Dr. Michael Collins: Crohn’s Disease and the Farm
In the presentation, Dr. Collins mentions the book “Spillover” by David Quammen.
It’s a real pleasure to be here. As Will said, I’m a veterinarian. I teach at the veterinary school at the University of Wisconsin in Madison, not so far from here. And I’m here because, really there is no longer the concept of veterinary medicine and human medicine. It’s referred to as one health. And the two professions have an awful lot to do to teach each other. Today I just want to answer two questions for you: What have we learned about MAP infections in veterinary medicine? We’ve been working with this infection for 120 years, so we have a few insights. And secondly, how could people be exposed to this infection? I talked a little bit about what we know about this infection in animals, and borrow from that to human health. And I’m also going to talk about how people can be exposed, because my primary interest in this symposium and as a veterinarian is not the treatment of Crohn’s disease, but rather the prevention of Crohn’s disease for generations to come.
So this is a picture of this pathogen magnified 50,000 times taken from a pure culture isolated from a cow with this disease. And this skinny cow is how this disease manifests in all of the animals that it infects; animals who go through their lifetime, they eventually develop chronic diarrhea, they lose weight dramatically and if they’re a dairy cow they stop producing milk. Inside the infected animal we find a damaged intestine. Most of the pathology is concentrated in the ileum just as with Crohn’s disease. Depending on the animal species we might find a pathology higher and lower in the GI tract as well. There is liver pathology and other peripheral lesions if the infection is very advanced. So here on top you see what a normal intestine should look like. It’s very thin actually and what happens with this inflammation is it gets very thick. Fundamentally it gets so thick that it can’t absorb nutrients and then the animal essentially starves to death even though it’s eating perfectly well. These animals, by the way, don’t behave ill. They eat just as much as the herd mates and in spite of eating well they have this diarrhea and weight loss.
So what’s the truism in this infection in all of the other species we studied. It is the very young that are the most susceptible. As animals age, they get more and more resistant to an infection. And experimentally we know if we gave a massive does to an adult cow we could get the cow infected but by and large under normal circumstances it is the very, very young that are the most susceptible. We don’t understand the biology behind why this is exactly true. We speculate that it has something to do with the immune system and the maturity of the immune system. It might have something to do with lymphoid tissue in the intestine called Peyer’s patches, which are very, very numerous and most active in the very young.
Oh so, this is the natural history of the disease in a dairy cow. The infection probably happens within the first few weeks of life between birth and weaning, which for a dairy cow is about eight, eight to nine weeks. Then eventually the infection will slowly replicate over time, increasingly damaging the intestine and finally there’s enough bacteria in the intestine that it begins passing out in the manure. And we can detect cattle as being infected only after they’re about two years and older. Eventually these animals will test positive on a blood test and still look clinically normal, and finally they develop this diarrhea and weight loss and everybody can see that this is a sick animal and there’s a question about what do we do with it.
The problem or the challenge of this infection to control on dairy farms is that the animal’s been infectious and has been passing the infection for a long, long time before anybody knew that she had this problem. And so it silently spreads to other animals that are born on the farm. They grow up to become cows that are members of the adult herd and so the infection perpetuates and it gets worse and worse.
So this is a line trying to depict the percentage of herds globally, dairy herds, that are infected with this pathogen. And the timeline begins in 1895 when this veterinarian name Hans Johne, a German (giving rise to the name for this veterinary disease, Johne’s disease); he recognized the disease in a cow in Germany in 1895. And he looked at the intestine and said, “You know this looks like intestinal tuberculosis but I can’t grow the bacteria.” And the disease went without an identity for several years until finally people learned how to grow this very fastidious pathogen.
About 1908 when the U.S. was building it’s dairy industry, we went to Europe, we went to Denmark and Germany and the Netherlands and bought the best breeding cattle we could. We brought them back to the United States and we brought Johne’s disease back with them. In 1908 we first recognized this disease in Pennsylvania, again in a Guernsey cow, and over time this infection has continued to spread within herds, among herds, between states and between countries. I’ve had the privilege of working in four different countries on Sabbaticals over my career and most recently worked in Chili. And Chili has made the exact, replicated the same mistake that the U.S. and Australia have made: Importing infected cows, resulting in their own native herds becoming infected, and the infection has spread.
