Februari 08, 2017
david ellis: good evening. and welcome to adelightful audience for what is goingto be, i think, a fascinating andchallenging lecture. i'm david ellis,the interim head of the harvard museumof natural history. and it's really my pleasureto welcome all of you here today for the thirdinstallment of the museum's four-part spring lecture series.
audience: it'snot working right. david ellis: tom, why don't yougo ahead and i'll read here. this series was startedearlier this month with a talk by nobelprize winner jack szostak from harvard medical school, whodiscussed his research on rna in unraveling the mysteryof the origins of life. iain couzin from princetongave a talk last month about collective democraticbehavior in groups of animals. and tonight, we have the thirdin our series, randolph nesse
from the universityof michigan, here to discuss the emerging fieldof evolutionary medicine. before i introduce dr.nesse, two announcements. the last talk inour series is may 2, by jerry coyne from theuniversity of chicago, who will discuss the thesis ofhis book of the same title, why evolution is true. that talk will be inour normal location next door, at thehmna, 26 oxford street.
now the two previous talksare now on our website. as will this one bein about two weeks. and we hope you'llavail yourself of that. it's really something. it's a great addition forthose who either can't be here, who would like to go back andreview part of what they heard. now, i'd also like to recognizedr. herman suit and dr. joan suit, who are with ustonight in the audience, for their generoussponsorship of this series.
herman and joan, thank you. [applause] tonight's distinguishedspeaker is dr. randy nesse, one of the foremostresearchers in the emerging field of evolutionary psychologyand darwinian medicine, with an emphasis on theorigins and functions of the emotions involvedin psychopathology. dr. nesse holdsseveral appointments at the university of michigan.
he's currently professorof psychology and professor of psychiatry, senior scientistat the research center for group dynamics, anddirector of the evolution in human adaptation program. dr. nesse is the authorof numerous articles and scholarly papers on variousissues in medicine and health, as well as an influentialbook for the general audience titled, why we getsick, published in 1995. his research and his ideashave contributed enormously
to our understandingof evolution, whether studied in academeor understood and of interest to the general public. and that could be evidenced bya very long list of distinctions and honors. now, we'd be here for a longtime if i read them all. so i won't. so i'll turn it overimmediately to dr. nesse. thank you.
randolph nesse: thanks somuch for that very generous introduction. it's great to be herewith you all tonight. and i especiallyappreciate dr. suit and dr. suit making thispossible for us. i also reallyappreciate jerry coyne, who i talked with at asse meeting last summer. and he thought thismight be a good idea. i'm really glad herecommended this.
i think it will allwork out very well. you see on the first slide, wehave my colleague and friend, george williams, whopassed away two years ago, without whom wewould not be here. this whole field would notexist if it wasn't for george. and it also wouldnot exist if it wasn't for theuniversity of michigan museum of natural history. i'm not sure exactly what iwas thinking of when i had just
finished my residency programand i was a junior faculty member. i do know what iwas thinking of. i was thinking about senescence,even though i was young. and i was thinking aboutwhy senescence exists, which is a problem thatpreoccupied me ever since i was a sophomore undergraduate. and so i started hangingout with the biologists at the museum.
and i didn't know these guys. there was this guynamed bill hamilton. he seemed really smart. for those of you whomight not be biologists, he's one of the leadingbiologists of the 20th century. george williamscame by quite often. richard alexander helped. barbara smuts was there. richard wrangham was there.
all kinds of the greatestpeople in the world were there. and i just thought theywere regular folks. but they were prettynice to me, as a doctor who was interested, butignorant about evolution. and a lot has come from it. and i startedtrying to figure out if i could find abiologist to work with, to develop evolutionaryapplications in medicine. and lo and behold, thisfellow george williams,
who i hadn't realized hadrevolutionized certain areas of biology, said, well,i'm looking for a doctor to work with, to write a bookon evolution and medicine. first, we wrotean article, which he insisted ongrandly titling it, "the dawn ofdarwinian medicine." i said george, can't wedo something more modest? he said no. and so how aboutevolutionary medicine?
he said darwin discovered it. we're giving him credit. ok. i was more successful in some ofmy other arguments with george. but for those, he won. a lot has come from this. it's been 20 years now. first, what we're talking about. this is evolutionary medicine,the same as darwinian medicine.
this is just the fieldthat uses the basic science of evolutionary biology totry to understand problems in medicine and public health,to understand, prevent, and treat disease. it's just like genetic medicine. but the basic scienceis not genetics. it's evolutionary biology. you might thinkthat this had been done 50 years agoor 100 years ago.
and i keep wonderingif we're going to discover a bunch of textbookssitting there, we never found. but it turns outthat there's been this big gulf betweenevolutionary biology and medicine, which it's up tomany of the people in this room to help bridge. so we begin with the realbeginnings of it, with darwin. there's somethingfunny about this slide. "the purport on the followingpages," darwin says,
"is an endeavor to reduce thefacts belonging to animal life into classes,orders, and species. and by comparingit with each other, to unravel thetheory of diseases." did you know darwin was thevery first evolutionary medicine guy? but there's somethingfunny about this. darwin was not a twinklein his mother's eye even, charles darwin, in 1794.
this, in fact, waserasmus darwin. and these are thevery opening lines of zoonomia, his famousand somewhat sexy poem, that took thebritish isles by storm. he was a rotund physician. on his carriage,he had his motto, "everything from snails." and the local vicarsaid, sorry, dr. darwin. get that off your carriageor i will see to it
you have no more cases. so he painted itover on his carriage. this conflict kind of stuff hasbeen going on for a long time. so what are the originsof evolutionary medicine? first of all, erasmusdarwin, a physician. his son, robertdarwin, a physician. and these physicians ate well. robert darwin was 350 pounds. this is a well-fed physician.
