September 13, 2005  

Speakers: Pete Myers, Theo Colborn, Mary Bachran, Ana Soto


Key Outcomes from the call:
1.    To develop a network of researchers who are looking across health endpoints at fetal origins of disorders and disease.
2.    To push for more research of fetal origins of disease. Prioritize research time and investment based on plausibility and “bigness” of the health endpoint.
3.    To continue the larger discussion of where we take cancer research next. We have explored the epidemiology and the fetal origins. It was suggested that we consider a paper or inquiry into the mechanisms of cancer.
4.    We are transitioning staff at CHE. Michael Lerner will be the main contact for this group until late Fall. If anyone has ideas about a new coordinator, please contact Frieda Nixdorf at info@healthandenvironment.org.


Call Transcript:

Jeanette Swafford: I’d like to welcome all of you to the quarterly call of the CHE Cancer Working Group.

Our call today is on exploring the fetal origins of cancer. We’ve invited the CHE Fertility and Pregnancy Compromise Working Group to join this call, as well. So, I’d like to extend a special welcome to those of you who are not normally part of this working group. A list of call participants will be distributed, along with notes – probably mid-next week.

We’ll begin today’s call with brief updates, and then we’ll move into our main discussion. Our speakers today are Dr. Pete Myers – the CEO of Environmental Health News, Dr. Theo Colburn – the president of The Endocrine Disruption Exchange. Dr. Mary Bachran – also from the Endocrine Disruption Exchange, and Dr. Ana Soto from the Tufts University School of Medicine.

On a personal note, I wanted to mention that this is the last call I will be coordinating for the cancer group. I’ll be taking sabbatical to be with my family, starting in October. I wanted to say thank you to everyone for a fabulous experience. I have thoroughly enjoyed working with this group. It’s been an engaged, intelligent gathering of people. I will really miss it. I will follow it from afar, though so good luck.

In my absence, Michael Lerner of Commonweal will be acting as interim coordinator, until someone new is formally announced. If anyone on this call has suggestions for a new coordinator, please let us know by e-mailing Frieda Nixdorf, info@healthandenvironment.org.

UPDATES:
Dick Clap, Molly Jacobs and Gen Howe have been working on a summary paper on environmental and occupational causes of cancer. Many people in this group provided important feedback on an earlier call, this spring. This is a very important document that will be a great resource for many of us. Molly, can you give the group an update on the status of the paper, and how people can access it, if they’re interested?

Molly Jacobs: As Jeanette said, I along with my colleagues, Gen Howe and Dick Clapp, are extremely pleased to have a publication date in sight for our review of this data – this science – linking environmental and occupational exposures to cancer.

As Jeanette mentioned, this is the same report that the CHE Cancer Working Group reviewed and provided feedback on in March. It doesn’t present new research, but rather compiles an immense body of science on the role of environmental and occupational risks of cancer in one document.

The goal for this paper is to demonstrate that cancer risks associated with the environment are known and extensive, and need to be given fair consideration by individuals, and institutions concerned with cancer-preventive efforts.

The paper, as you may recall, also makes clear new knowledge about multiple causes of cancer including factors such as involuntary exposures in early life, synergistic effects and genetic factors. These make it impossible to achieve a nice clean percentage to categories of causal factors. As we all know, this is the exercise that is widely cited in the 25-year old paper by Doll and Peto that attributes 2-4 percent of all cancer to occupational and environmental exposure. This 2-4 percent attribution is probably the reason why the environment has received little attention from agencies such as the American Cancer Society.

The paper only reviews epidemiologic literature. The value of which was the subject of debate during our call in March. However we felt, and the group concurred, that another companion paper is warranted, that reviews what we know about the state of the science regarding environmental risks to cancer, from the field of toxicology.

We are working on issuing a report early next week, and a copy of the paper will be posted on the CHE website. [NOTE: This paper is now available in the Resources section of the Cancer Working Group on the CHE website: www.healthandenvironment.org.]

That’s great. Thank you, Molly. Is Steve Heilig on the line?

Steve Heilig: Yes. Hi.

Steve’s from the San Francisco Medical Society, and is in the early planning stages for an important event. Steve, can you tell us more, please?

Steve Heilig: I would like to add to Molly’s remarks, and say that Dick Clapp and colleagues are also preparing a summary of that paper for the San Francisco Medical Society Journal. The January issue of 2006 will be another of our ongoing series of CHE-themed environmental health journals. There’ll be a lot of those papers in there. We’ll be sending out that information in the CHE newsletters to all the CHE partners.

