Science

Cloning the Thylacine

The impact of Australian science has been declining for at least ten years. We need “thylacine” projects to demonstrate our scientific confidence: if we can’t be prepared for big challenges (and possibly failure) then the nation must inevitably become a scientific backwater.

—Don Colgan and Mike Archer, January/February 2000

In January 1999, Professor Mike Archer was appointed director of the Australian Museum. It is customary, indeed expected, that new CEOs will set new directions for their institutions, and Archer did not wait long before launching what would be the most controversial initiative of his five-year tenure as the head of Australia’s oldest natural history museum. He proposed that an attempt be made to clone the extinct thylacine, or Tasmanian tiger, using DNA from one of the Museum’s most valuable specimens, a thylacine pup preserved in alcohol since its death in 1866.

On May 12, 1999, Archer announced that due to its fortuitous preservation in alcohol instead of the usual formaldehyde the pup could provide the genetic material for an attempt to clone the species. The next day he said he would make the pup available to “any scientist with a serious proposal to take the first steps to bring a thylacine back to life” and, in a curious caveat, who also came forward with “optimism and not rampant pessimism”. As the last thylacine had died in 1936, this project was nothing less than an attempt to bring an extinct species back to life. If this were to work, extinction would be a “curable disease”. It would mean the “end of extinction”. The project was announced, perhaps not entirely fortuitously, a few days before the Museum’s annual open day. The public was invited to come and look at the pup in its bottle.

The pup certainly had public appeal. Resting upright in its bottle of clear alcohol with its front paws raised in a slightly supplicating posture and its eyes closed, it seemed to be in serene repose, just waiting for some genetic Prince Charming to bring it back to life. The pup in its bottle would obviously become the icon for any attempt to clone a living specimen from its DNA.

Originally, there was no suggestion that the Museum itself would take on the project, which is perhaps not surprising as the Museum had virtually no experience working with the DNA from preserved specimens, so-called “ancient DNA”. But on September 7, 1999, the sixty-third anniversary of the death of the last thylacine, the Museum announced that it would take on the project itself. It also announced that it had set up a trust fund to start the project based on a large, but undisclosed, donation from two brothers who wished to honour a Tasmanian convict ancestor and a smaller $20,000 grant from the New South Wales government. The funds were thought sufficient for the first three years of the project.

The Museum also launched a prospectus, which described the project, to solicit additional funds from the corporate and private sectors. On the day of the launch, Archer said, “This may well be the single most important announcement any of us here today will attend.” Bob Carr, then Premier of New South Wales, apparently agreed, saying it was “the most important launch I will ever be to”.

Why the Museum, which arguably had the expertise for only the earliest and easiest parts of the project at best and absolutely no expertise in the later and more difficult stages, including whole animal cloning, had decided to take on the project was never explained. There are, however, two clues. The first comes from one of the private donors, who was reported as saying that he and his family had decided to back the project “after reading about it in a Sydney newspaper”, at a time when the project was still being offered externally. And the second comes from the Museum’s 2001–02 annual report, where Archer wrote:

This year has … seen the Museum attract worldwide attention with the groundbreaking advances made in the Thylacine cloning project … As the Museum debates new strategies in the way it presents itself to the community, this level of interest is extremely positive.[emphasis added]

The unsolicited offer of some big private seed money with few, if any, strings attached, plus an opportunity to ride the virtually open-ended public interest in the project may have been irresistible.

Archer is a palaeontologist whose enthusiasm is boundless and, to some, highly infectious. He is also one of Australia’s great science and technology spruikers. But the technological aspects of the project were beyond his professional expertise, and to make it work within the Museum, he needed help. And as chance would have it, the molecular geneticist/taxonomist in the Museum, Dr Don Colgan, the head of the Evolutionary Biology Unit, turned out to be equally enthusiastic about the project. This was luck, indeed, because very few of Colgan’s peers gave the project much chance of success.

Initially, the team that set off to clone the thylacine consisted of just Archer and Colgan. But Colgan, as head of the Evolutionary Biology Unit, was very busy, and towards the middle of 2001 he hired Dr Karen Firestone, a conservation geneticist from Sydney’s Taronga Zoo, to do most of the lab work. These three, then, constituted the cloning team. In their core roles, Archer was the project’s point man, Colgan the co-ordinator, and Firestone the researcher/technician. A brief protocol for how the project might proceed was included in the prospectus and later in a short article in an Australian science news magazine.

Archer and Colgan gave varying estimates of how long the project would take, what it would cost and what their chances of success were. They opined on various occasions that “people could own Tasmanian tigers as pets within 50 years” (May 1999), twenty years (early 2000), fifteen years (May 2000), “within the next ten years” (May 2000), “a few years to a decade” and ten to fifteen years (May 2001), “within a decade” and eight years (May 2002), twenty to twenty-five years (mid-2002) and 200 years (May 2002). They estimated the total costs, variously, as $20–30 million (September 1999), $60 million and $80 million (May 2000). And they gave the project’s probability of success, variously, as 2 to 5 per cent (early 2000), 8 to 10 per cent (May 2000), 30 per cent (May 2002), 5 per cent (June 2002) and 4 to 10 per cent (July 2002).

The project’s first success came approximately one year after it began, when the Museum announced on May 4, 2000, that the team had extracted some DNA from the pickled pup. In the press release, Archer called the extracted DNA “good quality”, and Colgan called it “of high quality”.

In a television interview that evening, Archer ventured that the achievement was “the biological equivalent of that first step on the moon”. He went on to say that they had gotten “huge chunks of DNA”. Later, in a newspaper story, he said, “There were an enormous number of very excited people around the Australian Museum,” and “I would expect that excitement will become a plague that will overtake the world.” In a Catalyst interview he said, “I think this is the most exciting biological project that’s going to occur in this millennium.” In another newspaper story, Colgan said he was “confident it contains multiple copies of nearly every Tasmanian tiger gene”.