and then there's a morelightweight fellow in terms of his robustness,charles darwin, who tried medicalschool and dropped out. who inspired darwin to getinto all of these ideas? people talk about creationismand intelligent design, and that kind of thing, whichis not our business here. but it's important to recognizethat william paley, who wrote natural theology,really the foundation stone for a lot ofintelligent design,
he was the inspirationfor darwin. darwin read thisbook at cambridge. and what darwinsaid about it was, "the logic of paley'sevidences of christianity and of his natural theology gaveme as much delight as euclid. the careful study of theseworks was the only part of the academiccourse at cambridge for four years, which wasof the least use to me in the education of my mind."
why? because it's a wonderful book. it's just a wonderful book. if you want to look at someoneanalyzing nature and the body with extreme acute observation,it's just a wonderful book. he was really spot on. paley's explanationfor these things was somewhat different thanthe ones darwin would describe. but observation is wherewe start in science.
and it's good no matterwhat theory you used. darwin observed pigeons. and he raised pigeons. he would ask thequestion, do they all come from thesame stock or do they come fromdifferent species? and i use a slidelike this when i'm trying to explain toaudiences about selection. selection is when inheritedvariations in a trait
influence thenumbers of offspring. the trait will changeover generations. i try to make it assimple as possible. and it doesn'tmatter how simple. it turns out it'sa subtle concept, this business of selection. and i learned that almosttraumatically at a meeting in italy a littleover 10 years ago. we were at the spoletoscienza,dedicated entirely
to evolutionarymedicine and a audience of a couple of thousandpeople just outside of rome. and steve gould was there. and i wondered what he wasgoing to say about my talk. because a lot of my talk wasabout adaptation and things that he sometimes had a littlebit of skepticism about. so i was very eager to seehis response to my talk. and steve says,nice talk, nesse. and i though, ah.
and then he goes on. and he says, butthey had no idea what you were talking about. i said, what do you mean steve? and he says, youdidn't explain how selection works in evolution. you assume they know that. they don't understand that. so ever since, forevery audience,
i try my best, in twominutes, to at least talk about what we're talking about. selection, i think we getourselves all tangled up in knots talking aboutnatural selection. let's talk about selection. selection is whatwe're talking about. if individuals, of any kind,tea cups, pennies, coins, vary on a trait that influencesthe number of offspring passed on, and that variationis passed on,
then the group will changeover the generations. this is not a theory. this has to be true. and most of you haveat home a penny jar. i'll ask you toexplain for me why is your penny jar colored brown,and not a nice mixture of brown and silver. it's selection. your penny jarstarted off like this,
with a nice mixture of coins. you throw a randombunch in there. but you take out a nonrandomcollection of coins. and after a few months, yourjar starts looking like this. eventually, you get to takeit to the grocery store and dump it into a machine. whenever variation influencesfuture representation in the group, the groupis going to change. for students who are livingin really cheap apartments
near cambridge, ifthere are any still, you probably have a collectionof glasses in your cupboard. and i can tell you what yourcollection of glasses are like. they're a motley mixture allkinds of glasses that are not too fragile, those arebroken; not too nice, those have been stolen; nottoo small, those are useless; not too large, those don'tfit in the dishwasher. it's a motley collectionof sturdy glasses nobody else wants.
and the explanation forthose glasses is selection. it's everywhere. what's on television? we could go on. selection alsoshapes adaptations. and the key principlehere is it's "within species variation." all of those graphsshowing humans emerging from some others,that's confusing.
within species-- these arehawaiian honeycreepers. and there's one thing differentabout all of these individuals. they have differentcurves of their beak. that one has kind ofa really short one. that's a very crudebreak, very curved beak, that's kind of a straight beak. these honeycreeperslive by getting nectar from flowers that are curved. this one has a beak toocurved to get into the flower.
this one has a beak that'sa little bit too straight to get into the flower. this one has a beakthat's just right. it gets more nectarthan the others. it has more eggs. it has more offspringthan the others. and as a result, overtime, the honeycreepers become more like this one. if the flowers change,the beak would change.
there's nothingmysterious about this. you can study this inthe hawaii honeycreepers. and it's lovely tostudy them in hawaii because we know they allcame from the same stock. and we can trace, on theone hand, their phylogeny, showing that stock and how theyall diverge from each other. this is the one iwas just showing you. they all have differentbeaks because they eat different foods.
thick beaks for hard seeds. fine beaks for grass seeds. but notice that there are twodifferent things that darwin discovered. and people don't oftenappreciate that enough. one is the phylogeny andthe unity of all life. but separately, andpossibly more important, definitely moreimportant for medicine, he discovered thereason for why traits
work so well, adaptation. why the beak is so wellsuited to its function. in medicine, we alltalk about the eye as being so incredibly perfect. and it's really fabulous. why is it that the onlyclear tissue in the body is right there, justwhere it belongs? that's so neat. and then there's an iris thatgets bigger when it's dark
and smaller when it's-- and theneyes can move right and left. and it's just fabulous. darwin, in fact, himselfsaid, i can hardly believe that somethinglike this could be shaped by natural selection. so if you havetrouble believing it, you're in very good company. but this is the first twoyears of medical school. let me take youto the second two
years of medical school,when you go into the clinic. what do you see then? somebody blew it-- blind spots. would you have a camerathat has a big hole in the middle of the film? no, no, no. you'd never do that. our eyes have a blind spot. vessels block the light.
