RESEARCH

Winner of the 2003 DWAA Maxwell Award for "Best Subject-Related Series in a Magazine"

An experienced breeder gathers volumes of data and writes to a researcher; she never gets a response. An owner with a sick dog and disposable income offers thousands of dollars for research and no one seem interested. A breed health advocate documents a common inherited problem only to be told by a board certified veterinarian, "That doesn't happen in your breed."

These true incidents exemplify the frustration dog people sometimes experience interacting with the research community. The author has worked with a number of researchers in canine genetics and hereditary disease and networked with numerous breed health advocates. The discussion that follows is drawn from our successes as well as our failures. I hope it will help you understand the research process and enable you to avoid common pitfalls that lead to misunderstanding between the research and dog communities.

Worlds apart

The dog world and the world of genetic research revolve around stars sometimes light years apart. If we in dogs are to interact successfully with geneticists and research veterinarians we need to study their world so we can understand how they work, what issues concern them, and how we can best facilitate their efforts.

Things that seem important to us may not be fruitful avenues for current research. The minutiae of breed type and behavior often cannot justify the time, effort and expense required to determine their inheritance on a molecular level. Adequate research funds are not likely to be available for the esoteric details of canine structure and breed type. Most researchers don't breed, work or compete with dogs. They may be utterly baffled by why we think some things important. Just as we don't always understand their jargon, they may be confused by ours. No one will investigate a trait he cannot understand and may be unable to recognize.

Even a disease won't always provoke immediate scientific enthusiasm. In order to gain acceptance scientific discoveries must be published in peer-reviewed journals or, in recent times, result in patents or produce a marketable test. We in Australian Shepherds knew by the mid-1980s we had Collie Eye Anomaly in our breed. However, no researcher had yet investigated and published it. Lack of a reference led some veterinary ophthalmologists to tell breeders CEA didn't occur in Aussies.

Even after publication the process isn't necessarily final. Other experts may disagree. When a study of CEA in Aussies was finally published (Rubin, et al 1991) there were those in the research community who disagreed with some of the conclusions. The article provoked a spirited rebuttal in an editorial appearing in the same journal issue. Researchers debate canine genetics with as much fervor as any group of dog breeders. Until the scientific dust settles on a disputed point, breeders must rely on their own experience and the best current scientific information available. However, we must resist the temptation to subscribe to the viewpoint that is most convenient to our personal breeding plans.

One of the hallmarks of scientific investigation is that no theory, no matter how well established, is immune from reasoned debate. Given sufficient compelling evidence, a generally accepted view will change. Sheila Schmutz of the University of Saskatchewan, studied a gene called melanocortin receptor 1 (MC1R) which is the same gene Clarence Little, an early researcher in canine color genetics, referred to as "E." Little proposed that in addition to versions of E that resulted in black or yellow (fawn) dogs, one type produced the brindle pattern and another produced black masks such as are seen in Mastiffs and Great Danes. This is the model that dog breeders have long used for the inheritance of mask and brindle. But Little worked long before scientists were able to pick apart the molecular structure of individual genes; his conclusions were based on breeding trials. Using DNA from a litter of Great Danes and their parents, Schmutz found that a certain version of MC1R could clearly be tied to the mask pattern, but none correlated with brindle. Little was right about mask but erred concerning brindle. As of this writing no one knows what gene causes it.

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Sometimes these winds of scientific change slam hard against the monolith of purebred dogdom. We operate in a world steeped in tradition. Our actions spring from a body of knowledge handed down from one generation of breeders to the next, often in the form of oral history. We must be willing to set aside what we have believed for decades when new science demonstrates our viewpoint has been flawed. This isn't easy to do. Recent discoveries about gene function and interactions as well as the long established but unfamiliar principles of population genetics stir heated debates and fierce resistance from dogdom's traditionalists. Likewise scientists tend to put more stock in published findings than breeder information and if the two don't match, the breeder's idea will not be taken seriously. We need to do our homework. Acknowledging that "although Smith (1980) found that........, our data suggest this is not always the case in our breed" may make scientists take breeders more seriously from the outset.

The current state of genetic science may impede getting answers to some of our questions. After nearly a century of canine research, many single gene traits have been described and their mode of inheritance established. Any dog breeder worth his salt understands the genetics of this type of trait and can apply that knowledge to the betterment of his breeding program. But many issues of inheritance that puzzle us today are tougher nuts to crack.

Recently, researchers at the University of California, Davis, asked a group of breeders what we wanted to have studied with the ultimate goal of developing screening tests. Our list consisted of diseases that are polygenic or which result from an interaction of genes and environment. Complex traits are difficult to pin down at the current state of the art; screening tests will be a long while coming. Even so, we should keep asking because someday science will be able to tackle them. In the meanwhile, we need to concentrate on issues that are genetically simple and with which the researcher can have reasonable hope of success.

