Guests: Dr. Chris Ashwell & Chandler Keck from North Carolina State University Tonight, we're going to switch it up a little bit and address some issues within the monogastric realm, but the ideas are ones that are generating a lot of interest across all segments of animal agriculture. And that topic is transgenerational inheritance.
Guests:
Dr. Chris Ashwell, North Carolina State University
Chandler Keck, Graduate Student, North Carolina State University
Tonight, we're going to switch it up a little bit and address some issues within the monogastric realm, but the ideas are ones that are generating a lot of interest across all segments of animal agriculture. And that topic is transgenerational inheritance.
Dr. Chris Ashwell discusses different research studies supplementing nutrients inside of the egg. He described a study that introduced a nutrient to the egg that ultimately had a negative influence on another trait. Trying to understand the equilibrium is always important. 10:30
Chandler Keck described his research and dissertation focusing on various stressors, mainly stocking density and feed restrictions, in poultry and how they affect each bird, as well as the transgenerational effects to the progeny of that bird. 13:45
The conversation then went on for Dr. Chris Ashwell to discuss clones of highly productive milking females in the dairy industry and how that relates to the poultry industry. The difference between species is, birds and reptiles have higher rates of new mutations, or variants in their sequences. The poultry industry is taking advantage of that by focusing on specific characteristics within superior individuals to change the heritability of these characteristics over time, instead of cloning. 20:00
Adding to the conversation, cohost Dr. Zack Lowman discussed a few research projects he worked on regarding early life feeding changes. Some producers are trying to get the birds as big as they can, as fast as they can, but their skeletal structures cannot support the weight at that early stage. He also discussed the research being done on sex ratios, and the statistical differences in poultry. 23:33
We continue with Dr. Chris Ashwell discussing the importance of more data for industry efficiencies and optimization of animal agriculture. But we also must be aware of how consumers are viewing our products in terms of animal welfare. We can grow a safe, efficient food supply, but must be cognizant of consumer concerns. 25:29
Both our guest experts discuss the financial impacts of restricted feeding and if the resources used on the individual bird will be amplified in the enormous population structure in a positive or negative way. 38:07
Closing out the conversation, Dr. Chris Ashwell discusses the idea of machine learning for big data. In machine learning you can analyze data you are currently focused on, while also seeing trends over time. Patterns might be discovered that are not being seen when focusing on certain values. 59:03
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Scott Sorrell (00:00:07):
Good evening everyone. And welcome to the Real Science Exchange. The podcast where leading scientists and industry professionals meet over a few drinks to discuss the latest ideas and trends in animal nutrition. Tonight, we're going to switch it up a little bit and address some issues within the monogastric realm, but the ideas are ones that are generating a lot of interest across all segments of animal agriculture. And that topic is transgenerational inheritance. Hi, I'm Scott Sorrell, one of your hosts at the Real Science Exchange. We'll have all first-timers joining me tonight. First, Dr. Chris Ashwell from North Carolina State University has joined us at the pub. Chris, we talked to you during the real science lecture series back on May 11th about the epigenetic impact on poultry, and we're excited to continue that conversation here tonight. First, what's in your glass? And then you mentioned during your webinar that the first 1000 days of human life, starting at conception is very important for programming us for the rest of our lives. And then you made the analogy that the broiler spends their entire life in this early window of influence. Can you expound on that just a bit for us?
Dr. Chris Ashwell (00:01:13):
In the glass is a gin and tonic- just in that light and refreshing mood today. And I appreciate the question. So in the human world, that first 1000 days is thought to be when a lot of environmental, environmentally controlled aspects of development are modulated. And if you use that thousand days, so let's just take a round number, the first three years of development in a human based on its projected lifespan. And then we convert that back to, uh, poultry or chicken. Um, the broiler that we incubate and hatch and growto go into the meat market is still within those first 21 days of incubation and 42 days of, of growth within that first 1000 days. So equivalent to humans. So I think there are lots of opportunities, uh, to influence the performance of thoseanimals so that we can maximize not only production efficiency, but minimize environmental impact, create product that is wholesome andgood quality. Quality matters of course and, and provide, uh, nutrition for our growing population. Hmm.
Scott Sorrell (00:02:37):
Very well, thank you for that. And Chris, I see you brought a guest with you here tonight. Would you mind introducing him?
Dr. Chris Ashwell (00:02:44):
Uh, thanks God. So, uh, Chandler Keck is joining us today. Chandler is at the end of his PhD program. He is a PhD candidate in the comparative biomedical sciences program at NC State University. So welcome Chandler.
Scott Sorrell (00:03:01):
Yeah, welcome! So Chandler, welcome to the exchange. And first I'll ask you the same question. What are you drinking tonight? And then I'll ask to see if you've got a story about Chris that you can share with us.
Chandler Keck (00:03:12):
First off I'm drinking, uh, Heaven's Door Bourbon that was graciously provided by you guys. First time having it, and it’s apretty good si. As for a story for Chris. Um, if, if anyone knows Chris, he's a hands-off kind of leader, tells you what, what, what the expectations are and lets you go from there. He's seen me waddle around a couple of times and in some experiments, but he, he finally, uh, steps in at the right time and helps out then. And I think the biggest example of that is, is the first project that, uh, first grand scale project that I ran at Piedmont research station, he kind of gave me the keys and let me run with it. Um, I made some mistakes around along the way and at the very end of it, he finally asked, he said, okay, what would you do different? And I think that that really spoke to how the way he, he mentees somebody, or mentors somebody. And I think that really helped out to get a much broader look at things instead of trying to focus on all the small details that go along with a project, he made sure I stepped back and looked at the overview and the impact of it.
Scott Sorrell (00:04:29):
Nice story. Nice story. And thank you again for joining us here tonight. Um, I also have a new co-host tonight for tonight's conversation. Dr. Zach Lowman is the monogastric technical lead for Balchem. And he's also from a graduate of North Carolina State. Um, Zach, what are you drinking tonight? And do you also have a story about Chris?
