It’s not just that such company-directed testing might miss (or cover up) a dangerous product. Chemical-intensive farming has also led to a tremendous loss of biodiversity—both above and below ground, Vandermeer says. From the massive genetic biodiversity of traditional agroecosystems, we now have millions upon millions of acres planted with the same hybrid corn variety. Soil, a fantastic ecology of interdependent living organisms, has been reduced to a medium “as devoid of life as possible,” Vandermeer writes.
This positive feedback loop—vast acreage planted with single crops, all propped up by rivers of chemical fertilizers, which then cause the monocultures to flourish—has also created a dramatic increase in the potential for collapse. All it takes is for an insect (or a virus) to pick the lock of a plant’s defenses, and an entire crop can disappear. A nineteenth-century blight in Ireland ruined a potato crop, and fully a million people starved to death. In the 1950s, the Gros Michel banana—planted on monoculture plantations across Latin America—was virtually wiped out by a fungus. Today, the Cavendish—the Gros Michel’s successor and likely the only banana you have ever eaten, whether you’ve eaten it in Los Angeles, New York, London, or Hong Kong—is grown on vast plantations in Asia, Australia, and Central America. And a fungus, called Tropical Race 4, has picked its lock. Unless breeders (including geneticists) can figure out a way to get banana trees to develop resistance, there will likely come a day very soon when we—outside the tropics, at least—will have no more bananas.
Here at home, this system also means that companies get to decide what products to create. In the United States, GMOs are designed more to make corn for cheese puffs and cheap hamburgers than to develop nutritionally dense food for people either here or in developing countries. Such uses cheapen the promise of food technology by using it to create empty calories and poor nutrition, serving industry profits but not the general welfare of either people or the planet.
Without broader research conducted outside the food industry itself, the editors of the scientific journal Nature say, the development of genetic engineering “will continue to be profit-driven, limiting the chance for many of the advances that were promised thirty years ago—such as feeding the planet’s burgeoning population sustainably, reducing the environmental footprint of farming and delivering products that amaze and delight.”
Leaving the power of GM technology to a group of global food conglomerates is plainly problematic for a whole array of reasons. But there are small pockets out there, mostly in university and other nonprofit research labs, where an entirely different approach to genetic engineering is taking place. Because while most GMOs currently bolster the production of cheap, unhealthy, processed food, there are scientists at work developing foods that could actually change the world for the better.
3.
Mapping and Engineering and Playing Prometheus
As you walk into the Delaware Biotechnology Institute, the first thing you see is a giant double helix engraved on a large piece of Plexiglas. Inside, adorning the walls, are vivid, Technicolor photographs that look like images beamed back from the Hubble Space Telescope: streaks and smears of purples, greens, and reds that could be gas clouds swirling through star clusters. They aren’t. They are pictures of cellular components like mitochondria, taken with nanoscale bioimaging so impressive that its inventor won a Nobel Prize—and so sensitive that an entire wing of the building had to be built on a special slab to prevent vibrations from ruining photographic precision.
Deep inside the building, Blake Meyers leads me through a room given over to racks of whirring computers. There are wires and carcasses of old machines everywhere, and a power generator the size of three refrigerators, whose excess heat is balanced by an air-conditioning unit mounted on the building’s roof.
These computers are “energy hogs,” Meyers said; if the power goes out, the backup batteries can support them for only about fifteen minutes. The day I visited, Meyers said one of his servers had been crunching data for one project for six weeks straight.
Meyers is a prominent plant geneticist, with degrees from the University of Chicago and UC-Davis, who also did postdoc work for the agrochemical giant DuPont. He is a vegetarian and deeply conscious of environmental problems. Engineering new kinds of plants, he says, could fix problems on a global scale.
Take nitrogen fixation, Meyers said. Modern agriculture uses huge amounts of natural gas to make and add nitrogen fertilizer to fields growing corn, because corn plants suck so many nutrients from the soil. But if you could engineer corn to pull nitrogen straight out of the atmosphere, think of how much synthetic nitrogen you could stop making and applying.
“This is science fiction right now, but if we could produce corn that fixes nitrogen, we could eliminate hundreds of millions of units of natural gas, plus eliminate massive environmental sources of nitrogen that currently are emitted or run off,” he said. “You would have done a really beneficial thing. You would be one huge step closer to growing corn under organic conditions.”
Meyers lists other promising projects: creating a calorie-dense rice that also fixes its own nitrogen and resists insects and resists drought. “Think of what you could do,” he said. “You could create a supercrop. But you’re not going to get there through natural selection and traditional breeding. This would be like super-speeding evolution.”
Meyers is also entirely skeptical about the ability of small-scale farming to feed the world.
“We’re looking at a future with 9 billion people, and it may be as many as 12 billion—how are we going to feed them, plus generate sustainable fuels and bioproducts?” Meyers asked me. “Through small-scale farming? There’s not an ice cube’s chance in hell that we can do that. We need substantial bumps in agricultural productivity if we’re going to provide the resources that people are expecting. Addressing that need is going to take every tool in our toolbox. That’s why we think GM technology has to play a role in this.”
