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interview: Dr. Jamie Grifo
Dr. Jamie Grifo is Director of the Division of Reproductive Endocrinology at New York University Medical Center.  He is working on a revolutionary new technique that could someday rejuvenate an older woman's eggs. One of the amazing things about this whole area of infertility medicine is how it keeps evolving, how it changes. What is that about?

Well, it is about experience, research and a field that is really driven by a need for patients and competition. So it makes us want to try new things and be better than we are. I remember doing IVF with a 10% pregnancy rate, thinking that was great. Now, you'd be hung if you had a 10% pregnancy rate.

... One of the things people talk about is the amount of, by necessity, experimentation that has gone in this. Do you see that as unusual for medicine?

Well, it is unusual in certain respects. In many areas of medicine, basic research is done and then that is applied to medicine. But in this field, we were never really given the ability to do the proper research in humans ... There was a steep learning curve that we had to do in the early days, because no one would let us do research on embryos. We just had to do the best we could with patients and learn as we went along. That is kind of unfortunate, because it really slowed us down. We would have gotten to where we are now much faster, had we done it the other way, but it was just too controversial and no one wanted to let us do that.

What do you mean, you weren't allowed to do that?

Well, embryo research, especially in the States is something that is frowned upon. It's fraught with a lot of political ramifications and there is this great confusion between infertility and abortion politics. And it really is strictly confusion, because I don't think people understand what we are about. We are about helping people have babies. Somehow, we get caught in the fray of the abortion debate and abortion politics. That is unfortunate, because it has hurt our patients. We are not about abortions. We are not trying to do abortions. We are trying to help people have babies.

How has it hurt your patients?

It has hurt us, in a sense, that there is no federal funding for research, so we have had to finance all of our research with clinical dollars. In fact, all of our research for pre-implantations genetic diagnosis has been done with private funds. But mainly from clinical dollars generated by the practice and some patients have donated money to help us, but there are no federal funds for these types of projects. So that's been a big problem, but in terms of infertility, in vitro fertilization treatment per se, there really hasn't been a concerted scientific effort from the National Institutes of Health and other federally funded research organizations to benefit this field. It has all been done privately.

Some people are concerned that there is, as a result, a lot of experimentation on humans. What do you think of that?

It is a naive view of what's really happened. In a sense, medicine has been a human experiment since the beginning of medicine. I mean, we've always learned. That is why we call it the art and the science in terms of medicine. There is a learning curve, and we are still learning that we know very little about many diseases that we currently treat today. It is through research and ethical human experimentation that we make progress. So it is naive to think that human experimentation doesn't exist or shouldn't exist because the absence of human experimentation makes us do poor quality, poorly understood bad medicine. That is not what anybody wants ... You have to do these things with ethical guidelines, in a very thoughtful way that really looks at patients--their desires and needs--and make sure that they understand what is going on. When you do that, then research is good and we have proven that.

It is different than other areas of medicine? There isn't the same sort of work to prove its safety and efficacy before being used more broadly.

Well, that is a difficult thing to do. For instance, let's give you an example. A heart transplant. Someone had to do the first heart transplant. How do you do a safety study before you do it? Well, you do stuff in animals and it works and then you say, "Okay, now we are going to try it on a human." You take the most desperate case and you do the research, you do the experiment. The first guy has a little bit of success and then dies, but you get better at it.

In this field, we were never really given the ability to do the proper research in humans ... There was a steep learning curve in the early days, because no one would let us do research on embryos. We just had to do the best we could with patients and learn as we went along.  Well, our evolution is not much different than that. We have used IVF as a last ditch effort for all the other standard treatments that haven't worked. And we have gotten better and better at it ... Our patients don't die of infertility, but ... it is a horrible disease and I don't think people view it in that context ... they view it kind of as a cosmetic thing. "... you'll adopt or you won't have children, you'll be fine." Those people saying that have kids. But if you are infertile, you understand what I am saying. If you are not infertile, you may or may not understand what I am saying.

Marie and Doug Arcurie were very convincing in talking about that and the problems that they faced ... Once there was a fix for Marie's genetic abnormality, was the process of getting pregnant easy?

Well, no, it wasn't that easy, because part of her problem is her ovary has a lot of eggs that are missing X chromosomes. That had a lot of impact on her fertility. In fact, it made her infertile in the standard way, the natural way. Even with IVF, it limited our ability to be successful. In fact, the first time we were successful, it was touch and go in terms of the stimulation and number of eggs we were able to get, but we were fortunate and things worked out.