The other thing we’re working on, as some people may recall, we did a First National CHE Conference a little under 2 years ago here in San Francisco, at the University of California Medical Center. We are working on another one, it looks like, for May. The date that I’ve got on hold right now is the 19th – which would be a Friday. This, again, would be an all-day update – featuring science and clinical information – particularly with the focus, this time, on cardiology and cancer. We would be looking at some of the more-compelling evidence and actual interventions and clinical care that people can take.

Two of the co-chairs of that are getting very interested in this. One is Dr. Gordon Fung, who is the president-elect of the Medical Society, and a professor at UC. The other is Dr. Brian Lewis, who is professor of oncology. These are both prominent physicians here in town who have been starting to get very interested in CHE, and some of the issues, here. So there’ll also be a lot more information coming on that, of course, as we pull it together.

That’s great. Thank you, Steve.

I just have one note. On our last cancer call in June, on breast cancer and the precautionary principle, a subgroup developed that will be focusing on how to engage the National Breast Cancer Coalition more deeply in the environmental health discussion. They will be meeting tomorrow, via conference call, at 10 am PT.  If there’s anyone here on this call that might be interested in working with that group or learning more, please let me know. All are welcome.

Steve Heilig: Jeanette, this is Steve, again.  I ought to mention – I just thought of one other thing. The journal that I mentioned,San Francisco Medicine, the archives of that are available on the website, including the previous environmental health issues. But also, just in April, a recent one was cancer in the Bay Area. It did feature a piece by Dick Clapp and others on there. You can find those. We could send them out via link, as well. The archives are all there, and the April issue is the last one that has really a whole spectrum of articles related to cancer.
[NOTE: http://www.sfms.org/sfm/sfm405.htm San Francisco Medicine - April, 2005 Cancer in the Bay Area. In this edition of San Francisco Medicine, we deliver a wide range of articles that report on the disturbing and increasing incidence of cancer in both children and adults.]

That’s great. Thank you, Steve.

MAIN PRESENTATION:
Let’s go ahead and move into our main discussion. This call today represents one year of the Cancer Working Group’s continued exploration into the research on environmental exposures to cancer. We’ve featured the epidemiology of environmental and occupational exposures. We’ve featured breast cancer and precautionary work and biomonitoring. We’ve looked at the state of the science. Now we’re looking at fetal exposures.

This research project by TEDX, which is The Endocrine Disruption Exchange, was designed to search for the literature for evidence that some postnatal cancers may be determined prior to birth. Scientists in this cancer group had been reviewing the document for approximately 6 months or so. It’s now a completed database, which Mary and Theo will tell you about.

I’d like to start by turning the floor over to Pete Myers, who -- along with Theo Colborn -- authored the seminal book Our Stolen Future, about 10 years ago, now. Pete will set the context for why we’re having this discussion on fetal origins of cancer, and where it fits in with the larger conversation that’s going on with fetal exposures and gene expression.

Pete Myers: Thanks very much, Jeanette. We’ve had strong evidence that fetal exposure can lead to cancer in adulthood, at least early adulthood. Since Howard Ulfelde, Arthur Herbst and David Poskanzer discovered that exposure in-utero to DES – diethylstilbestrol – causes vaginal clear cell adenocarcinoma in young women, in 1971, the question is, “Is DES an exception?” Or does it represent a common pattern?

Most epidemiological studies of cancer risks that have been published since this discovery in 1971 have assumed it’s an exception. And they’ve focused their measurements on associations between adult exposures and adult risks. Many of these studies of many contaminants have included using the model that specific contaminants are not risk factors for cancer. Many of our current regulatory standards have been heavily influenced by those negative results. The scientific research in several areas is emerging to suggest that the DES pattern – fetal-exposure/adult cancer – may be more common than many people assume.

Animal research summarized several years ago, in a really excellent review in Environmental Health Perspectives by Linda Birnbaum and Suzanne Fenton, shows a series of examples in which fetal experiences alter adult cancer risks in animals – and/or increased sensitivity to cancer-causing agents, later in life. I know Ana Soto will be talking about her own excellent research on this, during the call, today.

Some epidemiological research has shown associations between exposure and cancer risks that are consistent with fetal origins. The most striking of these is work by Hardell et al, published in 2003, showing that a mother’s body burden of hexachlorobenzene is a better predictor of the son’s risk 20-30 years after he is born… his risks of testicular cancer… than is the son’s body burden measured at the time of cancer diagnosis.

This result is consistent with a large body of work that I’m sure a lot of you are familiar with, by Nils Skakkebaek , in his lab – demonstrating that the origin of testicular cancer in young adulthood lies in the failure of specific cells within the fetal testes, to differentiate properly in people.

