Denialism (24 page)

He was absolutely right. As is the case with heart disease, diabetes, autism, and many other conditions, there will almost certainly prove to be many causes of Alzheimer’s. One theory holds, for example, that in some cases cholesterol may play a significant role; people with Alzheimer’s often accumulate too much of a substance called amyloid precursor protein (APP). We all produce APP, but in people with Alzheimer’s disease the protein gives rise to a toxic substance called beta amyloid that builds up and eventually causes plaques that kill brain cells. There remains much to be learned about this process, but some doctors recommend that people with a family history of Alzheimer’s disease take statins, which help to reduce cholesterol levels even when the results from standard cholesterol tests are normal.

This is when I realized that becoming an early adopter of personal genomics isn’t like buying one of the first iPods or some other cool technological gadget; there is a lot more at stake. My tests showed that I have a significantly increased risk of heart attack, diabetes, and atrial fibrillation. These are not solely diseases influenced by genetics, and effective measures exist to address at least some of those risks—diet and exercise, for instance. That’s the good news. Adding that data to my family history of Alzheimer’s disease suggests that it would probably make sense for me to begin taking a statin drug to lower cholesterol (even though mine is not high).

But complex as those variables are, it’s still not that simple. About one person in ten thousand who take statins experiences a condition known as myopathy—muscle pain and weakness. (And since millions of Americans take the drug, those numbers are not as insignificant as they might seem.) It turns out that I have one C allele at SNP rs414056, which is located in the SLCO1B1 gene. That means I have nearly five times the chance of an adverse reaction to statins as people who have no Cs on that gene. (It could be worse; two Cs and your odds climb to seventeen times the average.) Now, what does that mean exactly? Well, if the study is correct I still have far less than a 1 percent chance of experiencing myopathy. I’ll take those odds. As 23andme points out in its description of the statin response, “Please note that myopathy is a very rare side effect of statins even among those with genotypes that increase their odds of experiencing it.” The risks of heart disease, however, and, in my family, Alzheimer’s disease, are not rare.

CRUISING THROUGH ONE’S genomic data is not for the faint of heart. Thanks to 23andme, I now know that I am left-eyed and can taste bitter food. Cool. But I am also a slow caffeine metabolizer. That’s a shame, because for people like me coffee increases the risk of heart attack, and I already have plenty of those risks. The information, though, helps explain a mystery of my youth. I drank a lot of coffee, and periodically I would see studies that suggested coffee increased the risk of heart disease. Then other reports would quickly contradict them. With this new genetic information those differences start to make sense; some people react badly to a lot of coffee and others do not. I ended up with genetic bad luck on the caffeine front and have no choice but to drink less of it.

I’m not resistant to HIV or malaria but I am resistant, unusually enough, to the norovirus (which is the most common cause of what people think is stomach flu; actually, it’s not flu at all). My maternal ancestors came from somewhere in the Urals—but I also have a bit of Berber in me because at some point seventeen thousand years ago, after the last Ice Age, my paternal line seems to have made its way into northern Africa.

If the calculations provided by these tests fail to satiate your curiosity, you can always analyze the million lines of raw data that spell your DNA (or at least as much of it as these companies currently process). You can download the data in a Zip file as if it were a song from iTunes or some family photos. Then simply plug that information into a free program called Promethease that annotates thousands of genotypes and spits back unimaginably detailed information about whatever is known about every SNP. Promethease is not for everyone, or really for very many people. It’s so comprehensive that it is difficult to interpret—sort of like getting all the hits from a Google search dumped in your lap (and for most people, in a language they don’t speak).

These are still early days in genomics, but it won’t be long until people will carry their entire genome on their cell phone—along with an application that helps make sense of it all. When you pick up those dozen eggs at the store your phone will remind you that not only do you have high cholesterol but you have already bought eggs this week. It will warn a diabetic against a food with sugar, and a vegan to skip the soup because it was made from meat stock. It would ensure that nobody with hemochromatosis slipped up and bought spinach, and in my case, when I buy coffee beans, it would nag me to remember that they had better be decaf.

