In the Bruce Effect, when you expose a pregnant mouse at an early critical stage of the pregnancy, I think up to about day three, if you expose the pregnant mouse to the order of what is referred to in technical terms as the non-stud male, that is a male who did not father the pregnancy, she will miscarry the pregnancy.

She will abort it. Now, that's an insane decision made by the female here, right? Because she's invested quite a lot in this, right? In biological terms and in forming this pregnancy and maintaining it. And yet she drops it on the basis of an odor. And this effect is remarkably robust.

And what do I mean by remarkably robust? So this will occur on about 80% of exposures. Now, as you know, 80% is 100% in biology, right? I mean, there's nothing that happens at more than 80%. So it's a remarkably robust effect, this dropping of the pregnancy. And we know it's mediated by chemo sensation through the nose.

For sure. And we know in the following way. So first, it's enough to just bring the odor of the non-stud male. You don't have to bring the male himself, right? So you just can bring bedding from a non-stud male and that will induce the Bruce effect. But of course, the most telling set of experiments is that if in the female mouse, you ablate the vomeronasal organ, you just burn this tiny structure in the nose, and the effect disappears.

So the effect is completely dependent on the former nasal organ. And I find this utterly a remarkable effect, right? I mean, because again, because of the extent of cost that the female takes on here, based on this information and smell. Now, humans, the sort of the going notion in olfaction is that humans don't have a functional vomeronasal organ.

So we don't have that functional organ in our nose. Now I'll point out, we actually do have the pit. So the structure or the outlining structure is there. But the pit that we have is considered vestigial and non-functional. And what about this thing I learned about at Berkeley in integrative biology class that we have something called Jacobson's organ?

This is the same organ. So Jacobson organs is the vomeronasal organ. It's also called Jacobson because I think Jacobson was a military physician in like the 1800s in Holland or something. And he found it in a soldier he was operating on or something like that. But the story comes from something like that.

But the Jacobson organ is another name for the vomeronasal organ. These are one in the same, the sensory organ of the accessory olfactory system. And again, the going notion is that the human Jacobson organ or vomeronasal organ is vestigial. It's non-functional. Does that necessarily mean that we don't have these pheromone effects?

No, it does not. So first of all, we know that lots of what are considered pheromonal effects, namely social chemo signaling in rodents, are mediated by the main olfactory system. We know that for sure. There are several examples for this in mice and rats and rabbits and so on and so forth.

So A, these can be mediated by the main olfactory system. And I'll come back to that in a second. But first to finish the Bruce effect. And second, and I'm going out on a limb here, but I'm willing to take that risk. For me, the jury is still out on human vomeronasal organ.

The decision or the notion that it's non-functional relies on about one and a half papers, post-mortem, looking for the nerve that connects this thing to the brain and failing to find it using staining and so on and so forth. But staining post-mortem studies in humans are notoriously complicated. Basically, you know, for many reasons, one of them is that the material is just always has gone through, you know, it's not ideally set as it is when you sacrifice an animal and and study its tissue.

So based on really, really a paucity of studies that fail to find this nerve, the notion is that the structure is vestigial in humans. I don't have any evidence that it's functional, mind you, but I'm just not sure that it's not. But what we do have a suspicion is that humans may experience something similar to Bruce effect.

So, first of all, humans have an enormous number or ratio of spontaneous miscarriage. - Are they occurring more often in the first trimester? Because you mentioned that in the Bruce effect in the mice is in the first three days or so following pregnancy, which in the mouse gestation, as I recall, is about 21 days in the mouse.

You're talking about one seventh of total gestation. So, I'm not quick enough to, nor is it important to translate, but this would be first trimester. - Yes, which is indeed when most miscarriage occurs. Now, humans have, again, a huge number of miscarriages and the numbers, I'll soon share them with you, they sound odd.

And the reason they sound odd is because if you have what's sometimes simply referred to as failed implantation, right, this can occur, you know, in days one, two, nobody ever knows. Okay, so some papers talk about 90% of all human pregnancies end in miscarriage. This is counting a failed implantation in day one, two, et cetera.

