The GMO That Needs Us BY MONICA KORTSHA Illustrations by Douglas Pollard
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f humans were to disappear, our pets and livestock would live on by returning to the self-sufficient ways of feral relatives. Housecats would start hunting in earnest; domesticated dogs would scavenge on the waste we left behind; and horses left in pastures and paddocks would go the way of wild Chincoteagues and Mustangs. Through interbreeding and natural selection, distinct breeds would be replaced with wild varieties that show that—even after thousands of years of selective breeding—almost all groups of domesticated animals can still fend for themselves, that the survival instinct is still intact. The glaring exception to this is a plump, powdery-white insect: the Bombyx mori, or domesticated silkworm, the only completely domesticated animal on the planet. Without humans around, it would be gone in a matter of days. For more than 5,000 years silkworms have been selectively bred to do two things: spin cocoons, which are unwound to make silk thread, and make more silkworms. As a result, features that the domesticated silkworms used to share with its closest wild ancestor, a silkworm called Bombyx mandarina, have atrophied. The mori has lost its color, can’t climb well, and, most necessary for independent survival, won’t forage for food. The silkworms must have a meal of fresh mulberry leaves delivered every few hours to the flat enclosures where they’re raised. In fact, they expect it. “They’ll stand in place, raise up, and swing in a circle, waiting to be fed,” said Michael Cook, a hobby sericulturist. “They won’t leave the leaf they’re on for another unless the leaves are touching.”
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Cook raises domesticated silkworm varieties, as well as wild, silk-producing caterpillars that are native to the U.S. Each spring he sets aside a month to rear about 2,000 Bombyx mori silkworms, which he calls his “tiny masters” because of the care they demand. In the four weeks it takes for the silkworms to go from tiny black hatchlings called “kego” (Japanese for hairy baby) to cocoon-ready, the worms go from once-daily feedings to being fed four times per day. After spinning itself inside a cocoon, the silkworm begins its transformation into a silkmoth. Only a small portion of silkworms complete metamorphosis— reeling silk requires boiling the cocoon and unwinding the silk from around the pupa like bandages from a mummy. But those that make it show, like the larva they came from, evident signs of human selection. While the Bombyx mandarina moth is angular, camouflaged and airborne, the Bombyx mori is globular, a similar shade of white as the worm, and stranded; The Bombyx Mori silkworm.
Mythic Origins
The Bombyx Mandarina moth.
they’ll vigorously buzz their wings but can no longer fly. It’s a trait that’s assisted arranged mating for centuries, helping boost the chances that desired traits are passed to the next generation, which emerge from brown pinhead-sized eggs that female moths deposit from oversized abdomens. The silkworm’s total dependence on humans is a testament to the power of selective breeding over time. Through it alone, humans have created a biological silk-making machine that has churned out the luxury fiber for millennia. But with the advent of hereditary research and gene-editing technology, science and industry are finding new uses for the silkworm and are leveraging its silk-spinning ability to new ends—creating silk that fluoresces, contains spider silk proteins, or other chemical building blocks that can be used to make new materials. The silkworm is a genetically modified organism that fits all definitions of the term, being shaped by traditional breeding and biotechnology. The relationship humans have with the silkworm has changed, too, going from being a secret known only to royalty to having its genetic instructions made part of the public domain.
