How Plastics & Chemicals Affect Fertility & Babies | Dr. Shanna Swan & Dr. Andrew Huberman

00:00:00.000 | Are there things in our environment, including our food, that are diminishing our reproductive

00:00:10.720 | and overall health?

00:00:12.160 | So my answer to that is yes.

00:00:13.840 | I think there's no question about that.

00:00:16.320 | The question comes down to when and in whom and what dose and so on and so forth.

00:00:24.200 | But whether there are, let's just say broadly, things, yes, of course.

00:00:30.180 | My thesis is that chemicals in the environment, that's a very broad class, so we'll have to

00:00:36.540 | say some chemicals in the environment, at the right time, to the right organism, affect

00:00:42.840 | fertility.

00:00:46.280 | And let me just say fertility is one area that I've focused on, but actually this class

00:00:52.180 | of chemicals that I'm primarily interested in are those that affect the body's hormones.

00:00:58.360 | So those are known as hormone-disrupting chemicals or endocrine-disrupting chemicals, hormone-altering

00:01:06.560 | chemicals, whatever.

00:01:07.560 | You know, there's a lot of names.

00:01:08.560 | But that helps you focus on where to look for the effects.

00:01:13.760 | Because if it's hormone-altering, you can now have something to really ask.

00:01:17.160 | Okay, here's a chemical.

00:01:19.360 | Does it affect a hormone?

00:01:21.840 | Which hormone?

00:01:22.840 | When?

00:01:23.840 | How?

00:01:24.840 | And then you start, that's almost laying out an experiment right there, right?

00:01:29.040 | So focusing in on hormone-disrupting chemicals I think is useful.

00:01:33.920 | I studied environmental chemicals, not so much pharmaceuticals, for quite a while when

00:01:43.060 | I was at the California Department of Health Services.

00:01:46.600 | And then I had an aha moment.

00:01:52.080 | I was flying to Japan with my friend John Brock, who's a chemist at CDC, wonderful chemist.

00:02:02.680 | And we had long flights, we were talking about this and that.

00:02:05.000 | And he says, Shauna, you should look at phthalates.

00:02:08.040 | And I'm going, why should I look at phthalates?

00:02:09.760 | I never heard of phthalates, right?

00:02:12.960 | And he said, well, we can now measure them at the CDC and we see they're in everybody.

00:02:18.960 | They're in women of reproductive age.

00:02:21.160 | Fact one.

00:02:22.480 | Fact two, colleagues at the NTP have shown something they are calling the phthalate syndrome.

00:02:32.560 | And so he explained.

00:02:33.960 | What is NTP?

00:02:35.600 | National Toxicology Program.

00:02:36.600 | Sorry.

00:02:37.600 | Thank you.

00:02:38.600 | For using alphabet.

00:02:39.600 | No, it's quite all right.

00:02:41.000 | National Toxicology Program, a governmental research center.

00:02:46.040 | And their job is to look at chemicals and see what is the toxicity.

00:02:50.600 | So it could be reproductive, it could be carcinogenicity, it could be neurotoxicity.

00:02:55.940 | That's what they do.

00:02:57.840 | And so they had signaled out these phthalates as being reproductively toxic and specifically

00:03:06.880 | to males and specifically when exposure is in utero.

00:03:11.520 | Pregnant mom is exposed to phthalates and somehow the fetus is disrupted.

00:03:19.760 | Yes.

00:03:20.760 | If you don't mind, I'd like to know, is mom ingesting phthalates in the form of food?

00:03:25.840 | Is she inhaling phthalates?

00:03:27.420 | Are they landing on her skin?

00:03:29.120 | What are the modes of entry into the body of the mom that, let's just assume it goes

00:03:34.280 | through the placental barrier into the fetus and is impacting fetal development?

00:03:38.160 | Right.

00:03:39.160 | So in those experiments, it was through food, but we are exposed in all those ways you mentioned.

00:03:46.120 | Every way that something can get into our body, phthalates get in there.

00:03:49.920 | But let's come back to that.

00:03:50.920 | Let me go to the experiment at NTP.

00:03:52.840 | So what they did at NTP, National Toxicology Program, they fed mother rats various doses

00:04:00.620 | of these various phthalates.

