by Tracie White
“In 1955, when I was 14,” Ron replied. The chemist just shook his head in disbelief.
Over the many nights he spent reading journals in the dark, Ron had discovered another chemical compound powered by nitrogen like his rocket fuels that caught his interest, and slowly a new fascination began to take hold.
“That’s when I stopped making rockets and started reading about DNA and about Watson and Crick, who discovered the structure of DNA,” he said. Nitrogen is one of the building blocks of the four bases that are part of the DNA molecule.
The year was 1955. During the decade following the end of World War II, what Ron didn’t know was that a revolution was occurring in the world of science. Almost a century had passed since the discovery of units of heredity called genes had been made by the monk Gregor Mendel in 1865—in experiments crossbreeding pea plants. Until the 1940s, little more had been known about how these genes worked. In the years after the war, the federal government took note of the power of science to keep the nation strong. And federal health agencies like the National Institutes of Health emerged with federal dollars to spread to researchers at home and abroad.
The NIH actually traces its roots back to 1887, when it was just one institute housed in a single room before moving to its current campus in Bethesda, Maryland, a former estate. In 1940, President Franklin Delano Roosevelt, speaking from the steps of the most stately of the campus buildings, dedicated a new cancer institute and ushered in an era that would expand the institute into today’s twenty-seven institutes of health.
On the verge of the US entering World War II, Roosevelt gave a prescient speech to the country from those steps, spotlighting the importance of public health to the security of the nation.
“We cannot be a strong nation unless we are a healthy nation, and so we must recruit not only men and materials, but also knowledge and science in the service of national strength,” he said into a cluster of microphones. He then offered prophetic words of warning on the future dangers facing any nation ill prepared for public health disasters: “Now that we are less than a day by plane from the jungle-type yellow fever of South America, less than two days from the sleeping sickness of equatorial Africa, less than three days from cholera and bubonic plague, the ramparts we watch must be civilian in addition to military.”
Researchers, many of them at the country’s most prestigious universities, with new federal research dollars, made new discoveries about the inner workings of genes. First, it was discovered that the method used by genes for exchanging genetic materials was achieved through a large molecule made up of sugar, bases, and phosphoric acid, known as deoxyribonucleic acid, or DNA. By the 1950s, the hottest story in the world of science consuming scientists across the globe was the race to uncover the molecular structure of DNA. Understanding its structure was the first step toward understanding how DNA worked and thus the key to human life.
When the double helix, the twisted-ladder structure of DNA, was finally uncovered with much fanfare in 1953 by scientists James Watson, Francis Crick, and Rosalind Franklin, it set the world of science on fire.
Reading by flashlight in the university library stacks late at night, Ron had stumbled upon the building blocks of human life. And he was hooked.
Meanwhile, what no one realized, not even Ron himself at the time, was that during all those months spent trapped sick on the couch, unable to go to school or play in the woods, he had begun developing unique skills that would enable him to use his brain in strange and new mind-bending ways. Ron had learned skills that would make him a great scientist one day.
In the evenings, he’d join the family to listen to the old-time radio shows like Fibber McGee and Molly, The Green Hornet, and The Lone Ranger. But during the long daylight hours, when he was lonely with nothing to do, he figured out that if he concentrated really hard he could create far more interesting worlds to escape to deep inside his brain.
“I could literally become any size or shape I wanted,” he said. “I could make myself an ant and crawl through the outlet and explore the copper circuits inside the walls. It required me to create images in 3-D so that I could rotate things in my brain. But anything spatial was always very easy for me. It defied the laws of physics. I’d love to get into that state. I’m sure it was some kind of self-hypnosis or meditation because it would really feel real. I didn’t realize I was actually developing these spatial skills that would help me someday as a scientist.”
When the family bought one of the new black-and-white TVs, he started waking up on his own at six a.m. to watch educational programs on chemistry and physics. And when he got pocket money from working for his dad, he spent it on chemistry and physics books, staying up late at night reading, completely absorbed by the sciences. Since math was helpful in understanding this new world of chemistry, he asked his sister to teach him all the math she was learning in school. Patty, who didn’t want her younger brother to be stupid forever, got out a chalkboard one day and willingly began to oblige.
When Ron entered high school, his reputation as a low achiever had already been cemented. His guidance counselor told him he wasn’t college material and signed him up for shop class. He said OK, but he also wanted to take algebra. When the counselor said no, he wasn’t qualified, Ron showed up to class anyway, eventually forcing the counselor to register him for the class. The same thing happened the next year with chemistry. And it was there he began to really shine. Remembering molecular structures was a breeze by then, and his chemistry teacher didn’t care that he didn’t know how to spell.
In 1960, when it was time to graduate from high school, it was Ron’s biology teacher, Charles Compton, who, along with his chemistry teacher, told him he had to go to college.
