Category: Dr. Pedersen

Posted on

Fifty years’ fascination with FIP culminates in a promising new antiviral

3/25/2019, Translation 5/1/2021
Niels C. Pedersen
Original article: Fifty years' fascination with FIP culminates in a promising new antiviral

Feline infectious peritonitis (FIP) has fascinated me for the last 50 years. Although FIP is caused by a virus, it most closely resembles mycobacterial infections, which cause tuberculosis and leprosy in humans and cats. The disease revealed its secrets very reluctantly, and each new discovery led to further questions. As Robert Frost's famous poem puts it: "We dance around the ring and assume, but the secret sits in the middle and knows." I'm lucky to have reached the last milestone of my career when I identified safe and effective FIP treatment. We were able to reach this vase only thanks to hard work and great cooperation with teams of people in the USA from places like Kansas State and Wichita State University or Gilead Sciences.

We know that small molecules targeting specific proteins involved in RNA virus replication are able to safely treat various forms of FIP. These small molecules include the protease inhibitor GC376 and the nucleoside analog GS-441524. Both are based on drugs that are currently used to treat common human diseases, such as hepatitis C and HIV / AIDS, and are tested for exotic infections called MERS (Middle East Respiratory Syndrome), SARS (Severe Acute Respiratory Syndrome). and Ebola.

It is important to note that the small clinical trials we have completed and published are intended primarily to validate the concept, but unfortunately not to be quickly translated into approved and commercially available products. Some investigational drugs may be preferred (and thus delayed for veterinary use) in human medicine, and all will require a lengthy process to obtain final approval, even for animals. Private veterinary pharmaceutical companies will ultimately be responsible for their marketing. Is the demand for such medicines and the willingness of owners to bear the costs a sufficient incentive for these companies?

The FIP relinquished its secrets with great reluctance, and each new discovery led to further questions.

Figure 1. Bubba was originally found as an abandoned 3-week-old kitten by its owner in Florida, USA. He was diagnosed with dry abdominal FIP at the age of 7 and enrolled in treatment study GS-441524.
(a) In May 2017, just before the start of treatment, Bubba weighed 6 kg (13.5 lb). In the first week of the 12-week treatment, his owner stated that he "ate alone, alert, energetic and playful."
(b) Bubba, shown in January 2018, weighing 9.3 kg (20.5 lb).
Acknowledgments: Adel Gastle

Unfortunately, initial reports of successful treatment only stimulated the desperate owners' efforts for immediate access to these drugs and created a growing black market. Therefore, I suspect that we will test our patience and ethics over the next few years. None of this should detract from the fact that, after more than 50 years of research, we have reached this important point. Much more is waiting to be discovered. How does virus replication in macrophages lead to immunity in many cats, while in unfortunate individuals it leads to disease? Can this knowledge finally lead to effective vaccines? What is the best way to care for kittens in kennels, shelters and deposits to minimize FIP losses? Are even better drugs awaiting their discovery? Can small molecule inhibitors act in synergy with each other in a completely different treatment modality?

I will leave these and other questions to my scientific colleagues in the field of FIP.

Niels C Pedersen DVM, PhD
Center for Pet Health,
School of Veterinary Medicine,
University of California, Davis, USA

References

  • Pedersen, NC, Perron, M, Bannasch, M. Efficacy and safety of the nucleoside analog GS-441524 for the treatment of cats with naturally occurring feline infectious peritonitis. J Feline Med Surg 2019; 21: 271–281.
    Google Scholar | SAGE Journals | ISI
Posted on

Ending FIP, Is There Hope? A Summary of Dr. Niels Pedersen’s Presentation at the Winn Feline Foundation Symposium

Original article: Ending FIP, Is There Hope? A Summary of Dr. Niels Pedersen's Presentation at the Winn Feline Foundation Symposium (29.6.2017)

Summary: Carol Johnson DVM, PhD. A Heather Lorimer Ph.D.
For clarification, additional information from literature articles by Dr. Pedersena.

