natural treatment for the disease of asthma in children

- [narrator] this ucsd-tvprogram is presented by university of california television. liked what you learned? visit our website or followus on facebook and twitter to keep up with the latest programs. - [narrator] we are the paradoxical ape. bipedal, naked, large brained. long the master of fire,tools and language, but still trying to understand ourselves.

aware that death is inevitable, yet filled with optimism. we grow up slowly. we hand down knowledge. we empathize and deceive. we shape the future from our shared understanding of the past. carta brings together expertsfrom diverse disciplines to exchange insights on whowe are and how we got here.

an exploration made possible by the generosity of humans like you. (mellow piano music) - i have been a professor of medicine and a clinical cardiologistat ucla for about 25 years. but about 12 years agoi got a telephone call that changed my life. and that call came fromone of the veterinarian's at the los angeles zoo.

and he called me becauseone of their chimpanzees had woken up with a facial droop. they were concerned thatshe might have had a stroke. and he asked if i'd come tothe zoo and image her heart to look for blood cloths and other things that might have been the problem. and this is the hospitalat the zoo that i went to. and this is actually me withme my first non-human animal, and i'm going to come backto her in just a moment.

but a few weeks after ivisited with this chimpanzee i was asked to rule out atorn aorta in a gorilla. and not long after that there was a california condor that they noted a heart murmur in and they asked if i would look to see whether one of the valves was torn, which in fact it was. there was a california sea lion

whose lower body had filled with fluid and they were concerned aboutcongestive heart failure and asked if i'd come. and in this picture i'mlistening to the heart of a lion who had had a collectionof over 700 cc's of fluid in the sac in whichher heart is contained. and in a collaborative procedure involving veterinarian's and human cardiologist we drained the fluid from her heart.

and this by the way is a procedure that i have done onhundreds of human patients. but i must say that theprocedure itself was identical to the procedurethat i've done on humans with the exception of this. (audience laughing) and where is it? there we go, and that. let's get back to the my first patient,

this chimpanzee who hadthe suspected stroke. i remember when i first putthe probe into her mouth and slid it down the esophagus. i turned to the screenand this is what i saw. a four chambered beating heart, a left ventricle, a rightventricle, two atria, but i noticed that there were blood clots moving these round bouncing balls, and that the upper chambers were enlarged.

and as soon as i saw that picture it reminded me of a humanpatient i've imaged at ucla some weeks before who had the enlargedatria and the blood clots. and i realized that these two patients, one human and one chimpanzee had spontaneouslydeveloped the same kind of infiltrative heart failure that i have been treating for years

with high technology andadvanced pharmaceuticals. and i found myself beinga little bit surprised. but then i was more curiosabout why i was surprised. i mean, i certainly knew that we share the common ancestor with chimpanzees between five and seven million years ago, which of course is a blink in the scope of evolutionary time. and as an undergraduate,

i've worked for four years in a museum of comparative zoology. but when i gone to medical school and like most medical students today, what i have learned the connection between animal and human health was, was infectious, pathogenic, zoonotic. and of course there is no question that animals play an important role

in the transmission of diseases that have a high impacton human communities. even more so now the one health community is helping us realize that the majority ofinfections that will impact human populations are comingfrom animal reservoirs. but what i didn't learn andmost medical students don't, is that the father of modern medicine sir william osler is also considered

the father of modern veterinary medicine. and that one of his teachers,the father of modern pathology rudolf virchow wrote in the 19th century, "between animal and human medicine "there is no dividingline nor should there be. "the object is differentbut the experience obtained "constitutes the basis of all medicine." but what i was finding was that while i was taking care

of my human patients at ucla i would go to the zoo and i would hear the veterinarian discuss the management of metastatic breast cancer or the management of brittle diabetes, or the dosage of serotoninreuptake inhibitor drugs like prozac for some of their patients who are anxious or compulsive. and i realized that as muchas i knew about human medicine

i knew so little aboutveterinary medicine. and it turns out there has been a gulf between these two fields. now there are many reasons for that, some are historical, some are cultural, but i'm going to focuson two for a moment. the first i believe has to do with our essential ambivalence about embracing our own animal natures.

but the other is human exceptionalism. we all are scientist. many of us are scientist here, and we theoreticallyaccept that human beings are merely one species in aspectrum of other species. not uniquely unique butunique like all others. like this, and we can zone in and see, here we are. and yet, and yet, even the mostscientifically minded of us

may harbor some residualhuman exceptionalism. in fact, i believe thereis a medical expression of human exceptionalismwhich is contributing to this gulf between the fields. and i became curios. what is the extent of the overlap in the pathology of humansand animals and so i asked, do non-human animals develop heart attacks or failure?