More conservative studies talk about 50%. Nobody will argue 30%. Okay, so a huge number, a huge number of human pregnancies end in miscarriage. Now, out of these, there's a portion that are unexplained, right? So nobody knows why. I mean, there are portions that are explained by all sorts of genetic factors, developmental factors, and so on and so forth.

But there's also a proportion that are unexplained. And so all I'm saying is that there's a statistical backdrop or setting, if you will, for something like a remnant Bruce effect in humans. Now, with that in mind, we approached a group of, we enlisted a group of, they're not really patients and participants in a study of people who couples who are experiencing what is referred to as is unexplained repeated pregnancy loss.

So formally, if you have two consecutive unexplained miscarriages, then that is sufficient for the diagnosis of unexplained repeated pregnancy loss. However, in our cohort of 30, we had couples who experienced 12 consecutive unexplained repeated pregnancy losses. So the two is just the formal, all of our cohort was like 12, five, you know, so this is an emotional, difficult place to be.

And these are couples who are losing their pregnancy for no apparent reason. So they've gone through all the tests that you can imagine of, you know, genetic incompatibilities and all sorts of issues, clotting, all the known suspects for pregnancy loss. And the medical establishment remains totally at a loss as to why these pregnancies aren't holding.

And so we hypothesized that, that perhaps here, there's something akin to a Bruce type effect. Obviously, it's not going to be the same as in mice, but, but something like a Bruce effect. Now, of course, at that stage, we could not do anything causal to test this, right. But what we could do is to see, you know, to seek circumstantial evidence to see if, if where there's fire, maybe there's smoke.

And what we did was we tested, all faction and more specifically, the response to male body odor in, in the couples experiencing repeated pregnancy loss. And we found a few things. First of all, if you think of the mechanisms behind the Bruce effect, the Bruce effect implies that the female has to have a very clear memory of the fathering male, because if she's going to miscarry in response to the nonfather, she has to know father, nonfather.

I mean, that means that there's a pronounced olfactory memory at the moment of mating. Okay, and in mice, this has been very well characterized and attributed to the anterior olfactory nucleus structure in the brain. But you'd have to have this memory in order to make that decision. Now, so to address that, and here you're going to see that you and your childhood story from before stand out a bit as skillful, is that the first thing we did was just behaviorally test whether these women and control women could identify the smell of their spouse.

And you might be disappointed or, you know, we would all are probably a bit disappointed to learn that control women are very poor at this. So you would think that women would be good at identifying the body odor of their spouse. They're not. They're not far from chance. However, the women who experience uh, repeated pregnancy loss are more than, they're, they're double, um, at their performance level.

So this is not a nuance effect. Uh, women who, who, who, who experience repeated, uh, pregnancy loss can identify, uh, their husbands or their spouses, uh, by their body odor. With much greater acuity than the typical person? Double. A bit more than double. And, and way above chance. Yeah, no, I, I, sorry, I posed it as a question, but I meant, yes, with much greater acuity, uh, and double is, is a significant, um, improvement.

Are they much better at detecting any odor? No, they're not. We did the controls and they're not. And then, um, we also measured using fMRI. We measured their, their brain response to, uh, stranger male body odor. And there, and, and, and this was quite remarkable because, you know, we approached, so this was a full brain analysis.

So without a region of interest analysis. So it's not as if you're, uh, tweaking your statistics to look at one part of the brain, you're just looking at the entire brain in the response to male body order and asking, de novo, is there a difference between these two groups of participants?

And there was one huge difference and it was in the hypothalamus. And so there was a difference in response to stranger male body order, uh, between the two groups. Um, so, so olfaction is altered in spontaneous, repeated spontaneous, uh, pregnancy loss. We don't know this is causal, right? Uh, but, but that was enough for us to approach the ethics committee, um, to run a causal experiment.

Um, and we're at the beginning of that now.