Someday—and not so long from now—medicine really will be personal. Then everyone will be a member of his own race. When that happens one has to wonder, Will discrimination finally disappear, or will it just find a new voice? That’s up to us. In literature, scientific future is often heartless and grim. The 1997 film
Gattaca
was a work of science fiction about a man burdened with DNA he inherited from his parents, rather than having had it selected for him before conception. Most people were made to order. But not the main character, Vincent. He was a member of “a new genetic underclass that does not discriminate by race.” A victim of genoism. As he points out in the film, “What began as a means to rid society of inheritable diseases has become a way to design your offspring—the line between health and enhancement blurred forever. Eyes can always be brighter, a voice purer, a mind sharper, a body stronger, a life longer.”

Some people watched that movie and shuddered. I wasn’t among them. There are many worrisome possibilities about the future, questions of privacy, equity, and personal choice not least among them. Even the most ethically complex issues can be framed positively, though, provided we are willing to discuss them. There is no reason why the past has to become the future.

“Terrible crimes have been committed in the name of eugenics. Yet I am a eugenicist,” the British developmental scientist Lewis Wolpert has written. “For it now has another, very positive, side. Modern eugenics aims to both prevent and cure those with genetic disabilities. Recent advances in genetics and molecular biology offer the possibility of prenatal diagnosis and so parents can choose whether to terminate a pregnancy. There are those who abhor abortion, but that is an issue that should be kept quite separate from discussions about genetics. In Cyprus, the Greek Orthodox Church has cooperated with clinical geneticists to reduce dramatically the number of children born with the crippling blood disease thalassemia. This must be a programme that we should all applaud and support. I find it hard to think of a sensible reason why anybody should be against curing those with genetic diseases like muscular dystrophy and cystic fibrosis.”

You don’t have to be Dr. Frankenstein to agree with him. We need to address these issues and others we have yet to envision. There will be many ways to abuse genomics. The same technologies that save and prolong millions of lives can also be used to harm people and discriminate against them. But hasn’t that always been true? The stakes are higher now, but the opportunities are greater. We are still in control of our fate, although denialists act as if we are not. The worst only happens when we let it happen.

6

Surfing the Exponential

The first time Jay Keasling remembers hearing the word “artemisinin”—about a decade ago—he had no idea what it meant. “Not a clue,” Keasling, a professor of biochemical engineering at the University of California at Berkeley, recalled. Although artemisinin has become the world’s most important malaria medicine, Keasling wasn’t up on infectious diseases. But he happened to be in the process of creating a new discipline, synthetic biology, which, by combining elements of engineering, chemistry, computer science, and molecular biology, seeks nothing less than to assemble the biological tools necessary to redesign the living world.

No scientific achievement—not even splitting the atom—has promised so much, and none has come with greater risks or clearer possibilities for deliberate abuse. If they fulfill their promise, the tools of synthetic biology could transform microbes into tiny, self-contained factories—creating cheap drugs, clean fuels, and entirely new organisms to siphon carbon dioxide from the atmosphere we have nearly destroyed. To do that will require immense commitment and technical skill. It will also demand something more basic: as we watch the seas rise and snow-covered mountaintops melt, synthetic biology provides what may be our last chance to embrace science and reject denialism.

For nearly fifty years Americans have challenged the very idea of progress, as blind faith in scientific achievement gave way to suspicion and doubt. The benefits of new technologies—from genetically engineered food to the wonders of pharmaceuticals—have often been oversold. And denialism thrives in the space between promises and reality. We no longer have the luxury of rejecting change, however. Our only solutions lie in our skills.

Scientists have been manipulating genes for decades of course—inserting, deleting, and changing them in various molecules has become a routine function in thousands of labs. Keasling and a rapidly growing number of his colleagues have something far more radical in mind. By using gene sequence information and synthetic DNA, they are attempting to reconfigure the metabolic pathways of cells to perform entirely new functions, like manufacturing chemicals and drugs. That’s just the first step; eventually, they intend to construct genes—and new forms of life—from scratch. Keasling and others are putting together a basic foundry of biological components—BioBricks, as Tom Knight, the senior research scientist from MIT who helped invent the field, has named them. Each BioBrick, made of standardized pieces of DNA, can be used interchangeably to create and modify living cells.

