Extended Interview: Dr. Godfrey Oakley

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• SUSAN DENTZER:

  How did you first get interested in spina bifida?

• DR. GODFREY OAKLEY:

  Well, that's a very interesting question. I went to CDC thirty years ago in something called the Epidemiology Intelligence Service, a place they have doctors come for two years and work on a health problem, and the health problem I was fortunate enough to work on was birth defects.

  And one of the most interesting birth defects from an epidemiologist's viewpoint was spina bifida, and the reason for that is around the world the incidents varied by tenfold. Even within this country it varies from three times as high on the East Coast as it is on the West Coast. And those are the kind of clues that suggest to you that there might be something in the environment that might cause this birth defect. So people around the world were sort of rooting around with this one trying to find out what could it be that might be the cause.

• SUSAN DENTZER:

  Just on that point about the variation here in this country, East Coast versus West Coast, what potential explains that?

• DR. GODFREY OAKLEY:

  Well, I think folic acid explains, is likely to explain it all. But we didn't know that when I started working at the CDC in 1968. We just knew that there was these differences in where people lived. It varies by race. African-Americans are partially protected, for example. The rates are lower in African-Americans than in Caucasians, and it varied with time. The massive epidemic in the United States occurred in the '30s where one half of 1 percent of all babies had spina bifida and anencephaly, or an infant mortality rate of 5 just from those two birth defects.

  So all those things, when they change and you see these variations, it's sort of like the FBI and the CIA. How do you connect the dots? These were some clues, and when do the dots get connected, and how do you connect them? That's what epidemiologists do is to try to get those kind of bits and pieces, and it took another 20 years before the dots got connected, but I remember when the dots got connected for me.

  It was at 5:00 on June 24th, 1991, when I got a call from Professor Wald from England, who had done a randomized control trial in which women who had previously had children with spina bifida and anencepholi were randomly assorted, either to get folic acid, or a placebo, or folic acid plus other vitamins, and what they conclusively showed in that study was that the folic acid prevented — and it was just folic acid, not folic acid and other vitamins — prevented actually 72 percent, but to make it easy to remember, 75 percent of the cases of spina bifida among these women who had previously had affected children.

  And I was at a birth defects meeting with some of my new tenants, and we sat down that evening and said, you know, what we need to have happen is to have every woman in the world consume 400 micrograms of folic acid, and we've been working to try to make that happen since then.

• SUSAN DENTZER:

  And just to back up, you mentioned the epidemic here in the '30s. That was the Depression. Was it related to – apparently, was it related to poor diets during that period?

• DR. GODFREY OAKLEY:

  That would be my guess. This was discovered by Harvard professors in the late '60s or early '70s, so nobody really knows. But folic acid is so fundamental to life that it would be my sort of education guess or hunch that almost all the variation in spina bifida around the world is due to how much folic acid is in the diet.

  You can't make the base pairs of DNA, the ATCG that are the alphabet of life, you can't make those without folic acid. And the reason that's important to a developing fetus or embryo is it starts out as a sperm and an egg, it's got to make a gazillion cells, and every time it makes a new cell, it has to double the DNA. And if you don't have the building blocks for these base pairs, it all shuts down, and the cells don't divide, or you slow up the rate of division, and that's what leads to the maldevelopment.

• SUSAN DENTZER:

  So how do we think of folic acid? Is it part of the latter that links the base pairs?

• DR. GODFREY OAKLEY:

  Exactly. That's exactly it. You know, these letters — other people call them the alphabet of life — they come three at a time, and these three letters describe a particular amino acid. Then the amino acids make proteins and that's why your eyes are blue or brown or whatever is how that works out. And, of course, if you change one of those base pairs, that is one of the kinds of mutations, like sickle cell anemia in a whole string of whatever it is, 3,000 of these base pairs, there's one of them that's wrong, and that's what causes sickle cell anemia.

  For cystic fibrosis, it's much more complicated. Sometimes it's just a missing pair, other times it shuts down and you just can't make any more. But yes, it is exactly those base pairs that hold – that's the chemical electrical forces that sort of hold DNA together, and of course, the way you replicate DNA is you separate and then you make the mirror image.

  A fellow named, or a professor, a well-known professor, Dr. Bruce Ames from, I guess it's the University of California at Berkeley, has become very interested in the fact that you also need folic acid to repair DNA from the damage that sun does, and he thinks that probably folic acid or the lack of folic acid in people's diets is the most common cancer-causing exposure that we have, and may be a part of the colon cancer story.

  And then there's Walter Willett from Harvard, who has run this nurses' study forever. You know, there's 100,000 nurses. And the nurses that take a multi, just a simple multi-vitamin for 15 years reduce the colon cancer rate 75 percent, and Ames thinks that these two things fit together because if you don't have enough folic acid, you can't turn the U, which is uridine – or R cell that's in RNA – you can't turn that into thymodine, which is the T that goes, and if you don't have it, then you put uridine into the DNA and it's tough for the repair enzymes to fix the DNA when that happens, and that's a setup for a mutation.

• SUSAN DENTZER:

  So the bottom line is that folic acid is really integral to our existence as human beings, and we've just figured out one tiny little piece of this puzzle, which is that if you don't have enough in the very early stages of embryonic development, you get spina bifida. Is that fair?

