Jim Penman's Bold Plan to Solve the Birth Rate Crisis

So welcome to the first specific Jim Penman Conversations podcast interview. And what we're going to do today is we're going to ask you some questions about the birth rate crisis and what you've been working on. And we're going to do episodes about different countries and a different bit of research to give people updated until the books release later in the year. So the first question will be about the research updates, because we went out to La Trobe University and it was a pretty, pretty nice ceremony that they did there as well. And you went and looked at the lab and all that sort of thing. So do you want to, first of all talk about where your research is at and what was that sort of deal that you did with La Trobe?

Well, we're setting up a separate institute within La Trobe University. It's in a building that's dedicated to businesses that want to advance their technology in conjunction with the university. So it's good. It gives us a bit more independence in what we can do. We don't have to employ everybody through the university, do what we want. It's going really well, actually. One of the things we've been doing is testing. We're looking to try and reproduce the beneficial effect of food restriction, which has got many benefits for health, but also for psychologically very powerful benefits, including things like improving mental health and coping with drug addiction, those kind of things. So what we've been doing is looking at drugs that could potentially have these kinds of effects. We've tested about a thousand drugs in brain cells and it's done by having a lot of micro capsules and you put the drugs in, you look for the effect that we're after. So we tested about 1,000 drugs. Looking at one is appropriate. We found 61 very promising candidates. And what we're doing is we're doing further essays and tests of those. We're considering things like toxicity effects, some of them might be harmful. When we have a group later in the year, we'll be actually testing them in animals and looking for, you know, reducing anxiety and so forth and improving parental care.

Just real quickly, how do you. Well, how do you witness that in terms of reducing anxiety or.

Well, with rats, you do it through what's called an open field test or elevated plus maze. There's tests where you actually send a rat out and you look to what extent they go into the open, which for rats is a very dangerous place. So you're looking for reps that are more exploratory.

And with the lab itself. So it's part of it. Is it called Epigenes? Do you want to just tell people real quickly what Epigenes is and how that sort of relates to this?

Epigenes is the company structure. It's a not for profit business, but it's a company structure that is investigating this whole business on how to improve welfare.

And how big is the team currently? Because it's quite big, I think.

Or I think there's about 12 people working full time.

12 full time, yeah, because it's quite. Because we looked at the setup, it was quite impressive. I know it was the first time you went to the lab and I didn't know anything that was in there. And we met one of your lovely people that work for you and they were explaining it as well. But how exciting was it for you to be in that lab? Because I don't think you've. You've been there before.

That's great.

Yeah, it's great.

I've been directing experiments for many years, but I haven't actually seen the lab in the new building at all.

Is there anything that surprised you is like any bit of equipment or anything like that or.

No, I know pretty much what they're doing. I meet with team members pretty regularly and we have half days and go through the search and I know what experiments they're running because I'm part of the design and the writing up of the experiments. Yeah.

So you might say I've got a hypothesis or I've got this idea I want to test and then that day will then come up with the equipment that you need or how to do the test or how does it sort of work?

Yeah, that's right. I'll say we want to investigate, for example, the dopamine reaction system and dopamine receptors, which is a very important part of this whole. Whole system. And so I'll say, okay, I want to do this and I'm not a neuroscientist, so I really don't know the details of how it's done. But another kind of thing. I know the sort of receptors that should be activated when you do certain things.

It's quite impressive. At the Digital Innovation Hub in Latrobe, which is quite a impressive building there. And there's a lot of things happening there as well.

And yeah, they're on different floor. Yeah, we're in the sort of the.

Neuroscience biomedicine, I think, or the bio. Yes, on that.

And the next floor down is all the technology. It's. It's a great. It's a Great system actually, because one of the things they do is they bring together people from different companies that are working on sort of related topics. So there's a lot of interaction. You know, you're at the water cooler and you're actually talking to somebody on a different team. Oh, you did this way you got to learn from each other.

You know, it's quite impressive setup. I couldn't. Yeah, it was gaddle. The trade. It's been a bit of an unassuming uni and then you go inside there and it was quite. Very impressive with what the lab you had set up as well.

What we've got is very unusual actually. The problem, one of the problems with science these days is that scientists have found it very hard to get funding. So the great thing about. Because we've got this, this $3 million a year which we hope to be able to increase dramatically in the future, but we've got this steady funding. So instead of spending their time going for research grants, we actually spend their time doing experiments and we can track really long term, so we can do an enormously more. My research head, Terry, he's in his previous. He was running a brain cancer study. He would spend half his time fundraising. Whereas with me it's easy. He just meets me for lunch every couple of weeks. It's great. And the staff like it too because it gives them security of importance. So they can really work on long term.

