Masterminds: Genius, DNA, and the Quest to Rewrite Life

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?”

5

Melton presented the chimeras and clones as intellectual “puzzles” and has no plans to implement these notions. He makes it clear that he has no interest in experimenting on humans. Yet he would not be opposed to the chimera experiments if they were considered ethical and were allowed.

I wonder whether monkeys with human brains will one day seem as normal as heart surgery does today, or whether cloning will ever actually be preferred to “natural” childbirth. Melton’s obsession with “normal, normal, normal” is an intriguing one, because normality does keep shifting with new scientific advances and has since at least the day that Prometheus gave us fire—which must have radically shifted what was “normal” those many millennia ago. Also driving the issue of what is normal is Sam and Emma, whose father wants what any parent craves—to save his children from suffering. Yet as Bill Hurlbut of Stanford asks, How far do we want to go down the slippery slope? Or, as George Whitesides has said, Is there a possible scientific path that scientists could go down, but shouldn’t—when they should just say no? When one of the gifts offered by Prometheus is simply too dangerous, or too abnormal, as Melton would say?

In this sense, Doug Melton is simply another figure in an ancient question of whose normality is really normal with new science and technology, and whose is not. Ethics aside, I have to admit to a certain curiosity about what Melton would get in his human-monkey chimera. Perhaps the beginnings of a superrace of primates unimagined even by Michael Crichton, or a few poor horrific wretches that would be true Frankenstein creatures, wandering the Earth seeking revenge against their creators.

Later, on the phone, I ask Melton again whether he sees any dangers in stem cells, and chimeras, and the like. Is there a time when he would ever say no or halt an experiment?

“I don’t know what will come of this,” he says. “On the other hand, I think it’s uninteresting to live in a society where one is so afraid of the unknown that you won’t try new things. I’ll think about the dangers, because I haven’t thought about them enough. I should think about why one shouldn’t do that experiment.”

(#ulink_e30e7d4a-e396-5490-b65d-0f9f02c84658)In various twin studies, twins separated at birth or early in life manifested differences in how they acquired diseases and traits despite having identical DNA, suggesting that both environment and genes determine outcomes.

2 EVE Cynthia Kenyon (#ulink_ae6cb109-af57-518d-8fcb-17040f8842cb)

In principle, if you understood the mechanisms

of keeping things repaired, you could keep

things going indefinitely.

—Cynthia Kenyon

Cynthia Kenyon wants to live to be one hundred and fifty years old, if she’s young and engaged in life. “Who wouldn’t?” She asks in a breathless whisper, telling me that humans might be able to live a very long time, if not forever.

Kenyon’s long, angular face is framed by straight blond hair parted in the middle. She talks excitedly, waving long, graceful fingers as her words spill out almost too fast to follow about how her lab at the University of California at San Francisco (UCSF) has increased the life span of tiny worms called Caenorhabditis elegans an average of six times normal by suppressing a single gene. This regulator gene, she tells me, in combination with other genes appears to control an entire symphony of genes that direct aging not only in worms, but in similar genetic pathways in flies, mice, and, possibly, humans.

This is the equivalent of people living for four hundred years, she says, adding that there is more good news coming from her millimeter-long lab animal of choice. Our worms stay young for most of these extended life spans, she says.

“You mean this is a Fountain of Youth gene?”

She nods, delighted that I have made this connection. Yet I don’t know what to make of a woman who has just told me that I or my children might live into the twenty-fourth century. I remember a mid-seventeenth-century poem written by Andrew Marvell about growing old, “To His Coy Mistress”:

But at my back I always hear,

Time’s winged chariot hurrying near;

And yonder all before us lie

Deserts of vast eternity.

Thy beauty shall be no more found,

Nor, in thy marble vault, shall sound

My echoing song: then worms shall try

That long preserved virginity.

This is the poet’s attempt to persuade his lover to make up her mind about having sex with him, because life is short, and they both might grow old and die at the rate she is going. But what if life weren’t short? What if what works on Kenyon’s worms really will work in humans?

One outcome would be that a modern-day coy woman would be able to put off her would-be lover for decades, or even centuries—and would require a rewriting of Marvell’s lines to something like this:

Take your time, my coy lass,

Time’s winged chariot won’t pass,

For three or four hundred years, if ever.

1

Cynthia Kenyon talks with the slightly exaggerated facial expressions of someone telling and receiving juicy gossip—expressions of “Oh my gosh!” And “No way!” Her voice is soft and light, and she frequently says “cool” and “neat.” Yet her enthusiasm is infective. “Life’s too short to not be around nice people,” she says, this woman who is delving into the mechanisms of how to make life considerably less short.

As we talk—and she talks very quickly, as if she won’t have time to say everything she wants even if she lives for four hundred years—she offers me peanuts. I take a couple of nuts as Kenyon instantly shifts the topic we are talking about—she does that often—and explains to me that she has totally changed her diet, eliminating most sugars, including those found in processed flour. Hence the peanuts. An experiment with her tiny worms is responsible, she says; that experiment proved that sugar switches on a genetic sequence that increases the amount of insulin produced by the organism, and also shortens its life span. For Kenyon, this was startling because it fit with her lab’s previous discovery that decreasing the amount of insulin in the body extended the worm’s lifespan. “It was a revelation,” Kenyon says. She also drinks red wine and green tea, which her lab and others have shown help repair cells and contribute to an increased life span.