Later that year (November 17) in a radio interview, Archer maintained that they had “got massive amounts of … mitochondrial DNA [as well as] nuclear DNA in extremely fine quality” and that they had “this massive amount of high quality DNA”. He also said that “our geneticists … think they have the full genome of the thylacine in these massive chunks”.

However, it would have been surprising if the thylacine team had not been able to extract some DNA from the specimen. Researchers had been extracting fragments of DNA from specimens of other kinds of animals preserved in alcohol for eleven years, and no one seriously doubted that at least some fragments could be extracted from the thylacine specimen.

But in a remarkable reversal of fortune, it was subsequently discovered that “whilst there was some thylacine DNA in the extraction, the majority of the sample was from contaminating micro-organisms”. This should not have come as a surprise, because if researchers had looked closely at the pickled pup, they would have seen tiny spheres of fungi growing on it. These fungi are clearly visible on the skin in the opening footage of a documentary made on the project, and vaguely discernable internally in the footage of the tissue extraction. The fungal spheres on the skin, at least, are not evident in subsequent footage. But what happened to them is not clear.

It is also not clear when the team discovered that the pup’s DNA was hopelessly contaminated, because the contamination was only mentioned explicitly once in a public document—a résumé of the project posted on the Museum’s website some time on or after May 28, 2002. The date of this realisation is important, however, because journalists and the public were apparently allowed to continue to believe that DNA from the pup was being used in the project up to its very end. We will return to this point later.

Subsequent to the first announcement, work began on extracting DNA from other tissues in other specimens. In contrast to the soft tissues such as heart and liver from the pup, the focus was now on hard tissues such as bone and teeth from adults. Unlike soft tissues, hard tissues help protect the DNA from contamination. This work paid off, and on November 24, 2001, it was announced in a local newspaper article that the team had extracted DNA from the bones and teeth of two dried specimens.

This announcement was surprisingly low-key compared to the one that preceded it and the one that would follow it. It was reported by (given to?) only one local journalist, and only the most junior member of the cloning team was interviewed. There was no press conference; no national or international media; no superlative claims.

The project’s second and final success was announced at an international press conference on May 28, 2002, when the Museum reported that it had succeeded in making multiple copies of three of the thylacine’s genes, two from the mitochondria and one from the nucleus. Thylacines are estimated to have seventeen mitochondrial genes and about 30,000 nuclear genes. The DNA in the nuclear genes is what’s required for cloning.

In a television interview on June 1, 2002, Archer said they had extracted “large chunks” and “masses” of DNA and that it was “very good quality”. He also said, “we are in no doubt that we’ve got the whole genome”. And in a newspaper story three months later, he said, “we found great big chunks, torn into big chunks” and “we have the whole genome”.

It would come out in subsequent interviews, however, that the sequences for all three genes were not complete, only partial. Indeed, a day after the second announcement, Firestone was reported as calling them “very small fragments at that”. And in an interview with Firestone reported in January 2003, the journalist referred to the recovered DNA as being in “snippets” and “badly degraded”, descriptors that seem likely to have come from Firestone herself. In an interview in April 2003, Colgan would call them “damaged”.

The actual lengths of the extracted gene fragments were subsequently revealed, and these allow the second result to be assessed in terms of the total number of base pairs, the basic unit of DNA, in the thylacine’s whole genome. And the whole genome would be needed for the cloning to work. Colgan said that the largest DNA fragment extracted from the thylacine was 2000 base pairs, but the average length was “at least 500 base pairs”. The thylacine’s total genome is estimated to be 3.5 billion base pairs. Assuming, generously, a length of 2000 base pairs for each of the three fragments, then the total number of base pairs extracted (6000) was less than 0.0002 per cent of the total required. A few months after the project had been scrapped, Archer would recall these fragments as being “2000 to 3000 base-pairs long”.

The press release for the second result said the result was achieved in May, the same month it was announced. But it appears to have been actually achieved nearly three months earlier. According to the Museum’s annual report for 2001–02, it came in February. But the May press conference was not only about the scientific result. It was also the launch of the Discovery Channel’s documentary about the project, “End of Extinction: Cloning the Tasmanian Tiger”, which would be shown around the world five weeks later. The Discovery Channel had paid an undisclosed sum for the exclusive public rights to the thylacine project, and this was the first, and as it turned out, the only story they would produce.

In announcing the second achievement, Archer said, “Nobody has ever done what we have just done” and revisited his space exploration analogy in saying that it was “the biological equivalent of human beings taking the first step on the moon”. He called the result “a giant step” for the project and said there was now not a “massive technical barrier … only a hell of a lot of hard work” to complete the project. In an interview a few days after the announcement, he called the result “indescribably exciting”.

But again, the second result was unexceptional from a scientific point of view. The extraction of DNA from bone and teeth and its amplification using the by-now standard technique of the polymerase chain reaction had first been achieved, respectively, twelve and thirteen years previously. One expert called the second result “scientifically trivial”. A press release from a group of French biotech labs said that all that had been done was to “copy fragments of DNA” using “a technique [that] has been widely used for some 20 years to reproduce DNA fragments”.

So why did a scientifically trivial result get announced with much fanfare at an international news conference? The Discovery Channel’s vice-president for programming may have provided the answer when he said, “We needed to have a breakthrough to make the story worth telling.” One newspaper commentator said: “I smell a circus.”

In fact, even in terms of the history of thylacine DNA per se, the results of the second announcement were not original. Using tissue from dried specimens, other researchers interested in the phylogenetic relationships of the thylacine had extracted and duplicated part of one mitochondrial gene as early as 1989; part of another mitochondrial gene in 1992, and then parts of both “old” mitochondrial genes and one “new” nuclear gene in 1997.