Feline Infectios Peritonitis (FIP) is one of the most complex infectious diseases and is undoubtedly one of the worst diseases imaginable. It is caused by an RNA virus from the coronavirus family Nidovirales. Other RNA viruses that the reader may be familiar with include the Ebola virus, influenza virus, AIDS, and rhinoviruses. Coronaviruses are named after protrusions that look like a crown (or corona) when viewed under an electron microscope. Coronaviruses can cause disease in almost every animal species, but as such, coronaviruses are species-specific: feline coronaviruses do not infect humans, dogs, or other animals.

Feline enteric coronavirus (FECV, also referred to in the literature as FCoV) usually remains in the intestinal tract and infects the upper layer of cells lining the small intestine before settling in the large intestine. FECV can cause mild diarrhea and vomiting, but is not considered a serious pathogen in the intestinal tract.

An FECV-infected cat can shed the virus in large quantities and excretion can continue for months. Cats are obligatory carnivores and, as a result, have a very short digestive tract. This may play a role in high virus shedding. Immunity to FECV is usually temporary and previously immune animals may be reinfected. This is one of the reasons why vaccination prevention is difficult, if not impossible.

FECV specific mutations they allow him to leave the intestinal tract, where he infects cells of the immune system called macrophages, which usually help fight infection. This mutated version of FECV is called FIPV (feline infectious peritonitis virus). Infected macrophages spread the disease in the cat's body in a similar way as tuberculosis (TB) bacteria spread in humans or animals. FIPV-associated mutations occur in three parts of the FECV genome, but a particular mutation may be unique to each cat. As many as 20% FECV infections can lead to subclinical macrophage infection, but relatively few cats develop FIP. Similarly, up to 40% of the world's human population is infected with tuberculosis bacteria, but few people have developed complete tuberculosis. Unlike TB, FIPV is not transmitted to other cats; the transmission takes place via an unmutated FECV.

FIP is a population-related disease high-density cats, where kittens are part of the equation. Kittens are most susceptible to developing FIP and are usually infected with FECV at about 9 weeks of age. In general, FIP can also occur in a dense urban or rural population of free-range cats. In the United States, FIP is more common in cats and kittens from conventional, high-density shelters and feline shelters or rescue stations where kittens may be exposed to large viral loads. Another source of FIP are kennels. Not only are a number of cats concentrated in farms, but there may also be genetic predispositions that may also play a role (up to 50% in some cases). Although the genetic risk is clear, genetic analysis shows that susceptibility to FIP is likely to involve a large number of genes. As a result, inbreeding is associated with susceptibility to FIP, but genetic testing for this susceptibility is not currently possible. Overall, FIP occurs in about 0.3% cats, but can occur in up to 1-5% (or more) cats in high-density sites, such as kennels or rescue stations.

The FIP is on the rise probably due to the increasing number of rescued cats in which kittens can be fed from bottles, weaned prematurely and exposed to large amounts of FECV.

There is a dry and wet form of FIP, but there may be combined forms and it is possible to change from one form to another. In general, the moist form, characterized by effusion, which leads to enlargement of the abdomen or fluid in the lungs, along with other symptoms, has a rapid course and can kill the cat very quickly (in this case, it is often death due to euthanasia). The dry form can last for months to about a year, sometimes longer.

Risk factors for FIP development they include the prevalence of cats that shed FECV, the intensity of virus shedding, the number of cats aged 4 to 29 months (most sensitive) and genetic predisposition (in bred cats). FIP often occurs in young cats after a stressful event, such as castration or sterilization. In these cases, the cat may already have FIPV-infected macrophages in the lymph nodes, and stress allows FIP to break out.

FIP can also develop in older cats. It typically happens that one (or more) cats in a multi-cat household die due to old age and the owner feels that the remaining cat needs a new friend, so he gets the kitten out of the shelter. The older cat has long since lost immunity to FECV and is now susceptible to infection. Due to older age, an older cat may have a worse immune response than a younger animal and is more likely to develop FIP.