the vessels go between thelight and the receptors. it's stupid. nearsightedness,cataracts, farsightedness, retinal detachment,and glaucoma, who designed this thing anyway? it seems like some drunkon a friday afternoon. it's really a problem. and this is what struck meall through medical school. some things i saw wereso incredibly perfect.
it was very hard to believethat natural selection could do them. and some were suchbotched jobs that it was like some malevolentsomebody or another was just out to make our lives fullof suffering and sickness. how can we explain howsome things are so good and other things are so bad? now, the problem isthat natural selection seems to explainwhy things work.
so it doesn't seemall that relevant. first, let's have youall design a better body. especially for the kidswho are in high school here and those who don'tdo biology, you don't have to have afancy advanced degree. the first thing you do isget rid of the wisdom teeth. you don't really need them. how about the appendix? no thank you.
let's just pass on that one. how about makingyour bones stronger? good idea. improve the immune responses? not so much infection,that sounds good. enlarging the coronaryarteries, i'm all for that. i'm all for that. and then freud tried tofigure out what women want. he didn't know what women want.
i know what women want. women want-- ah, whew. come on, go back,go back, go back. women want a zipperso that babies can exit so much more easily. it's silly to gothrough a bunch of bone. and it's ridiculous. so again, why hasnatural selection made some of the bodyso perfect and parts
of the body botched jobs? this is the question. 153 years afterthe origin, there is still this huge gap betweenevolution and medicine. there are a few bridges,infectious disease; tracing phylogenies,especially phylogenies of people andbacteria; and genetics. but it's a giant, giant gap. very few doctors haveever had a chance
to learn even the rudimentsof evolutionary biology. and i keep beingsurprised by that. i keep, again, expecting thati'll somehow come someplace and all the doctors willreally understand evolution. and in 2009, this was the 200thbirthday of darwin's birth. and if you want tobe really famous, i encourage you to make sure youpublish your big thing exactly 50 years after you'reborn so you can celebrate the 150 and 200th all together.
it's was a great year. i got to travelall over the world and talk with audiencesabout this work. and i heard some of the world'sdistinguished scientists saying some things thatmade me really pause. for instance, somesaid adult diseases are common because our ancestorswere all dead by age 30. that's not true. the average lifespanmight have been 30.
but a lot of hunter/gathererswho lived to 30, lived to 50, or 60, or 70. and that's not true. aging exists to makeroom for new individuals so the species can evolve. now, i like that idea. that's the idea i had as asophomore undergraduate, that got me intoevolutionary medicine. and it wasn't until i reachedmy colleagues at michigan
and started talking with them. and finally, i got my nerve up. and i said, i've gotthis idea about aging. what do you think? and my dear friend,bobbi low, was the one, she's a goodevolutionary biologist. she says, nesse, i thoughtyou knew something. you don't know anything. you never heard ofgroup selection?
you've never read williams? what are you doing here? but she and everybodyelse turned out to be very nice to me in thelong run and explained to me the evolutionary biologythat now, i think, all doctors need to know. what flabbergastsme is we all should catch on to thiskind of thing by now. that doesn't work becauseit's group selection.
this is suggestingthat traits evolved for the good of the group. sorry, that doesn't work. cancer arises frommutations that are needed for evolutionto improve the species. one of the world's mostdistinguished cancer researchers, at a giantmeeting, said that. and that doesn't work. things can't work for thebenefit of the species.
new pathogens becomemild with time because there's no pointin killing your host. that kind of seems sensible fora bug to not want to kill you, so it can spread more later. but it doesn't care about you. all it cares aboutis doing whatever will spread itself the fastest. and, of course, it doesn'tcare about anything. it's just inevitablethat it will spread.
and finally, oldage diseases exist because selection can'tinfluence anything after menopause. and there's a verysimple theory, now it seems simple, that billhamilton came up with 1964, pointing out the same genes youhave are also in your children and in your brothers andsisters and your parents. and therefore, ifyou do something, even after you can'treproduce yourself,
that makes them live longer,or have more offspring, you're helping your own genes. a very fundamental advancein evolutionary biology, but most doctors haven'thad a chance to learn it. they've never heard of it. it is coming, however. these two scientists,rosvall and bergstrom, did an analysisof the connections in the literaturebetween these fields.
and this littleline is exciting. this is a line fromevolution and ecology, to medicine direct, withoutpassing through neuroscience, psychology, or molecularand cellular biology. this line didn'texist 10 years ago. but now there's a steady streamof people in medicine starting to make use of basic principlesin evolutionary biology. we have been celebrating thisyear the 20th anniversary. and it was verygratifying to have science
write a little article aboutour article 20 years later. they called it "darwinianmedicine's drawn-out dawn." and that's true actually. it has been somewhat drawn out. but it's getting there. there are all these thingsthat have happened though, that i'd like to convinceyou that this field is on a phase ofexponential growth now. this is the bookgeorge and i wrote.
this is one stevestearns edited, which is probably the definitivetext for the field now. a wonderful bookby anthropologists on evolutionary medicine. paul ewald is one ofthe leaders of evolution and infectious disease. and here's what's cool. there's the secondedition of that from oxford press two years ago.
the second edition ofthat from oxford press, completely rewritten. that's a new textbookof evolutionary medicine by peter gluckman, the onlynew zealander in the institute of medicine in this country. and finally, ofdeutsch, we have a book about evolution andmedicine as well. so it's comingpretty quickly now. there's not nearly enough.
but we're getting there. other things thatare happening, i had an opportunityto work with a group at the wissenschaftskollegin berlin for year, to try to figureout how we could grow this field ofevolution and medicine. we had a schwerpunkt, ahardworking, focused group. and it turned out tobe very productive. one of the thingswe did is decide
we need to communicate somehow. so we created ajournal online called the evolution ofmedicine review. and in that journal, you'll findeverything about conferences and meetings and coursesand especially new papers in the field. once or twice orthree times a week, you would get amessage if you join. this is the worldhealth summit meeting.