• DR. GODFREY OAKLEY:

  I think that's very fair, although the spina bifida evidence is new, and I think it's a second wave of what we've learned about folic acid. I mean, there was a huge wave of research done in the '30s and '40s. The folic acid was first determined to be a problem in people by an obstetrician, Lucy Wills, in India, who was seeing Hindu women die in late pregnancy from anemia, and she found out that yeast had something in it that would – that would prevent this or cure this. And that's the first human interaction with folic acid.

  It's sort of interesting that it was pregnancy and that it was a woman doctor that was involved in doing this, and then it – see, that was in the early '30s – '31 or '32, and then we moved to '91, what is that – that's 60 years. So for 60 years we didn't figure it out, but now we've got these two powerful new themes going on with folic acid now, one of which is the birth defect story that is absolutely certain.

  And then there is the story for adults — cancer, cardiovascular disease, stroke, and Alzheimer's — that's going on as we talk, and the science continues to go along. So you're right, it is integral, and in fact, I think people say well, how could it be so active in so many things. Well, it just comes back down to something that is so central to life. If you can't make cells, or if you can't make DNA and keep it repaired, your body is in trouble. You've got to have it.

• SUSAN DENTZER:

  So what is it that we think is the specific mechanism that leads to neural tube defects?

• DR. GODFREY OAKLEY:

  That's another really tough question, and we actually don't know the answer. I like to tease my more basic colleagues by saying epidemiologists do it, prevention before we know the mechanism. And so this is an exact place where we actually know how to do the prevention. Folic acid to all women of reproductive age, and we prevent these birth defects, and we don't know why.

  The two leading hypotheses of Klein – the one I favor is that you simply do not have enough of the building blocks to make DNA, and so the rate of cell division slows up.

  A developing 18-day embryo has a very fast rate of cell division. It does not have a placenta that works, and so this thing that's making cells as fast as it can possibly make them has to depend on rather inefficient diffusion of fluid with folate in it to the embryo from the mother's blood through her tissues and so on in a very inefficient way, and I think it probably just slows up the rate of cell division, and then after a while it's just too late to catch up and so you wind up having the neural tube be open.

  Now, there's another line of reasoning that's different from that, and it could be true. I can't say which is correct – and that is that the folic acid that you eat becomes something called 5 methyl tetrahydrofolite, and in order – and 5 methyl you can't make DNA out of.

  In order to make DNA with 5 methyl you've got to take the methyl group . . . one carbon group, and the body does that with an enzyme, and it takes the methyl group off 5 methyl and puts it on something called homosistine which goes through this reaction and becomes methionine, and methionine is very key to providing one carbon groups to metholate DNA, to metholate proteins and so on, and some people think it is the extra provision of these methyl groups that might be the key.

  My bet, as I said, is on the first hypothesis. I hope I live long enough to figure out what the answer is. And I hope that we've made spina bifida go away around the world actually before we know the mechanism because we could do that in 10 years if we rolled up our sleeves and worked around the world to pull this off.

• SUSAN DENTZER:

  Now, as I recall being told, you also have some direct experience with delivering babies. You were a practitioner at some point, right?

• DR. GODFREY OAKLEY:

  Well, that's a bit strong. I'm a pediatrician, and an epidemiologist, and a geneticist, and my clinical experience was as a pediatric counsel officer. And so when I finished my pediatric training, I actually don't think I had ever delivered a baby. I've actually looked after some very sick babies when they were handed to me, but I have not ever really delivered a baby, and I've looked after, you know, children with spina bifida, and I know adults with spina bifida and so on.

• SUSAN DENTZER:

  Describe to me some of the children you've looked after.

• DR. GODFREY OAKLEY:

  Well, spina bifida and its related birth defect called anencephaly are – I don't know any other term than to say they are big-league birth defects. They're birth defects a grandmother can make the diagnosis from, you know, from across the hall.

  And the most important thing, I think, to remember about spina bifida is that it causes paralysis. And the way I think about this embryo developing is that what's going to become of your brain and your spinal cord, is like a flat sheet of cells at 18 days after the time the sperm meets the egg. And for it to make a brain and a spinal cord, has to roll up into a tube called a neural tube, and that's why these are called neural tube defects. And it starts the zipper sort of in the middle of your back, and it zips up to your head, and it zips down your spinal cord. If this zippering process doesn't work right, then you get one of these two birth defects. If it doesn't work going forward, you get anencephaly, which kills babies usually during pregnancy or they die very soon after birth.

  If the zipper doesn't work going toward the tail end, then you get spina bifida, and the effect of it is it's as if this baby was developing just fine, and then was in an automobile crash and because it wasn't enough folic acid in the mother's blood stream or in the diet, it's as if the spinal cord was cut. And how much disability the child has depends on where you break your back. If you break your back really low, you don't have very much disability, and if you break it at your neck, you can't move your arms and your legs. And so that's the reason that most children with spina bifida have paralysis, because it's in the part of the – it's essentially as if it – by keeping the spinal cord from developing, it's as if it was actually cut and you lose function.

• SUSAN DENTZER:

  So when you saw some of these infants, what did they look like?