type i, type ii diabetes? brain tumors, concussions, strokes? asthma, allergies,breast cancer, leukemia, infertility, painfulperiods, sexual dysfunction? and of course the answer to everyone of those questions is yes. now of course our bad human habits amplified the risk of disease. it is the basis of preventative medicine.

and i have spent 25 years encouraging improved diets and more activity. and yet, although our bad human habits may increase the risk of disease, the essential vulnerabilityto disease is ancient. let's quickly talk about two big killers, breast cancer and heart disease. we know that breast cancerhas a high human impact on the human community,

it's the leading causeof cancer among women. but breast cancer is not unique to humans, in fact, many of youwho have cats may know that cats are at risk,dogs can be as well. this is a mastectomy scar from a cat whose owner felt a masswhen she was petting her. and in fact breast cancer has been found in mammals of almost everyvariety from polar bears to elephants, to marsupials, llamas,

marine marine mammals, beluga whales. in fact, notably, there seems to be a particularly high rate of breast cancer among some big cats. we can talk about that inanother time why that might be. but it's notable, onefascinating connection is that the reason that somejaguars have a particularly elevated rate of breast cancer is probably related to amutation of the brca1 gene.

and it is the same mutationthat makes some human females at elevated risk for breast cancer. now of course there areregions of the world where practices, habits,genetics, diets are different, and the rates of breast cancer are lower. but that merely underscores the fact that while our bad human habits may increase the risk of our disease, the age of mammals startedabout 200 million years ago,

and i suspect that thevulnerability therefore to breast cancer can be stated in a sense to be as old as that. what about heart attacks? so cardiovascular diseaseit is the number one cause of death globally. in the united states thosestatistics are amplified. and we know that mostheart attacks are cause by the progressive build up of

atherosclerosis in the arteries. that eventually thatatherosclerosis breaks, there is a blood clot that seizes the flow of blood through the artery and the muscle downstream dies. and in this section of an artery, you see the atherosclerosis, the plaque, it has fractured, there is a blood clot and this individual died of a stroke.

but this individual was not a human. what we see here is anegyptian vulture rather, flying in the base of the himalayans. and it turns out that if you look at a phylogeny of atherosclerosisacross avian species, every place that there is star, there's at least onespecies with in this order in whom atherosclerosisand stroke, heart attack, and other clinicalsyndromes have been seen.

now, of course our bad human habits amplify the risk of disease. i've spent my life as a clinician, helping patients modify their lifestyles. we know that. we know that bad human habits do contribute to heart disease but recognizing that after a sclerosis and heart attacks andstrokes have been identified

in animals as varied aswalruses, dolphins, camels, and of course human suggest that well bad human habits mayamplify the risk of disease, the essential vulnerability is ancient. and again, the timelinepointing to atherosclerosis. and, if this is trueof the somatic diseases like heart attack and breast cancer, it is also true for mental illnesses. there's a hair plucking syndromeseen here in this picture,

where people pluck out thehair of their eyelashes, of their, any part of their body. but it is remarkable thatthis bears a similarity to a hair plucking andfeather plucking syndrome that is seen in some bird species. you can see that this parrot has plucked, denuded his thorax. and it is notable that thecompulsive tail chasing seen in bull terrierstreatable with prozac.

or the flank sucking, the compulsive flanksucking seen in dobermans, treatable with prozac. there's similarities to thecompulsive behaviors we see in some humans with obsessivecompulsive disorder. and it is notable thatlike some human beings with anorexia nervosa, some non-human animalsrespond to social stress by starving themselves sometimes to death.

while others deal with stress by causing themselves to regurgitate. our bad human habits mayincrease our risk of disease, but the essential vulnerabilityto disease is ancient. why is this important? there are scientific and medical advances that can come of thinking comparatively, looking across species. translational medicine traditionally means

taking research that isbeing done at the bench in the laboratory andbringing it to the bedside. but i would suggest thatthere is another way of working translationally. and that is by looking acrossspecies and across time for connections thatgenerate novel hypothesis that can ultimately betranslated into science that can save lives. further more, i believe these insights

have the potential to reducestigma and increase compassion for people suffering from physical illness and mental illness. i would like to end by modifying the words of the late great susan sontag to reflect the species spanningnature of health and disease and the deep and ancientconnection we all share not just with other human beings but with all of thepatients on the planet.

she wrote, "illness is the night side of life, "a more onerous citizenship. "everyone and everything whois born holds dual citizenship, "in the kingdom of the welland in the kingdom of the sick. "and although we all preferto use the good passport, "sooner or later each of us is obliged "to identify ourselves ascitizens of that other place." thank you for your attention.