Finally, the discoveries that fetal starvation can lead to adult obesity – which was published in 1990, by David Barker – has launched a new field of research called, “Fetal Origins of Adult Disease,” or, “Developmental Origins of Adult Disease.” Strong evidence now exists – both from animal research and human epidemiology, that fetal conditions can influence, if not determine, adult health – across a range of health endpoints.

This collective body of work is indicating that DES isn’t likely to be an exception. I think the question is becoming or evolving to, “How many other cancers follow the DES model?” This is going to have profound implications for how we approach management of cancer risks. Thank you.

Thank you, Pete.

Theo – can you tell us more about how and why The Endocrine Disruption Exchange began this particular project? Then we’ll move directly into Mary’s work.

Theo Colborn: That was an excellent introduction. My story goes back to the early 90s as well when I was privileged, because I was working with Pete, to work closely with people like Drs. Fred Vom Saal, Ana Soto, Carlos Sonnnenschein, Howard Burns and even Nils Skakkebaek from Denmark – whose research suggested at that time, that prenatal exposure to endocrine disruptors could lead to cancers later in life. The idea kept nagging me for years. Yet those concerned about the increasing epidemics of breast, prostate and testicular cancers just seemed to not be able to grasp the idea and run with it.

I was sure that when Ana Soto’s and Carlos Sonnenschein’s book The Society of Cells came out in 1999 the idea would really catch on. Their book presented a case for the tissue organizational concept of carcinogenesis, which Ana – I’m sure, I hope – will mention later this morning when we hear from her.

Again, even with this easy-to-read, well-written book, the idea just sat out there, waiting to be recognized. And I continued to fail, as did many attempts, to convince several large cancer support groups and government groups, to focus more on fetal exposure as the etiology of the growing cancer epidemic. I suggested that they shift some of their research dollars from treatment and cure to prevention – but with no luck.

However, every now and then, when I ran across a paper that would be over-suggestive of cancer of prenatal origin, I put it in a separate file. Then, one day soon after Dr. Mary Bachran walked in my door looking for work, I figured out how to vent my concerns that society is sitting on a cancer powder keg and is doing nothing about it.

With Mary’s skills, it was time to get into TEDX’s search machine, to see what was out there in the peer-review literature. We had no idea what she would find, or how the data would fall out. But Dr. Bachran is here with me now, and she will tell you, basically, what she found. Mary?

Mary Bachran: Thanks, and welcome to everyone. Fetal origins of cancer database is a compilation of peer-reviewed articles from 1971 to present. The purpose of the research was to examine the published literature, looking for patterns, with an eye toward prevention.

Quickly, we realized that the literature was far more extensive than we had assumed, with a preponderance of studies on smoking and ionizing radiation. Decisions were made early on, to stop including articles on these heavily-researched areas, and rather to try to make the research as broad as possible. As such, the research collected in this database is not exhaustive of the subject.

Several exposure risks emerged, as we studied the database. As previously stated, smoking and radiation have research histories of over 50 years, and are thus prominent in the database. DES also has a long history of research surrounding it – which continues, today – as the DES mothers, children and grandchildren age.

Epidemiologically speaking, this drug presented a best-case scenario for linking prenatal events with postnatal cancers. The population was narrow and defined – that is, pregnant mothers – and could be relatively easily tracked, over time. In conjunction with this, the laboratory evidence confirmed, and in some cases predicted, the long-term effects of the drug.

Maternal conditions were shown in the database, also to be associated with postnatal cancers, particularly high levels of maternal estrogens. These estrogens have been linked to 12 different types of cancers, with a preponderance of evidence pointing to: Breast cancer, male-reproductive cancers, leukemia, lymphomas and cancers of the brain and nervous system.

The confounding factor is that most of the studies in the database base their conclusion on the assumption that maternal symptoms such as preclampsia, and infant parameters like birth order or birth weight, indicated elevated levels of endogenous estrogens.

However, no measurements of maternal hormones were taken – either during gestation or at the time of birth. The question remains, therefore, as to what was the actual cause of these cancers. Could manmade estrogens have contributed to the results, or been the deciding factor? That question remains open.

This leads us to another area of exposure – that of industrial chemicals. Twenty odd chemicals are included in this area, with most of the studies focusing on PCBs, dioxin and bisphenol A or BPA.

Most of the studies in this area have been done in the last 10 years and the vast majority show direct links to cancer or increased susceptibility across almost every system tracked. In this area, the chemicals have either been exclusively examined in the laboratory or in case-control or epidemiological studies. Further research directions might be to verify the lab results in the general population, and the human results in the lab.