As with so many other aspects of life, money can be a problem. Research goals often include finding the responsible gene. Doing so bears a big price tag. A huge donation, from our point of view, might be totally inadequate. Mark Neff, of Davis' Veterinary Genetics Laboratory, pointed out that laboratory consumables for a single researcher can cost about $2000 per month. Salaries of the people working on the project raise the monthly cost even higher. A successful research project, from initiation to publication, costs around $200,000. While the work is expensive, there are ways to maximize your contribution and make effective use of your money that will be discussed later in this article.

Prior to starting a project, the researcher will find out what is already known. He will determine whether anyone else is working on the topic. Another project in progress won't necessarily mean the end of yours, but knowing who else is interested may suggest a different approach or lead to collaboration. Or sound the gun on a race that can generate as much excitement as any contest between coursing hounds. Parallel genome sequencing projects conducted by the publicly supported Human Genome Project and Celera Genomics, a commercial lab, generated scientific enthusiasm and considerable media attention.

With groundwork laid, data gathering can commence. If the mode of inheritance is unknown, necessary data may be pedigrees of animals exhibiting the trait combined with photographs, screening reports, lab results, or other documents. These will be used to develop genealogies that illustrate patterns of inheritance. If a probable mode is identified, test matings may be done to confirm it. For decades, all studies of inheritance used this type of data and analysis. Today it's possible to find the responsible gene and this is often the preferable approach.

To accomplish this breeders and owners must provide not only demographic, pedigree and diagnostic information, but DNA samples as well, usually in the form of a cheek swab or blood draw. The samples cannot come from just any dog, but must be drawn from affected animals and their closest kin. Which dogs qualify depends on the protocols developed for the project. Submitting samples that don't meet the protocol wastes time and money.

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Science is unpredictable. As a project develops it may hit a snag or some finding may require a change of focus. The researcher will not be able to provide a hard estimate for a completion date and may or may not be able to provide an estimated timeframe. If the project isn't very complex and everything goes smoothly, a year might suffice but it may also take many years. Researchers don't want to discourage people with a lengthy projection or mislead with one that is overly optimistic. They may be uncomfortable committing to a schedule which circumstances could prevent them from keeping. Finding genes involves elements of looking for a needle in a haystack. Even with a big magnet, the researcher may need to probe from several directions before he finds that needle.

Most dog studies won't be the only thing a researcher is doing. Higher priority projects may be the ones that support your researcher so she has time and resources for yours. No one in academic (university based) research works solely on a single project. Most will have administrative, supervisory or teaching duties that occupy a significant part of their time.

Even with the best minds and material and plenty of money, not every effort will be successful. If things don't work out as you hoped, be philosophical about it. Negative results mean there is one more thing you know it is not. Somewhere down the road someone may have a new idea or turn up some other information that will help complete your abandoned puzzle.

As in the world of purebred dogs, every once in a while research goes awry for reasons having noting to do with the matter at hand. A project may languish because of people or politics. Employees come and go, student researchers may quit, leave or otherwise abandon their work, and politics within a company, university, or professional organization may delay or terminate a project. Sometimes people die. In such instances, it may not be possible to pick up the pieces.

Once research is successfully concluded, the funding source and who did the work will have a bearing on what happens next. If it was done by a commercial lab or funded by a corporation the results may be kept private or subject to patents. Dog breeders complain at the high cost of some tests, especially when they or their club provided some of the funds. Commercial interests expect to recoup their expenses and make a profit. If dog people provide significant funding, the club or other canine organization spearheading the effort should discuss the ultimate financial impacts with the researchers ahead of time.

Many universities now patent findings as well, primarily to protect the intellectual property of their researchers but also in hopes of generating income that will help underwrite future research. But university research is almost always published and becomes available to those who want to build upon it. Articles detailing findings are submitted to peer reviewed journals. Peer review is a process by which other scientists not directly involved with the project give critique. If the article doesn't pass muster, it doesn't get published. Before publication, the researchers must limit public discussion of their findings. Saying too much may prevent publication or jeopardize the entire project.

Another danger of releasing preliminary results is that as the project progresses, early interpretations may prove incorrect. The researcher does not want to confuse or mislead you by saying too much too soon. While you will not be able to get detailed reports prior to publication, major contributors should be offered periodic progress summaries.

Luck be a lady

Even in science, pure chance can play a role. Shortly after Dr. Schmutz located the canine brown (liver) gene, John Potter, a breeder of Dexter cattle contacted her. He believed his cattle were brown and, in spite of several prior rebuffs, persisted in seeking someone who would look at what he had. Receiving Potter's information at that particular time enabled Schmutz to do a follow-up study on the cattle version of the gene.