• DR. GODFREY OAKLEY:

  Well, they are – it depends upon how old they are, of course, you know, they grow. And when they're babies, and you have to do the surgery, and get the spinal cord covered up and covered with skin, and most of these children would develop hydrocephalous if they didn't have surgery, so they have surgery in there to put this tube that runs from inside the brain down into the body cavity so that the cerebral spinal fluid doesn't blow up – doesn't make hydrocephalous.

  A really nice parent story – this thing is called the Holder valve, and in 1954, I think it was, Mr. Holder, who was sort of a fancy plumbing technician, engineer sort of guy, had a baby with spina bifida, and the doctor explained to him, you know, this hydrocephalous occurs because the pressure builds up on the inside of the brain…[static]…the pressure inside there, and so they built this Holder valve, which is a one way valve, and when the pressure builds up too high it dumps cerebral spinal fluid out inside of the brain, down into a body cavity and prevents hydrocephalous.

  Well, the problem with that is that kids grow. So you put one in shortly after they're born, and sooner or later you've got to take it out and put another one in. So a lot of what you're early care of children with spina bifida is, is being concerned about that shunt becoming infected, because that's an infection in the brain, trying to figure out from all the other sort of usual pediatric feeders and so on, is this due to the shock or does the kid just have a bad ear that needs penicillin, and of course, if you make a mistake there, then you potentially have a really serious, serious problem.

  So that's what the early years of life – then these children, you know, develop and go to school. Probably the most difficult thing is being able to help children be able to control their bowels, because almost every child with spina bifida will have paralysis of bowel function, so an awful lot of energy goes in trying to just make the social graces work there. Then you try to let these children reach their potential, you know, like, and we have neurosurgeons, and school teachers, and all those things that they grow up to be.

  But still there's a major disability that needs some help, and you can't let your guard down. I remember a very good friend whose 15 year old, very with it, a kid with spina bifida, they changed settings. They went to visit an aunt, and while the family was out taking a walk, this child, this teenager decided to take a bath. And, of course, they're paralyzed.

  They don't have – they don't feel anything either, so they have lost sensation. And so it gets into a bathtub not knowing that the temperature in the hot water heater in his aunt's house is whatever it was, 20 degrees, 40 degrees higher than what it is in his own house. He didn't put his finger in to see if it was warm, and he came out with third degree burns after just taking a bath.

  So there are all sorts of things that have to be really structured very well to be managed, and this is clearly a birth defect that I think, you know, most people would like to prevent, and for me, when I heard the news in 1991, it was as if someone handed me the polio vaccine, and only about half a dozen people in the world understood what had just been handed to us.

• SUSAN DENTZER:

  What is the world-wide NTD birth defect rate and what could we do about that?

• DR. GODFREY OAKLEY:

  Oh, yeah, well, it's very high. There are roughly 500,000 children a year born with either anencephaly or spina bifida, and we would project that three-quarters of those we could prevent if we increased folic acid fortification around the world.

  I was just in India and was looking at – the rates there in India are about four times what they are here . . . [static]. . . and working in the Ukraine gives us this possibility of . . .[blank spot in tape]. . . we can prevent a thousand babies from having spina bifida and anencepholi in just one country of Ukraine and probably set the pattern for getting it all done throughout the USSR because the mills were all run by the Russians, and if we fix it there, we will have a blueprint that will make it go across the whole former USSR.

• SUSAN DENTZER:

  Why is it added to flour?

• DR. GODFREY OAKLEY:

  Why is it added to flour. That's a very good question. One thing, it's easy to add to flour . . .[blank space in tape]. . . has sort of less variance than many other foods. Like if you looked at milk, some people don't drink milk at all. But almost everybody eats either some flour or some grains in someplace, and in the U.S. it wasn't just flour, it was flour, and corn mean, and rice, and a lot of different places that it was required to go in. Of course, the way they changed the rule was to change the definition in a very legalistic way of the term enriched on bread, flour, spaghetti, whatever. If it says enriched, the FDA and the FCC says you have got to put folic acid in there. You've got to put iron, and thiamin, niacin, riboflavin in there, too, which now, you must have put folic acid in there.

• SUSAN DENTZER:

  You said FCC, did you mean FTC?

• DR. GODFREY OAKLEY:

  Maybe I did. I don't know which it is. What they did was they changed the definition of enriched, the FDA, and that means that if you want to send it in interstate commerce, you must put folic acid in it. Of course, before we had the folic acid rule, they had to put thiamin, and niacin, and riboflavin, and iron. This just added folic acid to it. Now, if you don't want to put the word "enriched" on, and you don't ship it in interstate commerce, you don't have to add folic acid. And I think we have a problem with corn meal that's used to make tortillas. There is a large company that makes unenriched tortilla mix that's very popular in the Mexican-Hispanic community that doesn't have any folic acid added to it.

  Even a joke on myself, two Christmases ago I got cornmeal from two places because I like cornbread, and one of them was from my favorite restaurant on the coast of North Carolina, and they make their hush puppies, which are the best cornbread in the world, out of unenriched flour – I mean cornmeal. Gee, guys, I wish you would fix that.

• SUSAN DENTZER:

  I need you to say what the current recommendation is in terms of the grams that are added of folic acid, too.

• DR. GODFREY OAKLEY:

  The current regulation requires that flour have 140 micrograms per 100 grams of grain, which the average American woman eats 80 grams of grain a day, which means she would get – the average woman would get 100 micrograms.