00:04:04.460 | And what they found was no changes in the females that they found at that time.

00:04:11.540 | The female offspring?

00:04:12.540 | Female offspring, sorry.

00:04:13.900 | But in the male offspring, they found that the genitals were, I summarize it by saying,

00:04:21.540 | incompletely masculinized.

00:04:23.040 | So I'll explain what that is.

00:04:24.740 | So for that, I have to back up and say something you probably know very well.

00:04:30.380 | But I'll just explain it.

00:04:31.820 | The genital tract initially is a ridge.

00:04:34.300 | It's a single ridge.

00:04:36.020 | It's the same in males and females.

00:04:37.840 | It's not sexually dimorphic at the beginning.

00:04:40.340 | And then under the influence of testosterone, in a very specific window called the male

00:04:45.780 | programming window, in rats, it stays, I think, nine to 12 of gestation, so a very short window.

00:04:52.540 | To orient people, I think rat mouse gestation is about 21 days or so?

00:04:57.100 | Yeah.

00:04:58.100 | Yeah.

00:04:59.100 | Okay.

00:05:00.100 | And that's the early first trimester.

00:05:02.340 | But that comes later.

00:05:04.180 | So at that time, if they feed their mother that chemical in her food, then her male offspring

00:05:14.860 | are born with changes in his genitals, or more likely to.

00:05:19.940 | And so what they tend to have is a smaller penis, less descent of the testes, more likely

00:05:27.820 | to have undersented testicles.

00:05:30.460 | There are internal changes that we didn't get into in our human study because we can't

00:05:36.380 | look there.

00:05:37.380 | But the epididymis, there are changes and so on.

00:05:39.900 | The whole genital tract is altered.

00:05:42.540 | And the most important measure for me, as it turned out, and for humans, and perhaps

00:05:48.940 | for animals, is something that the scientists, animal scientists had studied for a long time,

00:05:56.140 | for actually 90 plus years, but had never been studied in humans.

00:06:02.980 | And that is the distance from the anus to the genitals.

00:06:07.060 | This collection of changes in the male genitals was given the name the phthalate syndrome.

00:06:14.220 | And you, I challenge you to think of any syndrome, aside from alcohol, you know, there, fetal

00:06:23.300 | alcohol syndrome, of course, there's a syndrome.

00:06:25.980 | But note what syndrome is attached to a chemical class.

00:06:31.220 | One that comes to mind would be, for instance, the thalidomide babies, right?

00:06:36.580 | A miscarriage, anti-miscarriage drug that changed limb development.

00:06:40.600 | That's a very extreme example.

00:06:42.180 | There are a lot of things in development where hormones set up a potential to respond to

00:06:51.020 | other hormones later.

00:06:52.700 | It's not that testosterone grows the penis during development.

00:06:54.940 | It does that.

00:06:56.660 | But more so it establishes a potential for the penis to grow when exposed to things later

00:07:02.140 | during puberty.

00:07:03.140 | Do I have that right?

00:07:04.540 | Right.

00:07:05.540 | As far as the name goes, which is the phthalate syndrome, there is thalidomide.

00:07:10.060 | It's not usually called the thalidomide syndrome, but it could be, so you're right about that.

00:07:15.380 | But it's extremely rare.

00:07:17.100 | And there is no environmentally, you know, chemical in the environment as opposed to

00:07:23.740 | a pharmaceutical that is given a syndrome.

00:07:25.980 | So this is very, very unique.

00:07:28.540 | And so I thought, wow, John's telling me this on the plane, right?

00:07:34.780 | Something in the environment that is basically having an endocrine and body disruptive effect,

00:07:40.220 | at least on par with fetal alcohol syndrome and thalidomide syndrome.

00:07:44.860 | Right.

00:07:45.860 | Yeah.

00:07:46.860 | So when, well, at this point it was only animals, right?

00:07:50.180 | Because John was telling me about the NTP study, which was in rats.

00:07:54.540 | And so I thought, wow, you know, I like puzzles.

00:07:59.760 | So my first question was, is this happening in humans?

00:08:04.500 | You might ask that, you know, as a natural thing to ask.

00:08:07.380 | Great question.