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According to Chinese legend, the domestication of the silkworm began 5,000 years ago when a cocoon fell into a cup of tea belonging to Empress Leizu, the wife of the legendary Yellow Emperor. Noticing the cocoon’s loosened threads, the empress tugged on a strand and unwound the first cocoon into silk thread. The discovery set in motion sericulture in China. But the link between silkworm and silk was kept a secret to those outside of China for over 2,500 years after silk-winding technology was developed. Revealing the source of silk was considered a crime punishable by death, so alternate explanations for the lustrous fabric arose. One Chinese traveler is said to have told all foreigners that silk sprouted from a sheep fleece that was sprinkled with pure water while exposed to sunshine during a certain time of the year. Pliny the Elder, the Roman natural philosopher and historian, thought silk was collected from an especially downy kind of leaf. The explanations don’t sound so outlandish when one realizes the true source of silk is essentially worm spit (which is also the name of Cook’s silkworm blog) spewed by spinnerets located on the silkworm’s jaws. The secret of silk’s true origin came to an end with trade along the Silk Road. As merchants brought silk fabric from China to the Middle East and Europe, smugglers spread the silkworm with it. One legend describes a betrothed Chinese princess bringing silkworm eggs and mulberry seeds to her new home hidden in the folds of her turban. Another speaks of monks from Constantinople sneaking away silkworm eggs in the hollows of their bamboo walking sticks. Silk even spread to U.S. colonies, a crop that the British crown encouraged because it kept the colonists dependent on
its cocoon-processing equipment. And although colonists had largely traded silkworms for cotton and tobacco by the end of the American Revolution, Martha Washington wore a gown made of silk grown, reeled, and woven in Virgina to her husband’s inauguration as the first president of the U.S. Since its discovery, silk’s smoothness, luster, and rarity has linked it with luxury. For most of that time, the silkworm selection was constant, too. The silkworms that spun the best cocoons and exhibited the most desirable traits were bred to make the next generation. This selective breeding by visual observation was effective over time; all the most noticeable features that separate the Bombyx mori from the mandarina were honed through it. However, in the early early 20th century a Japanese agricultural scientist introduced a new method for selecting traits in silkworms that led to results faster, and changed breeding methods that had stayed the same for thousands of years.
for exploring heredity at the time,” said Lisa Onaga, a professor at Singapore’s Nanyang Technology University who studies the development of scientific information. “It was a very accessible organism, something that everyone was interested in, in order to understand how to make use of its nature.” By crossing silkworms from Japan with those from Thailand, Toyama showed that transmission of cocoon color follows Mendel’s laws, while revealing that the hybrid offspring were healthier and made higher quality cocoons than either of their parental strains, an example of what would come to be known as “hybrid vigor.” The discovery prompted the Japanese government to start hybrid
More than Mendelism
The rediscovery of Mendel’s laws of inheritance in the early 20th The Bombyx Mori century brought a new permoth. spective to breeding plants and animals. The laws described how organisms could pass traits on to their silkworm raising programs in 1911. offspring without expressing the trait By 1929, 100 percent of the country’s themselves, and how the percentage of recorded silk crop came from hybrids. offspring that would express a certain Along the way Toyama also encountrait could be predicted. tered inheritance patterns that deviated Japanese agricultural scientist Kamefrom Mendel’s predictions. Female taro Toyama, the founding headmaster moths that laid eggs that were always of the Fukushima Sericultural School, the same color as the egg they hatched thought that understanding how from were a clear exception to Mendel’s silkworm traits fit into the Mendelian dominant and recessive traits. And framework offered a way to boost silkgynandromorph mutants—worms that worm production for a newly industrialwere bilaterally divided into female and ized Japan. male sides— raised questions about “The commercial significance of [the selective expression of maternal and silkworm] made it really useful as a site paternal genes in different parts of the
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body. Because Toyama published his findings in English, other hereditary researchers around the world took notice of his work. Thomas Hunt Morgan cited Toyama’s observations on gynandromorphs as influencing research that led to the discovery of chromosomes as storehouses for genetic material—a finding that won Morgan a 1933 Nobel Prize and began the transformation of hereditary science into modern genetics. Toyama also communicated the concepts of his science directly to Japanese farmers who raised silkworms and other crops. But instead of talking about Mendelism, Kametaro talked about “honshō”—a term he coined to explain the range of traits an organisms could express. By understanding honshō, individual traits could be amplified, quieted, or expanded through careful breeding, a concept Toyama demonstrated through his own silkworm experiments. He split a strain of silkworm that made regular brown eggs into sister strains that produced a variety of egg colors, and mixed the domestic Mori with the wild Mandarina to create a hybrid he dubbed a “kuwago.” Through the concept of honshō, Toyama emphasized that organisms have the potential to undergo great change, but that there are also limits to what’s possible. “It’s the same idea behind the fact that an eggplant can’t grown from a watermelon seed, but a tadpole can become a frog,” Toyama is recorded to have said when describing honshō to an agriculture association in Niigata, Japan
