The Stem Cell Hope, page 23
When I arrived, I was shown into Hwang’s office—a small, crowded room with a single window—which also doubled as his assistant’s cubicle. Crammed near the door, oddly, were a small sink and mirror, along with two sofas arranged around a low table. There was no private washroom for Korea’s most celebrated scientist, apparently, but he did have his own sink for freshening up and brushing his teeth after meals, a habit about which he was apparently obsessive. His bookshelf included Christopher Reeve’s Still Me, as well as texts on veterinary science and cell biology. Sitting in small frames on the shelves that blanketed an entire wall of the small space were pictures of Hwang with a cow—the first successfully cloned Korean species—and various plaques lauding his scientific prowess. Apologizing for his poor English, Hwang invited a collaborator, Dr. Sung Keun Kang, another veterinarian in the department, to begin answering my questions.
Kang, a bespectacled, friendly man in his thirties, seemed well versed on the ins and outs of nuclear transfer. As a coauthor of Hwang’s 2004 paper, he detailed for me what he described as the innovations that the team had made in order to achieve their success with the human cells. He fleshed out some of the details from the Science publication, explaining how they took eggs donated by Korean women, removed their nuclei, and replaced each one with a donor’s skin cell. He brought up the chopsticks—how the dexterous and steady hands of the students gently squeezing the delicate eggs was the key to keeping the eggs intact and more willing to welcome their newly donated cargo. He then described how they played with waiting for different lengths of time between inserting the nucleus and activating it with a special brew of chemicals to start dividing. They waited for two, four, and six hours, and found that two hours was ideal for pushing the egg to transform itself into a dividing embryo. Kang proudly explained how after experimenting with different cocktails of chemicals the group also honed in on the best activation protocol for the human eggs. “We achieved maximum activation of 29 percent of eggs, which is almost what we obtain from bovine and porcine oocytes,” he said. Nineteen of the sixty-two oocytes that were successfully fused with their new genetic cargo began dividing.
As Kang talked, he became more excited, pointing out exactly where in the process he and his colleagues hoped to boost the efficiency even more. They had used 242 eggs to obtain one supposedly viable stem cell line, making the nuclear transfer process much less efficient than the already inefficient process of using IVF embryos.
“From IVF embryos, we can derive at least two stem cell lines from every five embryos,” Kang told me, making it clear that the team was on par with the rest of the world as far as its stem cell derivation skills. Their success, he claimed, lay in how they extracted the stem cells from the ball-shaped blastocyst. Some researchers were using immunosurgery—targeting the outer layer of blastocyst cells, which did not contain any stem cells, with antibodies that would recognize them, bind with them, and then kill them off, leaving behind the stem cells. Others relied on a waiting game, holding off on doing anything until the blastocyst naturally “hatched,” or attached itself to the uterus, at which point researchers mechanically sliced off the inner cell mass containing the sought-after stem cells. Hwang’s group used an amalgam of both of these methods, allowing the age and condition of the blastocysts to dictate which strategy would yield the most cells with the least amount of disruption.
Kang then went on to describe the most significant step in the process: confirming the identity of the stem cells. Like Thomson and Gearhart, in his paper Hwang detailed how the cells he grew in culture were able to form teratomas containing the three primitive germ cells that eventually give rise to all of the body’s tissues. On paper, at least, it looked as if he had generated stem cells.
Following the biology lesson, Hwang was ready and eager to lead me through a tour of his lab. What I saw during that visit was the animal half of his operation, which was confined to one side of a hallway that bisected the sixth-floor lab space. On the other side was a far more restricted area visible only through a small window cut into the hallway wall. It wouldn’t be until my second visit, several months later, that he would allow me into this sanctum of human embryonic cells.
