victim in this sorry saga of death and destruction.

However, the quagga is one perissodactyl that may not be doomed forever to the fossil record. The South African Museum in Cape Town is now attempting to re-create the quagga by selectively breeding Burchell's zebras (a close living relative) in the hope of creating a breed whose markings exactly mimic those of the quagga. This may seem an exciting and potentially very easy way of bringing extinct animals back to life, but nobody will ever truly re-create an extinct species in this way. What the South African Museum's experiment will prove, if successful, is not that it is possible to bring a species back from the dead, but that the quagga is not a species at all. It is merely a subspecies of Burchell's zebra (Equus burchelli), a fact that most zoologists now recognise. No genetically distinct species could be restored through a short breeding programme.

Breeding extant species to look like extinct ones is really an artificial form of convergent evolution - the phenomenon where one species evolves to closely resemble another fairly unrelated form. The thylacine of Tasmania (Thylacinus cynocephalus), for example, was almost identical in size and form to the domestic dog (Canis lupus familiaris), but nobody is trying to argue that the thylacine and the dog are the same species. They are genetically different, and have not shared a common ancestor since the end of the Jurassic period, 150 million years ago. Although they may look similar, a detailed study would almost certainly give away their different ancestries: for one thing, the thylacine is a marsupial with a pouch, while the domestic dog has a placenta and gives birth to well-developed young. In the same way, a quagga created by selectively breeding extant zebras would never be truly the same as the extinct quagga.

The thylacine
The thylacine

The thylacine and the quagga have something else in common: human hunters persecuted both and both met their final fate - extinction - in zoos, several decades ago.

Even though the current programme to re-create the quagga falls a long way short of re-creating extinct species, the quagga has been the subject of another important breakthrough, which may have far more significant consequences. This is the successful extraction of DNA from a 140-year old quagga hide by three Berkeley scientists. Using a small skin sample taken from a German museum specimen, it was possible to determine a long enough sequence of base pairs (the individual 'letters' that make a DNA sequence) to draw valid conclusions about the relationship of the quagga with living horses and zebras. It was largely this genetic evidence that led to the quagga's reclassification as a breed of Burchell's zebra.

If long sequences of DNA can be recovered, then I see no theoretical reason why the animal's entire genome could not be pieced together. This would inevitably require quite a large amount of DNA-bearing material, but there are many quagga skins around today (I have seen the animal on display in both the Paris Natural History Museum and the Tring Zoological Museum).

Is it possible to re-create animals that have only recently gone extinct using preserved DNA?

Clearly, the recovery of DNA in fairly good condition from animals that died out only in historical times presents no major problem, so long as we still have a good supply of preserved skins. The quagga, as I have already explained, is not really a distinct species, but there are many true species from which DNA could be recovered in a similar way. The thylacine is one. Another is the Great Auk (Pinguinus impennis), a large penguin-like bird that provided food for countless sailors on long voyages across the North Atlantic. It was the continual plundering of its island breeding colonies that eventually led to the bird's extinction. The world's collection of preserved Great Auks comprises 75 eggs, 81 mounted skins, 24 skeletons, and 2 sets of innards. The innards come from the last two Great Auks, a pair killed by collectors on Eldey Island off Iceland on 2nd June 1844, and could prove an invaluable source of DNA.

The first successful extraction of quagga DNA was done in 1984. At the time, nobody thought that the recovery of DNA from much older specimens could be achieved because scientific techniques at that time were not sensitive to the tiny quantities of genetic material that are preserved. This has all changed, however, since the invention of PCR (the Polymerase Chain Reaction), a sort of 'biological photocopier' that can take a small piece of genetic material (and lots of spare DNA base molecules) and make millions of identical copies. The idea is ingenious - it exploits the enzymes that all living things use naturally to duplicate their DNA. (The enzymes used in PCR are taken from bacteria that live in hot springs, since their enzymes can be heated considerably without being damaged, and heat greatly speeds up the reaction.) The inventor of PCR was awarded a Nobel Prize in 1993.

With PCR, scientists can take a tiny quantity of organic material and make millions of copies of any genetic material that it contains. It has allowed the DNA of much older remains to be examined. The DNA of moas (gigantic flightless birds that lived in New Zealand until the arrival of humans 700 years) has been examined using the small scraps of skin which still adhere to some of the preserved bones. DNA has been extracted from the brains of 7,500-year old American Indians that were found in a Florida sinkhole. It has been preserved sufficiently well for detailed analysis to be carried out, showing that the American Indians who lived in Florida then differed little (genetically, at least) from those of today.

Can the giants of the ice age be brought back to life?

