welcome. welcome to our thirdlongwood seminar of 2016. i'm gina vild. i'm the associate dean forcommunications and external relations at harvardmedical school. we're going to havea full house tonight, so may i ask you to pleasemove into the center so people who arrive latecan take the end seats and it doesn'tdisturb the speakers?
thank you so much. i'm happy to report that asa result of your attendance, both through livestreaming and in person, this has been the mostsuccessful mini-med school we have had to date. so i want to thank you. your engagement is impressiveand it is certainly appreciated. your completing theevaluation forms
helps us with ourplanning going forward. i encourage you to pleasecomplete the form tonight. that will guide us as wego into the next year. your help incrowdsourcing the topics helped ensure these wereboth timely and interesting to the community. and your engagementin social media, facebook, twitter, andinstagram has really helped expand knowledgeto the public.
so i invite you to join ourconversation tonight on twitter with #hmsminimed. i hope you'll join us for ourlast mini-med school longwood seminar on april 22nd. it's the new old age. and we will learn all about howour body ages, and importantly we'll learn howto keep it young. certificates of completionare available next week if you've attended threeor more mini-med schools.
if you can't be here,please send us your email address at theemail on the screen, and we'll mail it out for you. now tonight's topicon the seminar that you've all beenwaiting for is taking it all in, environmentaltoxins and your health. rachel carson, whoyou may know, she wrote in silent springone of the landmark books of the 20th century.
if we are going to live sointimately with chemicals, eating and drinkingthem, taking them into the verymarrow of our bones, we had better knowsomething about their nature and their power. in 1962 with thisbook, she sparked the modernenvironmental movement. silent springintroduced new ideas that rapidly became fodderfor public discussion.
people began talking aboutthe effect of toxic chemicals, especially ddt. their effect on wildlife,our environment, and on human health began to bequestioned for the first time. we've learned a great dealover the past 55 years about the interconnectionof nature and human health, yet thousands ofeveryday products are made with chemicals. clothing, cosmetics, toys, foodcontainers to name just a few.
and we know thatmany of the chemicals are not adequately regulated. rachel carson also wrote,if we have concluded that we are being asked totake senseless and frightening risks, we shouldlook about and see what other course is open tous, and that is exactly what we're going to do tonight. tonight, harvard scientistswho are experts on the nature and power of some commonenvironmental toxins,
will help us see what othercourse may be open to us. so let me introduce them. monica colaiacovo,who is a professor in the department of geneticsat harvard medical school. maitreyi mazumdar isan assistant professor of neurology atharvard medical school, assistant professor inenvironmental health at the harvard th chanschool of public health, and a pediatric neurologistat boston children's hospital.
but first we'll hearfrom david christiani, a professor of medicineat harvard medical school. he is the elkan blout professorof environmental genetics, and the director of theharvard education and research center at the harvard thchan school of public health. he is also a physician inthe division of pulmonology and critical care medicine atmassachusetts general hospital. doctor christiani hasexamined genetic factors that make peoplesusceptible to lung cancer.
at mass general,he also researches environmentalconditions of the lung. he runs a landmark 35-yearstudy of respiratory diseases that has determined the rateof loss in lung function among dust exposed workers. in 2012, presidentbarack obama appointed him to serve on the nationalcancer advisory board. please welcome ourguest speakers. thank you.
thank you all. thank you all, good evening. it's wonderful to see thebig turnout we have tonight. i'm going to useenvironmental cancer as an example ofenvironmental conditions that are preventable, eithercaused by the environment or to the extent thatwe know, environment contributes to theircauses, which is a problem. but it's also thesituation where there's
the opportunity for prevention. and so the title is preventingenvironmental causes of cancer. there are only a fewslides that are technical, and i'm going to reducethem very quickly to very understandable english. so i'm going to cover somebasic landmarks of what we call a cancer epidemiology,the study of disease distribution and riskin human populations. what's known aboutexposure and cancer?
why do we even make this link? and i'm going to touchon a presidential report that had implicationsfor a global cancer health. the report was focusedon chemicals in cancer. and then talk a littlebit about the challenges that we face inthe 21st century. so what are the landmarksin our understanding about how environment causescancer in human beings? in the 19th century,cancer was somewhat unusual
because people didn'tlive that long. and when it occurred, it wasgenerally considered incurable. 20th century, fastforward to about mid part of the 20th century,much of human epidemiology, particularly in europeand north america, shifted from the study ofinfectious diseases, flu, pneumonia, diarrhea, tochronic disease, ie now cancer. and then after world warii, cardiovascular disease. so you can see thisepidemiologic shift
in what causes morbidityand mortality in countries across the world as we movefrom infectious causes of death and perinatal andchildhood respiratory infection and diarrheato chronic disease. well, cancer is one ofthose chronic diseases. so exposures totobacco, diet, and some environmental chemicals--so that was about the time when researchers firstentertained the possibility that cancer can be preventedbecause we understand
the cause. you can't prevent something youdon't understand the cause of. so the late 20th century, early21st century where we are now, epidemiologic studies havegenerated population-based data identifying riskfactors for cancer that may have multiple riskfactors, not a single risk factor. and the developmentof new technologies to identify biologicalmolecules of exposure,
to identify geneticsusceptibility, and creating differentdeeper understanding of what causes it, and perhapsalso more opportunities for prevention. and that's where we are today. now cancer across theworld varies quite a bit. this is a busy slide, but allyou need to know is the colors. the red areas are veryhigh in certain cancers, and the green areas forthe same cancers are low.
so in the case of cervicaland stomach cancer, it's very high in certainparts of the world where there's not refrigeration. lung cancer is very highin the developed countries or industrializedcountries of the world, and those undergoing rapiddevelopment like china. so any kind of color mapyou use of cancer incidence varies a lotaccording to exposures and the economic status of thecountry which helps determine
those exposures. breast and prostatecancer, for example, are much more common in peoplein the industrialized world. and then if youlook here in the us, the number one cause of cancerdeaths in both men and women remains lung cancer. it's starting to trend downwardbecause of smoking cessation efforts that startedas early as 1964 when you see there wasstill a steep rise,
but real serious attemptsto restrict smoking that came into place inthe '70s and '80s where it was banned workplaces,public places, as you all know hotels, airplanes,et cetera, then you start to seeexposure patterns, use patterns ofcigarettes decline. and then there's a lag period. for a population to get sickfrom environmental cancer, usually there's abouta 20 year lag period
from when an exposure isintroduced into the population. so for cigarettesmoking in the britain, great britain, 20 years afterworld war i you see this peak. us, it was aroundworld war ii where there's a big bumpin cigarette smoking and when womenstarted to smoke more. and then you see 20 years later. well, it happens withthe other side too. when you start to see preventiveefforts be put into place,
it takes a whilefor the incidence to turn around andstart to come down, which is what you see there. this is women whereunfortunately lung cancer kills more women every year than thecombination of breast, ovary, and colon. and so it's still andwill be the number one killer for a long time inboth genders in the us. now i also want to touchon environmental cancer.
