Steve: Welcome to Science Talk, the weekly Podcast of Scientific American posted on May 11th, 2009. I'm Steve Mirsky. This week we'll talk about the science of beauty, which in the case at hand is mostly the science of skin. We'll talk with a couple of researchers from Procter & Gamble who work on skin issues. Plus, we'll test your knowledge about some recent science in the news.
ScientificAmerican.com this week features an In-Depth Report on the science of beauty. A group of SciAm staffers recently met with Procter & Gamble scientists Greg Hildebrandt and Jay Tiesman, who work with dermatologists on skin care products. You know, we mostly talk to academic researchers on the podcast, so in addition to the immediate subject of beauty, this is an opportunity to hear what life is like for the many scientists who work in industry. We wound up talking for more than 90 minutes, and I've edited that down to about 15 minutes of the most compelling material. In addition to me, you'll hear questions from Scientific American's Ivan Oransky, Peter Brown and Lisa Stein. The first voice you hear is Procter & Gamble's Greg Hillebrand.
Hillebrand: I'm a biochemist and I've been working in the skin aging area for most of my career, 22 years at P&G. We have had a very good understanding of the changes in the skin with age from a visible standpoint. Of course, we get lines and wrinkles and spots and that stuff, and we've got very sophisticated ways of measuring those changes and understanding how things happen over the course of a lifetime. But now more recently, we've got the tools to understand at the molecular level what's going [on] in the skin, and these expression genomics or transcriptomics are the, kind of, the way in which we're doing that; and that's Jay's forte here. So I think, you know, my particular expertise is more in the clinical side of aging and beauty and then Jay brings more the molecular aspects and so...
Steve: ... So, [in a nutshell] you're looking at expression levels of mRNA in different skin conditions of aging.
Tiesman: Exactly, that's correct.
Hillebrand: Young skin versus old skin and photo-damaged skin versus sun-protected skin and looking at the expression of various metabolic pathways in the two different skin types.
Tiesman: The whole point of it is that [it's] now [it's], whenever we talk to people or not—we know obviously you're familiar with the gene expression profiling. We've worked with beauty organizations since the late '90s and doing some gene expression
or been[and] trying to understand skin biology and all that. But actually brining it around to having it come out as, you know, information that went into that early investment coming out as a product kind of rounds that story [out].
Oransky: And is this something that has either gotten started since or accelerated since human genome project or is this something that has been around?
Tiesman: It started relatively early; it has accelerated drastically obviously since the human genome project. You know, we were some early adopters of microarray technologies. We've been using the Affy technology since about '98 or '99
Oransky: Is [that] the Affymetrix?
Tiesman: Affymetrix, yeah. The Affymetrix GeneChip and so we've working with them for a number of years; and we've actually done tens of thousands of GeneChips. You know, there is a lot of pharma groups that have done quite a bit, but we actually have a little bit of a different slant than what a lot of [the] pharma organizations have.
Oransky: And you're mostly interested, this probably varies by what you're looking at, but you're mostly interested in what gene expressions [is] happening in the human cells you're looking at or are there things growing on us that?
Tiesman: Actually, yeah there is both. We're interested in both. Obviously the Malassezia globosa study gave you a great example [of] our interest in dandruff. Yeah. You know, we're using the GeneChip technology; one of the things that we used here is to understand you know skin aging process. So we're looking at clinical populations of young skin versus old skin, photo-damaged, young and old skin versus non-sun-exposed young and old skin and trying to gain a molecular understanding of the pathways
than[and] the mechanisms involved in those. [And] we also are involved in understanding, you know, the host pathogen interaction and a good example of that is the dandruff work that we're doing. We've also done a lot of work, you know, uncovering the molecular basis of the fungus, and we've also done a lot of work trying to understand how the human scalp responds when it is infected with the fungus. And you know, host path—there is a couple things that are fundamental to our experimental programs. Number one is we have a lot of expertise in epithelial biology. If you think of a lot of P&G products, they impact the skin; you know, even our laundry care can impact your skin, but you know, we have our beauty group, our hair group, our feminine care group; even, you know, it's the skin on the inside and the outside gastrointestinal [and] respiratory and oral care. So we have a pretty deep epithelial biology expertise. [But] we also have a great interest in the host microbial interactions, as well.
