The Great LUA Debate by Ron Zimmerman, member Dalmatian Club of America

To the right is Aberdeen's Deal or No Deal (Dee Dee), a Low Uric Acid Dalmatian shown with breeder/owner/handler Denise Powell, the person responsible for reviving the Dalmatian backcross effort. Dee Dee cannot be registered or shown with the AKC. Photo by Irv Krukenkamp, MD.


Please email your comments on this essay. Corrections or suggestions for changes are welcome. Anyone wanting to add a post in disagreement, or support/furtherance will be accomodated.
Background on Hyperuricosuria (High Uric Acid)

Hyperuricosuria is a condition in canines characterized by High Uric Acid in the urine. Hyperuricemia refers to HUA in the blood, which is also part of the syndrome in Dals. We will generally refer to it just as HUA. The alternative is Low or Normal Uric Acid, which we will call LUA or NUA interchangeably.

Uric acid precipitates out in the bladder as crystals that become urate bladder stones. This is referred to as Urate Stone Disease. The precipation of crystals in dogs with HUA appears to be essentially universal, and conversely urate stones in dogs with low/normal UA is rare or unheard of. Stones or sediment in the bladder can cause obstruction of the urinary pathway, i.e. blocking, which is basically the inability to urinate. This is much more likely to happen in males than females as males have a more restricted or constricted urinary track, basically the os penis.

When a dog blocks, some form of veterinary intervention is required else the dog will progress to very painful and severe symptoms, including a birst bladder, likely to result in death. Blockage probably would never resolve itself untreated. A simple procedure that somethimes works is called "backflushing" - inserting a catheter and and forcing sterile liquid in an effort to move the stones back into the bladder. If that doesn't work, surgery becomes necessary. Usually this starts with cutting into the bladder and cleaning it out, often requiring incision of the urinary pathway as well (uresthrotomy).

"Sludge" in the bladder is often a pre-cursor to stones. This sludge is not harmless, as it forms clumps of concrete-like material which can also cause blockage, and is sometimes more difficut to remove as it becomes enmeshed in the wall of the bladder.

In chronic cases, to avoid the expense and pain of repeated surgery, there is a procedure to permanently re-route the urination tube so it no longer passes through the os penis structure (uresthrostomy). Essentially this makes the males urinate like a female. Since this process renders the penis non-functional, some surgeons go ahead and amputate the penis, although the general practice is to see amputation as un-necessary.

Bladder stones can have several possible compositions - Struvite, Calcium oxalate, Cystine, Xanthine, and Urate. Urate stones are essentially non-existent in dogs with normal level of uric acid (NUA). HUA is known to occur in several breeds, but it is endemic in Dalmatians, apparently from the breed founding stock.

There appears to be an association between the gene for HUA and spotting in Dals, explaining why it was inadvertantly selected for in breed development. I.e. LUA Dals sometimes have smaller "frosty" spots. However, as will be explained later, this connection seems not to be inherent. I.e. with selective breeding the spots on LUA Dals are just as good as the spots on HUA Dals. This probably means the association is not functional, but a correlation of locus - the genes tend to be selected together because of proximity in DNA.

Here's a few veterinary descriptions of HUA and stone disease in Dals, and its genetics:

  • Uric Acid Stones in Dalmatians from Veterinary Partner.
    says "it is not unusual for a Dalmatian to require several stone removing surgeries during his or her lifetime".
  • Dalmatian Update from Purina
  • Inheritance of Uric Acid Production by Mary-Lynn Jensen, Ph.D. (former board member of the DCA)

    Preventing Blockage - hydration, diet and medication

    Many breeders feel that risk of blockage can be greatly reduced by being sure the dogs dring plenty of water to dilute the UA in the urine. Low protein/purine diets are highly recommended. However, there are many reports of Dals blocking even under the best of care. There is also the issue of pet owners, where it informed and educated special care may not be given as readily as by show breeders and exhibitors.