interestingly, they cal;led thatworld health summit for leading hospitals from allover the world, the "evolution of medicine." and detlev gantenhelped that along. we had a symposium on diseasesof modern environments. a special issue ofpnas came out in 2010, with a bunch of special articlesabout evolution and medicine. and more recently,we've started a course at mount desert island,in arcadia national park.
we had the first one last year. and this is a picture of someof us at our concluding dinner. we're doing it againthis year in august. there's a few spots left, ifanybody's really interested. the focus is on evolution,infectious disease, and cancer. it's probably the only placewhere you can go and get cle credit for tryingto get your feet wet. it's more than your feet wet--a crash course in one week on how evolution canbe useful in medicine.
two journals are launching. paul ewald has stated onecalled evolutionary medicine. and steve stearns is goingto edit one called evolution, medicine, and public health. both should be on the newsstandswithin the next six or eight months. so this is all theorigins of new interest in evolution and medicine. where did it really come from?
what was the dealthat got this going? there's been a lot of evolutionin medicine all along, infectious disease,genetics, phylogenetics. that's not new. i think it's the question. it's not data. it's a questionthat got us going. joseph needham was afamous english philosopher of science, who says"progress in science
consists not so much infinding the right answers, as of deciding whatquestions are sensible." and you can find lots ofquotes from famous scientists. i also like jonassalk, "what people think of as themoment of discovery is really the discoveryof the question." so these are the characterswho i found so inspirational. george, standingback here, ernst mayr here, andjohn maynard smith.
i just appreciatedall of them so much. this was at the1999 crawford award. it's the nobelprize you get if you work in evolutionary biology. ernst mayr inspired mehugely with his book, the growth ofbiological thought. maybe some of you had theprivilege of knowing him. i so wish i had been able to. he says, "nobiological problem is
solved until feel both theapproximate and evolutionary causation has been elucidated." clearly, what's he's talkingabout is the mechanism and why it is that way. "furthermore, the studyof evolutionary causes is as legitimatea part of biology as is the study of the usuallyphysico-chemical proximate causes." i read that and ithought, oh, oh.
in my whole medicaleducation, i've only been studyingproximate causes. what if we applyevolutionary causes and try to understand diseasefrom that point of view? again, niko tinbergenand ernst mayr are the people wecan really thank for this profound distinction. and i consider it the singlemost important distinction in biology.
if you don't getthis one, you really can't make sense outof a lot of things. so george williams and i startedtalking for days and weeks. and this makes me sympathetictowards my students. we asked each other, so why didnatural selection shape cancer? why did natural selectionshape atherosclerosis? why did natural selectionshape kidney stones? we took these questionsvery seriously. we were treating these diseasesas if they were adaptations
shaped by natural selection. talk about a big mistake. it just was wrong. this is the wrong question. we were never goingto get any place. my students still do this. most people do, whenthey get into the field. but it's a mistake. when we were trying toask the right question,
we made progress. why has naturalselection left the body so vulnerable to disease? we don't want to explaindiseases through adaptions. we want to explain traitsthat could be a lot better, but aren't. parts of the body,again, are exquisite, much better than any mercedes. parts of the body are reallybad, worse than a yugo
on blocks. and the question is why? so the answer i wastaught in medical school, and that mostphysicians believe, is that the body isbasically a machine. and there are partsthat wear out or break. this is a proximate approach. and there are limits to whatnatural selection can do. and this is a profoundpart of an explanation
for why we'revulnerable to disease. however, whatgeorge and i finally did over the next year orso is try to figure out, so what are the evolutionaryreasons for the body not being so good? can you see howparadoxical this is? before we weretrying to figure out how evolution makesthe body good. now, we're trying tofigure out why evolution
makes the bodyreally not so good. how do you do that? six reasons, six reasons. the first is mismatch withthe modern environment. we can't evolve as fast asthe environment is changing. second is competitionwith pathogens. they evolve fashion than we can. no wonder we get infections. third, every traitis a trade-off.
nothing can beperfect in the body. constraints onnatural selection. a lot of things naturalselection just can't do. mutations happen. organisms, it turns outthey're not shaped for health. i find this verydisturbing still. organisms are notshaped for health. they're shaped for maximumreproductive success. and finally, defensesand suffering,
like fever, pain, andnausea, they're not diseases. those are useful responses,shaped by natural selection to help us in certainbad situations. so what i'm goingto do in a minute is give you quick examplesof each of these, ok. but first i want to emphasizethat this angle that george and i have taken is only a smallpart of evolutionary medicine. and it's so important to realizethat what george and randy are doing is a small part.
and there's thismuch larger field of applying evolution to allthe problems in medicine. in particular, threemethods well established. and the new questionsthat we're trying to ask, which turn out to be kindof difficult actually, but very engaging andpotentially very important. now, the examples. mismatch. what diseases are caused by usliving in an environment that
is very different from theone our ancestors evolved in? atherosclerosis, breastcancer, allergies, and autoimmune diseases. these three weremuch, much more rare even a couple of generations--well, couple of centuries ago. breast cancer, myfriends tell me, is 10 to 20 times morecommon, depending. what's going on? there's a frightening slide.