Zach Lowman (00:04:54):
I do! And I’m drinking a Miller light tonight. Oh, probably one of my memorable stories and some of the lab techs still make fun of me about it. This took us to a conference in Australia. It was my first presentation and we flew to Australia and I was pretty nervous and I'd never really given a presentation ,especially not in the national conference. And it was talking about, uh a novel heat shock protein. And I keptsaying “no veil” and several of the lab techs walk up to me and say “no veil”.
Scott Sorrell (00:05:39):
Well, that was a story about yourself, Zach. I'll have to remember that one. Well, I'm personally enjoying a, uh, Buffalo Trace tonight and I usually have a story to go with it. My story tonight is that my, my daughter got me this, this nice little snifter, uh, for Christmas and, uh, because we were locked down for COVID, she was unable to come home for Christmas. So I just recently picked it up a couple of weeks ago. So, uh, thank you, miss Hannah for this very nice class with the Ohio State Buckeyes on it. Appreciate that. So Chris, you received your PhD from the medical school at Wake Forest in biochemistry. Tell us how you came to be a researcher in transgenerational nutrition.
Dr. Chris Ashwell (00:06:19):
Um, so Scott, that's a funny story. Um, my work in, uh, in biochem at Wake Forest focused on, uh, how proteins get out of cells. And so we were really interested in tissues or organs that were responsible for protein secretion. So at a point in that time at wake forest, we would collect tissues as a source for that enzyme. And the source that we used was the Hanover duct. So this is a tissue in birds that were, is really solely dedicated to laying out, uh, the albumin of the egg white in an egg, and the machinery there was incredibly enriched in this enzyme that we were trying to study. So, for my PhD, we looked at substrate interactions with the enzyme and that sort of summarizes my, my PhD in biochem. When I went to look for a post-doc, there happened to be an opening with USDA agriculture research service up in Beltsville, Maryland, and they were interested in molecular factors that influence growth and appetite regulation in broilers.
Dr. Chris Ashwell (00:07:40):
And when I applied for the job, I think I might have been the only applicant that knew what it really, how to manage a chicken, how to necropsy a chicken and then work with the samples from there. So it was sort of serendipitous, but that created a pathway and a community and in, uh, poultry, genetics and genomics, which is quite small, uh, globally. And so there probably are about 20 or 25 folks that work in the area, uh, that I work in, which is, it creates a small community, but it also creates opportunities to come and talk to groups like you here today as a representative of that, that small community. So we all get on the speaker circuit, which is kind of fun and we get to visit folks in places that we never thought we'd we'd end up.
Scott Sorrell (00:08:34):
Hmm. Very interesting. Um, just kinda as a foundation for tonight's discussion, how would you generally describe or define epigenetics or transgenerational nutrition?
Dr. Chris Ashwell (00:08:45):
Well, so epigenetics is, in a nutshell, is any character that is transmitted from one generation to the next that is not encoded in the DNA itself. So epigenetic marks or epigenetic uh, signals or regulatory elements are those that are layered on top of that, uh, genetic information. And really what it's doing is telling the cell or the organ or the, the organism, uh, when to turn things on and off and, and that setting can be adjusted based on an organism's environment. Uh, so we talk about you just mentioned nutrition. So nutrition is part of an organism's environment. It can be excessive, or it can be restrictive. And so those aspects of nutrition can influence not only the organism that's consuming that diet, but also its offspring. And so we talked about that in our live session. And so the caring from, the experience that's being passed from one generation to the next is what we would describe as an epigenetic signal or a transgenerational effect.
Scott Sorrell (00:10:08):
Okay, interesting. Now, one of the things I got to, uh, to wondering was you know, if it's, uh, if it's a positive stimuli to the, the, the grandparent or the parent stock, does it always have a positive impact on future generations or can it, can a negative stimuli have positive impacts?
Dr. Chris Ashwell (00:10:30):
I think it can vary depending on the model and the, the sort of the, the approach and the tissue and what your target might be. And I'll give you an example. So we have a colleague here at at NC state, uh, that has worked on, uh, inovo nutrition. So supplementing nutrients inside the egg. And the idea initially was that if I provide the developing embryo with additional, let's say amino acids, let's focus on protein nutrition. That will upregulate, uh, the capacity for, uh, amino acids and protein absorption. Same thing could be true for adding carbohydrates that you may influence how carbohydrates are, you may up regulate that machinery to increase carbohydrate absorption. But what really happens is the, the bird is, uh, or the organism, is resourceful. So what happens when it's really easy and you have an excess of, let's say carbohydrates in the embryo they actually down-regulate some of that machinery because they don't have to work hard at it.
Dr. Chris Ashwell (00:11:47):
And they're looking for balance, they're looking for equilibrium. So there, uh, what actually happens is they will upregulate the amino acid machinery. And so there's this equilibrium that happens. And so we, we first observed that, gosh, it was a PhD student back when I first came to NC State AndalaFoi, she's Andala Tumor now. In the late 2000’s- 2004 or2005, something like that. Um, when they were trying to manipulate the early chick by, by adding nutrition into the embryo, what they saw was there was this compensatory effect. Um, the bird was, uh, happy with the amount of ability to uptake this excess nutrient. And so instead of worrying about that one, they upregulated the other machinery to try and compensate and create an equilibrium. So in that case, it was sort of a negative influence. You were of trying to effect change in one direction, but were ultimately affecting it in the other.
Dr. Chris Ashwell (00:12:49):
Uh, it always makes me think about resource allocation. So how an organism tries to take what it has available to it, and use it to its most efficient inthe most efficient way. And so when you make something more difficult for the organism to do, it will have to move resources to compensate for that. And so you may influence one thing that you're trying to move in a positive direction, but you may ultimately be negatively impacting something else in, in an, in an inadvertent way. And so trying to understand the equilibrium is always important to do. Hmm.
Scott Sorrell (00:13:31):
Interesting. Chandler, I understand you're going to be, uh, having your defense here in July. Uh, tell us a little bit about the, your time there at North Carolina State and, and, and some of the research you've been doing.