On that first visit, the animal lab was buzzing with activity; in the first room, about fifteen identically clad technicians in blue gowns were busy with cow and pig ovaries. Hwang received fresh ovaries from slaughterhouses three times a day. The organs arrived in thermos-like containers and were first cultured for twelve to forty-four hours to help the oocytes inside to mature. Then the students extracted the eggs, by hand, in a laborious and tedious process.
In a second, darker room illuminated only by the glow from eight heavy microscopes, a handful of students were putting their chopstick skills to good use, gently pricking the animal eggs and then squeezing out the genetic material. The eggs seemed to lose their filling the same way a jelly doughnut does with a bite. Using the same slit from which the gene-laden nucleus had just exited, Hwang’s students then injected a new cell, nucleus and all, to replace the oocyte’s missing DNA. The combination was then zapped with a jolt of electricity to fuse the disparate parts together. Chemicals then nurtured the hybrid to begin dividing. In five to six days, presto! A dividing embryo that was ready to be implanted into a surrogate animal’s womb in hopes of creating a clone.
Because nurturing cells is a twenty-four-hour, 365-day-a-year process, “there is no holiday in our lab, even on Korean Thanksgiving or New Year’s Day,” Hwang said. Then he laughed with the easy humor that endeared him to all who had met him. “A foreign scientist once called my lab the troops, and me the commander.”
It’s an interesting metaphor, and one that would prove prophetic in the following year, as revelations about misconduct in the lab exposed the extent to which the hierarchical structure of academic research departments and the cultlike devotion that Hwang inspired among his lab members contributed to a sense of invincibility that may have led to his downfall. For most of the students Hwang was like a second father, often referring to them with the Korean word for “children” and worrying about the extended hours they spent cooped up in the sixth-floor labs.
Jiho Choi, a master’s candidate at the time, remembers Hwang’s generosity when we talk about his former mentor years after Choi, now earning his Ph.D. at Harvard, graduated. “He was more than just a principal investigator,” he says. “He paid the tuitions of students and also a small stipend for room or a dormitory to live in for people who came from [distant] provinces. He did everything for us.” Hwang’s goal, says Choi, was to provide an environment where students would feel encouraged and inspired to focus on research without getting distracted by practical concerns, so he could seed a new generation of stem cell scientists in Korea. “If I had some problem or a difficult situation, then I could talk to him,” Choi says, still using the Korean honorific sunsengnim to refer to Hwang, a sign of respect for an accomplished and well-liked superior.
Over lunch at the faculty’s Chinese restaurant on campus, Hwang explained why, despite the added attention from a proud nation, he preferred to keep his lab small—his core team, not counting collaborators from other departments in the university, remained about the same size as it had always been: forty-five members. “In our opinion, this work must be done by hand,” he said. “This kind of work, you need to insert the spirit, and use not only machines, but the heart and spirit. You need a human touch.”
It was the first hint of spirituality Hwang had expressed. Like many Koreans he was a devout Buddhist who often traveled to temples for ritual spiritual cleansings and moral guidance. And as is the case with many scientists in the stem cell field, he had made his own peace with the apparent conflict between what he did in the lab and his spiritual perspective. In his view, he explained, the purpose of his work—to improve agricultural stocks, in the case of his animal studies; and to contribute to new treatments for disease, in the case of the human stem cell work—made the moral challenges justifiable.
As we picked our way through the traditional Korean meal of rice, banchan side dishes, and soup, I asked him about the one issue that puzzled many of the Western scientists struggling to do the same thing he was. Where, I asked, was he getting so many eggs?
Hwang talked about the unbelievable amount of support and attention his lab received in the aftermath of the breakthrough. Even before the paper was published, he told me, the generosity of women eager to contribute to the research provided him with enough eggs to practice and perfect the finicky technique of nuclear transfer with human cells. In complete contrast to the challenges the Harvard team was facing, Hwang, it seemed, had more than enough human volunteers for his stem cell studies.
