"(W)e can engage in all kinds of cross-talk with veterinarians about comparative pathology. The center I'm in currently, the Center for Comparative Medicine, is a joint effort by the two schools to develop a center in which MDs and veterinarians can work together."
—ROBERT D. CARDIFF, MD, PHD,
DIRECTOR, UNIVERSITY OF
CALIFORNIA-DAVIS MOUSE BIOLOGY
PROGRAM'S MUTANT MOUSE
Robert D. Cardiff, MD, PhD, is a medical and experimental pathologist with expertise in tumor biology and the comparative pathology of genetically engineered mice. As director of the University of California-Davis Mouse Biology Program's Mutant Mouse Pathology Laboratory, Dr. Cardiff conducts research involving the comparative pathology of genetically engineered mice used as models for human disease, particularly cancer. Several veterinarians work with Dr. Cardiff. He has recently organized the Center for Genomic Pathology with a faculty composed of veterinary and medical scientists who are concerned with education in comparative pathology.
Talk some about your research.
I am the service pathologist for the superstars. What I mean by that is I have around 300 client-collaborators who send me material dealing with genetically engineered mice. So, I have all of these marvelous people creating mice, and they send them to me for validation studies.
The basic idea about genetically engineered models is the genes that cause disease in humans cause the same disease in animals. If you take a gene known to be associated with diabetes in humans, you can test it in animals—the mouse has become the surrogate for modern biology. If scientists think that a gene might have an effect on cancer, they test it in the mouse.
How do veterinarians help?
Since I've been here (at UC-Davis), since 1970, I've been working with colleagues in the veterinary school. Our Department of Pathology has always been involved in comparative pathology studies. One of the major reasons for being in this environment is that we can engage in all kinds of cross-talk with veterinarians about comparative pathology. The center I'm in currently, the Center for Comparative Medicine, is a joint effort by the two schools to develop a center in which MDs and veterinarians can work together. Our director is Steve Barthold, a very well known veterinary pathologist.
So the one-health concept isn't new to you?
No, we've been practicing it for years.
What do you think about all the attention the concept is getting lately, especially from the AVMA and American Medical Association?
I think its salutatory. It's much needed. We've written several articles that have appeared in scientific publications that deal with how all of this came about, from our perspective, and what has happened to veterinary research, which has fallen on difficult times, in part because of economic considerations. We need more veterinary students going into research, because they're greatly needed.
What do veterinarians offer?
Specifically, veterinary pathologists and veterinarians involved in laboratory animal medicine know the animals, and specifically the mouse, in a way that few physicians do and certainly in a way that no molecular biologist does. So, where their colleagues might have a tendency to think of the mouse as a fuzzy test tube, the veterinarian knows it as a biologic entity. They know aspects of mouse husbandry and, in particular, aspects of infectious disease, and they're just very, very valuable. I've worked with veterinary pathologists in the context of the National Cancer Institute's Mouse Cancer Consortium, and it's been a real eye-opener.
Talk about the "other" one health.
We've been working on the premise that the same genes cause the same diseases in all animals and that we can learn a great deal from studying animals and animal models. The one-medicine concept has really come out of epidemiology and infectious disease. We've been working at a gene level and marveling over what we can do to understand the genomic basis of disease. Let's not forget that a lot of the powerful technologies that we can apply to emerging infectious diseases come out of the disciplines of molecular biology and genomics, and they're providing us with an enormously powerful technology.
You've written about the need for a "postgenomic" workforce that includes veterinary medicine. Please explain what you mean.
As you know, the entire human genome has now been sequenced, (as have) the entire mouse genome and the genomes of some 300 other species. The only way we're going to understand what we have is by phenotyping all the genes ... and that's going to happen through the mouse. The U.S. government, Canada, Europe, Asia—all have knockout mouse programs designed to knock out all the human genes, except they're doing it in mice. That will give us a great deal of information about the functions of the genes.
As we take Humpty Dumpty apart, we're going to have to put him back together again to validate the function of each of those genes. The estimate is that we are going to be creating, over the next 10 or 20 years, something on the order of 200,000 new strains of mice. There simply aren't enough comparative pathologists in the world to phenotype all those mice. We're very concerned about that and are trying to alert the governments and the agencies putting together these massive programs. In fact, rather than just simply expressing our concerns, we've moved ahead to develop an educational foundation, the Center for Genomic Pathology, designed to address these needs through offering training.
What we've been doing, particularly in the past 10 years under the aegis of the National Cancer Institute, has been working with people in both veterinary medicine and human medicine who are comparative pathologists and comparative medical scientists optimizing the use of these fascinating models. We desperately need people with a medical background, but it starts with scientists with a veterinary background if we're going to make use of these mice and translate what they can tell us about disease to humans.