so the reason i talkabout smoking, by the way, is there was a strongenvironmental causes of cancer, of lung cancer. we know what the cause iseven without teasing out all the chemicalsin lung cancer, and i'll come backto that in a minute. but you know that stoppingor cessation efforts leads to a decrease in incidence. so we're able to, byidentifying and intervening,
make a difference. now childhood cancer, there'sbeen a lot of debate about whether childhood canceris increasing in the us. it's the second commonestcause of death of children in the industrialized world. and about 10,000 to 11,000kids are diagnosed in cancer probably pretty much everyyear, and almost 1,600 will die. so just look at the line. if you look at the surveillancedata on children with cancer
and do all the differentstatistical adjustments over the decades of'75 to 2008, there has been a gradualincrease in us mortality for all childhood cancersunder the age of 20. we don't know why. we suspect environmentprobably plays a role. this is just a pie chartof the kinds of cancers that children get. by far leukemia and brain orcentral nervous system tumors
lead the pack with a varietyof very rare, much rarer ones in there. so what causes cancer? why do we focus onthe environment? well, there are a numberof external factors that give us opportunities tointervene in cancer prevention. so one is industrial exposures. almost everyone inthe room has probably heard of asbestosand the problem
that asbestos caused, andhas caused, and still is causing in parts of the world,including the industrialized world. but there are many others. high exposures tended tooccur in workplaces because of the handling ofthe material, less so in the general environment. but you can haveexposures to cancer causing agents in water,soil, such as contamination
with arsenic orother carcinogens. then of course thereare lifestyle exposures. they're just asenvironmental, but they involve personal choice,whereas workplace would be an involuntary exposureor in the general community. tobacco use, diet,physical inactivity, and in the case ofviruses, sexual activity can transmit carcinogens orcancer causing agents that can then gain access to the body.
naturally occurringexposures, and we should point out that noteverything natural is safe. so ionizing radiation,ultraviolet light from the sun, radon,arsenic, infectious agents, they're natural, butthey're also dangerous. medical treatments not to beunderestimated these days. chemotherapy, which curesa lot of people every year, but the agents themselvesare carcinogens and they put treated peopleat risk for second tumors.
radiation, immunesuppressing drugs all can be externalcauses of cancer. now there are also someinternal factors that are not easy to control, if at all. genetic alterations,hormone deficiencies, imbalances, immune deficiency. and some individuals aremore susceptible to cancer than others based on heritablegenetic traits we get from our parents, orsometimes rare mutations
that we don't knowwhy they happen. and then there's no otherway to talk about that other than bad luck. or what we call co-morbidities. if you have onedisease, it's not cancer but it's an inflammatorydisease like inflammatory bowel disease, thatinflammation over time can put you at risk of cancer. so you have one conditionthat's non-cancer
contributing tocancer development, so-called co-morbidities. so let's talk a little bitabout the history of exposures. the occupational exposures werethe most dramatic carcinogen experiences for humanbeings with reference to it dating backto the renaissance. but the first known descriptionwas by a doctor percival pott in london who describedan unusual form of cancer of the scrotum of young boyswho were chimney sweeps.
we've all read charles dickens. you suffered through dickensin your freshman year of high school. you know that theconditions of the working class in britain in the 18thand 19th century was very bad. these kids were small andthey were up in the chimneys sweeping out coal, soot. in the soot he foundhe didn't know what was in it that caused cancer.
he had no idea. but he just made theconnection between soot and getting into the foldsof the skin of the scrotum, and then had to teachthe kids how to wash, and they stopped gettingthis kind of cancer. every toxicologycourse on cancer talks about the firstconnection made between a definite external agentand cancer in the literature. it took another130 years before it
was identified what it wasin the soot, the chemicals, the polycyclic aromatichydrocarbons that caused the cancer. in the 20th century, we hadmany other examples because of the rise of industry. asbestos, benzene,coke ovens, things called amines, aromaticamines, dyes, et cetera. and still today, more inthe industrializing world, occupational exposuresprobably cause at least 6%
of cancers in thedeveloped countries, and much more exposurein the developing world. and so what pott didn'tknow about in the soot that they found out in the1930s and '20s was there's this group of compoundsthat's also in tobacco smoke. it's in diesel exhaust. it's an oil emissionsand coal emissions, and they're calledpolycyclics or pahs. and we now know that those area very active bunch of compounds
to not single onethat cause cancers, and not just lung cancer, notjust skin or scrotal cancer, but also bladder and gut cancer. and they're in oureveryday environment, not just in thechimneys of london or in the workplaces wherecoal and oil is burned. so urban airpollution is loaded. wherever combustiontakes place is basically polycyclics released.
there's a steel plant inchina that's obviously a polluted workplace, but theseare dormitories and buildings where people live right here. and so it's a very intenseexperience for them to live and work inthis steel industry. a lot of these are polycyclicaromatic hydrocarbons that are cancer-rich compounds. cigarette smoke hasit, plenty of them. and this tobaccosmoke carcinogens
themselves are amixed group, and can cause a series ofreactions that can lead to damage to dna,and then mutation, and then cancers likelung or bladder cancer. we looked at this ina group of patients at mass general as to whyyoung people who start smoking at a younger age are athigher risk of getting cancer later in life than old peoplewho started at older age, and found that thereare more of these pah
bound to dna inindividuals' lung tissue if they started smokingat a younger age than if they startedsmoking at an older age. so it looks like it's permanentdamage in the lung tissue that carries throughlater in life. and we found that thepeople with certain kinds of genetic variationand metabolism are more susceptible to formthese so-called adducts, which are bonds, chemical bondsto dna in lung tissue.
finally, we also found when welooked at blood versus lung, again this is a prettygood correlation line that circulating bloodwas a pretty good substitute, because we can't get lungtissue on people in population studies, was a prettygood substitute for lung in measuringthese things. so urban industrialair pollution, mainly of air butalso of water, are rich in thesekinds of compounds.
we also, as another example,took a very different tact, looked at leukemia inchildren in taiwan. again, it's a busyslide, but i'm just going to point to this lineright here where we looked at children with leukemia. their risk of having childhoodleukemia was about 54% higher if they lived within 1kilometer of a petrochemical refinery than kids who livedfarther than 1 kilometer, adjusting for all other factors.
so i wanted to touchon the cancer panel just for the lastcouple of minutes. the panel wasestablished in 1996 during bill clinton'sreign to address frankly as possible keyissues in cancer. and each panel is done by topic,and there are several experts who then go around thecountry, interview experts, and talk to people in the fieldand talk to community members about what concernsthem about cancer.
and they did acouple of reports. one was on lifestyle factorsassociated with cancer, such as tobacco, andthe other was diet, and a third was inactivity. and in 2006, the panel wasasked to talk about chemicals in cancer, realizing thatthese other issues have been dealt with. and so a committeewas convened, and they reported a fairlyhard hitting report
that generated some controversybecause the committee was shocked when it reportedthat 80,000 chemicals were on the market and only severalhundred had been tested, pre-tested for theircancer potential. since early '70s, theinternational agency for research on cancer hadevaluated some 900 suspected carcinogens and foundthat 165 turned out to be definite in human studies,and another 265 as possible. and so this is a smallgroup of chemicals compared
to what's on the market. and so they criticize thecurrent regulatory approach in the us as evaluatingonly when there's evidence of possibledanger and setting standards only when thereis evidence of severe health effects, rather than acautionary or preventive approach. so they were a strongletter to the president saying there's a growingbody of evidence linking
environmentalexposures to cancer, and the public is becomingmore aware and more concerned, is expressing theconcern, and that we need to do more about it. the panel highlighted anumber of things individuals can do to reduce their exposureto potential carcinogens. this generated some controversybecause a lot of them had not been tested in trials,although they are prudent, except for number fivewhich we all know,
eliminating exposure tosecondhand smoke is important. so then the wholeissue of lifestyle versus environmentalrisk come up. it's impossible toquantify these things. they're both very important. so that some 45% percentof cancer in the west is felt to be due toeither smoking, diet, or lack of exercise. but that leaves the other 55%that we need to grapple with.
