Translating Science: A Conversation with Pioneering Fetal Surgeon Michael Harrison
Michael Harrison
Young children sometimes play games in parallel worlds, even when occupying the same space.
The same can sometimes be true of science and medicine. Doctors and researchers might speak the same language and perhaps use some of the same tools, but their different “accents” (think brain surgeon and a protein structure expert) signal different origins – and often a different perspective on the big questions of human health.
In short, they need a translator.
This becomes obvious when an elegant scientific discovery or a searing insight fuses into a medical marvel. Only then do we truly hear the music of the spheres, as Pythagoras would say, and understand the underlying harmony behind it.
UCSF’s Michael Harrison, MD, professor of surgery, pediatrics, and obstetrics, gynecology and reproductive sciences and director of the Fetal Treatment Center, first “made music” for the world nearly 30 years ago. Filled with the indignation of a young doctor at the death of an infant, he challenged conventional wisdom by suggesting, testing and then performing with his colleagues the world’s first open fetal surgery.
In the decades since, Harrison has studied and devised remedies for a number of life-threatening fetal abnormalities. With each advance, the surgeries have become less and less invasive. And in keeping with the spirit of the times, he and his colleagues have also used stem cell transplants to treat a number of immune and enzyme deficiencies.
Even now, his work – which he describes as both science and art – still excites and entices him. And in the conversation that follows, he remains as optimistic about the future as ever.
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Related Links
- Fetal Treatment Center
- Fetal Treatment Laboratory
- Fetal Firsts at UCSF
- Study to explore using magnets to correct "sunken chest"
- UCSF News Services, Feb. 12, 2007
- Pelosi Celebrates Opening of New Fetal Treatment Center
- UCSF Today, Mar. 29, 2006
- Father of Fetal Surgery Looks Ahead
- UCSF Today, Mar. 28, 2006
Podcast transcript
Michael Harrison: The first surgeries were rather invasive. You opened the mom, perhaps open the uterus, do something to the fetus, close the uterus, close the mom. And then over the last three decades, we advanced in the same way that many fields have advanced, to less and less and less invasive techniques. So we went through the stage of converting our open surgeries, to fetoscopic surgeries, where you didn’t necessarily have to open the uterus, you could put a little telescope inside and work with little tiny instruments. We actually developed a whole series of techniques which in aggregate we called fetendo.
Jeff Miller: F-e-t-e-n-d-o?
Harrison: Exactly. And the reason is, we did it in the late ‘80s-early ‘90s when all our kids were playing Nintendo, and it’s pretty much that same kind of thing. You’re looking at a screen, with an image projected on the screen from your telescope which is inside the uterus, looking at the fetus, or sometimes it’s inside the fetus, looking at the inside of the fetus – on one screen, and on a screen right next to it you’re looking at a cross sectional image of the fetal part you’re working on and that’s done with sonograms.
It was quite revolutionary at the time to use two modalities simultaneously, side by side in real time. One, a visual image, through an endoscope, and the other a cross sectional sonographic image.
Miller: Has your willingness to tackle certain problems that arise in utero changed with the technology?
Harrison: Oh, very much so. Because with the old technology, there was considerable morbidity and some risk to the mother. So we couldn’t justify doing anything except in extremely serious and in fact life threatening conditions in the fetus.
Now, as you get less and less invasive and less and less risk and safer and safer, we can start thinking about doing things that aren’t necessarily life-threatening but are still very serious problems in the fetus. We can take on other problems.
Miller: Some examples?
Harrison: A good example is mylomalngmacil. Mylomalngmacil is the first non life threatening problem we took on. But of course it’s a very serious problem – I like to think of it as a life ruining problem, certainly limiting problem, and certainly worth our efforts to fix it. But the techniques had to be safe enough to justify going after that.
Another one might be stem cell transplantation, or any cellular therapies, or tissue engineering, which is you can do it through a needle; through a very tiny telescope; if you can deliver the cells; if you can deliver the genes, it’s certainly worth it because it’s quite safe. It wouldn’t be worth it if it required a big operation.
Miller: And how many surgeries like this are performed at UCSF every year now?
Harrison: Well, the total number of fetal procedures grows every year; it’s quite an active and good field. But the striking shift is the open fetal surgeries, the BIG fetal surgeries are becoming less and less of course, as we replace them with less invasive procedures. So the big open fetal surgeries from the past are down to a half-dozen a year, or less, and it’s going to be less and less, we hope.
Miller: And the number of the other kind?
Harrison: And the number of the other procedures is rising so that they’re probably one a week. SOME kind of intervention.
Miller: Well I’m curious since you pioneered this field, as you talk about these less invasive methods, were the actual techniques and the technology required, the result of you driving the creation of those implements and instruments? Because you said you needed it—if we had something designed like this we could do it this way and therefore be less invasive--, or was it an adoption and adaptation of something that already existed?
Harrison: No no, we had to make ‘em up from scratch. But the way I think about it is not so much that I drove the development, it’s that the patients drove the development because they had problems that needed to be solved and we just had to struggle in how to solve them. In many cases it meant making things up from absolute scratch. Instruments and just a myriad of little steps.