    There is a medication, allopurinol, that is given commonly. In affected dogs, taking allopurinol is necessary for lifetime. Blockage still happens even when breeders make every effort to prevent it environmentally and nutritionally. In some cases, other life threatening health problems result from vegetarian low protein diets or from allopurinol, which may cause xanthine stones.

    How Prevalent is Stone Diseaase?

    This is difficult to know with precision for a varitey of reasons. Indeed, establishing incidence for any condition dog populations is problematic. However, several studies have been done, noting various percentages. The Minnesota Stone Center reported that Dals are nine times as likely as other breeds to have stones sent in for assay. Dr Irv Krekenkamp, M.D. of the DCA has done a cross-study statistical analysis, and feels its safe to say that the incidence of blockage requiring intervention in males is at least 20%, possibly higher. In humans, this number can be called an epidemic.

    It should be noted that several prominent DCA breeders maintain that stone disease is not particularly a problem in the breed. This will be covered under "Arguments against the Backcross". Let me say though, that many other prominent DCA breeders consider it a very serious problem. One would think that if a significant subset of the club thinks it is a problem, then it is a problem. If others don't experience it in their line as thay claim, that doesn't mitigate the effect in the breed. I am told that in Cavaliers, most prominent breeders also deny the existence of Syringomyelia in their line, even though the incidence is reliably reported at 30% to 70%.

    Dr. Susanne Hughes has done an ultrasound study of Dal bladders. With a total sample size of 377, she found that 71% of the male Dals and 25% of the females she examined had significant "sludge" in their bladder. This is rare in other breeds. Furthermore, although not specifically evaluated statistically, it is reported that the dogs without sludge tended to be young or on medication for stones (allopurinol). The ones on medication obviously have a problem with stones, so the implication is that for untreated adult Dalmatians, the incidence is significantly higher than 70% - i.e. nearly universal. Depending on one's definition, dogs with significant sludge can be said to be suffering from urate stone disease.

    Understand that urate material is not the only source of stones. However, in Dals, urate has been shown to be the source of stones causing blockage in more than 90% of the cases. In other breeds, urate stones are rare and every case we know of has been associated with HUA.

    Here's some studies with quantification:

  • University of Minnesota Stone Center "The odds that uroliths (stones) from Dalmatians were composed of urate were 228.9 times greater than for other breeds. The odds that a Dalmation admitted was affected with urate uroliths were 122.4 times greater than for other breeds."
  • The Bartges Study - 22.8% of 2118 Dals had a history of stone disease, of which 91% of known composition are urate. Males are 6.5 times as likely to report stones, making the incidence of blockage from urates in males about 35%.
  • DCA Ultrasound Study 2005/2006 Susanne Hughes, DVM & Cynthia Wilson, PhD - of 377 Dals ultrasounded, 71% of males had substantial "sludge" in their bladder.

    The Original Backcross.
    To the right, Dr Bob Schiable with a LUA dalmatian. Photo by Irv Krukenkamp, MD.

    So if Dals have HUA, and other breeds of similar size, etc, don't, then the obvious question is what happens in a crossbreed? In the early 70's, Dr. Bob Schiable, a geneticist and respected Dal breeder, investigated this scenario. He found the HUA gene to be a simple recessive. This means that with the probabilities of regular mendelian laws, the LUA gene could be propogated into future generations of the "backcross" dogs when bred back to registered Dalmatians. So in a few generations, these dogs look very much like AKC Dalmatians, except with Low or Normal UA.

    In the early generations, spotting was noticeably different, but as explained above, by simply selecting the LUA Dals with the best spots to breed, the spotting began to look just like traditional Dals.

    Dr. Schiable was a member of the Dalmatian Club of America, and while this was not an official project of the DCA, Dr. Schiable took pains to keep DCA members informed, often taking his backcross dogs to shows so the members could see how it was coming.

    His collaborators included Dr. Holly Nelson, DVM, and Joanne Nash, an AKC judge, who raised litters on the West Coast.