  Now, there are other recommendations. There is a group in England, it's the committee on food and nutrition policy, has recommended fortifying in England at 240 micrograms per 100 grams, and one country has done it right. Chile has done it right. The folks in Chile say we want to make this birth defect go away, and the way to do that is to put enough folic acid in the bread that we'll make it go away. And the number for them was 220 micrograms per 100 grams because Chilean women eat roughly twice the amount of bread that a U.S. woman eats.

  And I've seen data that hasn't been published yet, but shows that they actually, when they did the fortification, they hit it right on the head. The average woman gets, I think, 405 micrograms of folic acid a day, and we're in the midst of seeing what that has done to prevent spina bifida and anencepholi. We'll know a bit more about that later. But I think Chile would be the first country to essentially make this birth defect go away, and we can do it all over the world. If we just – if Chile can do it, we can do it everywhere.

• SUSAN DENTZER:

  So at best, here in the United States women are going to get a quarter of their needs of folic acid supply through the food supply, is that right?

• DR. GODFREY OAKLEY:

  Through the required fortification of flour. Now, it's important…the average American woman will, through eating enriched grain products like flour and bread and hot dog buns will get, on the average, 100 micrograms of synthetic folic acid a day, which is one-fourth of what the Public Health Service recommends, and one-fourth of what the Institute of Medicine recommends.

  Now, are there other sources of folic acid? Yes. Could that estimate be wrong? Yes, it could be wrong. It could be that women eat more than 80 grams of flour a day, and in fact, we've been a little bit surprised at the blood levels. The blood levels are a little bit higher than we thought they might be. But nobody really focused on the blood levels before, and we're sort of doing catch-up ball in this, trying to figure this out.

  But it's complicated in the U.S., figuring it out, because one of the things that's happened has just been marvelous, is that the breakfast cereal industry has responded to this new science by putting more folic acid in many of their products. It used to be that most cereal products had 100 micrograms per serving, and there were just a couple, Total and Product 19 among them, that had 400 micrograms per serving. I usually say these are essentially, these are multi-vitamins that look like corn flakes, these that have 400 micrograms per serving.

  Well, now there are over 50 brands that have 400 micrograms. Even Wheaties with Tiger's picture on it has gone from 25 percent, or 100 micrograms per serving, to 50 percent, which gives Tiger 200 micrograms per serving, and maybe that's why he won the Master's this year, he went from 100 to 200.

  But the technical point is that it makes it very hard in our country to separate out how much any change in the blood level that you see in the average U.S. woman is due to what was added to bread and required as opposed to what was voluntarily added to cereal, or which a woman voluntarily takes as a vitamin supplement pill.

  And the best place to sort of see how much change really occurs will be out of Chile because in Chile, breakfast cereal we don't use very much, and there are no other sources for the synthetic folic acid essentially other than what's coming in bread. I'm really eager to see those data and see if they get published and so on.

• SUSAN DENTZER:

  As you said, we have begun to see some changes in the blood supply, the blood level that indicate that this is having an effect, and I assume you're familiar with the results of the…study – walk through those very quickly, what that has shown.

• DR. GODFREY OAKLEY:

  Sure. There have been two post-fortification studies that are, I think, very nice. One is to look at blood levels in a representative sample of American women, and what they've shown is the blood levels have gone up by threefold, that now the current median is higher than the 90th percentile was before. So a wonderful, wonderful thing has happened, and competent with that is what's happened in terms of health outcomes has also been good.

  One of the things that nobody ever talked about in any of this was what it would do to folic deficiency anemia, and folic deficiency anemia for people of all ages, or people above the age of two, has dropped off the face of the map in the United States and Canada. Nobody ever counted up what the benefit of that would be. But because we did this for spina bifida, we made this go away.

  Spina bifida and anencephaly have dropped about 20 percent. We thought it would drop more, and we still think that if we get more folic acid to women, either through putting more in flour, or having more women take supplements or eat breakfast cereals with folic acid in them, we'll do even a better job of prevention than we are currently doing.

  The other good news is that there were 5,000 fewer stroke deaths the year after fortification, and to me that is even a more remarkable story than the spina bifida side of this. The spina bifida, there were 800 fewer spina bifida and anencephaly kids, but there were 5,000 fewer stroke deaths. And there were 22,000 fewer heart attack deaths. And people argue a bit about how do you know that that's for sure due to folic acid.

  With a stroke the evidence is very good. There is a randomized control trial that folic acid will help do this, and lots of other studies that will suggest that it would, and they had for many years, being a reduction in the rate of stroke, that stops reducing in the middle seventies that started again when folic acid came online.

  So I think it may be that the most important thing that's happened to improve cardiovascular health in a long time was that folic acid was put in the flour in order to prevent birth defects, and because it was put in the flour, everybody in the country's blood folate level went up, and their homosistine levels came down. And homosistine, as you know, is a powerful new risk factor for cardiovascular disease that is viewed as being as strong as cholesterol, so another wonderful part of this folic acid story.

• SUSAN DENTZER:

  There is some controversy over what is behind the reduction in births of infants with spina bifida, stemming from the fact that we don't completely know how much of that has resulted from terminations of pregnancies, and sonography, testing, and the fact that parents can become aware earlier on now that their children may already have neural tube defects, what do you think is the actual story there?

