A ‘speed gene’ test for Galileo Gold is just the latest twist in a bewildering maze. Revolutionary science might seem to tempt us one way, tried-and-trusted horse lore another. Each new turn presents bigger questions – ever more exciting, to some; ever more frightening, to others.
If the following overview represents only the clumsy groping of a layman towards the potential for genetic testing in the thoroughbred – its legitimate aspirations, its possible limits – then perhaps that is apt enough. As such, after all, it shares the uncertainty of so many horsemen in a highly conservative industry. With all due humility, even so, two imperatives are proposed.
The first is for all sides to respect each other. This means both that traditionalists should grant the innovators a fair hearing; and that commercial application of the new knowledge should not be hijacked by snake-oil hucksters.
The second is to seek common ground in the long-term interests of the breed. That, after all, is what lies in the middle of the maze.
Thoroughbred breeders have been using a form of genetic selection for centuries – and pretty successfully, too – but persistent flaws in the breed have continued to defeat both their eugenic skills and advances in veterinary science. From 1990, however, radical possibilities began to open up.
The size and organisation of the genome is similar across all mammals. Could the information derived from the human genome project be used to map that of the thoroughbred? And, if so, what might be discovered about the breed’s physical deficiencies?
In 1995, 70 scientists from 20 countries convened in Lexington to plan the collaborative exploration of the equine genome. Initially this community set out to map the horse’s 32 chromosome pairs in a fashion that could borrow the advances being made in the human genome. This soon disclosed the genetic basis for such simple traits as coat colour and also some hereditary diseases, and triggered the commercial development of associated molecular tests.
In Britain, influential figures in the industry resolved to grasp the nettle – despite the jitters of commercial breeders, who were asking themselves what might happen if, say, the new science only fell within the reach of the very biggest pockets? Would these superpowers keep all their best stock, and offload only flawed goods at the sales?
C:Cs may win at longer distances at a lesser level, because quality can have an impact
But those trying to see the bigger picture agreed that if science was on this road anyway, the sport should try to retain some control of the steering wheel. A research body was duly instituted, in partnership, by the Animal Health Trust and the British Horseracing Board.
Its brief was to establish whether genetics might offer some reliable index of athletic capacity or physical weakness. The conclusions were sceptical, with regard to the former; and intriguing, with regard to the latter. Nonetheless the breeding industry remained extremely wary, the project lost impetus and the BHB stake was bought out by the AHT.
Internationally, however, the scientific landscape was meanwhile undergoing rapid change. Animal genes turned out to be both simpler and more complex than anticipated. Originally it had been posited that there might be 300,000 genes. In the event, the figure proved to be nearer 20,000.
At the same time, it was found that sequencing these would only uncover the margin of heredity. As much as 98% of genomic secrets instead lurked in what had been called “junk DNA”, which did not encode genes and was unique to each species.
Fortunately, the horse was then chosen as a model against which to measure differences and similarities in the human genome. This accelerated the DNA sequencing of some 30,000,000 genomic components. The genetic wiring of the horse was soon tracked with barely comprehensible intricacy: 20,000 genes and around 3 billion DNA bases. The question now was: who could gain what, as a result?
The ‘Speed Gene’
It seems important, at this stage, to stress that neither equine geneticists nor breeding professionals have a superior claim, as a community, to the moral high ground. Both will contain those who put short-term commercial opportunism ahead of the long-term interests of the breed; and vice versa.
It is against this background that the Thoroughbred Breeders’ Association has commissioned a review under the chairmanship of the respected and experienced veterinarian, Peter Webbon. He views his brief as a scrupulously objective one: to inform breeders about the options they have; the underlying science; and the potential consequences.
His preliminary assignment is to explore the tests currently available. Among these, none has gained a firmer foothold in the industry’s collective imagination than the one consulted by connections of the 2,000 Guineas winner, Galileo Gold, in pondering whether a fairly speedy pedigree might contain sufficient latent stamina to warrant a crack at the Investec Derby.
