Everybody, and welcome to this week's talking biotech podcast by Calabra. And we're back from hiatus and looking forward to doing a weekly podcast now from now until infinity and continuing to bring you the breaking news in biotechnology and the rationale for lots of good innovation so that you can participate in communicating how important this technology is to continue to drive innovations forward in agriculture and medicine so and conservation. Yeah, throw that in there too, but I figured the first step off should be a little explanation of where I was and what happened. We'll talk about that in a minute along with some really cool stories from what happened during that break. But before we get going, I wanted to talk to our sponsors.

So today, we're speaking with Aoi Senju. He's the what's your official title at Calabra?

I'm the CEO of Calabra.

The CEO of Calabra. Okay. So he's the CEO of Calabra. And, why don't you tell me a little bit about what Calabrio does? Let's start there.

Yep. So we build data management software for pharmaceutical enterprises, and we work primarily with preclinical discovery teams to make sure that the data is accessible, it's findable, it's searchable, and, solve a lot of the pain points that exist, in this space today.

Oh, very good. And and and why is talking biotech of interest to you? Like, why why is this podcast a good venue for you to have your name associated with and sponsor?

Yeah. So we first heard about Talking Biotech years ago, as listeners, and we loved the work that you were doing. We thought it aligned well with our target market. And we also wanted to, associate ourselves with the type of content that you are creating and the thoughtful type of leadership that you are, demonstrating, to your listeners. And so we reached out a couple of years ago now, and, we've been working together.

It's been great. We've really enjoyed it.

Yeah. I've enjoyed it too. You've been wonderful to work with, and I really appreciate all the assistance on many levels that have made this possible. For those who don't know what podcasting is like, the average podcast lasts 12 episodes for a reason. It's hard to get guests, it's hard to have good content, it's hard to, the production takes time, and these are all things that I are time and dollar consuming.

And so they're things that are usually in limited supply. And, and so, I always helped to open the the gates on that a touch and has taken many of the responsibilities, especially now as we kinda transition into this video format and some other additional formats. So what are some changes people may expect to see?

Yeah. So the first one is the one that you see in front of you, I guess, right now is the video component. Right? It's something that we've been talking about for a little while. And the great part about having a video component is that it supports panel type discussions because if you're having just a video component sorry, just an audio component, then it gets a little bit confusing if there's more than 2 speakers in that room.

But when you have a video component, then you can have a lot of different people. And what that means is that we can have a lot of new types of formats. So for 1, is the panel discussions, that we're currently structuring and getting ready and recording right now. Right? And in these panel discussions, we're inviting experts on subjects, that we might not have touched on in the past, because we personally lacked the expertise or there wasn't that much to talk about, on our own.

But now we're able to invite, a group of these experts, into that discussion and have, an effective discussion about new fields, whether it's about regulatory teams or translational teams or preclinical teams, and get a number of different perspectives on that.

Yeah. Although that's what I really like about it is it really expands my horizon. When it's me and a guest, I have to be the expert in the room talking to the other expert. And I have to kind of have a good plan going ahead as to where it's going to go. But when you have panels, I can kinda just be a fly on the wall and ask the dumb questions and let them kinda discuss and debate within themselves.

So I found it to be a very helpful format so far and, which some of these are recorded. That's why. They will be released over the subsequent weeks. So really good idea. Can you give us a few you mentioned the preclinical, the regulatory.

What are some of the other ones coming up?

Yeah. So we have a number of podcasts, on, like, business development type, discussions. So this is around, acquisitions, partnerships, licensing. So how do these big companies decide who they want to work with and how they're going to go go about working with them? We have a number of panels on regulatory side.

So how does the FDA, work with these big biopharma companies, and what are their incentives in playing a part in the, IND applications, the NDA applications, BLA applications. What we found, in starting to work with you in this podcast is that there's a lot of subjects that are quite complex, and it's a really rich field, and there's a lot of interesting things to dig deeper into. And we thought, it would be a great opportunity to, show the listeners, how rich this field can be through all these different top the topics.

Yeah. Yeah. It kinda lets them see behind the curtain, and that was always what this was missing. We talked about a good technology and maybe some guests would say, oh, the future application will be or it's in preclinical trials or it's in clinical trials or in some regulatory phase. And that was always kind of a black box for me as it well as many of the listeners.

So this gives kind of a texture and, maybe expands our potential listenership, which is what we would like to do. I guess I should mention that the monthly downloads have been the same for a long time and while many fields would say that's a bad thing in the world of podcasting where people get more and more choices, if you can keep the same audience, you're doing okay. So this big move seems to be something that will greatly augment, what we do and the number of people we can deliver to.

Yeah. That's the hope. It's to, cover a number of different subjects, and, we will still continue to hopefully produce engaging content that everyone has come to know and love. But we will be able to invite a number of these expert panelists to touch on new subjects to expand the listenership into, different fields that we might not have touched, touched on in the past and, in doing so, get new types of listeners that, would find this kind of content interesting.