According to the matrix, the cancers most-frequently found were the leukemias and lymphomas. As these cancers are often diagnosed in very young children. It is not surprising that they are more often linked with pre-birth exposures. Cancers of the brain and nervous system comprise a significant portion of these results, with exposure from a wide variety of chemicals linked to these tumors.

The reproductive system cancers, both male and female show stronger links with natural and synthetic estrogens than any other causes, while liver and respiratory system cancers are most-often linked with smoking and air pollution.

As for age-of-onset, as mentioned, the earlier in life a cancer is diagnosed, the more possible it is to make the links to prenatal conditions. That being said, some of the cancers in this database were not diagnosed until mid-life or later. It is a testament to the skill of the researchers that they were able to make any connections to exposures that occurred before birth.

In conclusion, I’d like to point out that much of the research contained in the database was done by scientists outside the field of toxicology. Much of the DES work was performed and initiated by the medical profession, while much of the work into the more recent chemicals of concern, such as BPA and the phthalates – is being done by developmental biologists and endocrinologists working in collaboration with chemists.

These people have opened the door for approaching the safety of chemicals with a much broader sweep than in the past. They look beyond the conventional point mutation, adduct and toxicological theories of cancer. Thank you.

Thank you, Mary, for this work and for your incredible contribution in pulling all of this together, and making it easy to understand.

Now I’d like to ask Dr. Ana Soto from Tufts, who’s actually actively engaged in doing research right now, to tell us a little bit about her current project.

Ana Soto: Thank you, Peter and Theo, for the wonderful introduction.

I would like to comment on two points that are related to the fetal origins of cancer. One is the view that cancer is a cell-based phenomenon, due to DNA mutation. It’s been challenged by epi-genetic views.

One of them is ours – that Theo referred to. In our view, we conceptualize carcinogenesis as development gone awry.

For example, a chemical needs not to be a mutagen to cause cancer. Actually, the carcinogen is supposed to alter the reciprocal interactions between these two components. These are the interactions that form a tissue during fetal life, and repair it through adult life.

The breast is probably one of the most obvious cases where development continues through the whole adult life of the woman. But it doesn’t stop in fetal life. It continues, and exacerbates in puberty. And then, through each cycle of pregnancy and then through menopause. So we have a structure that is continuously changing. That is one of the reasons to use breast cancer as a model.

The second point… I don’t know if I will have time to talk about that. But we have shown that if you separate the two main components of this tissue that have the stroma and the epithelium… And as you know, most of the breast cancers originate in the epithelium. Which have exposed the epithelium to carcinogens, and then to the stroma to carcinogen. The stroma - then we combine it with the epithelium. We observe that an older stroma is able to induce cancer in the epithelium – so demonstrating that the carcinogen doesn’t need to mutate the DNA of the epithelium, itself.

But I don’t want to go on with this, because that is something else. I want to talk about the chemicals that have been used – the bisphenol A – and which have exposed animals to environmentally-relevant doses of this chemical. That is, doses you and I are exposed to, today.

We observed that BPA produces long-term effects in the mammary glands, that become apparent a long time after exposure. If this effect was observed in humans, they would suggest an increased risk to develop breast cancer.

For example, we know that the main risk factor for developing breast cancer is the cumulative exposure to varied hormones – estrodial and progesterone. In our studies, perinatal exposure resulted in an increased sensitivity of the mammary glands to bisphenol form of estrodial. In other words, the mammary gland at puberty thought that there was more estrodial than it really is. And accordingly, it responds more.

This resulted in the increase of the number of cultures at puberty, and later on. These are the structures in which breast cancer arises, both in humans and in rodents.

Finally, the increased sensitivity to estrogen that I referred to already led to the overexertion of progesterone receptors. Progesterone – which is also produced in the ovaries – contributes to the risk of breast cancer. It induces lateral branching of the mammary gland ducts.

This results in an increased ductile density of the glands. In humans, we know that increased mammary density is also a risk factor for breast cancer. So, if these animals were humans, we would say, “Well, the risk has been increased in many ways.”

Why do I think that this is important? In the first place, because we are presenting epidemiological studies that maybe refer to comparing twins and single birth – revealing that the propensity to breast and prostate cancer is enhanced in females and male trends. And that when compared to single-situ pregnancies – and it is supposed that two placentas will produce more estrogens than a single one.

So our results were toward the notion that prenatal exposure to BPA, in particular, and estrogens in general, may increase the risk to develop breast cancer later in life. These effects are taking place at the doses that are current-exposure doses in humans.