And the actual carrying out of that essentially continuous innovation is really more attributable to our bright young people than it is to the old guys like me, because they’re constantly back here in the lab solving problems. And we’ve been exceedingly fortunate to have very talented people as research fellows in the laboratory who’ve really powered this.
Miller: So this is a science and an art?
Harrison: For sure.
Miller: The numbers of people who are practicing fetal procedures around the world right now, what would you guess would be the percentage of those who have trained at UCSF or at least passed through on some kind of fellowship or whatever?
Harrison: The way it worked out is the whole fetal enterprise was essentially founded here, and then a few very good colleagues around the world joined us, and it was only a few centers that did it. Then the young people started coming through our program went out into the world and essentially populated all real fetal centers, certainly in the U.S., and a little in Canada and sometimes overseas, and ran them. Very quickly though, they had their own colleagues and their own young people – and they’re wonderful. And certainly the Europeans have just taken off and done a great job. So it’s proliferated in the way that it should.
I don’t know how to answer the question of how many of the people all over the world doing fetal intervention are from here, it’s not that many anymore only because of this geometric proliferation. But the ones who started it, in almost every center, came from here.
Miller: How have the patients changed, if at all—are they more knowledgeable when they come?
Harrison: There’s a very interesting answer to that, it has to do with the internet. In the old days, it was the old system; the only way patients would learn that something was available or that someone was doing something interesting was they went to their doctor, and their doctor might happen to have heard of a journal article, or heard a talk in a meeting or something. That’s pretty hit and miss --- in most cases, miss! They don’t ever find out about us.
Now it’s totally changed, and we’ve been instrumental in this because we’ve developed a webpage specifically aimed at educating patients. When their doctor says, oh we looked at your fetus and he or she has x disease, they jump on the internet, Google it, and see where they go.
Well in most cases now they come to our UCSF fetal treatment website because it’s really good. It’s really informative; it’s really helpful to families. So that’s a HUGE difference. And by the way that also saves billions of phone calls and sending sonograms back and forth and all that. But there’s a follow-up to that that is even more interesting.
We work very hard on taking our webpage, which is informational to pregnant moms, and converting it to a web portal in which we interact with the families through the internet. And that has been wonderful. We actually have online patients now. And they interact with us through a secret portal just as if they were here. And it saves them the trip to San Francisco in many cases.
Miller: So this is just a way for them to transmit information about their particular child or and then for you to speak to the doctor as well?
Harrison: That’s a very interesting question because they usually go to their doctor of course and they find out what the problem is and then they get to our webpage, and through our page they say oh, we would like to get another opinion, and you manage this thing essentially over the web.
And then we have a relationship with them which is a very professionally protected relationship—they send us sonograms, they have a calendar, we have a calendar, we see them on the web, they see us on the web, and in that of course is their doctor. But the nest phase of it, which we’re just developing now, is a three-way relationship, in which the patient and the doctor interact with us through this portal.
Miller: I’m going to ask you to speculate a little bit now, when you think about the future, what might be the role of stem cells in all of this?
Harrison: There’s an interesting answer from the past for this. Before people got interested in stem cells, that is in the late ‘80s – early ‘90s, we were very very enthusiastic about doing hematopoietic stem cell transplantation in fetuses. And actually studied it like crazy in fetal monkeys and even did some very initial human work. And the general idea here was to take hematopoietic, the easiest kind of stem cell, and essentially do a bone marrow transplant in utero, taking advantage of the fetus’ privileged position, with the hope that we could cure a number of diseases that would require bone marrow transplantation after birth. Like sickle cell disease, hemaglobinopathies, immunodeficiencies, it would really be wonderful.
We and many others did a great deal of work on this, but we never really cracked the nut. It will be cracked, and folks are still working on it, we’re still working on it, it will happen and it’s going to be wonderful but we haven’t really solved the problem of getting sufficient ingraftment in fetuses.
It will happen, there’s a great future for it.
Miller: Any other future for stem cells, do you suppose?
Harrison: Well-- that business of working with hematopoietic stem cells does not actually get us into the controversial aspect of embryonic stem cells, that is the source of the stem cell you are going to use to cure the fetus was not much of a problem because hematopoietic stem cells are easy to harvest from the mother or the dad so that was a nice aspect of it.
In the future, and with all the wonderful sciences happening around stem cells now and once the controversy’s overcome—which I think it will be—I personally think that the biggest application, the best chance for really having an effect on a person’s life is transplantation in utero.
That is, however you get the stem cells, the place to cure those diseases is before birth for a couple reasons.
Number one: It’s going to be easier from an immunological point of view. Number two: many of the terrible diseases that we would target actually do damage before you’re born, so you better get there early. The third aspect of that is because we’ve been working on it so long that general idea of access to the fetus has become so much better, safer, and we can do it so much earlier that it’s really going to make it feasible.
Miller: Last question: Why did all this take place at UCSF—because of you?
Harrison: It’s a good environment for this, the enterprise is so difficult, I hate to say it, but it’s so difficult, from all kinds of points of view, from clinical, technical, ethical, that you need an incredibly supportive environment to push forward. You’ll always be—you just can’t make progress without that environment.
And by supportive, I mean some folks who don’t like the enterprise, who are willing to criticize you, correctly, and who are willing to question the enterprise but in the end will be reasonable about the scientific validity of it.
And there aren’t many places that have that environment, and we certainly do here.