Chandler Keck (00:13:45):
Yeah. So, uh, my dissertation focusses on various stressors in poultry and how they affect the transcriptome of the bird's experience, and that stressor, and also how it's passed on transgenerational effects to the progeny of that, uh, the bird experience and said stressor. And, uh, two of the main stressors that I have focused on is stocking density in broilers and also feed restriction of broiler breeders. And the feed restriction seems most important to this, this kind of talk, but in broiler-breeders, we've been selecting for these birds to have, uh, increased growth rate and performance standards. And because of this we've had to restrictively feed these broiler breeders to not allow them to be as big as they could potentially could to, uh, for reproduction purposes. And though this is, uh, has benefits for the reproduction purposes. It is an added stressor on these birds prior to them actually producing the next generation. So similar to what you've been talking about, this added stress at a such a critical time in these birds lives for development purposes, not only has an impact on them, but it also through what we found through our research, that it has an impact on the next generation.
Scott Sorrell (00:15:08):
And how would you quantify that impact? I mean, is it an economicallyviable impact?
Chandler Keck (00:15:14):
We didn't really look at it from an economic perspective. We looked at it we looked at it through gene expression parameters through RNA sequencing. Um, but we did see, uh, signals that seem to point to epigenetic mechanisms being induced due to this. We have not got around to actually measuring the DNA methylation, which is what, it's, what, uh, our data suggested. Um, though I do think it's, it's a, an avenue that should be explored further and upon funding, I think it's an avenue that I hope Chris pursues. Um, hopefully after I'm gone.
Scott Sorrell (00:15:49):
You have a job lined up yet? You know where you're going?
Chandler Keck (00:15:51):
Not yet. Um, I'm open ears. So, if you know of anything, please let me know.
Dr. Chris Ashwell (00:15:57):
You know, Chandler's project involves very specific feeding programming and management for broiler breeders and the, our collaborator, uh, whose name is Martin Sweedoffat the University of Alberta up in, up in Edmonton has developed, uh, this technology and it's, it includes, uh, something that they call a feeding station. And this is uh, I described the size of it as a uh, a dairy bull calf igloo, you know, one of those little uh, plastic contraptions, but this one is stainless steel and it sits in a pan of birds. And it has a little ramp where birds actually line up to go into eat because they're, they know where their food is. They go inside the door, the instrument reads the bird ID, figures out how heavy the bird is and knows what the bird's target weight is supposed to be.
Dr. Chris Ashwell (00:16:55):
So then the door opens and the bird is able to move into the feeder location. The feeder gives that bird, the amount of feed that should be consuming at a particular meal. And when it's finished, it opens a side door and the floor tilts a little bit and the bird comes out and then the next bird comes in. And I think I remember Martin saying that some birds will go to the feeder 20 to 30 times a day and eat lots of small meals and others will, will want to go in and any fewer meals, but at, you know, for a larger amount. And so all of that can be controlled which is really fantastic for trying to understand what the stressors are on these breeder birds, as it comes to feed restriction. I will just give you an example of a story when you're in a broiler breeder facility, conventional and the birds are on restricted feeding.
Dr. Chris Ashwell (00:17:48):
The, my experience birds that were on every other day feeding. So they're not fed on the odd day, but they know they get really excited and worked up in the hour before they know the feeder is going to go on and they they're, they get very nervous. And so that just as a demonstration, that there is something, you know, physiological happening with these animals as a result of that restricted feeding. Um, I think the precision feeding is a really fantastic way in, in a research setting. And it could be at some point applicable out in a commercial setting to really manage and understand how individual birds eat. I just think it's a great tool. Yeah.
Chandler Keck (00:18:37):
The technology is itself is really fascinating creating, uh, each individual bird being a replicant instead of having to work with a larger pin or et cetera, it really is advantageous for research, but the behavior aspect of the feed restriction and the different ways it's implemented is another area that's absolutely fascinating. Or to me at least.
Scott Sorrell (00:19:01):
So when you guys are talking about precision feeding, it's mostly around quantity, correct. And not necessarily the you're not controlling specific nutrients or individual nutrients.
Dr. Chris Ashwell (00:19:10):
Yeah, that's right. So it's a specific feed, but the, you can track how much feed that bird should be allocated in a given meal on a given day. And you're monitoring that bird's body weight, maybe, you know, 20 or 30 times a day as it enters the feeding station. I mean, for folks who like data, it is, you know, it's a, it is a dream come true that they can, they have tons of it to play with.
Scott Sorrell (00:19:38):
Interesting. So you guys were talking before that, you know, these chickens, even though they're there, they're bred very similarly and they're doing their very best to make sure that they're, uh, monolithic in, in, in, in their design, but they're not clones, they're all different. Um, do you see us getting to using clones at one point in time, sometime in the future?
Dr. Chris Ashwell (00:20:00):
Um, I, well, anybody else want to take that one on? Well, in cattle, and dairy cattle in particular, there has been, uh, an effort in creating, uh, cloned individuals, cloned cows. Not, not so much concern with clone bulls, uh, but those really high producing cows are being cloned and those clones are being used in the industry. Um, I think it's viable in that situation where you have one animal who is responsible for an incredible amount of production capacity. Hundreds of gallons of milk- I can't even remember the number it's, it's larger than you can probably imagine that some of these cows can produce. When we think about poultry on the other hand, the only way to me that that would make sense is perhaps at the breeder generation where you have really elite, almost perfect individuals that you may want to preserve and continue on, uh, beyond their normal reproductive lifespan.
Dr. Chris Ashwell (00:21:13):
Uh, what I will say is a phenomena in, in birds and reptiles, is birds and reptiles have a, uh, different mutation rate than mammals. They tend to have a higher rates of new... mutations is probably not the right word, but new variants in their sequence that pop up. And so agriculture is taking advantage of that with, with poultry and with large populations and large distributions of uh, of, uh, criteria for phenotypes, they can go in and select superior individuals with the characteristics that they're interested in. Once you have those, you just keep selecting and that increased, uh, rate of new variants popping into the population hasn't been exhausted yet. So the, the heritability and I, I didn't have Zack inanimal...did I have Zach inanimal breeding? No, I had Chandler inanimal breeding at NC State. So the heritability of these traits, over time is not going away.
