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Q & A with Dr. Leonard Bailey
From Scope, January-March, 1985

So far in your analysis of data gained from Baby Fae, what have you learned that makes you feel the next clinical trial will have better success?
We decided in advance our decision-making about the project will be based on five babies and not one baby. But from case to case, we can adapt based on the response of the previous baby. And there was a great deal of encouraging things about this first baby that suggest that we would be wrong in not pursuing the project from this point on.

One is that she had histology that was incompatible with lethal rejection. She had only a very slight rejection, immunological parameters were quiescent. While she was alive she did not have a major rejection.

What was the cause of her death?
She had myocardial necrosis, she had renal failure, and she had red blood cell abnormalities. We’re investigating that. We may not ever figure out why she died. We’re taking a critical look at the things done to her that we’re not used to doing in the laboratory—certain agents and certain carriers of agents and so forth.

A positive sign is that there was no evidence of infection, a serious problem in transplantation.

What other information have you learned from this first clinical trial?
In following her along there were some details of her biochemistry that we didn’t fully understand until now, in retrospect, as we are reconstructing it all. At the time they were changes, and we don’t know what they meant for certain. We have developed some unique tests of heart injury unique to this project. There is one very good test that is going to be as good or better than a biopsy. It’s a blood test that’s a little more sensitive. It’s not a test you can use in a human-to-human setting: you can surely use it here. And we didn’t know that until now.

It’s a pity to have to start up somewhere. That doesn’t eliminate the fact that there was certainly a ray of hope for her. The decision process was all right to do her. It offered hope that she didn’t have otherwise, and it had therapeutic intent. In reality, in being the first one, you have to have a lot of miracles along the way. You recall NASA lost several rockets trying to get them off the ground in the early days, and it was a frank embarrassment to space technology in this country. But eventually we succeeded. This is like trying to launch a rocket here. From an emotional point of view, it would be nice for all five babies to do well in the clinical trials. But I’ll be quite pleased from a scientific point of view, when one has lived months or a year. Then we’re already validating the program.

If several of them do live, what happens at the end of your program?
We’ll try to get some additional funding for the program and proceed if even one is a chronic survivor. And I have very little question that we will see that. The five have to do with operative survivors, you understand. There a lot of ways to lose a baby before, during, and right after an operation that have no relevance to whether or not the infant was transplanted. These infants are terribly sick, and one may have a stroke, another a hemorrhage, whatever. There are lots of ways to lose before you get into the follow-up care.

There was a lot of comment in the press about your not looking for a human heart. Would you explain why it’s so difficult to find a human heart?
That was an oversight on our part. We should have at least registered for a human heart. It is assumed that there aren’t any available. And I think it is a fair assumption, because up until now the procurement agencies never even kept files for newborns.

The reason that there aren’t going to be a lot of appropriate newborns is the problem of diagnosing brain death. The whole area of transplantation is predicated on a brain death diagnosis. Until brain death was established as death in this country, there was no serious transplantation. Criteria for brain death in newborns is debatable.

Is that because it is so difficult to tell when the newborn’s brain is dead?
It almost never can be done with certainty. A neurologist in any busy newborn practice is following kids that are running around and growing up, who had flat EEG’s (brain death) in the nursery.

There have been questions about using infants who are born without a brain.
There are a few anencephalics babies born with the higher parts of their brain. There are two problems. One may be relevant and one maybe isn’t. The one that maybe isn’t relevant is the fact that anencephalic kidneys have been used in transplantation and have not done well, in general. That could just be a technical problem, and not due to the fact that they were from anencephalic babies. So that may have very little applicability to heart and liver transplantation. The second is a “Baby Doe” issue. Defective babies have to be fed and receive the minimum of care. Just because you’re missing part of your brain doesn’t mean necessarily that you’re brain dead. It seems ludicrous, but brain death even in that setting hasn’t been well defined. So I can’t easily harvest a heart out of such a child even though the parents may say “We’d like you to do that.”

So what are your options?
When a baby is selected for transplantation, we’ll register it with the donor procurement agency, and ask them to find us a size matched, compatible human heart. If they happen to come up with such, we’ll use that option. But it has to be a clear brain-dead baby who is compatible and size matched. That is a lot of ifs.

While the procurement agency is looking for a donor heart, would you also go through the xenograft testing like you did with Baby Fae?
Yes, we’d work up the donor panel and choose a baboon, and use whichever came first.

How long do babies afflicted with hypoplastic left heart syndrome usually have to live without medical intervention?
Most of them will die in the first two weeks. Baby Fae was dying coming back into the hospital at 7 days, and had we not taken measures to help her, to put off dying for a few days, she would have clearly died that day. She was already very acidotic, limp, and lethargic, and she was going to go out that day. But with prostaglandin and ventilator support, we can usually postpone that event. We almost were headed out the bottom again the evening before surgery. Fortunately, we were able to control the acidosis with bicarbonate infusions until we knew which donor to choose at 5 o’clock in the morning. By 6:30 we were in the operating room.