- i think i'll start off with a evolutionarily very strange photo. this is heidi klum, thesupermodel, with her four children. and this is an almost unique sort of photo in the mammalian kingdom. and why is unique? you won't see a chimpanzee mother with four children underher care at anyone time. a chimpanzee mother raisesher offspring to independence

before she has the next child. same with gorillas with orangutans and pretty well mostof all other primates. a mother can only have another child once the previous child is independent. but here is heidi andshe's got four children all of different ages, and all of them dependentfor their well-being on parental care, maternal care.

now, raising four childrenat the time is hard work and there's an interestingevolutionary question how human mothers are able to do this. but it creates thoughts ofinteractions among siblings that you don't find elsewhere. i should point out that thereare of course other mammals that produce multipleoffspring at the same time. they produce it later, but in those cases all of thoseoffspring are the same age.

now the existence of multiplechildren all dependent for at the same time from maternal care means that tend tocompete amongst each other for maternal care and attention. and when i look at photos like these i always like to look where are the hands? and so if you look at this picture, here is heidi's right hand, is holding her youngest child.

her other hand is holding the hand of her eldest daughter here. and she is sufficiently rich that she can afford another pair of hands to look after her two other children. so here's one of herhands holding this child, and then the second hand of the helper is sort of hidden behind her body. so, raising children is hard work.

raising a child is not cost-free, and sometimes peoplechallenge me about that. but think about it, if raising children weren't costly, a natural selection x to maximize lifetime reproductive success. if there were no cost of child raising mothers would have evolved to produce an infinite number of offspring,

which they clearly don't do. offspring compete formaternal care and attention. that's if you're using yourright hand to hold one child, you don't have the right hand available to grab another child whenit's getting into danger. now there's another interestingthing about that photo, and this is that as it's well-known heidi's eldest daughterhas a different father from her other three children.

and this genetically createsan interesting asymmetry. so all of these four children are related to each other maternally. if you pick a gene in heidiits got a one chance in two of being present in each of her offspring. these are all maternal half-sibs. so they're all related maternally, but the paternal genes of this child unnecessarily absent fromthe three siblings there.

so this child is unrelatedfor her paternal genome to heidi's other three children. and this leadsevolutionarily to a conflict within the genomes of children over the extraction of care from mothers which ultimately translatesas cost of their care having impacts on their siblings who might be maternal half-sibs. so maternal and paternal genes of a child

disagree over the value of half-siblings who share one parent but not both parents. and so here's the sort of a graph that you've seen before in earlier talk. i put fetus here but i'm justreferring to a child here. we're looking at affectson fitness of the child. an affects on fitness of it's siblings. and just dividing this space. there are some sorts of outcomes,

some things that can happen that are a benefit to thechild and to its siblings. there are some thingsthat are a cost to a child and to its siblings. and then there is this own of trade offs where some action is benefiting one child at the cost to other children. that's the holding ofone child in your hand, meaning that that hand is not available

to look after other children. so these are the science ofa trade off in parental care. and so just looking atwhat natural selection maximizes in this situation, so first of all i'm going to look at natural selection actingon genes of maternal origin in a child with respect tocost on maternal half-siblings. the offspring of other fathers. and so natural selection is predicted

to maximize this sum here. this is the benefit to the child and this is the cost of thefitness of its siblings. the child values itself evolutionarily twice of your siblings because the gene in the child is definitely present in that child, but it's only got a 50% chance. this is a maternal gene ofbeing present in siblings.

so natural selection will favor behavior when this sum is positive, which is in this regionof the phase space, what's its called, matrilineal inclusivefitness is increased. but for paternally derivedgenes in a maternal half-sib, what's relevant is the effect on the fitness of the child itself because it is unrelated to its siblings.

so as long as the benefitfor the child is positive, natural selection will favor increasing demands on the mothers. so combining those two situations we have regions where there is an absence of evolutionary conflict between genes of maternal and paternal origin. this is where they both benefit. this is where they both suffer a cost,

a natural selectionwould act against genes with these sort of effects. but then we have a zone of trade off of conflict within the genome, where genes of maternalorigin would benefit, whether allocating moreresources to siblings whereas genes of paternalorigin would benefit from the child receivingmore maternal care itself. this is where the cost benefit ratio

is setting in between a half and zero. this is the zone of intragenomic conflict. and for the second half of the talk i'm just going to look atsome human genetic disorders where genes so calledimprinted genes have an effect, and these provide cluesabout the action of this evolutionary conflictduring human evolution. now an imprinted gene is a gene that is expressed differently