Re-creation of recently extinct animals would be a fantastic scientific achievement, but it is hardly the stuff of thrilling novels such as Jurassic Park. To find the youngest truly prehistoric animals (the monsters found in children's picture books and the potential crowd-pullers in a real-life Jurassic Park), you have to go back exactly 10,000 years, to the end of the last Ice Age. Before this time, during the geological epoch known as the Pleistocene, there were many large and exciting animals living in Europe - the famous Ice Age "megafauna". The woolly mammoth (Mammuthus primigenius), a hairy member of the elephant family with long, characteristically curved tusks, is perhaps the best known of these animals. The large European monsters disappeared quite rapidly about 10,000 years ago, probably due to a sudden climate change. We know that the great North American ice sheet slid into the sea at about this time, and the subsequent release of water into the environment transformed the dry grasslands on which the mammoths and their contemporaries grazed into the inhospitable, boggy tundra of today. The new, damper landscape couldn't support much plant life and was more liable to freezing; the mammoths couldn't cope with this new environment and quickly became extinct.

The woolly mammoth
The woolly mammoth

The remains of these extinct animals are everywhere. In some parts of Siberia, mammoth bones were once so abundant that the locals built houses out of them (the primitive peoples who lived alongside the mammoths during the Pleistocene also did this). In total, an estimated 96,000 mammoth tusks have been exported from Siberia. There are many localities, such as at the Rancho La Brea tar pits in Los Angeles, from which an exceptional number of fossil bones of Pleistocene age have been exhumed. However, any attempt at re-creation would probably require more than just fossilised skeletons.

In April 1984, an article appeared in the Massachusetts Institute of Technology's Technology Review, reporting that a Russian scientist had successfully created two elephant/mammoth hybrids (he apparently named them "mammontelphases"). The story was subsequently picked up by Sunday Weekly, a supplement distributed in over 350 newspapers. The article was, of course, a hoax (it was first published on April Fool's Day), but the fact that it fooled even a small number of people for a short period of time demonstrates that the scientific community treat the re-creation of mammoths far more seriously than Jurassic Park. Today, more than a decade after the hoax MIT Technology Review article, there are real Japanese scientists who are working on a project to resurrect the mammoth, using similar methods to those proposed in the article.

The source of mammoth DNA? Frozen bodies, embedded in the Siberian permafrost. Several of these bodies have been discovered - not just of woolly mammoths but also of woolly rhinos, a horse, a young musk ox, a wolverine, voles, squirrels, a bison, a rabbit, and a lynx. They are so well preserved that wolves often eat their flesh, and there is a report of scientists once being offered mammoth steak at a banquet! The Siberians regard them as "ice moles", animals that spend all of their lives burrowing in the permafrost and die if they ever see the sunlight. They simply cannot believe that such a fresh carcass could be tens of thousands of years and belong to a species that is no longer alive on Earth. Early zoologists also had trouble believing that the woolly mammoth was extinct.

The preservation of these animals really is truly remarkable. Frozen cells normally rupture due to the formation of ice crystals (this is one of the main problems facing those researching into cryogenics), but the cells of the Siberian specimens are fairly intact. There is food in the mammoths' stomachs (seemingly undamaged by the mammoth's digestive enzymes) and even between their teeth! The mammoths apparently fed on sedges and grasses, and the presence of flowers shows that the mammoths met their tragic end in late summer. This makes their sudden burial in ice even more remarkable, and many bizarre explanations have been put forward to explain it.

As far as I know, only mitochondrial DNA sequences from the mammoths have so far been examined (the fact that mitochondria could be isolated and examined highlights the truly exceptional nature of the preservation), but there is no reason why nuclear DNA should not also be preserved.

Unfortunately, the mammoth DNA is reportedly broken up into short fragments. Over an extremely long time, any large organic molecule will disintegrate in this way. Radiocarbon dating shows that the ages of the frozen mammoths fall into two groups: the oldest mammoths were frozen around 40,000 years ago, although others are only 10,000 years old. If DNA that is, at most, 40,000 years old is badly decomposed, then the chances of finding any recoverable DNA from older specimens are very poor. Another group of Pleistocene animals whose soft parts are sometimes preserved are the giant ground sloths. Originally an exclusively South American group, they were apparently so successful that they were able to migrate into North America when the Panama land bridge was formed about two million years ago. The largest of these lumbering giants, Megatherium, could stand fifteen feet tall on its hind legs, and its fossil skeleton is mounted in the London Natural History Museum where it is often mistaken for a dinosaur. All of the giant ground sloths died out at the end of the Pleistocene, yet their fossil bones are incredibly common. They were examined by Darwin on his voyage aboard the HMS Beagle, and may have helped him to formulate his revolutionary ideas on evolution.

