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Cow research benefiting human health? Yes!

Cow research benefiting human health? Yes!

24/10/2017
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Merogenomics


Everyone agrees on the importance of research to make medical progress. How this actually occurs is poorly understood in the general public, but it is assumed that once a treatment enters a clinical practice, it has been well researched. One of the areas of mystery is the role that research on animals plays in the progress of both human and animal medicine. But rather than getting into a debate on the ethics of animal research for human welfare, I wanted to point out a curious example in how agricultural research can also benefit human health. Prior to starting a business in genome sequencing consulting, I worked in agricultural genome studies research, specifically cattle. I wanted to increase my background in technology use, and took the first opportunity to enhance my education.

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It was a very rich and rewarding experience, especially on account of what I learned about animal welfare. I have always been sensitive to this topic, and even for a large portion of my life I was a vegetarian. Not because I think it is wrong to eat meat, but primarily because of my concerns regarding the treatment of animals. Well, my biggest surprise was to learn about the kind of effort the industry players went to towards ensuring the best animal welfare. I went to conferences, visited farms and research facilities, and my worries were completely turned around. I was in fact amazed at how well Alberta cattle are treated. Of course now I'm biased, but I think Alberta beef is going to be some of the best quality one could ask for. Now I am not going to preach that it is all because every single individual is some kind of animal worshipper. No, it's about business and money, but that also means making sure the animals are healthy and well, so that the meat is the best quality.

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And not that there isn't a sad side either. I studied and learned lots about what diseases plague animals and what infections kill them the most. But obviously no one wants that. And constant research is taking place to enhance animal health. It's not just about meat quality. The industry is keenly aware of the public desire and demand for meat of high quality, but also for well-treated and healthy animals, and the industry has definitely been trying to respond. What people don't know about is how many millions of dollars are being invested into research dedicated to these topics. It is an enormous investment, it is very complex and difficult work, and it is very high tech, including the deep analysis of animal genomes.

I quickly learned that advances or insights gained in livestock research (or animal research in general), can also be translated toward benefits in human medicine. I was one of the authors of a publication espousing the benefits of genome research towards improving cattle health from infectious diseases. One of the original sections that did not make the cut was actually one of my favorites, and that was the implications for human health. It is time to bring it to light.

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As the article was written for a scientific journal, this will be very heavy in science jargon, so be forewarned. It will be your chance to delve into the world of science as if you were a scientist yourself your whole life! Which is ok, because I always like to think that there is a bit of a scientist in every single one of us. ;) But before we proceed, let me introduce you to a term that is very hip in the molecular sciences world, and tossed around like candy on a Halloween night. So it couldn't be left out!

It is a biomarker. And to give you a clue as to how hip we are talking about, thousands and thousands of papers have been published on biomarkers, most of them probably not true, and will never be able to be confirmed (that's science for you, stumbling in the dark until enough evidence can be accumulated to produce the light at the end of the tunnel).

So what is a biomarker? I could give you a fancy proper definition but it would be a mouthful. It is basically anything biological that can be measured and that is clearly indicative of a specific biological event taking place. So in theory, even an image can be a biomarker (think of MRI scan), but most often it is associated with a measurable biological molecule.

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Another word to define is a phenotype. Ok, this is not a fancy hipster term, but it is related. It's been around for about a million years now, and it means the detectable presentation of a specific trait. Like your eye color, the size of your nose, the size of your anything, how much you produce something in your body, etc. You take this phenotype information and it can help you in assessing if you are sick or healthy, or it can help you prognosticate future outcomes. So a phenotype can be a biomarker, but it doesn't have to be. A phenotype is a broader term than biomarker.

Armed with that knowledge we can proceed.

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Knowledge of cattle biomarkers in response to invading pathogens could be used for future disease diagnosis. Knowledge of these biomarkers could potentially act as a preclinical model for human therapies. The potential benefits of such research investments will not only be realized in the lower costs of disease treatment in the cattle industry, but also provide important clues to the design of safer medicines for humans. As is the case with human medicinal research, costly mistakes in unexpected treatment side-effects do occur. Knowledge of phenotype – including biomarkers – due to targeted drug treatments, learned in attempts to improve the health of other animals, would be immensely valuable in guiding drug development for humans, where medicinal studies are increasingly more expensive, with decreasing probability of success. Livestock animals are particularly good candidates for genetic studies because a large number of animals with short lifespans and controlled mating are available, thus knowledge evolves more quickly than in human studies.