whether you get it from yourmother or from your father. it has an imprint a recordof its past history, what sex of body it was inthe previous generation, and that affects what it doesin the current generation. so paternally-derived genes in offspring are predicted to favor greater demands on mothers than willmaternally-derived genes in offspring. and so here we will look at an example of a chromosome regionon human chromosome 11

where there are some imprinted genes. let's focus here. this is a gene called igf2 forinsulin-like growth factor 2. here we're looking at the chromosome a child gets from its mother. and on this chromosomei've got a red dot there. the igf2 gene is not being expressed. where some the copy that thechild gets from its father the igf2 gene is being expressed.

igf2 is a fatal growth enhancer. this is a gene that ispromoting growth at the placenta and is increasing birth weight and it's not being expressedwhen it comes from the mother, but being expressed whenit comes from the father. now this is called imprinting because this hasn't anything to do with the dna sequence itself. in my body, the copy of igf2

i got from my mother is silent, but if i pass that silentcopy on to my children it's going to be active in my children because they got it from their father. in this chromosome regionthere is a second gene with the opposite pattern of imprinting. cdkn1c, this is acyclin-dependent kinase inhibitor. this is an inhibitor ofprogression through the cell cycle. so this is stopping cellsdividing and growing larger.

so this is an inhibitor of growth, and it shows the oppositepattern of imprinting. it's expressed off thematernal chromosome. so the gene coming from the mother is acting to reduce growth. whereas the gene copy comingfrom the father is silent. so, in the essence, we have a situation where simultaneouslyduring fetal development, we have a paternal foot on the accelerator

of growth here of igf2 being expressed from the paternalchromosome promoting growth. the maternal foot is off the accelerator, but the maternal foot is onthe break, reducing growth, and the paternal foot inthe child in the same cells is not applied to that break. and normal fetal development is determined by the balance of paternal acceleration and maternal breaking.

and so this internalconflict can be revealed in rare genetic disorders where parts of this process go wrong. so i'll start off with, i'll look at beckwith-wiedemann syndrome. this is a fetal overgrowth syndrome. so these children are born rather large. i have a friend who had beckwith-wiedemann syndrome as a child,

and she'd given me herbaby photo to look at. so here she is. she was about 13 pounds at birth. typical of beckwith-wiedemann syndrome, she has macroglossia, which is just what medicalpeople used to say, it's latin for having a large tongue. i suspect evolutionarily this is, the tongue muscle is thepump during breastfeeding,

and so paternal genes areparticularly involved in promoting the development of the tongue muscles. now what are the causes ofthis fetal overgrowth syndrome? in a number of cases, individuals turned out tohave two paternal copies of this chromosome region. this is called paternaluniparental disomy. so in this case, theyhave two copies of igf2. they have two paternalfeet on the accelerator,

and no maternal feet on the brake. so they have fetal overgrowth. it's also associated with a high risk of a number of childhood cancers. some other people with the same diagnosis of beckwith-wiedemann syndrome, the fetal overgrowth have a mutation an inactivating mutation inthe maternal copy of cdkn1c. so this is the break on fetal growth.

so the maternal copy whichis normally expressed is inactivated by a mutation. the paternal copy isinactivated as normally occurs, and so in this casethey've got a paternal foot on the accelerator of growth and no maternal foot on the brake. and this is associatedwith fetal overgrowth, and the similar clinical diagnosis. they'll apparently knotwith the increase risk

of childhood cancers. such a condition is interesting if, if a male who had this mutation, and had beckwith-wiedemann syndrome pass the mutant gene onto his children they would have normal development, because they would get anormal gene from their mother and the mutant gene that iscoming from the affected male would have been inactivated anyway.

so this is a case where a mutation is having an effect wheninherited from a parent upon sex but not from a parent of the other. silver-russell syndrome is a intrauterine growth retardation syndrome. and so here i have a pictureof two girls of the same age. this little girl here hassilver-russell syndrome, it's associated withvery low birth weights, not associated with catch-up growth.