way. These varieties aren’t bred in the traditional sense, but precisely engineered using gene-editing technology that has led to the creation of silk that’s valuable for more reasons than making luxurious robes or gowns. Experimental silkworms are producing silk laced with spider proteins, making it strong enough for body armor and flexible enough to reinforce tissue in medical applications. Other research involves engineering silkworms to produce cocoons coated in human proteins such as collagen, which can cleanly be collected from the cocoons during the silk-reeling process. While gene-insertion technology is creating silkworms with new functions, gene-sequencing technology is revealing how thousands of years of selective breeding have impacted the silkworm at a genetic level. A study comparing the genomes of the Bombyx mori with those from the mandarina found that 3 percent of the Bombyx mori’s genome has been changed by domestication, with most of the gene functions being related to reproduction and silk production. To put that change in perspective, the human and chimpanzee genome differ by about 2 percent. Value in Variation
Biotech Mori In the past 25 years, silkworms with new silk-spinning abilities have appeared, expanding the domain of “honshō” as Kametaro knew it along the
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Gene-transfer technology goes both ways. Just as it’s possible to put new genes into the silkworm, it’s also possible to insert the silkworm’s silk-making genes into a host that can make silk in batches larger than a peanut-shell-sized cocoon. That sort of transfer has already happened for spider silk proteins. Since the early 2000s, Randy Lewis, a professor at Utah State University, has been producing genetically modified goats that express spider silk proteins in milk. Machine processing turns the proteins into thread.
The goats have become conceptual poster-children for the possibilities of genetic engineering, but don’t yet produce spider silk proteins at a level that is commercially viable. For that role, some researchers and biotechnology companies have turned to genetically modified yeast or bacteria to pump out the desired protein. Raised in large vats and fed simple nutrients, these microorganisms are much simpler to keep than goats and silkworms alike. However, Katsura Kojima, a scientist involved with transgenic silkworm research at the Silk Materials Research Unit of Japan’s National Institute of Agrobiological Sciences, says he doubts that silkworms would ever be replaced. They’re just too good at spinning silk, he said. “The silkworm is an advanced organism just for silk production, they are not dispensable,” he wrote in an email. On another note, genetically modifying yeast or bacteria to do what silkworms have done for millennia would, for the first time, disconnect silk from the life cycle of the silkworm. For silk aficionados like Cook, however, the worm’s role in the process is part of what makes silk special. “Silk has a feel to it, sort of a spirit to it that you can’t get from the lab,” said Cook, who has worked with samples of lab-produced spider silk. “It’s got variation, some shapes that are created by the caterpillars spinnerets, it’s got characters that are a little bit different.” Silkworms may have been bred to be silk-making machines, but they still produce enough variation to notice, to select for, and appreciate. And although scientists are now applying the silkworm’s silk-spinning abilitiy to new ends, they’re continuing an ancient tradition of transformation. This close relationship—starting with a legendary tumble into an empress’ teacup, and persisting for millennia—stems from the silkworm’s malleability, for its
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receptivity to genetic modification by any means. This ability to change with us will keep the silkworm around as long as we humans want to care for it. But not any longer than that.
REFERENCES 1. Franck, Robert R. Silk, Mohair, Cashmere and Other Luxury Fibres. Boca Raton, FL: CRC/Woodhead Pub., 2001. Print. 2. Leggett, William F. The Story of Silk. N.p.: Lifetime Editions, 1949. Print. 3. Ma, Debin. “Why Japan, Not China, Was the First to Develop in East Asia: Lessons from Sericulture, 1850–1937.” Economic Development and Cultural Change 52.2 (2004): 369-94. JSTOR [JSTOR]. Web. 4. Onaga, Lisa. “More than Metamorphosis: The Silkworm Experiments of Toyama Kametarō and His Cultivation of Genetic Thought in Japan’s Sericultural Practices, 1894–1918.” New Perspectives on the History of Life Sciences and Agriculture. N.p.: Springer, n.d. 415-37. Print. 5. Xia, Qingyou. “Science.” Complete Resequencing of 40 Genomes Reveals Domestication Events and Genes in Silkworm (Bombyx) 326.5951 (2009): 433-36. Web.