So I think that we should think that maybe this has something to do with the increased breast cancer links we have observed – that increased three-fold. Women’s risk of contracting cancer in their lifetime was 1 in 22 in 1947. It rose to 1 in 14 in the 1960s, and is 1 in 7, today. This coincides with the increase in environmental factors such as BPA in the environment.

I think I took, already, my 3 or 4 minutes. There is a lot more, in addition to what I just said. Both regarding the theory of carcinogenesis and BPA exposure – but I will stop, here. I’ll leave the rest for the question and answer part. Thank you.

Thank you very much. I also wanted to thank you for accommodating your travel schedule, to be here with us, today.

Operator – let’s go ahead and open up the lines, please.

As a reminder to all the call participants – the lines will be open. This means that we can hear you and ambient noise. So please keep the ambient noise, down. This is a sensitive line. Please do not put us on hold, because we will hear your hold music, and it can be very disruptive. When you ask a question, please identify yourselves and your affiliation, when you speak.

We’ve received a few questions, and I wanted to simply say that – 1 – this call is being what they call, “Streaming Archived.” It’s not directly taped. We’re using that to create transcripts. That’s what we will use and distribute in our notes.

Sandy Ross asked a question for Theo. Why don’t you go ahead and ask that question quickly, Sandy.

Sandy Ross: Good morning, Theo and everyone. Thank you so much for all your brilliance. You did a fantastic talk at World Environment Day in San Francisco. I am wondering if you could possibly share that with the rest of the CHE network via e-mail. It was so good, but it was so rich, I couldn’t possibly take all the notes. Neither could either of the others – Connie or Ginger – when we were there.

Why don’t we help facilitate that? We can work with Theo to either get some information to you, or post that information, on line.

Thank you.

I’d like to open it up to others who have questions.

Lisa Ledwidge: This is Lisa Ledwidge, with the Institute for Energy and Environmental Research.
I want to thank you all for your great work. One thing that I noticed, in going through the abstracts that Theo and Mary put together – which were great – was that ionizing radiation is one of the few so-called well-established or definitely-related-to agents related to leukemia and other types of cancers that come later in life.

Combining that with the recent Natural Academy of Sciences study that came out on the health effects of radiation indicating that women are generally, for most cancers, at greater risk from radiation exposure than men. It’s really frustrating to my organization that the federal government still bases radiation protection standards on this hypothetical individual called, “standard man: a 154-lb. adult white male.”

So my question is sort of a general question to whoever knows but I wonder if this concept of, “standard man,” which is also called, “reference man,” is used in determining limits for chemical exposures – like drinking water, limits for lead or mercury or whatever.

Who would like to answer that, please? Do you know?

Theo Colborn: This is Theo. I wasn’t sure if we were on mute or not. Some of the drinking water standards are based on children – how much they will drink in a day, and how much they will drink over a week. Others are based on a liter or two a day. It is very, very broad – I would say “generous.” As a matter of fact, when I read these things, I think, “Oh, my goodness. I never drink that much water!” So it varies, depending upon the chemicals it’s being looked at, under. There’s no consistency.

Pete Myers: This is Pete. There are standards. There are safety factors built into the Food Quality Protection Act that specifically are supposed to lower thresholds, because of the general perception that children and developing organisms are more sensitive than are adults. At least in that area, the law, this sort of issue is addressed. How adequately certainly remains to be determined, given that many of the current thresholds were established a very long time ago. But there is a lot of sensitivity to this, and an effort to readdress it.

Thank you. Next question?

Michael Lerner: This is Michael Lerner. I thought those were really brilliant presentations. I just think it’s remarkable, how we’ve evolved as a community, in terms of our capacity to explore a very important area of science. Fetal origins of cancer, specifically, and communicate among each other so well.

Two points. One is that I’d like to ask Theo to address the capacity of TEDX to do these fetal-origin reviews across a considerable range of the diseases, disorders and conditions that CHE is concerned about. And what future areas they’re looking at, and how we might explore what the highest priorities might be, to look at fetal origin reviews like this.

Secondly, I wanted to ask Julia Brody – whom I believe is on the call – to what degree the paper that Silent Spring is doing for the Komen Foundation – has reviewed the fetal-origins issue. And for any comments she may have about her own review of this area.

Theo Colborn: Michael, you put me on the spot (laughter). Well, we did the files here and there recently, over the years of various fetal origins of disorders. I don’t call them diseases. I call them disorders.

We started, and I have not promised anyone we would do this because I’m not sure we have, right now, the financial support to continue doing this kind of thing, but we have diabetes. We have many papers related to intelligence and behavior in children, as they get older.

