Looking at Life

MAF’s Canine Lifetime Health Project

by C.A. Sharp

First published in Double Helix Network News  Fall 2012

 

Life is filled with events.  Some are unique, others flow from one to another, and still others may influence future events for days or weeks or even a lifetime.   Health is part of life and has its own chain of events, whether that life be our own or our dog’s.  Since health issues don’t arise for reasons, though the reasons may not be clear:  Autoimmune diseases are presumed to be triggered by something though we often don’t know what that something was.  Therefore, considering health issues in context with the rest of life, played out over time, can give valuable insights unobtainable in isolated visits to the vet.  Lifetime studies help researchers and care providers understand the process that is health in the context of living, changing beings.

The Morris Animal Foundation (MAF,) located in Denver, Colorado, has initiated what will become the largest and longest-running dog research project ever:  the Canine Lifetime Health Project (CLHP.)  This is not only the first lifetime study for dogs but the first such study in all of veterinary medicine. Over its own lifetime the effort could have a tremendous impact on our dogs’ health through the new knowledge and insights it will surely provide.

 The Long and the Short of It

A lifetime study is a type of longitudinal research project.  Longitudinal studies follow a group of subjects over a period of time, anywhere from a few years to throughout their lives, to see what happens.  Such studies can focus on almost any aspect of life common to the study group, be it cultural, behavioral or medical.  Other types of studies essentially take a snapshot of their subject groups, gathering data as of single point in the subject’s life.  The various studies that produced the array of DNA screening tests we now have for dogs are examples of this kind of study:  DNA samples were collected from a cross-section of dogs, usually of a single breed.  Some of them had the target disease and some did not.   Samples were evaluated and a causative gene version identified.  But many diseases, including inherited diseases, aren’t due to the sole action of a variant found in a single gene.  Often nature and nurture combine in a complex web of interactions between genes and environment.  This is where a longitudinal study comes in.

In lifetime studies researchers follow a group of individuals, called a cohort, throughout their lives.  All members of a cohort have something in common: They may have been born during a particular period of time, live in the same place, or have been diagnosed with a particular disease.  The cohort is defined to ensure that the study is well focused and to reduce “noise” in the data that may arise from environmental or cultural influences.  In veterinary medicine focusing on single breeds serves the same purpose.

During the course of a breed study under CLHP the subjects will periodically be examined and their owners will need to fill out questionnaires.  The specifics would vary with the focus of each study.  If the breed under study were the Australian Shepherds, study researchers might focus on the cancers hemangiosarcoma and lymphoma, epilepsy, hip dysplasia, and/or autoimmune disease, all of which are common breed health issues with serious economic and quality-of-life impact.  Even behavioral traits, like sound sensitivity, might be a topic of investigation.

These studies are observational, following events as they unfold.  They differ from a retrospective study, which looks back in time by reviewing and analyzing or comparing data previously gathered in other studies.  The observational approach allows the collection of far more and more-detailed data.  Studies of this type can indicate prevalence of a disease in a population.  For dogs that are diagnosed with disease, study results may increase our knowledge of disease progression or the efficacy of treatments.  It may even give us better ways of predicting which dogs will get sick and which of those will develop the most serious form of the disease.

Plusses and Minuses

There are advantages to longitudinal health studies that the more usual “snapshot” approach lacks.  In addition to the great wealth of data they provide, researchers are able to observe how things play out over time and determine temporal order of events.  The length of these studies can also help eliminate factors which may appear significant in a “snapshot’ but prove to be minor or even coincidental when followed over the long term.

There are some disadvantages to this type of study, as well.  Understanding these helps determine whether a longitudinal study will or will not be useful in answering the questions a researcher wants to answer.  For example, these studies are less able to clearly define causal relationships than would an experimental study, where as many variables as possible are eliminated.  Longitudinal studies are inconvenient because the timeframe requires dedication and commitment.  Subjects (or dog owners) who must return again and again and repeatedly fill out forms may lose enthusiasm for the effort.  These studies also require a lot of staff effort.  These projects need a steady hand on the tiller, so MAF brought in Michael Guy, DVM, PhD, to direct CLHP.  Dr. Guy has long experience directing scientific studies, having previously managed them for a clinical laboratory and a veterinary products company.  He oversees two staff members.  Because of the considerable staffing, materials and other support costs, these studies also take money, a lot of it.  But more about that later…

 It Takes a Village

Perhaps the most famous lifetime health study is the Framingham Heart Study, initiated in 1948 and still going today, now recruiting its fourth generation of subjects, all residents of a single town in Massachusetts.  Framingham researchers have been gathering cardiovascular disease data among the town’s adult residents that has greatly contributed to our present knowledge of heart disease.