i like to go pastit pretty quickly. but before i do, you allare told by your doctor, keep your cholesterol below 200. and yet a lot of peoplestill get heart attacks. it turns out if you look,with data from boyd eaton, at the levels of cholesterolin cultures where they don't eat as well or sit ascomfortably as we do, they're more like 120 to130, not anywhere near 200. the norms that we set inamerica for our physiology
are just way off. this is anotherfrightening slide, the epidemiological transition. just in our lifetimes,for those of us who have been around a fewyears, rheumatic fever, hepatitis, all the infectiousdiseases have plummeted. triumph, mostlyof public health. on the other hand,at the same time, we have exponentiallyincreasing rates
of multiple sclerosis, crohn'sdisease, type 1 diabetes, and asthma. what is going on? i can tell you wedon't really know. but there's something aboutour very modern environments that's making us very vulnerableto autoimmune diseases. this is a brave doctor whorealized that culture started getting autoimmune diseaseof crohn's disease, causing terrible abdominalpain and diarrhea,
inflammation in thesmall bowel, mainly after they had been dewormed. in the south pacific,well-meaning doctors, and helpful doctors, wentand dewormed whole islands in the south pacific. and 20 years, later epidemicsof crohn's disease and asthma began. so he thought, ok,i'm going to try to treat some of mypatients with worms.
that's kind of bold. it turns out thoughthat about 2/3 of them got remissions fromtheir crohn's disease that they hadn't gotten before. now again, i should say,before i go on step further, that you'll noticethat i'm giving you about 120 examplesin about 60 minutes. and i try very hard to keep upwith all of these and i can't. so i rely on audienceslike you to set me
straight about anyerrors you detect. that helps me a lot. this one, i have donesome further reading on. and it looks like, withall new published results, the follow-up studiesare not as strong. but it still looks likethere's an effect here. there's something aboutworms that protects us. how about myopia? how many of you hereshare my nearsightedness?
and if we were on the africansavannah, what would it be like? for us it would belike, oh, hello, kitty. [laughter] i asked my professorin ophthalmology in medical school, isaid doctor, how can it be that there are these genesfor myopia when it would make us just fatally flawedon the african savannah? and he said, dr. nesse,mutations happen.
you've got to get used to it. natural selectionisn't that great. but now i get my revenge. because in fact,mutations do happen and natural selectiondoes have severe limits. but that's not theexplanation for myopia. myopia is a genetic quirk. it's a quirk inthat these are not abnormal genes thatare causing myopia.
they are genes thatinteract with something in our modern environment. and exactly whether it's readingor our diets remains uncertain, which is bizarre to me. here's an epidemic thataffects 30% of people in modern populationsand we haven't really figured out what itis that's doing it? we're right on the vergeof figuring this out. and right here, i'vehad a delightful time
talking with dan liebermanin your department of human biology. and how many people herehave plantar fasciitis, or bad knees, or bad backs? i mean everybody. 80% percent of people have badbacks at one point or another. and dan points out that theway that hunter/gatherers run is fundamentallydifferent from the way you run once you get inmodern running shoes,
with a big built-up heeland no flexibility here. essentially, you loseall of your muscular tone that makes your gait haveits spring and all the rest. and you weaken these muscles. and then when youdo go out running, you get plantar fasciitisand other kinds of injuries. whoever thought thatorthopedic shoes actually could be the problem,not the solution? and he's very firmabout saying don't just
start going runningbarefoot tomorrow. it's a slow transitionyou would have to make to get tomore normal running. but it's fascinating thatthe number of things we do, that we think are helpful, thatare in fact causing problems. competition with otherorganisms is the second reason. this is a nice study. of 480 kinds of bacteriafrom around the earth, how many antibioticswere they resistant to?
well, on the average,about seven or eight. now, you've got tothink for a minute. so have humans been peeing onall parts of the earth enough to make organisms resistantto all these antibiotics? that doesn't make any sense. where do antibodies come from? they come from fungiand from other bacteria. because these guyshave been involved in biochemical warfarewith each other,
not just for a million years,not just for 100 million years, but for a billion years. and they have beeninventing, evolving, all kinds of molecules that getthem an advantage ever since. and we exploitthose temporarily. this is penicillin resistanceto strep pneumonia. when my kids wereyoung, you gave kids a touch of penicillin. all gone.
now, we're edging up towards50% resistance or more. you all know aboutantibiotic resistance. there's no point intalking about it. it's a huge, hugepublic health crisis. we really can't keep ahead ofhow fast bacteria can evolve. one reason, perhaps, isthat we're not really using evolutionary biology. a wonderful articleby antonovics in plos points out that medicaljournals are nervous somehow
about using the e-word. in medical journals,only about 10% or fewer use theword "evolution" to describeantibiotic resistance. in proper evolution journals,it's more like 60% or 70%. i don't know why doctors arenervous about the e-word. but it's surprising. is it significant in any way? it's very significant.
this is my friendcarl bergstrom, who is a mathematicalevolutionary biologist. and this next parti'm going to tell you is grossly simplified,but still useful. sometimes doctors who wantto do evolutionary medicine have thought, ok, let'sprevent antibiotic resistance. how about if we allagree in this hospital we use antibiotics a forthe first six months? and then we'll allswitch to antibiotic b.
and then we'll allswitch to antibiotic c. this was actually donein a number of hospitals. but you can't justhave an intuitive feel about how naturalselection works. you've got to do the math. and if you do themath, carl demonstrated that what these well-meaning,so-called evolutionary doctors were doing was almostthe optimal way to generate multi-drugresistance quickly.
it's serious, this lackof evolutionary thinking in medicine. here's a good recent one. about 15% of the sugar inmilk from new mother humans can't be digested by the baby. now, that's the kind ofthing-- you could think, oh, natural selectionblew it again. but let's think for a moment. why would naturalselection make a sugar
that babies can't digest? well, what can digest it? it turns out thatbifido can digest it. and bifido are the good bacteriathat you want in your bowel. and this gives them a head startagainst all the other bacteria, really good stuff. example three, why ourbodies aren't better? if you have a kidwho is skateboarding, or you have done ityourself, you probably
have fallen forwardand your wrist always breaks in exactlythe same place. it's called a colles'fracture, right through the headof the bone there. why didn't natural selectionmake that bone thicker so this didn't happen? we've been falling longbefore skateboards. the answer is this. this is one of themiracles of human anatomy.