Writing in July 2002, Colgan noted that the cloning team had used earlier researchers’ DNA sequences to confirm that their own extracts contained thylacine DNA. What he could also have said, but did not, was that the team’s fragments were from the same genes as those of the earlier researchers. This would have been evident only to those with knowledge of the field. In essence, what the thylacine cloning team announced with great fanfare in May 2002 was work that simply duplicated what other researchers had already done (and published) quietly five years earlier.

It is clear from the description of the tissues that provided the DNA on which the second announcement was based that this DNA came from the two dried adults and not the alcoholic pup. But the press release did not reveal this fact. Nor did it come to light during the course of the media conference, judging from the way journalists reported that announcement. In fact, journalists never were disabused of this assumption in subsequent interviews. And the Discovery Channel documentary implied that the DNA for the project had come from the pup, because it mentions no other source specimens.

Furthermore, members of the cloning team continued to refer to the pup as if it was a source of useful DNA. Archer himself continued to imply, and even say, that at least some of the DNA that had been amplified had come from the pup. In a newspaper story the day after the second announcement, he said, “It means that the dead DNA extracted from the tissue of a preserved pup has been made to act in the same way as live DNA …” As late as August 2002 he said that “the DNA from the pup was of a high quality”.

The closest anyone on the team ever came to admitting to the shift, publicly, was in a brief presentation that Colgan and Firestone gave at the 2003 International Congress of Genetics in Melbourne. A synopsis of this presentation makes it clear that the DNA on which they were reporting was from the two dried adult specimens and not the alcohol-preserved pup. And well after the project collapsed, Archer wrote, “against the odds we sought and found thylacine DNA in the teeth and bones of preserved museum specimens”. Not a mention of the briefly famous, but now forgotten, pup.

It’s not clear why the cloning team was so coy about admitting that the little pup in its bottle of alcohol, the “miracle bottle” as Archer once described it, was in fact a dud and the project’s emphasis had shifted to dried adult specimens. Perhaps they didn’t wish to tarnish the project’s de facto icon, especially as it featured prominently in the commercial documentary on the project.

Because the work reported in the second announcement was completed in February 2002, the team must have realised by at least this date that the pup was a fizzer as far as its DNA was concerned. But how much earlier may they have known? One’s mind goes back to the low-key announcement of November 24, 2001, of the extraction of DNA from the two dried specimens, and asks if this initiative was driven by a need to find a better source of DNA so that the project could proceed. Four days after this story was published, a journalist in Sydney wrote another story clearly stimulated by the earlier one, in which he said, “scientists say the DNA recently extracted from a tooth and part of a femur is of much higher quality” than that extracted earlier from the pup. This understanding is compatible with the pup’s DNA being virtually worthless.

In fact, the choice of the pup as “the” specimen was a bit unusual in the first place, as researchers in this area had realised from the earliest days that dried tissues and hard tissues were better sources of DNA than alcohol-preserved tissue. One wonders if the early obsession with the emotive little pup did not set the project on a different course from what a coldly rational assessment of all the available specimens might have suggested. After all, the two dried specimens that eventually supplied the “much higher quality” DNA had been sitting in the Museum collections all along.

The next step of the project was to have been the insertion of the DNA fragments into bacteria for long-term storage in the so-called genetic library. Once all the fragments had been collected in the library, work could begin to try to put them in the proper order. A start was made on the genetic library, and Firestone opined that they would have one “hopefully by the end of the year [2002]”. But the work failed for reasons unstated at the time. As the Museum’s website says in an unattributed piece:

The lack of success with attempts to clone … [the] fragments hugely magnifies the difficulty of making a genetic map of the thylacine for the genomic sequencing planned as the third immediate goal of the project.

It was not until the Museum officially abandoned the project that the source of the problem became apparent: “the Thylacine DNA is far too degraded to even construct a DNA library”.

Considering the acknowledged “lack of success” in creating a genetic library, it is odd that the Museum’s annual report for 2001–02 states that in May 2002 the duplicated fragments were “cloned into bacteria”. And Archer even said at one stage that they had “already begun to have success” with it. However, this “result” was never alluded to again. And it certainly wasn’t mentioned in the press release or press conference of May 28, 2002, where one might have expected it.

After the second achievement was announced in May 2002, the project went off the boil. The only mention of it in the Museum’s annual report for 2002–03 is a one-line item noting that a program to attract Japanese students to the Museum to learn about opalised fossils and the thylacine project was a significant success.

In the latter half of 2002, work shifted to trying to fix the “badly degraded” DNA. This work apparently led to a technique to repair and modify DNA prior to inserting it into a bacterium. Colgan and Firestone described this result in an oral presentation to the International Congress of Genetics in Melbourne in July 2003. However, nothing more seems to have come of this potentially interesting work.

Firestone’s contract ended in late 2003, and the Museum advertised a one-year position for a technician with “demonstrated skills in multiple techniques of genetic library construction” with a closing date of November 28, 2003. A person was hired but quit for another job about halfway through the following year. The project seemed to be dying.

Archer’s five-year contract as Director of the Museum also expired at the end of 2003. But in early March 2004, despite no longer being in the Museum and hence no longer officially part of the cloning project, Archer went to Tasmania to lobby the state government to set aside a reserve in the Styx Valley, one of the last strongholds for the thylacine before it became extinct. The request was knocked back, a spokesman for the Tasmanian Premier reportedly saying the plan was “in the realm of science fiction” as there was “no proven technology to clone thylacines”.