Well, very good. Well, thank you very much, Al. We really appreciate all your support and for making this possible. It's exciting to enter into a new phase of this particular podcast. So thank you very much.

Thank you very much.

And for the rest of us who are sticking on, let me tell you a little bit about what happened to me last November when I had to go on hiatus. And this podcast, as I mentioned, is actually very energy dependent. It takes a lot to book these interviews, to arrange to do the interview, study ahead of time, and then do the production afterwards. And it's a lot for anybody to do and and for me, we, you know, my normal job as a professor, I'm teaching, I'm doing research, I have lots of undergraduate researchers, 4 really good undergraduate researchers who love lots of time, many things in my life. Just had a baby last year, you know, she's 10 months old now, and all these things together and then helping my wife farm.

She, you know, we're at the farmer's market every Saturday morning loading a truck at 6 AM. And usually that is preceded by me uploading the talking biotech podcast after engineering and producing it at midnight or 1 a. M. And so it has always been a very, demanding add on to our already busy schedule, but it's worth it. It's worth every minute and now after eight and a half years, I found myself just in a position where I couldn't continue.

It's mostly health related and those who you who remember I was in the hospital with a problem that nobody really could figure out. I was before Thanksgiving, actually the month of November, I was running fevers, high fevers, like 103 and more. And every day, every day running high fever, running, every night, running high fevers, and they would break, but then they would kick back on. And the continual rise and fall of the fever was something that a physician I went to, said this is very concerning. Let's, do all the blood work and and figure it out.

And I had all kinds of problems with liver enzymes. I had problems with, blood count was all over the place, and she suggested that, I, go for more testing. And she signed me up for all kinds of stuff from looking from everything from your regular cells that would be indicative of different blood cancers all the way through, ticks and other types of parasites. So it was a pretty wide range of potential problems. I have no no digestive no respiratory symptoms just high fevers and I had scored a false positive on a test for sepsis.

So apparently, I was, in bad shape with a blood infection and had to be moved to the hospital very quickly. So I went to emergency room and, a team of infectious disease specialists would see me daily and they could not figure out what was wrong. They ran every test in the book, did every scan they could do, and there was nothing to be found. And after a week in the hospital, they said, you know, still running fevers. So we're sending you home and see where it goes.

And, it was I was subject of grand rounds, which I thought was kinda cool. And they just couldn't figure out what was wrong. And there was one thing that was high, and it was cytomegalovirus. Cytomegalovirus, I wanted to get somebody on the podcast to talk about it. Cytomegalovirus is a common virus that infects 70 some percent of people.

It's one of these persistent viruses that just is circulating among a human population, and it's in the herpes virus family. It's, ubiquitous. I mean, everyone, most people have it and it's rarely pathogenic. But it can be in people who are immune compromised. So those who have organ transplants, things like that, you can see cytomegalis virus levels go up and it become pathogenic.

And these are the symptoms I was experiencing without, a, at least as far as I know a donated organ and so it was a real shock they to not know what was going on and the high levels of cytomegalovirus may not have been causal. They may have been a symptom of, so we don't really know what happened. All we know is that I had, as they said relapsing fever, which can be a rather insidious symptom. And the good news is, is that I didn't have any, recurrence of this. And they said, and if it comes back now, we get to look a little harder.

And in late December, I started running fevers again, feeling awful, and I thought, shoot us back. And it turns out it was only COVID. Best COVID test I ever saw. It's positive, so I got really happy about that. So bottom line is is I seem to be in perfect health.

Everything seems good. I'm excited to take over a new line with this video format and, continue with the talking biotech podcast. So what happened while I was away? All kinds of fun things. Yank over my notes here.

The video format is something I'm going to have to get used to dealing with because it's a whole another thing, and I just in the interviews I've already done, it's been a challenge to kind of do this without staring at a computer screen. I'm not sure how folks do it, but I won't do it very much. The big story while I was away was the release by the American Academy of Pediatrics. And I won't go into all the details on this, but they had a what they called a clinical report about the dangers of feeding genetically engineered or ingredients from genetically engineered crops to your kids. So American Academy of Pediatrics, a very respected, very historically, important organization for pediatricians and parents published in the journal Pediatrics that genetically engineered ingredients from genetically engineered crops are, your kids should avoid them.

And the article, what read like an anti GMO website, It used all the same types of mistakes. That it was and at first, I gave them the benefit of the doubt. They just made some mistakes, dumb mistakes, whatever that that we haven't done enough research on BT to know if it's if it's dangerous or not. Well, they say, well, we need more research before we know. They had a whole thing on glyphosate and how dangerous it was and cited work which either had severe limitations or was statistical machinations of existing research.

