Award-winning Biologist Offers Fresh Hope for Species Resurrection

And there’s a selfish reason to save species too: How does the naked mole-rat live so long, and cancer-free to boot? Prof. David Haussler, recipient of the 2015 Dan David Award, tells Haaretz.

Ruth Schuster
Ruth Schuster
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The woolly mammoth may be extinct, but might not stay that way.
The woolly mammoth may be extinct, but might not stay that way.Credit: Wikipedia
Ruth Schuster
Ruth Schuster

The Sixth Extinction is upon us, and this time the depopulation of the planet is Man’s fault. But the upside of mankind is his mind, and breakthrough technologies could save at least some of the species on the brink of extinction. Through genetic sequencing, futuristic but foreseeable genetic editing technologies and an enormous amount of work, extinct animals could even be resurrected, according to bioinformatics expert David Haussler, one of whose missions is to collect and study the genomes of as many animal species as possible – for the greater good of humanity.

Saving species isn’t just a moral question of fixing the damage we have done, says Haussler, professor of biomolecular engineering at the University of California in Santa Cruz and scientific director of the Santa Cruz Genomics Institute.

“At least some animals have remarkable properties in their genes that we are just starting to recognize and understand, which could be of great benefit – like why the naked mole-rat lives five times as long as rats, and doesn’t get cancer, either. That could be a useful trait to study and adopt, if we can,” he explains in conversation with Haaretz.

Haussler is being methodical about it, too, through his flagship Genome 10K Project, founded with fellow scientists Oliver Ryder and Stephen O’Brien. Genome 10K aims “to understand how complex animal life evolved through changes in DNA and use this knowledge to become better stewards of the planet”, its website explains.

Put otherwise, this “genomic zoo” project aims to sequence the DNA of 10,000 species of animals, with two key end-games in mind: to save the animals and better the lot of humans. For instance, by helping to create better therapies for cancer though better understanding of genetics: “The simple fact is that cancer is caused by DNA mutations, period,” says Haussler. “Most cancers require five or six mutations before they get rolling. Now, for the first time, the mutations behind the disease can be read, which raises hope for targeted therapies.”

It is for these and his other many achievements that Haussler, who posted the first draft sequence of the human genome on the Internet, was awarded the 2015 Dan David prize in Tel Aviv this month.

The bottleneck and the black-footed ferret

It’s hard to know how fast humankind is destroying the planet’s biodiversity, since nobody knows how many species there are. Or were. Scientists estimate the pace of species loss today at 1,000 to 10,000 times higher than the background extinction rate (an averaged “normal” rate of extinction on earth before people started ruining the environment). Biodiversity experts estimate that between 10,000 and 100,000 species are dying out each year, including everything from the clouded leopard of Formosa to fingernail-sized poisonous frogs.

Black footed ferret.Credit: Wikipedia

As the number of individuals dwindles, inbreeding ensues. Eventually the lack of genetic diversity can doom a species. (Why? The whole point of sex, with all due respect to orgasm, is to perpetuate the species through genetic diversity – the wider a species’ gene pool is, the more likely it is to have genes that help it survive changes and challenging circumstances).

The cheetah can provide a long-term perspective on inbreeding, since a bottleneck apparently due to climate change some 10,000 years ago left a mere handful to perpetuate the species. Today’s cheetahs are a mess. “The cheetah is unusual ... in exhibiting near genetic uniformity at a variety of loci previously screened to measure population genetic diversity,” wrote Mauth Menotti-Raymond and O’Brien in a PNAS paper on the cheetah bottleneck . Their fertility rates are low: The quality of the males’ sperm is terrible. Even artificial help can only go so far – IVF on cheetahs doesn’t work as well as in tigers and domestic cats.

And no, not a single species has been brought back from extinction yet.

So what the devil is the point in sequencing the DNA, not just of the ferret but of each of the last seven black-footed ferrets on the planet, or any other species, if inbreeding would doom them anyway?

“If you only look at very narrow, pragmatic questions, you will not learn, really, how the universe works,” Haussler points out. “It’s basic research. You never know what you will find.”

The genetics of the ferret, or the harlequin frog, or Sue next door are all more pieces in the magnificent puzzle of evolution, he explains. “Evolution is a molecular process that creates different life forms. Every individual life form on the planet has a unique story to tell – we learn more about biology and more about how life works every time we sequence a new species.”

Nor should this vast effort be concentrated on species that we suspect will be useful to us. Take the black-footed ferret, which nobody expects to save us from cancer or anything else. Why sequence it, let alone all of the (very few) remaining individuals?

“God knows what crazy things the black-footed ferret does,” Haussler says.

And from this we’re going to save species? Sounds far-fetched. But Haussler radiates an infectious optimism. Collecting the genomes is just the first part. Analyzing them, including for the sake of seeking “interesting” genes, is the just second. Then there’s the editing.

Woolly mammoth 2.0

Gene editing means to get rid of a bad gene and replace it with a good one. Or add or delete a characteristic. Sounds simple. It isn’t. In fact, it hasn’t been done yet.

So, say Bob the black-footed ferret can’t produce motile sperm but has a beneficial gene that kills parasites, and Joe the black-footed ferret has gorgeous frisky sperm but is terribly vulnerable to the parasites. Theoretically, one could take the good sperm gene from Bob, the good malaria gene from Joe and : “That is, in my opinion, the future, but it’s very unexplored at this point. The editing part of it has not been accomplished yet, but the path is clear,” says Haussler.

He isn’t arguing that it is good enough just to sequence a species, he stresses: “Complete DNA sequencing is not a replacement for preserving the living species. You shouldn’t spend all your money on sequencing, in exclusion of making sure the species has a good habitat and all the reasonable things – that’s still that’s first priority.”

The fact that genetic editing is still theoretical doesn’t mean that controversy isn’t raging about how much editing is “good,” “okay,” “not okay” and “downright horrible.” But it seems there will be little choice but to “edit” when it comes to species resurrection. And never mind Lazarus, the dream has been to resurrect the woolly mammoth.

“This is a serious thing and they’re seriously undertaking this,” says Haussler, noting the work of Beth Shapiro of Princeton.

Could it be done with existing technology? “With existing technology stretched to the limit – yes,” says Haussler. “It would take enormous amount of time and effort and money, but in theory it could be done.”

Just knowing the sequence of the mammoth’s DNA isn’t enough to produce a viable furry baby. “There are all kinds of mysteries, such as whether it requires special hormones or this or that secret sauce – we don’t know for sure,” he puts things into proportion, and continues with his trademark optimism: “Usually there’s a fix to the secret sauce problems. You discover it and you add the secret sauce. This just adds time and money.”

But is it appropriate to invest that much time, money and brainpower in resurrecting the woolly mammoth, rather than dealing with the world’s other problems – such as the galloping extinction of species that still, albeit barely, exist?

“Certainly you have a pressing issue of global warming and you don’t want to divert resources from fixing that into resurrecting the woolly mammoth,” says Haussler. There’s a balance, but you need to have a little bit of both. I’m all for broad science.”

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