“When your hard drive dies you can go to the nearest computer store, buy a new one, and swap it out,” Keasling said. “That’s because it’s a standard part in a machine. The entire electronics industry is based on a plug-and-play mentality. Get a transistor, plug it in, and off you go. What works in one cell phone or laptop should work in another. That is true for almost everything we build: when you go to Home Depot you don’t think about the thread size on the bolts you buy because they’re all made to the same standard. Why shouldn’t we use biological parts in the same way?” Keasling and others in the field—who have formed a bicoastal cluster in the San Francisco Bay Area and in Cambridge, Massachusetts—see cells as hardware and genetic code as the software required to make them run. Synthetic biologists are convinced that with enough knowledge, they will be able to write programs to control those genetic components, which would not only let them alter nature, but guide human evolution as well.

In 2000, Keasling was looking for a chemical compound that could demonstrate the utility of these biological tools. He settled on a diverse class of organic molecules known as isoprenoids, which are responsible for the scents, flavors, and even colors in many plants: eucalyptus, ginger, and cinnamon, for example, as well as the yellow in sunflowers and red in tomatoes. “One day a graduate student stopped by and said, ‘Look at this paper that just came out on amorphadiene synthase,’ ” Keasling told me as we sat in his in office in Emeryville, across the Bay Bridge from San Francisco. He had recently been named chief executive officer of the new Department of Energy Joint BioEnergy Institute (JBEI), a partnership between three national laboratories and three research universities, led by the Lawrence Berkeley National Laboratory. The consortium’s principal goal is to design and manufacture artificial fuels that emit little or no greenhouse gases—one of President Barack Obama’s most frequently cited priorities.

Keasling wasn’t sure what to tell his student. “ ‘Amorphadiene,’ I said. ‘What’s that?’ He told me that it was a precursor to artemisinin. I said, ‘What’s
that
?’ and he said it was supposedly an effective antimalarial. I had never worked on malaria. As a microbiology student I had read about the life cycle of the falciparum parasite; it was fascinating and complicated. But that was pretty much all that I remembered. So I got to studying and quickly realized that this precursor was in the general class we were planning to investigate. And I thought, amorphadiene is as good a target as any. Let’s work on that.”

Malaria infects as many as five hundred million of the world’s poorest people every year. For centuries the standard treatment was quinine, and then the chemically related compound chloroquine. At ten cents per treatment, chloroquine was cheap, simple to make, and it saved millions of lives. In Asia, though, by the height of the Vietnam War, the most virulent malaria parasite—falciparum—had grown resistant to the drug. Eventually, that resistance spread to Africa, where malaria commonly kills up to a million people every year, 85 percent of whom are under the age of five. Worse, the second line of treatment, sulfadoxine pyrimethanine, or SP, had also failed widely.

Artemisinin, when taken in combination with other drugs, has become the only consistently successful treatment that remains. (Relying on any single drug increases the chances that the malaria parasite will develop resistance; if taken by itself even artemisinin poses dangers, and for that reason the treatment has already begun to fail in parts of Cambodia.) Known in the West as
Artemisia annua,
or sweet wormwood, the herb grows wild in many places, but until recently it had been used mostly in Asia. Supplies vary and so does the price, particularly since 2005, when the World Health Organization officially recommended that all countries with endemic malaria adopt artemisinin-based combination therapy as their first line of defense.

That approach, while unavoidable, has serious drawbacks: combination therapy costs ten to twenty times more than chloroquine, and despite growing assistance from international charities, that is far too much money for most Africans or their governments. In Uganda, for example, one course of artemisinin-based medicine would cost a typical family as much as it spends in two months for food. Artemisinin is not an easy crop to cultivate. Once harvested, the leaves and stems have to be processed rapidly or they will be destroyed by exposure to ultraviolet light. Yields are low, and production is expensive. Although several thousand African farmers have begun to plant the herb, the World Health Organization expects that for the next several years the annual demand—as many as five hundred million courses of treatment per year—will far exceed the supply. Should that supply disappear, the impact would be incalculable. “Losing artemisinin would set us back years—if not decades,” Kent Campbell, a former chief of the malaria branch at the Centers for Disease Control, and head of the Malaria Control and Evaluation Partnership in Africa, said. “One can envision any number of theoretical public health disasters in the world. But this is not theoretical. This is real. Without artemisinin, millions of people could die.”