As we tried the second time, there were several attempts and Marie was not responding well, which is in direct correlation to the genetic defect that she has and her ovaries are really petering out so to speak, because of this genetic defect. I even actually said to her, "You know Marie, we should stop trying 'cause I don't think this is going to work." But it is always where the patient sometimes has [more] wisdom that then doctor. She didn't want to stop and we had lots of talks about this ... she wanted to proceed ... I gave her my estimate of what her success rates were. We were thrilled and, actually, a little bit surprised that this last cycle worked. We had one embryo transferred; usually, you are not that successful in that circumstance. I am glad to have been proven wrong and my hat is off to Marie for persisting, because if she had listened to me she probably wouldn't have the second child.

In this last case of the last child, there was one embryo ...

... We transferred it at the egg cell stage or the day after the biopsy was done because we didn't really feel there was a reason to wait any longer. It was either going to make her pregnant or not, we might as well put it back, so that is what we did.

Explain what you are doing with the egg itself to do the biopsies?

Well, the way the process works is we do in vitro fertilization, we get eggs, we fertilize those eggs and make embryos. On day three, after fertilization, the embryos are usually between five to eight cells and in the morning of that day, using a micro-manipulator, which is just a fancy microscope that allows us to use these robotic instruments, little glass pipettes that we forge to do microsurgery on an embryo and what we do is we take this eight-cell embryo and pluck one of the cells out so that we can do a genetic analysis on that single cell. Those embryos then put back in an incubator until we get the result. Then we select which embryo which is healthy to be put back for transfer and those embryos that are genetically defective, we don't transfer.

Now why is that an advantage?

... Patients who are at risk for transmitting a genetic disease have a 25 to 50% chance of transmitting that disease to their offspring. Were they to get pregnant, they run a very substantial risk of facing the issues of: Do I terminate this pregnancy? Unfortunately, they can't find that information out until about 12-16 weeks in their pregnancy.

A lot of these patients who have used this transplantation genetic diagnosis technique either have a child with a serious illness, have lost a child from a serious illness or have found out they have had a pregnancy that has been affected and had to terminate the pregnancy. That is why they are motivated to go through this process and what it allows us to do, the exact thing that we do at 12 or 16 weeks, except that we can do it at the embryo stage.

So we are not really doing anything that different, it is just that we are doing it much earlier so that we can put back an embryo that won't make them pregnant with an abnormal embryo. We can save and avoid a termination that might have to occur and with a 25 to 50% risk. You can see where that is an advantage.

Is there a sense of a cure, a way of eliminating some of these horrible illnesses?

Well, in a sense, yes. If everybody used it. But these techniques are very limited, they are very costly, not everybody has access to them and not all diseases can be treated in this way or avoided in this way. So we have a long way to go before that becomes a question that has meaning in terms of wiping out genetic disease, but the key to genetic disease is prevention. It is much easier to prevent a genetic disease than it is to treat it. So this is really an extension of what medicine has done for the last 30-40 years, but it is just an earlier stage and a better way for patients who suffer from these problems.

In the literature, some people have said that while it is wonderful, it does sort of raise ethical questions about who gets it and who doesn't. Could there ... be a genetically privileged group in some way?

Well, I think very strongly about the ethics of this and I understand and have been involved in many discussions, have actually been on the Ethics Committee of The American Society of Reproductive Medicine, and there are many critics of these techniques. But I'll tell you one thing. There is not one critic who has the disease that we are treating. There is not one critic who understands what these patients go through the way I do. If you see these patients, you sit with them, you talk with them--this makes perfect sense.

But for the critics and the ethicists and all the people who worry about the misuse of this technology, they forget about who is benefiting and they forget about who is driving the technology. They think it is a bunch of wacky scientists trying to do all sorts of crazy things and they don't understand that there is a patient on the other side of this technology that needs our help. Everybody ignores that patient because they get so involved in politics and ethics, and what is forgotten is the most important thing. So I'd be willing to argue with any ethicist about this. They don't get it if they haven't seen my patient.

You are obviously very passionate about this. Why don't they get it? What is it?

I guess people are afraid [that] with these technologies and I am, too, I could misuse this technology, but I don't. I don't because there is a group of patients who benefit from it and that is why I developed it and that is why I have spent the 11 years in my spare time working on this technique. And spending lots of money on it, because we have lost tons of money in research and development that will never be recovered. Because there is a group of patients out there who need it. I don't understand the critics, I think they have these tremendous fears ...