This so-called ‘speed gene’ test traced to the discovery of Dr Emmeline Hill, a University College Dublin geneticist, that a single gene – myostatin – governed muscle mass development and muscle fibre type in the thoroughbred. On this basis, since 2010 Hill has been able to propose predictable patterns of precocity and stamina in the careers of tested horses. The resulting test is the headline service offered by Equinome, the company she founded with the eminent trainer and breeder, Jim Bolger. (It has since merged with the nutrition firm, Plusvital.)
The test is based on a DNA variant within myostatin, labelled either C or T. Each individual inherits two copies of the gene, one from the dam and one from the sire, giving rise to three possible combinations: C:C, C:T or T:T. In analysing nearly 13,000 horses, including 1,000 black type winners, Hill and her colleagues have suggested a massive preponderance of early-maturing sprinters among C:C types, and late-maturing stayers among TT types.
Moreover their genetic legacy at stud is also stipulated: the CC to produce only C:C or C:T progeny; and the T:T, only T:T or C:T. The C:T, predicted an intermediate stamina range, can breed any of the three types.
“What’s extraordinary is that the more research we do, the more evidence we find of a very large and singular influence of this gene on the distance trait,” Hill says. “That seldom happens in science. The myostatin gene has been studied in 20 scientific papers since 2010, in thoroughbreds and other horse breeds, and these have continued to validate both the findings and the interpretation.
Its contribution to this trait is probably stronger than any gene in any other livestock populations. That’s because of the strength of historical selection in the population.”
After Galileo Gold returned a C:C, his connections elected to persevere at a mile in his next race – albeit while leaving the door ajar to longer distances, depending on his performance there. It was the test’s most public vote of confidence to date. But without prejudice to the findings of his review group, Webbon reminds horsemen that the prediction, first and foremost, is about the build of an animal.
“All it does, really, is tell you what sort of shape a horse might take,” he says. “Myostatin governs muscle development, so that you can imagine its use in breeding something like Belgian Blue cattle. Dr Hill came up with this notion that a horse’s genetic make-up could more or less predict whether it would be short-coupled, stocky and muscular, or rangy and lighter; a Linford Christie or a Seb Coe. This was called the ‘speed gene’ – but it actually tells you about shape, about physiques that are considered self-evidently typical of a sprinter or stayer.”
Hill qualifies that by noting that myostatin also influences the proportion of “fast-twitch” muscle fibres, associated with sprinting. But even a plain prediction of physique does not, in itself, entitle a traditionalist horseman to scoff that C:C, C:T and T:T merely condense his own seasoned assessment of a horse’s pedigree and conformation.
As Hill emphasises: “The difference is that we can take a genetic test of a foal the day it’s born. I challenge anyone to say, at that stage, what they might be able to see later in the life cycle.”
And that is where Bolger feels he can get a head start, certainly as a trainer. “Our foals are hardly dry on the ground before they’re tested,” he says. “Even when they’re mature they won’t tell you for certain, through their pedigree and physique, whereas from the day they come in as yearlings I know I’ll be looking at the C:Cs and the C:Ts first. I won’t be worrying too much about the T:Ts until the following April or May, because I know they won’t be running until August. So you don’t have to be getting them half-ready to do a gallop and find out what trip they might want. It’s easier on the horses themselves and easier on the owner’s pocket as well.
“Remember, if you cross two C:Ts, 50% of the progeny will be C:T, but 25% will be C:C and the other 25% T:T. There’s going to be a world of difference between those last two. That’s why a Derby and Oaks winner together might produce both a sprinter and a Gold Cup winner.”
“Nothing is black and white,” Hills accepts. “C:Cs may win at longer distances at a lesser level, because quality can have an impact. Or it might be that a CC could do so in Australia, where the proportion of those horses is much higher, simply because a race might be full of them. In North America, equally, a large majority of the races are around a mile. So you will find idiosyncratic patterns depending on the race pattern.
Remember, if you cross two C:Ts, 50% of the progeny will be C:T, 25% will be C:C and 25% T:T
But when you’re pitching the top against the top, you need everything going for you. And looking at the data tells us that there is a very small chance of CCs succeeding at that level in Europe at longer distances.”
