It is one of the curiosities of science that by the time a researcher has gained an international reputation, it is likely that he or she is no longer able to do the work that made their name.
Cathryn Mellersh, head of the canine genetics research group at the Animal Health Trust (AHT), is a globally important figure in the study of inherited diseases in dogs. She has probably done more than any other UK scientist to track down the mutations in the DNA of pedigree breeds that are responsible for serious genetic disorders.
And how much time does she spend at the lab bench these days? “There aren’t many times that I am able to put on a white coat,” she says with a rueful shrug.
But while she is no longer engaged in the front line of the battle against canine genetic disorders, she is not far behind directing the efforts of her crack squad of postgrad and post doctorate researchers.
So it is for both her past and current efforts that Cathryn was given the Kennel Club’s international veterinary research award. The prestigious International Canine Health Award (ICHA) recognises the contribution she and her colleagues have made over the past two decades in advancing our knowledge of health and welfare problems in the dog – and is a tremendous psychological spur to even greater efforts in the future.
Equally important, the award came with a cheque for £20,000, a sizeable sum in the field of companion animal research. Here, there is little or no government support, and most scientific progress is driven by the relatively small sums available from animal welfare charities, breed clubs and philanthropic foundations.
The funding provided for the Kennel Club awards scheme by the US banking entrepreneur Vernon Hill and his wife Shirley, is being used by Cathryn to reinforce her team and launch the research careers of three talented young scientists.
James Oliver is the oldest of the trio, having qualified as a veterinary surgeon from the University of Bristol in 2002. At vet school, he was fascinated with the diagnosis and treatment of eye diseases and went on to gain postgraduate qualifications in veterinary ophthalmology. After joining the Animal Health Trust’s clinical ophthalmology service in 2013 he has become equally curious about the underlying cause of the diseases he was treating. As a result, and has begun a PhD looking at the genetics of inherited glaucoma in a range of breeds, including the Welsh springer spaniel, the Dandie Dinmont terrier and the Basset hound.
The award is also supporting the PhD studies of two young biologists who joined the AHT as research assistants. Rebekka Hitti had worked at the trust during the final year project for her biological sciences degree at Nottingham Trent University. Her doctorate studies will attempt to identify and develop genetic tests for the defects that cause the common eye disease, progressive retinal atrophy in different breeds. Meanwhile, another chunk of the award is supporting the PhD studies of Chris Jenkins, who graduated from the University of East Anglia in 2010. Later he worked at Sheffield University developing his expertise in molecular biology and advanced analytical techniques. Those skills are now being applied in his studies into the genetic basis of inherited epilepsy in a number of different pedigree breeds.
Cathryn is engagingly modest about the achievements of the inherited diseases team at Newmarket. “Ours is the less glamorous side of the trust’s work,” she says.
Certainly, their efforts don’t help to create the medical and surgical treatments that vets at the AHT have used to save the lives of individual patients. But arguably the genetics unit will have a much a greater long term impact by preventing dogs being born which go on to suffer from various painful, debilitating or life-threatening conditions. The problem is that it is impossible to quantify the effects of an event that doesn’t happen – “the benefits of this work are intangible,” she says.
Staff at the trust developed two of the first genetic tests for dogs in the late 1990s for progressive retinal atrophy in Irish setters and copper toxicosis in the Bedlington terrier. Overall they have been responsible for developing tests for 20 mutations in 35 different breeds, or roughly 10 per cent of the total number produced by research labs across the globe.
When Cathryn joined the group as a senior postdoctoral research scientist in 2000, there was a lengthy and somewhat hit or miss procedure for tracking down a disease-causing mutation. The first task was to identify exactly how the mutation is passed on, by examining the numbers and distribution of both diseased and healthy animals in a pedigree line.
The next stage involved taking DNA samples from those animals and looking for sections of redundant code that can provide signposts for pointing out the position of the disease-causing mutation. Those samples are treated to break down the long chain of DNA into much shorter chunks and the closer the mutation is to the gene marker, the more likely they are to end up on the same fragment.
Since then there have been two significant developments in gene technology that have provided more precise tools for locating a relevant gene mutation. First came the gene sequencing technologies used first to unravel the complexities of the human genetic code, and which have since been applied in a wide range of species, including dogs.
A first draft of the dog genome was first published in the scientific literature in 2004 and since then developments in automation have significantly reduced the costs involved in gene sequencing. The original human genome project completed in 2001 required input from a number of research labs across the world and cost millions of dollars. Now a sample can be taken from just one individual, sent of to a company offering gene analysis services and sequenced within a few weeks at a cost of around £2000.
That makes it economically feasible to examine the genome of dogs from a particular breed and identify the causes of any breed-specific conditions by comparing the results with those of another in which the mutation is absent.
So the AHT launched the Give a Dog a Genome project earlier this year (2016), which is being funded by the Kennel Club Charitable Trust and 75 of its individual breed clubs. When the results of the programme to sequence a typical representative from all 75 breeds have been completed and analysed over the next year or so, it will greatly shorten the odds of successfully locating a disease- causing mutation.
Cathryn explains that the new method for identifying a defect depends on a technique known as filtering. “There are 2.4 billion pairs of nucleotides - the four letters that form the DNA code - in the canine genome of a dog and between any two individuals there will be perhaps two or three million places where there are differences.”
“We can directly compare the DNA from any one dog with every other one in the bank of genomes that we will be building up. The more we have, the more efficient the process will be. We can eliminate those differences found in parts of the genome that we know are not involved in coding for a protein and eventually we will have just one difference in a protein that is known to be relevant in the particular disease that we are studying.”
Of course, that is the simplified version and some defects will be more difficult to spot than others. That is particularly true for cases in which a long sequence of DNA has inserted into a chromosome the wrong way round. But the Trust’s lengthy experience of DNA analysis in dogs mean that its staff will be better than most research teams at spotting any anomalies.
So in each of the breeds that are supporting the project it should be possible to develop a test that will allow breeders to plan their future litters with the assurance that puppies will be free of a particular disease. “If all goes well we could have a genetic test for inherited glaucoma, or for the form of progressive retinal atrophy that we are studying, within 12 months or so,” she says.
It is unusual for a scientist to make such a bold prediction, but she is confident that her team has the skills and the tools to make rapid advances in canine health and welfare over the next few years. She is insistent that any progress is the product of teamwork effort and was delighted that all her colleagues were able to attend the conference where she received her ICHA award, held just down the road from her lab in Cambridge.
“Everybody likes a pat on the back every now and again and it was really encouraging to have that public recognition for the work they have put in. It is very much a group effort for which my colleagues should take the credit, as it is they that do the work. My job is to organise the projects, write grant applications and to bring in the money that is essential for this research to continue – their job is to spend it!” she says.
Nominations are currently being sought for the next awards which will be presented at a ceremony at the Kennel Club in London on 24th May 2017. With a prize fund totalling £65,000, the Kennel Club Charitable Trust is urging people to nominate themselves or their peers by 13th February 2017. The awards will be judged by representatives from the veterinary profession and the world of scientific research, including experts in each of the nominees' selected fields. For more information about how to apply visit the Kennel Club’s website now.