so if not treated, thisindividuals grow up to be very small adults. it's also associated with severe feeding difficulties as an infant. some individuals withsilver-russell syndrome have two maternal copiesof this chromosome region. so now they have no paternal foot on the accelerator of growth. and two maternal feet on the break

associated with intrauterinegrowth retardation and small birth weight. other individuals have aloss of dna methylation at what is called the imprintingcontrol region 1 here. this leads to the inactivationof the paternal copy of igf2. so now they have no foot onthe accelerator of growth, and that's associated withintrauterine growth retardation. for the final part of the tour, i want to talk about adifferent pair of syndromes

that are associated withthe different cluster of imprinted genes. this reside on human chromosome 15, and here the imprintingis specific to the brain and doesn't occur in most of her tissues. i won't go into the detailsof naming these genes, just to point out thatthere are some genes, like this one here, that are not expressed onthe maternal chromosome,

but are expressed onthe paternal chromosome and other genes with theopposite pattern of expression expressed on the maternal chromosome, but not on the paternal chromosome. some interesting things in this region. here is where thesingle-nucleotide polymorphism, that in european populationsmakes the difference between blue and brown eyes resides. and sitting here,

a gene that i won't talk about. this gene mkrn3, so this is a gene that is only expressed when you get from your father but not expressed from the mother. when children have a mutation in this paternally derived gene copy, recent work from brazil said, they have precautions puberty

that they go through pubertyusually before age of 10 years. so this is suggesting that the paternally expressed gene on this chromosome is inhibiting pubertal progression, which raises some interestingevolutionary questions. okay, so here is a young childwith prader-willi syndrome. i'm going to focus onthe childhood symptoms of prader-willi syndrome. these children, some of you might know

in studying in the secondto third year of life, they go from being anorexic,having no appetite, to becoming hypophagic andthey become massively obese. but i'm just going to be focusing on the symptoms that these children have in the immediate perinatal period. so this girl is showing the hypotonia most individuals withprader-willi syndrome have a deletion of the paternalcopy of this chromosome.

so they've only gotmaternally expressed genes coming from this regionand no paternal copy. a few other people have twomaternal copies of this region, and they have prader-willi syndrome. so what this is showing is the prader-willi syndrome is caused by the absence of expression of genes that come from the father. interestingly, an individuals

with maternal uniparental disomy, this is one of the mostpenetrant causes of psychosis. sitting down in this region of the region, this is a gabaa-receptor cluster. and there appears to be some sort of parent of origin effect occurring here that predisposing these individualsto developing psychosis. so prader-willi syndrome is associated with the absence of expressionof paternally derived genes.

and therefore evolutionarilythis leads to a prediction that prader-willi syndrome should exhibit an exaggeration of traitsthat reduce demands on mother. so this region containspaternal accelerators on offspring demands on mothers. we're taking away those paternal genes, and so you should see in the child reduced demands on the mother. so let's look at the neonatal phenotype

in prader-willi syndrome. it's associated with low muscle tension, neonatal hypotonia. with a weak cry, these are low maintenancechildren, and with poor suck. so this children have littleto no interest in feeding, and they have very weak ornon-existing suckling reflexes. usually they have to have achew put in to the stomach, gavage feeding, to givethem adequate nutrition.

they show excessive sleepiness. the child was put to thatbed and it stays asleep. so this suggest that paternal genes that are absent in prader-willi syndrome promotes suckling and theyalso promote wakefulness. so in their absence you havea child that doesn't suckle and a child that sleeps through the night. and i have suggest that evolutionarily paternal genes are promotingmore intense suckling

and also night wakingin children in babies as a way of essentially exhausting mothers and delaying her return to fertility, delaying the conceptionof a younger sibling who will compete formaternal care and attention. interestingly deletions of precisely the same chromosome region caused a completely differently syndrome. this is a boy with angelman syndrome.

the majority of cases, 70%of cases of angelman syndrome have a deletion of thesame chromosome region, but in this case it's a deletionof the maternal chromosome. so they only have a paternalcopy of this region. so now we would expect anexaggeration of behaviors that increased cost to mothers. we know of couple of cases of women with prader-willi syndrome who had a deletion oftheir paternal chromosome

that were fertile and had a child and passed the deletiononto their children. their child got it from their mother, so the child of aprader-willi syndrome woman has angelman syndrome. some other individualswith prader-willi syndrome have been activating mutations. in this gene here ube3a, which is normally expressedonly on the maternal chromosome.

so now the maternal copyis inactivated by mutation, and the paternal copy isinactivated by genomic imprinting. and this suggest that angelman syndrome most of the symptoms are causedby the absence of expression of the maternally derivedcopy of this gene ube3a. so angelman syndrome ispredicted to exaggerate traits that increase offspringdemands on mothers. and i'll just look at some of the symptoms of angelman syndrome.

so angelman syndrome is associate with uncoordinated suck and swallow, but these children donot need to gavage fed, as it if there's hyper activityin the suckling reflex. they get adequate nutrition, so they don't show failure deprived. they have adequatenutrition as i've mentioned. they are hypertonic rather than hypotonic. they have ataxia, hyperactivity.