In South America there is a deep cave, the Cueva Eberhardt, in which the remains of several ground sloths have been found. Besides a number of fossil bones, there are several pieces of preserved hide, still with dried muscles and ligaments attached. These apparently survived the passage of time by being partly buried in the dry environment of the cave.

A giant ground sloth
A giant ground sloth

The pieces of hide belong to a type of ground sloth known as a mylodon, smaller than Megatherium, but still an extremely impressive animal. The hide is possibly a hundred times older than the quagga's, yet researchers at the University of Munich claim to have extracted DNA from such specimens.

Is preserved amber a potential source of dinosaur DNA?

Amber is perhaps the best preservative of all. When an insect becomes stuck in tree resin, and the dried resin is buried and transformed into amber, the insect stays inside, completely safe from chemical or physical interference from the outside world. Some of the fossil insects that have been found in amber go back beyond the Pleistocene, beyond the Pliocene, beyond the Miocene - right back into the Age of the Dinosaurs, over 100 million years ago. Although the insects' own gut bacteria sometimes damage trapped insects from the inside, it is still possible to make out incredible detail on the specimens. Using an electron microscope, scientists have reportedly seen detail inside the cells of a 40 million-year old gnat: mitochondria, and the nuclei containing the chromatin that binds together chromosomes.

The big question, of course, is whether these insects contain recoverable DNA. In 1992, scientists at the American Museum of Natural History claimed to have extracted DNA from a 25 million year old termite. They also claim to have analysed the termite's DNA, concluding that termites did not evolve directly from cockroaches (as was previously believed), but evolved alongside them. George and Roberta Poinar (two experts in the recovery of ancient DNA whose contribution to the field was acknowledged by Michael Crichton at the end of Jurassic Park) claim to have extracted DNA from a fossil beetle dated at 125 million years old. This is nearly twice as old as the youngest dinosaurs, which were tragically wiped out at the end of the Cretaceous period about 65 million years ago.

Unfortunately, many of the discoveries of ancient DNA are highly controversial. The PCR technique used to duplicate the DNA for analysis is so sensitive that it will copy anything - if even the smallest trace of modern organic material got into the sample its DNA would be copied. It may, in fact, have been modern DNA and not ancient DNA that was being detected. A fairly sure way to ensure that the DNA is authentic is to analyse it properly and compare it to those of living organisms. If the team who extracted the termite DNA really did successfully analyse it (as they claim to have done), then it shows that the DNA involved might actually have been genuine.

Unfortunately, recent investigations have been unable to duplicate the results of earlier researchers. Richard Fortey, in his book, Life: An Unauthorised Biography, describes miserably how he and his colleagues failed to successfully repeat the experiments carried out by the Poinars and others. For, even though the amber protected the insect's genetic material from the environment, there is one agent that will inevitably damage any ancient DNA - time. And the time that has elapsed since the dinosaurs' demise may have destroyed all of the DNA once present in these ancient insects.

Just supposing that it was possible to extract small fragments of insect DNA from Cretaceous amber, we would still be a long way from resurrecting the dinosaurs. Nobody has even claimed to find the DNA of another animal inside an insect, although I doubt that anybody has tried. There certainly are bloodsucking insects in Cretaceous amber (specimens collected from the 95 million-year old New Jersey "treasure trove" include a mosquito - the oldest known - and a biting black fly), but whether these contain dinosaur blood is extremely doubtful.

Even if an insect started out with blood in its stomach, digestive enzymes might have all-but destroyed it even as the insect lay entombed. However, as the Jurassic Park scientists pointed out, the extraction of DNA from dinosaur blood might be considerably easier than the extraction of DNA from more recent mammalian blood. The red blood cells (erythrocytes) of mammals contain no nucleus and, therefore, no DNA, so the only cells from which DNA can be extracted are the much less numerous white blood cells. Dinosaur red blood cells, however, probably did contain a nucleus and DNA, since the red blood cells of their closest living relatives - reptiles and birds - certainly do.

To make the problems even worse, many of the insects found in amber are extremely rare specimens, and these specimens must be damaged in order to extract DNA. Many argue that only the most common amber specimens should be used for DNA extraction, preserving the rarer ones for visual study.

Even if specimens as old as Cretaceous amber do not preserve DNA, there are numerous remains from more recent animals (great auks, thylacines, ground sloths, and even woolly mammoths) that do preserve recoverable DNA. It might be possible to use this DNA to re-create the species from which it came, but there are many other problems that would first have to be overcome.