look at how you can do it. do you ever think about that? and if you do that,you can do this too. and that's very usefulfor early humans. if that bone was thicker,you couldn't do it. it's a trade-off. some people have this ideathat evolutionary medicine says everything in thebody is perfect. if you take nothingaway from this talk,
please take this away. nothing in the body is perfect. it can't be. everything is a trade-offwith something else. and there are a lotof other good reasons why nothing's perfect. another favoriteone-- i wish i'd learned this in medical school. bilirubin is the stuffthat makes your eyes yellow
when you have jaundiceand your liver is failing. so why does thebody makes jaundice? why does the bodymake bilirubin at all? it's a breakdownproduct of heme. but it turns out that biliverdinis more water soluble. and the body spends energy tomake this water soluble stuff into something that's toxic,and not water soluble. doh, i mean somebodygoofed in this one. but again, pause.
maybe there's a reason for it. and one of theplaces in our book where george and i reachedand made a good guess, with some information, bilirubinis a pretty good antioxidant. now, people say how do youtest theories like this? is this all just those stories? no. you can really test them, thesame way you do other science. in this case, youdo a knockout study.
this is the cycle that goesfrom biliverdin, the water soluble stuff, tobilirubin, that makes you yellow with jaundice. and it turns out that sendakand snyder made a knockout. it turns out every timethe cycle goes around, it knocks out alipophilic-reactive oxygen species. those are the thingsthat glom onto cells and essentially fry them.
and if you knockout thegene that makes bilirubin, cells die very quicklyfrom damage from oxygen. pretty good evidence thatthe bilirubin is there for a good reason. the question i asked myselfas a sophomore undergraduate is why is there aging? i'd never found williamsfamous 1957 paper, in which he pointed out thatthere are two possible reasons. one was already well known.
hey, after a certainage, selection isn't working anymore. at least by age 100,selection is not working. kin selection not excepted. however, what about genesthat might be selected for even though they cause aging? what if a gene makes yourbones heal more quickly, but it also causescalcium deposition in your coronary arteries?
and he pointedout, hey, that gene is going to be selectedfor, even if it eventually kills everyone. this is called thepleiotrophic theory of aging. "pleiotrophic" justmeans multiple causes of the same gene. a profound advance that'sled to a revolution in gerontology andstudies of aging. this is a graph i hadmade to amuse myself
once upon a time about whatif we eliminated aging? what if the mortality ratethroughout the entire human lifespan stayed thesame as it is at age 18? well, in that luckyinstance, about a third of us would live to be1,000 years old. but we don't. that's too bad. beta amyloid is the nasty stuffthat collects on your neurons and causes alzheimer'sdisease, at least
it's very strongly associated. and eli lilly did a giantstudy the last few years with a chemical that blockedbeta amyloid synthesis. and they were hoping that ifyou get rid of the beta amyloid, you would relieve theprogression of alzheimer's disease. nothing is moreneeded in medicine now than some way tocounter alzheimer's disease and obesity.
those are the two big ones. this fellow thought for a minuteand said, well, maybe there's some reason the bodyis making this stuff. i think i'm going to grindup some brains of people with alzheimer's disease andsee what they do to bacteria. he found out that theystop bacteria from growing. and then he used syntheticbeta amyloid and found out that they do stopbacteria from growing. and then in the coup, hereverse synthesized the sequence
for beta amyloid,the other direction. it turns out if you synthesizeit the other direction, it's not a good antimicrobial. isn't that cool? now, this doesn't leadto any conclusions. it doesn't tell you thatit's really an antibiotic. it just tells you we should bethinking about why it's there, instead of just assumingit's something bad that we're going to get rid of.
and this littleescapade cost eli lilly about $200 million or more. and we're stilltrying to find things that interferewith beta amyloid. and maybe that will work. i'm not saying weshouldn't do that. i'm just saying we should think. here's another good one. how about this one?
this fellow publishedan article saying that genes for type 1diabetes, the kind that means you need to useinsulin, might have evolved to protect against tissue deathand from freezing in the ice age. and the evidence is thatthere are lots of animals, like frogs andfish, that increase the glucose in theircells when they almost freeze in the winter.
and it protects theircells from damage. now think with me for a second. type 1 diabetes, insulin? no insulin, what happens? you die. this doesn't sound likeanything natural selection would actually shape, does it? and, in fact, when a newspapereditor called me and asked me about this article, isaid, are you kidding me?
don't you know that diabetesis an autoimmune disease that kills people? and this is preposterous. please don't publish this. but they did. and it spread allaround the world, in all the leading newspapers. and there's a messagein this for us that's terribly important.
the messages is that thisis very difficult science. now, this was a leading scienceeditor for leading paper. this is very difficult science. and a lot of times,smart people think things are true, when they'rereally preposterous if you look into them in any detail. now, this led me to spend alot of the last year writing an article called,"ten questions for evolutionary studiesof disease vulnerability."
if any of you teach coursesin this or are interested, please take a look at that. i wrote it because iwas so sick and tired of my students writingpapers that were kookie. and i wanted themto have some guide. if you can answer these 10questions and get through it, then you got a goodstart on something that might be sensible. there are so manyelementary mistakes
that are so easy to make. this is very hard science to do. four, constraints. there's a lot of naturalselection can't do. path dependence and mutations,a little quickly here. the octopus eye, no blind spot. how come we have a blindspot and they don't? it's just bad luck in theorigins of the tissues that led to our eyes andtheir eyes being different.