    After 4 generations, in 1981, with the assistance of several prominent Dal breeders, notably Alfred & Esme Treen who wrote the original and classic book on Dalmatians, and with the official consent and support of the DCA Board of Directors, AKC agreed to register 2 of the backcross Dals.

    The Controversy

    When the board proudly announced to the club that the backcross dogs had been registered, the reaction by the club members was not favorable. In fact, it might be said pandemonium ensued. Many members favored the backcross, but many were adamantly opposed. It has been said it split the club. There was a very heated debate, and friendships were torn asunder. Each side was adamant and emotional. Many felt the board should have sought the consent of the club before AKC recognition.

    Certain things aren't exactly clear in retrospect, especially some chronology (i.e. what happened when and in what sequence), but as a result of the controversy, AKC was prevailed upon to place the two backcross registrations on "hold" status. It's not clear if this was the result of a club vote, or if it was a result of the controversy and the vote came a bit later. Subsequently the club voted to not only stop the registration process for the backcross Dals, but to ban the topic from future club discussion, as well as any overt effort to assist or promote the backcross effort. The exact working of the questions voted on in 1984 was this:

    “The D.C.A. should stop all efforts regarding possible future A.K.C. registration of the descendants of the Dalmatian-Pointer backcrosses.” 62% were in favor of stopping.

    “I am (in favor/not in favor) of continuing the testing and breeding of the Dalmatian-Pointer backcrosses.” 52% were not in favor.

    I will point out that this vote was interpreted to prohibit discussion of backcross in any official capacity, such as club meetings and board meetings, although the rationale for that in the wording is a bit hard to fathom. It was also used to deny publication of articles in the club magazine, The Spotter, regarding backcross. I suppose discussion, or reading articles in the magazine, was held to be a form of effort, although it seems unconscionable to suppress information and an exchange of ideas. There is a section later on the substance of the arguments presented in this debate.

    For an in-depth blow-by-blow look at the history of the Great LUA Debate, check these pages:

  • Dalmatian Backcross Project - Past, Present and Future by Mary-Lynn Jensen, Ph.D. (board member of the DCA)
  • An Overview of the Backcross Project - Part 1 by James E. Seltzer, Ph.D.(member, DCA)
  • An Overview of the Backcross Project - Part 2 by James E. Seltzer, Ph.D.
  • Ramblings by Joanne Nash (long-time Dal breeder and AKC judge)
  • Backcross Project: Long-Standing Issues by Robert H. Schaible, Ph.D. (Founder of the Backcross effort)

    And for some editorials on the subject:

  • Dogs in Review - April 2009 - Editorial by Christi McDonald
  • Doge in Review - Letters, etc.
  • Terrierman Blog - December 2008

    After the Blowup

    After the big bruhaha, things died down. But there are several items that should be noted.

    One of the allies of Dr. Schiable was Dr. Holly Nelson, DVM. Holly continued to maintain a colony of LUA Dals and conduct important research. Unfortunately in about 1990 (*?) Holly died very suddenly in her sleep. This was a tremendous blow to the continuing backcross effort, as well as a huge personal loss for the club and many individuals. Before people could really get their thoughts together about the dogs and how to proceed, Holly's mother had either placed as pets or euthanized all of the dogs involved in the backcross research.

    Dr. Bob Schiable did maintain a minimal colony of backcross dogs - enough to keep the line alive - with little fanfare.

    A friend told me she saw Bob at a National Dal specialty in the early 90's. They were walking and talking, and as they approached the main area of the show, Bob said very seriously - you probably don't want to be seen with me. He felt like an outcast, a pariah, as even the supporters of the backcross effort had moved on, and what was remembered was the vehement animosity.

    Genetic Research - "within the breed"

    The concern about stone disease died down for a while, but it resurfaced. One of the argument agains the backcross effort was that it should be possible to distinguish why some dogs blocked and others didn't within the context of HUA rather than taking the "drastic step" of introducing alien genes. This seems reasonable, and there was an initiative to move in this direction.