So close, yet so far apart

Some critics of Michael Crichton's Jurassic Park have complained that, "by the end of the book and the film you felt bludgeoned by the connection between birds and dinosaurs". However, those who made these criticisms may have rather missed the point. Before you can re-create any extinct animal, it is vital to understand its extant relatives, and the continual avian imagery in Jurassic Park gave people an appreciation of this.

Why is it so important to identify the animal's living relatives?

If you can't get a complete DNA strand from an extinct animal, you can attempt to "fill in the gaps" using DNA from living animals. This only works because many complex organisms share large sections of their DNA. The Histone-H4 gene, for example, is found in both cows and pea plants, two organisms that we don't normally think of as even being related. In Jurassic Park, frog DNA was used to fill in missing pieces of dinosaur DNA, but this was merely a crude attempt by the author to work spontaneous sex-changing into the plot (the dinosaurs supposedly acquired frog genes allowing them to change sex and breed, even though the original population was entirely female). However, real scientists would have used DNA from a closer relative - a reptile or a bird. This makes sense, since the more closely related two organisms are, the more DNA they have in common. (When I say that two animals are closely related, I mean that they shared an evolutionary common ancestor relatively recently; the time that has passed since the ancestors of two organisms diverged is a rough indication of the amount of DNA that they have in common.)

Even for comparatively recent animals for which we have a virtually intact DNA sequence, it is still important to identify their extant relatives. This is because a DNA strand alone isn't enough to create an animal: you need a fertilised egg cell into which to insert the DNA, ideally taken from a close relative so that it is chemically compatible. Once the egg cell has begun to divide and develop, you need to provide it with an environment in which to grow. The embryo of a placental mammal must be implanted into the uterus of another animal; the embryo of a bird or a reptile must be provided with an egg (complete with yolk, porous shell, and membranes). Either way, you need to find a closely related animal, to act as either a surrogate mother or to help provide eggs in which to grow the embryos.

It is becoming clear that an animal's chances of re-creation depend not only on how well its DNA is preserved, but on whether a living relative can be found. Living relatives are important to help fill in the genetic gaps, to provide an egg cell, to help the egg cell develop into an animal, and probably for numerous other purposes as well. A baby mammal, for instance, would need to be provided with milk of a suitable nutritional composition, presumably supplied by a living relative.

What are the living relatives of the more famous extinct animals?

Here is a list of some well-known animals that have recently become extinct, and what (if any) close living relatives they have...

Great auk
Pinguinus impennis
The Great Auk was the first bird to be described as a "Penguin", and it retains the scientific name Pinguinus. However, it is not a true penguin, but a member of the auk family, Alcidae. Its closest living relatives are the many other members of the auk family, especially the razorbill.
Tasmanian wolf
Thylacinus cynocephalus
The thylacine was the last living member of its family, representing a lineage that had been evolving independently of other marsupials for over 10 million years. It therefore has no close relatives; it may be distantly related to the dasyurid marsupials (quolls, Tasmanian devils, etc).
Giant ground sloths Like the thylacine, the giant ground sloths represent a distinct family that has been completely wiped out. They are distantly related to the living sloths.
Dodo
Raphus cucullatus
Four hundred years ago, the family Raphidae contained three or four species: the dodo and various solitaires; all flightless island dwellers. Unfortunately, the entire family was wiped out by early sailors, leaving the dodo with no close living relatives. The Raphidae might be distantly related to the pigeons (some classify the dodo together with the pigeons in the order Columbiformes), but this is debatable.
Woolly mammoth
Mammuthus primigenius
The mammoths' closest living relative is the Asian elephant, Elephas maximus. The pattern of ridges and grooves on the molars is just one of the many features which confirms this classification. The teeth of Elephas and Mammuthus both have a series of straight grooves and ridges but the teeth of the more distantly related African elephant Loxodonta africana have an unusual diamond-shaped pattern. However, the mammoth and the Asian elephant diverged at least two million years ago.

What are the dinosaurs' closest living relatives?

With an animal as old as the dinosaurs, determining its living relatives is no so easy. Firstly, the dinosaurs do not fall into a clear modern class, such as mammals, or birds, or reptiles, but straddle the boundary between two groups (reptiles and birds). Secondly, the dinosaurs are a massive group, and the close relatives of one dinosaur species might not necessarily be closely related to another species.