Dr. Pedersen is of the opinion that FIP can usually be diagnosed relatively easily. Kittens or young cats with a viscous, slimy, yellow-colored fluid in the abdomen or thoracic cavity are likely to have FIP. The dry form of FIP may be more difficult to diagnose, but in young cats it is usually a combination of symptoms associated with chronic ill health, including weight loss, cyclic fever, characteristic blood count (anemia, decreased albumin, increased globulin, low albumin to globulin ratio, increase in absolute neutrophil count, decrease in absolute lymphocyte count, increase in bilirubin, etc.) and coronavirus titre ≥ 1: 3200, which helps to guide the diagnosis of FIP. Dry FIP may present with neurological symptoms such as convulsions or ocular lesions. Autopsy of most cases confirms characteristic lesions and leads to characteristic histological findings. Tissue or histological specimens can be further tested by various techniques, such as polymerase chain reaction (PCR), immunofluorescence (IFA) (frozen tissue only) or immunohistochemistry (IHC) (formalin-fixed tissue), but Dr. Pedersen considers these tests to be confirmatory. He believes that in almost all cases it is possible to diagnose FIP by routine examination. Some diagnostic tools lead to false negative results. For example, PCR, a commonly used diagnostic test, has about 30% false negative results.

Traditional treatment does not work. Immunosuppressants such as corticosteroids may make the cat feel better, but the course of the disease will not change. Biological agents do not work. Vaccines do not work because the kitten is usually infected with FECV before vaccination and because the immunity is only temporary. The most common cause of death in cats with FIP is euthanasia due to loss of quality of life as the disease progresses relentlessly. Although the wet form of FIP is often very fast, some cats may live longer with supportive care than one might think (weeks or months). Pulmonary fluid should be aspirated, but abdominal fluid should generally not be aspirated. Dry cats can stay alive for months or more. Spontaneous remissions may occur, but usually all cats eventually succumb to FIP.

Hope comes in the form of new antivirals. RNA viruses share many of the same types of genes and therefore present similar goals in drug development. This means that drugs designed to block one type of RNA virus may prove useful in the treatment of another type. Two potential drugs that may be effective in the treatment of FIP are protease inhibitors and nucleoside analogs (NUCs), which specifically target viral enzymes. RNA viruses often form one very large protein, which is cleaved by very specific proteases into the individual viral proteins needed to assemble new viruses. Drugs that inhibit specific proteases have been developed as antiviral drugs for various viruses. NUCs used to prevent HIV genome replication (reverse transcriptase inhibitors) in AIDS patients may also block RNA-dependent RNA polymerases that replicate the coronavirus genome. Cats, like all mammals, do not have an RNA-dependent RNA polymerase, so it is an enzyme specific for a given virus. Protease inhibitors act in the late phase of cell infection, while NUCs act in the early phase.

GC376, a protease inhibitor, was the first drug of its kind to be studied in cats. Dr. Pedersen worked with a team of veterinarians and chemists at Kansas and Wichita State Universities to treat cats experimentally infected with FIP, and later naturally infected cats. The treatment included 20 naturally infected symptomatic cats with FIP. Thirteen eventually died, some relapsing after remission and death due to neurological FIP. Seven cats survived and now appear to be free of disease, one to 1 year after treatment. A study in symptomatic, naturally infected cats determined a safe dose of drugs and determined an optimal treatment time of 12 weeks. However, treatment of cats with neurological symptoms was not successful, probably because the drug does not cross the blood-brain barrier. The drugs had few adverse effects; one of the most pronounced was the inhibition of adult tooth formation, which is a known side effect of this group of drugs. The limiting factor in the study was the final amount of drug produced.

EVO984 is a nucleoside analogue - reverse transcriptase inhibitor developed by Gilead Sciences. NUCs may have some advantage over protease inhibitors because they act in the early stages of virus infection of the cell. Gilead has provided several NUCs for which Dr. Pedersen tested their effectiveness against FIPV in vitro, followed by a pharmacokinetic study and finally a study in cats with artificially induced FIP. UC Davis needed to obtain extensive documentation and knowledge before treatment could be done on client pets with naturally developed FIP, and this study is underway right now. The drug appears to be safe, has been able to reverse the symptoms of FIP, including effusion, and some cats have successfully entered remission. Like GC376, EVO984 is not effective on neurological FIP because it does not cross the blood-brain barrier well. Although this study has only been running for a few months, it looks more promising than GC376. The test has only lasted 12 weeks, but all 24 cats that took part are currently alive.

Translator's note: EVO984 later became known under a new name, which is known to almost everyone who treated a cat with FIP. EVO984 is nothing but GS441524. In addition, GS441524 has been shown to cross the blood-brain barrier at increased doses and thus to treat neurological forms of FIP.