Brown: Do you guys publish in the dermatological journals as well as all trade secret type of work or do you...?
Hillebrand: ...We publish in the derm journals and present at the derm meetings and, you know, as an industrial scientist that's always kind of a frustration for us because we have our academic roots; and so, yeah, we do publish...
Hillebrand: ... and present at the major meetings.
Tiesman: Right, and we've just recently had our respiratory care study [was] published in the American Journal of Respiratory and Critical Care. We just have our oral care study looking [at] experiments o[n] gingivitis was just submitted to the journal Periodontology, and so there are a lot of other journals that we do as well; and then obviously [the] Malassezia was in PNAS.
Stein: So what did you find out? I guess, you got all these creams; you got a million creams on the market; you slather them on, okay, [but] they're not really doing anything. So what is different about this?
Hillebrand: I want to tell you...
Tiesman: That's a good thing you said [that].
Hillebrand: When we leave today, I'm going to remove the doubt in your mind that these don't do anything.
Stein: What are you going to [give]
do me a face[lift]?
Stein: Okay. Yeah, tell me how, so it is in the genes,—you know, you got the good genes, so you know, your grandma looks good; God help you [if] she looks like she was run over by a [Mack] truck. What are all these creams going to do? And what's better, you know, if you're just putting it on the skin, sort of burning off a layer of skin and getting what's underneath, you know.
Tiesman: Right, obviously there was a combination right, so there is the genetics and then there is where, if you have the good genes, you're gonna [have] good skin. There's the environment, where obviously UV is a major aspect of that, but there is a lot in between as well, and there is a lot of room to understand the mechanisms, how the environment and the genes interact and trying to understand pathways that can lead to skin wrinkling or that can lead to areas like that.
Hillebrand: I think I'll give one example. In the epidermis stratum corneum, you know—and that's the protective barrier that prevents water from escaping, otherwise we'd all dehydrate in about 10 minutes—also prevents the nasty bugs from entering and anything else from getting into our body. Well that barrier is composed of bricks-and-mortar types of structures with proteinaceous squamous and the lipid cement and one of the aspects that came out of the old skin-young skin study was that the enzymes involved in cholesterol biosynthesis were coordinately down-regulated in the old skin versus the young skin. That was very interesting. It wasn't like some were down-regulated and some were up-regulated; there was a coordinate down-regulation of cholesterol biosynthesis.
Steve: So it means there's not enough cholesterol.
Tiesman: That's exactly it, yeah.
Hillebrand: And that makes up about 25 percent of the mortar that builds the brick-and-mortar stratum corneum. You know, then a screening study program was done to try to identify agents that could help to take the lipid biosynthetic pathway of older skin care tenor sites to make them produce more cholesterol. And one of the actives that came out of that was hexamidine; and then that was put into one of the products, the hydrafirming cream here and its ability to repair the barrier function was proven in a clinical study. So, the cycle goes, like: genomics, identify the targets, identify actives that are aimed at those targets, formulate them in the products, prove their clinical efficacy and then, you know, publish and then we see this as a cycle.
Steve: Clinical efficacy based on cholesterol levels or based on objective views of the skin.
Hillebrand: Well, both visual assessments, a bit dependent on what we're looking for, okay, and we have recently completed a study where we focused on fine lines and wrinkles, but simultaneously we also measured the barrier function using what's called transepidermal water loss, which is the escape of water through the skin; and after six months, [it was a] six-month study, there was a significant improvement of the barrier function after six months.
Steve: Do we know that the cholesterol was what's actually involved in the improvement though? [Have] you measured the actual cholesterol levels?
Hillebrand: We have not. We have taken, though—and this work is in progress—tape strips of the subject's stratum corneum from the face, where they were treated and those are going through the genomics expression profiling. So that work closes the loop on that cycle, and that's work that's in progress, [and]...Oransky: Where is that by the way?
Tiesman: The RNA is about half isolated. It's a lot of clinical samples and its tape strips on faces, and so it's difficult to get, but the RNA is about half isolated.