Her numbers, in fact, suggest that under 8% of elite European CCs show their optimum form over ten furlongs; and less than one per cent at a mile and a half. Harry Herbert, racing manager to Al Shaqab, felt that these trends demanded respect as they debated options for their Guineas winner.
“I’m as gung-ho as anyone to win a Derby,” Herbert says. “But on gut feeling I didn’t have that ‘we-must-go-to-Epsom’ bell ringing with this horse, with a real speed sire on top – albeit out of a Galileo mare, but with speed there too. So Hugo [Palmer, his trainer] going down that route, it was really interesting. If you’re told you have a 1% chance of staying a mile and a half it’s going to be very brave to run him over a mile and a half.”
Even Bolger evidently has sceptics among his patrons – after all, he ran Dawn Approach in the Derby for Sheikh Mohammed after his 2,000 Guineas winner had been tested as a CC – and there are also differences within the scientific community.
Dr Stephen Harrison, who founded the British firm of Thoroughbred Genetics Ltd as early as 2000, instead bases correlations of speed and stamina on certain energy release genes. “It’s a shame Galileo Gold didn’t come up CT because then I would have laid him!” he jokes. “We don’t focus on a single gene because we feel selection on that basis – say nobody wanted to breed a TT horse – might cause a restriction in genetic variability. If a single gene has such a high correlation to distance ability, you should be able to tell by looking at a horse.”
But Hill stresses that myostatin analysis is not so much intended to supplant the wisdom of the ages, as to complement and inform it.
“Of course, the trainer wouldn’t just take our information into account,” she says.
“Hugo Palmer only did the test because he had reasons for doubt. We always say that genetics is a tool to be used alongside, and in partnership, with the knowledge that comes from the people who manage the horse.
Prediction of performance calibre
If some people are a little uncomfortable with the attribution of muscular development to a ‘speed gene’, then at least everyone should be able to agree there is some heritable component doing a specific job. And, whether you view the information as a reiteration or a revelation, there do seem to be measurable patterns associated with myostatin.
But claims that the genome can identify in advance a horse’s performance potential on the track seem harder to pin down. Webbon does not mince his words. “Fool’s gold,” he says succinctly. “Performance testing is a completely different ball game. It begs the question how much genetic make-up can influence performance. You come back to the old adage: breed the best with the best and hope for the best. Only a relatively small proportion of horses are as good as their parents.”
Geneticists credit between 30 and 50% of performance to heredity, the rest coming down to such environmental variables as training or nutrition.
“There are so many other influences,” Hill admits. “We recognise that the heritable factor is only a portion of the whole: in the very basic formula of the science, genetics plus environment equals phenotype. Elite performance is of course a complex trait and requires an optimal combination of genes for adaptation in the anatomy, physiology and metabolism – as well as an optimal environment.
But with the sophisticated tools we have now we can scan the entire genome to pull out data patterns. It is important to have a very large sample set of horses, acting as a reference population, separable into high and low grade horses. To date we’ve tested over 4,000 horses and 48,000 units of genetic information to try and capture as much variation as possible. When we apply these methods, the relationship between genetic prediction and actual performance is very strong.”
To a degree, of course, 300 years of selective breeding have been predicated on some presumed ingredient of performance. As a breeder, indeed, Bolger sees performance properties even in the ‘speed gene’ test. “I made a lot of mistakes breeding to Galileo early on,” says the man who can comfort himself with Teofilo and Soldier Of Fortune. “If I’d known then what I have learned since, I would only have sent C:C mares to him, so that I’d be sure I would get C:Ts. Instead I sent him T:T mares and got some that wanted four miles.”
But it is the attempt to decipher the deeper genomic mesh that needs to become more coherent. Nobody pretends that it is easy, but that is not to say that it is pointless. For Harrison, genetic profiling is all about fine-tuning. “I don’t think you can actually predict performance per se,” he says. “But I do think there is a major correlation between performance and consistency. You definitely can reinforce what people see physically, in terms of performance. But the main thing is to put things together in a more targeted way, to seek better consistency.