• DR. GODFREY OAKLEY:

  Well, while I was at CDC and since I left CDC, I put a fair amount of energy into trying to figure out how to count not only the babies that are born, but the babies that are aborted with spina bifida in certain parts of the country, and it is from that work that we estimate that there are 4,000 pregnancies affected with these two birth defects, and the estimate is about 1,500 of those were prenatally diagnosed, and the woman elected an abortion, leaving about 2,500 that were born.

  So I think we have that – it's difficult to cover, but I think we have that fairly well covered in at least – in a few places in the country, enough to make inferences about the rest of the country.

• SUSAN DENTZER:

  so we now believe it's more accurate to say that there are 2,500 babies born a year with spina bifida and 1,500 pregnancies terminated.

• DR. GODFREY OAKLEY:

  That's right, and you might even say less if you take the 800 that the fortification has prevented, you take the 2,500 and subtract, so it's 1,700 maybe is where we're down to now.

  Of course, the really difficult question is – and nobody knows this. I don't know this, nobody else knows it – what is the absolute minimum when there won't be any more folic acid preventable birth defects, and I wish I knew the answer to that. I wish there was a bar code on the babies that said, you know, this one is – we don't have any more folic acid preventable spina bifidas, but we don't have that. And my position on this has been folic acid is safe, we ought to get as many women to take enough as we can, and if we find out that we have got enough, then we can back off. But there is certainly not any reason not to prevent all of these serious birth defects that we can prevent.

• SUSAN DENTZER:

  You're an advocate, as I understand it, of continuing to raise the fortification efforts, and add more folic acid to food. Where do you think we should go?

• DR. GODFREY OAKLEY:

  That's a very good question, and I think that, you know, you get more and more data, you have other things to look at. As I said earlier, there's no question that we've made a major impact with the fortification that was done in terms of blood levels, and we're still guessing about could we look at the blood levels and guess at how much folic acid women are actually eating, which is sort of a long, almost backwards way of getting at the right answer, but we sort of use that – my sense is that we would be I think around the world we should do no less than what was recommended by the British committee, which was 240 micrograms per 100 grams of grain, and I would do that in the United States tomorrow. I would even be happy with it going higher, but certainly that's been recently reviewed, and everybody agrees it's perfectly safe. It should be easily doable.

  If I were to have my own way, and the way I look at it, I would say it would be at least what the CDC recommended before, which was 350. And I only back off from that or stall for just a minute, is that if for some reason we learn that American women are actually eating more flour than it was estimated prior to the modeling, then one might not go to 350. One might stay at the 240 or something like that.

  And I think maybe part of the obesity – probably – maybe we miscalculated when we did those surveys, miscalculated how much flour was actually eaten by women of reproductive age.

  And the other thing I would do is that I would – and not because there's folic acid in flour, but the Institute of Medicine recommended in 1998 that everybody over 50 consume 2.4 micrograms of Vitamin B-12, totally unrelated to the folic acid story. And so far the FDA hasn't moved to make that happen. I don't understand why. It's a very easy, simple, cheap thing to do, and I think that what needs to happen, there needs to be a serious forthright look at the science, look at the new data, sit down with people who are as unbiased as they can be to look at the data. You call me an advocate, but I feel like I'm a data driven – let's see what the data are, and then we can decide what the inference is, and then you decide whether it's just going to happen, or do you have to get out there and fight for it. And so I think we need to have that discussion now on folic acid – more folic acid in the bread, and adding Vitamin B-12 to the bread.

• SUSAN DENTZER:

  So in effect you're recommending, and people who take your perspective are recommending that we at least double, if not triple, the current supplies.

• DR. GODFREY OAKLEY:

  right. And interesting — some very new interesting data that I'm just onto, there is a guy in Australia named Finnich – his last name is Finnich, and he has looked at the classic markers of mutation in people's blood or in cells from humans, and he's done a calculation about how much folic acid you'd have to eat to drive that to a minimum, and his number is 700 micrograms a day. He didn't come at it the way I came at it, but, you know, it's clearly not 100, you know, and 400 is maybe enough, but here's a guy who is sort of close to that, is saying 700, and that's a synthetic folic acid, and you would have to double that, so it would be 1,400.

  So I think if we get everybody up to consuming 400 micrograms, that would be a really nice step in the right direction, and in order to do that, we need to put more folic acid in the bread than we have now. But it does need – don't misunderstand – there does need to be a serious review. But it shouldn't sit around for ten years before we have it. We should have been having it yesterday, people sitting down and saying now here we've got this, now what are we going to do? We're going to put more in, and my view is that we should do that, and of course, more importantly is the countries that haven't done it yet, in my view, are committing public health malpractice.

  Nobody in Europe has put folic acid in the bread yet. I mean, it's just absolutely absurd. And they're actually causing people to have heart attacks, and to have kids with spina bifida. They could make – they've got the money, they've got the factories, and it's food politics within Europe that's keeping it from happening. That food politics ought to change, in my view, so we can start preventing the birth defects.

  Around the world it's not nearly as much a problem. Most of the Central and South American countries have done it. They're doing it in parts of the Middle East, they're doing it in the Far East, but Europe has got this thing and they haven't moved on it, which is really unfortunate. They should move.

• SUSAN DENTZER:

  What about the role of health care providers? Are health care providers doing enough to advise women of these very substantial risks and very easy steps to take to rectify them?

