Читать книгу Masterminds: Genius, DNA, and the Quest to Rewrite Life - David Duncan Ewing - Страница 12

In Melton’s office he shows me his personal bench, telling me it’s a little unusual for a principal investigator in a large lab to do basic experiments. Typically, these are done by graduate students and post-doctoral students. He also points out that he intentionally has no windows here to prevent distractions. He tells me that the lab is using frogs, chickens, and zebrafish, but primarily mice for their experiments. The lab has tracked the phases of development of a pancreas from embryonic stem cells that form the endoderm and then go through a complicated series of steps involving the activation of genes and proteins that cause different organs to develop according to a programmed schedule in their DNA. Melton says that researchers have learned a great deal but still don’t know all of the genes and steps needed to drive stem cells from their undifferentiated state to fully formed islet cells.

“What are you actually doing in your lab?” I ask.

“In here now, mostly what we’re doing is trying to turn embryonic stem cells into pancreatic beta [islet] cells that make insulin,” he says. “And so we do that with two approaches: one is to take the human ES cells and just try to make them do that, and the other is to study how mice and chickens and frogs normally make a beta cell, and then use that to inform our thinking about humans.”

“So you actually have some stem cells right here in this lab?”

“They’re in the incubator down the hall.”

“And you’re using private money?”

“It’s a mix. I’ve had Howard Hughes money but more than half my lab’s funding comes from the federal government. But we’re not allowed to use the federal funds on these human ES cells.”

I ask him why he thinks people fear this sort of research.

“I think that’s a deeply interesting subject. What is the source of that fear and maybe to take a digression on it, I would tell you that my own view is that there is an innate fear to crossing boundaries; people feel secure with boundaries. Why have ideas of chimeras fascinated man for millennia? Minotaurs and mermaids? Why is that so intriguing? If you think about it, the whole idea of classifying animals, which must have been invented in about the eighteenth century, that you could find a thing called ‘species,’ gave one a sort of stamp of approval on the idea that there is a natural order, there are boxes, there are shelves where everything has its so-called natural place. What is natural and what is antinatural changes with time, and is a very difficult subject. I’m thinking of offering an undergraduate course on the concept of nature.”

“But you now have the ability to create real chimeras—a human brain in a dog, or something,” I say. “This is upsetting to some people.”

“People get the heebie-jeebies when you talk to them about putting a human brain into a dog,” says Melton. “In fact, I would suggest that there are two contexts where I think there might be an interesting connection. There is something like a natural double-take when you see a person who’s seriously deformed. People mostly say, when you see a burn victim or a person who’s had an arm amputated, that the reason you’re drawn to look, or to stare, at these poor people is the fear that it could happen to you. I actually think it’s something deeper than that. I think it has something to do with an affront to this idea of the natural order of—that person doesn’t fit into this box. I hate to say this, and it might get me into trouble, but that’s what I suspect.

“Look at the literature about science,” he says. “What was the significance of Mary Shelley’s Frankenstein? Why was Frankenstein considered an important book? Certainly not in the same way we think of Harry Potter as some kind of cheap science fiction. It wasn’t just science fiction. It was, in my view, because it addressed what is the essence of being human.

“So this relates to—if I can get this back to where I started—we were talking about ES cells and why the nation is so excited about where they come from. This issue is one that I have of necessity delved into quite a bit. It would take too long to talk about the various religious views of why one should isolate ES cells and not and whether cloning should be allowed.”

“Have you written about that?”

“No, but I have to talk publicly about it often, like with Catholic priests and with the Board of Overseers of Harvard. So I actually have educated myself quite a lot on the various religious views. I don’t really want to get into it, and the reason is I don’t think it’s fundamentally interesting. It largely has to do with the trivial concern of trying to put a tag on when life begins. What I do think is deeply interesting is this issue of chimeras. So bear with me for a minute on a couple of very broad themes that I think human ES cells opened the door to.”

I nod as he shifts from biologist to impassioned philosopher.

“Let’s say that, at a minimum, there are two areas of behavior in which our government spends an enormous amount of money. Both of them indirectly struggle with the question of whether phenotypes for the final product is a consequence more of nature or more or nurture. One of these is public education. So if you think about the whole philosophy of it, the idea which I think is a commendable one is that everyone has equal potential, and given equal opportunity will produce results. The other has to do with criminal behavior. I heard on the news this morning that for the first time now, two million people—one percent of our population—is incarcerated. It’s a number I find fascinating.