Next steps: While the studies appear promising, many unanswered questions remain. Dr. Pedersen believes that if his study is successful, it will likely need to be confirmed by a second group. It has been pointed out that additional funding may be needed through the Winn Feline Foundation’s Bria Fund, which has invited contributions for future FIP research. Gilead is excited about the preliminary results, but the company develops drugs for human use and does not have an animal health division. Gilead has indicated to Dr. Pedersen that if the results continue to be promising, they may pursue it or seek a partner that specializes in animal health products. However, given the overall prevalence of FIP worldwide, the drug may not be attractive enough for large pharmaceutical companies. However, Dr. Pedersen pointed out that there may be a way to find a way around it using provisions of the FDA’s Minor Use and Minor Species Animal Health Act of 2004.

Questions and Answers:

The question was asked why more cats could not be treated in the study. The drugs are experimental and have limited supplies. Dr. Pedersen feels that he only needs about 20 cats to draw conclusions, as this is usually a deadly disease. He also said that the desperate owners sometimes offered him a large amount of money so that their cat could be included in the study. He said it was very sad, but strict criteria had to be followed to be included in the study and it was not possible to meet everyone.

Asked about the genetic predisposition and whether it is possible to select purebred cats resistant to FIP, Dr. Pedersen shared his experience with randomly selected breeding cats experimentally infected with the highly lethal FIPV laboratory strain. Despite infection, about 20% cats did not develop FIP. When these cats were housed together, their kittens did not develop FIP in only about 10%. When the second generation of surviving cats were bred together, FIP developed in all their offspring. Dr. Pedersen believes that these results support the concept that the most resistant cats are crossbred cats, where many immune system genes are heterozygous (having two different versions of each gene), so that a cat's immune system can respond and attack a wider range of pathogenic targets. He believes that when cats are bred, the cat's immune system becomes more homozygous (they have two copies of the same version of each gene), which reduces the variety of targets to which the immune system can respond. Because mutations that change FECV to FIPV vary, cats with a broader ability to respond to small viral changes are likely to be better protected. Breeders should minimize the use of males that have fathered kittens that have died of FIP. Why males? Because individual breeding males generally produce more offspring than breeding females, they therefore have a greater impact on the next generation of cats.

Posted on

Evaluation of a commercial test for genetic resistance to feline infectious peritonitis

Original article: Evaluation of a commercial test for genetic resistance to feline infectious peritonitis, year 2015

Niels C. Pedersen, DVM PhD,
Professor Emeritus,
Center for Pet Health,
School of Veterinary Medicine,
University of California, Davis

The laboratory called AnimalLabs © in Zagreb, Croatia, offers a test that they say identifies cats that carry a genetic marker of resistance to FIP (http://www.animalabs.com/feline-infectious-peritonitis-dna-test-for-resistance/, accessed 7 October 2015). The same test is offered by Genimal Biotechnologies in France (https://www.genimal.com/dna-tests/cat/feline-infectious-peritonitis-resistance/, accessed 29 October 2015). AnimalLabs © has provided two links, one to a research article describing this marker1 , and the second review article on the FIP, which I published in 2009.2 The first article is freely available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041894/pdf/1297-9716-45-57.pdf. A summary of my 2009 review article is available at: https://sockfip.org/wp-content/uploads/2019/04/FIP_Synopsis_Jan13_09-1.pdf. I want to assure you that listing my review article does not support this test. In fact, I believe that the research behind this test was flawed in several respects and should be considered preliminary at best.

