Vale Cedric

Cedric the Tasmanian Devil is dead. For a short time, this one Devil carried the hopes of the world that at least some Devils might be able to mount an immune response to the facial tumour disease ravaging the species and that it might be possible to develop a vaccine against the disease. But at the beginning of September 2010 researchers revealed that Cedric had been put down at the end of August after they discovered a primary tumour on his face had metastasised to his lungs, putting him beyond both surgery and chemotherapy. Staff at the Menzies Research Institute Tasmania, who had experimented on Cedric, buried him. They said there would be no memorial service, but they were “considering ways of remembering him”. One researcher said “we would like to remember him as a symbol of the fight against DFTD [Devil Facial Tumour Disease]”.

Perhaps. But Cedric might be equally well remembered for another feature of the fight against DFTD: the tendency to publish scientific discoveries via the media instead of the scientific literature.

Here is Cedric’s full story, as pieced together entirely from media stories and one second-hand comment in one scientific publication.

Early in 2007 researchers decided to try and elicit an immune response in two Devils with potentially resistant genes by injecting them with tumour facial disease cells. They were probably motivated by the published knowledge that the unaffected populations in the north-west part of Tasmania differed genetically from the affected populations in the east, and perhaps also from the unpublished knowledge that at least two wild-caught individuals from a peripheral north-west population appeared to have developed antibodies to the disease.

They chose two captive-bred Devils, named Cedric and Clinky, for their experiment. The two Devils were half-brothers. They had the same mother but different fathers. Cedric had all western genes, because his father and mother were both from the west coast of Tasmania. Clinky, however, had half western genes from his mother and half eastern genes from his father, although his father’s provenance was only ever revealed indirectly. Apparently, the idea behind the experiment was to see if either animal could raise antibodies to the disease and how an animal with both western and eastern genes might respond.

So sometime not long after February 20, 2007, Cedric and Clinky were injected three times in the cheek with irradiated, that is, dead, facial tumour cells. Subsequently, Cedric developed “high titres of tumour-specific antibody”, but Clinky did not. This result was first announced in late November 2007, although Cedric’s positive immune response and Clinky’s negative response would probably have been evident much earlier.

In December 2007, researchers injected live cells from presumably the same strain of the tumour into two sites on the head in both Cedric and Clinky. On June 2, 2008, a few days before the state budget was to be handed down, a University of Tasmania media release announced that Cedric “showed an immune response” and remained tumour-free whereas Clinky had not developed an immune response and had developed a tumour. A researcher said, “We are 90 to 100 per cent certain that Cedric is resistant to the disease.” The research team’s vet said there was a plan to treat Clinky with chemotherapy. And there was indeed a preliminary study in which cytotoxic drugs were trialled on diseased Devils, but this was only partially effective. Whether Clinky was part of this experiment is unclear. In any event, Clinky eventually died from the disease. Although Clinky’s tumours were announced on June 2, 2008, they were apparently known to researchers as early as twelve weeks after the injection of live cells, that is, in March or April 2008.

In July 2008, researchers injected Cedric with live cells from a second strain of the tumour in order to test how long his immunity would last. This seems like an odd protocol, because if Cedric did develop a tumour how could researchers tell if this was due to his having lost his immunity or to his inability to mount an immune response to the different strain?

In any event, by mid-December 2008 Cedric had developed small tumours where he had been injected the second time. Subsequent analysis showed that these tumours were from the second live strain, although the team’s vet seemed to suggest in a much later interview that it was now uncertain which injection (strain) may have caused the disease. Cedric had his tumours removed surgically instead of being treated with chemotherapy as had been foreshadowed with Clinky.

And then the surprise announcement on September 1, 2010, that Cedric had been put down in the preceding week after his facial tumour had spread to his lungs, rendering his condition hopeless. Vale Cedric.

But just a few weeks before his death, Cedric had one last entry added to his CV, although it wasn’t announced until about three weeks after his death. Apparently he was one of only three Devils to have had their entire genome sequenced. The results will now help pave the way for a gene-by-gene comparison between normal Devil cells and the mutated cell line that underlies facial tumour disease.