Get the ball rolling

Successfully instigating research on your own is a daunting task. It requires many hours, incredible effort, and meticulous record keeping. You also need well-developed people skills and a degree of obsession that might justifiably be called crazy. A better approach is to gather a group of like-minded individuals to share the load.

Ideally, such a group would work under the auspices and with the support of a breed club or breed health organization. Sometimes that is not possible. If so, an ad hoc group will do so long as everyone involved is clear on the common purpose and goals and is willing to share in the work.

A project must stir interest within the breed community to generate data. Health surveys can be an excellent tool to determine what breeders and owners feel is important, as well as provide some indication of what data might be available. Statistics from health registry and veterinary school databases can also point you toward potentially fruitful topics.

Education is everything

Once a subject is identified, the first task is to convince others that research is needed. Do some homework to get the facts. Learn what research has already been done on other species in addition to other breeds of dog. Have some idea of how frequent the trait is in your breed. Put your findings to work in an education campaign designed to inform the average owner or breeder. Use the Internet and e-mail discussion lists. Put articles in club newsletters and breed magazines. Talk to regional clubs and other interested groups. Set up an information booth or hand out pamphlets at major breed events. Reach out to dog owners as well as breeders. Those not involved with the breed mainstream may have dogs valuable to research.

If information is too technical, you lose people. Keep initial efforts at a level most people will comprehend. Append a list of references and resources for those who want to learn more. Be positive. The danger to the breed should not be soft peddled, but launching a campaign with an accusatory tone will turn people off.

Present the problem. If necessary, indicate that some people (not all) are acting in a manner detrimental to the breed. If you do this, also provide suggestions for positive action. Do not propose punitive measures against malefactors; witch-hunts are counter-productive.

Keep the issue current. The more people hear -and the more sources they hear it from -the more likely they are to acknowledge its importance. If you find articles by people from other breeds or, better yet, people well known for their involvement with canine genetic issues, ask for reprint permission in breed publications or on a website. Most writers are happy to cooperate.

If you have an interested researcher who can effectively communicate with lay people, arrange a speaking engagement. Make sure you handle your end professionally. Determine whether you need to provide transportation and housing, have an appropriate venue, and make sure you can get any necessary equipment or supplies. Be organized and ready to start on time. Poor hospitality and sloppy event management may burn an important bridge. Don't oversell: If you promise a huge audience and only five people show up, you risk discouraging and embarrassing your speaker.

The right man (or woman) for the job

Once people are aware and concerned, it's time to start looking for a researcher if you don't already have one lined up. Know who is currently working in the field and whether they might be interested in dogs. Initiate contacts. E-mail is the most convenient and effective route. Universities often have faculty directories and commercial labs will have contact information on their websites. If you can't find an e-mail address try a letter or phone message, but be aware these sometimes don't reach the intended recipient or might get set aside in the press of other business. Follow up after a while if you don't receive a response, but don't be rude or become a pest.

However you make contact be brief, businesslike, and to the point. A breeder who had a unique and valuable set of data sent a long, detailed letter to a researcher and never got an answer. She was understandably unhappy at being ignored after all her effort. Coincidentally, I happened to attend a meeting at which that researcher was present. In a discussion about dealing with dog people, the researcher mentioned receiving a letter so long and detailed she didn't have time to plow through it. The researcher's frustration is also understandable.

Be patient and persistent; finding the right researcher can take time. I spent several years trying to locate someone interested in reviewing the Collie Eye Anomaly data on Australian Shepherds. A number of researchers acknowledged I was on to something, but they were involved in other projects or it wasn't in their area of interest or expertise. I kept at it, eventually obtaining introduction to Lionel Rubin of the University of Pennsylvania, who ultimately wrote journal article.

If you meet with researchers, set aside any preconceptions you may have about what a scientist should look like. There is no conformation standard requiring white lab coats, pocket protectors and horn-rim glasses. If you are accustomed to conducting discussions and negotiations in formal business settings, don't assume the researcher must wear a three-piece suit to be worthy of consideration. If you meet at or near the place the researcher works and she shows up looking like she spent the night in a barn, she may have had to do just that. What is important is not what researchers look like, but their training, prior research and willingness to consider your project.

Good people skills on the part of the researcher are helpful, but not vital. A friendly, accessible researcher will engage people. Our dogs are our friends and family members. We want to feel the researcher cares. However, the best researcher for the job may not be good at schmoozing or have the time to engage in public relations efforts. At a meeting between researchers and breeders at the University of California-Davis in January 2003, researchers bemoaned the level of involvement and response often demanded by dog people. A board member of one of the major grant funding agencies remarked, "We are a needy bunch."

And so we are, but we need to be aware that not every researcher will be comfortable with intense relationships with dog owners or being bombarded with calls, letters and e-mails. Stick to business unless invited to do otherwise. You should not expect a researcher to engage in social chit-chat or extended back-and-forth about minor details. That is not to say that you might not develop a friendship, but this is not your purpose.