JAY KEASLING is not a man of limited ambitions. “We have gotten to the point in human history where we simply do not have to accept what nature has given us,” he told me. It has become his motto. “We can modify nature to suit our aims. I believe that completely.” It didn’t take long before he realized that making amorphadiene presented an ideal way to prove his point. His goal was, in effect, to dispense with nature entirely, which would mean forgetting about artemisinin harvests and the two years it takes to turn those leaves into drugs. If each cell became its own factory, churning out the chemical required to make artemisinin, there would be no need for an elaborate and costly manufacturing process either. He wondered, why not try to build the drug out of genetic parts? How many millions of lives would be saved if, by using the tools of synthetic biology, he could construct a cell to manufacture that particular chemical, amorphadiene? It would require Keasling and his team to dismantle several different organisms, then use parts from nearly a dozen of their genes to cobble together a custom-built package of DNA. They would then need to create an entirely new metabolic pathway, one that did not exist in the natural world.

By 2003, the team reported its first success, publishing a paper in
Nature Biotechnology
that described how they constructed that pathway—a chemical circuit the cell needs to do its job—by inserting genes from three organisms into
E. coli
, one of the world’s most common bacteria. The paper was well received, but it was only the first step in a difficult process; still, the research helped Keasling secure a $42.6 million grant from the Bill and Melinda Gates Foundation. It takes years, millions of dollars, much effort, and usually a healthy dose of luck to transform even the most ingenious idea into a product you can place on the shelf of your medicine cabinet. Keasling wasn’t interested in simply proving the science worked; he wanted to do it on a scale that would help the world fight malaria. “Making a few micrograms of artemisinin would have been a neat scientific trick,” he said. “But it doesn’t do anybody in Africa any good if all we can do is a cool experiment in a Berkeley lab. We needed to make it on an industrial scale.”

To translate the science into a product, Keasling helped start a company, Amyris Biotechnologies, to refine the raw organism, then figure out how to produce it more efficiently. Slowly, the company’s scientists coaxed greater yields from each cell. What began as 100 micrograms per liter of yeast eventually became 25 grams per liter. The goal was to bring the cost of artemisinin down from more than ten dollars a course to less than one dollar. Within a decade, by honing the chemical sequences until they produced the right compound in the right concentration, the company increased the amount of artemisinic acid that each cell could produce by a factor of one million. Keasling, who makes the cellular toolkit available to other researchers at no cost, insists that nobody profit from its sale. (He and the University of California have patented the process in order to make it freely available.) “I’m fine with earning money from research in this field,” he said. “I just don’t think we need to profit from the poorest people on earth.”

Amyris then joined the nonprofit Institute for OneWorld Health, in San Francisco, and in 2008 they signed an agreement with the Paris-based pharmaceutical company Sanofi-Aventis to produce the drug, which they hope to have on the market by the end of 2011. Scientific response has been largely reverential—it is, after all, the first bona fide product of synthetic biology, proof of a principle that we need not rely on the unpredictable whims of nature to address the world’s most pressing crises. But there are those who wonder what synthetic artemisinin will mean for the thousands of farmers who have begun to plant the crop. “What happens to struggling farmers when laboratory vats in California replace [wormwood] farms in Asia and East Africa?” asked Jim Thomas, an activist with ETC Group, a technology watchdog based in Canada. Thomas has argued that while the science of synthetic biology has advanced rapidly, there has been little discussion of the ethical and cultural implications involved in altering nature so fundamentally, and he is right. “Scientists are making strands of DNA that have never existed,” Thomas said. “So there is nothing to compare them to. There’s no agreed mechanisms for safety, no policies.”

Keasling, too, believes we need to have a national conversation about the potential impact of this technology, but he is mystified by opposition to what would be the world’s most reliable source of cheap artemisinin. “We can’t let what happened with genetically engineered foods”—which have been opposed by millions of people for decades—“happen again,” he said. “Just for a moment imagine that we replaced artemisinin with a cancer drug. And let’s have the entire Western world rely on some farmers in China and Africa who may or may not plant their crop. And let’s have a lot of American children die because of that. It’s so easy to say, ‘Gee, let’s take it slow’ about something that can save a child thousands of miles away. I don’t buy it. They should have access to Western technology just as we do. Look at the world and tell me we shouldn’t be doing this. It’s not people in Africa who see malaria who say, ‘Whoa, let’s put the brakes on.’ ”

Keasling sees artemisinin as the first part of a much larger program. “We ought to be able to make any compound produced by a plant inside a microbe,” he said. “We ought to have all these metabolic pathways. You need this drug? okay, we pull this piece, this part, and this one off the shelf. You put them into a microbe and two weeks later out comes your product.”