Following lunch, Hwang had planned a trip to the pig farm, where he intended to perform one of the hundreds of embryo transfers that his team conducted every day to grow clones. “He can do the transfer in twenty seconds,” Byeong Chun Lee, a close collaborator, informed me, clearly impressed. “Watch him. You will be surprised.”
But going anywhere with Hwang was not a simple thing. Like the president, Hwang moved with a security detail, including two bodyguards assigned to him twenty-four hours a day. Aside from driving him to the lab every morning, they also accompanied him on trips overseas, where he was becoming a popular conference speaker. During the day, they haunted Building 85, alternating between the elevator on the sixth floor and the garage beneath the building, where Hwang’s car was always at the ready. They came courtesy of none other than former president Roh Moo-hyun himself. A little embarrassed, Hwang admitted that he initially refused them, but apparently it’s difficult to turn down the president.
As soon as we emerged from the cramped streets of the city, the landscape began to change. The urban collage of neon, glistening steel, glass, and concrete was gradually subsumed by thicker growths of trees and what seemed like endless stretches of farmland. Lush rice paddies blanketed much of the scene that rushed past our windows. As the last vestiges of Seoul slipped by, the increasingly pastoral landscape must have reminded Hwang of his own childhood home in the countryside, and he started to open up about his remarkable road to science superstardom.
Hwang was born in 1953 in Chungnam, South Korea, a rural province three hours outside the country’s capital. It was just after the Korean War, and like many families not fortunate enough to be living in metropolitan areas such as Seoul or Busan to the south, where jobs and economic recovery came more quickly, the Hwangs barely had enough to eat. His father passed away when he was five, leaving his mother to raise her brood of six children alone.
For families such as theirs, farm animals were the key to survival. Young Woo Suk quickly learned to love his duties caring for the three cows the family managed to obtain. “Even those,” he admits, “were not really our cows; we rented them from our rich neighbors.” The young boy, just tall enough to look a cow in the eye, felt a special affinity for the animals, and would talk to them constantly, vowing always to look after them. There was something about their serenity that appealed to him, and the daily task of feeding and cleaning up after the animals may have given the young Hwang a sense of rootedness. It was during those afternoons in the company of cows that Hwang began to dream of becoming a veterinarian.
In high school, Hwang’s grades were good enough for his teachers to suggest that he consider medical school at Seoul National University, the nation’s most esteemed college. Competition for admission to SNU was fierce, but the studious boy earned one of the coveted spots in the freshman class of 1977. In one of his first acts of stubborn defiance, however, Hwang refused to become a doctor. Instead, he enrolled in SNU’s veterinary school, still determined to study animals. After earning his Ph.D. in animal reproduction, he left Korea for the first time, hopping over the Sea of Japan for a fellowship at Hokkaido University. As a fellow, Hwang became interested in the delicate process of embryo splitting. It was something nature did on its own every once in a while, in producing identical twins. But Hwang wanted to bring more consistency to the process. It was his introduction to cloning.
When Hwang returned to Korea, he came back to his alma mater. Growing up in Chungnam, he says, there were only two things he had desired—to become a scientist, and to become a professor at SNU. He arrived with valuable skills and an understanding of how to optimize the reproductive process. His goal was to improve the yield of milk and meat production in cattle—something farmers and agricultural experts had been seeking for centuries. Hwang thought he could do it with the help of technology, by applying what he had learned in the lab to the barn. He wanted to clone the most desirable cows—the “elite” animals—and thereby seed the Korean cattle population with only the premium producers of milk and meat. In 1993, he produced the first test tube cow, using in vitro fertilization to inseminate a bovine egg in a dish and then transferring the resulting embryo into the womb of a surrogate cow for gestation.
Two years later, Hwang managed to successfully split an embryo and produce the first cloned cow in Korea. But embryo splitting wasn’t truly cloning. Technically speaking, it was twinning with a hand from science. Then came news from Scotland of Wilmut’s success in producing Dolly, a true mammalian clone who was the exact genetic copy of an adult ewe. As it did for so many scientists in the field, Dolly’s existence had a profound impact on Hwang’s thinking at the time. Her birth convinced him that more wide-scale cloning of animals, using nuclear transfer, was possible.