how much of that is environmentis still up for grabs, except we know that probably7% to 19% percent of that 55% is due to environmentalexposures. the thing to be carefulwith all these percentages is sometimes they interact. you can have a lifestyle factorand an environmental factor adding up to problem,bigger problem, such as asbestoslike in this picture. and asbestos andsmoking together,
rather than simplyadd risk to 15, multiplies the riskto greater than 50. so we have to do a lot to adjustour environments to minimize exposures topotential carcinogens. and some colleagues have raisedthe concept of the exposome. we have the genome. we have metabolome. we have the exposome,life-course exposure starting prenatally throughout life.
what can we do tominimize exposures to harmful agentsthat cause conditions like cancer and others? so the challengein our studies are to do better exposureassessment, where we can actually inour population studies figure out what we're exposedto, when, and for how long so we can get betterestimates in our studies. so global cancer epidemiology--this is what i want to end on.
we should keep in mind that morethan half of new cancer cases and deaths each year now occurin low to moderate income countries. it's no longer just a diseaseof industrialized nations. as infectious diseasecomes under control, you see more chronicillness like cancer and cardiovascular diseasecausing mortality in the world. and the spread of theso-called western lifestyle is an important factor, butalso the exposure potential
for industrial chemicals likeasbestos, benzene and silica. so we don't want to have theseoutdated assumptions of well, there's exposureswe choose to have, the exposures wedon't choose to have, and we can only control thosethat are lifestyle factors. and we reject that just as thepresident's cancer panel did, that industrialchemicals are still an important part of cancerin much of the world, and we need to control cancerby controlling these as well
as controlling those causedby tobacco, alcohol, diet, inactivity. they should becomplementary strategies. finally, gene-environmentinteractions. a lot of questions aboutgenetic susceptibility. some tumors are due tovery rare mutations that are inherited, makingsome people more or less susceptible to cancer. if they're veryrare, sometimes it
makes people very susceptible. but most of thegenetics we study, they make someone susceptibleonly if they're exposed. if we remove the exposure,the genetic variant by itself is not harmful. those are so-called commonvariants rather than rare mutations. so the contributions ofenvironment to cancer remains underestimated.
we know it's a problem. it's a bigger problem inthe rapidly industrialized countries of the world,and it spanned the gamut of traditional exposures we'veknown a lot about combined with new chemical exposures. and the contributionsof mixed exposures to cancer in bothwork and community still remain relativelypoorly understood, and we need to leap in ourexposure assessment tools
to get a handle on this sowe can prevent cancer rather than treat late stage cancer. so for clinicians, be moreaware of potential hazards. use the databases online. advise patients toreduce exposures to what they cancontrol, smoking, diet, plastic containers, et cetera. so thank you. i will end there.
so now it's my to introducedoctor monica colaiacovo. doctor colaiacovo is a professorin the department of genetics at harvard medical school. she studies howenvironmental exposures impact biologicalmechanisms that are critical toreproductive health. she's one of the nation'sleading researchers in cell divisionprocess of meiosis, which results in theformation of eggs and sperm.
and she has a rapidscreening process of how everydaychemicals affect dna that illustrates thecost of an increasingly artificial environment and toequip the world with accurate information to enhancepublic awareness. doctor colaiacovo isan associate editor in several key journals of theworld such as genetics, plus genetics, and she's arecipient of a number of prizes in science, the most recent theharold golden lampert research
award at harvardmedical school in 2013. so we're very fortunate tohave her speak to us today. monica? so i'd like to start bythanking both angela [inaudible] as well as dean vildfor the opportunity to be here and tell you alittle bit about our work. and thanks to davidfor the introduction. so as you probablyalready had a feeling for in this introduction, thereare various different chemicals
in our environment. we're only startingto understand how they can impact health. and they can havevarious different kinds of effects on health. and so in my laboratory,what we're interested in is understanding theimpact of these exposures on reproductive health. and that's why thetitle that i put up here
says germline exposure toour chemical landscape. we're assessing the effectsand the mechanisms of function as a result of those exposures. and what i hope you can geta hint of from this title is that because thebasis for reproduction, the formation of thesereproductive cells, egg and sperm, are happeningat a moment in time where it's ethically andtechnically impossible to look at thisdirectly in humans,
we rely on the use of modelorganisms to study this. the one that we're focusedon in the lab are worms. and i will introduce you tothis model organism in a minute. so as i mentioned brieflyin the title introduction, meiosis is this specializedcell division program that is the basis for reproduction. it's the celldivision program that will allow you to formthe egg and the sperm. and the reason why meiosis isdifferent from a mitotic cell
division is that atthe end of the day it results in the reductionof the number of chromosomes that you have by half. and the reason whyyou need this is so that the egg and the sperm,which now carry only half the number of chromosomesthat other cells would have, when you undergofertilization, as shown here, you will be able to reconstitutethe right number of chromosomes in the new cell that is formed.
but what we allknow is that meiosis is an imperfect process. there are problemsthat can happen. there are errorsthat can happen. and that will resultin the formation of cells that do not carry theright number of chromosomes. and that's what werefer to as aneuploidy. the consequences of aneuploidy,the formation of egg and sperm or embryos that don't carry theright number of chromosomes,
can be severely deleteriousfor reproductive health. and so on the nextcouple of slides, i will introduce you to howserious this problem can be. if you look atthe leading causes of infant deaths inthe united states, exemplified here as thedata for 2011 and 2012, what i hope youcan appreciate is that the leadingcause at the top here are congenitalmalformations.
and that is farhigher than something that we hear a lot more inthe news such as sudden infant death syndrome. it turns out that thesecongenital malformations are a result of problems,errors during meiosis. not only that, 35%of all clinically diagnosed miscarriages--so this is probably an underestimate--are due to errors during that processof meiosis, as are
4% of all still births and birthdefects such as down syndrome, trisomy of chromosome 21. and so it becomesvery, very important to understand not onlythe genetic drivers of the process of meiosis, butalso the environmental impact on this process. and that becamevery apparent to us because we were abasic genetics lab. we were identifyingall these genes
that are important forthe process of meiosis, so trying to understand whatdrives this complex biological program. and then a few years agowe realized we live also in a very complex environment. there are over84,000 compounds that have already been produced. at least 1,000additional compounds are added into theenvironment every year.
and when you lookinto the literature and try to find outhow many of these have been tested for animpact on reproductive health, it's really very few. so we really do not understandhow these two are superimposed onto each other. we know that there are variousdifferent exposures, agents, environmental factors,that have been correlated with an impactin reproductive health.
for example, as mentionedin the introduction, use of chemotherapeuticagents, exposure to pesticides, plastics,all the way to maternal age. and so we came up withthe following question in the lab, which is ifwe want to understand the environmentalcontributions to aneuploidy, to the formation ofthese egg and sperm that don't carry the rightnumber of chromosomes, can we use this roundworm--it's a microscopic model
organism called caenorhaditiselegans-- to investigate the impact of ourchemical landscape and here's a photo of theteam both past and present that are currently engagedin this research in the lab. and so let me just remindyou really quickly about what happens during meiosis. so prior to entranceinto meiosis, your genome is fully replicated. your duplicate allthe dna that's there.
and then a series ofchallenges start to come up. first, now you have thesetwo identical copies for every chromosome. they have to find each otherand pair with the right partner. we know that also there isexchange of genetic information that takes place during meiosis. you basically swap bits of thedna between these chromosomes. that is why meiosis providesfor genetic diversity in the population.