Long term thinking in the program as opposed to maybe short term stuff. Yes. And I was going to say as well, you actually sent your research head on a around the world trip. So what was that involved? What was involved in that or what was the sort of the point of that one to do.

Well, he's talking to different. One of the best ways to do research is actually do you. Do you work with other research teams? So there's research teams in the US working on things. Animals like prairie voles, which are very interesting because prairie voles monogamous and they have strong males, have a strong role in looking after the offspring. So in some ways they're a better model for helping humans. And also looking at naked mole rats, which they've also got colonies in the US and they're very interesting animals because in a naked wombat, only the one female breeds and the rest are kind of a subordinate, but they have a very strong sense of community. So we're looking at how that's how that comes about, what changes are made when a queen becomes dominant and what's the effect of food restriction on that Society.

And you mentioned about calorie restriction. Now obviously there's a real well known drug, obviously Ozempic, which is calorie restriction. And they're sort of saying it's got all these other effects about other things. So how does that sort of relate to. What are your thoughts on those?

Well, some of these seem to have. Some of these drugs seem to have the kind of effect we're looking for in terms of people who take these zempic and so forth, more likely to stop smoking as an example, which is another effect we would have. So you can look at some of these. What they're doing though, what you do is you have a drug that does what you want and then you tweak it. It's what they've done with the weightless drugs. For example, you have the basic drug, it's 15% weight loss and then they come up with versions which is a 25% weight loss. And now they get versions which you can actually take orally instead of having to inject it and so forth. So that's the basic model. You look for a drug that does what you want and then you tweak it to get rid of side effects. And these weight loss drugs do have side effects. That's one of the problems with them. So you try and minimize the side effects, you try and make them more effective. But once you've got a good product, you sort of work from there. So the drugs that we're investigating, those that we know affect similar pathways in the brain.

Okay, so your product that you're. Because ultimately it's going to be, you're hoping to develop a product or a treatment with what you're doing would hopefully do. Would probably do more than what people know this or is that the goal or.

Yes, well, the basic. If we could develop a treatment that does what we want, it'll have multiple effects. It'll make people less anxious for a start, less likely to be depressed. There's a rising level of anxiety, depression, suicide, drug addiction, alcoholism. There's all these problems. They're called deaths of despair for a reason, because they're sort children mentally. Now our treatment would be aimed to deal with that in particular. And as long as we can get something that actually has some effect, if it makes it sort of say 10% more likely, somebody can recover from drug addiction. That's the kind of start. And you say, okay, what about making it 25% more likely? And what about making it, you know, 50% more likely? So once you've got a treatment that works, then you can improve it the way they're doing with these weight loss drugs. But we're not looking so much weight loss that that could be a side benefit. We're looking at the psychological changes, the reduced depression, anxiety and so forth.

Well, is it promising to you then, that treatment has been developed? Because obviously showing, I guess, you know, yours will do, hopefully do similar a lot more, but it's at least this one's to market. And it's.

We are actually testing some of these weight loss.

Okay, right.

We're looking to see if we can have. Find some effects that we're looking for with indications that they are. Yeah, but it's a look, it's a long process. You can do a lot of drugs which can have effects and then you've got side effects and so forth. The actual real aim would be to use crispr, which is actually instead of having a drug that directly hits certain pathways, you actually go directly into the gene that you want to do and you switch off, take off the methyl groups and so forth that are causing these problems. And if you know exactly where you're going for, then you can have exactly the effects you want and nothing else. That's very, very exciting. It's the sort of thing you could actually get rid of. The malign effects of bad child rearing, for example, or experiences in your life which can cause terrible problems. And they're very, very hard to shift because the brain is very plastic. When people are young, it changes in ways that are quite drastic and you can't do it when they're older. So if we can actually go in and we can make just the precise changes we want that make a person into a drug addict or make them chr. Depressed, that's really, really powerful stuff. And the fascinating thing is that it's something that you couldn't even dreamed of even just a few years ago. But now, if I can explain what CRISPR is, it's a system that it's the targeting that you want. There are genes that are switched off when they should be on. That's basically the problem when you've got these kinds of changes. You want to send something in to do it, but you've got to get exactly the right spot. And you don't want to have effects over here which might have other effects. So what's happened recently is that they've become much, much better at targeting. And now, for the first time ever, you can actually have the potential to make very precise changes. And it's not easy to do because it used to be in the brain and certain organs in the brain, it's in the limbic system, it's the midbrain, not the neocortex, to do with logic, but more to be the emotional section of the brain. And that's what we studied in rats, because rats and humans are pretty much the same in this area.