“With cattle or sheep, it’s a lot simpler because you’re trying to achieve something relatively straightforward: high weight gain, say, or milk production. With racehorses it’s a lot more difficult to pinpoint where you’re trying to fix genes: because the mares don’t produce litters, because the timescales involved, and so on. It’s a very difficult animal to study. The ratios aren’t there. There are so many nuances: for example, longer-distance horses tend to be better when more outbred, and shorter distance horses to be better when more inbred.”
And that brings us to the first of two areas that should surely stimulate everyone’s imagination: the specific measurement of inbreeding.
For the time being, once again, science can only provide information. It still remains up to breeders, with their expertise and instincts, to interpret it. But the fact is that they have hitherto been making unprovable connections between targeted inbreeding and dividends on the track.
“Genomic inbreeding” tests expose previous “pedigree inbreeding” strategies as guesswork. The Equinome version ranks low, medium and high levels of homozygous variants; identically derived, that is to say, from both parents. And it has recorded cases both of stallions returning a “high” score even with zero duplicate ancestors in five generations; and a “low” score with no fewer than eight duplicate ancestors in the same span.
“Using genetic information we can now measure the actual level of inbreeding in an individual: the relative level of the same version of genes inherited from both dam and sire,” Hill explains.
“The thing about thoroughbreds is that they all come from a very small number of founding animals. There’s been a closed Stud Book for a long time with very strong selection. When we look at genomic inbreeding – looking across the entire genome for measures of sameness – you might, just by chance and because of the nature of the population structure, find a much higher genomic inbreeding level in a horse with no common ancestor in the first several generations than in, say, one with five shared individuals.
“You can make an estimate from pedigrees, a best guess. But now you can unlock that and describe exactly what that individual has inherited. At some point you would hope to be able to look for signatures of past historic influences in the genes of modern-day horses.”
Who could fail to be interested by that possibility? In the meantime Harrison, whose very first test was focused on inbreeding, stresses the value of information already available. “The inbreeding test helps to provide basic breeding information that should be the first stop for every domesticated species,” he says.
“We helped to breed a multiple G1 winner in Australia, Sacred Choice, from a highly inbred mare, primarily by taking inbreeding level into consideration. We term it the GhP test – genetic health and prepotency. We find that there is an optimum value that provides a balance between maintenance of genetic health, the ability to pass on characteristics more consistently and performance to an extent.”
The wrong kind of inbreeding can, he recognises, be detrimental. “But to a degree I don’t think thoroughbreds tend to be inbred enough,” he argues. “Most of the time they tend to mongrelised. People aren’t putting all the right components together. It’s about grouping for distance, precocity and so on within a safe inbreeding zone.”
Welfare of the breed
The second area of incontrovertible value, you would hope, is the quest for a sounder, healthier thoroughbred. Certainly this is the over-riding priority of Webbon’s review. “It doesn’t matter how good a horse’s potential if you can’t get it on the track,” he says. “If we can improve the soundness of the breed, many more horses will realise their true potential.”
Webbon has long ago been persuaded by genetics as a reasonably reliable indicator of, say, risk of fracture or laryngeal paralysis. “Obviously there are all kinds of other factors,” he says. “Not least, with fracture, the trainer involved. But you can get some measure of susceptibility. Of course horses can win with these heritable weaknesses, in durability or health or soundness, but those aren’t the tests that are being made commercially available. That’s often the way in racing, of course. People work to the short term, they’re not that interested in committing to the ten or 15 years required to make a more durable generation.
“The type of tests that might make most short-term profits are not necessarily in the long-term interest of the breed. And if we’re looking for a quick fix without fully understanding the consequences, then we must bear in mind that some of those consequences may be deleterious.”
He will find no argument from Hill there. Nobody should forget that most equine geneticists were first drawn to their trade by a love of the horse. One of the great sponsors of their collaboration has been the Dorothy Russell Havemeyer Foundation, which was lavishly endowed in the cause of equine welfare. Hill herself is the grand-daughter of that top amateur rider, Charmian Hill, owner of Dawn Run.
