by Tim Folger
Those fears have existed since humans began to transplant genes in crops. They are the central reason that opponents of genetically engineered food invoke the precautionary principle, which argues that potential risks must always be given more weight than possible benefits. That is certainly the approach suggested by people like Jim Thomas, of ETC, who describes Endy as "the alpha Synthusi ast." But he also regards Endy as a reflective scientist who doesn't discount the possible risks of his field. "To his credit, I think he's the one who's most engaged with these issues," Thomas said.
The debate over genetically engineered food has often focused on theoretical harm rather than on tangible benefits. "If you build a bridge and it falls down, you are not going to be permitted to design bridges ever again," Endy said. "But that doesn't mean we should never build a new bridge. There we have accepted the fact that risks are inevitable." He believes the same should be true of engineering biology.
We also have to think about our society's basic goals and how this science might help us achieve them. "We have seen an example with artemisinin and malaria," Endy said. "Maybe we could avoid diseases completely. That might require us to go through a transition in medicine akin to what happened in environmental science and engineering after the end of World War II. We had industrial problems, and people said, Hey, the river's on fire—let's put it out. And, after the nth time of doing that, people started to say, Maybe we shouldn't make factories that put shit into the river. So let's collect all the waste. That turns out to be really expensive, because then we have to dispose of it. Finally, people said, Let's redesign the factories so that they don't make that crap."
Endy pointed out that we are spending trillions of dollars on health care and that preventing disease is obviously more desirable than treating it. "My guess is that our ultimate solution to the crisis of health-care costs will be to redesign ourselves so that we don't have so many problems to deal with. But note," he stressed, "you can't possibly begin to do something like this if you don't have a value system in place that allows you to map concepts of ethics, beauty, and aesthetics onto our own existence.
"These are powerful choices. Think about what happens when you really can print the genome of your offspring. You could start with your own sequence, of course, and mash it up with your partner, or as many partners as you like. Because computers won't care. And, if you wanted evolution, you can include random number generators." That would have the effect of introducing the element of chance into synthetic design.
Although Endy speaks with passion about the biological future, he acknowledges how little scientists know. "It is important to un pack some of the hype and expectation around what you can do with biotechnology as a manufacturing platform," he said. "We have not scratched the surface. But how far will we be able to go? That question needs to be discussed openly, because you can't address issues of risk and society unless you have an answer."
Answers, however, are not yet available. The inventor and materials scientist Saul Griffith has estimated that powering our planet requires between fifteen and eighteen terawatts of energy. How much of that could we manufacture with the tools of synthetic biology? Estimates range between five and ninety terawatts. "If it turns out to be the lower figure, we are screwed," Endy said. "Because why would we take this risk if we cannot create much energy? But if it's the top figure, then we are talking about producing five times the energy we need on this planet and doing it in an environmentally benign way. The benefits in relation to the risks of using this new technology would be unquestioned. But I don't know what the number will be, and I don't think anybody can know at this point. At a minimum, then, we ought to acknowledge that we are in the process of figuring that out and the answers won't be easy to provide.
"It's very hard for me to have a conversation about these issues, because people adopt incredibly defensive postures," Endy continued. "The scientists on one side and civil society organizations on the other. And to be fair to those groups, science has often proceeded by skipping the dialogue. But some environmental groups will say, Let's not permit any of this work to get out of a laboratory until we are sure it is all safe. And as a practical matter that is not the way science works. We can't come back decades later with an answer. We need to develop solutions by doing them. The potential is great enough, I believe, to convince people it's worth the risk."
I wondered how much of this was science fiction. Endy stood up. "Can I show you something?" he asked, as he walked over to a bookshelf and grabbed four gray bottles. Each one contained about half a cup of sugar, and each had a letter on it: A, T, C, or G, for the four nucleotides in our DNA. "You can buy jars of these chemicals that are derived from sugarcane," he said. "And they end up being the four bases of DNA in a form that can be readily assembled. You hook the bottles up to a machine, and into the machine comes in formation from a computer, a sequence of DNA—like T-A-A-T-AG-C-A-A. You program in whatever you want to build, and that machine will stitch the genetic material together from scratch. This is the recipe: you take information and the raw chemicals and compile genetic material. Just sit down at your laptop and type the letters and out comes your organism."
We don't have machines that can turn those sugars into entire genomes yet. Endy shrugged. "But I don't see any physical reason why we won't," he said. "It's a question of money. If somebody wants to pay for it, then it will get done." He looked at his watch, apologized, and said, "I'm sorry, we will have to continue this discussion another day, because I have an appointment with some people from the Department of Homeland Security."
I was a little surprised. "They are asking the same questions as you," he said. "They want to know how far is this really going to go."
Scientists skipped a step at the birth of biotechnology, thirty-five years ago, moving immediately to products without first focusing on the tools required to make them. Using standard biological parts, a synthetic biologist or biological engineer can already, to some extent, program living organisms in the same way a computer scientist can program a computer. However, genes work together in ways that are staggeringly complex; proteins produced by one will counteract—or enhance—those made by another. We are far from the point where scientists might yank a few genes off the shelf, mix them together, and produce a variety of products. But the registry is growing rapidly—and so is the knowledge needed to drive the field forward.
