The Independent newspaper today ran a front-page story about the success of initial results from trials of a gene therapy treatment to treat a rare form of hereditary blindness. The article pointed out that the technique had already been shown to work in animals.
But what are the implications?
Only last week the Independent ran a front-page story about the lack of hope in finding an HIV vaccine. This they said was despite many years of tests in animals—some of which showed positive results but subsequently failed in humans.
These simplistic comments are a sad reflection of the failure of the Independent to get to grips with how animal research works. Whilst it is understandable that news pieces are short, the Independent is the only quality broadsheet that has repeatedly failed to give a more in-depth analysis. Contrast, for example, with the more sophisticated approach from the Guardian Comment is Free blog.
For all we know, some years in the future the outcomes of these news stories could be very different. If we do ever gain a successful vaccine against HIV, it could be that animal research plays an important role in its development. And it is not impossible that the results of the gene therapy trials for blindness turn out to be less spectacular than first thought—it would not be the first time.
We already know that some animal studies give results which translate reasonably well in to medical advances for people. Inevitably, in other cases, significant differences between the animals and humans, or problems in experimental design, or insufficient animal research, mean the results are less helpful. The Independent could do more to inform readers about the nature and intricacies of medical research. An occasional science column along these lines would be welcome.
The following statement in last week’s Independent tells only half the story:
‘One of the major conclusions to emerge from the failed clinical trial of the most promising prototype vaccine, manufactured by the drug company Merck, was that an important animal model used for more than a decade, testing HIV vaccines on monkeys before they are used on humans, does not in fact work.’
The failure of an HIV vaccine candidate to protect humans from infection in the STEP trial may represent a failure of the SHIV monkey/virus model but it represents a vindication of the SIV model. The vaccine showed promise against the SHIV model but not against the SIV model.
One important lesson of the STEP study is its indication of which model we should be using for future research. We should also note that these models are more than simply animal models. SHIV and SIV are used as two ‘models’ of Human Immunodeficiency Virus, just as uninfected rhesus macaques are used as ‘models’ of healthy humans. Post-vaccination infection of monkeys with two viruses closely related to HIV constitute two different disease models of HIV in humans. The SIV disease model was warning us that this vaccine might not work for humans - the promise held out by the SHIV model proved to be unfounded. Whether or not it was intended, STEP turned out to be an excellent experimental test of the two models.
It was not only the SHIV model which failed to predict the effect of the vaccine. The usefulness of the ELISPOT immunogenicity assay has also been brought into question by STEP. With the exception of the SIV model, pre-clinical and early clinical testing of the vaccine failed to predict the effect of the vaccine on humans.
Amongst the lessons of STEP are that we need more basic research to improve understanding of how HIV undermines the immune system and we need candidate vaccines which can offer monkeys real protection against realistic SIV challenge.
Finally, let it be said that pessimism is a luxury which we cannot afford. We need ever greater determination with each new setback.