Dinosaurs are descended from the same ancestor as crocodilians (crocodiles, alligators, and the gharial); they diverged about 235 million years ago. However, birds are actually the descendants of dinosaurs, so birds are genetically closer to the dinosaurs, or at least to some dinosaur groups. (The notion of dinosaurs becoming birds was once controversial, but it is now all but certain that birds are descended from certain dinosaurs. The recent discovery of the remains of "feathered dinosaurs" in China helps to confirm this.) However, although birds are almost certainly close to the carnivorous dinosaurs from which they are descended (the theropods), it is not certain how close all dinosaurs are to the bird/theropod lineage. Even if all of the dinosaurs prove to have been genetically closer to birds, they may have been physiologically closer to crocodiles, since birds have undergone considerable development since they diverged from dinosaurs while crocodiles are virtually unchanged. How far dinosaurs had gone along the road leading to the warm-blooded, highly developed birds is fiercely debated among scientists. Perhaps dinosaurs were a strange intermediate halfway between birds and reptiles, which would make any attempt to re-create them very difficult indeed.

Relationship between birds, crocodiles, and dinosaurs
Evolutionary tree showing the relationship between birds, crocodiles, and dinosaurs

If living birds do prove important for the re-creation of dinosaurs, then the easiest dinosaur to bring back should be the one that is most closely related to birds. Perversely, this is the one dinosaur that nobody wants brought back to life - Velociraptor, a small carnivorous dinosaur from the late Cretaceous (their relatively young age also makes it potentially easier to re-create them since their DNA is likely to be in better condition than the DNA of older dinosaurs). These fierce little creatures were the villains of Jurassic Park.

Velociraptor
Velociraptor, one of the easiest dinosaurs to re-create?


Cracking the genetic code

Why must an animal's genome be pieced together from fragments?

However exceptionally an organism might be preserved, it will inevitably have sustained some damage to its DNA. An organic molecule as large as DNA is not inherently stable, and liable to disintegration. During life, a cell has enzymes that repair genetic damage, but after death, breakages and damaged bases rapidly accumulate in the cell's DNA. Before an animal can be restored, its DNA must be perfect, and reconstructing DNA strands is possibly the most serious difficulty involved in recreating an extinct animal.

How easy is it to reconstruct ancient DNA?

If you have enough fragments of DNA then, even if the fragments are not particularly long, it should be theoretically possible to piece the message together. The fragments mustn't be too small, of course, since a fragment of just a few base pairs does not really tell you much. Any sequence of less than 16 base pairs is not likely to be unique - it will probably turn up in more than one place on the genome - adding to the problem. If the DNA in really old specimens, such as Cretaceous amber, has degenerated into really tiny fragments, then piecing it together will be virtually impossible.

Another problem with DNA is the sheer amount of data involved. If the DNA is from a recently dead animal and is therefore in fairly good condition, the damaged fragments could perhaps be spliced together in the laboratory, but the reconstruction of more fragmented DNA would need to be done on a computer. A computer involved in reconstructing an animal's genetic code would have to be capable not only of storing and processing billions of characters, but of sorting through them at high speed to find a matching piece of data. (In the Michael Crichton novel, Jurassic Park's computer engineer describes his incredulous reaction when told of the specification for the park's computer system.) Computers are good at working on small tasks one at a time, but a DNA-processing computer would have to be capable of considering an organism's entire genome all at once. This would require a phenomenal amount of memory and processing power.

Being able to reconstruct an organism's DNA, then, is not just about extraction techniques or genetic technology, but about computing power. Luckily, there are continual new developments in computing that may make massive data handling tasks such as DNA reconstruction much faster and easier. One such new development may be the Dynamic Associative Access Memory (DAAM) chip, an intelligent computer memory chip. Normally, a computer's microprocessor has to search through each memory chip in turn to find a particular piece of data, but a DAAM chip has its own mini-processor and is therefore capable of searching itself and then reporting back to the main processor, greatly speeding things up.

The reconstruction of DNA on a computer raises two immediate issues: getting the DNA into the computer, and turning the computer data back into chemical DNA. The latter procedure - the production of DNA with a particular sequence of bases - can be done relatively easily using modern techniques. In fact, there are now many companies who offer custom-produced pieces of DNA for sale.

How do you "read" and "write" DNA?

Reading off the DNA sequence in the first place - gene sequencing - poses a greater problem. The laboratory techniques used for this are still extremely slow and laborious. They include: the use of bacterial enzymes to cut DNA wherever a specific sequence occurs and deducing the DNA sequence from the position of the cuts, the separation of DNA into strands of different lengths using electrophoresis, and the creation of a sequence of bases that complements and sticks to a particular piece of DNA which can then be marked with a fluorescent dye. It is taking many years and vast amounts of money to sequence the genome of one living animal - Homo sapiens - so the idea that Jurassic Park scientists could sequence the genomes of fifteen extinct ones within a short time frame is a bit far fetched.