• DR. GODFREY OAKLEY:

  I think that depends upon how widely you define health providers. My view on this is that if the FDA wasn't going to put enough folic acid in the bread, the CDC should have been given $100 million a year to build a program that would teach health professionals and have marketing programs that would teach women that don't come to health professionals about folic acid. So far, no president has asked for that money, and the Congress hasn't appropriated it, so the CDC has had almost no money to deal with this, and it's been wonderful that the March of Dimes stepped in, spending about $3 million a year.

  So sort of what we have is something that needs $100 million a year, $2 million a state, and the March of Dimes is able to put $3 million a year in, and that's been wonderful, but we're not there. As you know from their survey, only 30 percent of women of reproductive age are taking enough folic acid, and in that survey, of course, they said – they gave the idea that if health professionals recommended, that women would be more likely to take it.

  And so my view is I'd like to echo what Dr. House, the president of the March of Dimes, says is that every health care person – pharmacist, nutritionist, ought to be saying to every woman of reproductive age at every encounter, are you taking your multi-vitamin, and if you're not, start taking it.

  But the food politics on this is terrible. I mean, for example, we tried to get – you can't buy vitamins with food stamps, and Senator Harkin, you know, worked really hard to get it in the Senate Farm Bill, it wasn't in the House Farm Bill, and all that money went into the farm bill and that provision got taken out because of food politics. And so women on food stamps and women in WIC clinics can't use those vouchers to buy vitamins.

  It's silly. We have a public health recommendation, an Institute of Medicine recommendation that every woman should get 400 micrograms of folic acid, and the women that are the toughest to reach, which are low income women, young, low income women, where they get their medical care and where they get their source of food, people are saying we're still not going to permit them to use these to buy vitamins. I don't understand it. It's just driven by food – it can't be cost.

  I have in my suitcase and I will give you a bottle of CVS vitamins that I bought on the way over to the studio today, it cost me one penny a day to buy a multivitamin from CVS, and I'm sure the Farm Bill had enough room to give the 50 million women of childbearing age enough money to cover their folic acid.

  But again, to me, the more effective way to do this is to turn to CDC, the Center for Disease Control and Prevention knows how to prevent disease. We know how to make – my colleagues still at the CDC know how to make immunizations work. Our kids were immunized, you know, immunized around the world. We know how to make that happen. But the CDC has a billion dollars a year worth of money to do that.

  There's a new birth defect center at the CDC that its total budget is only $100 million for everything that it does. The CDC spends $150 million helping India stamp out polio a year. Now, that's a wonderful thing to do, but to me, it just shows how underfunded the CDC birth defects are. Basically we need a war on birth defects, and we have a war on cancer, but we need for President Bush to stand up and say we need a war on birth defects, and the first thing I'm going to do is get $100 million to make sure we don't have any more folic acid preventable birth defects in the U.S., and then maybe we'll find some money after that to try to get this job done in Ukraine and China and India and other places.

• SUSAN DENTZER:

  We've also been told that Medicaid will not pay for multi-vitamins for low income women.

• DR. GODFREY OAKLEY:

  Medicaid is different. Medicaid, at least in Georgia, I know will pay. I think the issue with Medicaid is that in order – you have to create a market for that vitamin. I mean, the fact that Medicaid says I will pay for it is not the same thing as having a woman come ask for it.

  And so, I mean, what we need to do maybe is to work with the guys in the cigarette industry who know how to change behavior who are adolescents, and to get those techniques, that's marketing. In the public health world it's called social marketing. And so where do we get the money to do that social marketing, and Medicaid doesn't want to spend any money that way, and to me it doesn't make any sense. They could spend money on social marketing that would prevent spina bifida, instead of having, you know, a million dollar baby, they'd have a baby that wasn't.

  And again, you know, two babies a state is the $2 million we need, and I'm confident that if we had $2 million go into Georgia where I'm working actively, or $2 million a year to go — in fact, it's been shown in South Carolina. If you put that kind of money into South Carolina, you can change the behavior of women consuming vitamins. But other states haven't done that, and of course, the simplest way to do that would be to get the Congress to put $100 million in there.

  I mean, another parallel story is the hermaphilis influenza vaccine was invented at the same time we got the story about folic acid. But the vaccine industrial complex works. We don't have hermaphilis influenza meningitis anymore. It is a remarkable victory of pediatrics in this country, and around the world, that this vaccine has been given.

  The vaccine industrial complex knows what to do. The vitamin industrial complex is still dysfunctional, nobody has actually asked for the money. We need to get, you know, the war on birth defects going, and to get some money to that new center at CDC which will work with the March of Dimes, and the Spina Bifida Association, and the American Academy of Pediatrics and all the other people that you have to work with.

  But you've got to have a focus, and really proud of that new center that the March of Dimes helped get done, and there is now at one place in the government a unit with a high enough rank that we have an admiral run it. Admiral Jose Cordero is in charge of the National Center for Birth Defects and Developmental Disabilities at CDC. Admiral Cordero needs some bullets. He needs some money to buy some bullets, and those bullets with the first priority would be to buy a program that would increase the number of women that consume enough folic acid either through eating, or either taking vitamin supplements, or eating these cold breakfast cereals that have 100 percent of the USRDA of folic acid in them.