Is there any example that people might be familiar with of crispr, where it's being used to do something like that?

Well, the sort of thing they're using it for is stuff like the treatment of sickle cell anemia.

Yes. Okay. Yeah.

Where you actually take somebody's cells out of their body, which is unable to make. Because sickle cell anemia is caused by a genetic change that causes the red blood cells to become wrong shape. And it's agonizingly painful, particularly people with African ancestry. Now what they can do is they take these cells out of people's body and they use direct manipulation to change them, and they put them back in, and then they start generating positive, more healthy blood cells. It's actually phenomenally effective, what they've done. The trouble is it costs like millions of dollars to treat one person. But that kind of technology is very, very exciting. What we're talking about, though, in our research is not so much genetic changes as epigenetic changes. We don't want to change the genes at all. The DNA is fine. What you want to do is to switch on genes that have been switched off.

And how do you think AI is going to help with your research with this sort of thing with crispr?

Well, it does help because you can do things on a much quicker scale. This kind of mass testing of drugs is something you couldn't have dreamed of a little while ago. It's a very, very new technology. So all the time, it's. The technology is advancing really, really fast. I dreamed of this stuff back in the 70s and 80s when I worked out something was going wrong with societies. And in those days it was just impossible. We hardly knew what epigenetics was in those days. But recently it's tremendous advances.

And ultimately the vision for epigenes is to develop this treatment that will do. That's the end goal. Yes. Yeah, yeah.

It'll be a treatment that would make people, help people to be happier, mentally healthier, more likely to engage with community, less interested in drugs and alcohol, less likely to commit suicide. All the things that are going wrong mentally, people are just trying to deal with those now. It would also help people, once it's developed, to Work harder and more effectively. So to have economic consequences, Somebody could be more disciplined, more long term thinking. That's one of the key elements of this whole thing. And we also make people more positive about families. So what you've seen is a collapsing birth rate, which is part of this whole trend. It makes people interested, they make people help people who enjoy being married, less likely to want to stray, less likely to want to use something like poor and more happy with their wives or their husbands and more interested in children. I find children really fun to be around. I love kids, always have. I just enjoy them so much. So that's why I have so many. That's why I've got 10. If you can help people to develop a frame of mind that makes them less anxious, less depressed, more positive, more long term thinking, they'll also be more positive about children. They'll find that attractive. They'll want to get married, they'll want to have kids and they'll say, this is great, I love doing this, people. There's funny findings. You find that on average people who with young children tend to be less happy than those without. And yet people who really like children, like myself, are distinctly happier with young children around. So if you change the attitude, the birth rate is going to shoot up.

Naturally and you would have an absolutely massive. If it does happen, it would be the biggest single thing or treatment in history. Like if you look objectively, it would.

Make changes actually to make the weight loss thing look trivial by comparison. It would have dramatic changes on social, on health and well being. You know, it's just different things like a suicide rate. There's an interesting graph in a book I was just reading about the rate of suicide based on the year of birth. And it went down and down and down and down and it went up in a very smooth trend. And we've got this epidemic of suicide going on. You know, last week two Jim's franchisees committed suicide. That is so horrifying. That is so appalling. We've had franchisors commit suicide. We had a staff member commit suicide. It's an epidemic. It's getting worse and worse and worse. You had this trend, it went down and down and down. What was the bottom thing? I asked this, a test. What do you think? The bottom. What do you think the year of birth when you were least likely to commit suicide? 1936, right in the core of the Great Depression. The thing about prosperity, people think it's always positive, but it's not. Sometimes you need to have a bit of a tougher life experience. And that's what we're going to do with this drug. To actually put something without actually having to have a depression, a great depression or recession. You can actually help people to have some of the benefits of a somewhat tougher upbringing.

We'll leave it there, Jim. So thank you very much. This is the first episode dedicated to the Conversations with Jim Pemmin podcast as well. We've got a link in the description to sign up to the birth rate crisis mailing list. So when the book comes out, it's going to be awesome. It's very unique and looking forward to it. So thank you very much for your time.