Steve: You want to know that the mechanism you think you are working with is actually the one that's happening, right?
Tiesman: Oh absolutely sure! You bet, and obviously with the tape strips, we're just getting some superficial epithelial layers, we did not do biopsies; and so we'll get some information about what's going on at that top layer.
Oransky: You probably work with academic medical centers to do these or do you, you know, do them in-house?
Hillebrand: It's a combination.
Oransky: This is something where I go to clinical trials or go over something, and I say what do you say, you say free face cream or what do you say that...?
Tiesman: To get people to come?
Oransky: Ugly people?
Hillebrand: Do you mean for the registered trials?
Oransky: How do you approve?
Hillebrand: That's a good point. This you mean, how do you find out more about this study or?
Oransky: I mean, where somebody...
Tiesman: How do you recruit people?
Oransky: How do you recruit people?
Hillebrand: Ah! Recruiting.
Oransky: You know, age your skin.
Steve: You know, you ride the New York City subways and you
can see these ads, you know.
Tiesman: We have multiple ads in our local newspapers. I've seen them, and I said, I know that's a for a P&G study.
Hillebrand: Yeah, radio...
Tiesman: So, there is a lot of recruiting like that radio, TV.
Hillebrand: And then they come in and they go through our clinical grading to see if they meet certain you know inclusion and exclusion criteria in the questionnaire.
Oransky: And you are dealing mostly with healthy people in those trials once they get to phase III or not; you know, phase I trial, it should be healthy people, but those are very small; but you are actually you know testing some of the unhealthy people so that's a basic question of you know, I'm just curious about how that differs from trials that people are you know, really kind of desperate to get into and if you have a terminal cancer where there is no treatment and you want to be in a trial, how do you...
Tiesman: We pay them; paid clinical subjects, correct?
Steve: Anyone who caught last week's episode of 30 Rock knows that members of different racial groups may appear to age at different rates because of the different properties of the skin. Our diverse staff brought that subject up with the P&G researchers.
Hillebrand: For fine lines and wrinkles, there probably is not any difference between whites and blacks and Asians. Only the onset time, you know, when they start to see the appearance of these problems. They were delayed because they have been afforded the protection of about an SPF between 2 and 4.
Hillebrand: From their inherent melanin concentration, perceptibility of some of these problems like wrinkles and fine lines might be more difficult to see because of the dark background, basically. Because you are looking at shadows, so shadows on a dark background are harder to see and, you know, we do a three dimensional analysis too. You know, I've done quite a bit of studies on the epidemiology of aging in different ethnicities around the world and looked at big, wide age ranges and the African-Americans are delayed significantly versus Caucasians and then the Asians also, you know, had really, really good skin too for any given age. They're fortunate, they get about a decade or so of time before, you know, their wrinkles start to show up.
Brown: So SPF 2 to 4 is worth a decade.
Hillebrand: Well, I think, it's hard to estimate exactly how much that's worth.
Tiesman: Yeah, there may be other factors as well. SPF might help.
Brown: You mean like heart disease or something?
Steve: No, no, I mean there might be other factors within the skin itself that might be inherently higher cholesterol level, and I mean I'm just [throwing stuff out there] but there could be multiple factors.
Hillebrand: [A] genetics-based [study] comparing the aging of [a] population of women who lived in northern than Japan versus a population that lived in southern Japan—and what I love about Japan is that there is this homogeneity of the population—the differences in the UV beam reaching the earth in northern Japan versus southern Japan was 1.5 difference; and you can equate that directly into a SPF of 1.5. And there was significantly less wrinkling in the northern group, and it was visibly less, than in the southern group. And I could tell you that the number of years difference for 1.5, I think in wrinkles was, like about eight; now that's a published paper. [It's] about eight years.
Steve: Some of the skin studies wind up leading to more internal research.
Tiesman: There is the respiratory study that we've done, where we infected college students who volunteered to be infected with rhinovirus and we did a nasal scraping.
Stein: How much did you pay them for that?
Tiesman: I don't recall how much it was. Enough [for] beer money for awhile, right.
Stein: Right, that's all that they care [about].