00:08:08.380 | And then I thought, how would we find out?

00:08:12.840 | And answering that question took me 10 years, okay?

00:08:18.640 | And so if you think about, okay, phthalate in the mother, changes in the genitals of

00:08:27.840 | the offspring, connect them.

00:08:30.340 | How do we do that, right?

00:08:32.100 | So we have to start with phthalates in the mother.

00:08:34.660 | So how do we know that?

00:08:37.220 | Well, fortunately or not, I had stored a lot of urine from pregnant women from a study

00:08:46.760 | that I was doing on sperm count.

00:08:49.160 | I just got the women's urine coincidentally, if you will.

00:08:52.320 | I thought, well, save it.

00:08:54.040 | You know, it's not expensive and not hard.

00:08:57.280 | Minus 80 degree freezers, doesn't take a lot of room, put it in there.

00:09:01.600 | So I had this urine save from pregnant women, and then I knew from John that we could look

00:09:09.920 | in the urine for phthalate metabolites.

00:09:14.520 | So these are products that the body forms when they're exposed to phthalates, and you

00:09:19.160 | can measure them in urine.

00:09:20.780 | So I thought, okay, I could get that urine, I could look at the phthalate metabolites,

00:09:26.180 | and then I'd know what the mother was exposed to.

00:09:30.100 | And based on the animal data, we have good evidence that it actually makes its way to

00:09:35.740 | the fetus.

00:09:38.060 | So then I thought, okay, then maybe there's a change in the babies.

00:09:43.560 | So then I had to get the babies.

00:09:44.820 | So fortunately, I had done this study on pregnant couples, pregnant women and their partners,

00:09:52.720 | and I was able to call them and say, would you come in and let us measure your baby's

00:09:58.160 | phthalates?

00:09:59.160 | Right?

00:10:00.160 | How willing were parents to let you do that?

00:10:03.000 | It seems-

00:10:04.000 | They were okay.

00:10:05.000 | Most of them were okay with that.

00:10:06.000 | Were they?

00:10:07.000 | Yeah, yeah.

00:10:08.000 | Well, they trusted us.

00:10:09.000 | They had been in a study with us, and we were reputable.

00:10:12.560 | Those babies were still-

00:10:14.280 | Young, but not newborn.

00:10:16.340 | So this was a while later.

00:10:18.520 | The babies that we actually got were, on average, I think about a month, 12 months old.

00:10:23.240 | So not ideal maybe because the rats had been measured at birth.

00:10:28.520 | The rat genitals had been, but that's what we could do at that time.

00:10:32.880 | Yeah.

00:10:33.880 | The reason I ask is there's always the potential for ongoing phthalate exposure to the newborn.

00:10:38.000 | Sure.

00:10:39.000 | Absolutely.

00:10:40.000 | But I suppose in either case, you're able to draw some potential link between, or potentially

00:10:45.480 | draw a link, I have to be careful with my language there, between phthalate exposure

00:10:50.160 | in utero and ex-utero and these external biomarkers.

00:10:53.720 | Yeah.

00:10:54.720 | Given that the critical window is quite short and quite early, by the way, let me just say,

00:10:59.280 | when the rats, they did a lot of work on this critical window, and when the rat moms were

00:11:03.320 | exposed before day nine, it did nothing.

00:11:07.000 | And when they were exposed after day 12, it did nothing.

00:11:10.880 | So it was only the exposure during that critical window is very delicate, and it's by the way

00:11:17.440 | true of the brain as well.

00:11:19.040 | So teasing out what is the critical window is one of the challenges that we have when

00:11:24.120 | we work with these chemicals.

00:11:25.760 | So I wasn't so much worried about exposure in the delivery room and in their feed in

00:11:33.600 | the first year of life, because I knew that it was unlikely to change these measures.

00:11:39.280 | To my knowledge, this is the first time it was used as a toxicological measure in humans.

00:11:45.360 | So we did that study.

00:11:49.500 | We related those measurements to what CDC had measured in the urine of our women, collected

00:11:55.480 | while they were pregnant, and we found the phthalate syndrome.

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How Plastics & Chemicals Affect Fertility & Babies | Dr. Shanna Swan & Dr. Andrew Huberman

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