I would like to summarize the research that Hsieh and his colleagues did in the article.1 The researchers hypothesized that interferon-gamma is involved in protecting against FIP, a reasonable assumption based on previous research by other scientists. They sequenced the feline interferon-gamma gene (fIFNG) and identified differences between cats (i.e., genetic polymorphisms) at three different positions, which they designated 401, 408, and 428B. These polymorphisms included a single nucleotide polymorphism (SNP) at each of these positions. These SNPs were not located in the parts of the genes that code for the fIFNG protein (i.e., exons) but rather in the regions that surround the exons (i.e., introns). Intron regions are known to contain both nonsense sequences and genetic elements that regulate the level of protein expression by the gene. They then collected DNA from 66 healthy cats and 60 cats with FIP. They found no relationship between the differences in SNPs at positions +401 and +408, but there was a relationship with disease status for the SNP at position +428B. I quote their work – “of all SNPs tested; only fIFNG + 428C/T was shown to be significantly associated with infection outcome. At position +428, there was a higher frequency of the CT genotype in asymptomatic control cats (19.5 %) than in cats with FIP (6.3 %) and the data showed a significant correlation with disease resistance (p = 0.03) (Table 2).” It is noteworthy that among the 66 healthy and 60 cats with FIP, only cats that had CC or CT were present; no cats that had TT were present in either population. The table showing the relevant findings is given below:

Healthy catsFIP cats
+428 SNPs(% of cats)(% of cats)
CC66 (80.5)60 (93.8)
CT16 (19.5) 4 (6.3)
TT0 (0.0)0 (0.0)

The authors concluded that the difference between 16 healthy cats with CT (19.5 % healthy cats) was significantly different from the 4 FIP cats with CT (6.3 % cats with FIP). Using the odds ratio (OR), they calculated that the odds of CC in FIP cats were 3.6 times higher than in CT cats, and concluded that the T SNP is dominant over C. There were two problems with this conclusion, however. First, no cat in their study was TT, and given the fact that 20 cats in both populations carried the T SNP (20/126=15.8 %), one would expect 9 % (0.158 x 0.158=.092), or 11 cats out of 126 cats to be TT. This suggests that either TT is embryonic lethal or, more likely, the populations studied were not a random representation of all cats. Statistical comparisons are only valid when the populations are randomly selected, and special care should be taken when the significance level approaches the minimum P value of P ≤ 0.05 and the number of cases and controls is small. The null value for TT cats in the population also made it impossible to assess whether cats containing two copies of the “protective allele” also had significantly higher resistance than cats that were CC. One would expect that if T is dominant and CT is protective, TT would also be protective. Knowledge of the incidence of cats that are TT at +428 is crucial to the use of the test, because the only way to breed to the CT genotype, if it is the only genotype associated with resistance to FIP, is to maintain CC cats in the population. If TT cats are shown to have a similar degree of resistance to FIP as CT cats, then it is theoretically possible to breed for the T allele alone (CT and TT) assuming that the T allele is indeed associated with resistance. Therefore, the value of the test depends on the prevalence of the CC, CT and TT genotypes in the populations in which it will be used. It is likely that some breeds will be homozygous for the common C allele and therefore will not be covered by the test. Although unlikely, some breeds may have a high prevalence of T and again assuming that both CT and TT are protective, testing may not be cost-effective. If the prevalence of T is low, positive selection for T carries a risk of inbreeding (see discussion below). The bottom line is that breeders should not pay for this test until they have the information they need to use it properly in their breeding programs.

The authors had the biggest problem explaining the biological significance of the T SNP polymorphism. Most significant genetic mutations are found in exons (protein coding regions) and not in introns (non-protein coding regions). To provide biological relevance, the authors had to demonstrate that an intron mutation caused an increase in fIFNG production. The usual way to do this would be to isolate a normal gene with a CC SNP and an alternative gene with a CT SNP and show that there was a difference in the expression level of fIFNG between the two genes in a test system (ie in-vitro). The simplest test would be to identify a large group of cats that are CC, CT or TT, isolate their blood lymphocytes, stimulate them to produce IFNG, and then compare the levels of either specific RNA (by qRT-PCR) or the actual protein by ELISA or other assay. If their observations are correct, cat lymphocytes that are CT or TT should express more fIFNG than cats that are CC. Instead of this complex experiment, the authors decided to only measure fIFNG levels in the plasma of cats with FIP, arguing that cats with FIP and CT SNPs would have higher plasma levels of fIFNG than cats with FIP and CC SNPs. They found that 12/12 cats with FIP with CC SNP had very low levels of fIFNG, while all three cats with FIP with CT mutation had high levels. The conclusion was that the CT mutation allows for higher expression of fIFNG. There are several serious problems with this conclusion. First, it is paradoxical to conclude that a CT mutation confers resistance to FIP and that this resistance is associated with increased fIFNG expression, but then to prove this using plasma from CT cats that have suffered from FIP. The second problem is that there were only three cats in the CT group and 12 cats in the CC group, which makes any statistical comparison irrelevant. Finally, there is no good evidence that cats develop FIP because they are unable to produce sufficient levels of fIFNG. Several FIP studies have measured cytokine expression in cats with FIP.3 These studies were more concise when they showed an increase in FIFNG in the serum of cats with FIP and an increased production of blood lymphocytes in cats with FIP after stimulation. In fact, the general conclusion is that IFNG is stimulated rather than inhibited in cats with FIP.