Frank Howarth, a New South Wales career bureaucrat, became the Museum’s new director in early 2004. After his appointment, another year passed with no news of the thylacine project. Then on February 15, 2005, Howarth and his newly appointed Head of Science, molecular taxonomist Les Christides, announced that the Museum was scrapping the project, because the thylacine’s DNA was “far too degraded” to proceed to the next stage, the construction of a genetic library. Ironically, this is precisely the stage at which informed critics implied the project would founder, because it had reached the technological fringes. Archer would later interpret the Museum’s termination of the project as a matter of costs and not feasibility.

Over the course of its short life, the project to clone a living thylacine attracted commitments of just over $400,000. This was made up of an undisclosed amount from the private donors; an undisclosed amount paid by the Discovery Channel for the exclusive rights to the story as it developed; $20,000 from the New South Wales state government (courtesy of Bob Carr), and in-kind support of one-quarter of Colgan’s annual salary for about four years, which at a conservative $20,000 per annum amounts to about $80,000, also from the state government. Later it was revealed that “private benefactors”, including for certain the Discovery Channel and presumably also the private donors, had provided a total of $337,000 between them.

It’s not clear from the public documents just how all the money donated to and earned by the project was spent. Archer said after the second announcement that the total cash, which he put at “less than $300,000”, didn’t go very far and that it had “enabled [them] to put on Karen Firestone, buy her a tiny second-hand chair and a couple of used chemical jars”.

Despite the project’s two achievements, described by Archer as: “miracle results”; “pushing the frontiers of research with non-modern DNA”; having produced “exciting new science” and “important discoveries [that] had already flowed [from the project]”, and “succeed or fail … Australian science will acquire an immense store of knowledge that will, in turn, inspire further inquiry”—none of the team, to date, has published any of their results in a scientific journal. Aside from talks by Firestone at the annual meetings of two professional societies, one in July 2002 (overseas) and another in July 2003 (domestic), the results were only ever presented in popular articles, popular or non-specialist talks, science news magazines, press releases, press conferences and a television documentary.

There was talk of a scientific paper on three occasions. Firestone was reported in June 2002 as saying that they were “at least two months away from publishing”. Colgan said in April 2003, “Just now, we’re starting to prepare to submit the first scientific manuscript …” And in a piece on the Museum’s website almost certainly posted on or after May 28, 2002, and undoubtedly written by Colgan, one aspect of the work was described as forming “the substance of a research paper now being written”. In fact, the project was never peer-reviewed, because not only was no paper ever submitted to a professional journal for publication, no project proposal was ever submitted to an independent funding or assessment body.

Remarkably, however, the thylacine cloning project still had legs, at least as a story. Three months to the day after the Museum scrapped the project, Archer, now back at the University of New South Wales from where he had taken temporary leave to become the Museum’s director, said that the project was being picked up by a group of universities, including his own, and a research institute. He did not name the other institutions involved, pending their formal commitment to the project. Plans to bring the project back to life had no further public airing until September 6, 2005, when Archer reiterated his intention to re-start the project. He said Australian and US researchers would be involved. But aside from an allusion to discussions in the previous year that he had with Craig Venter, a kindred spirit who headed one of the two teams that sequenced the human genome, he still gave no names. Since then: the silence of the crypt.

In hindsight, it is remarkable how much was expected of the thylacine cloning project in addition to its stated primary goal of re-establishing a viable population in the wild. Archer thought there was a “moral imperative” to re-establish the thylacine in the wild and thereby lift the “complex web of guilt” engendered by its extinction. He also thought it would open up the possibility of allowing other extinct species to be “reborn”. The cloned animals would even “be ambassadors for a moral approach to genetic engineering”. He also believed it was the kind of project that would stimulate young minds. And, of course, there were the old perennials of technological spin-offs and tourism benefits.

Colgan hinted at a specific biological reason for the project when he said, perhaps somewhat hyperbolically, that the extinction of the thylacine was the “equivalent to the loss of all the cats—the panthers, tigers, lions—all at once”. Presumably, he meant that humans had been instrumental in removing a large predator from the Australian landscape, and returning it, even after more than half a century, would restore an ecological function. Archer and Colgan also mentioned, on occasion, the additional knowledge the project might have given about the two living species that might have provided a surrogate mother to a cloned thylacine embryo, the numbat and the Tasmanian devil.

The private benefactors believed their foundation donation would be supporting “internationally cutting-edge research … in this country”, and there would be “all sorts of medical breakthroughs along the way”.

And shortly after the Museum took on the project, it was given an even weightier burden. Archer and Colgan wrote that the project might help reverse what they saw as a ten-year decline in Australian science and demonstrate “our scientific confidence”. As Colgan said, “It would be a triumph for Australian science.” No one seemed to consider what a huge long-term project, introduced with great fanfare but then collapsing in a heap within three years, would do for the image of Australian science.

A more entrepreneurial mind might delight at all these noble reasons and wonder why anyone would go to all the time, trouble and expense of bringing an iconic species back to life, and— not to put too fine a point on it—not cash in on the investment to the hilt instead of just giving it away, as it were. In fact, a similar thought may have also crossed the mind of someone on the cloning team, because the original prospectus for the project mentions, “It is possible that there could be long-term commercial benefits arising from this research.” And one of the listed examples was: “viable thylacines”. In other words, it had occurred to someone that cloned thylacines could be flogged off or hired out, presumably under highly restrictive licences. The market among wealthy individuals and public entertainment institutions such as zoos would have been enormous. The prospectus, issued early in the project, was the only place where the possible direct commercial benefits of the project were ever mentioned. Perhaps it became quickly apparent that the commercial prospects sat too uncomfortably alongside the non-commercial reasons for the project.

In the end, of course, all of these additional expectations for the project, except for capturing the public imagination, came to nothing.

Looking back over the history of the thylacine project, it is interesting to see how the various interested groups reacted to it.