“In the book Madness in Civilization, by Foucault, he says that one way to characterize a society is to hold a mirror up to it. And that mirror is, who does the society contend is nuts? It’s a very interesting thesis. You learn more about the reflection of a society not by talking about their kings and queens and the middle class, but whom the society is fearful of. Because that defines them in a way. So if you were to accept this—and I can think of better examples—that the government spends wads of money addressing indirectly this question of nature and nurture through incarcerating people. Now, is this our genotype driving this, or our environment?

“Now bear with me as I tell you two kinds of experiments that will give hard numbers on what I’m saying. I’m not suggesting that this will answer the question. What I’m saying is it’s going to give hard, factual information that will be useful. So the first one is these identical twin studies done with humans that were separated at birth. I find that fascinating, principally because it says there’s more to the genes than you want to imagine.^* And now let’s do an experiment where we clone animals so we have twins, genetically identical individuals. And let’s take an animal that has interesting behavior. It’s hard to argue that gorillas and/or chimpanzees don’t have behaviors that are very similar to humans.

“So that’s what I want my experiment to be. To clone gorillas or chimpanzees. It’s expensive, but that’s why I introduced it with the cost we spend on prisons. And now we have behavioral tests, and I don’t actually care what the tests are. In the identical twin studies, they were ‘what’s your favorite color?’ Which is a very interesting question because it’s so meaningless and stupid, and yet the fact that identical twins had an 80 percent correlation coefficient on that, even though they’d been separated at birth, I find fascinating. So let’s take gorillas. What do they like to eat better, bananas or mangos? How do they do that test? How did they do on visual acuity?

“So what you get as a result of that is numbers, hard numbers on the extent to which behavior is modified by a gene. Now, for the more interesting experiment. We take a human ES cell and we inject it into a monkey blastocyst [the first cells in a newly formed embryo]. Now you know that if you take a mouse ES cell that is, say, labeled so all of the developed cells will be blue, and you inject it into a mouse blastocyst, you’ll get a chimera where different parts of the mouse will be derived from the injected ES cell. So it might have a blue liver and some blue muscle cells, and that’s what I mean by a chimera.”

“That’s something you do today?” I ask.

“Yes. But now let’s do it with the human ES cells into a monkey, and we make chimeras. This is different from cloning now. We’re purposely trying to make a chimera—one hundred chimeras from one hundred monkeys. And now we’re going to look through their bodies and we’re going to look to see what parts of the body the human ES cell makes. Now, there’ll be a monkey where the only thing that was made that is human is the big toe. That’s completely uninteresting; no one will argue about that. No one will say that’s an experiment you shouldn’t do. And then we’ll have a monkey with a human heart. Three centuries ago, if we found a monkey whose heart was human, people would have freaked out because the seat of the soul was the heart. Now, no one really thinks that.”

He’s talking very fast now, and I’m trying to keep up, though I think he just said that no one would object to growing a human heart in a monkey. I consider this, and decide that I am okay with this in terms of trying to come up with, say, a heart for transplant into someone’s grandmother who will die because there currently aren’t enough hearts available. But Melton is already plowing ahead with his hypothetical experiment to create chimeras out of stem cells, and I’m wondering how far he will go with an idea that is already treading close in many people’s minds to Frankenstein territory with this talk about human toes and other body parts growing on, and inside, monkeys.

“But the brain is different,” he is saying. “These days, if we’re forced to pick a body part where our soul is, we say it’s connected to our mind, which is connected to our brain. And that comes back to this idea of what is natural, because that’s a relatively recent thing. So now, we have our hundred monkeys; one of them has a blue big toe; another one has a human heart. But now the interesting part of the experiment is that we can make chimeras which have different parts of our human brains, and different parts of a monkey brain.

“And one of the first level questions we might ask is, What part of a monkey has to be human in order to have speech?” He is very animated now. “I find it really intriguing, as in the movie Planet of the Apes, to walk into a lab here at Harvard and have one of the monkeys say to you, ‘Hello.’ That makes you wonder immediately, what does this monkey think? So what you want to first know, is this just mimicry, like a parrot? And it gets back to Wittgenstein, who talked about, what is the relationship between language and thought? So you ask me what am I excited about, that’s it.”