Up to this point, I assume that this research is justified and that further research is needed. The problem is to make a huge leap from some weak research findings to practical applications. There is already ample evidence that FIP resistance cannot be attributed to a single polymorphism in a single gene. Our attempts to find the only gene responsible for FIP resistance in field studies with Burmese cats4 and randomly bred cats in our own experimental breeding program5 did not allow us to identify a single genetic marker of FIP resistance / susceptibility that we would consider significant. In fact, the only genetic risk factor we were able to identify for FIP resistance was kinship crossing itself.6 Breeding resistant cats with resistant cats did not increase the resistance of their offspring, but rather made them even more susceptible. This is exactly what you would expect from a genetic trait that includes many different genes and gene pathways. The more you try to select a single resistance factor, the more you inadvertently limit the role of multiple genes and gene pathways. Interestingly, the current recommendation is still the best, ie to avoid inbreeding and not keep cats that have fathered kittens with FIP. This recommendation is based on the theory that such cats carry a greater proportion of susceptibility factors than cats that do not produce kittens that have developed FIP and will produce kittens with an even higher proportion of risk factors when bred together. Based on these findings, selection for resistance to FIP using a single genetic marker is more likely to favor inbreeding and, in fact, increase the incidence of FIP. Finally, it should be recalled that heredity explains only 50 % susceptibilities to FIP, 7 the remainder being attributed to epigenetic (genetic changes that occur after birth) and environmental factors.

Although a simple genetic test that would significantly reduce the risk of FIP does not seem realistic, there is reason to continue to look for genetic explanations for why some cats may appear to be resistant to FIP and others succumb to it, and why some cats develop a wet form of FIP and in others a chronic dry form. These studies should focus on farms where FIP exists, where pedigrees are known and where genetic traits can be easily traced. However, the cost of such research should not be at the expense of breeders who order the test. The normal procedure for placing a genetic test for a disease trait on the market is to verify it before it is offered to the public. I don't think this test has been sufficiently researched.

Cited literature

  1. Hsieh LE, Chueh LL. Identification and genotyping of feline infectious peritonitis-associated single nucleotide polymorphisms in the feline interferon-γ gene. Vet Res. 2014, 45:57.
  2. Pedersen NC. A review of feline infectious peritonitis virus infection: 1963-2008. J Feline Med Surg. 2009, 11 (4): 225-58.
  3. Pedersen NC. An update on feline infectious peritonitis: virology and immunopathogenesis. Vet J. 2014, 201 (2): 123-32
  4. Golovko L, Lyons LA, Liu H, Sørensen A, Wehnert S, Pedersen NC. Genetic susceptibility to feline infectious peritonitis in Birman cats. Virus Res. 2013, 175 (1): 58-63.
  5. Pedersen NC, Liu H, Gandolfi B, Lyons LA. The influence of age and genetics onnatural resistance to experimentally induced feline infectious peritonitis. Vet Immunol Immunopathol. 2014, 162 (1-2): 33-40.
  6. Pedersen NC, et al. Immunity to feline infectious peritonitis virus infection is diminished rather than enhanced by positive selection for a resistant phenotype over three generations.Manuscript in preparation.
  7. Foley JE, Pedersen NC: Inheritance of susceptibility of feline infectious peritonitis in purebred catteries. Feline Practice, 1996, 24 (1): 14-22
Posted on

DR. PEDERSEN’S AUTOBIOGRAPHY

Original article: DR. PEDERSEN'S AUTOBIOGRAPHY
Published 18.3.2014, Translation 29.1.2021

I was born in 1943. My father was a Danish emigrant and my mother was the daughter of Danish emigrants. However, I learned that I also have Swedish roots after my father's line. I spent the first 14 years of my life in Southern California (Azusa and San Dimas), where my parents rented and then owned several family poultry farms. Although wholesale and retail eggs were their main business, they also raised ducks, geese and turkeys for the holidays. My father liked cats, but not pets. He always kept a large number of them on the farm to keep the rodent population low and their diet was supplemented by blood eggs. I loved all sorts of animals and bred pigeons, pheasants, wild ducks. As a pet, I even had a goat and a rabbit. However, my greatest love was the cats.