that's why i don't look thesame as david and david doesn't look like my tray. so that's why meiosisis so important. and as you proceedthrough meiosis, actually thechromosomes are fully zipped up as well by a scaffoldthat holds these chromosomes together. that zipper goes away. but now the chromosomesremain attached
because of the swapping ofthat genetic information that took place. and now they're under tension. so when thesemicrotubules that are like cables thatattach to chromosomes and then pull them apartso that they can divide, when that happens, nowthese identical chromosomes are separated apart. that's the firstmeiotic cell division.
but what makes meiosisvery interesting is that you followed a singleround of dna replication by two subsequent uninterruptedrounds of cell division. so that now again this geneticmaterial, this blueprint gets split in halfthrough what's called the secondmeiotic division. and you end up withthe egg and sperm that now carry only halfthe number of chromosomes. so the question, and ihope you can appreciate
from this simple cartoon, isthis is not a trivial process. there are many differentsteps that can go wrong. and what we wantedto ask is where can environmental exposures beaffecting any of these steps during meiosis. the model organism thatwe use in the laboratory is this worm thati'm showing you here. when it's fully grown, it'sabout only one millimeter in length.
and it offers a series ofadvantages for those of us who want to look at whathappens in the germline. the first one i hopeyou can appreciate from this movie which is thatit is a transparent organism. we can look at everything that'staking place inside this worm. and with the advent of thingslike green fluorescent protein and so on, we can actuallylook at specific tissues in real time and followwhat's happening. this system also shares,believe it or not,
a tremendous amount of geneconservation with humans. it turns out that anywherebetween 60% to 80% of all the genes in the wormare also present in humans. and what i hope you canappreciate from this cartoon is that 50 percent ofall the cells in the worm are contained in thisstructure that i highlighted in blue, which is the germline. so for those of us want to lookat what happens in meiosis, 50% of everything in thisworm is undergoing the process
that we want to focus on. if you dissect thisworm, if you cut it here and you isolate only oneof these two gonad arms, and you now stain chromosomesso that you can look-- imagine that this is a tube. it actually is. the nuclei are aligned onthe walls of this tube, and they're moving. and what i hope youcan see is everything
that's in white here representchromosomes in these nuclei. and here i'm showing youhigher magnifications. you see a time courseof progression. you can see changesas you proceed through the process of meiosis. and chromosomes organizewithin these nuclei in very characteristic ways. and i should add, thesechanges and how chromosomes are organized, they arethe same whether you're
looking in yeast, in worms,in flies, or in humans. but what this allowsus to do is easily identify situations in whichyou can perturb this process, where you've either affectedthe timing with which things are progressing, orthe actual organization that these chromosomes acquire. and we use various differentmarkers and reagents to try to understand wherethere might have been a problem. so when we started withthis in the laboratory,
we chose to focus on a veryhighly prevalent chemical that's in the environment. and our compound of choicewas bisphenol a, or bpa, which many of you musthave heard a lot of. it's highly prevalentin the environment. it's a very commonlyused plasticizer. is in the inner lining ofcans because it protects the product in the can frombasically damaging the metal container.
it's present in dental sealants. it's present in fabrics. so we are exposedto it every day. it actually exhibitsan exergenic activity. it's an endocrine disruptor. but it turned out that studiesthat initially came from japan show that there was anassociation between the risk for miscarriageswith women who had a very high level of bisphenola either in their blood
or their urine. and when they analyzedthe chromosomes for the miscarriedfetuses, what they found was that the number ofchromosomes were not normal. so remember, that's aneuploidy. so they started to make acorrelation between perhaps high levels of bisphenola can result in a higher probability of miscarriage. and it was years laterthat very elegant work
done in a model organism, inthis case the mice, that they showed that indeedexposure to bisphenol a can directly affect that verybasic process of meiosis, resulting in problems with howthose chromosomes are fully in line by that scaffold, thesynapses resulting in problems and aberrant morphology,shape, and organization of the chromosomes, alteringthe way that genetic swap of information, therecombination process takes place, andultimately not allowing
for an accurate partitioningof the chromosomes when the cells divide. so here's an image fromone of these papers that show youchromosomes are in red. those cables that arepulling them apart, the microtubules are in green. and instead of having all thechromosomes aligned right here, which is where theyshould be, what you would see after abisphenol a exposure
is some of these chromosomeswere not at the right position. and then subsequently whenyou start repartitioning them, you're not going todistribute them properly. so this created a veryinteresting situation for us, which is given that we alreadyknew what was happening in the mammaliansystem, could we identify whether bisphenol acaused a similar kind of effect in our model organism? but the second question was,can we take it a step further?
and perhaps because our systemis so easy to manipulate, can we identify the mechanismby which bisphenol a is causing these problems? so can we identify themeiotic stages and processes that are affected as well asthe genes and the pathways that are altered? where is this bisphenol a goingto be working in this germline? and i'm going to justreally succinctly elaborate on some of the keyfindings, which
is that at a very highconcentration of exposure, one millimolar, this was theequivalent of an intake of two parts per million. so what this was within therange of the mouse studies that i just showedyou before, it was within therange of people who, because of occupationalhazards, are exposed to high levels of plasticizersor who manipulate cash register receipts, which arecoated with bisphenol a.
so at that level of highexposure, what we saw was a dramatic effect on thefertility of these worms. so now they were unable tolay normal numbers of eggs. there was a lot of sterility. and we also saw that the feweggs that were laid, very, very few were able to hatch. and all of the eggshatched, those larvae never progressed into adults. so the impact of bisphenola exposure was very severe.
and it resulted in exactlythe same phenotype, the same defects that had beenreported in the mouse model studies. we saw problems withthe ability of how things were gettingrecombined, the ability to repair dna damage. we saw problems withthe quality of how these chromosomes look like. we saw the fragmentations,the aggregations.
but in addition tothat when we looked at the first embryoniccell division, and here's an example ofwhat happens if you expose these worms only to ethanol,which is what we were using to dissolve the bisphenol a, andwhat happens if you expose them to bisphenol a. again, ingreen what you're seeing are those cables that are goingto pull the chromosomes apart. in red are the chromosomes. instead of nicely aligningat this central position
as it does in thecontrol, chromosomes never fully progressed. they didn't quitealign properly. but more importantly,and i hope you can see it indicatedby the yellow arrow, we started to see thesebridges, these connections that had never been resolvedbetween the chromosomes. and you can imagine that asthese masses are being pulled away from each other,if they're interlocked,
you're going tomechanically damage them. and so this also explained alot of the embryonic lethality that we were seeing. we also saw formationof abnormal spindles, which are these structuresat the tips here. and ultimately thesecells during mitosis we're not capable of fully dividing. so we were detectingproblems in meiosis says that we're getting carriedall the way into mitotic cell
division and affectingembryogenesis. but what was very criticalabout these studies is that we alsofound out that there was a conserved set of genes. there were specificallythree to four genes that are conserved andpresent all the way to humans and that are very,very important for dna repair that werenot being expressed normally following bisphenol a exposure.