Dr. Chris Ashwell (00:22:21):
So that tells you that you still have potential to keep selecting for these, uh, economic traits generation after generation after generation, which is fantastic. Um, I think there is an example of the longest running project I think is in maize and corn. Um, and they've been selecting for, uh, over a hundred years and they have not observed any loss in the ability to improve those traits. Um, so I think poultry has a long, uh, future for continuing to be able to select for these positive traits. So I don't think clones are the answer. Got it.
Zach Lowman (00:22:59):
Yeah. And in poultry they do four way crosses typically, just because usually you're super high producingbig breasted birds that people desire aren't necessarily reproductively sound. So they have lines that are more egg based, fertility based, and then ones that are meat based and you cross them down so that your final production, your final terminal crosses great big, fast growing one, but your higher ups usually don't produce super great if someone, until you get them cross together.
Scott Sorrell (00:23:27):
Zach, while you have the mic there. Tell us a little bit about the research that you, uh, you performed there at NC State.
Zach Lowman (00:23:33):
I did alot of, I guess it was a nutritional environmental type conditioning. So I did some projects on, uh, calcium phosphorus conditioning, uh, in early life. I did some stuff with hypoxic incubation. Uh, also I did some work with, uh, an emufarm. It was, it was pretty exciting. But emuhave a lot of issues and there they've not been researched very much. So I did a lot of early life stuff on them because they it's very, really fast early on. So you actually have to slow them down or else their legs give out because they're such big birds, uh, similar to turkeys, but much, much worse because they're so big. So a lot of the producers aresmall backyard people that are doing it. So they're trying to get them as big as they can as fast as they can, which it doesn't work out very well for, for emu,
Zach Lowman (00:24:18):
And I also did some interesting stuff on, uh, I guess it was the sex ratio because it's resource allocation. Uh, it was actually one of our undergrads ideas and, uh, he was excited and actually there's some... Kade, he's actually a vet now. We're working on that paper a couple of weeks ago, and finally got it submitted for publication. But a wild birds...so depending on where you're at and stuff, you know, in, in the wild resources are sometimes more available and sometimes less available. And there's actually quite a bit of research on it where the birds will skew the sex ratio based off which one, uh, I guess, is more desirable or less I guess, least costly nutritionally to produce. So, uh, we, we actually kind of worked on that in layers in this case because the layer industry has a real issue with extra males. Uh, so we, uh, we kind of found a little bit of a skewing and we found a massive statistical differences in this poultry, also.
Scott Sorrell (00:25:23):
Chris, any other, uh, areas we need to drill down in, on this precision feeding concept?
Dr. Chris Ashwell (00:25:29):
Well, I, I think it's definitely a useful tool. Um, I think we have not exploited all of the avenues that it could be used to investigate,because the equipment is, is not, it's not expensive and it's not off the shelf right now. Um, there are sort of equivalent systems in, uh, that are used in cattle and small ruminants and in and swine,but primarily they're used in the breeding, uh, process where they're trying to identify animals that they want to include in their, uh, selection programs. Um, some, some poultry producers are using something similar as well that track the individual behaviors of, of individual animals. What they tend not to be doing is distributing feed based on that particular animal's dataset. They're just tracking, they're not, uh, controlling, which is a little bit of a different perspective that precision feeding has.
Dr. Chris Ashwell (00:26:35):
I think the trend is, is clear in modern agriculture, that more data is better and, uh, uh, well in, in all probably science and that sort of realm more data is always better. And so I see it having, uh, being a major player moving forward and trying to understand how animal agriculture, uh, can be optimized. Um, we're, we're always under pressure to, to justify management technique. You're justifying feeding programs. You're justifying whether the animals are experiencing positive welfare and so on. And the more data that you have, the easier it is to defend that the animals are experiencing a, uh, and that have a positive life experience. I mean, they don't exist unless they're, they have a purpose. Um, we wouldn't be breeding as many broilers as we are. If there was no market for them to be consumed by, uh, us humans, or maybe they go into the pet food supply, wherever they go.
Dr. Chris Ashwell (00:27:45):
Um, there's there they exist because there's a place for them to, to end up uh, animal agriculture is has its own dilemmas because we've gotten really good at growing animals, uh, really efficiently. Um, and, uh, the safety is great and but yet we get criticized because those animals are ending up in the food supply. So it means you have to understand why they exist. And then if the more data that we have that the life of the animal is a, is a positive one. Um, you can, uh, re easily argue away those notions that the animals are being treated in a, in a poor way. Mm Hmm.
Scott Sorrell (00:28:32):
Very well Chandler. I know you're looking forward to being gainfully employed here, not too distant future, but, but if you were to stay, uh, and, and continue to research, what direction would you take that? What, what do you think needs to be done next? What's what would be the next step?
Chandler Keck (00:28:50):
Yeah, so I, I still think there, there is a further room for investigation of the, of this feed restriction. Um, from our perspective, we didn't really look at, uh, the physiological response, our team at, uh, university of Alberta. Our collaborators, uh, did work with, with some performance parameters based stuff, but we didn't really look about stress induction, and to characterize how much restrict to feeding actually induces this stress, whether it's anything under ad lib feeding, induces a stress, or is it a, is there a threshold to, to signify this, this stress induction. And as our data suggests there is implications of this, uh, feed restrictions on these brawlers. And it does point towards epigenetic mechanisms such as DNA methylation being, being a factor, or being induced by this feed restriction. And we, we do need to look at the actual methylation patterns of, of, uh, the samples to actually fully conclude this, this, uh, finding that there is epigenetic mechanisms at work here.