A lot of these people raise what seem to be valid concerns--that we do have the power to change ourselves in some way and to create different classes almost.

They absolutely are important concerns, but most of these concerns are more fear of the technology than the actual reality of what we can do. What we can do now is really the same thing we could do before except at 12 to 16 weeks. We can't use this technique to select for intelligence or hair color or eye color. We could potentially use it to select gender. We haven't done that because we have self-regulated.

I understand those people's concerns, but to me the issue should be between the physician and the patient who has the problem. It shouldn't be decided in some dark room where people don't understand what is going on. People have to be able to make their own decisions about what they want to do and how they want to conduct their lives and this kind of experiment or this kind of technique that we are using for these patients has no negative impact on people who don't agree with its use. It has a tremendous positive impact on these people with the diseases that we're avoiding ...

You make two points here. There is sort of a self-regulation and that we don't yet have the power to do all these things. But pretty soon we are going to have the power to do a lot. It is concerning to people that it is up to individual doctors and patients, because there is certainly patients that would like to choose intelligence, cosmetic things, whatever.

I understand that, but we are not going to be able to do those things, not soon, because they are too complex. When you talk about selecting against a particular genetic disease, that we have worked out the mutation for, yes, we can do that. But things like intelligence are so complex and there is more to it than genetics that I don't think we can use this technique in that way.

Even if you could argue, "Well, is that so bad, to help people be more intelligent?" I guess some people would argue, "Yes, that is bad, we're playing with nature." But if we weren't playing, if you took a purist approach of not playing with nature, why do we have doctors? Why don't we just let people die. Why don't we just not have medicine? If you want to take that naturalist view.

We're trying to help patients with medical problems. That is what we do. That is our job. Yes, we create problems with our technology. We also solve a lot of problems, too. This group that has been involved from the beginning of this field, has spent a lot of time talking about the issues, proactively preventing these issues from being problems and from really focusing on what these patients need and helping this group of patients. And we have done a very good job without regulation.

And I can tell you this. Everybody wants to regulate us. Well, any regulator who wants to regulate us, make them be held to the same standard that I am held to in terms of knowing what the regulations do, knowing if they are effective and knowing what their costs are and making sure that those things are in balance with what they are trying to accomplish. Because most of the regulations that we have cost money, do not prevent the things they are trying to prevent and they create a paper trail, bureaucratic nonsense, make work type of things for me to do so that I have less time to do what I should be doing, which is taking care of patients.

When you look at that image of taking out one of the cells ... it is amazing that you can sort of pull it out of there and not damage the embryo in some way ...

Well, it is a striking image. And you say, "Well, gee, if you take that cell out, what is going to happen to that embryo?" But if you understand enough of the biology, what you know at that stage is that all of those cells are undetermined at that point. That what goes on to make the hair and the eyes and the bones is not determined at that point. The loss of a cell at that stage is really well-tolerated by the embryo.

In fact, from our research, we know that embryos often jettison off some cells that have some slight damage to them and get rid of them naturally. We also know from our experience with frozen embryos that it is routine when you thaw an embryo that one or two of the cells does not survive, but the other cells do and those embryos make babies. They make babies that are as healthy, perhaps a little bit more healthy, than unfrozen embryos. Why is that? Because the hearty ones are the ones that survive and the less hearty ones don't make it ... But, yeah, it is frightening. If you are frightened by it and you want to understand it, read the scientific literature and you will understand it and you'll see that it is not as frightening as it seems.

How many illnesses can you diagnose? How many do you do here?

Well, personally at our center, we do gender selection for X-linked disorders to avoid diseases such as hemophilia, muscular dystrophy, X-linked mental retardation. Those types of disorders. Cystic fibrosis, 0 syndrome ... We have done a Tay-Sachs patient who is patient. We are about to do a patient with Von Hippel-Lindau disease. These are diseases a lot of people have never heard of. And that's the thing. There are not that many people out there with these problems and everyone is trying to say, "Well, you guys shouldn't be doing that stuff." But what about these patients? The small group of patients that are being ignored by the rest of medicine. We need to help those patients.

You are fighting it on all fronts in this research ... there is the religious community, the regulatory community, even some of your colleagues, to some degree.