this was the first timethat this was reported. a few years after that,several mammalian studies reported the same finding, whichis that bisphenol a exposure is causing many of thesedefects that i just described because you're deregulatinghow certain key genes that are important for repair tobe present at the right time at the right level. their products are not there atthe right time and right level. so that also meant that wecould use this model organism
to really tease apart the wayin which many of these chemicals might be impactingreproductive health. and so one of the things thatwe got interested in the lab is, ok, we can identifya chemical that might affect reproduction. we can understand the mechanismby which it's doing this. can we go bigger than this? can we start looking at hundredsof chemicals and really, in a very quick manner,take advantage of the fact
that this worm goes from an eggto an adult in just three days, and then it lays 300 eggs? a single worm will lay 300 eggs. that set of eggs willonly take three days to become an adult again. so if you thinkabout the life cycle, it means that we can look atmultiple generations in a very, very short period of time. and it's a veryamenable genetic system
because you have hundreds ofoffspring that you can look at. you have the power of numbersas well in looking at an effect. can we harness that? and this is a costeffective system. we keep these worms in petridishes in a regular incubator. it is highly predictive ofmammalian reproductive toxicity based on several otherstudies that i'm not going to go into details today. can we use this to screenhundreds of other chemicals
and identify those that might beimpacting reproductive health? and one way in which we'vebeen doing this in the lab is taking advantage ofanother interesting feature of this model organism,which is c. elegans exists in two flavors. they're eitherhermaphrodites, meaning they produce both egg andsperm and can self-fertilize. they carry two copiesof the x chromosome. or they can be males,which carry just a single x
chromosome. a self-fertilizinghermaphrodite most of the time will only layhermaphroditic progeny. males are very, veryrare in the population. less than 0.2% of those eggsare destined to become a male. and that's because, if youthink about it, to become a male it means you carrya single eggs, it means there must have beenan error in how chromosomes were partitioned.
it means that yougenerated either an oocyte or a sperm that simply didnot have an x chromosome. and when it matchedwith let's say it was an oocyte thathad no x chromosome and it got fertilized bya sperm that carried an x, that's how you recoverthe single eggs. so males are very, very rare. but we know that ifyou affect meiosis, you start to randomlyhave problems.
you start to randomlypartition these chromosomes. the frequency with whichyou might have errors and how that x chromosomegets partitioned goes up. and in fact, if you lookat meiotic mutations, we now start tosee 30%, 40% males in the population versus 0.2%. so it's very easy todetect something that's messing up of with meiosis. so we could usethis, what is called
a high incidence of malesoutput or phenotype as a readout to understand what chemicalsmight be causing problems and that became even easierbecause we could actually take advantage of the following. barbara myers labat uc berkeley had identified somethingcalled xol-1, x-o-l 1, which is amale-specific promoter. that means it only drivesexpression of a gene in males. she fused it to the greenfluorescent protein.
n. villanova atstanford university then used this construct, whatwe call a reporter construct, in a very clever way. she thought, if imutagenize worms to identify actualgenetic mutants that might be importantfor meiosis, and i have the worms carryingthis reporter construct, if i start to see moremales in the uterus, they will glow green.
i know that those eggs aredestined to become a male. i must have hit something that'svery important for meiosis because males are rare. so can i see these greeneggs in the uterus? and it turns out thatthey're very, very obvious. this is a snapshot of whatthat uterus looks like. you can really seethese green eggs. and they would normallynever be there. so we then decided, well,we can use this strategy
in a slightly different way. what if we now use that samereporter construct and expose our worms to chemicals? we can do this withmulti-well plates, so we have variousdifferent chemicals, various differentconcentrations. they're swimmingin this liquid that has whatever toxicagent we want to test. can we then see if wesee these green eggs?
and to make this even morerobust system, what we did is we introduced this geneticmutation on a collagen gene called col-121. and the reason we didthat was to break down the cuticle barrier of theworm so that we can really now introduce very,very low concentrations of the chemicals. for example bisphenola, we can significantly dial down the concentration.
it's no longer 1 millimolar. it's 100 micromolars. it's very, very low. now we can work withinthe range of what's used in cell culture experimentsand all these other systems. can we see an effect? so can we see these green eggs? but to make ithigh throughput, we can take advantage of stillanother technological advance,
which is that therenow is a machine that allows you to fact sort yourworms based on fluorescent. so you put these lifeworms through this machine and it will detectwhether you've got green eggs in theuterus or not and how many. so what's the fold increasecompared to, for example, the vehicle alone? and so we've been successfullyapplying this strategy. and i'm just goingto quickly show you
a slide that exemplifiesthe kind of library that we've beeninvestigating now in the lab. we've been lookingat components that are using hydraulicfracturing, components that are used in theprocessing of crude oil, various different pesticidesand antimicrobials, phthalates, which are highly prevalentin the environment because of plastics, cosmetics,what you spray on crops, showercurtains, and it's
been working very successfully. we've been able to identifywhich of these are causing problems in reproductivehealth, and now we're starting to investigate whythey're causing such problems, because that's the final step. we want to understand thepathway, the mechanism by which they're affecting this. and ultimately wewant to find out chemicals that might exhibittrans-generational effects.
so a single exposureof mom that can lead to effects not only in thechildren and the grandchildren, but in the greatgrandchildren as well. so with that, ifthere's one important take home message that iwant to leave you with, it's that we can start tounderstand very important steps of this complexbiological program by taking advantage ofbasic model organisms. this can inform what happensin the human scenario.
questions that areraised in humans can be answered by whathappens in the worm. so these can feedbackinto each other. this is not perfect. you need a combinationof different systems to ultimately get a full pictureof what might be happening. but we hope that this is oneelement in a cascade of things that might be used inassessing what chemicals might be doing before they'redelivered into the environment.
and with that, i'll thank thelab as well as funding sources. thank you monica. last speaker before questionsis doctor maitreyi mazumdar. doctor mazumdar is anassistant professor of neurology atthe harvard medical school in bostonchildren's hospital where she's anassistant professor of pediatric neurology. and also she's anassistant professor
in the department ofenvironmental health at the harvard th chanschool of public health. her research focuses onenvironmental exposures to compounds like arsenicand neural tube defects like spina bifida. her studies takeplace in bangladesh where there's an estimated70 million people who've been infected by arsenictainted drinking water. in 2016, doctor mazumdarwas the recipient
of the outstanding newenvironmental science award from the nationalinstitutes of health. this is quite a thrill. thank you for inviting meto participate in this. and i have to say this is great. you can't hear me? is the mic on now? now it's on? ok.
maybe it's too far away? i want to get itright because what's the point if you can't hear? all right, is it better now? so i'm a pediatricneurologist, and i've come to talk to youabout children, children and environmental chemicals. and i'll just giveyou a quick overview about what i'm going to cover.
we'll spend a littlebit of time talking about why kids might be morevulnerable to environment environmental chemicals. i'll use leadpoisoning as a paradigm to discuss developmentalneurotoxicity. lead poisoning is inthe news these days. and i think in additionto being a timely topic, it's one that really has beenstudied well and studied well in boston in particular.
and then the end withjust a plea as david has already mentioned abouta precautionary principal in our approach toenvironmental chemicals. so why are kids different, orwhy might be kids difference, or why might kids be morevulnerable to the things that we're talking about? and i think kids have anumber of different things they put them at higher risk. they have differentand unique exposures,
which we'll talk about,different from adults. they have a physiologythat's very dynamic. they're growing,and their growth provides windowswhere they may be more susceptible to harmfulchemicals in the environment. they live longer, sothey have a longer chance to develop problems even froman exposure early in life, and we'll talk alittle bit about that. but i think mostimportantly, they rely on us,
they rely on adultsto protect them. they can't make a lot of thechoices about where they live, or their lifestyle,or what they eat, or what they're exposedto, or what's regulated in their environment. they don't vote. and so they are vulnerablejust because of there situation or their positionin our society. so let's talk a little bit aboutdifferent and unique exposures.
so in addition tobreathing the air and eating food anddrinking the water, children are exposed tounique exposure pathways. they get chemicalspassed through them through the placenta, throughthe umbilical cord, which can be a veryprotective environment. the placenta often doesshield out a lot of chemicals, but it's not perfect. they are exposed to chemicalsthrough breastfeeding,
which is just a very differentway of getting exposure to a chemical inthe environment. they have exploratory behaviorsthat are different from adults. they put things in their mounts. a train toy that we mighthave on our desk, my son puts in his mouth. what can you do about that? so they are different. they have different statureand micro environments.