I’m looking at Mary, because she’s getting this wastepaper basket together and organizing it. Of course, we have the brain, the thyroid and definitely, pancreatic issues.

Mary Bachran: All of the systems that we looked at in the fetal origins of cancer [inaudible] were going to look at disorders, as well as the behavioral disorders, such as autism and ADHD.

Well, we’re going to look at obesity. We have just barely begun to put some kind of organization on this. Then as I pull the research down, we may have to sort it into, uh, we’re not quite sure what kind of segments – depending on how much literature we have in the different areas. But considering all the literature we found on the fetal origins of cancer, I’m suspecting we’re going to have 3 and maybe 4 times as much literature on this.

Sandy Ross: This is Sandy Ross. What it sounds like to me is that if we all kicked in $500, Theo could have an extra assistant, and the papers could come out much faster.

Theo Colborn and Mary Bachran: Sounds like a deal! (laughter)

Pete Myers: If I could make a suggestion, it would probably be worthwhile to look at the University of Southampton’s website on fetal origins of adult disease. If you Google fetal origins of adult disease, you’ll find their website. You’ll begin to get an appreciation for the range of adult conditions that people now are looking at, as likely to be influenced by the fetal experience.

I would suggest that you do that. Then, we should look at how big those endpoints are: Diabetes/metabolic disorders/obesity. That’s big. Asthma. That’s big. Prioritize peoples’ investment and time, based on the plausibility of, given some of this work that Southampton’s doing… They’re mostly focused on nutrition, but they’re beginning to look at other factors, also.

Plausibility and bigness. That’s my suggestion.

Michael Lerner: That’s a really interesting suggestion, Pete. I hope we can follow up on that with Theo and others who are interested. So we can make this fetal origins’ work of CHE systematic in the way Pete is suggesting.

Pete Myers: I’m sure Alison [Carlson] would appreciate it if fertility issues were a part of that. That’s big, and it’s certainly plausible.

Michael Lerner: Julia Brody – are you on? Can you comment on this?

Julia Brody: Yes. Well, breast cancer is an important place to look for these kinds of effects. We see in the example of radiation – we know that girls who were younger at the times of the atom bombs have higher breast cancer risks than those who were adult. So we have a model that tells us that environmental exposure at younger ages can matter.

Our review this year is not going to focus on this in a lot of detail. But we have proposed to do a detailed review of fetal origins of breast cancer for next year. Also, of the endocrine-disruptor mechanism, which will lead us into this area, as well.

Many of the chemicals that we’re interested in came into use in the late 1940s. So women who were exposed prenatally are now in their 50s, and just beginning to be of an age where they’re at higher risk of breast cancer. We may see much more evidence unfolding in the epidemiology in the next several years.

Ana Soto: This is Ana Soto. If I may add something regarding breast cancer – at least in animal studies, sensitivity to carcinogens decreases with age. Which means, therefore, that in the moments in which there is more developmental activity of the mammary gland, there is more risk to disturb it and end up with cancer, which again brings us to the tissue organization theory, and to the fetal or developmental origins of the disease.

Thank you. Next question.

Neil Gendel: This is Neil Gendel, and I’ll just take a chance because I don’t really know what I’m talking about. I hope it’s a good question. Obviously, we’re interested in protecting children from exposures. Most of the discussion has been around the results through the years on adults. Is there some good information on fetal exposures and how the disease develops?

Mary Bachran: This is Mary. Absolutely. The leukemias and lymphomas are very directly connected to fetal exposures. There are also brain and nervous system cancers in children that have a pretty good research history.

Theo Colborn: Also, just again, there are developmental effects in children that are not carcinogenic.

Neil Gendel: I’m very interested in that kind of stuff.

Marian Feinberg: This is Marian. There is also a whole bunch of research – some of which is ongoing – about fetal exposures and development of asthma. There’s a whole bunch of work that’s come out of the Columbia Center for Children’s Environmental Health. That follows a cohort from time of pregnancy.

It actually measures maternal exposures during pregnancy, to certain agents. Then, it looks at the kids, afterwards. Two of the tracks that they’re really looking the strongest at are developmental effects and asthma effects in the children.

There’s even stuff that’s just been circulating around that I’ve seen in other places about maternal exposures to VOCs – like cleaning chemicals. Common household cleaning chemicals and development of asthma in children, also.

Part of my question is kind of like, “How do we tie up some of this other research into fetal exposures which lead to other kinds of diseases, which people are currently looking at through this cancer stuff.” Is there sort of a way to begin to weave a tapestry together on the one hand, and on the other hand, to be able to start to do some advocacy around it?