Chandler Keck (00:29:58):
We just looked at the end result, looking at the gene expression to see if there is differences observed first. So that was the first step of, of seeing if there is any implications at all because of this feed restriction next, just trying to figure out what is the actual mechanism at play. And, uh, and even more difficult question is, uh, why these birds are trying to, to prepare for this, because as we talked previously, if a bird's not in a good...doesn't have available food, why would they choose to reproduce? So there has to be implications on the reproduction side of things because of this feed restriction. And they're trying to prepare their offspring that they do reproduce for this time of feed restriction. So they're trying. And then compounding that there, then they're feeding the broilers ad libitum trying to grow them as fast as they can. Sothis is very conflicting ideas. Um, and this is a biological bird living organism. It's gonna, like, Chris's alluded, there's, there's give and take, there's balance to to these systems. So trying to figure out that balance while still having maximizing production is, is, uh, a tall task with a lot of questions. And I think I could spend years, years looking at it, I guess, if the funding was there for it.
Scott Sorrell (00:31:23):
Mm. Yeah. Great answer. So you brought up a topic, uh, DNA, methylation, methylation. Um, Chris, I think you've done some research on that. Uh, can you talk to us a little bit about that? Why is it important and exactly what is it?
Dr. Chris Ashwell (00:31:38):
So, uh, thanks, Scott. So DNA methylation is one of the mechanisms of epigenetic coding or tagging that can be done in the genome of an organism. And we've, uh, discovered this, uh, process, not, not myself, but the, the academy has discovered this process in most higher organisms, including plants. And it is a way for the, the organism to tune its experience based on its environment. And as Chandler alluded to, uh, that tuning prepares the offspring of that individual to be ready to experience that same environment. And so DNA methylation uses methyl donors, uh, that are present in the normal biosynthetic pathway, uh, that actually get, get shunted out of the one carbon cycle into, uh, labeling regions of the genome that really signal whether or not this particular gene should be turned on or turned off, uh, at a particular period in time or, uh, under a period set of conditions.
Dr. Chris Ashwell (00:32:58):
So it's, it's a valuable next level regulatory element in the genome, and it can be even nutritionally modulated. Because if DNA methylation is needed, and there's an inadequate source of methyl donors, then you're not going to get the appropriate methylation conducted on the, in the, at the genome level. Um, we've done some work where we have provided excess methylation resources or methyl donors in the diet, uh, that's um, in, can include folate, choline... It can includethe B vitamins. So they're, they're valuable, uh, components of that metabolic cycle. And by manipulating those, we've seen that we can have effects multiple generations later without any environmental stress just by providing the birds additional, uh, methyl donors in their diet. So I think it would be interesting to look at Chandler's description of the experiment where you've got where you've got, uh, precision feeding happening.
Dr. Chris Ashwell (00:34:17):
So you're, you're managing the diets of, uh, these breeder birds to be either close to ad libitum or to at a breeding company, target weights. Which in theory are supposed to optimize reproductive life later on and, and have that replicated with a standard commercial diet, but then have the replicare have excess, uh, methyl donors in the diet so that those birds may be better able to adapt to that environmental condition. What I, what I think is is really it's, it's in conflict. And Chandler described, this is in the breeder generation. We want to hold those birds back. We don't want them to grow as quickly as they possibly can. And so they are experiencing a restrictive environment, but we want their offspring to grow as quickly as possible. And we provide them with an excess, excess resources in their environment.
Dr. Chris Ashwell (00:35:34):
So what, what is that doing? What is the, what is the consequence, maybe the fact that we are feed restricting the breeder birds results in accelerated growth of the broiler generation and makes them more efficient because they were programmed, or they were tuned to be prepared for an environment that had limited resources. And then all of a sudden they're given, you know, you know, it's this unlimited supply of food. So I mean, I can imagine myself if I had been dropped on a desert island and I had nothing to eat, but, uh, coconuts for a month, and then I get picked up by cruise ship, I'm going to the buffet. Um, and I'm just gonna plop right beside the, the line and keep it, keep shoveling it in and, and maybe that's what's happening. And that, that might be okay. But I think without understanding the mechanism of how that's working, it becomes difficult to argue in favor of the feed restriction component, because there's, obviously we are able to see stress related pathways and molecules elevated as a function of that.
Dr. Chris Ashwell (00:36:55):
And my description of walking into the breeder house an hour before the feeder comes on and they get, they're already ready to go there. They're anticipating that feed. That tells you that there's something happening. Um, but, but that might be a reasonable uh, cost in order to make their progeny incredibly efficient. You know, it's, it becomes a, a big math problem that you have to be able to weigh what's happening, what I do here and what the costs associated with in the breeder generation. And then how does that translate to the economics of the larger scale broiler production? Because it's a, you know, it's a factor of a hundred or so maybe even more. How many- okay, experts, on the panel, how many broiler chicks result from one broiler breeder hen?
Zach Lowman (00:37:56):
Oh, so they average probably what, 200, about 180 eggs a year. So 80% hatch rate, and that’s on the good side.
Dr. Chris Ashwell (00:38:07):
There you go. SO what you're doing that to that breeder, that breederhenand how you're influencing her, ultimately results in 180... it's her contribution times 180 basically is what I'm trying to say. So the, you know, the expansion you just, it's a math problem, and the folks can do that math on, not me, but other folks can do that math and, and figure out if what is happening at the breeder level makes sense. And maybe it costs you a dollar per hen to do what you need to do, but it might have $180 impact on those broiler progeny. So I think it's, you have to look at it, you have to take a step back, right. And look at it. Um, we, I wanna know what's happening within the animal, and what's happening at the bird level, but you also have to take that step back and say, okay, whatever's happening at the bird level gets amplified in this enormous population structure.