    Now we come to the subject of what happens in breed clubs when the subject of research into genetic conditions rears its ugly head.

    For an outsider, this may be difficult to understand, but for breeders the success and viability of their line is very important to them, is an important aspect of their identity. So what happened in the Dal club was that there was tremendous resistance to conducting research of this nature. Research into the genetic basis of practically anything considered a problem is very likely going to result in a recommendation to breed away from affected individuals and those closely related. Thus, some "lines" of the breed are going to be disfavored. Consequently, people become very uncomfortable with the prospect of an investigative process that could affect their line negatively. In the case of Dalmatians, it was openly said that since all Dals have HUA, all are equally at risk for stone disease. The implication being that which ones form stones and block must be random, and therefore there is no reason to discriminate against even active stone formers for breeding. And apparently if this isn't true we don't want to know.

    So there was much resistance to calls for research in the genetics of stone disease. In fact such research would be virtually impossible give that powerful interests in the breed were aligned against it, some not even participating in the dialogue. Many said it is probably nutritional or environmental, so we should research that connection.

    Finding the Gene for HUA

    In around 2000, Dr Danika Bannasch, a research fellow at the UC Davis school of Veterinary Medicine, and a noted Dalmatian breeder, became involved in this process. I believe her original objective was to find a genetic disctinction for dogs with active stone disease, thinking it probably related to UA level within the high range. She submitted a proposal to the DCA Foundation for funding for a project of that nature and it was rejected by the Dal club in favor of a proposal to study how best to care for and feed Dals with stone disease, but she found funding elsewhere. Her studies and experiments soon led her to believe she could actually locate the gene for HUA. [Danika, please correct me if there is any misinderstanding here.]

    Feeling that she was closing in on the gene, she let some friends in the Dal breeder community know this, and one decided that was a good reason to re-open or re-invigorate or revive the LUA backcross issue. This was about 2003, and the person primarily responsible for this revival was Denise Powell. In a very real sense, the revival of backcross was a result of the inability to push through a study on genetics within the breed. (Although I must say that now most believe the factors determining which dogs with HUA form active stone disease are likely several and complex and possibly not subject to simple selective breeding.)

    In about 2006, the gene was located with confidence by Danika's research team, and it took an additional 2 years to develop the publicly available genetic test and get the study published in a peer-reviewed journal. The scholarly scientific article appeared in Nov, 2008 and was accompanied by a press release from UC Davis, which caused the news of the gene discovery to be carried in virtually all of the major news sources, as well as veterinary publications.

    Revival of the Backcross

    Following repudiation by the club, and the untimely death of Dr. Holly Nelson, Dr Bob Schiable had kept the backcross line of Dals in existence, but barely. Joanne Nash, a well respected Dal breeder and AKC judge, had also been involved in breeding backcross litters in the early days, but had given up by the time of the revival.

    Denise Powell, a successful Dal breeder and exhibitor approached Dr. Schiable about getting a LUA bitch from that line to start her own LUA breeding program. Dr. Schiable readily agreed.

    Shortly after that, this came to the attention of the club, and the battle lines began to form.

    Recent Votes

    The first question was - what to do about the votes in 84 to not allow discussion or "testing and breeding" related to backcross. In 2006, there was a club referendum on undoing the second of these restrictions, about testing and dreeding, which passed. However the club never subsequently was involved in any official way regarding testing and breeding. In fact many club members were incensed whan an ad for the backcross dogs appeared in the club magazine, the Spotter.

    In this time period, any discussion of backcross was likely to at least lead to nasty words, so the internet email groups available to Dalmatian fanciers were virtually unamimous in banning the topic of backcross or LUA Dalmatians.