Research in Endy's Stanford lab has been largely animated by his fascination with switches that turn genes on and off. He and his students are attempting to create genetically encoded memory systems, and his current goal is to construct a cell that can count to 256—a number derived from the mathematics of Basic computer code. Solving the practical challenges will not be easy, since cells that count will need to send reliable signals when they divide and remember that they did.
"If the cells in our bodies had a little memory, think what we could do," Endy said the next time we talked. I wasn't quite sure what he meant. "You have memory in your phone," he explained. "Think of all the information it allows you to store. The phone and the technology on which it is based do not function inside cells. But if we could count to two hundred using a system that was based on proteins and DNA and RNA—well, now, all of a sudden we would have a tool that gives us access to computing and memory that we just don't have.
"Do you know how we study aging?" Endy continued. "The tools we use today are almost akin to cutting a tree in half and counting the rings. But if the cells had a memory, we could count properly. Every time a cell divides, just move the counter by one. Maybe that will let me see them changing with a precision nobody can have today. Then I could give people controllers to start retooling those cells. Or we could say, Wow, this cell has divided two hundred times, it's obviously lost control of itself and become cancer. Kill it. That lets us think about new therapies for all kinds of diseases."
Synthetic biology is changing so rapidly that predictions seem pointless. Even that fact presents people like End
y with a new kind of problem. "Wayne Gretzky once said, 'I skate to where the puck is going to be.' That's what you do to become a great hockey player," Endy told me. "But where do you skate when the puck is accelerating at the speed of a rocket, when the trajectory is impossible to follow? Whom do you hire and what do we ask them to do? Because what preoccupies our finest minds today will be a seventh-grade science project in five years. Or three years.
"We are surfing an exponential now, and, even for people who pay attention, surfing an exponential is a really tricky thing to do. And when the exponential you are surfing has the capacity to impact the world in such a fundamental way, in ways we have never before considered, how do you even talk about that?"
For decades, people have invoked Moore's law: the number of transistors that could fit onto a silicon chip would double every two years, and so would the power of computers. When the IBM 360 computer was released in 1964, the top model came with eight megabytes of main memory, and cost more than $2 million. Today cell phones with a thousand times the memory of that computer can be bought for about a hundred dollars.
In 2001 Rob Carlson, then a research fellow at the Molecular Sciences Institute in Berkeley, decided to examine a similar phenom enon: the speed at which the capacity to synthesize DNA was growing. He produced what has come to be known as the Carlson curve, and it shows a rate that mirrors Moore's law—and has even begun to exceed it. The automated DNA synthesizers used in thousands of labs cost $100,000 a decade ago. Now they cost less than $10,000, and most days at least a dozen used synthesizers are for sale on eBay—for less than a thousand dollars.
Between 1977, when Frederick Sanger published the first paper on automatic DNA sequencing, and 1995, when the Institute for Genomic Research reported the first bacterial-genome sequence, the field moved slowly. It took the next six years to complete the first draft of the immeasurably more complex human genome, and six years after that, in 2007, scientists from around the world began mapping the full genomes of more than a thousand people. The Harvard geneticist George Church's Personal Genome Project now plans to sequence more than a hundred thousand.
In 2003, when Endy was still at MIT, he and his colleagues Tom Knight, Randy Rettberg, and Gerald Sussman founded iGEM—the International Genetically Engineered Machine competition—whose purpose is to promote the building of biological systems from standard parts. In 2006 a team of Endy's undergraduate students used BioBrick parts to genetically reprogram E. coli (which normally smells awful) to smell like wintergreen while it grows and like bananas when it has finished growing. They named their project Eau d'E Coli. By 2008, with more than a thousand students from twenty-one countries participating, the winning team—a group from Slovenia—used biological parts that it had designed to create a vaccine for the stomach bug Helicobacter pylori, which causes ulcers. There are no such working vaccines for humans. So far the team has tested its creation on mice, with promising results.
This is open-source biology, where intellectual property is shared. What's available to idealistic students, of course, would also be available to terrorists. Any number of blogs offer advice about everything from how to preserve proteins to the best methods for desalting DNA. Openness like that can be frightening, and there have been calls for tighter control of the technology. Carlson, among many others, believes that strict regulations are unlikely to succeed. Several years ago, with very few tools other than a credit card, he opened his own biotechnology company, Biodesic, in the garage of his Seattle home—a biological version of the do-it-yourself movement that gave birth to so many computer companies, including Apple.
The product that he developed enables the identification of proteins using DNA technology. "It's not complex," Carlson told me, "but I wanted to see what I could accomplish using mail order and synthesis." A great deal, it turned out. Carlson designed the molecule on his laptop, then sent the sequence to a company that synthesizes DNA. Most of the instruments could be bought on eBay (or, occasionally, on LabX, a more specialized site for scientific equipment). All you need is an Internet connection.