Well, it is not easy. There are more critics than there are supporters, no doubt. When you go to a national meeting in Washington, D.C. and you hear somebody stand up and say, "Embryo biopsies should not be done. The Americans for Disabilities Act ... says this is discrimination against embryos and it shouldn't be done." You sit there and you go, whoa, where is this person coming from? Have they ever met a patient with any of these problems?

Yeah, we are hunkered down and trying to fight a lot of things. We have no research dollars, we have very little support. We have only critics. And yet, talk to our patients. See what they say. They are the ones who keep us going. So it is hard.

What drives you?

It is exciting being able to help people in this way, it is just a gift that you can't imagine. You go to work and you accomplish something like this, it's immeasurable. You can't explain it. I know Guy and Marie's life, for the rest of their life, will be changed by what I was able to do. That is an incredible feeling. There is no amount of money in the world that makes you feel as good as that. So it is very satisfying.

The other thing is that these people who go on and have babies from these techniques. These babies are some of the most loved babies in the world, and loved babies do great. That is really what it is about. They are lucky kids to have their parents who are heroes to go through this stuff to have them. You know that these kids are going to go on and do great things, so it is a way of contributing to society, to have an impact that is a positive one instead of a negative one.

... What was the issue [with Marie]?

Well, Marie is a very unique person. She has Turner's, a form of Turner's Syndrome. Actually a very mild form, in a sense. She has a very small percentage of her cells that are missing an X chromosome, whereas many patients with Turner's, most of their cells are missing an X chromosome. But the meaning of that for her was that she was unable to have a pregnancy occur. The embryos she were making were missing chromosomes and not making viable pregnancies and she was unable to get pregnant and what we were able to do was find those few embryos that had the right chromosomes so that she could then go on and have a baby or two.

So effectively she could have had a normal, happy, health baby, but the odds were against her.

The odds were way against her. If you look at fertility, fertility is a very inefficient process. It takes 13 months for a 100% of 25-year-old fertile couples to get pregnant. It is pretty inefficient.

So you imagine if you threw a few things in there to make it less efficient, you can understand why someone like Marie and Guy, after years of trying, were unable to get pregnant. What our techniques do, is we are able to get lots of eggs and lots of embryos and find the one that is going to make the baby ...

Do you think it is amazing, the level that we are able to actually manipulate and change embryos' eggs.

Well, we have a long way to go. It is miraculous that we are able to do this. When I started working on this 10 years ago, it was a big question mark whether or not we could do it. We are at the diagnostic phase now. We are at the phase where we can take an embryo and make a diagnosis, but not every gene. We can only look at one particular gene at a time, so we're very limited in what we can do.

An idea eventually might be that you could find the defect and then correct it in the embryo ... I don't think that is where we are headed. I don't think that is where we are going to be able to go because it is just too complicated. This will be more of ... help us avoid a disease type of technology than, than a way to manipulate the genes.

There is a lot of fear about us being able to do gene manipulation. The fact is, we are really not. We are just assisting nature in doing natural selection or genetic selection that goes on in nature. We are just trying to refine that process so that people can have healthy babies.

Don't you expect this to eventually lead us to the ability to do that sort of genetic engineering?

It is absolutely possible, but when you know the science behind it and when you have seen what I have seen and gone through what I have seen, that is a long ways away. I mean, a lot of these genes ... we haven't isolated. We don't know how to figure out which gene will make that particular characteristic that we are interested in and that is a long way away.

But is it possible? Sure it is possible. But will it happen in the next 10 years, 20 years, 30 years? I don't know, but I don't think that kind of use of this technology will happen for 20, 30, 40 years. I don't think that is the way the field is going. I don't think we want to do that with this field. I don't think we are trying to do eugenics. We are just trying to help people have normal healthy families.

Do you think that critics in general tend to get

ahead of themselves?

Well, the pendulum has swung. It used to be that the critics were way behind the technology and everyone got very upset about that. But now the pendulum is the other way. The critics are way ahead of us. They are criticizing things before we have even have the ability to do what they are worried about. Sometimes they lose sight of what it is we are actually doing because they are so bogged down in the theory that they don't just look at a particular situation.

Any critic of what we are doing who actually sat down with Guy and Marie and myself and had this thing explained would say we did a great thing. But there are people out there who are probably watching this and saying, "Hey, man, I am not so sure this is a great thing." But when you really sit down and look at it, I haven't found anyone who has criticized a particular situation. They criticize us in general for the possibilities. That's okay, but that is not what we are about. We are about helping these individuals with a problem, and very few people criticize that.