The reaction of scientists was mixed. Among those with expertise in the field, a few gave it general support, but most were highly critical. Archer asserted on various occasions that he had received widespread support for the project. For example, in May 1999, he said, “There’s been several geneticists [note the plural] who are saying it’s not a joke, it’s not silly, it could be done.” And in June 1999, he said that “when geneticists are responding to this story the response is not whether it can happen, it’s when”. At the beginning of the project in November 1999, Archer and Colgan did indeed convene a workshop in the Museum at which the “technological aspects of DNA recovery” were discussed, and he is reported as having said that “almost all the geneticists present thought it should be possible”. But the “it” appears to have been only aspects of the DNA recovery and not the whole project. Few, if any, geneticists would have doubted that any competent genetics lab could recover fragments of DNA from an alcohol-preserved specimen.

Colgan indicated in July 2002 that much of the support for the project may have, in fact, been private instead of public when he wrote, “The Museum’s staff is, however, aware that individuals—known to us by their personal letters and emails—are investing hope in our efforts.”

When Archer first proposed cloning the thylacine, but not necessarily in the Museum, only two experts went on record in support of the idea. Hans Graser, Director of Animal Genetics at the University of New England, was reported as saying that the “project was not nonsense, but there were significant hurdles to overcome”. And geneticist Mark Westerman at La Trobe University said that with funds and application, it was possible the thylacine could be cloned in the “not too distant future”. However, Westerman’s enthusiasm seemed to wane as time went by. After the second announcement in May 2002, he said, “They’ve got one hell of a job to do, and I don’t know how they’ll attack it.” And when the project was scrapped in 2005, he had come to believe that “What they are trying to do is far too difficult, given our state of knowledge.”

When Archer announced that the Museum itself would take up the project, he had another important supporter, Professor John Shine, Director of the Garvan Institute of Medical Research in Sydney. Shine was not only one of the project’s few independent expert supporters, he was also its most consistent. Most of his reported comments were in the vein of: “You’d be a brave man indeed to say it’s not possible”; “it’s a very brave and stupid person who says it’s impossible”; and “if you don’t aim for the stars, you only get the moon”. More specifically, he thought the project might have “potential spin-offs for human medical research”, and that it was the kind of project that “captures the imagination of young people and is very important for the future of science”. And even as late as March 2004, Shine joined Archer in his attempt to lobby the Tasmanian government to set aside a reserve in the Styx River valley.

But even some of Shine’s comments were a bit cautious, at least early on. Shortly after the Museum announced it was taking on the project, he allowed that it “sounds a bit like fiction”; the “technology just doesn’t exist yet to clone a complete animal from a dead specimen”; and “at this point in time, the technology is not there to generate a complete living Tasmanian tiger by cloning from dead cells from the preserved specimen”.

Archer maintained throughout the project that other institutions were interested in becoming involved. The September 1999 prospectus that kicked off the funding drive for the project claimed that “additional public institutions [note the plural], including genetics laboratories, are now seeking involvement as co-participants”. Towards the end of 2000, Archer mentioned “our partners who are working [note active tense] on this project”. On July 4, 2002, he was reported as saying that “there’s … been a huge response from other groups [plural], genetic research organisations and museums keen to be part of the project”. And even as late as August 2003, shortly before the end of his tenure at the Museum, he asserted that “genetic laboratories [plural] from all over the world were eager to lend their expertise to the Australian world-first endeavour”.

The only institution that was ever formally identified as part of the project, however, was John Shine’s Garvan Institute. The prospectus seeking donations said the project would “establish collaborative interactions with cell culture facilities such as the Garvan Institute”. Shine attended the launch of the fund-raising drive, and several media stories about the launch reported that the Garvan would be offering the project “backing” and “help”. The Museum’s press release for the first announcement said, “Later stages of this project will see the Australian Museum drawing on the scientific expertise of the Garvan Institute.” After the first announcement, Shine reiterated that “the Garvan is supporting this project”. The Museum’s annual report for 1999–2000 noted in a bullet-point paragraph: “commencement of initial studies, supported by the Griffiths family and the Garvan Institute, into the possible cloning of the thylacine, with good-quality DNA extracted from the Museum’s Thylacine pup this year”. After the second announcement, a story in which Shine was interviewed reported that “the Garvan … has offered the … project advice and support”. Another story reported that Shine had “offered the institute’s expertise in molecular genetics and DNA techniques”.

In the light of these indications of the Garvan’s involvement with the thylacine cloning project, especially in the prospectus seeking money from the public, it is odd that there is no mention of the project in the Garvan’s annual reports for the years 1999 to 2005 inclusive.

In the end, however, the resources of the Garvan were never utilised. The perfect time to have called for the Garvan’s help would have been when the cloning team was having problems inserting the extracted fragments of DNA into bacteria to make a genetic library. Indeed, one journalist had understood after the first announcement that the Garvan’s role would be to “undertake research to build up a DNA library of the thylacine”. But whether a call for help was ever made, or if it was made, what the answer was, is not in the public record.

Most experts who went on record about the project were what might be termed, politely, highly sceptical. At the beginning of the project Dr Jeremy Austin, then a research fellow at the Natural History Museum in London and an expert in the extraction and duplication of DNA from recently extinct animals, just like the thylacine, said, “The whole story is science fiction; it’s big time dreamtime.” He pointed out that the thylacine pup was relatively large for an alcohol-preserved specimen and even with a large slit in the body cavity and frequent changes of alcohol, the specimen’s “DNA would have been degrading like crazy”. Dr Ian Gunn and Professor Alan Trounson, of Monash University’s Institute of Reproduction and Development, said the project was a “futurist’s dream”.