“It’s extremely important to emphasise that the goal of genomic sequencing is the improved health and welfare of the horse, the betterment and long-term sustainability of the breed,” Hill says. “One of our key goals is to maximise the genetic potential of each individual but we’re also looking to ensure a sustainable thoroughbred population in the future.”
And while Webbon’s review will certainly measure current commercial tests against these worthy aspirations, the racing and breeding industries are themselves hardly immune from tough questions. “You can’t go through 300 years of breeding without subconsciously hitting on the right thing,” Harrison muses.
“But I think some of the things people do are not in the breed’s best interests: not getting rid of mares that don’t come up to scratch, for instance, whether physically or in terms of performance. Obviously people have put a lot of money into these animals, and the last thing they want to do is get rid of them, but that’s how commercial considerations can get in the way of what you want to do scientifically.
Nobody should suggest to any breeder that this is what you should do; only that this is what you can do
“Other pedigree species would weigh up both sire and dam, but so often the dam hasn’t even won a race. You look at operations like Juddmonte or the Aga Khan Studs, and you suspect that they almost get their own populations; that they fix the genes themselves. Obviously they’ve started with better stock and in that instance breeding the best to the best does work, because they’ve a higher level of culling and mare selection.”
There will be no more heads in the sand with Webbon steering the TBA review. Here is a man with the breadth of insight, rationality and experience both to challenge and reconcile the ideas of the scientific and breeding communities.
The first phase, as already noted, is to examine the existing commercial tests. “The idea is to look at what they’re claiming to reveal, and to try and make some judgement on whether these will have a good or bad impact on breeding,” Webbon says. “The TBA are keen that we essentially provide information, to help breeders to decide whether these opportunities fit their strategies. Not for one moment is the intention to say: ‘Don’t touch this or that with a bargepole.’ Fundamentally, it’s about being able to make an informed choice.”
The second stage is to assess the wider world of animal breeding. “Genetic evaluation is widely used in virtually every other species – dairy and beef cattle, sheep, pigs, now even dogs – and we should see what lessons can be learned from the techniques being used, and to ask to what extent they could usefully be applied to horses,” he says. “We need to ask what other tests, not yet on the market, might be in demand by the industry.”
He hopes to tackle both these initial briefs within a year. “But the third stage is more blue-sky,” he says. “And that’s to try and develop ideas for a longer term programme of breeding, employing whatever genetic techniques might be available to achieve the things we want for the breed: not just athletically, but for a fitter, healthier breed, better able to fulfil its potential.
“Nobody should suggest to any breeder that this is what you must do; only that this is what you can do. The choice is yours. But breeders of other species have appreciated what horse breeders will rapidly come to recognise: that it’s always only a small part of the jigsaw. The danger is that people will view one test as the be-all and end-all, and that’s just madness.”
Understandably, many breeders fear that their clients would not prove quite so wise. Already Bolger admits that he would not set out to buy a T:T yearling unless he happened to be seeking a Cup horse, or one to go jumping down the line. “But having said that, Galileo was a T:T,” he says. “If you were up front about it, when selling foals or yearlings, you might find that half the people would no longer be interested.
But the other half still would be, provided you were offering them a nice-looking animal that looked like a racehorse. Who knows? In time, there might be some questions for breeders to answer under the Sale of Goods Act. We’ve come a long way from the days when all you were told was: ‘Easy to box, clip and shoe’.”
For all the nervousness this kind of talk may cause among horsemen, Hill takes heart from the way increasing numbers are at least trying to weigh up the broad precepts of what remains a young and fast-changing field of science.
“Genetics is a tool that sits alongside traditional horsemanship,” Hill says. “We’ve never made any claims to offer a silver bullet, by any means, we’re just trying to help people make more informed decisions.
“It is important to point out that the information we’re providing doesn’t exist in any other form. The fact is that in a single training yard, all horses have the same opportunity: the same training, nutrition and management environment. Yet one might win the Derby while another ponies it to the start. All you’re trying to do is establish what sets them apart.”