Chandler Keck (00:39:09):
I also think it is important to note that, that these practices have restricted feeding date back to decades. And though there, there are a ton of great things about agriculture industry, one thing that that is prevalent, that I think is a weakness, is once we adopt a, a practice, you stick with that for long periods of time, without fully understanding the ramifications of that. And we've just recently been able to have the technology available to us to actually start exploring what is, what this these practices are causing. So I, I think taking us, like Chris said, taking a step back and looking at, okay, why do we do this practice? What are, what are the actual input implications of this? And why is this bird trying to adapt to this? To actually fully understand that, I don't think it's it's on our fingertips yet, but I think there's, there is an avenue for exploration that, that this could happen within reasonable time.
Zach Lowman (00:40:08):
So has Martin actually carried any of these, uh, test birds out to lay?
Dr. Chris Ashwell (00:40:14):
Um, yeah. So wait a minute. So let me ask you which what you're talking about. So you're talking about you, you would be, I think, asking about feeding great grandparents, influencing the breeders, and then the breeders influencing the layers.
Zach Lowman (00:40:31):
And how long has he tracked us out through it? I guess looked at his work recently.
Dr. Chris Ashwell (00:40:35):
My understanding is he has been doing the work in the breeder generation, so only one generation above the commercial bird. And then he's used the precision feeding equipment to, to manage the broiler generation. So you can use it for both. I think that's a great question because we don't have a whole lot of access to those, uh, birds higher in the population structure above the broiler breeder. Um, but a breeding company might be interested in looking at how the earlier generations may be influencing the progeny, for sure.
Zach Lowman (00:41:19):
Cause it's interesting on the pedigree lines, especially, I mean, it depends on which side and which line you're talking about, but on your meat line, do you usually do full feature pedigrees all the way up until, uh, up until market aids, but then instead of marketing them, you actually cut them back to restricted feeding to bring them back down so you can reproduce them. So, uh, you, you gotta go up then go down then restricted, then go back to full feed.
Dr. Chris Ashwell (00:41:43):
And some, some breeding programs we'll do SIB testing. So they'll have, uh, pedigree, birds that are, you know, in part of that population. And rather than challenge all the birds, they'll divide the families and they'll say, okay, well, this half we're going to hold onto and keep them ready to reproduce, but this other half we're going to treat them like they're broilers or whatever the model is and, and grow them, uh, you know, as quickly as possible and see then, okay, this guy is great or this hen is great. Um, but we grew them so large so quick, they won't be able to reproduce, but we have their siblings held back so we could use their siblings in our breeding program.
Chandler Keck (00:42:31):
That's very interesting. Um, I'm not as familiar with the grandparent, uh, feeding programs, but mammalian and human past studies have the time leading up to conception is just as valuable, from an epigenetic and effects on the next generation as the actual time ingestation of earth, time and pregnancy. So if they're having to restrict these birds prior to implementing this, this layingcycle, that's got to have a significant effect on the next generation as well.
Scott Sorrell (00:43:10):
What's kind of amazing me guys is, I mean, there's a lot we know already, right. But there is so much, we don't know... just so much we don't know. And we were talking one little slice, we're talking about nutrition, but I remember Chris in your presentation, you talked about using an example of, of, uh, a grandmother that smoked and the impact that, that had on the great granddaughter in terms of, uh, obesity. And I'm just wondering, you know, what other things is, what impact does heat or, or cold, or, you know, all of those things. And it's going to keep people like you, Chris, and, uh, employed for a very, very long time to try to figure all this out. Where's it going? What's next?
Dr. Chris Ashwell (00:43:55):
Wow. Okay. So there are so many variables, right? So you can't possibly test them all. I think it, no one could possibly test them all. And so trying to understand some of the easier ones to manipulate. So you mentioned heat or temperature. Um, I think that's a great one because, uh, I I've, I'm familiar with, uh, some of the work that's been going on in incubation and manipulating incubation conditions that, uh, birds, uh, some, it's almost like magic. The birds can be manipulated in side the egg during incubation, by altering gases in the incubator or the temperature of the incubator at particular times during incubation. And they are able to reset the body temperature of the bird. So they've been able to increase or decrease the resting body temperature of the bird, which to me is fantastic. How, how was this working?
Dr. Chris Ashwell (00:45:00):
Um, the, the, the idea is, you know, if the resting body temperature of a bird, let's just say it's a hundred degrees and that requires some metabolic maintenance, right? So there's energy being expelled to maintain that average body temperature. Well, if you can drop that body temperature by half a degree, the nutrient requirement for that half degree reduction multiplied by the entire life of the animal could be a tremendous savings on resources that don't have to go into maintaining that higher body temperature, as long as you're not always... here's that resource allocation idea. Again, as long as that adjustment is not setting the animal up to be more susceptible for disease, less able or less efficient at absorbing or metabolizing nutrients, then you've created almost a new, a new beast. You know, you've got a new variety available. Uh, we didn't, we didn't talk about this before, but I always like to tell students this, when you go to the, the hardware store, you go to Lowe's, you go to home Depot and you buy a tomato plant or a cucumber plant.
Dr. Chris Ashwell (00:46:19):
You almost always will see the word hybrid in there somewhere. And the reason is because the crossing of, of particular animals and plants with traits of, of positive effect. They don't always correlate with one another. Uh, as Zach said, you may have one that grows really well, but reproduces poorly. So then you have another one that reproduces really well, but grows poorly. So you just cross them. And the way hybrid vigor works is you tend to get animals or plants that are hybrids that perform the best. And so I think that it, it's our take, you know, sort of a real-world example of where, uh, genetics plays a huge role in, in folks' lives. And the future of animal agriculture is going to rely extensively on technology. Chandler mentioned that we're just now getting accustomed to using the tools that we have available to us. I don't think we fully understand the potential of using some of those tools yet. Um, but it's a process and it's constantly evolving.
Chandler Keck (00:47:36):
Similar, similar to what you just said. Um, you talked about all these different factors or variables that, that come into play, but you also had to think of it from an animal perspective. They don't see in the same light spectrum that we see, they don't smell the same things that we smell and relating it back to the technology that Chris talked about. Um, therehas been discussions with him about this new technology will say something about a nose. What was the name of it? Um,
Dr. Chris Ashwell (00:48:05):
Yeah, that's an artificial nose that can measure odor in the air. Um, do you want...go ahead!