After the first announcement, the critics remained unimpressed. Gunn said, “I don’t believe it can be done.” Dr Alan Cooper, then Director of the Henry Wellcome Ancient Biomolecules Centre at the University of Oxford, said bluntly, “it’s not going to work, and it’s a total waste of money”. Dr Alan Colman, who was involved in cloning Dolly the sheep, was reported as telling a Sydney audience that the thylacine would not be returned from extinction, because the recovered DNA would be too damaged to be useful. Other experts were more circumspect. Dr Marilyn Renfree, a zoologist at Melbourne University, said diplomatically, “I think the scientific community thinks it’s a very long shot.”

And after the second announcement, the critics were still unimpressed. Steve Cooper, a molecular evolutionary biologist at the South Australian Museum, said the project was “the stuff of science fiction”. Alan Cooper felt that it was “just a large publicity stunt designed to attract funding”, and was concerned “that such science fiction is doing a lot of damage to the field of ancient DNA—and getting us ridiculed”. Trounson said, “No amount of wishing and really good science will ever bring the thylacine back. It’s gone.”

Ashley Dunn, of the Ludwig Institute for Cancer research, wrote, “The notion of cloning the Tasmanian tiger from cloned DNA is utterly fanciful, and it is mischievous of Mike Archer to argue otherwise.” Later he went further, saying, “It is a public relations exercise that exploits the lay person’s inability to separate the likely from the unlikely, and the possible from the currently impossible.”

The editor of a local science news magazine, Australasian Science, called the second announcement a “PR stunt” to promote the Discovery Channel’s television documentary, although he noted, without apparent irony, that the project “brought in new money that wouldn’t otherwise have been spent on Australian science”. When the project was finally scrapped, the international journal Nature noted that “it had generated considerable scepticism in scientific circles”.

Perhaps the last word should go to Dr Harry Griffin, the Assistant Director of Scotland’s Roslin Institute, which cloned Dolly the sheep, one of the inspirations for the thylacine project: “There’s a snowball’s chance in hell of this project being successful. But as a PR stunt, it seems irresistible.”

In the light of the informed criticism of the project throughout its history, one wonders what was going through the minds of the private benefactors who provided the funding that kick-started the project. The person who fronted for the benefactors said that they went into it with “open eyes and knowing that it might go nowhere” and that it was a “madcap venture”. And once they had made their commitment, they were rarely again in the public eye. As private individuals, of course, they could do whatever they liked with their money and were accountable to no one.

What may have been going through the minds of the members of the Australian Museum Trust is more intriguing, because its members are ultimately responsible for how the Museum is managed, both conceptually and financially, and for ensuring that its integrity is maintained. In fact, the Museum Trust was the only responsible body in a position to pass judgment on the merits of the project and determine whether it went ahead or not. Did they seek their own independent assessment of the project at any stage? Or did they think the media’s enthusiastic response was the most important consideration, and the consequences for the Museum’s reputation as a research institution were insignificant in comparison? Or were they simply caught flat-footed by their new director, and once the story was up and running they could do no more than hang on and hope for the best?

The role of the media, which came from all over the world to report on the project, varied from totally accepting to bemusedly sceptical. But they rarely looked deeply and were never overtly critical. Archer made many assertions about the project that invited pointed questions, but these were rarely forthcoming. He referred on several occasions to how the project was continually overcoming the objections of critics. After the first announcement, he said, “that was a major overturn of what was supposed to be a fundamental obstacle”. After the second announcement, he said, “Already we’ve overcome obstacles that critics tossed up in front of us, saying these couldn’t be overcome … Sure, we keep running into brick walls, but they keep falling brick by brick”; “the project has moved forward against all expectations”; and the team had already “surmounted barriers people thought were impossible”. He also started referring to “criticisms”, “naysayers”, “negativity”, and claims of “impossibility” about the project. The media simply passed these assertions on without asking just what exactly these criticisms were and who was making them. And in doing so, they created the impression that the project was indeed overcoming major obstacles. The fact was, however, that the project had not yet even come to the problems that the critics said would be insurmountable.

What Archer, a palaeontologist, was effectively doing with all this talk of naysayers and negativity, of course, was putting his understanding of the field of molecular genetics and cloning against those with real expertise. That the media found nothing unusual in this marked asymmetry of knowledge and experience is remarkable.

The cloning team rarely responded specifically to the critics, and when they did, they sometimes got it wrong. In replying to criticism from Alan Cooper at the end of November 2001, Archer said, “I remember it was Alan who made the statement that … we would never, ever get DNA out of this thylacine [the pickled pup] … because he’d tried to get DNA out of other pickled specimens in another situation and hadn’t done it.” When this statement was brought to Cooper’s attention, he noted that what he actually said was that there would be no way to get a genome sequence, or intact DNA molecules, from pickled specimens, as he (and others) had done many DNA extractions from such specimens and the DNA was inevitably highly fragmented. He went on to suggest that “Archer may have confused ‘intact DNA molecules’ with ‘any DNA molecules’, which is an easy mistake for a non-specialist to make.”

In another instance, when a molecular taxonomist criticised the project for having said it would extract intact chromosomes from the pup, Colgan wrote in a letter to the editor that “We have made no such suggestion” and asked the critic to name her source. But he seems to have forgotten that the extraction of whole chromosomes was a clearly stated goal of the project, at least in its early stages. The project’s prospectus says, under item 3 in the “project details”, that they will “Extract whole chromosomes in whatever remains of the cells of the Museum pup”. And several news stories following the launch of the project understood that, as one story put it, “instead of extracting DNA, the team … will more likely take whole chromosomes from the bottled specimen”. Even after the first announcement, Colgan said, “If we can’t find the impact [sic; intact] chromosomes we’re going to have to resynthesise the chromosomes.”