As can be seen from the Framingham study, lifetime studies are nothing new.    The first (and also still running) was the Terman Study of the Gifted.  Started in 1921, it has followed the development and characteristics of 1528 gifted children into adulthood.  About 200 of the subjects are still alive and remain in the study.  Animals have also been the subject of lifetime studies.  One many dog-lovers will probably be aware of is the Isle Royale Wolf and Moose Study (1959 – ) which has followed behavior and interactions between generations of predators and prey species on an island far enough from the mainland to form a closed environment.

There have been long-running human health studies focusing, separately, on physicians and nurses.  Comparing findings of these two studies helped reveal that some diseases, notably heart disease, manifests differently in men than in women.  Prior to these findings women were assumed to have the same symptoms and disease progression as men.  Canine lifetime studies might reveal similar differences between breeds, or perhaps between giant breeds and toys – knowledge that would lead to better diagnosis and treatment.

Good as Golden

CLHP will ultimately provide an umbrella for multiple studies, but the first study focuses on Golden Retrievers.  Since this is not only a new effort but a new type of project for MAF, they wanted to start with a single breed at first in order to get their system rolling smoothly.  The various aspects of the work with Goldens, while gathering important data on that breed’s health issues, will also to some extent be a learning project for MAF’s CLHP team.

The Golden Retriever seemed an excellent place to start.  It is no secret to anyone familiar with the breed, that Goldens have substantive cancer issues.  Over half of them will die of cancer.  In addition, the most common cause of death for dogs as a species is cancer, so what is learned from the Goldens could have broad applications.   The breed’s potential contribution to cancer genetics studies, the breed’s sizable population, and its motivated and generous breed community made it an excellent candidate for CLHP’s first study.

The Golden study will recruit up to three thousand Goldens between the ages of six months to two years.  They will be followed for up to 15 years.  Each dog’s owner must be at least 18 years of age and the dog must reside in the contiguous United States (to facilitate required periodic exams and timely shipment of biological samples.)  The dogs must be healthy when they enter the study.  Owners will be required to submit a three generation pedigree.

Golden owners interested in applying for their dogs to participate in the study can do so on-line.  Those dogs that meet the initial qualifications must undergo a physical exam to verify that the dog has no health issues, and the owner will be asked to fill out a detailed questionnaire.

If a dog is accepted into the study, the owner must agree to participate for the life of the dog and select a veterinarian who agrees to participate.  Each dog will undergo an annual exam and owners will need to submit responses annually to an online questionnaire covering the dog’s nutrition, environment, behavior, and health.

The dogs’ annual physical exams will include the collection of hair, blood, urine, fecal, and toenail samples.  If the dog becomes ill, other biological samples may be required; in the case of the Golden study this would include biopsies of cancerous tumors.

Perhaps the most difficult thing asked of owners is that they consider allowing a post-mortem examination.  Many people are very uncomfortable about having this kind of exam done on their beloved dogs, but the knowledge that can be gained from this procedure is invaluable.  Participants should give very serious thought to complying with this request.

The veterinarian’s role in this study is equally important to that of the owner.  Participating vets must be willing to register for the study, maintain timely reporting and communication via e-mail and on line, perform initial eligibility and annual exams of participating dogs including collection and shipping of any required samples.  When owners of enrolled dogs bring them in for non-study related visits, the vets must file reports on those visits.  Finally, and again a difficult task, they must counsel participating owners about the options available for necropsy and the value of the samples obtained.

The emphasis of the Golden study is cancer.  The principal investigator is Dr. Rodney Page, Director of the Colorado State University Animal Cancer Center.

Over the next few years MAF will initiate additional studies in other breeds, with specifics appropriate to each breed.

Money

Longitudinal studies of this magnitude can’t take place without significant funding.  The Golden Retriever Foundation generously provided $500,000 for its breed’s project, but the bill for the total effort is expected to come in at about $25 million. The cost may seem huge but keep in mind that it will be going on for 15 years. There is software to develop and maintain that will track the data, long-term storage for blood and tumor samples that may contribute to future projects, and staff to make sure it all happens when and as it ought.

MAF realizes no single breed community can support such a project alone, and few breeds can boast the numbers and the resources of the Golden community.  MAF will be utilizing some of their own resources and seeking corporate partners to ensure sufficient funds will be available to carry forward this study and future efforts under the CLHP umbrella.  The foundation’s long experience as the preeminent granting agency for companion animal health research will serve it well in this regard.

The Payoff

MAF intends to make the findings of the Golden Retriever Lifetime Study, as well as those that will follow it broadly available to the public as well as academic, research, and commercial entities.  The availability of CLHP data will facilitate the work of researchers focused on a wide range of canine ills, leading to better methods of prevention, diagnosis, and treatment.