So statistical massages like what happened by Zhang et al 2019, was looked at later by Cabot and Terron and others who were experts in, in cancer epidemiology. They looked at these things and explained that they were using inappropriate comparisons. And so the long story short, the AAP article used information they should not have used to come to a conclusion that was not supported by the scientific consensus. So this was a problem, and I wrote right away to doctor Lewis First, who's the, the doctor Lewis First is his name. I didn't write to doctor Lewis first before I did anything else.

Doctor. Lewis First, he's the editor in chief of pediatrics, and he seemed to be sympathetic to the idea. And he said this is a report that goes out as peer reviewed. It's looked at by many people, so I don't know who peer reviewed it. I could guess.

And, it also had Phil Landrigan on the author list. So doctor Phil Landrigan has been historically associate at the Ramazzini Institute, the, what is it called? The American high Heartland initiative, whatever that thing's called, and all these kind of anti GMO history, organizations. So I complained about this to Doctor. First and instead of saying, what do you find objectionable?

You know, can we talk about it? He said, well, this is the way it goes. If you want to submit 500 words to post at the end of the article, then we can do that. So the invitation to post 500 words seemed ridiculous, especially when you're debunking a significantly large article that's got many, many mistakes. And those have been discussed elsewhere.

By the way, I have a YouTube video with Doctor. Nicole Keller and was on unbiased science podcast with doctors Andrea Love and Jeff Steiner and we discussed all of the mistakes so that's out there already Also wrote a very ranging piece for genetic literacy project where I dissected the darn thing line by line. So that that's that's out there already. Here's what you need to know about the AAP is that I submitted my 500 word rebuttal or not rebuttal, but just very soft correction. And, they didn't post it.

Went right in the trash, I guess. I also hosted an online webinar with, Doctor. Nicole Keller, who's a pediatrician in the Chicago area. And, and we invited the authors to join us on this webinar and didn't even get a response. So the, the journal will not correct it.

The authors will not participate in the discussion. And, then after this so I'm starting to see how this looks. Were these really just innocent mistakes, or is there an agenda here? And then a few weeks later, maybe early January, the AAP puts out their newsletter for physicians and features an article that matches in concept. The clinical report and cites the dangers that are cited in the clinical report.

The report suggesting that parents go organic and don't feed their kids anything with ingredients from genetically engineered crops because they're full of glyphosate and gonna kill you right that kind of thing that whole that whole story. All right. So the problem here for me is is that we all we talk about is why we should trust science because it's self policing. And here we did some good self policing that needed to be done, and it was ignored. And this is what bothers me as a scientist is that if I made a mistake in an article and someone called me and said, you know, you made a mistake, this isn't right.

I would be petrified. Back when I was a grad student, our post doc, I published an article where I accidentally put a micro instead of a 1,000,000 instead of a micro for a solution that needed to be made, and people couldn't make the solution because you couldn't dilute the stock enough to get to the to to that at a milli level. Anyway, when I found out about this, I couldn't sleep for weeks. I mean, I was absolutely crestfallen because my, is my master's degree advisor said things stay in press an awfully long time And here was this really cool technique that very few people could execute that had an error in the solution needed to make it happen. And it bothered me so much that, it just was amazing to me that ever since then I've been extremely careful to proofread everything a million times over.

It's just so important. But the fact of the matter is is that here I was correcting scientists and physicians about errors that were in their printed work and they didn't care. And this shows you the agenda. Their job was to push the anti GMO message. And, of course, this was very well received by USRTK, by GM Watch.

They're like, see, the physicians say it's bad. And decades of good progress in education around genetic engineering or crops and and the relative risks and benefits of the products is starting to unravel by people who should be on our side. And this is a major problem. I I just was so disappointed that, that the AAP Journal responded the way they did and that these, physicians responded the way they did. Because instead of engaging and figuring out what is right, here's where you're wrongful to here's what we know.

They ran from us and they hid from us and they refused to engage. So their mission is accomplished. This information is published in a prominent journal, and in that place, they will continue to misinform physicians and parents, which means every one of you listening needs to work harder at properly informing physicians and parents and getting out into social media and doing a better job helping to separate the myth from the fact and discuss the realities of risk and benefit. So one of the other big things that happened was that, what else did I have here? That, the, therapy for sickle cell disease became approved by the FDA.

And they approved 2 drugs that were the first two gene therapy treatments for sickle cell disease. And back in the Talking Biotech podcast series, I spoke with the researchers from Vertex Pharmaceutical who discussed what this was and what this wasn't. And what this is so why this is so amazing is because about a 100,000 Americans, African Americans usually of recent African descent suffer from sickle cell disease And it's debilitating. It's painful. And at very young age causes a very, severe problems in quality of life.