• SUSAN DENTZER:

  Has there been a benefit cost analysis done suggesting what – you mentioned the $1 million baby. Is that a real figure?

• DR. GODFREY OAKLEY:

  Yep. I mean, not as much of that has been done as there should be. The average cost of a medical cost for a family with a child with spina bifida for, say, 20 years is about – ten years ago it was about a quarter of a million dollars. That's the average cost. That doesn't count the kids that die. So on the other end, there will be some up there in the million dollar range.

  In fact, the former president of the Spina Bifida Association of America kept saying to me, "Godfrey, can you add? Let me show you how much our child has cost." And I forget exactly what his was, but it was more than $250,000. That was the average cost.

  Medicaid, at least in Georgia, pays for 75 percent of the cost of care of children with spina bifida until they get to the age of five. And everybody, I think, who has a kid with spina bifida becomes eligible for Medicaid because of the disability associated with it.

  So, again, it may be sort of like the FBI. I mean, the Medicaid agency really isn't into prevention. They're into paying for care. They sort of need to change the culture. The Congress could help them do that. The congress could help them do it – would be to put money into – into prevention. Get the messages out to women of reproductive age.

  I mean, what are the messages that need to go? We need the calcium message, we need the HIV message, we need the protection message, we need the folic acid message. And why can't we figure out how to get that message to low income women in a way – and men – that is effective. And why not have Medicaid pay for some of that.

  I mean, I think the smoking money is a nice example. All of that smoking money came, and they built campaigns to try to keep adolescents from starting smoking, and in Florida it apparently worked. It worked well for a year, then they stopped doing it. Well, you can't stop doing it after a year. I mean, there's a new crop of 14-year-olds every year, and you've got to have that message there until it becomes a part of everybody's culture. And I think the folic acid story, you know, done enough, we'll make it a part of everybody's culture.

  Ten years from now there won't be any health care professional not talking about this. And my guess is that what the health care professionals that I talk to sometimes don't know is the amount. Let me just say this so if any of them are listening, they'll know what that is, and that is the recommendation is that for every woman who could get pregnant, not for women just planning pregnancy, but for any woman who could get pregnant, 400 micrograms of synthetic folic acid a day, and the two easy places to get that is from a multi-vitamin or from a cup of a breakfast cereal that has 400 micrograms per serving in it, and that's easy, simply, it ought to be said to every woman who walks through the door, and I would like it if every hairdresser, and every dentist, and every dental technicians, and anybody in McDonald's telling the kids when they come in, my daughter is looking for new stuff to sell. I wondered if maybe they would get into the multi-vitamin business. That might be an interesting things for McDonald's to do. It would do a lot toward helping us reach an audience that we're trying to reach that we haven't been able to reach.

• SUSAN DENTZER:

  So what's your dream?

• DR. GODFREY OAKLEY:

  Well, my dream is a world in which we don't have any birth defects, and I believe we can do that. And in just about my lifetime the view on that has changed. A few years before I was born – I was born in 1940. Up until 1933 it was assumed that all birth defects were genetic, and that the mammalian uterus was so good, it protected the baby, the fetus from all noxious influences.

  And then a veterinarian – and this is not a nice story. You never know where the smart guy or gal is that comes up with the science. This was a veterinarian at Texas A&M in 1933 published a paper that showed that if pigs got pregnant when they were Vitamin A deficient, they had pigs with no eyes, and that was the first demonstration that you could change the environment in the mammalian system and make birth defects. And then, of course, in 1941 Rubella was shown to cause birth defects. And so forever that myth was gone.

  But I think the public at some level, and I think maybe the reason we haven't had people really get out there and fight for the war on birth defects is that at some level it's like well, fate made this happen. Well, fate didn't make this happen any more than fate made cancer happen. This is just — what we have to do is to do the science that finds out what are the things that actually make this happen, and then alter those things that we know how to make happen.

  Some of those things we aren't going to be able to alter very easily. Some of those are clearly going to be genetic things that we won't be able to alter, or it will take us a long time. But there is even some good news there in the sense that the Rh factor problem, that was a major killer of babies for years, is a genetic disease that we cure – not that we cure, that we prevent with an immunization. And so it's a genetic thing with an environmental intervention, and PKU is the genetic thing with an environmental intervention.

  So some of these things will be like, will be purely genetic. They will have an environmental intervention. The others will be like folic acid where it's mostly an environmental story, and that we need to change the nutrition and to make it happen.

  I mean, the other thing that I would do in this dream is I think we have, as a society we have misappropriated our attention, and we think that the man-made chemicals are the source of all of our problems. But the big causes of birth defects that we know about are fetal alcohol syndrome, that surely must have been made shortly after Eve left and Adam left the garden. I mean, it's been around forever. Frolic deficiency birth defects, and the congenitive Rubella syndrome – those have absolutely nothing to do with man. They've been here forever. It turns out that we can fix them.

  So with things like acutane and other things that are really important, they're important for individual families, and we need policies to minimize that, I think we haven't turned our scientific scope to try and define what are the causes of birth defects that have been causing children to have birth defects since the time of Adam and Eve.