    In 2008, the board decided it was time for another vote on removing the 84 prohibition against discussion of registration. The ballot initiative was worded: "Is it time for DCA to discuss the possibility of AKC registration of the descendants of the Dalmatian-Pointer cross?" The lists opened the topic for discussion, and the exchanges were . . . extensive and not friendly.

    So, after a very heated online debate on the topic, the vote was taken and the results tabulated. The result was YES: 279, NO: 324. Many felt that the question was unfortunately worded to sound as if they were voting on registration not just allowing discussion of registration. The proponents felt they had not asked for a vote, and felt it was not yet time for a vote, and that the board, unquestionably against the initiative in the majority, had called for the vote prematurely. While the opponents said - you pushed for this vote, now go away. The proponents felt they had been rebuffed, slapped in the face, and many essentially opted to not participate with DCA in further efforts regarding backcross, to take their case to the public and participate in showing under the UKC.

    Arguments Against the Backcross

    The arguments for the backcross are very simple, that stone disease is a serious problem, and the gene for LUA is a successful solution. I suspect many other breeds with difficult health issues wish there was a simple genetic solution available to breeders.

    Many will be wondering - just what was said against the backcross effort? I will do my best to characterize the arguments against fairly.

  • Of course, the background to all arguments against is that allowing registration of these dogs is a very serious matter which should be permitted only with extreme caution. There seems to be little if any understanding of the problems and dangers of "closed gene pools", and the dogma of gene purity is unquestioned by the opponents. One might ask they do some homework in the annals of academic genetics. The backcross dogs were called "mutts" and "hybrids" - as if all Dalmatians and most other breeds are not hybrids.

  • For the most part, what people said was that more study was needed before taking this drastic step. There was a very large concern that some unknown alien influence form the Pointer breed might come across and survive the 12 generations. This is really the fundamental fear pertinent to any outcross. The opponents demanded a very carefully controlled "proof" of no deleterious influence. They seemed to envison something like clinical trials worthy of a pharmaceutical company testing a new drug, while at the same time arguing and voting that the club should not spend money on this effort.

  • There was a lot of effort to minimize or understate the problem with stone disease. This was mostly based on people saying it had never occured in their "line". I discussed this briefly earlier. It didn't seem to matter that there was a substantial segment of the club saying it has been a problem for them, and it didn't seem to matter about how serious a problem it is for pet owners, and the existing studies didn't seem to matter, nor the ultrasound study showing conservatively 69% of the breed with "sludge" in their bladder. At a meeting of the board of DCA, an informal poll was taken of those present, some of the most prolific show breeders in the history of the breed, and all agreed that they had never had one occurrence in their breeding, not one, zip, zero.

  • Many were concerned that the LUA Dals had spots that looked different from the HUA Dals, somewhat smaller spots, maybe not as distinct, even calling them "ugly". As I already indicated, there was a tendency in that direction, but it has been overcome. As one geneticist involved said - it only takes one example of a LUA Dal with good spotting to show that the connection is not inherent. Look at the photo at the beginning of this essay - Dee Dee has great spotting, by anyone's standard. Besides, the Dalmatian standard calls for spots from a "dime to a half dollar" in size. Most of the currently successful champions have spots appreciably bigger than a half dollar. That has become the norm. So it is likely true that LUA spots are more correct than "normal" Dal spotting. It is also true that if LUA Dals don't have good spotting they won't be successful in the show ring. In other words, if they aren't successful in the show ring, then they won't be widely bred.

  • There was a general feeling that there was inadequate "proof" that stone disease is really caused by HUA. One prominent club member even wrote a series of articles accepted for publication in the club magazine, saying things like there is not a shred of evidence that stone disease is caused by HUA, and the fact that not all Dalmatians block proves HUA is not the cause. In his articles he even said it was incumbent on the backcross proponents to prove that HUA is the "only" cause of stone disease. I would not even mention the ramblings of this individual, except that many club members picked up his repeated mantra that there was no proof. I will provide a link to his latest article, so you can see for yourself: The Chicken or the Egg Furthermore, he says that we cannot understand stone disease well enough to proceed with this course unless we understand the "triggering cause" for why stones precipitate from elevated levels of Uric Acid.