Applying the technique to cow eggs, in just two years Hwang had his own cloned cow via nuclear transfer. But he never published his experiment in a scientific journal, choosing instead to announce the birth in the press—the first cloned Korean cow, Hwang said, as a gift to the Korean people—complete with photo ops. Other scientists could neither confirm nor deny nor learn from his attempts.
Halfway into our journey back to the labs, I asked Hwang about the challenges of keeping human embryonic stem cells happy—of maintaining the cultures so they remain pure and stemlike, resisting the urge to differentiate into some other cell.
He nodded, reflected a bit, and then responded. “I always worry about contamination,” he said. “Especially in the human stem cell lab, because I had a painful experience. Some human embryonic stem cells became contaminated, and were discarded. It took six months to get over the contamination.”
It was a surprising revelation, and if true, a potentially telling one given the events that transpired over the next six months. Losing stem cell lines is a big deal, but losing human embryonic stem cell lines is a disaster. Human eggs are difficult enough to come by for a research lab, and even Hwang’s efficiency at the time in turning those eggs into stem cells was pretty dismal: He reported in 2004 that it had taken 242 eggs to produce one stem cell line.
I asked how many lines were destroyed.
Some, but not all, he answered. Construction on the ventilation system in the building had apparently contaminated the relatively sterile lab; pathogens in the air that wouldn’t bother the average person could settle onto a cell culture and wipe out the colony.
Following that mishap, the government stepped in, quickly renovating the space with a more reliable ventilation system and creating the separate, strictly controlled space that became home to the human side of the stem cell lab. At that point, anything Hwang wanted, Hwang got.
It was astounding that a scientist could hold that much influence with the country’s top political leaders. But that was the nature of Hwang’s new stature in Korea. He was by then no longer simply a scientist, or even a professor at the nation’s most competitive university. He was a national hero, and for better or worse, an icon both for what Korea was and for what it wanted to be. A month after my visit, the title of “supreme scientist” of Korea was bestowed upon Hwang, a new honorific concocted by the government to recognize his efforts in leading the nation onto the world’s scientific stage. In Hwang, President Roh saw a chance for Korea to finally step up to the head of the line and bring the rest of the world along—behind it. With stem cells, Korea had an opportunity to establish an infrastructure and expertise that Roh and his administration thought would yield dividends both financially and politically in the global economy.
But it wasn’t just political opportunity that Roh seemed to see in the veterinary scientist. Roh, like Hwang, was a self-made man who had grown up in poverty, and worked his way through law school. In Hwang he had found a brother, a kindred spirit who had earned his way into the upper echelons of power and influence in a hierarchical society where such feats were rare, if not unheard of.
“President Roh said to me, ‘I want to be recorded as the president who concentrated on developing science and technology,’ ” Hwang told me, before adding with a trace of boastful pride, “I promised him [he would] be.”
At the time, I didn’t appreciate the full import of Hwang’s words. But they would prove pregnant with deeper meaning. In 2009, Roh committed suicide in the midst of a bribery scandal. And that promise, and the expectations inherent in the pledge, may have been the beginning of the end for Hwang.
“I got the impression he was under tremendous pressure,” says Insoo Hyun, who spent the summer of 2005, the height of Hwang’s popularity in Korea, in the cloning lab. A professor at Case Western Reserve University, Hyun traveled to Seoul on a Fulbright-Hays Faculty Research fellowship to study the informed consent process in Korea. Like many others, he was interested in learning how the Koreans were able to obtain so many eggs from female volunteers for their stem cell work, and how the informed consent process was set up to protect donors. Why, he wondered, had the breakthrough occurred in Korea? Why were so many women there willing to donate eggs for research?
