“If I gamble, I usually gamble at high-stakes, high-payoff games.” That’s a boast not from James Bond, but from a chemist speaking to the prestigious journal Science (the July 14 issue, from which all quotes but the last one in this column are taken). His name is Peter Schultz. He works at Scripps Research Institute and at a new Genomics Institute created by Novartis, a company deep into genetic engineering. What he’s gambling with is the chemistry of life.
Image: Courtesy DOE Human Genome Project.
To understand his bold scheme, we need to take a short detour here to remind ourselves of that chemistry.
Everything starts with the DNA molecule, a long chain with billions of links. Each link is one of four chemical “letters,” C, G, A, or T. A sequence of three letters (TAC or GCT, for example) makes up one “word” of genetic code.
Through a set of exquisite translations, the code tells living cells how to build proteins. Proteins are chains with tens of thousands of links, each of which is one of 20 different amino acids. Each triplet in the DNA code stands for one kind of amino acid. CTA stands for leucine, GCA stands for alanine, and so forth.
How does a code for proteins specify how to build a bacterium, a lily, a cow, a chimpanzee, or you? Well, the proteins coded by DNA are enzymes. They supervise and enhance chemical reactions. If you have brown eyes, your DNA carries the code for an enzyme that helps synthesize brown pigment. Enzymes direct the unfolding of the developing embryo, the branching of nerve networks in the brain, the ability of the stomach to digest carbohydrates. DNA even carries code for enzymes that turn on and off the production of enzymes — so the brown pigment is made only in the eye and carbohydrate digestion happens only in the stomach.
The orchestration is stupendous. The chemistry of life, so common around us, not to mention within us, is awesome. Let us pause here for a moment of humility and wonder — feelings that, to judge from the Science article, Peter Schultz is far too busy to indulge in.
“Here’s a guy who runs at 800 miles per hour,” reporter Robert Service writes of Schultz. “You have a conversation and he’s three thoughts ahead of you. You start to say something and he answers your question saying ‘I know what you’re going to say.’” He even knows what God was going to say. He summarizes his research question: “If God had worked a seventh day, what would life look like?”
To put it more concretely, why should there just be four DNA letters? Why that boring CGAT? What if we put in an X or a Y? And why code for just 20 amino acids? Let’s invent some new ones that life has never seen before and then invent some DNA to code for them!
“What we really want to do,” says Schultz, “is build an organism — a living organism — where you can add a 21st amino acid to the growth medium and it takes up that amino acid and puts it selectively into a protein.”
He hasn’t done that yet, but a colleague says, “I think if anyone can do it, Pete Schultz’s lab is the place where it can get done.” He has already tricked cellular translators into sticking more than 80 non-natural amino acids into proteins, but so far the process is low-yielding and hit-or-miss. He has already added a new “letter” to DNA and gotten enzymes to copy it. “I think it’s no longer a question of will it work, but how long it will take.”
The possible benefits of such research cited in the article are mainly scientific. To add a fluorescent tag to show where proteins end up in cells. To build in heavy atoms that will aid in protein crystallography. To show how life might have evolved on another planet. Maybe to design better drugs or better catalysts for industrial processes.
One of Schultz’s colleagues sees larger consequences; it “means reengineering 3.5 billion years of evolution.” That’s not meant as a criticism. All the scientists quoted, including the Science reporter, seem to be dazzled, maybe jealous, but not disturbed. The only note of caution comes from a graduate student: “I used to joke with [Schultz] that we would know the project was complete when we saw people protesting outside the window.”
The Science reporter does admit: “Such experiments are likely to make many people a little queasy and raise prickly questions about safety and ethical concerns.” Then he quotes Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, who says, “At the end of the day, I don’t see any fundamental amorality to making synthetic DNA to regulate a synthetic life-form.”
I would have quoted Erwin Chargaff, one of the grand old men of molecular biology, who wrote in the mid 1970s, also in Science, “You can stop splitting the atom; you can stop visiting the moon; you can stop using aerosols; you may even decide not to kill entire populations by the use of a few bombs. But you cannot recall a new form of life. … It will survive you and your children and your children’s children. … Have we the right to counteract irreversibly the evolutionary wisdom of millions of years in order to satisfy the ambition and the curiosity of a few scientists?”