“I was not even thinking about going to college,” Ron said. “I was thinking about trying to get a job at a chemical factory. The guidance counselor said he wouldn’t help me get into college or get a scholarship because I was a waste of his time. But based on my vocational and other test scores I had the aptitude to be a carpenter or a mortician. My English teacher sympathetically told me, ‘Oh no! You shouldn’t go to college. You’ll never make it.’ But Charles Compton told me, no no, you’ve got to go to college. Fortunately, the town had a college, and I knew the library there quite well,” he said chuckling. By then, Ron had been sneaking into the college library at night for years. Patty, who had always thought of her little brother as something of a wuss, admired her older brother, whom she described as being like “James Dean in the movie Rebel Without a Cause.” Who knew Ronnie was the real rebel after all?
Ron’s dad was totally opposed to the idea of college, but he said he wouldn’t stand in his son’s way. He would allow Ron to keep living at home for free and attend the nearby Eastern Illinois University, but Ron had to pay the tuition and fees. So Ron found a way to rent textbooks to save money and quickly got a job on the college campus working in the chemistry department’s stockroom. “Of course, I explored every chemical there,” he remembers all these years later with unrestrained glee. Next, he proceeded to take every math and science class available on campus in order to balance out his poor English grades and keep a high grade point average. He ended up qualifying for degrees in math, chemistry, physics, and botany.
“It was my physical chemistry teacher in college who said, ‘You have to go to graduate school,’” Ron said. “I assumed he meant the University of Illinois in Urbana, but no, he said, ‘You need to set your sights higher. You need to go to Caltech or Stanford or Berkeley.’ I said, ‘What? You think I can get into those schools?’” Ron had dreams of moving out West, far away from his small town. It was the sixties. Out West, he imagined, there were all kinds of new worlds to learn about. He wanted to grow his hair long and meet a California girl. So he shrugged and went ahead and took the Graduate Record Examination (GRE) required for the application. When he got the scores back, he scored in the 99.9th percentile on the science and math portion of the test (Ron is still arguing a
bout that one question he missed). In the English section, he scored in the bottom 17th percentile.
Next, since applications to graduate schools were free back then, he sent his off to each of the three schools out West, along with the one in Illinois, and waited for rejections. When he heard he’d been accepted at all four, he was “blown away.” He’d read about a Caltech professor named Linus Pauling who’d won the Nobel Prize in chemistry. That impressed him, so he chose Caltech, got on a plane for sunny Pasadena, and never looked back.
Chapter 6
Blood Trails
THE STANFORD GENOME TECHNOLOGY Center is a modern office building with long fluorescent-lit hallways and a wide-open lounge space on the first floor, where Ron’s office is also located. Underneath this spacious lobby, in the basement is the “wet lab,” rooms where the science experiments get conducted under overhead hoods filled with expensive lab equipment like mass spectrometers, high-speed centrifuges, and high-tech microscopes along with many custom-built instruments unique to the lab.
It was first built for a now-failed Silicon Valley startup, Ron told me once when I asked why it wasn’t like the other science labs I’d visited on campus, which tended to be in older, darker buildings with lab equipment crammed into every open space. This building was spacious and had a high-tech feel. Ron told me the lab was first set up in a different building across town two decades after he got his PhD at Caltech. By then, Ron was well established as a tenured professor at Stanford and reaping the rewards of monumental discoveries made over his career in the field of genetics. Terms I didn’t yet understand like “sticky ends” and “polymorphisms” linked Ron’s name to the eventual launching of the Human Genome Project. He became codirector of the Genome Technology Center in 1989 and a few years later became director, remaining at its helm ever since, mentoring reams of PhD students and other young scientists as they’ve passed through the lab. It was his current cohort of budding scientists that Ron turned to in order to build an ME/CFS research team.
His first recruit was Laurel Crosby, an engineering research associate who knew Whitney back then as “the boss’s son” and the guy who did photography projects at the lab. She had been through a similar situation to that of Ron’s family: she had spent two years getting a rare diagnosis for her infant son.
“There is something about the feelings of helplessness that parents feel when their kids are suffering, no matter what their age,” she told me. “It wasn’t work at that point, just discussions about how to tackle something so baffling. Ron would later call ME/CFS ‘the last major disease we know nothing about’—an enigma just waiting to be solved.”
I first met Laurel during my research for the Stanford Medicine magazine article. Two years later, we crossed paths again in a hallway at the lab when I was there to sit in on one of the ME/CFS research team’s weekly strategy meetings. Laurel, whose dark, curly hair showed touches of early gray, stopped to talk.
“Hi Tracie, how are you?” she asked. “I’m glad you’re here.” She remarked, “This illness is like a jumble of hidden clues, so it’s like working on a giant puzzle.”
I told her that I’d decided to write a book about Ron’s story, that it was my way of helping, to spread the word about this disease, and asked if she had time to sit down and talk for awhile.
On a couch in an empty hallway, we sat together, me sipping coffee. I didn’t want to interrupt her work, but I also knew that all researchers love to talk about a project they’re passionate about. I’d talked to so many researchers at Stanford about their work and was inspired by the endless hours of tedious hard work they spent alone in their laboratories, sometimes working for years on end trying to solve some basic science question. It could take decades before their discoveries resulted in creating new treatments or curing disease. I was still hoping that potential treatments, even a cure, would come much faster than that for these ME/CFS investigations.