and there's noother explanation. but once you godown that path, you can't evolve in a way thatleads to 10,000 generations of blind humans inorder to fix it. this is just nevergoing to happen. and finally, we goto somatic selection. that means selection ofcells lines within your body. and unfortunately,one place this happens is the immune system,which is nice.
but in this one, it alsohappens in cancer tumors. and something i'vejust begun to grasp, when you think about cancer,it's this awful image. there's something inthere and it's growing. and it just grows, right? but think for a moment, whatpercentage of new cells that bud off of that tumorsurvive in the tumor? about 1%, 99 out of 100 die. this means there'svery strong selection
in the tumor forthose cells that can survive andbe the most nasty. this is profoundlyimportant for deciding on cancer chemotherapy. and again, when i was aresident physician, just learning medicine,i was taught we're going to use differentanticancer agents, one at a time, so that wehave one left in reserve in case we need it.
if those doctors hadreally understood evolutionary biology,they would have realized theyshould move quickly to triple therapy,which is what we do now, using multipleagents all at once to prevent these cellsfrom breaking through. david haig is one of yourtreasures here at harvard. and i won't try to explainhis ideas in great depth. but one simple-- simple?
one complicated, rich setof ideas he's developed is about igf-2, insulin-likegrowth factor 2. and the trick to thisis that it turns out that it's imprinted differentlyif it comes through the mother or through thefather, the same gene. it makes babies grow. and if it comes through thefather, it's not imprinted. if it comes throughthe mother, the mother puts a methyl group on itso it can't be expressed.
there's also another genecalled igf-2 receptor, which is exactly the opposite. and it's imprintedonly if it comes through the father,and not the mother. and he points out, what onearth is going on with this war going on between the maternaland paternal genomes? it turns out that hesuggested that maybe this has some selected benefit inthat maternal genomes benefit from limiting theamount of investment
in that particularoffspring because you'll be save them from the next one. paternal genomes benefit fromextracting as much nutrition from that particularfemale as possible, for this particular baby. it's very hard to provethis theory in a way that everybody will go along. but it's such creative thinking. and it might wellturn out to be right.
profound implicationsfor birth size, infants that are born with lowbirth weights, and the like. health is not selection's goal? well, how couldthat possibly be? well, think aboutit for a moment. there's a mutation thatmakes some individuals have more babies that die young. what happens to that mutation? it spreads.
do we have any examples of this? we do actually. there's one sex among usthat is relatively feeble, from an evolutionarypoint of view. you know who you are. if you go to a nursinghome and you look around, there are very fewof us guys left. we die, on the average, sevenyears younger than women. i tried to find that number,seven years, couldn't find it.
but the worldhealth organization has all the data you need fora great summer in your basement with an excel spreadsheet,which is how i spent my summer. looking at the mortalityratio of male mortality to female mortality,anything over 1.0 means that more men are dying. and they have the data by age,by sex, by decade, by country. so dan kruger and i have had agood time publishing on this. this is our most famousgraph, showing that even
before puberty, men aredying 50% more than women. and in boston today, for every100 women who died at age 20, about 300 men will die. can you believe that,three times as many? anybody want to startmen's health programs? there is a verysimple, small operation you could do tominimize your risks. nervous laughterindicates you understand. notice also the differencebetween countries.
it's dramatically differentin different countries, with columbia and russia wayat the top, and singapore and others at the bottom. it's of great heuristicvalue, this evolution stuff. it gets you to asknew questions you just wouldn't have asked before. and you see things that youwouldn't have come up with. last, defenses and suffering. it seems like somebody was beingquite nasty in designing us.
a lot of diseasesare-- seizures, cancer, those are diseases. but a lot of the problemspeople bring to the doctors are defenses, fever, cough,pain, anxiety, and depression, or at least low moods. these aren't diseases. these are usefulresponses if they're expressed in theright circumstance. and it was ed wilson whoinspired me about this.
i was in my psychiatryresidency, on the ward. there was all ofthese people with terrible emotional disorders. and i read this paragraph. "love joins hate; aggression,fear, expansiveness, withdrawal, and soon; in blends designed not to promote happinessof the individual, but to favor the maximumtransmission of the controlling genes."
i thought, oh, my god. i haven't understood the body. i haven't understoodanything about-- i had the entire wrong impression. i thought everybodybehaved to maximize health. and it's not true. and it just hit me likea bolt of lightning. and then i decided to get reallyserious about this evolution and medicine stuff.
in my work as apsychiatrist, i see a lot of peoplewith panic disorder. and for years, i triedto explain to them it's not your heart. no, you're not having seizures. it you're locus coeruleus inthe brain firing too much. it's the noradrenergicstimulation. oh? and my patients said, thankyou very much dr. nesse.
do you know acardiologist i could see? so finally, i startedrealizing a panic attack is afight/flight response. that's a false alarm. and this made me startwondering what is it we're doing inmedicine when we're blocking defensive responsesright, left, and sideways. are we hurting people? if natural selectionis so great,
you just think it wouldexpress defenses only when they're really needed. if that fellow is comingtowards you, should you run? yes. if you are at a watering holeand you hear a little noise behind a rock, that soundslike this-- ergh-- what should you do? it could be a lion. it could be a dog.
it could be a monkey. it could be just rustlingof leaves in the wind. should you run? well, it's anotherkilometer back to camp and you'd like to bringwater to your family. so you don't want togive up too easily. but on the otherhand, if it's a lion? so what do you do? you've got to calculate this.