Inside his laboratory, Meyers drew me near a machine and asked a lab assistant to punch up a screen. There appeared before me an image of a grid, three squares by three, labeled “Tile 13.” Again, if I hadn’t known better, I might have assumed I was looking at a photograph of distant galaxies: blurring patches comprising thousands of tiny spots of black, white, and gray.
What we were looking at was in fact a constellation of “small RNAs” from soybean leaves. It is in this laboratory that Meyers—like scientists all over the world—is either (depending on your point of view) extending a long tradition of plant breeding or taking a Promethean leap once left to the gods.
The Genetic Equivalent of War and Peace
Understanding genetics is frequently compared to learning a language. Just as letters and words are arranged in certain patterns to transmit information on the page (the metaphor goes), so are microscopic elements inside cells arranged in predictable ways. Once these elements have been assigned letters, their combinations (or sequences) can be read just like words, sentences, or entire volumes. And just as the twenty-six letters in the English language can lead to more than a million words (and a virtually infinite number of unique sentences, paragraphs, and books), so do the four letters at the foundation of genetics lead to an unimaginably diverse number of organisms.
The “letters” of genetics, called nucleotides, are A (adenine), T (thymine), C (cytosine), and G (guanine). Inside the nucleus of all living cells, these nucleotides form chains that microbiologists can read: AATTCCGG, for example. Given their chemical makeup, each individual nucleotide is attracted to a very particular mate: A (which has two rings of nitrogen) will bond only with T (a single ring); the two-ring G will pair only with the single-ring C. This makes the pairing of letter chains very predictable: our chain of AATTCCGG, for example, will bond (and form a genetic “word”) with a complementary, mirrored chain of TTAAGGCC.
Complete sequences (the “chapters”) of these genetic words are called chromosomes, wh
ich can be made up of thousands of different genes (and therefore millions of individual nucleotides). Chromosomes are so densely packed that, linked together and stretched out, the DNA molecules in just one of your cells would be taller than you are. Lined up end to end, all the DNA in all your cells would stretch—in a very thin line—some 6 billion miles.
All together, an organism’s chromosomal chapters make up its entire book-length genome. It took about 3.1 million letters, 588,000 words, and 365 chapters to make War and Peace. It takes 3.2 billion nucleotide base pairs, 19,000 genes, and 23 pairs of chromosomes to make a human genome. More relevant for Blake Meyers is the soybean genome, which has more than 1.1 billion base pairs, 46,000 genes, and 20 chromosomes. Or the maize genome, which has 2.3 billion base pairs and 32,000 genes.
Counting genes is one thing. Understanding how they work has been another thing entirely. Scientists once summed up the way genes control cell function with a simple formula known as the Central Dogma: DNA codes for RNA and RNA codes for protein. DNA contains a cell’s blueprint; RNA transmits the blueprint to create proteins; proteins carry out a cell’s functional tasks, which in turn determine the structure and behavior of the organism itself.
As our understanding of genetics has sped up, however, new molecular worlds have opened up. When scientists sequenced the human genome a decade ago, it was somewhat like looking at a blueprint in a foreign language—everything was marked in its proper location, but no one could tell what it all meant. Less than 2 percent of our genome seemed to code for proteins that actually do anything, so the vast majority of our DNA has been like biology’s dark matter, acting in ways that remain mysterious and only partially understood. For years, long stretches of noncoding genes were simply tossed off as “junk DNA.”
That view has changed. A five-year project called ENCODE—for “Encyclopedia of DNA Elements”—found that as much as 80 percent of the human genome is biologically “functional,” meaning that even if certain genes don’t directly code proteins, they can still influence how nearby genes are expressed, and in which types of cells. These noncoding regions of DNA can have major bearing on diseases and genetic mutations. Because the genes of an organism are interconnected, a single disturbance in gene organization (or function) can affect multiple gene systems. This has potentially serious implications for cellular function and the overall health of the organism. Consider that altering a single letter of the genetic code of a single gene can be a significant step leading to cancer—a disease that involves alterations in the function of multiple genes, proteins, and cellular systems.
So if every cell in an organism has the same DNA—if the cells in your eyes contain the genes for your toes, and vice versa—why is it that cells are so different from one another, and do one thing, and not another? In other words, why do cells allow you to see out of your eyes and not out of your toes? In the plant world, why is a leaf cell not the same as a root cell or a flower cell? Understanding this requires going back to the idea of genetics as both a code (an “alphabet”) and a language (a mode of “expression”).
The answer lies in the way genes are expressed. Since every cell in an organism contains exactly the same genes, it is in this “expression”—as genes are either “turned on” or “turned off”—that cells become distinct. It’s gene expression that causes them to become either a root cell or a leaf cell, and collectively create plants—and whole other organisms—that are distinct. Changing a single letter can make a huge difference. Just as the difference between the words “tasty” and “nasty” is a single letter, so (in humans) a slight shift in nucleotide sequences could cause changes in amino acids, the building blocks of proteins, that can cause sickle-cell anemia, or Parkinson’s, or Alzheimer’s.