Archer was also given to making strong assertions about the magnitude of the project’s achievements, which the media just let go through to the keeper. He said the project was “pushing the frontiers of research”, “moving forward against all expectations”, achieving “miracle” results and that “no one has ever done what we’ve just done”. Most of the media dutifully reported these assertions without getting more than the obligatory contrary view, and even this was often gleaned from earlier stories. Indeed, some of the media even joined in on the puff stakes, comparing the project to the space race and the attendant spin-offs in telecommunications. Only two journalists, both from the Australian, Leigh Dayton and Donna Maegraith, noted in stories after the second announcement that what the team had done had, in fact, already been done by others some years earlier.

After both the first and second announcements, Archer said on several occasions that the thylacine project was further ahead than any other project that had attempted anything remotely similar using “ancient DNA”. However, he never mentioned what those other projects were, and the media never seemed curious enough to ask. Hence, it was never possible to test the aptness of the favourable comparison, especially with regard to the quality of the source specimens and the seriousness of the intent.

Archer, Colgan and Firestone all claimed or implied on various occasions that they had extracted a complete, or nearly complete, set of thylacine genes. In the press release for the first announcement, Colgan said, “The preparation has enough DNA for us to be confident it contains multiple copies of nearly every Tasmanian Tiger gene.” A few months later, Archer said, “our geneticists … think they have the full genome of the Thylacine in these massive chunks”. In 2003, Firestone said of a bone specimen, “If you ground up the whole bone, you could probably extract every gene in the genome.” Even after he had left the Museum and the project had been scrapped, Archer was still saying, “We’ve undoubtedly got the whole of the genome in the recovered DNA.” However, these claims were never supported by any evidence, other than the amounts of DNA extracted. And no journalist asked for the evidence of the “whole genome” or, for that matter, even the rationale. Perhaps if journalists had realised just how mistaken the cloning team had been about the nature and quantity of the pup’s DNA, they might have started asking such questions.

For a seasoned media performer, Archer seemed remarkably surprised at all the media attention the project attracted. Two months after the second announcement, he said:

The publicity wasn’t something we went out to seek. It sort of sought us. We announced we were doing this project, and we were beset by hundreds and hundreds of media groups desperately wanting to do a story on this.

Media stories are not meant to be forensically critical. Journalists are just there to report the news as it happens or is presented to them and perhaps, at best, ask a few clarifying questions and seek an external opinion for a bit of balance. Investigative journalism is the place to look at issues in greater depth. But while the Australian media are good at investigative journalism when it comes to politics and business, they are abysmal when it comes to science. There are two reasons for this. First, investigative science journalists have to know almost as much about the subject as the scientists themselves. And second, investigative journalism, to the extent that it is done at all, is usually pursued as a sideline to everyday journalism. And journalists who get a reputation of being too fond of looking deeply at what they are being fed might find themselves cut off from the daily flow of stories that are their bread and butter.

It is difficult to know what the public thought of the cloning project. There appears to have been no opinion poll. The Museum ran a poll on its website asking people to vote for or against the idea of cloning the thylacine, and the last reported numbers had 9300 for and 1100 against. Such a poll, however, was not about feasibility, just desirability, and this could have encompassed anything from moral conviction to entertainment. In any case, such a poll would be biased towards the pro vote, because supporters are more likely to visit the website than are detractors. Nevertheless, if this is a true reflection of the popular sentiment, it highlights just how different the public and the expert perceptions of a project in science can be. Museums are eternally anguished in planning their public programs about how to balance what the public wants and what the experts think is important, and the thylacine project shows just how out of sync the two views can become. The only other indicators of public sentiment were letters to the editor, and these were all critical. But this forum is also biased, in this case on the side of detractors.

There were other criticisms about the thylacine cloning project besides those centred on the technological aspects. Most of these criticisms were premature, because they were predicated on being able to clone the thylacine in the first place. But one criticism was immediately relevant, because it questioned how limited funds should be spent on endangered species. For many critics, the project was a waste of money that could have been spent on other more urgent and feasible conservation projects. Indeed, the only question about the project ever raised in the New South Wales state parliament was on this very issue.

Archer countered this criticism by saying that “the people who want to put money into this project have no interest in conventional conservation. They’re doing it because they’re fascinated by a technologically incredible project.” The private donation may have been non-discretionary, but the other funds were not. Arguably, the state government’s cash and in-kind contributions, totalling about $100,000, nearly a quarter of the total, could have gone either directly or indirectly to other projects on endangered species. Also, the money paid by the Discovery Channel would have been discretionary within the Museum. Bob Carr replied to the question in parliament by saying that most of the money was private and only “a small percentage of the salary costs for the initial research will come from the salaries budget of the Australian Museum”. In fact, Colgan’s salary contribution estimated (above) at $20,000 per annum was just over 20 per cent of the estimated total annual salary expense.

Colgan offered a slightly different reply to the criticism, saying that the millions that would ultimately be spent on the cloning project were insignificant compared to the sums that would have to be spent buying up “all the land” necessary to preserve currently endangered species. In fact, the current pattern of land purchase for conservation purposes is one of incremental purchases for a few million dollars each.

Many criticisms were based on actually being able to solve all the technical problems of getting a developing thylacine embryo. One was that in the absence of a thylacine female into which the reconstituted thylacine embryo could be implanted, another species would have to be used as the surrogate mother. But the two species suggested as possible surrogates, the Tasmanian devil and the numbat, last shared a common ancestor with the thylacine about 28 million years ago, since when the two branches in this part of the marsupial phylogenetic tree have diverged to such an extent that their member species are classified into two different families. What were the chances that the reproductive physiology and immunology of either of these two distantly related species would accept a thylacine embryo? When palaeontologist Archer was thinking about resurrecting the project, he replied to this criticism, based on embryological and immunological concerns, by stating confidently that “For a Tasmanian devil to give birth to a thylacine wouldn’t be a trouble at all.”