Theo Colborn: I think there is, and I think this is the way we need to go. By weaving it together. There is a great [inaudible] looking in the field of neurotoxicology, at prenatal development where the development of the brain, where chemicals along that pathway from birth-to-conception can interfere with how the brain develops but it may not be expressed until some of these individuals reach adulthood.

I just had a paper come online this week in EHP. The idea of long-term effects. One of the things we’re working on here now, and I have a wonderful intern working with me from the University of Florida – where we’re trying to produce a picture of what happened to each developing system in the body. Developing from Day 1 to Day 365, or the 40th week of gestation. As you look across this board, you see that there are concurrent developing system. One is not developing alone. There are a whole bunch developing at the same time. Then if you decide to throw something into that system, somewhere along the way – the third or the fourth week – you will begin to see that not only can you expect impairment in the development of the brain or sexual development. You will see it across this period of time. You would expect more than one kind of a health expression later on in this individual’s life.

That’s another thing we’re trying to do, here, to produce a sort of picture of what’s going on for those 40 weeks. Yet, we have a lot of chemicals now that we know, in the laboratory, if you throw them into the soup you’re going to see these changes.

Also, I think that Shanna Swan’s work definitely revealed that the phthalates at about the 6th to 7th week on this human picture that we’re drawing, apparently interfered with the external genitalia development of the boys that she looked at.

Michael Lerner: I think Marian has asked a really key question. I’m glad Theo responded. I’d like to ask Pete for his comments.

It seems to me that, Marian, in asking how we weave these together – and Theo, pointing out all the areas in which this can work… this goes back to Pete’s suggestion that we look at the Southampton website and other sources, and that we prioritize further work – in terms of both the size of the literature and the plausibility.

It seems to me that what we’re talking about is a kind of strategy of scientific inquiry and appropriate advocacy for CHE, that would play across this whole set of fields. Pete – you’ve spent a lot of time on science strategy. Can you say more about how you can imagine us thinking together on this, and how we could operationalize what Marian has asked us about, and what Theo has suggested as the scope of the issues?

Pete Myers: That’s a good question. I’d like to respond first, a little outrageously. I’d like to say that if I had to bet right now, I’m going to bet that 20 years from now – hopefully sooner – we’re going to understand that the origins of most breast cancers and most prostate cancer – and certainly most testicular cancers are the result of failures of proper development in the womb in key tissues.

We need to keep pushing to make sure that the science that’s underway today doesn’t continue to feed us with false negatives, based upon simplistic studies, looking at adult exposures and adult risks.

I think we have to push, constantly. Not insisting that we’re right, but insisting that they have to be testing this hypothesis – at least as rigorously and as aggressively as the one that has been so typically off base, and has failed us, heretofore.

That’s a bit of outrageousness for us.

I think that we’re going to be learning. Certainly, the work being done at Southampton and labs actually around the world, on fetal origins, is saying that many health conditions arise from altered hormonal sensitivity, where hormone receptor-density is set in the womb….some of the stuff that Ana was talking about.

That’s the science. Where we go with organizing thoughtful advocacy – science advocacy and then public advocacy about that is… I’m not sure. I think we start asking questions when the opportunities arise. We ask them consistently.

I have to admit, I just returned from the neurotoxin conference in Raleigh-Durham. Elise Miller as some of you know, at Learning and Developmental Disabilities Initiative in Washington, is a CHE member, organized a really excellent session. It was a community meeting at the scientific meeting on autism.

The people representing autism-based groups were remarkably effective at getting their questions to become the focus of the meeting. It was because they were there. There were many of them there. They were from different organizations. And they asked the questions consistently. That’s where we begin.

Ana Soto: I would like to add just a little thing to what Pete said, now that you are talking about autism. I want to stress that during that, animals that have been exposed to BPA at miniscule doses have all kinds of alterations in their behavior. I wonder in a way if it wouldn’t be good to get into forming a network of people working on different endpoints, so that we can investigate the same animals for these very different endpoints. All of this happened after fetal exposure.

Michael Lerner: That’s a very interesting suggestion, Ana. Any comments on that?

Theo Colborn: That’s the one that we have tried to work with over and over again with EPA. When someone is testing a chemical on an animal, they’re only looking at one system, generally. To try to get them to look across the board with all of these animals. But also, one of the things they never look at is – believe me, I’ve sat in on too many years of this… They don’t look at the heart. Yet, one of the most-frequent birth defects or problems are heart problems in babies. They throw the hearts away. Those hearts should be sent off somewhere, to some university, that would be willing to begin to look at the differences in the hearts of those animals that are exposed to different chemicals.