However, gene sequencing is becoming increasingly automated, and soon it may be possible to sequence an entire animal genome in a short time and at a low cost (much to the annoyance of the governments who have already invested millions in the Human Genome Project). One company claims that its sophisticated gene sequencing machines can sequence the entire human genome in three years at a cost of £200 million, much less than the time and money that has been spent on the Human Genome Project. Such improvements in genetic technology will be vital if anybody is ever going to bring an extinct species back to life.

How can you tell if the DNA sequence is correct?

One scientific development that may help to ensure accuracy when reconstructing DNA strands will be an understanding of what the DNA does and how it works. If scientists can identify that a particular DNA sequence produces a particular protein that does a particular job, then they can analyse the gene on computers and assess whether it has been correctly put together. An understanding of what the genes do, combined with a complete DNA strand from a living animal, could allow scientists to reconstruct even badly damaged DNA with reasonable accuracy.

If it proves too difficult to asses a gene by using computer models in this way, then the only way to tell whether a DNA sequence is correct is to try and use it to re-create the animal. This method of debugging the DNA creates numerous problems. Firstly, you can't try anything out until you have compiled a complete genome; a small fragment of DNA will do nothing. Secondly, if an animal dies, it is hard to know which of the hundreds of thousands of active genes is responsible. Worst of all, a mistake might not manifest itself until late in the animal's development: a cruel blow to scientists who have reared a baby dinosaur (or another extinct animal) only to find that it dies upon reaching a certain age.

An even worse problem facing anybody who wished to clone dinosaurs using DNA preserved in amber is determining which species of dinosaur the DNA belonged to. In Jurassic Park, the scientists described how they often didn't even know what species of dinosaur the DNA belonged to until they had hatched the animal. Telling the dinosaur DNA apart from insect DNA or bacterial DNA can easily be done by comparing it with that of living species, but telling different species of dinosaur apart from their genes is virtually impossible. However, there is a serious flaw in the Jurassic Park "wait and see" approach: the DNA involved might have come from more than one species. An animal whose DNA was half-Tyrannosaurus and half-Triceratops, or was half-Stegosaurus and half-Diplodocus, would not even develop past an egg, let alone survive into adulthood. Perhaps it would be possible to distinguish between the DNA of different species by chemically studying the blood cells from which the DNA was extracted. If fragmentary DNA can be extracted from fossil bones, this could also help to identify the species of dinosaur from which a DNA sequence came.

The extraction of DNA from any fossil remains is a tricky, slow, laborious, and expensive task. Yet, for any scientist who succeeded in piecing together the genome of an extinct species, the biggest problems would be still to come.


From chemicals to creatures

Can extinct species be hybridised with living ones?

In the now-infamous MIT Technology Review article of April 1984, it was claimed that two mammoth/elephant hybrids had been created by fusing an unfertilised egg cell extracted from a frozen woolly mammoth with sperm from a living Asian elephant. It sounds a good idea: there is no need for advanced gene sequencing techniques to reconstruct the damaged DNA because the hybrid is guaranteed to get at least one good copy of each gene, from its extant father.

However, the approach has several problems…

Regardless of whether or not it could be done, creating a half-extinct hybrid is not the same as truly re-creating an extinct species.

How do you get from a DNA strand to a complete egg cell?

It isn't possible simply to insert a DNA strand into an egg cell and expect the egg cell to divide and grow into an animal. Firstly, the DNA needs to be assembled (together with the protein chromatin) into chromosomes; this DNA then needs to be packaged into a cell nucleus. As far as I know, neither of these steps has ever been attempted in the laboratory using pure DNA as a starting point. For extinct animals with no close living relatives, we don't even know which piece of DNA goes on which chromosome.

Getting ordinary chromosomes assembled with the correct pieces of DNA on them might not actually matter too much. After all, chromosomal aberrations are a part of every animal's evolutionary history and the individuals in which they first appeared went on to have healthy offspring. However, in the case of the sex chromosomes (X and Y in mammals, Z and W in birds), mistakes in knowing which DNA sequence goes where could have serious consequences.

In the case of the dinosaurs, we don't even know if they had sex chromosomes or not. Birds (which are descended from dinosaurs) do possess sex chromosomes, but in many of the dinosaurs' living reptilian relatives (crocodilians and most turtles), sex is determined by environmental factors such as the temperature at which the eggs are kept. Once the chromosomes had been assembled and packaged into a nucleus, they could be inserted into an enucleated animal cell, creating a living adult cell containing the genes from an extinct species.