My first feline companion was a white, short-haired female with brownish ears, called MoMo (the mother of a cat in my child's tongue). She lived with me for 14 years and regularly and later irregularly gave me kittens. I also befriended many wild cats and one of my tasks was to sit with a box of kittens when customers came to buy eggs. I found homes for many kittens and once in a while I got 25 or 50 cents. I got to know the character and personality of cats more than anyone else. My life changed in 1956, when a huge summer fire in the hills around our San Dimas farm caused the temperature around the chickens to rise to more than 53 ° C and we lost all the water used to cool them. Sixty thousand chickens died within a week as a result of the sunburn. This unfortunate incident was, in fact, a blessing, as small family poultry farms in Southern California were rapidly becoming unprofitable, and this event forced my father to leave poultry after 30 years. He monetized all the property, which had some value, and exchanged it for a small warm spring resort in southern Nevada, and since then my family has been a real middle class. The resort was located in a valley called Upper Muddy, which also housed a large cattle ranch. The high school was 20 miles from Overton and the school started by 6:30. I started high school as a freshman with great tremor and on the first day of school I immediately fell in love with my future wife (Gerie). A small high school and living in a Mormon farming community have given me all sorts of experiences I wouldn't have had if I attended a much larger high school in Southern California. Every capable boy competed in sports and there were many interesting courses and extracurricular activities. Each student had to participate in several activities. My greatest high school experience was with Future Farmers of America, and I eventually became an FFA civil servant.

In 1961, I was accepted to the University of Nevada in Rene for scholarships from the Union Pacific Railroad and the Max E. Fleishman Foundation with the intention of becoming a teacher of professional agriculture. I soon realized that this was probably not the best career choice, but I had no idea about anything else. At the end of the first year, however, I switched to Animal Sciences and in the second year I began to attend much more demanding subjects in preparation for a possible Ph.D. in this field. My life changed again when I enrolled in a veterinary course led by one of the two veterinarians who were responsible for the small veterinary program at UNR. I have never had any direct experience with veterinarians before. Dr. Marble started my interest in veterinary medicine and even allowed me to help him with some of his experimental operations. I was immediately caught up in it and at the last minute I applied to three veterinary schools, UC Davis, WSU and CSU. I was accepted to all three schools, but I decided to go to UC Davis, California, which was closer to my home. I'm a native Californian (and an adapted Nevada). I was also fortunate that my tuition was paid by the state of Nevada under the Western Interstate Compact for Higher Education (WICHE).

I entered veterinary school in September 1963 with the intention of becoming a general practitioner for cattle (my second and third loves are cows and poultry). I worked on several science projects over the weekends and holidays, and I fell even more in love with research. In August 1964, I married my high school love Gerie. In my spare time, I worked with one of the graduate pathology students on a new feline disease called feline peritonitis and co-authored my first scientific article on FIP in 1964. I was horrified by a lack of knowledge about cats and their diseases, but that didn't stop me. After graduating from veterinary school, I graduated in internal medicine for small animals and surgery at Colorado State University, which significantly affected my future life and career. Once again, I realized how little we knew about cat diseases, and I became even more aware of my lifelong affinity and understanding with this species. Prior to my internship in 1967, I was accepted as a graduate student at the John Curtin School of Medical Research (JCSMR), Australian National University, Canberra, ACT, Australia. Australia has fascinated me all my life and JCSMR has given me not only a great research experience, but also my first experience with this vast and beautiful country. After graduating, I worked briefly as a celebrity practitioner in Hollywood to earn money to get my family (I already had a daughter) to Australia. Studying research at the Department of Experimental Pathology at JCSMR was unmatched, but not entirely related to my future career. But I learned about experimental methods. In 1972 I received my Ph.D. from experimental pathology and immunology with honors in. My love for Australia, which I cultivated in books as a child, became a lifelong passion. My hobby is identifying and photographing Western Australian plants. At our house in Winters, California, I have a large collection of photos of the flowering shrubs of Western Australia.