There’s a gold mine of work out there, without having to kill any more animals, but to use just what we have. That’s another strategy we have to work on, as well – and I don’t know how to break the thinking on this. Mostly, it’s because there’s not enough money to ship the animals, to store them – timing… There are a tremendous number of difficulties trying to do this. So we’re wasting a lot of time, looking at one chemical at a time and one system at a time.

Pete Myers: The Southampton Research Group is looking at cardiovascular effects.

Michael Lerner: Let me also just mention that CHE partner Betty Mekdeci has done a lot of work with the online groups working with heart defects. In human children, they’re really heart-rending issues. So there’s a whole set of online support groups of parents of children with heart defects that Betty’s involved with. Also, we did a call on environmental cardiology. As Steve Heilig pointed out, that will be one of the two subjects of the upcoming CHE conference in the spring – along with cancer. Cancer and heart disease.

I think that with heart disease, we have to be sure that we’re looking not just for the arthrosclerosis, but also at heart defects and related issues.

Pete Myers: Michael, you should have some people from Southampton talk about fetal origins of adult heart conditions.

Michael Lerner: That would be terrific.

I think that this idea of the network of different endpoints is excellent. I’d love to see the cancer groups initiate some of that discussion, going forward. We have time for one more question, and Marcia Marks has one. Marcia, can I turn it to you?

Marcia Marks: My question was, are there similar studies being done on environmental exposures to male sperm at the time of conception? Or changes to male genes? Such as what’s happened during the Vietnam war. My concern is, is all of this pointing to the dangers to the fetus? Will it cause problems with allowing women in the workplace?

Thank you. Who’d like to take that answer?

Ana Soto: Well, I only know from Vom Saal and Skakkebaek, that they are studying effects in males. So that is underway, as well. Although we are very few people that study these typesof things, at least regarding endocrine disruptors. Pete, would you like to add something?

Pete Myers: Well, not in any detail. But there is literature on the male father exposure, and the effects on fetal development and problems in childhood. For example, a study published a couple of years ago on EHP looked at male DDT exposures in relationship to birth defects in offspring. They find results. They find significant associations.

Ana Soto: Yes, and the cigarette. I don’t know if it was published already, but it’s a paper by a French group. The senior author is called Vignay or Cordiet. They found that I think the endpoint was brain tumors. It’s not the mother – the one that needs to smoke. It’s the father.

Marcia Marks: I just think it’s important to balance out these factors, so that we don’t just point to female exposure.

Marian Feinberg: I remember reading maybe 15 years ago in the New York Times, actually, about a whole study to do with incidence of birth defects related to plants or occupation. Such that auto mechanics’ babies tend to have more of certain defects, et cetera – and went down the line. I know that stuff is published in occupational literature about this.

Marcia Marks: I think that data needs to be gathered, to balance the picture.

Pete Myers: I’m not sure it’s going to balance as well as it should be, because of the fact that the fetus is in the womb for 9 months.

Michael Lerner: As we close the call, let me say this has been a very rich call, and extraordinary material. First of all, I just know we’d all like to thank Jeanette for her extraordinary contribution to CHE, as a whole – and to the cancer group, specifically. Jeanette, I know you’re going to stay connected to CHE. We look forward to many future years of collaboration with you. Thank you so much.

Multiple voices: Here, here! Yes. Thank you.

Michael Lerner: Secondly, just to try to cull a couple of the key points… Ana’s suggestion of a network of researchers, which Theo was also speaking to looking across endpoints. That’s one thing I think we should follow up on. Then, the point about looking across research areas, and prioritizing Pete’s point, as a second area that we want to follow up on. Then, specifically, on the cancer work, we have this wonderful paper from TEDX, now.

We have Dick Clapp and his colleague’s important work. The question on where we take the cancer research, next, is – I think – an important question for the working group to think about. Those are at least 3 of the major areas.

I also – just in closing – since this is a joint call with the Fertility and Pregnancy Compromise Working Group, I want to mention that Alison posted something from the Resolve website. It’s an extraordinary piece of work on fertility and pregnancy compromise that includes contributions from Pete and other CHE partners. For those of you who want to see our CHE at work – actually moving into the fertility and pregnancy compromise area – Resolve’s collection of papers on this is a wonderful example.

Jeanette, I turn it back over to you.

Jeanette Swafford: Yes. Well, we are at the top of the hour. So I wanted to thank everyone for joining us. A special thank you to our speakers. I appreciate everyone’s help in making this a great call, today. I look forward to seeing the way things develop.

Thank you, everyone.

[End of call]