De-extinction: what if we resurrected a mammoth and then a dinosaur?

MIGUEL PITA PhD in Genetics and Cell Biology, Autonomous University of Madrid

The first time I mentioned de-extinction in public was in a radio talk show on a wide variety of topics. My main contribution was to comment that a team of scientists had managed to reactivate the DNA of a small Australian frog that had been extinct for nearly 30 years.

In addition, I ventured to predict that, once this milestone was achieved, it would not take long to try to de-extinct a mammoth. The humorist Dani Martínez participated in that gathering, who replied to me: "good warm up." Then he added a joke of the type: "come on, we already have the little frog, hold my drink and let's go for the mammoth." This original debate took place about a decade ago and there is still no resurrected mammoth, but there is an ambitious project to achieve it.

De-extinction seeks to use genetic and cellular tools to restore life to living beings of extinct species, as occurs in Jurassic Park and other science fiction stories. However, there is debate in the scientific community about whether this is really possible or whether we are selling smoke.

Mom elephant, son mammoth

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First, let's see what the matter is. Let us imagine that we propose to resurrect mammoths. The key will reside in reactivating your DNA. To do this, we will start from samples of genetic material isolated from pieces of meat extracted from one of the frozen specimens from the tundra. This DNA will serve as an instruction manual for producing mammoths: if read by the appropriate machinery, it will direct the production of the embryo, legs, hair, tusks, and so on.

But for this it is necessary to introduce it into a cell that is alive, that has fully operational DNA reading and processing equipment. Since there are no living mammoth cells, we'll have to turn to some nearby species, where DNA feels almost at home. For example, an elephant egg that will have its own DNA replaced by that of a mammoth.

This cell that houses the DNA of the species to be extinct is the other basic piece of the process: it contains the machinery that knows how to read. Since life cannot be created from scratch – it must be inherited – the first resurrected mammoth will be the child of elephants, not 100% mammoth. That is why many scientists affirm that de-extinction is impossible. And strictly speaking, they are right.

The extinct mammoth will have the vast majority of mammoth characteristics produced by its DNA, but the elephant egg will also leave its mark. To begin with, because a small part of the elephant's DNA remains in the emptied egg; for example, that of some important organelles called mitochondria.

To continue, because the gestation will be the responsibility of an elephant, not a non-existent mammoth mother. It could be tried in an artificial laboratory womb, but it would be a great added difficulty.

A failed experiment: the case of the bucardo

The first extinct animal was the bucardo, a Pyrenean goat. It had been threatened for decades when a skin sample was taken from the last specimen and preserved frozen. A couple of years later, DNA was extracted from those cells and implanted into an egg cell (without its own DNA) from a domestic goat, an evolutionarily close species.

Several processes were tested simultaneously and several goats carried surrogate pregnancies with their own eggs and DNA from extinct buchards. One of the pregnancies was successful and the new bucardo was born, but it died a few minutes later due to respiratory problems.

The problem in this procedure is the inadequate quality of the DNA of the extinct species. The skin sample harbored specialized veteran DNA. And that is not a suitable material to start the life process in an ovum that has to give rise to an entire embryo of a future newborn.

Although we may think that every cell in our body has identical copies of our unique and personal DNA molecule, this is not entirely true. It is true that the 40 trillion cells that make up an organism come from the geometric expansion of a single original cell, a fertilized maternal egg that carries a mixture of DNA from our parents. However, these reproductions are specialized, which means that they subtly modify the DNA they contain.

When a copy of a copy of what was once a fertilized maternal egg acquires the fate of becoming, for example, a brain or skin cell, it is because it reads a specific part of the information from the DNA molecule. Simultaneously, it chemically archives another part that you won't need. That is, although all our cells receive an identical copy of our DNA, they censor different parts.

Therefore, when the scientists used DNA from the skin of the last bucardo, they were using an instruction manual with some of the text crossed out. That's why it failed.

With the help of genetic cut and paste

Today there are gene editing tools, such as the popular CRISPR-Cas9, that can try to compensate for this setback. The objective is to correct the text of the DNA, that is, to recover the unused or lost fraction through genetic manipulation.

However, this approach means making up some of the content, or copying it from a similar kind. For example, if the text to produce functional lungs was crossed out in the DNA sample recovered from the skin of the last bucardo, an attempt would be made to replace that fragment of the molecule with the instructions for producing lungs present in the DNA of the domestic goat.

The strictest analysts will affirm that a bucardo that has goat's lungs (and is also born from a goat mother) will no longer be exactly a bucardo. So how much DNA does have to be original to be considered a bucardo? If 100% is necessary we must assume that it will never be possible.

We have to accept that the de-extinction processes are going to require that they donate the spark of life, that is, at least one host cell from another species and, almost always, cut-and-paste repairs of DNA fragments. The latter will mean importing or copying genes from nearby species. And of course, it will imply another series of considerations far from genetics, from legal to ecological.

Next targets: the dodo, the passenger pigeon, the Tasmanian tiger…

Although it is a matter that progresses much more slowly than promised, today there are numerous companies and research groups interested in de-extinction. Part of the challenge is to develop genetic tools with the immense degree of sophistication required. Techniques that, in addition, could have applications in medicine or bioengineering.

Another part of the challenge is based on the pure interest of recovering species such as the dodo, the passenger pigeon, the Maclear rat or the Tasmanian tiger. In this group we can also include the surprising proposal to resuscitate the Neanderthals, which will encounter ethical conflicts before it is even attempted.

Finally, other work teams probably only want social impact and profitability through amazing initiatives of the Jurassic Park type. That is why the mammoth is a priority objective, despite the fact that none of the more modest attempts at extinction have been really successful (and this is the "heat" predicted by Dani Martínez).

dinosaurs will never come back

In this sense, although the mammoth is an accessible challenge that will surely (or not) appear in a few years thanks to the elephants, the dinosaurs, extinct 65 million years ago, will never be. The essential DNA molecule cannot maintain its integrity for so many millions of years, so too much of the text would have to be invented, because there are no close relatives to copy it either.

However, that does not seem to have discouraged true fans of the subject, such as the galactic paleontologist Jack Horner, who has spent decades dreaming of extincting dinosaurs. Since he hasn't been successful in the way of recovering what was lost, years ago he decided to give it a try by genetically modifying chickens (let's remember that birds are dinosaurs). A notable achievement of his collaborators has been to get chickens with teeth that, fortunately, retain their small size.

The conclusion is that the vocation of Doctor Frankenstein of the human species remains incombustible despite the difficulties (and the terrible outcome of the novel). It would be great if the vocation to preserve was just as powerful as that of resurrecting.

This article has been published in 'The conversation'.