One of the other areas you have been working on in research is nuclear transfer. What is the purpose of that?

Well, one of the problems with fertility, especially in the female, in fact, exclusively in the female, is age affects fertility. Now why is that? Well, in men, every 90 days new sperm is made. Men have germ cells that make new sperm all the time; women don't. Women, when they are a fetus at 20 weeks have 7,000,000 eggs. That is the most they have in their lifetime and through a process called atresia--the egg is used up. At birth there is 1- to 2,000,000. At puberty there is 300,000. Ninety-nine percent of your eggs are gone before you are fertile as a female. Those eggs sit waiting to jettison half of their chromosomes because eggs and sperm have half the number of chromosomes that a regular cell does.

Well, a germ cell egg, an immature egg, has 46 chromosomes. It is waiting to be ovulated and fertilized before it kicks out those extra set of chromosomes so that when the sperm then unites, then you form a normal cell with a normal number of chromosomes. If that process happens when you are 20, you get a different result than if it happens when you are 40. Because now we are delaying child-bearing more and more, what we are starting to realize is that peak fertility is really in the 20s, not in the 40s.

But most of us are still at our lessons 'til we are 40 and starting to have kids when we are 40, when we really, biologically, should be doing it at 20. So what is happening is we are getting busier as fertility specialists because patients are trying to get pregnant when it is less likely to occur. The real defect is the egg, and what happens to it with aging.

Now for patients in their late 30s, early 40s, who fail assisted reproductive technology techniques (i.e., we do several attempts at IVF; they are not pregnant.) If you look at their embryos, what we find is they are chromosomally abnormal in the majority of the cases. What we end up doing to treat those patients is saying, "Well, here we found the problem. It is this old egg that is not taking the chromosomes and doing the right thing. So let's stop this treatment and let's do egg donor. Let's take a young woman's 25-year-old egg and use your husband's sperm. Make an embryo, put that in you ..." so all of a sudden this 42-year-old who has a very low chance of getting pregnant, now has a 50% chance of getting pregnant in one cycle of egg donor. The problem with that is nobody wants somebody else's egg. They want their own egg.

So what is driving this technology is we are trying to understand the mechanisms where these chromosomes get scrambled. We have done a lot of research and we think the process occurs because the machinery that moves the chromosomes around gets damaged. We are trying to work on a method to take those chromosomes out of that bad environment, put it into a young environment, where that doesn't happen, can we then correct that defect? And make an embryo that is like that of a 25-year-old, even though the woman is 40 and has her own chromosomes and her own baby. So that is the focus of this research.

Now, it is an experiment. We tried it on two patients. There are no babies. We were able to reconstruct eggs. It is miraculous. We were able to get those eggs to fertilize. That was a scientific feat [getting] those embryos to develop. But we haven't made a baby from it yet. There are a lot of things that we have to do to make that process better if it is ever going to work. It may never work, but the fact is, that would be a very powerful alternative to egg donor for this group of patients. That is getting more and more common. Again, this technology is being driven by these patients who want to have their own baby.

Is infertility on the rise?

... It is probably not so much on the rise as just delayed childbearing is making patients less likely to get pregnant, thereby, more patients exist. But I don't think the infertility rates are reported at that much higher a level than they were 10 or 15 years ago. But we have more patients who use these technologies because they work better and they seek treatment. That is really what it is. It is not so much an increase in infertility as it is a delay in childbearing.

So instead of doing nuclear transfer and all of this research on it, why not just do egg donor? We offer that to patients and this is, right now, the best treatment. This nuclear transfer is an experiment that hasn't work ...

But that is not what patients want. Many of these patients are told, "Look, we can do another IVF cycle. You have a 5% chance of getting pregnant or you can do egg donor and have a 50% chance of getting pregnant." And they look you right in the eye and they say, "I don't want egg donor. I am going to be ... one of those 5%. I am going to go for it." Because they don't want somebody else's egg. Now, eventually, many of these patients are forced into that option ... but most people ... want to have a baby with their own egg and this nuclear transfer is an attempt to get that much closer to what these patients want ...

It is just shocking that you can effectively reengineer an egg.

Well, it is miraculous, but these experiments weren't done in a vacuum. These experiments have been done in animals. There is many years of animal research leading up to doing this in humans and then there is many years of human research, before we even attempted to make an embryo with this, to see if we could do it safely and effectively.