they're shorter andcloser to the ground, so they're closer to the carpetsthat might have chemicals. they're just there. we're up here. they're there. they breathe different airbecause they're shorter. what comes to them intotheir respiratory passages may be different fromwhat comes there. and they don'tunderstand danger.
if you say don't go over,there it's dangerous, that will be the firstplace that they go. so children are different. and you have to thinkabout them differently when you're designingstrategies to protect children. so some of these i'vealready talked about, their breathing zones. children are differentwithin themselves. a crawling childmight be more at risk
than a child thatcan be put in a crib unless the cribitself is dangerous. like i said before there,they're closer to the carpet. they also breathe moreair per surface area. for their weight, for theirbuilt, they're taking in more. they have a higher intakeof food for their weight, and they eat different things. so they have a different diet. they have milk maybe more.
they may have different types ofthings that are in their diet. i'm a pediatric neurologist,so when i talk about children, i talk about children's brains. and it's just a modelof an organ that is undergoing development,that's growing very, very rapidly all the wayfrom the in utero period through adolescence. and as monica mentionedwhen she walked us through the steps of meiosisand gamete formation,
brain development is also avery, very complicated process that has many places wherethings could go wrong. so just to talk aboutthem or to highlight them, for the brain to develop, it hasto do many things in sequence in a very programmed,very predictable way that involves many differentthings, including genetic influences,nutrition, but also can be disrupted bychemicals or other things in the environment.
so just to walk throughthem a little bit, proliferation is the first step. the cells in the brainhave to multiply in number. then the cells,once they multiply, they have to travel towhere they're going. so that's a really excitingpart of brain development to study and to watch,to see the brains form from the inside out. they start in themiddle of the brain,
but then have to make their wayup to the ends of the brain. they form these connections,which is called synaptogenesis. and then there's also avery predictable trimming of connections as well,which is a natural part of brain development. it's called pruning. within that there is a verysophisticated formation of transmitters and receptors. and all of these thingscan be influenced
by substances inthe environment, by experiences in theenvironment as well. so children develop on avery predictable course and in sequence. and so this is a slide fromchuck nelson's group, who's at boston children's, showingthat within the first year of life there are developmentsof vision and hearing pathways, followed bylanguage, followed then by higher cognitive function.
and this is all related to braindevelopment in this pathway that these series of stepsthat occur within the first 15 or so years of life. so why is that important towhat we're talking about? well, the reason iwent through that is because i wanted to makethe point of what happens to the brain of a personwho's exposed to chemical can depend on wherein that process they are when they'reexposed to the chemical.
so this is a cartoonfrom pathology from brain cuttings of apopulation of japanese people who were exposed tomercury through dumping of industrial waste into a watersource and minamata, which is an area in japan, in the 1950s. and these are their brainsor cartoon of their brains in cross section. and if you look at theadults who are here, children who were born afterthe poisoning incidents,
and the brains of childrenwho were in utero, whose mothers were pregnantat the time of this poisoning, they were all exposed tothrough drinking of water, though this population wasexposed transplacentally or in utero, you can seethat their pattern of injury is different. and so these dots are meantto represent areas of injury. so in adults, the damage wasmore focal, more restricted to certain parts of the brain.
but in those who wereexposed prenatally or while they werein utero, the damage was much more widespread. so just the age andthe developmental stage that these individuals wereat at the time of exposure affected how theyresponded to this exposure. so that's an overviewof developmental windows of toxicity, or whyi think children may be more susceptible.
and now let's talk about lead. and once again, thereare many chemicals in the environment thatwe could talk about, but lead is really the paradigmand also it's very timely. so right now because of thesituation in flint, michigan, we're learning a lot aboutlead in the water and lead in water pipes. but it's important to rememberthat led is really everywhere in the united states.
and there are multiple sourcesof exposure for children, even though it'simproved substantially over the past decades. so in flint, asmany of you know, there is lead in the water thatis related to leaded pipes. in boston, the mainsource of lead exposure is leaded paint from housesthat used lead paints prior to the ban of lead in the 1970s. and then every sooften there's a story
about lead in paint from toysthat are imported into the us. prior to the removalof lead from gasoline, lead in the air fromgasoline admissions was really the major source. and elevated bloodlevels affect the brain, and we'll talk aboutthat to some extent, but it really affectsevery part of the body. at high levels, solevels at about 100 or 150 micrograms perdeciliter, children
used to die from leadexposure, and still do in many parts of theworld, such as nigeria where children are exposedto lead in lead mines. we'll talk a little bitabout developmental toxicity and the studiesthat were done here in boston where lead was shownto be associated with decreased iq, decreased hearing,decreased growth, and other maybe lessdramatic but still substantial neurologic outcomes.
actually, even thoughwe're talking about lead, the story of lead is really oneof our biggest public health successes. blood leadconcentrations in the us have reduced dramaticallyover the past decades. in the 1970s and 1980s, themedian blood concentration among children, medianlead blood concentration was around 15, whichis a level that would be considered completelyunacceptable by today's
standards. and now it's less than 2. and this has to dowith restrictions on the use of lead-basedpaint, and also the phasing out of leaded gasoline. but let's talk aboutwhat lead does. and we'll talk a littlebit about studies that were done here at bostonchildren's hospital and just down the street.
so in the 1980s, one ofthe very first studies done to look at the effectsof childhood lead exposure showed that if you lookedat the teeth of children who were exposed to lead, ifyou looked at children who had high levels of lead intheir teeth by some measure, and those that have low,the iq, the verbal iq scores of the group withlower lead levels were higher. so there was a drop iniq scores among children who had higher levels oflead in their teeth, teeth
being a measure ofchronic exposure. the number of iq pointswasn't very high. that change was around4 iq points, which may not seem like a big change. but if you look over apopulation over a big period of time, these children who wereexposed to lead consistently were doing a little bitworse than their peers who were not exposed to lead. this started a number ofstudies, tens and twenties
of studies all over theworld to look at lead and iq. and you can see that theresults were really very varied with different estimates ofthe effect, different shapes of their curves,different ranges, both of iq and of blood level. but when you sort of combine thedata and look at them together, you can see that there's apattern that at lower blood level concentrations,there's a steep drop in iq with this being sortof a range of iq.
and as you go out, the shapeof this curve flattens out. so there's certainlyeffects of lead that are seen throughoutthis range of exposure, but at the beginning,at these lower levels is where maybea little bit of lead is the most harmful. this and these publichealth interventions that i mentioned before has ledto a drop in the level of lead in the blood that weconsider to be harmful.
before we used to say thata level over 60 was harmful and under that was probably ok. and then that threshold havecome down over the past set number of decades. when i was in medical school, itwas 25 and then reduced to 10. and now as we understand thatlower and lower levels of lead can still cause this dropin iq or other measures of neurologic function, wedon't even call it a threshold anymore.
we say it's a referencelevel, that there's no level of lead that's ok. and this level of 5,which is the level that was used in flint to identifychildren with high levels, is still somethingthat we're trying to get lower and lowerand lower every year. so those are theeffects on children. but are there effectsthat last longer? how long do these effects last?
so there's certainlya hypothesis that's out there that childrenwho were exposed to lead, or exposure tochemicals early in life, has not only effectson the number of cells, or you can use thisas cognitive function of a number of differentoutcomes on this y-axis. not only do people who areexposed to this chemical exposure early in life, sothis is let's say prenatally, and then this is their lifespan.