particularly tiring for parents, they have excessive wakefulness as babies. i know of clinical reports of babies who were awake 21 hours out of 24. parents are advised to get some sleep. sometimes they put thechild in a darkened room and close the door. angelman syndrome isassociated with happy affect, the laughing smiling child yousaw in the previous picture.

this is particular in interactionswith potential caregivers and it's associatedwith frequent laughter. these are happy smiling children. curiously, this is associatedwith a complete absence of the development of speech,or even of sign language, so these children have somedegree of cognitive delay. but the absence of speechseems to be out of proportion to the cognitive problems. it seems to be a specific deficit

in this imprinted disorder. the suggestion is the childrenwith angelman syndrome exhibit exaggerated attachment behaviors, but normally engage maternal attention and elicit maternal care. this is the laughing, smiling baby that the mother wantsto give attention to. and i'll finish with another photo. and just look at the hands in the photo.

so here we have mom holding onto the hands of two children and this child misses out anddoesn't get a maternal hand. thank you. - when we talk about medicine. i think it's quite important to think about what is medicine? it is the study, an intervention of humanphysiological systems and physical systemsand psychiatric systems

when they are dysregulated. to attempt to correct what is going on. to improve human health. and in order to do that we have to have a deep understanding of not only the dysfunctionof these systems, but how they function when doing healthy things within our bodies. and so to me the termmedicine really means

applied human biology. and as every biologist knowswe have a favorite quote which is that "nothingbiology makes sense, "except in the light of evolution." and this means that to understandthe organizing principles of any organismbiologically on this planet, we need to understandits evolutionary history and the theories of selective pressures that have shape that organismto function the way it does

in the particular contextin which it finds itself. and as an anthropologist who studies maternal health and infant development, i have a particularly favoriteadaptation that i care about. and it is the systhesis ofmilk from mammary glands which is the defining characteristicof our mammalian class. it's as barbara pointed out, why mammals are at risk of breast cancer? because we have mammary glands.

and mother's milkinitially a random mutation for a minor secretion thatperhaps hydrated young or provided rudimentary immunofactors has been shaped by hundredsof millions of years of evolution and natural selection to become increasingly complex, such that it providesnourishment for young. it provides comprehensiveimmune protection for the pathogens babiesare likely to encounter.

and it also provides bioactive hormones from maternal circulation thatcross over into the infant and influenced infantphysiological regulation. it is due to this complex biofluid that is food, medicine and signal that has led every major governmental and nongovernmental organization to recognize mother'smilk as both liquid gold. and breastfeeding as the gold standard

of early life input from the mother. however, because of the ubiquity ofmilk within our environment and it seeming replication in the form of artificial breast milks thatyou can buy at the store, we have come to take milk for granted and think of it as a standardized, systematized simple kind of thing, and we've lost side of the things

that make it incrediblycomplex and special. and it's that we havenot actually identified what are liquid gold standards. we do not have a systematicunderstanding of milk, how it varies? what does variance doeswhen ingested by the infant? and these are fundamentalthings that we need to uncover in order to better manage infant health within the neonatal intensive care unit,

and better target ourpublic health intervention. and so, i think anevolutionary perspective is incredibly importantin order to both design and effectively target research studies, but also to help inform our understanding of this dynamic system. because lactation is acomplex adaptive system in which natural selectionhas shaped mother's physiology and their mammary glandsto synthesize milk

in complex ways. and there's a fundamental thing that i think is very challenging when we're thinkingabout managing the health of a mother and an infant. because we think about how do we optimize that infant's outcome in thatparticular time and place for the challenges that infant is handling or trying to handle.

and this is challenging, because natural selectionhas not shaped mothers to optimized the outcomeof a particular infant. natural selection hasshaped mother's physiology to allocate investment in young across an entire reproductive career to maximize her reproductive success across her reproductive lifespan. and because of this,

we see that there are goingto be a number of tradeoffs in how she allocatesresources between her own body and how she is nourishing her infant. just like i can only spend a dollar once, an organism can only burn a calorie once, and if that caloriesburned on immune function it's not available to allocateword infant development. and we see the signatureof these tradeoffs broadly in how mothersare synthesizing milk.

but this evolutionarylife history perspective have not been systematically integrated into medical approacheswithin infant care management. the important thing there is that those food, medicine and signal of milk is going to vary across all mothers. the presence and abundanceof particular milk bioactives is not standardized, and in fact the signature in milk

across each individual motheris going to be different. when we look at milk synthesis across every single potentialscale of consideration, we find that milk varies. it varies across species. it varies acrosspopulations within species. across individuals within population. within individual across lactations. within individual within a lactation.