So it is miraculous. But what we have learned is that gametes are pretty hardy structures and you can do a lot to them. They either don't survive the process at all or they survive and are fine. That's the beauty of working in this system and that is why we are able to do a lot of the things that we do.

One of the issues it raises is that, effectively, you create an embryo that has, to some degree, genetically two mothers.

It is interesting because ... it was presented at a scientific meeting, but the press picks it up and the first thing they say is, "Gee, this baby has two moms." Well, no, that is not really true. I mean, let's not make a sound bite out of it. Let's really look at this and what is behind this statement, what is driving the statement.

An egg has a nucleus. Ninety-nine percent of the chromosomes are there. Ninety-nine percent of the DNA is there. But in the cytoplasm are these things called mitochondria. Mitochondria are bacteria that have hitched a ride on the human cell. You carry our system way, way back when and in that are some chromosomes. There is actually 13 genes. Those genes code for the enzymes that take glucose and make energy out of it. Okay?

Those genes, yours and mine, are the same. There's very little difference there so when you do germinal vesicle transfer and you take that nucleus out and put it into a different egg, yes, the mitochondrial DNA is from a different mom, but it is not different than the original mom. And yet, people are saying, "Well, gee this baby has two moms." Well, these 13 chromosomes compared to these 500 or 5, 000 other genes that are really the ones that determine the difference ...

When you talked about this research earlier, when you published it, what was the reaction?

... We presented these initial finds and the significant thing about the initial findings was we could reconstruct an egg, we could fertilize it and many an embryo out of it. We didn't make a baby. We reported what happened. There were some initial scientific interesting things and breakthroughs really. Unfortunately, it became developed in the media that a lot of the critics came out of the woodwork and made it a very hostile environment for us to work. The government called us and some things came to us that really made our Institutional Review Board stop us from doing this research until we thought this out a little bit more, and made sure we were doing this in the best way possible and to alleviate any of these negative criticisms.

Ultimately, wasn't the fear that it was too close to cloning.

Well, the misconception was that it was too close to cloning. But this is not cloning at all. Not even close to cloning ... The confusion is when you say nuclear transfer people equate that with cloning, but they don't understand. Nuclear transfer is one step of cloning; but all nuclear transfer is not cloning. This has nothing to do with cloning.

What is the difference?

The difference is what we are doing is taking the DNA, the nuclear material out of an old egg and putting it into a young egg. When you clone, what you do is you take a living individual and made a copy of her or him and make a baby from the exact same chromosomes. What happens with this nucleus that we take out and put into an egg, it has been fertilized with sperm and it becomes an embryo just as if it was her own egg. It is not a clone.

But isn't the technique of doing it--is effectively the same thing that would allow us to clone?

The techniques are similar. Will our research make cloning technology more likely? I doubt it. It would be the other way around. If cloning technology got better, maybe we would be able to do what we are doing better. But, no, we are not cloning. This has nothing to do with cloning except that one part of the technique is the same as cloning ... But ... people get confused by that. They hear the word clone and the lights go off and they don't try and understand. They just hear the sound bite and they don't understand the details ...

The research that you are doing here in this lab would be illegal in California because they would consider it cloning?

It is not clear if it would be illegal or not, and this is a problem. Regulators write these laws, and you know what their intent is, but they don't have the sophistication when they write these laws to understand the science ... they write a law and it is very confusing. You can't interpret it ... You just can't take the risk, you can't do it. So if I was in California, no, I wouldn't be doing this with the legislation that has been written. Now, I am sure it was well meaning legislation, but it missed the point. It doesn't understand what we are doing.

Why are you doing all this ...

Because the patient tries this technology. We have patients who have a disease. It is a horrible disease. It is called infertility. They are as depressed as cancer patients, their lives are turned around ... It is as bad as any disease out there ... They want to be treated. They want success. And they are driving it. They are the ones who, when you see them and you talk to them and you see their pain, that is the reason you go to work every day because you really want to help this group. And you know what? This group could be you, it could be me. It could be my sister. It is all over. So that is what drives it.

But you could do a lot to help that patient population without taking on some of these areas that are so controversial ...

Well, look at it this way. I could just go out and be an IVF doc and just do IVF over and over and I would help a lot of people that way. But if we develop a breakthrough or if we generate a new technique that is going to help more people and then that technique is then given to other centers around the world.