  • The same gentleman demanded proof that the backcross dogs were really LUA, suggesting the "spot" test for urine Ph commonly used was not sufficient, and a 24-hour test was needed collecting all of the urine for a day and analyzing it. The proponents declined to do this, thinking it was completely unnecessary to subject dogs to this procedure. The 24-hour test is for subtle differences, and the difference between a LUA and HUA dog is ten-fold. The Ph ranges are distinct and non-overlapping. As a matter of fact, HUA urine is easily recognizable, as crystals form and visibly precipitate so it turns cloudy when it is chilled. This is called the refrigerator test, and although not what veterinarians use, is entirely reliable.

  • Another article published in the Spotter began by saying it was the stated goal of the backcross proponents to get rid of the gene for HUA, and went on to calculate how long this might take given that its more difficlut to eliminate a recessive characteristic than a dominant one. The only problem is that to my knowledge "getting rid of" the HUA gene was never mentioned as a goal. The goal is rather to reduce HUA and give breeders the option of breeding healthier Dals. It was always assumed some breeders would probably hold onto some HUA Dals, and how long it might take is really not relevant. Kind of like arguing that if we can't eliminate the problem quickly, we'd best do nothing.

  • Some have argued that HUA might be a good thing, after all it can be classified as an anti-oxidant, and we know that anti-oxidants fight cancer. Therefore, it's possible, although not remotely substantiated, that HUA dogs might conceivably have a lower rate of cancer. Do I need to comment on this?

  • Many opponents had the feeling that we shouldn't talk about this matter, at least not publicly; that anything we do will increase public awareness and promote the perception that Dals are not a healthy breed.

    If you want to see what the opponents of the backcross effort are actually saying, check these sources - all published in the DCA quarterly magazine, The Spotter:

  • Why I Remain Unconvinced About Backcrossing - Part 1 by Carroll H. Weiss (Former Director, DCA Study Group on Urinary Stones)
    compares LUA to Thalidomide and says since not all HUA Dals form stones, HUA must not be the cause of urate stones.
  • Why I Remain Unconvinced About Backcrossing - Part 2 by Carroll H. Weiss
    says we don't have enough LUA Dals yet to draw conclusions, and HUA is not the real cause of stone disease but one of the symptoms.
  • Which comes first, The chicken or the Egg - Part 3 of a Series by Carroll H. Weiss
    says backcross proponents must prove HUA is the ONLY cause of urate stone disease, and that we must first identify what "triggers" precipitation of UA into stones.
  • Defending an Ancient Breed by Ed Petit (AKC Judge)
    talking about this issue has done permanent damage to the breed, and stone disease is caused by stress, not HUA.
  • Questions on LUA for All DCA Menbers to Think About by Scott E Facey
    says that it will take a long time to completely eliminate the recessive HUA gene - as an argument against doing anything.
  • Before You Vote, a letter by Sue MacMillan urging DCA member to vote against discussing registration of the backcross Dals

    Hidden Agendas

    Regarding the argument that we have to be extremely careful about introducing alien genes into our beloved breed, to the point that people would scarifice breed health - I actually have a difficult time believing that argument is sincere. In other words, I really just can't quite imagine, given the known lack of complete integrity in the studbooks of AKC, and the fact that all breeds were developed from disparate sources, that until relatively recently it was the norm to intorduce genes from any dog a breeder thought might improve the breed, and in some cases just accept accidental matings and go on, that people really get that worked up about the prospect of a loss of "purity" that remote. The stud book was open until the late 40's. Either these people really are Eugenicists at heart, or this is a disingenuous argument. You can't rebut or refute a reason if it's not really a reason. This would imply that there is some other hidden reason, not being spoken openly. Not speaking one's motivation usually implies it is not honorable. I have some suspicions about that, about the real reasons, some speculation.