award-winning biologist offers fresh hope for species resurrection

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1 of 4 02/08/2015 09:09

Award-winning biologist offers fresh hope for species resurrectionAnd theres a selfish reason to save species too: How does the naked mole-rat live so long, and cancer-free to boot? Prof. DavidHaussler, recipient of the 2015 Dan David Award, tells Haaretz.By Ruth Schuster | May 27, 2015 | 12:28 PM

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

Saving species isnt just a moral question of fixing the damage we have done, says Haussler, professor of biomolecular engineering at theUniversity 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 greatbenefit like why the naked mole-rat lives five times as long as rats, and doesnt get cancer, either. That could be a useful trait to study andadopt, if we can, he explains in conversation with Haaretz.

The naked molerat. Photo by Roman Klementschitz, Wikimedia Commons

Haussler is being methodical about it, too, through his flagship Genome 10K Project, founded with fellow scientists Oliver Ryder and StephenOBrien. Genome 10K aims to understand how complex animal life evolved through changes in DNA and use this knowledge to become betterstewards 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 theanimals and better the lot of humans. For instance, by helping to create better therapies for cancer though better understanding of genetics: Thesimple 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, wasawarded the 2015 Dan David prize in Tel Aviv this month.

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2 of 4 02/08/2015 09:09

Prof. David Haussler: 'If you only look at very narrow, pragmatic questions, you will not learn, really, how the universe works'

The bottleneck and the black-footed ferret

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

As the number of individuals dwindles, inbreeding ensues. Eventually the lack of genetic diversity can doom a species. (Why? The whole point ofsex, 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 tohave genes that help it survive changes and challenging circumstances).

Newborn black ferret kits. Photo by U.S. Bureau of Land Management, Wikimedia Commons

The cheetah can provide a long-term perspective on inbreeding, since a bottleneck apparently due to climate change some 10,000 years ago left amere handful to perpetuate the species. Todays cheetahs are a mess. The cheetah is unusual ... in exhibiting near genetic uniformity at a varietyof loci previously screened to measure population genetic diversity, wrote Mauth Menotti-Raymond and OBrien in a PNAS paper on the cheetahbottleneck . Their fertility rates are low: The quality of the males sperm is terrible. Even artificial help can only go so far IVF on cheetahsdoesnt work as well as in tigers and domestic cats.

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


3 of 4 02/08/2015 09:09

Cheetah: Doomed by poor genetic diversity? Photo: Wikimedia Commons

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 anyother 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. Its 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 learnmore 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 tosave 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 were going to save species? Sounds far-fetched. But Haussler radiates an infectious optimism. Collecting the genomes is just thefirst part. Analyzing them, including for the sake of seeking interesting genes, is the just second. Then theres 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 isnt. In fact, ithasnt been done yet.

So, say Bob the black-footed ferret cant produce motile sperm but has a beneficial gene that kills parasites, and Joe the black-footed ferret hasgorgeous frisky sperm but is terribly vulnerable to the parasites. Theoretically, one could take the good sperm gene from Bob, the good malariagene from Joe and : That is, in my opinion, the future, but its very unexplored at this point. The editing part of it has not been accomplishedyet, but the path is clear, says Haussler.

He isnt arguing that it is good enough just to sequence a species, he stresses: Complete DNA sequencing is not a replacement for preserving theliving species. You shouldnt spend all your money on sequencing, in exclusion of making sure the species has a good habitat and all thereasonable things thats still thats first priority.

Might these roam the range again some day? Maybe. Photo: Wikimedia

The fact that genetic editing is still theoretical doesnt mean that controversy isnt raging about how much editing is good, okay, not okayand downright horrible. But it seems there will be little choice but to edit when it comes to species resurrection. And never mind Lazarus, thedream has been to resurrect the woolly mammoth.

This is a serious thing and theyre 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 enormousamount of time and effort and money, but in theory it could be done.

Just knowing the sequence of the mammoths DNA isnt enough to produce a viable furry baby. There are all kinds of mysteries, such as whetherit requires special hormones or this or that secret sauce we dont know for sure, he puts things into proportion, and continues with histrademark optimism: Usually theres a fix to the secret sauce problems. You discover it and you add the secret sauce. This just adds time andmoney.

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

Certainly you have a pressing issue of global warming and you dont want to divert resources from fixing that into resurrecting the woollymammoth, says Haussler. Theres a balance, but you need to have a little bit of both. Im all for broad science.


4 of 4 02/08/2015 09:09

award-winning biologist offers fresh hope for species resurrection

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