Tiesman: It was at the University of Virginia, actually. I was down there when they were conducting those studies, and so we did nasal scrapings, and we were checking how the nasal epithelium was responding to be infected with the rhinovirus identified.
Stein: Did you come up with something that would actually work?
Tiesman: Well, actually, yeah. We found, really, there was this overresponse that the rhinovirus has been really, you know, its relatively mundane virus, but your body doesn't seem to know that. It's just attacking it's like [it's] HIV.
Stein: So it overreacts like an autoimmune [response]?
Tiesman: It does.
Hillebrand: These viruses are closely related to some pretty nasty things.
Tiesman: Exactly, exactly. So your body can't tell. So what's really happening is you're getting this big overreaction. So if there is ways that we can either pre-prime your body so that it doesn't overreact in such a way, or somehow alleviate those symptoms of that over-reaction then we think that it might lead to new stuff for a fix. We see a lot of changes in the immune-specific markers either because of recruitment of immune progenitors—you know, you could have, you know, macrophage recruitment or something along those lines; or we could actually see some changes in, for instance, interleukins, specifically when the epithelial cells are changing. So it depends on which study we perform, but you can actually see, you are either sending our signals to recruit immune components or your gene expression is changed because you actually recruit in the immune components. [We're] trying to dissect that part out; [we're] trying to figure our what's the SOS signals and what's the response of those signals. We were really not studying the rhinovirus itself, but we were studying the host effect, the host response of the rhinoviral infection; and so we're hoping that will alleviate symptoms of the infection as opposed to fighting the actual virus.
Steve: For more about the kinds of scientific research going on at Procter & Gamble, just go to www.pg.com/science.
Now its time to play TOTALL....... Y BOGUS. Here are four science stories; only three are true. See if you know which story is TOTALL....... Y BOGUS.
Story number 1: Moderate alcohol intake can make your mind wander, while at the same time making you unaware that your mind is wandering.
Story number 2: Researchers have found a gene strongly associated with narcolepsy, where you just, kind of, fall asleep at any time.
Story number 3: Rather than increase the trafficking of precious archaeological finds as some feared, the advent of eBay has actually lowered high-end antiquities trafficking.
And story number 4: An analysis of the foot bones of the extinct tiny hobbit people of [the] island Flores shows that they could have probably outrun all but the most accomplished modern human marathoners.
Time is up.
Story number 1 is true. A study published in the journal Psychological Science finds that a moderate dose of alcohol can make your mind wander and reduce the likelihood that you'll realize that your mind is wandering. Technically, this is called impairment of meta consciousness also known as smashed, bombed or wasted. The study had men who had who had consumed alcohol reading passages from War and Peace seriously. And then something happened and then I was working on this podcast and anyway....
Story number 2 is true. A gene strongly associated with narcolepsy was identified by researchers at the National Institute of Neurological Disorders and Stroke, who published in the journal Nature Genetics. The gene has a known role in the immune system, which suggests that narcolepsy may have an autoimmunity component.
[And] story number 3 is true. eBay has lowered high-end antiquity's trafficking because it has encouraged a booming fake antiquities market at low prices. For more check out the May 6th episode of the daily SciAm podcast, 60-Second Science.
All of which means that story number 4 about the Flores hobbits being great long distance runners is TOTALL....... Y BOGUS, because an analysis of the foot bones shows that parts of them are more similar to other great apes than to Homo sapiens which means they would have been lousy marathoners. That's according to
a research published in the journal Nature, which features the hobbit's skeleton on its latest cover. Hobbits would also have had trouble officially finishing marathons because they would have had to jump way up in the air to break the tape as they cross the finish line.
Well, that's it for this edition of Scientific American's Science Talk. Check out www.SciAm.com for the latest science news, the In-Depth Report on the science of beauty and our In-Depth Report on the science of Star Trek. I saw the new movie on Sunday, and it's awesome. For Science Talk, I'm Steve Mirsky. Thanks for clicking on us.
Procter & Gamble scientists Greg Hillebrand and Jay Tiesman talk about scientific research related to beauty products and cosmetics. Plus, we'll test your knowledge of some recent science in the news. Web sites related to this episode include www.pg.com/science