He pauses for air, and I tell him I was with him up to the point where the monkey is linking thought and speech. “I have to admit that this would give me the heebie-jeebies,” I say. “A human brain in a monkey that is conscious, it would be a horrible freak, worse than the Elephant Man.”

“I’m not suggesting that this chimera would have the intelligence of a human.”

“But how do you know it won’t?”

“It’s an interesting question; I find it highly unlikely that this would happen. I don’t think it would. There would be just parts of the brain that were human.”

“It still sounds potentially dangerous,” I say.

“You know, people once thought cutting into the body was a sin,” he says. “Now it’s normal. That’s what I’m saying. Let me put it another way. I introduce you to a young woman, and you like her, and then I say, ‘David, she’s actually a test-tube baby.’ Would you recoil in repulsion, thinking it was unnatural? People thought this would happen. And it relates back to talking about what I said, that decades ago the heart was the seat of the soul and no one thinks that now. My point is that what we consider to be natural is largely a function of time. And that society’s increase in knowledge and practices and beliefs can have a serious effect on what’s natural. So if you look at the argument about why one should not isolate human embryonic stem cells from leftover fertilized eggs, they are conflicted by the tortuous politics in this country of abortion on the one hand, by an enormous confusion on the answer to the question, ‘When does life begin?’

“And superseding all of that is the idea of what’s natural. Natural childbirth, natural conception, natural, natural, natural. Now let me say two things to you about this. One is, what I find people don’t ask themselves about enough is, if everything is supposed to be about controlling man’s intervention, why do people take antibiotics? Because that forces people to think about, what is their idea, what is a natural event and what is man’s dominion over natural events.

“Now let me explain a trick, a kind of philosopher’s game about natural conception. If you look at the legislation that’s been proposed in most countries, they have to rule out the problem of making a genetically identical individual as a reason to ban cloning, because of the existence of twins. If you didn’t do this, you would be obliged to kill one or two twins. So they have to rule out that line of argument, because it doesn’t make any logical sense. So what they’re left with is that it’s medically unsafe, which is absolutely true. I suggest to you that this reason is really a surrogate for a fear of doing something where they don’t know the consequence, by which I mean they are afraid, and I’ll tell you why. Here’s my puzzle. Right now, in natural childbirth, a certain percentage of all natural fertilization events end in something we call ‘diseased’ or ‘abnormal.’ So if you go to MGH [Massachusetts General Hospital] over here, for a certain small percentage of all children, the child has a heart defect problem. So now let’s look ahead: Fast-forward two generations from now, and I will contend that it will be possible, by medical advances, to make cloning by nuclear transfer safer than natural childbirth. That the cloned embryos will now have a defect rate, let’s call it, of less than one percent.”

“When will that be?”

“I’m not saying this will really happen, but let’s say twenty years from now, or two generations from now. I don’t know. But here’s the point. Let’s suppose the failure rate is now below what you and I call the ‘natural birth’ rate. Here’s the puzzle. Would the government then be justified in telling the population you can no longer create children by what you and I call ‘natural’ childbirth, because the probability of defect is higher than it is by cloning?”

“But there are methods being developed where you could repair those defects.”

“That’s right. But there is another point, which comes up in my discussions at the Catholic Church: There is something I think you call ‘natural abortion’—where biology removes fertilized events by not allowing them to implant.”

“You mean spontaneous abortions, or miscarriages.”

“Yes. I have a hard time finding the number because books seem to give different numbers, but people have agreed on a surprisingly high number. If you take one hundred fertilized eggs, let’s say only 20 percent of them are going to implant and make a baby. Of the fertilization events, most of them fail. If that’s true, the Catholic Church has a major problem that they fail to face up to, if life begins at fertilization. There are thirty million Catholics in the United States. If you said that 1 percent of them tried a mating event tonight, that’s three hundred thousand. And if 80 percent of those died, that’s two hundred forty thousand deaths of souls for which they should be holding a funeral tomorrow. And when I pointed this out, they find this to be a puzzle that they don’t know how to answer. One answer is that this is God’s will, and that’s fine, but then that gets you into this really complicated business of, Is it not then God’s will to have a person like me wanting to work on human embryonic stem cells?”