Intriguingly, there was a third Devil involved in this story as well—a dark lady, as it were. At some unspecified date, a female named Christine was injected with dead tumour cells and developed an immune response. At a later date, again unspecified, she was injected with live tumour cells. In July 2008, she was reported to have mounted an immune response. And later in the year, she was revealed to have remained disease-free two months after first showing an immune response. This Devil, first confusingly called “another Devil”, was later revealed to be none other than Cedric’s mother. As such, she must have had all western genes. What has happened to Christine is unclear.

There were also reports of work being done to determine a possible immune response in other Devils. In June 2008 in conjunction with the then good news of Cedric’s apparent resistance, a University of Tasmania media release said that a “special six” Devils from the west coast and with DNA similar to Cedric’s were to be investigated “to determine if they are also resistant to infection”. Nothing more has been heard about this intended work.

And in December 2008, after the first bad news about Cedric had been released, a journalist reported that “dead cells would be injected into more than 20 other Devils to try to replicate the immune response”. But again, nothing more has been heard about this planned work.

The research on Cedric, Clinky and Christine seems to have resulted in several important findings about the Devil’s immune response to the disease. First, at least some Devils can mount an immune response to at least one strain of the disease. But, also, that immune response may be insufficient to stop the disease. Second, immunity raised by one strain may not be sufficient to confer immunity to another strain. Third, the tumour can metastasise at a very early stage in the growth of the primary tumour. And fourth, a metastasis can take up to eighteen months to noticeably affect the health of an animal. If these results are correctly inferred, they have important implications for understanding about the disease.

Strangely, work testing the general competency of the Devil’s immune system has been published in a timely fashion, often in only a few months, but the work on the Devil’s specific immune response to the disease as revealed by Cedric, Clinky and Christine and the other Devils remains unpublished. This is remarkable considering the significance of the apparent results. All but the most recent results arising from Cedric’s death are now more than a year and a half old, which is well within standard publishing times, especially online.

A researcher, speaking when Cedric’s death was announced, said, “Cedric has played an important part in helping us to understand more about the disease”. But this “understanding” can only be validated by publication in the scientific literature where it can be scrutinised by those who know what to look for and what hard questions to ask. Certainly, if Cedric is deserving of any memorial, it would be to have the results of his life’s work, so to speak, published in the scientific literature.

Publication by media is an all-too-common aspect of the Devil research program. And the reason cannot be solely to satisfy the intense public interest, because for many of the foreshadowed results the time to publication has been so long it is reasonable to ask if they ever will be.

The reason for this may lie in the fact that Devil research and conservation are funded largely by private donations, including those from school children, and by direct bulk grants from the Tasmanian ($13.5 million) and Commonwealth ($10 million) governments. This kind of targeted funding, made available in a crisis atmosphere, is especially responsive to good-news stories, promising results and verbal assurances from experts with a vested interest. It is not dependent, like other scientific projects, on the cool scrutiny of disinterested peers in a wider context.

The central program is the Save the Tasmanian Devil Program (STDP), which is co-ordinated by the Tasmanian Department of Primary Industries, Parks, Water and Environment (DPIPWE). The STDP solicits public donations through its Save the Tasmanian Devil Appeal (STDA), which is run by the University of Tasmania Foundation. STDA’s goal for individual donations this year is more than one million dollars. The STDA in turn distributes funds for research through the Devil Research Advisory Committee. The current Committee is made up of six representatives from the University of Tasmania and one from the DPIPWE. As of early 2010, about 74 per cent of the STDA research funding had gone to University of Tasmania staff and students.

Naturally enough, scientists like being able to access specific-purpose bulk funding. Such funding offers researchers a better chance of success than the normal government scientific funding programs, such as the Australian Research Council, where success rates can be less than 25 per cent and further funding dependent on a timely flow of peer-reviewed publications. So when the rare chance of a large amount of “less demanding” funding comes along, there can be a strong temptation to keep the good times going. And this can lead to some “out of character” behaviour. We’ve seen it with other high “public interest” science projects, such as the discovery of the Wollemi Pine and cloning the Thylacine. And we may be seeing it again with the Devil’s facial tumour disease. 

Allen Greer is a biologist who writes about science and nature. A referenced version of this article is available from him at [email protected].

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