A related criticism was that in the absence of a thylacine egg into which the recovered and reconstituted nuclear DNA could be injected, the egg of a close relative, again the devil or the numbat, would have to be used. But because that egg would contain the surrogate species’ mitochondrial DNA in its cytoplasm, the embryo and eventual pup would not be 100 per cent thylacine. A small part would be the surrogate species.

Another question was where the essential microbial fauna of the thylacine’s gut would come from in the absence of any living thylacine, let alone a mother, the one who passes these organisms on to her offspring.

Critics also wondered who would teach a cloned thylacine all the behaviour that is learned from other individuals of its own kind, especially how to hunt. Archer’s reply was that from his experience raising the young of other marsupial species it appeared that much of the group’s behaviour is innate and not learned. Perhaps. But how important might that small learned component be, and would a cloned thylacine be the full quid without it?

Another criticism was, if the thylacine had been driven to extinction on the mainland due to competition with the dingo after that species was presumably introduced into Australia about 4000 years ago, wouldn’t dingoes or even wild dogs just do the same thing again? Archer countered this argument by saying that the cloned animals could be released onto an island free of these ferals or, even more technologically enterprising, the thylacine, having come through the wash of cloning, could then be put through the ringer of genetic engineering to make it even larger and more competitive.

Archer is, in fact, a fan of genetically engineering nature to “survive” anthropogenic change. After the first announcement, he said, “I don’t think life will respond quickly enough using traditional natural genetic engineering processes. We are changing the world so rapidly that we have a concomitant responsibility to help life change.” But whether the product of genetic or any other form of human manipulation of nature is still nature is, of course, one of the fundamental questions underlying humans’ treatment of nature.

And a final criticism was that even just talking about bringing back species from extinction might make people blasé about the loss of species in our own time. One consequence of raising issues about what to do with a cloned thylacine was to give credibility to the effort to clone the animal itself. A naive person might well think that if people are already talking about what to do with the clone, then it must be a pretty sure thing.

The basic scientific flaw in the thylacine cloning project was that it was, in fact, many separate projects. The initial stages were relatively easy, and these were accomplished. But the later stages were either at or well beyond the frontiers of current technology. And when their time did come, the foundation work would be done first using living animals and not extinct ones. This basic insight was usefully provided in a letter to the editor as early as June 8, 2000. For example, the reconstitution of DNA fragments and their re-stitching together in the proper sequence will be tackled using purposely fragmented DNA of a living species whose entire genome has already been sequenced and can, therefore, provide a standard to assess the efficacy of the re-stitching techniques. Likewise, with partitioning the genome into chromosomes, inserting the chromosomes into a nucleus and getting a distantly related mother to accept the implanted fertilised cell. But to have partitioned the project into separate sections as ends in themselves and committed to doing only the first ones, say up to the point of a gene library, a laudable end in itself, would have robbed the project of its most exciting feature, humanity’s eternal intrigue with a return from the dead.

One of the rationales for the project was that it would stimulate young people to go into science. No doubt some young people are stimulated by reach-for-the-stars projects. But probably more get hooked by more down-to-earth events such as holding a fossil for the first time or wondering how snakes can move without legs. Regrettably, these opportunities are becoming rarer by the day, thanks to the destruction of nature, society’s increased concern about safety, and the legal prohibitions against collecting fossils and “disturbing” native fauna.

Projects like the one to clone the thylacine are terribly seductive to your average hod-carrying scientist. Working diligently day in and day out and consumed by anxiety about where the next research grant is going to come from, they face a Faustian pact when they are suddenly presented with the opportunity for fame and fortune—for their research, anyway. In a day when form shines over substance, it needles the hell out of good workaday scientists to see a colleague, lab or institution, whose work is perhaps no better than their own, suddenly burst into the public consciousness because they have made an interpretation or proposal that, while not strictly wrong, is so outlandish that most scientists would blush even to read it let alone embrace it. Add to this the admiration of such publicity-attracting capers from your own institution’s managers and its political masters (note Bob Carr’s presence at the thylacine project’s launch and second announcement), and you begin to wonder just who is the mug.

This is what seems to have happened to the Royal Botanic Gardens when they decided to pitch the discovery of the Wollemi pine as being the equivalent to discovering a living dinosaur. The pitch worked, and the publicity and commercial opportunities flowed. And it is difficult to believe that the same temptation did not, at least in part, drive some people’s enthusiasm for the thylacine cloning project.

There is a widespread feeling in Australia that natural history museums and the research they do are largely kids’ stuff. Art galleries are for adults and natural history museums are for kids. And because natural history is for kids and largely for fun, it is not very important. Projects like the thylacine cloning project, as it was conceived, managed and publicised, only contribute to this perception. Indeed, the Premier of New South Wales, Bob Carr, said after the project’s first announcement that it brought “hope that one day Australian children may get to know the Tasmanian tiger from a living animal rather than a faded black and white photo”.

That the Museum’s wound was entirely and wilfully self-inflicted, makes it all the sadder. One only has to compare the general passive acceptance of the thylacine project in comparison to the outcry that would have arisen if the same approach had been taken to a project in medical science to gauge just how irrelevant, other than for entertainment, natural history and, by extension, natural history museums have become.

Finally, what happened to the individual members of the cloning team after the project collapsed? Firestone returned to Taronga Zoo, from where she was originally recruited on a temporary basis. Colgan is still at the Australian Museum but no longer head of the Evolutionary Biology Unit, although for reasons unrelated to the thylacine project. And Archer went back to the University of New South Wales, from where he had been recruited, and where, upon his return, he was made Dean of the Faculty of Science.

The author was an employee of the Australian Museum during these events.

0 comments
Post a comment