and we can actually seethe synthesis of milk and the composition ofparticular bioactives shift from hour to hourthroughout the day. and so to kind of thinkabout what are the signatures that we see in a milka mother synthesizes. so dr. elizabeth quinn has shown that just the fat content in milk, you can go to the store and it's processed and you can get it at 3%, 2%, 1%

or where the fats entirely removed, but across human populations the mean value of thefat content in their milk is substantially variable. we see gradients betweenrural and urban communities in things like theirminerals, fatty acids, hormones and sugars within milk. we see the signature of cultural ecology in the form of subsistencepatterns in their milk.

this has been shown forfatty acids, immunofactors, sugars and minerals. melanie martin now atyale university has shown that among horticulturist in the amazon that the omega-3 fatty acidconcentration in their milk is not only higher than that which is found in the breast milk of women living in the ohio river valley. but their ratio of omega-3's to omega-6's

is closer to what we consider to be most healthy for infants. across individuals, when we look at dairy cows asa model for lactation biology, humans and monkeys as anothermodel for human biomedicine. we find that maternal characteristics are going to lead their signature in milk. mothers who have better body condition, lower parasite loads, andgreater social capital

or access to resources aregoing to synthesize milk in different ways than motherswho are more constrained. we see this in the volume ofmilk that they're producing, the fat concentrationand hormonal signals. similarly across the same species we find that the infants characteristics are also implicated inthe variation of milk that mothers are synthesizing. so the age of the infant at birth

in terms of gestational age, the infant's sex whetherit's male of female. and whether or not the infant is sick are all implicated in different aspects of milk composition and production. these differentiatedbiological recipe in milk has been found broadly across a number of different mammal species. and it's important to understand

that these does not necessarily mean that mothers are makingbetter or worse milk for either sons or daughters. but where sons and daughters have different developmental priorities, different developmental trajectories, we can expect that the milk that mothers used to nourish them is going to influenced aspects

of those developmental trajectories. when we go to the grocerystore or the pharmacy there's different deodorantfor men and women. right? but when we go into theinfant formula section in the grocery store, it's one size fits all. and we do not yet have enoughinformation scientifically to say that that's not best practices.

we haven't allocated theresearch effort to understanding, could we get better infantdevelopmental outcomes if we had more tailored milk for them? for infants who don't have access to breast milk for whatever reason. across time, we see that mothers early in their reproductive career, dairy cows, seals andmonkeys i worked with that adolescent mothersmake different milk

than mature mothers, that across parties, mothersmake different milks. this can be the nutritional components as well as a hormonalcomponents of their milk. and the signatures that thismay leave in infant development are still poorly understood. so lactation is anadaptive contingency system in which mothers haveaccess to more resources are able to up-regulateaspects of milk synthesis.

or mothers that are constraineddown-regulate milk synthesis to protect their conditionfor future reproduction. and this is shown both through the milk that their synthesizing and their behavioral dynamic with their infants. and this is a functionof maternal resources and their allocations amongdifferent tradeoff priorities. an adolescent 13 year old human mother is going to be constrained

in her capacity to synthesize milk. so that means that clinicalsupport for that mother infant that is going to have totake into consideration that the cascading trade-off allocations between her condition andthe condition of her infant. and this important because where milk production is constrained, where milk production is insufficient we see impacts on infant developments.

so milk composition andmilk volume is implicated in infant growth, their immune function, how microbes colonizedtheir intestinal tract, their cognition and their behavior. you see this in animal model systems in a variety of different human settings. and this is quite importantbecause in the media we're seeing a lot of push back on the specialness of breast milk

or the importance of breast milk because it's really centeredaround the narrative of best case scenario. for full term infants that are born healthy and raisedin an incredibly protected and buffered environments, the effect size that'stransferred by being breast fed or formula fed is goingto be fairly moderate. but when we anchor the narrative

to those best case scenarios we lose sight of many situations in which the consequencescan be quite a bit dire. so if we think about thepremature infant born in less than 39 weeks, that ends up in, a very,very young infants, 25, 27, 29 weeks of age that spend a substantial amount of time in neonatal intensive care unit.