  We don't have – EPA doesn't do that. They spend all their money on stuff that's been made in the last 50 years. And so that's what I'd like to see grow is the research arm of this new center at the CDC. It needs to focus on taking all this wonderful genomic data that's come down, and doing the best job we can to find out about the other environmental issues whether they're man-made or in the natural environment like infections and nutrition, and tease these associations apart, and then implement the programs that need to be implemented to do the prevention. And right now we've got this – we've done Rubella in this country. We are wonderful with that. Rubella has not been done around the world. It's sitting there for somebody to do around the world.

  Folic acid, we're getting started on. Fetal alcohol syndrome and all the damage inuteral alcohol does, we haven't even begun to scratch the surface on. That's a tough one. I mean, you just can't put something in flour and make that go away. I mean, it's tough, and it needs a lot of work, and it's not going to be as easy as the folic acid one.

• SUSAN DENTZER:

  Specifically, what is your dream vis-à-vis spina bifida ?

• DR. GODFREY OAKLEY:

  Oh, my dream with spina bifida is that we eradicate, that we have the total prevention of folic acid preventable spina bifida by the year 2010, and if we roll up our sleeves and make the political commitment to do it, we will make it happen.

• SUSAN DENTZER:

  What is your ribbon?

• DR. GODFREY OAKLEY:

  The ribbon is a ribbon that grew out of the folic acid campaign, I think, in North Carolina. The original folite and the activity of folite came out of was first isolated out of a ton, actually four tons of spinach. So one of the natural sources of folate are dark green, leafy vegetables. So this is either the folic acid ribbon – I really like to call it the war on birth defects ribbon. I just wish it was funded a bit better.

• SUSAN DENTZER:

  On the question of the natural food supply, in what foods can folic acid be found, and what are the limitations of getting it out of your diet?

• DR. GODFREY OAKLEY:

  Folite was first discovered in spinach, and so I have hanging on my wall the original description of four tons of spinach. They got some folite activity out of it. So folic acid comes from foliage, so dark, green, leafy vegetables are a very good source.

  Citrus fruits are another good source. Orange juice is a good source of this. Apples, unfortunately, are not, but, I mean, citrus fruits and dark green, leafy vegetables are the – are good sources.

  But having said that, we don't know that you can change your diet by increasing your consumption of fruits and veggies to have the full protection against having a baby with folic acid preventable spina bifida. And to show you how this plays out, it turns out that the average diet has 200 micrograms of natural folate in it, which is worth only 100 micrograms of the synthetic folic acid, and what we know is that if you add 400 micrograms of synthetic folic acid, or four times – not four percent, but four times that amount, you get the full protection for preventing spina bifida . Well, how much spinach would you have to eat if you had to eat four times the amount that you're currently eating now? Would that be a lot? And four times the amount of bell peppers, or broccoli, or for the former President Bush, Brussels sprouts, for goodness sakes. It would take an awful lot.

  So, I mean, to me, I think it's – the simple message on this is that sure, we should all eat a nice diet. We should eat a diet that's rich in folate that has at least five fruits and vegetables a day. We ought to control calories and fat, but we ought to also consume a multi-vitamin that's got folic acid, and for people over 50, has synthetic B-12 in it.

• SUSAN DENTZER:

  To the question of doctors, are doctors telling women enough about how to prevent these birth defects, and giving them the tools to do that?

• DR. GODFREY OAKLEY:

  I don't think anybody knows for sure, but the survey that the March of Dimes did suggested that women learned about folic acid from their doctor about 35 percent of the time, and other times they learned about it from TV programs and the media.

  I think that could be better, and I think like doctors and health care professionals, like everybody else. They've got a learning curve that has to be put in, and it would be very nice to see that all of them made it a part of their routine, that when they saw women of reproductive age, whether it was for a PAP smear or whether it was for a sore throat or whatever, to ask the question, are you taking your multi-vitamin, and if you're not, telling them why it's important to take that multi-vitamin that has 400 micrograms of folic acid in it.

• SUSAN DENTZER:

  Good. That definitely does it. Is there something I should have asked you about that you would like to say?

• DR. GODFREY OAKLEY:

  Well, there is something I'd like to say. I always like to conclude by saying that all of us get invited to weddings, and one thing we can do is to give the bride a year's supply of folic acid or a multi-vitamin, and tell her why it's important. And, of course, if you happen to be invited to the party the night before doing the toast, you can have the folic acid to healthy babies. One way to really do that practically is to have the folic acid toast. So I invite everybody in the country to join Maryann and me in this tradition that we are trying to add to our wedding routines.

• SUSAN DENTZER:

  Do you do that?

• DR. GODFREY OAKLEY:

  I do, yep.

• SUSAN DENTZER:

  And would you say that you and your wife –

• DR. GODFREY OAKLEY:

  Oh, yes, sure. Well, Maryann and I, my wife, have started for a number of years now, every time we are invited to a wedding, we give the bride a year's supply of folic acid, and we tell her why. And, of course, my kids say to me, "Well, you know, Dad, not everybody waits to have sex until they get married," and I say, "Well, I understand about that, but this is the best we can do under these circumstances, and we invite everybody to join us."

• SUSAN DENTZER:

  I'm told also you've shown up at wedding receptions and passed out folic acid from time to time.

• DR. GODFREY OAKLEY:

  That's correct. In fact, I usually carry them in my brief case, and I actually had to buy some, because I have some for you and for others that have been working on this program today. It's very important for everybody to take their multi-vitamin.