The next step would be the tricky procedure of transferring the nucleus from the living adult cell into a fertilised egg cell (also supplied by a living animal), which can then be made to develop into a baby animal. This has already been done, of course, with Dolly the sheep, who was created when genes from an adult cell were inserted into a fertilised egg cell. However, the egg cell into which the nucleus of Dolly's single parent was inserted came from the same species - another sheep. With an extinct species it would probably be necessary to insert the nucleus of one species (the extinct one) into the egg cell of a different species (an extant one). Cow egg cells with their nuclei replaced by those of another species fail to develop to maturity, presumably because cow egg cells are chemically different from the egg cells of the species to which the nucleus belonged. This problem might possibly be overcome if the extinct species was very closely related to the egg donor, and their egg cells were therefore chemically similar.

How do you provide an embryo with an environment in which to grow if its mother is extinct?

The embryo of a placental mammal (such as the woolly mammoth) must be implanted into a living animal so that it can grow into a baby animal. However, if the species to which the embryo belongs is extinct, then the surrogate mother will have to come from a different species. Unfortunately, if the implanted embryo is not genetically similar to the surrogate mother, it will be treated as a foreign organism and expelled. This problem can be eased slightly by the use of drugs to suppress the mother's immune system and by using a surrogate mother belonging to an extremely closely related species, but the risk of rejection is still high.

The Danish embryologist Steen Willadsen, a man whose work inspired Ian Wilmut to create Dolly the sheep, proposed a cleaner solution to this problem. Using nothing more sophisticated than a fine pipette, he carried out research into chimeras: embryos containing a mixture of cells from two different species. Willadsen hoped to find an easy way to clone endangered species for which surrogate mothers could not easily be found. He proposed that, if you could create a chimera with the foetal cells of a rare animal but the placental cells of a much more common one, the common animal might then carry the rarer one to term without rejection. This is because its immune system would identify the placental cells as genetically similar to its own and not notice the foetal cells embedded inside. Willadsen found that his idea worked when tried with domestic animals, but so far nobody has used the technique on endangered animals. However, I see no theoretical reason why the idea should not be possible not only with endangered animals, but with extinct ones.

A medium-sized ground sloth (such as the mylodon whose pelt was found in the South American cave) could be grown inside a modern cow using Willadsen's method. Ground sloths and cows are about as genetically different as it is possible for two placental mammals to be, but they are about the same size and there is no shortage of cows to act as surrogate mothers. By creating a chimera with a cow's placenta and a ground sloth's foetal cells, the genetic differences between the surrogate mother and the embryo could be overcome. It is important that there should be a good supply of potential surrogate mothers (in other words, the surrogate mother should belong to a common species, preferably a domestic one), because it would probably take a lot of attempts to get a single live birth. It took 277 attempts to create Dolly, and any project to re-create extinct animals would inevitably be far more ambitious and therefore far more likely to fail.

When re-creating some animals, there may be serious size differences between the extinct species and their extant surrogate mothers. A 15-foot Megatherium would be a very heavy baby for any extant mammal to carry to term. The woolly mammoth was actually about the same size as the modern Asian elephant (although some other Mammuthus species were much larger), but elephants are endangered and nobody is going to provide 277 for some mad scientific experiment. The trick of making a chimera and implanting it into a cow would be difficult for size reasons. Any project involving elephants would also be limited by the fact that elephants have an extremely long and complex reproductive cycle.

With marsupial mammals such as the thylacine, things might be slightly easier. A marsupial does not have an intimate physiological relationship with its mother during development; it develops from a tiny egg inside its mother and grows up in her pouch. It might be possible to do this entirely in the laboratory - an artificial pouch might consist of nothing more than a warm bag and a bottle of milk with a suckable teat.

Where do you get ancient eggs?

In the same way that a mammalian embryo needs a surrogate mother, a bird embryo needs an egg in which to grow. Eggs can easily be taken from other species of bird, but getting a new embryo inside without damaging the delicate membranes on which the growing chick depends could prove extremely tricky. It would presumably have to be done at an extremely early stage, while the embryo was little more than a ball of cells that could be injected into the right part of an egg without causing irreparable damage. A few extinct birds, such as the larger moas (including the appropriately-name elephant bird), produced eggs that were significantly larger than those produced by any extant bird. Where do you get such large eggs? (A few are still preserved in museums, but these are rare specimens and not suitable for being wasted by the hundred in an embryology experiment.) In Jurassic Park it was suggested that it might be possible to come up with an artificial material that exactly mimics an avian egg. This is a tricky task, since an artificial egg must be equipped with a porous shell and semi-permeable membranes to let in just the right quantities of oxygen and let out waste carbon dioxide, allowing the embryonic chick to breathe. But it might one day be done.