Then, all of a sudden, instead of treating one patient, we are treating thousands of patients ... they are not necessarily in your clinic, but you are helping more people that way. So, yeah I could be just a practitioner, but I didn't go into academic medicine ... I did it so that I could push the forefront of medicine to help more people. That is why we do it. And, yeah, it is hard. It is a lot harder than being a technician, absolutely; but it is also a lot more rewarding.

Do you feel like we are at an exciting moment in terms of this medicine. Where are we in that?

This field has been exciting since the IVF first happened and every year brings new things, so the excitement in this field will be there for a long time, because the more patients we're able to do, the more patients we're able to help, the more excitement it generates. I don't think we are at any big crossroads right now, where we are going to cross the line and create some huge problem. Everything we have ever done in this field has been criticized.

When IVF first started, clinics were petitioned and people said this shouldn't be done. Now people accept IVF as a treatment, in general, although there are many critics. When assisted hatching started, people started saying, "Well, should you be doing that? ICSI, why are you taking this next step. Should it be done?" There are still some very violent critics of that technique now. Embryo biopsy, the same thing.

For some reason this area of medicine creates a lot of controversy and it is because it is talking about embryos. It is talking about life. It is talking about people helping people have babies, and that generates a lot of passion and politics.

Do you think that in 20--50 years, whatever, cloning will be offered in a fertility clinic for a small number of patients?

It is an interesting question. Personally, I can't think of a clinical situation where cloning would be a better treatment than any other treatment that I could offer. I have no interest in cloning a human being. I don't think there is any need to do that.

Now, in spite of that, nature has already cloned. People don't realize it. Identical twins are clones. Nature has already done the experiment and what is the result of that experiment? Have you ever seen identical twins? They are very similar, their genes are much closer than yours and mine are, yet they are two very different people. They are two different individuals with two different souls. So I don't know that it necessarily would be something that bad, but I don't see any reason for us to be doing cloning. I don't see a clinical problem that is solved by cloning that we can't solve in other ways with assisted reproductive technology. So I have no interest in it. Can it be done? I guess it could be done. Is it going to be done? I doubt it. I don't think people are really working in that direction.

The fear is that somebody somewhere, a renegade probably will do it. Do you think that is science fiction?

I definitely think it is possible and if someone said, "You and your lab have to clone and could we do it," I bet we could, but I have no interest in that and I am not going to do that. Will somebody do it? Perhaps. How bad would that be? How terrible would that be? It probably wouldn't have very much of an impact at all, although it would be highly sensationalized, I am sure. But I don't see any need to do it and we are not working in that direction.

But I don't think fear of cloning is a reason to say, "We had better stop all this assisted reproductive technology because now look what they are going to do. Now they are going to clone." That is what a lot of people are doing. Well, if you do that, what about all these patients who need us ... Do we just say, "Forget it. Can't help you anymore because we are afraid that someone is going to clone?" It doesn't make sense ...

You said ... you don't have an interest in moving forward with cloning because you don't see a clinical use for it. Obviously, cloning technologies are, potentially, incredibly valuable scientifically ... Where do you think cloning will head?

Cloning technology, in terms of assisted reproduction, is not something that is really going to have much of a future. There aren't really clinical situations where that would be a better treatment than what we could already offer, so I don't think it is really something that is going to affect our field. But a lot of the research from it will help our field in terms of being able to do better embryology and micro-manipulation. So I don't think there is much of a need for cloning. In the animal industry, [there is] tremendous need and that's where it was developed and where it will probably continue to be used. But for treatment of disease, I don't see it as much of a discipline.

What has been the effect on this field of the human embryo research path?

It has had a very negative effect. It is a tough topic to talk about, embryo research, because what does that mean and how do you do research on an embryo. There are people in society who think that an embryo is a baby. Certainly, I treat every embryo with respect that is a potential human. But if you look in nature and you know what I know and you have seen what I have seen, what you learn is that embryos are made all the time, we just don't see them. Most embryos don't make babies.

Just look at your front lawn, look at the tree. How many seeds get thrown down. Each one of those seeds is a potential ... tree. Yet, how many of them actually make a tree. Well, that is reproduction. Reproduction throws lots of seeds and very little results.

It is the same in humans. Humans make lots of embryos, you just don't see them. Or when you do IVF, all of a sudden you see them. And what do you learn? You learn that most of those embryos don't make babies and we did IVF early on without a lot of knowledge about how to optimally culture embryos and what happened was is we were bad at IVF, we didn't do very well. So we had to spend years, and patients, in a sense, had to go through some optimal treatments for us to learn in the field. The ban on embryo research did that ... we could have been as good at IVF 10 years ago, had we been able to do the right experiments first. But we weren't.