The code itself, the sequence of A’s, C’s, G’s, and T’s, is inscribed in DNA. But for this code, known as an organism’s genotype, to orchestrate an organism’s structure and behavior, known as its phenotype, the code must first be “transcribed” (inside the nucleus) from DNA to RNA and then “translated” (outside the nucleus) into a protein. And that requires an understanding not just of DNA, but of RNA as well.
To continue the book metaphor, think of an organism’s DNA as a very expensive, rare edition; it is the original version of an organism’s genetic story. If it is changed or damaged (if it “mutates”), the organism may no longer be the same.
RNA is like a photocopy, a “transcription,” of paragraphs out of this rare book: it is not the original version, but it contains all the genetic information contained by a short section of the DNA. Unlike DNA, RNA has the capacity to travel: it can move outside the cell’s nucleus, into a cell’s cytoplasm, or it can travel between cells. Some recent studies have even shown RNA moving between organisms. Once in the cytoplasm, the RNA can be “translated,” converting the genetic code into a language made of different letters, the twenty amino acids that make up proteins. These proteins interact with and can make or modify other proteins, lipids, and carbohydrates—an organism’s plumbers, carpenters, and electricians—that carry out the work of a cell.
Here’s how it works: Just as it does when a cell begins to replicate itself, a sequence of DNA that is being transcribed first unwinds inside the nucleus. But in this case, rather than replicate into an identical double helix of DNA, one strand of the DNA falls to the side, and the other serves as a template for a new strand of RNA. This “transcript” resembles DNA in almost every respect, except that the RNA contains the nucleotide U (for uracil) instead of T. So a DNA strand of AGCT would be transcribed into an RNA strand of UCGA.
Once the transcript of the RNA from the gene is complete (its start and expression activity determined by the “promoter” at the beginning and its length determined by the “terminator” sequences at the end of the original strand of DNA), the single strand of RNA separates from the single strand of DNA, which then twists up again with its original mate. The strand of RNA (known as messenger RNA, or mRNA, for the protein “message” that it encodes) then migrates outside the nucleus, where it binds to a ribosome and the ribosome begins (with the help of transfer RNA, or tRNA) to “translate” the information the mRNA contains from the DNA into the language of amino acids.
But it gets more complex still; it turns out that the Central Dogma—DNA makes RNA, RNA makes proteins—may have been a bit too dogmatic after all. There are RNAs that influence gene expression that are themselves influenced by small or micro RNAs. Some scientists estimate that, in the human genome, a third of all genes may be regulated by micro RNAs—amazing given that no one even knew about them twenty years ago. And the growing field of epigenetics has shown that gene expression can be determined not just by genetic information alone, but also by stored chemical influences from outside a cell, or even outside the organism. (Some research suggests that even mental health and stress affect an organism’s genetics and its offspring via epigenetic mechanisms, though there is still much to learn about this.)
Understanding the science of the genome and genetics is vital to the GMO debate. Genetic engineering is fundamentally different from conventional plant breeding. With conventional breeding, you take pollen from one plant and put it on the stigma of another, and hope for a beneficial outcome. It’s a comparatively uncontrolled process, and in some cases, depending on the complexity of the trait you’re studying, you don’t know if you are going to find what you’re looking for.
Typically, when you have a breeding program, you’re trying to improve the bearing height of a tree, or the taste or texture of the fruit, but there are a million other things going on at the same time. There’s never really proof that something will work, there’s only history—these combinations have worked this way in the past. But within this process there remains a degree of mystery. Flower color and disease resistance can be predicted pretty accurately, because they’re controlled by just one or a few genes. But yield and adaptation to environment—these are much more complex be
cause they involve multiple controlling genes and are influenced by environmental conditions. This work requires many more plants and growing them in numerous locations.
Exploring these complexities, especially at the level of small RNAs, is what interests Blake Meyers. Working with colleagues from Stanford and UCLA on a sizable grant from the National Science Foundation, Meyers recently helped sequence the small RNAs in the genes of corn anthers, the male reproductive organs in corn plants. He and his colleagues are also creating an “atlas” of the small RNAs in different plant organs, tissues, and cells; they have worked out a spatiotemporal map of these molecules in the anthers to help them understand how, where, and when they develop and function in maize reproduction.
“The work is slow, tedious, and expensive at this point, so we only design the experiments that we think will tell us something really useful,” Meyers said. “You never know where the breakthroughs will come for practical purposes. Who knows when we’ll find a key regulator that will fix drought resistance or assist with fertility or hybrid seed production? The odds of one lab finding it are low, but multiply that by the hundreds of labs doing this type of work, and I’m optimistic that the field will come up with some important solutions. The rate of discovery is good and picking up speed.”
Working backward, then, the science of gene sequencing is the effort of pulling apart the genetic book to examine how its individual chapters and sentences and words are constructed and arranged. How does their order affect the behavior of the organism as a whole?
This is the mysterious world that Blake Meyers has spent his career trying to penetrate.
“Remember, there are millions, billions, or even trillions of DNA/RNA/protein/gene-expression processes under way that led to every bite of food that you eat, from every plant or animal that has been consumed in the history of the world,” Meyers told me. “I would say all but a relative handful of those have never been studied, perhaps never even characterized, and perhaps vary from one bite of food to another.”
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