breast milk or bioactivefeatures of breast milk can be absolutelycritical for their health. if we think of childrengrowing up in spaces with substantial infectious disease risk, then the immunofactors thatare present in breast milk and not found in other alternatives are going to be very important. in settings in which there'sthis substantial risk of development of allergies or other kinds

of autoimmune kinds of challenges, then breast milk maybe a buffer to that. and even when we think aboutthat best case scenario where individuals are most buffered and the affect sizes are most moderate. when we scale those up across a population the health consequences add up, and the healthcare dollarcost add up substantially. so we need to think aboutnot just best case scenarios,

not just one child interactions, but at public healthpopulation levels as well. so this is a complex adaptive system. and we can use thatunderstanding of these systems and how they've beenshaped by natural selection to identify particular strategies and targets for interventions. so some aspects of milk synthesize are going to be quite flexible,

some are going to represent constraints, and some are going to be fixedas a function of genotype or other kinds of variables. in this situations where this represent trade-offs of the mother, we can use public interventions,access to resources, social justice and publichealth interventions like the wic program, to help improve the resources

so mothers are not tradingoff to the same extent as they are when theyhave fewer resources. when the constraints become more fixed, when there isn't a capacityto influence mothers to up-regulate their milk synthesis or shift their milk composition, then we have opportunities inwhich evolutionary insights can yield important advantages to how we approach milk management.

so right now we seethat 20 million infants are born premature acrossthe globe each year. the vast majority of these are happening in the global south. and these infants are administered milk as a clinical intervention. so this is either donor milk, formula, or other kinds ofcommodified milk products, which have their ownbioethical considerations.

right now these milksrepresent mean values as though we know the gold standard. and this is erasing ofa lot of the individual or more specialized tailoredfeatures of the milk. and these products and interventions are based off of mean valuesamong what we would call or what joe henrich wouldcall weird populations. westernized, educated, industrialized, rich, democratic populations.

okay, weird. they're weird. and they do not necessarilyreflect ancestral conditions or the diversity of milksthat mothers are making. but if we make this our gold standard and it's not actually the best target for us to replicate or match, then when we're goingdown suboptimal pathway. so we can think about,

what do we know about milk? what has already been found out? and can we from theredesign clinical trials and other kinds of studies to see if there's added valuespace within clinical care? so right now in the nicu, some form of milk is being provided. can we do better if we start thinking in terms of precision milk

along with other aspectsof precision medicine? so can we do better ifwe match milk for the, whether the child or thebaby is a son or a daughter? can we do better if we givemorning milk in the morning and night milk at night? adults and childrenhave a circadian rhythm, in which are glucocorticoidsare higher in the morning and lower in the afternoon andevening and while we sleep. babies don't have a circadian rhythm,

they get informationabout a circadian rhythm through their mother's milk. so what happens when weprovide day milk at night? does that excite the baby's systems? this is a empirical questionfor which we do not have published information at this time. for babies that get milk. could we do better if we matchdonors in a selective way? that we add value by picking milk

from particular life history stages, or mothers of particulargenotype in the donor options. it's an empirical question,we don't yet know. the fut2 genotype influences what sugars and whether or not they'refucosylated are present in milk, and these are important for influencing the microbial colonization'sof the infants guide. can we target pooling milk across mothers to create a super milk that'sgoing to be quite important

for particularlyvulnerable or sick infants? can we mix glycans to maximize the health of the microbial systemscolonizing the infants gut? can we provide particularmicrobes to those infants? right now, all of themilk processing techniques in the neonatal intensive care unit involved neutralizingthese components of milk that we know arepotentially quite important. and lastly,

can we co-opt andbioengineer milk bioactives from other species that aresolving evolutionary problems that have importance forinfants in the nicu today? so when you look the marsupials, kangaroos, wallabies,they're born at very, very early stages of development. they have very undeveloped lungs. and there's milkbioactives within the milk that their mother synthesized,

that accelerate the developmentof their lungs specifically. could it be possible toreplicate or bioengineer that in ways that we can provide it to these 25, 27, 29 week oldinfants who had huge risk for pneumonial disease becausetheir lungs are undeveloped. and there are people in australia working on answeringthat question right now. they're using an evolutionary perspective of how natural selection has shaped

adaptations to solve problems, that had implicationsfor the unique challenges that humans faced in ourparticular cultural context. when most of these have been talking about donor milks and bioengineering, but there are many infantswho do not have access to milk for a variety of reasons. their metabolic disorders, other kinds of illnesses in which mothers

are not able to synthesize milk. there's historical traumasand cultural context that make it very difficult. there are infants who are raised by wonderful familiesthat don't include a mom. and these families rely invery important ways on formula. artificial breast milk. how do we make a betterartificial breast milk that delivers more of theimportant bioactives in milk

to help enhance those infants development? these are the kinds of things where we can take anevolutionary perspective, apply it to a variety ofclinical and cultural settings to improve human health. and this is what it means tobe thinking evolutionarily to approach medical conditionchallenges of human infants.