this would benormal development. there's some cognitive functionand then some normal decline. i've taken the ages offhere because i'm reaching the point of inflection. i don't really wantto acknowledge that. but let's sayyou're exposed here and then there isa measurable change in your performance on testsbecause of your exposure to lead.
so this has been shown,but there's a hypothesis that it also causes adecline, a more rapid decline as your age goes on. now how would you testthat, though, in people? so in our studies, the onesthat i mentioned briefly, you can look at kids andsort of get some estimate of their early life exposureeither through biomarkers or teeth or some other thing. but if you're,let's say, 70 or 60,
how do you estimatewhat this exposure is? it's really hard to do. this is a hardhypothesis to test. so this is where weoften go to animal models because, like worms, theyhave a shorter life span. and so there's this veryinteresting study that's out there in the animalliterature-- this is from mice, and this is a group in rhodeisland-- that gave lead to mice early in life.
so this is their lifespan. and these are controls. so these are mice thatwere treated with lead, and these were controls. and they were treated withlead and they followed them through their life span,which is about two years. and as they got older,their expression of genes that are involved inprotein folding, genes that are involved in processesthat are similar to those
of alzheimer's disease,expression of those genes went up. and then later if youlooked at the neuropathology of these animals,you could that they had more information of theseplaques and accumulations, i guess. there were more inthose that were treated with lead than those without. so the hypothesis fromthe animal literature
is that early life lead exposuremay be a risk for later life alzheimer's disease. so once again, it's hardto test that in humans. let's say i decided to start acohort now, or when i was 30, and then followthem for 70 years. by the time it comes the timeto evaluate them, they're 70 and i'm 100. so you can't really dovery much about that. so we went back to ourcohorts of children
who were born inthe '70s and '80s, and then we tried to seewhat they were doing. and i'll run throughthis quickly. we saw that we were able toget about 80 kids, 80 adults, 30-year-old adultswho we had information about their umbilical cord lead. and we saw that they still haddecrements in their iq when compared to those whowere not exposed to lead. and we also saw,using a biomarker
for alzheimer's disease, wherelower levels is associated with a higher risk ofalzheimer's disease, we found that-- let'sjust use this one-- that those who hadhigher cord blood lead concentration had loweramounts, at least nothing in this area of theseparticular proteins. so it's an interestinghypothesis. it's one of many,but it's there. so what we think weknow-- i'll just end now.
we know a lot aboutlead, but we really don't know much aboutthese other chemicals. and there are many chemicalsin the environment. lead is a paradigm becauseof its effects on the brain, because we have a lotof literature about it. but there still arethese other things that we can use a similarapproach to study. and as davidmentioned, we should apply a precautionaryprincipal, and not
wait to demonstrate thatthese things cause harm or to see that they causeharm, but especially in the case of children,err on the side of caution. so our conclusion is thatchildren have heightened vulnerability because ofthe developmental processes, because of theirposition in society. and that leadpoisoning illustrates the developmental toxicity. there is increasing recognitionof effects at low levels.
the effects arelong term and there may latent effects, such as anincreased risk of alzheimer's disease, and that we shouldapply a precautionary principal for the introduction ofchemicals into the environment. and that's it. thank you, maitreyi. we're going to give people about30 seconds to clear the room, and then we'll startwith questions. thank you for your questions.
we have quite a few veryinteresting questions that were written down. excellent questions. ok, good. so we'll start. ok, so we'll startwith questions. the first two formonica colaiacovo. one is, since human oocytes aregenerated early in development, at what period do exposureshave their main effects?
and for example, doesa mother exposed to bpa have risk of offspring withaneuploidy, or do her children? so the process ofmeiosis is happening inside that developing fetus. so if the mother getsexposed, what's happening is you're affectingthe meiosis that's taking place inside that baby. so ultimately, whatyou're doing is you're affecting the quality,for example, of the eggs
that that child willeventually produce. the impact is going tobe on the grandchild. so that child might have ahigher incidence of aneuploidy because it got exposedwhile it was in utero. having said that, meiosis isa process that takes decades. it's initiated inthat developing fetus. it's then arrested. and then later as thechild reaches puberty, that's when you startto complete meiosis.
so you're in what'scalled diapause. you're arrested at astage called diakinesis, and then you resumemeiosis and you complete it, which means thatadditional exposures that can take place even in that nowadolescent woman, for example, can then impact the subsequentend-tail steps of meiosis as well. so it's not limited towhat happens in utero. you can have additionalexposures in your lifetime
that can affectthings later as well. thank you, ma'am. so one more, monica, for you. there are actually manyin there about chemicals. but what aboutthose of us over 50, outside of ourreproductive window? do we have to worryabout plastics? should we throw out allour plastic containers? so i focused a loton what happens
in terms of reproductivehealth, but yes, you need to be but awareof the fact that exposure to this plasticizerand plastics in general can have various differentdeleterious effects. the exposure to bisphenola has been associated with cardiovascular disease,with diabetes, with it possibly being what we callan obesogen. it can be affecting the ability togain weight and be associated with the obesity epidemicin the united states
and other developing countries. so a couple ofthings that people should be constantly awareof is you do not want to heat plastic containers. do not microwave anythingthat has plastics. you do not want to, if youcan, put anything that's plastic in a dishwasherbecause of the high temperature that that will achieve. so you watch thingsby hand and you
have to use very,very gentle detergents and try to use thenon-abrasive side of a sponge, for example, when you'recleaning the container because you don't want tofacilitate leeching out from that plastic intowhatever you're going to put in that container later. so that's somethingthat you need to be very consistently awareof, because the impact is not only about reproduction.
and in the case of men who arebeyond where spermatogenesis is happening all thetime, this is an issue no matter what, even inthe context of reproduction in older men. so in my household, i basicallyeliminated as much of plastics as i can, and i'mvery, very cautious about what i do or do notput in contact with plastics. another question. can being exposed,not wearing a covering
to protect you to x-raysbe harmful to you? the answer is yes. you should always beprotected with lead aprons or the equivalent,basically lead aprons when you're being x-rayed. it's cumulative, however. a single time it happensis unlikely to increase your risk a lot. it's cumulative over many years.
another cancer question. you mentioned a lot ofcarcinogenic substances. which single one shouldbe targeted first? the obvious smoking. well, actually it'sa good question. you can go on to the epawebsite, environmental protection agencywebsite and look at carcinogens, which issimilar to the international agency for research on cancer.
in the group that's 1,known human carcinogens, and 2a, probablehuman carcinogens, the total is about400 chemicals. definitely 1 and 2ashould be avoided. then there's possibleand then there's unknown. and so i think the list islonger than you'd expect, beyond just things like smokingand a few others i mentioned. but most of them are notnecessarily in everyday use. that's why the epa siteexplains it a little better.
let's get a lead questionfor maitreyi there. we dealt with microwaving. literally everything ismade up of chemicals. how do you deal withself-proclaimed scientists in social media who saythat any chemical that you can't pronounce is dangerous? actually, it's a good question. in a way, and i'll see whatmaitreyi and monica feel about this, to say thateverything causes cancer,
everything causes brain damage,everything causes reproduction has a long nameis disempowering. it's not empowering. we really want toknow a couple things. one is, not everychemical is harmful. of the 80,000 on themarket, i'm fully prepared to realize or understand thatthe majority probably do not cause cancer or anyserious effects, but we just need to know.