We were told, "You make an embryo, you can't really do research on it. You transfer it or you freeze it but you can't do research on it." So what happened? We had patients with infertility, we knew IVF could work, we made embryos, we did the best we could. Some of them got pregnant, most of them didn't. It was because we didn't have the right techniques. That we only learned over time of doing this over and over and good science and good research in this clinical situation. But had we done the right experiments, we would have gotten there much faster.

But again, it is politics. It is bureaucracy. It has gotten in the way. And who has been damaged? Who has been hurt the most. Our patients. Because they got suboptimal IVF for many years while we learned how to do it better because we couldn't do the right research. So it has been a big negative and I don't think anyone every looks at it that way ...

How did it actually prevent you from doing the research you needed to do?

Most research has been done by federally funded research grant. It hasn't really kept us from doing good science and research, because we have done that and paid for it out of clinical receipts or private donations, but it really showed us down. Had their been a concerted effort from Washington saying, "We are going to do this, we are going to do this right, we are going to really develop these techniques because there is a group of patients in need and this would really benefit them," we would have done it much more quickly, effectively and we would probably be a lot better at what we are doing now even, had that occurred, but it didn't.

In effect, you have had to charge patients in a way, to experiment upon them?

Well, in simplistic terms, I guess that statement is correct. But really patients have subsidized their own research, yes. Absolutely. Physicians, scientists have subsidized this research by either donating our time, money to it and patients have paid for it in an indirect way, as well.

What about nuclear transfer, did the patients pay for that?

It is very complex, because in order to do nuclear transfer we have to do a donor egg cycle--you have to find a donor, you have to screen a donor, you have to stimulate a donor. That part of the process is extremely expensive, so the patient is asked to pay for that. Everything else, they don't pay for. We pay for. We spend a lot of money doing these kinds of experiments. But we are committed to doing these things, because we are trying to help these group of patients.

In effect, are you making patients pay for saving them from this disease in some way?

In preimplantation genetic diagnosis, since I first started doing it in 1992, I have never charged the patient for the embryo biopsy procedure or the genetic analysis. Because in my view, those were experimental techniques. Now, with over 100 babies born by the technique in the world and in my personal experience, over 35 babies being born from this experience, it is no long an experiment; yet, we haven't charged patients for that.

Because, first of all, you can't charge enough to recover the costs. It costs you much more to do it than you could ever charge and recover the cost. The only way you could do it is if you did so many cycles that you could generate enough income to pay for the costs of doing it. The patients have paid for the IVF, because IVF is not an experiment. It works, it is good, you have seen the results of it, it doesn't work for everybody. Patients know that.

So, no, they haven't paid for embryo biopsy. We've paid for it. We have subsidized it. We have donated our time, energy and money to make this happen and I have spent, really 15 years of my life working on this research, not every day, but a bit portion of my career has been spent doing this with no pay. But that is okay. I am happy to do that because I am interested in developing the field. I generate enough income from other sources that I can do that and that is just my personal choice. But the patients haven't been asked to pay for this, no.

Finally, you have talked about the great increase in your success rates, but ultimately, most people don't succeed in becoming pregnant.

See, that is not a true statement. If patients are willing, and it depends on what the patients do, because if you take a group of patients, there are a subset of patients where you can say when they walk in the door, they have a very low chance. But the average patient that walks in has an excellent chance of being successful. From the first day they set foot in the clinic for the treatment of their infertility, whether it includes in vitro fertilization or the simpler things that go up to it, most of the patients actually get pregnant.

The misconception is that nobody gets pregnant. It is true that on a given cycle, most people don't get pregnant on a particular thing, although we are at a point where for a woman under the age of 35 who does IVF, we are in the 50% range in terms of having a delivery from that cycle. If patients are willing to repeated cycles, most people do get pregnant. It is unfortunate that there are many patients who do lots of things and still end up not pregnant. That is definitely true. Fortunately that is getting to be a smaller and smaller percentage of the total patients that we treat but that is the hardest situation. That is gruesome. It is frustrating for me as a clinician for not being able to pick those people out before we start their treatment and just say, you know what, it is not going to work. Don't even try. We don't have ways of doing this. Unfortunately, the only way you find out who that patient is, is by the treatment and fortunately it is not a large percentage, it is a small percentage. But the misconception is that it is the majority of patients and that is just not true ...

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