"Strict regulation doesn't accomplish its goals," Carlson said. "It's not an exact analogy, but look at Prohibition. What happened when government restricted the production and sale of alcohol? Crime rose dramatically. It became organized and powerful. Legitimate manufacturers could not sell alcohol, but it was easy to make in a garage—or a warehouse."
By 2002 the U.S. government had intensified its effort to curtail the sale and production of methamphetamine. Previously, the drug had been manufactured in many mom-and-pop labs throughout the country. Today production has been professionalized and centralized, and the Drug Enforcement Administration says that less is known about methamphetamine production than before. "The black market is getting blacker," Carlson said. "Crystal-meth use is still rising, and all this despite restrictions." Strict control would not necessarily insure the same fate for synthetic biology, but it might.
Bill Joy, a founder of Sun Microsystems, has frequently called for restrictions on the use of technology. "It is even possible that self-replication may be more fundamental than we thought, and hence harder—or even impossible—to control," he wrote in an essay for Wired called "Why the Future Doesn't Need Us." "The only realistic alternative I see is relinquishment: to limit development of the technologies that are too dangerous, by limiting our pursuit of certain kinds of knowledge."
Still, censoring the pursuit of knowledge has never really worked, in part because there are no parameters for society to decide who should have information and who should not. The opposite approach might give us better results: accelerate the development of technology and open it to more people and educate them to its purpose. Otherwise, if Carlson's methamphetamine analogy proves accurate, power would flow directly into the hands of the people least likely to use it wisely.
For synthetic biology to accomplish any of its goals, we will also need an education system that encourages skepticism and the study of science. In 2007 students in Singapore, Japan, China, and Hong Kong (which was counted independently) all performed better on an international science exam than American students. The U.S. scores have remained essentially stagnant since 1995, the first year the exam was administered. Adults are even less scientifically literate. Early in 2009, the results of a California Academy of Sciences poll (conducted throughout the nation) revealed that only 53 percent of American adults know how long it takes for Earth to revolve around the sun, and a slightly larger number—59 percent—are aware that dinosaurs and humans never lived at the same time.
Synthetic biologists will have to overcome this ignorance. Optimism prevails only when people are engaged and excited. Why should we bother? Not just to make E. coli smell like chewing gum or to make fish glow in vibrant colors. The planet is in danger, and nature needs help.
The hydrocarbons we burn for fuel are believed to be nothing more than concentrated sunlight that has been collected by leaves and trees. Organic matter rots, bacteria break it down, and it moves underground, where, after millions of years of pressure, it turns into oil and coal. At that point, we dig it up—at huge expense and with disastrous environmental consequences. Across the globe, on land and sea, we sink wells and lay pipe to ferry our energy to giant refineries. That has been the industrial model of development, and it worked for nearly two centuries. It won't work any longer.
The industrial age is drawing to a close, eventually to be replaced by an era of biological engineering. That won't happen easily (or quickly), and it will never solve every problem we expect it to solve. But what worked for artemisinin can work for many of the products our species will need to survive. "We are going to start doing the same thing that we do with our pets, with bacteria," the genomic futurist Juan Enriquez has said, describing our transition from a world that relied on machines to one that relies on biology. "A house pet is a domesticated parasite," he noted. "It is evolved to have an interaction with human beings. Same thing with corn"—a crop that didn't
exist until we created it. "Same thing is going to start happening with energy," he went on. "We are going to start domesticating bacteria to process stuff inside enclosed reactors to produce energy in a far more clean and efficient manner. This is just the beginning stage of being able to program life."
BRIAN BOYD Purpose-Driven Life
FROM The American Scholar
[Darwinism] seems simple, because you do not at first realize all that it involves. But when its whole significance dawns on you, your heart sinks into a heap of sand within you. There is a hideous fatalism about it, a ghastly and damnable reduction of beauty and intelligence, of strength and purpose, of honor and aspiration.
—George Bernard Shaw, Back to Methuselah (1912)
EVOLUTIONARY THINKING has lately expanded from the biological to the human world, first into the social sciences and recently into the humanities and the arts. Many people therefore now understand the human, and even human culture, as inextricably biological. But many others in the humanities—in this, at least, like religious believers who reject evolution outright—feel that a Darwinian view of life and a biological view of humanity can only deny human purpose and meaning.
Does evolution by natural selection rob life of purpose, as so many have feared? The answer is no. On the contrary, Charles Darwin has made it possible to understand how purpose, like life, builds from small beginnings, from the ground up. In a very real sense, evolution creates purpose.
Evolution generates problems and solutions as it generates life. Rocks may crack and erode, but they do not have problems. Amoebas and apes do. Natural selection creates complex new possibilities, and therefore new problems, as it assembles self-sustaining organisms piecemeal, cycle after cycle, by generating partial solutions, testing them, and regenerating from the basis of the best solutions available in the current cycle. In time, it can create richer solutions to richer problems.