Moas are not the only extinct animals for which outsized eggs would be required. We know from fossil evidence that dinosaurs hatched from hard-shelled eggs just like those of their avian descendants, and big dinosaurs need big eggs. Luckily, the eggs of the very large dinosaurs are not as monstrous in proportion as might be supposed, because there are physical limitations on the size of an egg. An egg more than a foot long would collapse under its own weight, unless its shell was incredibly thick, but this extra thickness would inhibit the embryo inside from breathing. Therefore, the eggs of fifty-ton dinosaurs are no larger than those of the largest moas. (Perhaps we could first re-create moas and then use them as a source of dinosaur eggs!) Smaller dinosaurs, of course, have smaller eggs, and the recent experiments in ostrich farming could provide a good supply of moderately large eggs in which to grow medium-sized dinosaurs.

If it is necessary to create artificial dinosaur eggs, there are certain things that we first need to know. For instance, exactly how porous were the shells? Some scientists have studied fossils in an attempt to answer this question, since the pore density of the dinosaurs' egg shells can give valuable clues about dinosaur metabolism (the more pores in the egg, the higher the oxygen requirements of the embryo). Even if these studies do not bring us any closer to the continual question of whether or not the dinosaurs were homiothermic (warm-blooded), they may be of use to anybody wishing to create their own dinosaur egg. (Of course, re-creating the dinosaurs would answer the homiothermy question once and for all!)


An alien planet

You've done it! You've brought an extinct species back from the dead! Now you are faced with one final problem - keeping it alive.

Firstly, you have to decide what to feed your baby dinosaur. A palaeontologist might tell you something about a dinosaur's dietary requirements, but most of its favourite food plants are probably extinct, and the experts' opinions on dinosaur diet might be wrong, anyway. A baby mammal needs milk, but what sort of milk? How much fat? How much protein? How watery do they like it? Is there a secret ingredient that you should be adding?

Then, there is learning. Some dinosaurs had notoriously small brains, but the more bird-like dinosaurs (like Velociraptor) had large brain cases and were probably extremely intelligent. In the wild, a baby raptor might have learnt skills such as hunting from its parents, but who is going to teach it to hunt in the modern world. Luckily, a laboratory animal doesn't need to hunt (in fact, it's safer that way!), but a lack of natural skills would make a serious behavioural study of an animal very difficult.

Your baby dinosaur might not even be able to breathe our modern air. At certain times in Earth's history (including during the dinosaur era), atmospheric oxygen concentrations were higher than they are today. Perhaps the dinosaurs needed this extra oxygen to be able to grow to their titanic sizes. Their flying contemporaries - the ancient bird Archaeopteryx and the reptilian pterosaurs - would almost certainly have fallen off their perches in today's oxygen-poor atmosphere!

Worst of all, a long-extinct animal would have little or no immunity to our modern diseases. They would have to be kept in a sterile environment at all times, not in the carefree enclosures of Jurassic Park.


Conclusion

The dinosaurs are almost certain to stay extinct. Modern scientists certainly don't have either the equipment or the knowledge to re-create them, but this is just a matter of time and technology. The crucial factor in determining whether dinosaurs will ever be re-created is how well (if at all) their DNA is preserved: if there is no meaningful DNA, then there can never be a real dinosaur. Even if it is physically possible, who is going to fund such a project?

However, I am confident that other extinct animals will one day be brought back from the dead. The thylacine, the great auk, the ground sloths and the mammoths will all have pride of place in a zoo of the future (if zoos have not by then become socially unacceptable), because we have large amounts of preserved DNA from all of these. One day, we will have the power to turn this DNA back into a living, breathing animal.

The monsters of the past live on through their bones, their trackways, their dried skins, and their amber-preserved remains. In some parts of Siberia, the entire economy was once based on animals that last wandered the earth ten thousand years ago. Some of these animals might actually live on (there have been many hundreds of thylacine sightings since the animal was officially declared to have become extinct in 1936), but others are gone for good.

Yet, most of all, prehistoric monsters live on in our imagination. Even if dinosaurs are never truly brought back to life, we may yet get the chance to wander among them in a virtual world, a computer-generated reality in which anything is possible. Of course, these virtual reality animals will not be the real thing, they will merely be approximations based on our current, limited knowledge. But, though extinction may be forever, the children of the future will one day be able to put on a virtual reality helmet and take a trip into Jurassic Park.


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© Andrew Gray, 1998