that's the one thing. we have a right to knowwhat does and doesn't cause, realizing perhaps the majoritydo not cause any problems. therefore you focus on theones that are the problems and become empowered to minimizeor eliminate those exposures. so when you thinkabout it, if you say, well, everything causes disease,that's very disempowering. because what arewe supposed to do? so the facts, that's whywe do scientific research
to prioritize those things. all right, maitreyi,you're not off the hook. let me see. water safety. is it safe to drinktap water in the us? is filtered tap waterbetter than unfiltered? what about boiled tap water? boiled. boiling it like they doin much of the world.
well, certainly tapwater is in the news. and i think i might needhelp with this from david. i think it depends onthe region where you are. and i think this isan example of how different areas anddifferent municipalities handle things differently. so i think in manycommunities, the water that comes from the pipes and tapwater is probably very safe and is well treated andcleaned without significant
contamination with chemicals. but it is very area-dependent. i agree. and also, within an area thereis going to be some issues. boston, we're fortunate. the quabbin reservoir isa very good water supply. however, we have conduits inboston that are very old pipes and can be leaded. so the water supply isactually outstanding.
but when it cuts tothe house, if you have lead pipes, conduits inthe house or aging lead pipes, then that house can have aproblem or the group of houses. so i agree with maitreyi. it's regional, butit's also very local. and so it is worth thinkingabout looking at your locale, what's been knownabout it and what testing you may have to do. finally, boiling water isdone in a lot of the world
to avoid infectiouscontaminants. we never really recommend that. so think about highschool chemistry. if you're worried aboutmetals and you boil the water, what happens? you concentrate the metals. because you'reboiling off steam. you're letting those nicewater molecules go away and you're concentratinglead, arsenic, or manganese.
there's no reason toboil it in the us, although there may be situationswhere the water is not safe. and the other thingis bottled water. there was a study donesome 20 years ago of some of the popularbottled waters around, and they had higherlevels of contaminants than the municipalwater supplies in places like new york and boston. so certainly be aware of it.
now with the internet youcan get a lot of information on your local water supply. ok, next question. series of questions. is secondhand smokestill a problem? yes, but it'sdeclined a lot because of regulatory andeducational efforts. secondhand smoke, a spouseliving with a smoking spouse has about a 30% increasedrisk of getting lung cancer.
so your spouse is thenumber one target. but in terms of the workplaceand the general environment, there has been in the us ithink significant, really significant progress in this. pcbs. there's a question aboutpcbs in a site in hyde park. the company wants to put themunderground and vaporize them. they probably wantto incinerate them is what it is, which iswhat happens sometimes
at superfund sites. that sounds weird, butsometimes high temperature burn for certain organicchemicals is actually one of the ways of remediating it. it's not that they justtake the chemicals. it's the soilthat's contaminated. and so they basically burnthe entire several feet or whatever the hydrogeologyand the environmental engineers say you need to go downto get to clean soil.
and so that is still anacceptable environmental engineering procedure,realizing that the controls on their emissions have to bequite strict and the latest technology. lead in chocolate andarsenic in bottled water. maitreyi? so i don't know aboutlead in chocolate. i think the issue aboutlead in food products, however, is certainlyone to talk about.
in the us, foodand food products, at least when itcomes to metals, are quite well regulated, orat least that's my opinion. in the rest of the world andthe rest of the developing world especially, leadis used as something to brighten thecolors, to increase the weight for spicesand other things that are sold by the weight. and so lead contaminationof food products and spices
is a very big issue. we, both david and i wereboth involved in a study not very long ago wherethe us had recalled batches of turmeric that had beenshipped to the united states because their own testing--so they do testing fairly regularly of imports-- hadshown very high levels of lead in these food products. and in the sites wherewe work in bangladesh, we found that we had high levelsof lead among the children.
we didn't really knowwhere it was coming from. we went to their homes andwe tested a number of things, including their turmeric. and we foundastronomically high levels of lead, which has norole except it's probably part of a dye to make thisorange spice more orange, because there's no reasonto think that it would be in the ground or the soil. so whereas i don't think it's abig issue in the united states,
i think contamination bymetals and other chemicals in the food by lead isincreasingly recognized as a health hazard to children. great. another one for you, maitreyi. how does medication affectusing for attention deficit disorder affect children'sbrain long term? so attention deficit disorderis a particular diagnosis, one also that has a bodyof literature relating
it to lead exposure, early lifeexposure, which is an aside, and not really the answerto this particular question. so the medicines that are usedto treat attention deficit disorder generally area class of medications called stimulants, not unlikethe coffee and the soda that we as adults use toincrease our concentration. and the long termeffects on children, one, they're short actingdrugs, so they don't accumulate inthe body like some
of these other chemicals do. but the long term effectsof these medications are related to the side effectsof the medication, which include decreased appetite. so when we think aboutwhat the long term effects of thesemedications are, it's more to do with reducedappetite and reduced food intake relating toslower growth, which has been shown to reverse whenyou take the medications away
and kids get hungrieragain and then eat again. so i think in terms ofaccumulating damage, there's not evidence forthat in the literature. ok, a couple morecancer questions. what, if any, toxins contributeto skin cancer, melanoma. actually, it'snot so much toxins except arsenic cancause skin cancer. there are some hot spots in thecountry, new hampshire water supply and some otherparts of the southwest.
but mainly skin canceris ionizing radiation, ultraviolet light problem here. so that means sunbathing,tanning booths. really i think tanning boothsshould be banned, frankly. should we limit dentalx-rays and mris? medical x-rays should belimited, as we mentioned, to the extent possible. you need them. you get them, but you haveyour thyroid and other parts
of the body coveredwith a lead apron. mri contrast do not emitany ionizing radiation, so there's not acancer risk for mri. why do children of ahigh risk of leukemia? actually, i might havegiven you a misimpression. it's not that theyhave a high incidence. it's actually these tumorsare rare in children. it's just when theyget it, they're grouped into these bigcategories, and leukemia's one,
and it's probably disorderedimmune system from pre-birth. and so it's not really thatthey have a high incidence, it's just that whenthey do get cancer, they tend to group intothese categories, leukemia being a big one and centralnervous system being another. how can we preventthese chemicals from ending up in our products? so that's a policy question. so we're scientists here.
we're trying to provide theknowledge base which should then be translated into action. some of that action is policyon the part of government to regulate thesethings so that they don't get intoconsumer products, into our homes and workplaces. and the other partof translating scientific information is tohave the public be informed, because sometimes thesechemical compounds
can't be totally eliminated,but need to be avoided. so i think it'sa great question. and it differs alot where you live. the european uniontends to be much tougher using theprecautionary principal than we are in terms ofthe amount of evidence needed to ban a compound. it's actually quite hardto ban compounds in the us. but that's why we do this work.
we got a couple more minutes. i've observed the peoplewho are heavy smokers rarely live beyond the age of 60. yeah, not much morecan be said about that. i think it's a veryastute comment. it's a sad one. and it's obvious what needsto be done to control that. the good news aboutthat, by the way, say you've smoked for 20 years.
and you say, ok, it's toolate, i'm already too far gone. not true. you stop smoking, yourrisk of lung cancer goes down 50% overthe next two years. so when someonesays that, just say, wow, you're really afatalist, because you still can do something about this. if a person has ablood transfusion, can they get cancer?
no. serious question,and it's actually no is the answer because youusually get red blood cells. the blood has been treated. cancer cells, evencirculating cancer cells occur in very low frequencyin the blood of patients with cancer, althoughthey do occur, but it's not atransmissible disease. at least theoretically, evenif one cell got through,
your immune systemwould take care of it. it's a very goodquestion, but we're not talking about infection. all right, so isee the red light. i think we got through asmany of these as possible. thank you all somuch for coming.
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