Try to determine researchers' comfort level with owner contact. If it is low, arrange for some kind of intermediary who can answer simple questions for dog owners and offer a sympathetic ear, succinctly restate information and pertinent questions for the researcher, and then relay the response back to the owner in language she will understand.

Some labs and universities have research coordinators who field all contacts from breeders and dog owners. The University of Missouri and the commercial lab VetGen have both done this for their separate canine epilepsy research efforts. They currently have excellent individuals filling those positions. The right person makes people feel comfortable and confident in their dealings with the project. This facilitates communication and provides positive word-of-mouth promotion. Financial constraints may render some university research programs unable to support this kind of position. In that case, the club, breed foundation or other group should offer to help.

Brass tacks

Once researchers are involved, get organized so you can facilitate their efforts. Someone should be designated as the group's liaison with the scientists. Preferably this should be a person with the knowledge and expertise to handle technical issues and render them into lay terminology. The dog world has it's own jargon and every breed has additional unique language; the liaison may also find himself translating "dog speak" for the researcher.

Someone should be the primary public spokesperson to club members and other dog people. This might be the researcher liaison but can also be someone else. Whoever has the job should be experienced with public relations or education, both as a writer and speaker. This individual must be able to present information in a manner understandable to the average person. Avoid assigning anyone highly controversial. People may refuse to cooperate with the research because they are in disagreement with the spokesperson over some other issue.

For both liaison and spokesperson, people skills are key. Polite and friendly but professional individuals will get better response from dog people and researchers alike.

Avoid discouraging volunteers. If someone wants to help, try to find something for him to do. If he offers a good idea, be sure to include him in its execution. If the idea isn't workable, politely decline and try to involve him in another way.

Pulling it all together

Gathering sufficient samples is the key to success. The journal article on CEA in Aussies got written because I had previously accumulated the pedigrees and CERF forms that made up the data. Where DNA samples are necessary, the cooperation of numerous owners and breeders is required. Samples will in most cases be gathered after the commencement of the project, though a gene or DNA bank is an excellent tool for storing samples against future need. Lacking sufficient data or banked samples, it takes publicity, loads of encouragement, and maybe a few sample-gathering clinics to get enough to do a study.

Make sure both you and the researcher are clear about how samples are to be handled and what is to be done with them. Someone needs to maintain a log of all samples received, including their current location and status. The researcher should see that this is done, but if a club or other group is responsible at any level it should keep its own log. Know what will happen to the samples once the project is complete. In some cases, they will be discarded. In others, they might be kept and stored for use on future projects. Determine this up front and make sure donors are so advised.

Confidentiality is key. Hereditary disease is an emotional issue. People must feel that the data they provide will not be abused or used in a manner they didn't intend. People who are actively breeding or competing should not have access to detailed information on who has participated, if at all possible. This includes researchers who happen to be active in the breed under investigation. One such breeder-researcher set up procedures that assigned someone else to review incoming samples and maintain the full data files. That individual assigned an ID number to each sample. When the researcher got them, she had no idea what specific dogs they came from.

People take pride in the fact that they and their dogs contributed. They want to know how it all comes out. Study results should be made available on websites or in breed publications at the conclusion of the project. People who contribute may want to know specifically what was learned from their own dog's sample. Donors need to be informed that this information is rarely available.

$$$$$$$$

Data alone is not enough. Locating a gene can cost $50-100 thousand dollars or more. Dog groups should be willing to provide at least some of the funds but few clubs have the ability to raise that much money. Even fewer have the expertise to review grant applications and oversee recipients. Clubs, breed health organizations and groups of concerned individuals can team up with organizations like Morris Animal Foundation and AKC's Canine Health Foundation to provide more financial support than your group could gather on its own. The foundations have trained staff who provide the necessary review and oversight. Joint fundraising efforts, like CHF's "Donor Advised Funds" also provide a method of making donations tax deductible.

Financial benefits can flow two ways. If your club or health organization will provide most or all the data for research likely to result in a screening test or marketable product, you might want to bargain for some level of return for your effort, like a certain number of no-cost screenings for those individuals who provided data or a testing fee discount for club members over a defined period of time. Such negotiations are best done up front.

The end of the road

Not every research project will be fruitful. Not every relationship between researchers and dog people works out. If it doesn't, accept the situation without blame or recriminations and resolve to do better next time. Choose your subsequent effort carefully. Too many spectacular failures chill response.

The road to a successful collaboration between dog people and researchers may sometimes be long or difficult. Understanding how research works and what is required of you can smooth over the rough spots. Make the effort to build that bridge from our world to theirs. The journey will ultimately benefit both science and our dogs.