Chandler Keck (00:48:13):
The artificial nose able to, to pick up things that the human nose isn't able to you and I can't smell when we walk in, we smell the ammonia and we're like, all right, we're overwhelmed by that sense. And we don't actually pick up the subtleties that are available there and, and there's opportunities to use this artificial nose, to detectthings that it could be nutritional deficiencies in the feces. It could be pathogens, some odor that's associated with those specific pathogens. So I think the, uh applications of these new technologies examine way, way beyond just the nutritional aspect of things, but there are ways to tie everything together. And it's just fascinating the, the opportunities that that can come, uh, come about by these technologies.
Scott Sorrell (00:49:03):
Yeah. Interesting. Chris, I kind of wanted to go back to the comment you made about being able to reset that, that the temperature of the chicks in the egg I'm reminded of something you said during your webinar, which is there's no free lunch, right. There's always, there's always a price to pay. And so I'm wondering what are, what's the unintended consequences of that? Is it going to impact them?
Dr. Chris Ashwell (00:49:25):
Think that, you know, you have an intended, you have a target, right? So there, the design of that experiment was, is there some way we could reduce resting, metabolic rate or a resting need for energy to come in and and they can do it, but then the question, my question then becomes, okay, what, what is, what are you giving up as a price for making this adjustment? And that's of course, limited to the things that you test. Um, we've seen lots of examples of, uh, things that have had really positive technology, uh, based um, implementation. And then later on you figure out, oh, when we did this there was this unintended consequence and we have to go back and fix it. And the, the dairy industry uh, breeding and the Holstein breed is a great example of that where one sire, uh, really was popular at one point because of, and I think it was protein percent in that, uh, bulls uh, profile for his offspring, for his daughters and unbeknownst, uh, there was a variant that came along with that increase in one trait that they cared about that caused a drop in fertility.
Dr. Chris Ashwell (00:50:57):
And if you can't reproduce, it's not getting you anywhere. And so they had to go back. So they went back and bred that back out of the population. So it was an unintended consequence. Uh, I don't know. Um, I mean, there are examples in the poultry industry that we've seen come and go. Um, when I was, uh, in my postdoc, we, uh, experienced this problem with ascites, which was a uh, an accumulation of fluid in the abdominal cavity of rapidly growing broilers. And then it kind of went away after about 15 years. And some of that has to be attributed to the breeders making selection choices that shift the population in a different direction. Um, we, we are experiencing, uh, wooden breasts that were experiencing muscle myopathies now. Um, I suspect that is it has a genetic component. I think they (breeders) have accepted that and they can select against it rather quickly, but there must be some positive correlation between a trait that they care about and muscle myopathies, otherwise it wouldn't have showed, uh, wouldn't have surfaced.
Dr. Chris Ashwell (00:52:21):
And so the, the reality is those breeding decisions. Between a breeding decision and when you can see the outcome in the birds, that we is like five years. And so it's a slow process. It does, you can't turn on a dime. Um, and so I, I trust the breeding companies to, to turn that around, uh, but then when they turn it around, what's the next thing going to be, you know, in five, five years from now or 10 years from now. So the, the sort of the beauty of epigenetics and manipulating the environment is you don't have to worry about making breeding decisions. You can control it to some degree, won't say you control everything by how you control the environment of that, uh, animals development.
Scott Sorrell (00:53:13):
Interesting. I'd like to turn it back just real quick, uh, back to DNA methylation, uh, our company Balchem has a ruminant division and we sell choline, uh, for dairy cattle. And we did an experiment at University of Florida where we had the treatment group. Um, the, the, the dams were fed cholineand, and another, the control was they did not have, uh, cholinein the diet. And we found that the offspring had enhanced immune function for the animals that came from the mothers that, that consume choline. And so they were exposed to choline in your grow. Has anything like that been done if you looked at, uh, immune function and DNA methylation in poultry?
Dr. Chris Ashwell (00:53:58):
So uh, that's a great example Scott of, of where andI suspect that the goal of the experiment was not to manipulate the immune function. It just happens to be that's what you saw. Right? So one of the, my former students who worked with methyl donors in the diet, and I think I talked about these in the, in the webinar also looked at, uh, performance traits and one of them was egg size. And so she saw an effect of egg size in subsequent generations. The other thing that she was she saw was, uh, the birds whose, and then I have to think of exactly what the conditions were. I think it, the birds whose grand parents, not their parents, but their grandparents experienced the high methyl donor diet had a higher immune response to an exogenous antigen.
Dr. Chris Ashwell (00:54:58):
And so in, in poultry, we typically use sheep red blood cells, as as a model antigen that's not infectious and the birds elicit an immune response against it. And then days later we can take, uh, a blood sample and measure uh, titr and just hemoglobination, simple assay. And I think she, if I remember correctly, it was about a 50% higher. I'd have to pull the slide... 50% higher, I think immune response in the birdswhose grandparents had the high methyl donor diet, uh, than the birds whose parents are grandparents, sorry, had a control diet. And remember the, the birds that we're testing all on the same diet, no high methyl donors, their parents, all on the same diet, no, no methyl donors. It was their grandparents are the only ones that had the nutrition manipulated. So that's just like, what the heck, how is this happening?
Dr. Chris Ashwell (00:56:05):
Where is this coming from? And, uh, some of the work that that Chelsea did was doing methylation sequencing. So, uh, she was able to, and we had, we had time and resources at the, at the moment to sequence the, the methyl sites in the entire genomes of those birds, the grandparents, and then two generations down. And what she was able to do was identify, and the number escapes me, but it was thousands of locations within the genome that had significantly higher methylation status or significantly reduced methylation status. And then the next step, which she's off in a career path now, but the next step for another student would be okay, what is, what are these changes in methylation at these specific locations in the genome actually doing in the animal? Um, so Chandler described this, but, but we were kind of on a fishing trip when we were doing his project with the precision feeding and multiple generations, and we collected a bunch of samples, but we said, okay, let's look at the extremes and see if there's anything else, if there's any differences. And if there are, then we'll follow them. And I think we actually, I was actually surprised at the number of differences that we saw. I thought it wouldn't be as, as, uh, numerous as, as we were able to detect. So then that leads you to say, okay, well, if I'm looking at the extremes, what's happening and, you know, sort of in a graded fashion all across the, the distribution of those extremes. As you said, it's a job security to try and understand where that's going.