So we’re up to a place now that, depending on which country you’re in, somewhere between 50 and 90 percent of the dairy herds are infected. The official USDA estimate in the U.S. is that 91 percent of US dairy herds are now infected. This was not always the case. This has been a chronic, slowly progressing infection that has spread from herd to herd.
Where does Crohn’s disease fit? Crohn’s disease fits on this timeline in 1913. Is that a coincidence or is there some causality here? I work with this disease mostly in dairy cattle because I’m in Wisconsin, but this infection affects all ruminants. Those are animals that eat grass, chew it up and turn it into meat and milk proteins. That includes sheep, goats, buffalo, even giraffes. It’s most recent diagnosis that hit the press is in the Saudi Arabian prince’s racing camels, which has brought some additional funding. It has twice been identified in non-human primates. One of those, a mandrill baboon, was diagnosed at the Lincoln Park Zoo in Chicago. Curiously, one of the keepers that spent a lot of time with that animal, had Crohn’s disease.
The big question today is: Among this large collection of diverse animal species that are susceptible to this infection, are humans among them? So it’s very popular today to talk about diseases that spill over from animal populations to humans. In fact as David Quammen’s book nicely describes, 70 percent of the new infections we’ve recognized in humans today originate in animals. Some of them are very dramatic and they capture the headlines, like the Ebola virus. That’s a zoonotic infection. It originates from animals, and it will continue to originate from animals. MAP might just be one of those. So I’m not sure what this summary exactly says, but we know a lot about MAP infections. We know how they progress. We know it starts in youngsters. We know it targets the ileum. We know it causes chronic granulomatous inflammation in that intestine, that pathologically and clinically looks very much like Crohn’s disease; and a whole range of animal species are susceptible. So it’s not a big leap, a scientific leap of logic to think that humans might be among them.
So the question is then: How can humans get exposed to this? You’re not dairy farmers. You’re not out there working with animals every day. The fact is that most of these infections are in dairy cattle and other food producing animals. And the milk that comes from those herds that are infected is contaminated with these MAP bacteria. Sometimes because the bacteria goes right through from the intestine into the blood stream and out in the milk directly. No matter how cleanly you collect it, it’s coming out in the milk. But also because there is some fecal contamination that happens. Milking is not a surgical procedure. There’s a lot of preparation in the teats before you collect the milk, but there will be some fecal contamination. We depend on pasteurization to clean up all of the bacteria that might get into the raw milk, and this organism has found a way to get past the pasteurizer. Multiple studies, multiple countries including the United States, show that when we go to the store and we buy retail pasteurized milk, and we bring it back to the laboratory, we can culture live MAP bacteria. Not a high number, and not every sample; about two percent of the samples that they’ve tested, but this has been replicated in the UK, Czech Republic as well as the U.S. So this is a very clever, wily pathogen, even when it comes to manufacturing practices that we use to try to clean up our products.
And who consumes most of these products? Well, it’s young children. So it’s a very important risk factor because of the age at which humans are being exposed. Based on estimates of how many MAP bacteria survive, we estimate that children, a child might consume between 1,000 and 100,000 MAP bacteria by the age of ten. We’ve also found MAP bacteria in other dairy products. There’s not just milk. It can survive cheese manufacturing and quite probably yogurt and maybe even ice cream. And if you think that all your products are coming from down the street and that you’re really eating locally, this is really no longer the case. The globalization of the food industry means that your products are coming from all over the world. And it may not make a lot of sense, but you are in fact, probably consuming in things that you don’t even think are dairy products, like muscle milk or sports drinks. If you look at the protein and where it comes from, it comes from powdered products, either skim milk, or dried whole milk or whey products that are by-products from cheese manufacturing. And some of that, much of it actually, originates from New Zealand, a country that has an abundance of paratuberculosis. The product of greatest concern, in my estimation, is infant formula. Epidemiological suggest that, in humans, the longer a woman breastfeeds her baby, the lower the likelihood the baby might develop Crohn’s disease. So the flip side of that is, if the baby’s not drinking mom’s milk, what is it drinking? Usually it’s a canned, powdered formula product made from bovine milk.