and you're not goingto use calculus. all organisms have to makethese kinds of decisions. how do they do it? so i ended up havinganother long summer, learning math i neverthought i'd want to learn. let's pretend, for instance,that the cost of fleeing is 200 calories. the cost of not fleeing, if it'sa lion, is 200,000 calories. so it's optimum to flee wheneverthe probability of a lion
is greater than 100,000. do you know what that means? this means that 999 times outof 1,000, the panic attack will not be necessary, butit will be perfectly normal. again, this changedmy fundamental view of what i was doingas a physician. natural selection has all kindsof defensive responses going off, too much, too early, ortoo large and too intensely, pain, fever, nausea,and all the rest.
this doesn't meannatural selection goofed. this is the signal detectiontheory analysis you need. we call this the smokedetector principle. you can look it up thatway, if you want to. it means that falsealarms are normal. what do general physicians do? half of what they do is blocknormal defensive responses. so why aren't their deadbodies outside the door of your own physician's office?
and the answer is thesmoke detector principle. we can block these responsessafely, except for that one time in 1,000. and the mission here isnot to have doctors not treat with aspirin oralways treat with aspirin. the principal is we'd liketo teach doctors to think, using proper evolutionaryand mathematical principles about when and which patientsshould get which substance to block theirdefensive responses.
you all have smoke detectors. you put up with lotsof false alarms. because if that's happening,you want to know very early and get out. this is the slightlyfancy math that you use to actually figureout what the threshold is. it depends on thecost and the benefits and the signal to noise ratio. it's fun math, if youwant to get into it.
so summarizing thispart, and i only have a little part after this. why is the body better? six good reasons, we'vegone through all of them. and the point is notthat every disease needs an evolutionaryexplanation. i should change that. it is that every diseaseneeds to be considered in terms of why the bodyisn't shaped in ways that
make the body moreresistant to that disease? it's vulnerabilitieswe're trying to explain. now, i'd like to emphasize onceagain that this business of why bodies are not betteris but one subfield of evolutionary medicine. it's by no means the wholething, lots of other areas. so this is just one small parti'm talking to you about today. but i think there is a giantchange that all of this implies, that againhas helped me.
i've always basically thoughtabout the body as a machine. that's what we're all taught. and it's been agradual transition to realize that's not right. bodies are not machines. we use this metaphor. it's helped us toavoid vitalism. the body is shapedby natural selection. and my recent hobby horse is thephrase, "organic complexity,"
which is different from anykind of mechanical or computer complexity. not just more complex,but differently complex. the body's not a machine. it was not designed. it was shaped bynatural selection. this is the body, with arecurrent laryngeal nerve, for instance, goingdown from the brain, down around the aorta,and coming back--
a cockamamie scheme, you know. it's because it's shapedby natural selection. and just for thoseof you who are in medical schoolor physicians, you had to memorize the krebscycle at least six times, and parrot it back. but i'd like to tell youthat they were tricking you into thinking that it's simplethis is the real krebs cycle. that's much more ofwhat's really going on.
you also had to memorizehow different white cells interacted with each other. but if you lookat this, it's not like any engineer would design. you can't see thesmall parts here. but interleuken 4 goes fromt-cells to basal cells. it also goes fromt-cells to sb cells. it also goes from macrophages. all these substances areswirling back and forth
between all of these differentkinds of white cells. you could try to programit and decode it. but this is nothing likeanything an engineer would do. our models that we use, withlittle arrows and boxes, just can't do justice tothe kinds of complexity we see in evolved systems. the last example,the clotting cascade. another one any doctor memorizesonce or twice, at least, in their education.
and our human mindsneed this kind of thing to try to make sense of things. what's really going onin the clotting cascade? well, it's much more like that. and you can't memorize that. so it's no surprise youcan't get it in a textbook. but we should be trying to helpour students realize that this is the kind of thing thatnatural selection shapes. and this is why it's so hardto have targeted drugs that
do everything youwant and nothing else. a point, the body is not likea watch, nothing like a watch. it's nothing like any machine. it's much more likea tangled bank. it's a more organic,ecological, set of interacting cells andgenes and all the rest. so the conclusion, evolutionoffers medicine a lot. it offers specific methods,such as tracing phylogenies and calculatingpopulation genetics.
it offers a frameworkfor physicians to organize those 10,000facts you need to learn. it offers a biologicalview of the body. and i think for mepersonally, it just gives you a feelingfor the organism, in a very famousbiologist phrase. that's very differentfrom the feeling you get from a non-evolutionaryview of the body. we do need some things now.
education at alllevels-- how many medical schools have a coursein evolutionary biology? zero, in the world. how many have at leasttwo hours of lecture? about four or five in thiscountry, more in europe. it's really pathetic. but medical schoolsare like the human eye, a product of path dependence. and it's very hard forthem to make big changes,
especially since they don'thave evolutionary biologists on the faculty. but i think they will. it may take another 20 years. but we'll try to speedit along, those of us who are working in this area. we're creating training programsfor evolution and medicine researchers. and what'sdesperately needed, it
means nih does not haveresearch funding for any of the questions i justtalked to you about. and it's no wonder. it's a combination ofpolitics and people not really recognizingthat you can scientifically address these questionsabout adaptation. but i think it'll come. a lot of young people whoare interested in this kind of thing, will go dophds, and do research,
and become physicians. and they'll become deans. and everything will be fine. anyone who's interested,again our course is at mount desert island,if you're interested in that. probably there's about threeor four days until it fills up. and this is where we end. the bridge is growing. new bridge of askingevolutionary questions,
growing nicely. and if you wantmore information, it's at evmedreview.com. thank you very much.
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