She appeared to have no ill effects from being that sick ahead of time, which is encouraging.

Did the public’s reaction to the surgery surprise you? Baby Fae became their baby, too. Were you expecting that type of concern from the public?
Not in that magnitude. I thought it might stir up some local interest and that sort of thing, but not a nationwide or worldwide sort of identification with the baby. The videotapes we released may have played a part in that. They did focus on the human issue at hand, and for that reason it was valid to release them. But it made everyone sort of unconsciously adopt the child.

What was your reaction to the press coverage?
First of all, there was more press than any of us expected. In many ways, the additional stress rendered post-operative care more complex. Most members of the press were trying to do their honest best, others were simply creating issues. Interacting with the press is an unavoidable by-product of our project.

We have nothing here to promote. We’re just trying to investigate this therapeutic option.

The issues cut across so many lines and facets and interests of people. It makes awfully good copy. I think I’ve learned a lot about how the press functions.

What kind of personal experiences did you have with the press?
To mention one, some folks from the LA TIMES wandered into the area where our house is and hopped out with their microphones and pads. My wife didn’t have any comment for them, but our pet crow that we had raised from just a little ball of feathers moved in and started pecking them. They jumped in their car and left. The crow is like a watch dog!

Have you heard any comments from other researchers across the country since Baby Fae?
Yes. The messages and phone calls I’ve had personally have been most favorable. A number of prominent people, people who are pioneers in xenotransplantation, have been very supportive.

Some people who read that the surgery cost a million dollars were wondering how people could afford that. If it became more commonly done, would it cost more than a human-to-human transplant?
No, probably about the same.

What is the difference between hospital care for Baby Fae and another one who has undergone open-heart surgery?
The differences are length of time in the hospital (the transplant would be longer), the barrier system in the room to prevent infection, testing for rejection or infection, and types of drugs used.

Recently the NIH accepted your invitation to look at the procedures involved with the Baby Fae case. What was the result of that visit?
Six individuals representing the NIH came out and spent 48 hours on campus. They held all-day sessions both days and had opportunity to look into every detail, every facet of the program. They interviewed individuals privately as well, to get their reaction. They wanted to see what the process was like, whether it was valid or whether it was invalid in terms of not only the IRB but the whole process.

The more they knew, discovered about what happened, the internal mechanism, the background of this whole thing, the better they felt about it.

In their exit conference they indicated that they were quite pleased at the whole process and specifically that there was in fact more than adequate consent information.

Would you tell us a little bit about what types of people are on the IRB at Loma Linda?
It’s a mixture of people from on and off campus. There’s a Jewish rabbi, a businessperson, an attorney, a housewife, a dentist, three to five people with medical degrees, several PhD’s, a sociologist. There’s no way that medical people have an edge. That’s one of the things the NIH wanted to look at—was there a medical block of votes that outvoted all the others on the panel?

That didn’t happen. In fact, at first there were more dissenters among the medical people than the others. Interestingly, of the dissenters, most of them have come full around as the project has matured.

Is the IRB the only approval hurdle the program had?
No. We started there because we had nowhere else to start. Where do you start in a project like this? It was an absolute that you had to have IRB approval. So we started there. And while the IRB approved the project tacitly, it was with restrictions that even if a comma of the protocol was changed, it had to come back for approval. The IRB approval kicked the whole thing off. We had internal review, and ad hoc committees, pediatrics department and surgery department committees—everybody got a piece of the action. And all those came out with recommendations about strengthening the protocol. So even though the IRB gave us the approval, all the other internal reviews were satisfied too.

There were several dozen different internal mechanisms coming to bear on the project that really helped in the checks and balances and shored things up, showing lights in dark corners.

Will Dr. Nehlsen-Cannarella be working with you on the next phases of the trials?
One of the nicest spinoffs of this is that Dr. Cannarella is going to join our faculty on March 1. I think it’s a major move for her and definitely good for us. We’re going to give her some options that she just didn’t have. She needs some research time, dream time. We’ve guaranteed her some here. She also has a chance to set up and develop her laboratory from the bottom up.

She will have a large square footage area that I think will become one of the finest in immunological transplant laboratories. She will dovetail her experience with existing mechanisms in the department of pathology. Her primary appointment will be in the department of surgery.

Are there any other plans?
Yes, we are setting up an active adult cardiac transplantation program. That’s something that is long overdue here. We’re also anxious to participate with Stanford University in experimenting on a left ventricular assist device to be a bridge for later transplantation.

 See the full issue of Scope, January-March, 1985.

 



 

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