Painful disorders, problems in joints, all kinds of other issues with anything that's got a small diameter blood vessel and and it becomes very debilitating and it causes a short life. And the new therapy is fantastic and we go into those in detail there, so I won't go into detail here, but it basically involves taking someone's red blood cells or their actually another stem cells separating out their stem cells, taking those stem cells and engineering them to produce the correct version of beta hemoglobin, not the mutant form that leads to a sickle cell. You engineer the, the STEM cells, ablate the bone marrow chemically or with radiation, probably chemically these days, and then, put the bone marrow cells or the stem cells back into the bloodstream where they find their way into the bone marrow. That's where they go. They know how to get there.

It's pretty cool. There they populate the bone marrow with the new and corrected version of beta hemoglobin, which is the one that causes the problem in sickle cell disease. The first people who've had this treatment are fine, cured. And some of the big, you know, debates have been more along the business side. Like, how do we how do we price a therapy that someone only has to get once that costs a lot to develop?

You know, those are good problems to have. So, a something like sickle cell disease may be a thing of the past and for those of us who are interested in science communication, it's a sterling example of how these technologies can be used in very favorable ways to help eliminate disease and suffering. So I hope you learn more about that. Revisit that version of the podcast and share with friends because that's a huge breakthrough for for all of us and and for those who suffer from the disease and their families. Closer to home, we've had a real science breakthrough on a different level That here in Florida, USA, we've had citrus disease that's led to about a 60 some percent decrease in the crop of juice oranges.

And it's a huge blow to our state's economy, where we used to have packing houses and logistics and trucking and all the places that went along with the farming. The farms are being converted into office complexes and sprawling suburbs of Orlando and, and then further downstate. And once that land is out of agriculture, it's gone. So a state industry, that made us, you know, agriculture was always number 1 or number 2 in the state is, waning because one of our anchor industries is suffering. And years ago, those who were in charge, like, actually Coke and Pepsi, big organizations that, that, produce the juice for Tropicana and, Minute Maid, Coke and Pepsi, Coke, Minute Maid, Pepsi, Tropicana.

They decided they didn't wanna have genetic engineering used in any of the new varieties. And back in 2,005, many of us said, why not? This is what we need. We need to have all tools on the table. Maybe there's something that'll come from traditional breeding and and some stuff did come from that, which shows greater tolerance.

But we need to have genetic engineering as part of this equation. And over the years and the 20 years since then now, researchers have found solutions that have been confined to greenhouse space. They look good. Many cases, not perfect in many cases, but seem to have an effect at least in slowing the progress of the disease. Maybe they have an effect on yield.

There's a lot of, you know, asterisks on this, but other issues that would be worked out down the road. But, but we saw a complete abandoning of a technology, back then, at least as far as the industry was concerned. Move ahead to 2023. And at the end of last year, there was discussion about how the industry would be fine to support it if we could try it now. I gave a talk at the International Citrus Beverage Conference in, in, whatever September.

And my my topic was, what if we could have a do over? Would we do it differently? And here's what we know now that we didn't know back then, and here's where we might be if we would have done. I would have not excluded technology from the possible solutions and someone in the audience from Coca Cola thought it was such a brilliant talk. He invited me to Coca Cola where I spoke to a large group of folks including administrators and upper level folks who heard the message that maybe we need to do this again, rethink this.

And at the same time, the growers were very excited to hear that industry was changing its tune not because of me by the way, it was it was in concert with my talk. I think most of these changes were well underway before I gave my presentation. But they have approved money for a citrus transformation center. So University of Florida will be producing the next generation of trees, which may or may not contain, genetic tweaks through genetic engineering and that, there's breeders that are doing a great job at increasing tolerance of rootstocks and cyan varieties. So the the part underground, the part above ground, that is resistant to the disease or at least tolerant of the disease.

So you, the difference between resistance and tolerance. Resistance is you don't get it. Tolerance is you get it and you live through it. And I think the trees that now can become infected and still survive, are looking much better. Now with some genetic engineering tweaks, maybe that will even be better.

So significant investment in the future of citrus and, very exciting times ahead for the citrus industry. I think, time will tell, you know, it can, can the speed of technology implementation and then creating 60,000,000 trees go faster than the, the need for development for old people from all over the world moving to Florida. Your retirement dollars go farther here. We have a 1,000 people a day that move to Florida. So 7,000 people a week need a place to live.

And this is where our agricultural industries are feeling a little bit of pressure. All right. So those are 3 news stories. In the future going forward, we will have panel discussions. We'll talk about news stories.

We'll, have some other types of, of of media that will happen more likely than once a week, which will be a new thing for me and lots going on going forward. So thank you. Thank you. Thank you for coming back to the talking biotech podcast as we move into episode. I think this is 431.

We'll regain the weekly series if not more frequently, starting now. So thank you very much for listening and for watching, And we'll talk to you next week.