“How did you first get started researching ME/CFS?” I asked.
“One day Ron walked into the lab and handed me a box, asking me to study the specimen inside,” she said. “It was a box of Whitney’s poop!” We both burst out laughing.
When Laurel first started this investigation, the lab had little money for ME/CFS research, so most of the recruits had to carve out a few free hours from their other, better funded research projects. Because of the lack of funding, all that the small cohort of scientists could really afford at first was to study one patient. Luckily, Whitney had volunteered. He donated not only blood samples but urine, excrement, and saliva to the cause. Ron also planned to study all the microorganisms in his son’s gut, referred to as the microbiome.
“We were given a task,” Laurel said. “Our task was to get Whitney out of bed.”
Laurel, eventually joined by others in the lab, also volunteered to help with on-call pick-up duty when Whitney’s blood samples were ready, so that Ron and Janet didn’t have to drive over at night. Usually she’d be at work in the lab when she’d get a phone call from one of them in the late afternoon. She’d drive over to Ron’s house as quickly as possible, pick up the vials of blood, and speed back.
“When I got there, I would walk around to the back of their house to the screen door, and Ron would hand me a Ziplock bag with one or two tubes of blood,” she said. “It takes me about twenty-five minutes to get back to the lab, but worse during Palo Alto rush hour traffic, so I kept to the back roads with the Ziplocked bag tucked upright into my cup holder.”
Back at the lab, she walked briskly down the long, white hallways, to the stairway that led to the basement’s biohazard lab. There she pulled on a white lab coat and a pair of white plastic gloves and started the processing of the blood. Using a much fancier centrifuge than Ron kept in his toolshed back at home, she watched Whitney’s blood spin around as it separated into its separate parts—red blood cells, platelets, and plasma. Then she ran the different components through a saline wash three or four times. After counting each of the cells, she then handed off the suspension to a lab tech to continue the process. They further divided the blood into its even smaller parts—white blood cells and DNA.
“With Whitney having a messed up day-night sleep schedule, it meant that everyone else had to work nights,” Laurel said. “Essentially everyone was on standby.”
I had always been impressed by Laurel’s and the other lab members’ dedication to the work, but now I was even more so. Their investigation was motivated by more than scientific passion; it was motivated by compassion for the boss’s son.
When the job was complete, usually around seven or eight p.m., some of the blood samples got handed off to other lab recruits, who worked long into the early hours of the morning to get the job done.
While Ron and his team at the lab continued to build on their research findings, doing the best they could with what limited funding they had, Whitney continued to deteriorate. He stopped listening to music on his iPod. Only white noise came through his earphones now. The further Whitney slipped away, the more intense Ron’s research became.
Whitney had begun to write notes to his mother on index cards. Janet would cut dozens of them in half and leave short stacks held together with rubber bands on the left side of his bed within arm’s reach. When he could no longer write, he spelled out his needs using Scrabble tiles. Then there was almost a two-year period when he could no longer use the Scrabble tiles, and he stopped communicating at all.
Ron began to dream of science experiments at night, then wake up in the morning with a new piece to add to the ever-growing puzzle expanding in his lab. He’d fallen into a routine in which he would come home around four p.m., care for Whitney in the afternoon, hand over the caregiving to Janet for the night, and then go back to work, disappearing into the library with his laptop, lost in the science and hunting for answers.
Back at the lab, Whitney’s blood samples were being put through hundreds of thousands of tests, using the advanced technological equipment at hand. Wh
en that wasn’t enough, Ron sent off samples to other high-tech startups, often run by his former students, for other tests, including one to measure all the metabolites in Whitney’s blood. Or his lab would create new testing technologies. By now, the $3 billion cost to map one human genome had fallen into the thousands. Ron was able to get Whitney’s genome sequenced three, four times. Each time it came back, they ran it through more analyses, hunting for hidden viruses, bacteria, and genetic mutations. They were looking for abnormalities, defects, and any unusual patterns.
Finally, results began to come in. The scientists started to uncover abnormalities in the cells, including an overactive immune system and unusual gene mutations. Ron was already beginning to formulate his next plan for what he called a “big data” study. He wanted to run similar tests on twenty other severely ill ME/CFS patients like Whitney, as well as some healthy volunteers.
Much of science is based on replication of results and finding trends in larger population samples. Any single result needs to be tested over and over again before it can be trusted. Ron believed the molecular signals for this disease would be strongest in the most severe patients, like Whitney. No one had studied this group of patients before because they were housebound and couldn’t travel to medical clinics. No one really even knew where they were. But first, before that next hurdle could be crossed, the team needed more funding. Money from the Gruber Prize had run out. And the family’s efforts, spearheaded by Ashley, to raise funds through the Stanford CFS Research Center just weren’t bringing in enough.
One day, Janet attended a Bay Area support group meeting for ME/CFS. Whitney had gone several times when he was still healthy enough. She was too busy to go often, but she went when she could to meet people in the community and get ideas for things that might help her son.