Dr. As longtime director of the Center for Pet Health (CCAH), Pedersen led a team that raised money and designed his current home. The CCAH building was completed in 2006 at a cost of $ 16 million, all of which was obtained from private sources. It is considered one of the most beautiful and functional buildings in the complex and is home to five clinical services and four major research programs.

In early 1972, I returned to the United States for a research position at the School of Veterinary Medicine at UC Davis, where I studied animal cancer associated with retroviruses. This was my first experience with the feline leukemia virus, which we saw during my studies in many cats, but whose cause was unknown at the time. My first year in research did not go well for me and I was considering moving to a postdoctoral position in transplant immunology at the University of Washington. Before formalizing this position, however, the dean of the Veterinary School called me and asked me if I would consider accepting a position at an internal medicine clinic for small animals. Dean Pritchard was tired of hiring doctors with rich clinical experience but weak scientific skills. He decided to try to admit to the clinic people with great research experience and good clinical potential. I became the first of a large number of employees at UC Davis with a professional background of this kind. It turned out to be a very wise decision, as the clinical program at UC Davis soon became world famous not only for its high clinical level but also high level of research.

I have worked at UC Davis since 1972 and retired in October 2013 as Professor Emeritus. I spent the first 17 years in clinics, teaching and working in research. For the rest of my time at Davis, my career was much more about administration and research. After serving as chair of the department, I became the founder and director of the Center for Pet Health and a few years later the director of the Laboratory for Veterinary Genetics. This latter function has rekindled my interest in the role of genetics in disease. Research into infectious and immunological diseases in cats and dogs has accompanied me throughout my career. I am still working and continuing my first love, research. I have no plans to retire if my health allows it, because for me, retirement in research is much better than retirement.

Although I have studied many infectious diseases of cats, FIP remains my first love, if the term can be called a disease that is still so widespread and almost always fatal. I learned to look at the FIP as a "worthy adversary." It is undoubtedly one of the most complex and challenging infectious diseases in existence, and trying to find prevention and treatment is what drives me the most. I realize that the answers don't just come. It's not like researching human diseases that have no problems with funding, whether from individuals or organizations that have a personal interest in discovering treatments. I hope that I will continue to strive to keep the disease at the center of attention, and I can say that I am not alone. I have recently reviewed more than 100 clinical and scientific publications on FIP submitted by research groups around the world since 2008. No other cat disease has received so much attention.

I enclose a more detailed biography of my career with an emphasis on FIP research, which still engulfs me. My biggest career achievements have been in the field of feline infectious diseases such as FeLV, FIV, FCV, FECV and FIPV. My textbook on diseases in a multi-cat environment, which has become a classic today, is perhaps my best creative work. However, my wife, three daughters, a son and 7 (soon to be 8) grandchildren, all successful so far, are my greatest legacy. But I hope that at least for a while, my "paw prints" will remain visible through the literature on cat diseases. And something like pets I've always had cats - always only two and always males.

–Niels C. Pedersen

Note: When Dr. Pedersen mentions a more detailed career CV, meaning mainly a number of published articles that you will find in scientific journals.

This is a 1991 photo when I received the first Jean Holzworth Cat Research Award. Dr. Holzworth was for me the best feline medicine expert he had ever lived. She graduated from DVM at Cornell University and spent her entire life at Angell Memorial Animal Hospital in Boston. She wrote the first modern textbook on cat diseases and I considered her a good friend and inspiration. She convinced me of something I've always believed in - you can't be a great veterinarian for cats without deep and confidential knowledge of this species, including everything from anatomy and physiology to behavior. -DR. P.

Wife of Dr. Pedersen Gerie with the newest members of the SOCK FIP family - recently adopted two brothers Piper (right) and Frodo (left). Frodo and Piper are among the many former experimental cats that the Pedersen have adopted over the past 40 years.

en_GBEN
sk_SKSK en_GBEN