In a very recent study using very elegant, new technology that is much more sensitive than past technologies, in cooperation with a researcher in Belfast, we tested 60, over 60 products from around the world, finding 40 percent of them positive for live MAP bacteria. In the U.S., in the subset of samples that came from the U.S., the number was 56 percent. And again, these products are being imported. They’re made from powdered products that, powdered milk and whey products that originated from all over the world. So I’m very concerned that we may be exposing the most susceptible human being, the newborn infant, through contaminated infant formula products.
This is another dairy product, that it may not be very tasteful to think about, but when dairy cows end their productive life, when the farmer says, “You’ve given me enough milk, you’re no longer making as much money as other herd mates,” the cow is sent to slaughter. These cows that are sent to slaughter are bright, alert, ambulatory. They have no fever, they’re not behaving sick. They’re just skinny. And so they pass inspection as a live animal. They go to the slaughterhouse and the inspectors look at the carcass and they pass inspection in the slaughter plant because there’s no pathology requiring condemnation. And these cows become hamburgers. So what we do on the farm, because we have no way to treat these infections; There’s absolutely no treatment in veterinary medicine for this infection. We kill all of the animals that we find that are test positive. But sadly, as we work to control the infection by killing these animals, they’re simply being fed back to the public. And not all Johne’s cows are thin. This cow was in a study I did in nine dairy herds in Wisconsin proving that we can control this infection, and this cow was selected out of the herd because she had a strong positive blood test. The protocol said this farmer had to kill that cow; send her to slaughter. He didn’t believe me that the cow was infected, so I bought the cow. I don’t think I got a good deal, but it was for $1,000. I took the cow to the university and took it apart like we would do an autopsy, and we found paratuberculosis bacteria everywhere; blood stream, liver, spleen, intestines, it had a disseminated infection. All parts of that animal were infected. That animal became a kid’s meal. Americans consume about 50 pounds of ground beef per year, so it’s an easy, logical vehicle. And the hamburger, which really made its appearance in the global food supply only in the 1950’s, is now obviously a major staple of the diet, not only in the U.S. but elsewhere in the world. Will heating kill it? Only if you cook it to a very well done condition. And there’s only one or two research papers that have attempted to verify this, but if your hamburger still has flavor in it, then it probably hasn’t obtained a sufficient high temperature.
And this is another dairy product. This manure is very high in nutrients and in a best effort to recycle these nutrients in nature we spread manure liberally around the land to rejuvenate the soil. And this organism, when spread on the land, will contaminate the land, and stay contaminated for about a year. But more importantly, when it rains it will run off with that rain water into lakes and streams which may become part of the domestic water supply. Some cities will use deep well water, like Madison, Wisconsin. Other cities on the coast will use lake water. And chlorine will not kill this pathogen. So in summary, there are many, many sources. It could be a variety of dairy products. It could be meat products. It could even be surface waters distributed through the domestic supply system. And there’s a susceptible host which I think, if it’s a human at all, it’s going to be the very young human. And it may not take very many of these bacteria to cause infection in a human. What will happen then? Many, many years will transpire before that young human shows up with clinical disease. In animals, we know that the dose of bacteria that they ingest as youngsters strongly affects the rate of the progression of this infection. So for some it will be very quick, before the age of 10. For others it might not be until the age of 30, or longer. There already are agencies, international agencies, suggesting that the best way to deal with this is to make sure all of the raw products originate from herds that are totally test negative for this infection. Your meat, your milk, your cheese; everything should come from a test negative herd. This is not being implemented yet.
So let me cut to the chase here. You’ll probably find this extremely distasteful and you might find it appalling, that veterinarians, and farmers, and the USDA, and the FDA are allowing this to happen. But the kicker here is that nobody in the medical community has said this is a human pathogen, so there’s no obligation for the food industry or anybody else to prevent this from getting into the food supply. So if and when the medical profession decides that this is in fact a zoonotic infection, jumping from animals to humans, then there is a strong infrastructure in place to be able to control this problem, get rid of it in herds and assure that all of the raw products going into the food supply originate from non-infected animals. That’s my message. Thank you.