Chandler Keck (00:57:59):
Relating it back, back to my work, we actually saw a significant differences in a similar test as Chris described of the effect of stocking density on immune function. And then when you look at the subsequent, uh, transcriptome profiles of these birdss, you do see genes associated with reduced immune response. And you're trying to connect the dots here, obviously that there's no full known association, but obviously these methyl donors provide them, provide these animals with more availability, to be able to pick and choose and adapt to these responses. And I think one of those key responses is obviously immune function to adapt to whatever environmental stressor through immunity to get through and provide for a next generation.
Scott Sorrell (00:58:52):
Good stuff, gentlemen, uh, any big ideas, big thoughts that we haven't covered yet, that, that the audience needs to hear about?
Dr. Chris Ashwell (00:59:03):
One thing that it's fascinates me is a new area of data analysis called machine learning. This is my new sort of favorite thing. And we're living in a, an era of big data where lots of data is being collected. And the typical way we look at is to say, okay, I've got this group of data and I've got this group of data. I'm going to do some statistics and are they different from one another? Or how different are they from one another? And machine learning is, is gonna bring in a new era of pattern recognition because the differences in these groups might not be statistically different, but the patterns that are occurring within them will be detectable by machine learning because it's, it's looking for a commonality in the data. And I can't, there are so many student presentations and faculty presentations that I've seen at conferences where they say, yeah, we saw this, but it, it was only approaching significance or it, it was numerically different, but not statistically different. And it makes me think and feel that, you know, if there was enough data there and they approached it from a different analytical model, that they might be able to discover patterns that they're not seeing, just because they're relying on a P value. Um, I think that's going to change a lot. Hmm.
Scott Sorrell (01:00:33):
Wow. That's a big idea. Yup. Very well. Gentlemen, they just called last call and it's a good thing. Um, I'm about out here, uh, like to get a couple thoughts from, uh, all three of you, uh, what are the next steps in epigenetic research in poultry would be one. And how will the imp how will that impact, uh, commercial production. Let's start with Zach.
Zach Lowman (01:00:57):
Well, clearly my interest currently is in choline. So I think it'd be interesting instead of using a, I guess, a methyl cocktail as I've used before to look at the actual choline, uh, affects to see if it has similar effects or if it's one of the other methyl donors or if it's just a combination of them. So I think that would be an interesting thing to see inpoultry cause especially since we've looked at it and, and, uh, the cattle we've actually been doing some, some, there's a huge trial there. I think it's at UNC inhumans that they're doing, isn't it? Scott? Yeah. They've been working on for several years, but I think it'd be interesting to look at it in the poultry side, them as far as Colin goes. Yeah.
Chandler Keck (01:01:36):
Relating it to that. I think if, if you do provide the, these animals with the ability to adapt more easily through these epigenetic mechanisms, you're going to see a lot of downstream effects of these, of the practices that we do do use in this industry. Um, cause I think it's going to exaggerate the actual results that we've previously seen in these subsequent generations. So I think providing these birds with these methyl donors will allow us to exacerbate the actual impacts of the, these decisions we're making. So I think it, it can only help to add these methyl donors to allow them more, more room for response to these different choices we are actually making on these birds.
Dr. Chris Ashwell (01:02:28):
See, I like that. I like both of those ideas. Um, the reality is you have to be able to do this across multiple generations to see what's really going on. And you know, humans...that's a challenge because you've got a lot long, a generation interval there. Cattle, a little bit shorter but doing it in poultry. And some of the work that we, we sort of started this with was in quail where we had really short generation intervals. Um, and you could go from one generation to the next, in two to three months which is really terrific. It's, it's the mouse of the poultry world. Um, and that the, you know, you can do things in small scale too, because they don't need as much as, as, uh, chickens do. And then follow that through multiple generations. I, I like the idea of, of using a single donor like choline, but as Chandler mentioned, I also agree that I think it will provide the birds with the enhanced means to adapt.
Dr. Chris Ashwell (01:03:31):
And so not just feeding them choline, and not feeding them choline, but adding on an additional challenge to try and force them to adapt in one direction or the other, and maybe that's temperature. That's an easy one. Um, it could be another, we may pull another nutrient out of the diet as a challenge could be feed restriction. It could be, it could be lots of things, but I think having some stressor there to push the birds to try to adapt or to that stressor, and then the having the methyl donor like choline either there or not there provides them the fuel for that adaption to happen. Um, I think that would be a great experiment.
Scott Sorrell (01:04:16):
Excellent. Chris, thank you for, uh, joining us both at the webinar and here at the exchange, exciting stuff you're working on. I really have enjoyed getting to know you and, and, and having here at the exchange Chandler, you're an exceptional young man. Uh, I'm a fan already. I wish you the very best, and I look forward to following your career. You know, this is, this is next level of nutritional impact is so important for all species and will continue to be a point of interest for years to come. I also want to thank all of our loyal listeners for stopping by at the exchange and sit with us while and have a few drinks and share some conversation. If you like, what you heard, please remember to drop us a five-star rating on your way out. And remember, you can also get a really cool Real Science Exchange T-shirt just by, uh, hitting the like, or subscribe button on your favorite podcast platform. And then sending us a screenshot along with your, uh, shirt size and address send that to anh.marketing@balchem.com and we'll send it out to you. Our conversations continue on the real science lecture series of webinars, uh, visit balchemanh.com/realscience to see upcoming events and past topics, or to view Dr. Asheville's full presentation. We hope to see you next time here at the Real Science Exchange, where it's always happy hour and you're always amongst friends.