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For example, work with bovine respiratory syncytial virus (BRSV), has potential benefits to human health, as BRSV has a high degree of genetic and antigenic similarity with human respiratory syncytial virus (HRSV). HRSV is the single most important cause of acute lower respiratory infection in children under five years of age, and is one of the major causes of childhood morbidity and mortality worldwide.

Due to the similarities of infection pathogenesis in bovine and human versions of the virus, the development of a BRSV vaccine could have important consequences for humans, for whom no vaccine is available. This can be demonstrated with recent experiments involving calves infected with BRSV, precisely as a potential animal model for the process of discovery with human benefits in mind. Affected animals treated with an experimental GS1 compound showed reduced viral load, disease symptoms, and lung pathology. GS1 is a close structural analog of GS-5806, an inhibitor of the fusion between the viral envelope and the host cell membrane, and which recently was also shown as a potential successful treatment in humans. As exciting as these promising results are, novel antiviral compounds such as GS-5806 also need to be investigated for their impact on viral resistance development.

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Many of the pathogens affecting livestock can also infect humans. Mechanisms of disease propagation for zoonoses [disease agents that can infect multiple species] among livestock is of enormous importance to human health, illustrated by the fact that the majority of emerging infectious diseases are of this type.

For example, the sequencing of the Campylobacter jejuni NCTC 11168 genome allowed analysis of the genomic variability of the pathogen in Alberta feedlot cattle and in clinical human isolates. The high degree of similarity of the isolates suggested transmission of the pathogen between cattle and humans, which could account for the fact that campylobacteriosis is one of the most common bacterial enteric diseases in the Alberta human population. In a clear example of how the continuous building of sequencing databases aids in understanding zoonotic infections, genome sequencing was utilized to demonstrate the direct transmission of a bovine retrovirus from a calf to a human infant which resulted in diarrheal illness and the hospitalization of the infant.

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In another example, a 2012 outbreak of Escherichia coli O157:H7 in Alberta, a major foodborne pathogen with cattle as the principal animal reservoir, resulted in 18 people becoming ill leading to a $4 million lawsuit settlement, and imparted significant economic losses to the beef industry. Genome sequencing of E. coli O157:H7 (strain SS17) isolated from a super-shedding cattle allowed for a comparative analysis with additional O157:H7 strains and identified nearly 60 potential targets that could be contributing to this health risk phenotype. Identified variants pointed to an increased virulence of the SS17 strain, and suggested a relationship closer to human rather than typical bovine E. coli O157:H7 isolates, an important implication for public health.

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The article continues with more technical information, but data of this kind continues to emerge all the time. In another great example, one study linked bovine leukosis to breast cancer in humans. We are talking about leukemia virus from cows as a potential causative agent of breast cancer in women! I would say definitely worth further investigation.

Here is another surprise twist: the treatment of cows with ivermectin drug to combat the spread of human malaria. The premise is simple: feed a compound to cows that is non-toxic to them, but will kill the mosquitos feeding on the animals.

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But it can get a whole more complex than this. How about genetically engineering cows to produce human antibodies against the Ebola virus? Yes, this is real. Cows that have been genetically manipulated to no longer produce their own bovine antibodies, while containing active artificial chromosomes to produce the human counterpart, were injected with fragments of the Ebola virus to produce viable antibodies against the virus. It worked, at least in mice infected with the virus and treated with the purified antibodies.

The goal is to bring this research into a clinical trial to test if the antibodies could successfully be used in humans. The amount of work, planning, and scientific execution behind the development of such euphemistically called “transchromosomal bovines” is just staggering. So could be the payoff considering the potential of biologicals in therapies to numerous disorders.

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Other benefits are also present. By now more cattle have been genotyped than humans, with the Council on Dairy Cattle Breeding or the Canadian Dairy Network reporting more than 1 million genotyped animals late last year. This provides an important opportunity to actually showcase the advantages of such efforts in reducing morbidity and mortality and how such technologies could positively relate to benefit people. Knowledge transfer based on the development of methodologies in technologies can also be applied in humans, including data processing and management. This is definitely being investigated in humans, but why not showcase it with fanfare in animal studies?

I bet you never knew that so much could be learned from cows for human health benefits! Not to mention direct benefits to the animals themselves! That was one of the reasons that attracted me to that work so much as well. This message is often lost, but my work with an agricultural research company highlighted to me how much effort is being done to keep our animals healthy. And while normally the goal of Merogenomics is to help people gain access to genomic techonologies for personal use, if you are a cattle farmer and are curious how this technology can help your livestock (and your profits), we have amazing options available in Alberta to help you. Bottom line is, everyone wins with a healthy livestock.

 

This article has been produced by Merogenomics Inc. and edited by Kerri Bryant. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

 

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