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At first she told no one. Not her twin sister. Not her mother. Not even her father the scientist.

Six-year-old Jenna Smith knew better than to pee when she was in the bath. But on that night in 1992, in her family’s home in Iowa City, the water felt so comfortable against her skin that she didn’t want to get out of the tub. It seemed like such a small thing. Who would know?

Seconds later the water around her waist turned reddish pink. Blood? It had to be. Jenna wondered if she’d hurt herself. “I was six years old sitting in a bathtub, watching a few seconds of my world stop making sense,” she would recall years later.

She kept the blood a secret because she didn’t want to admit that she’d peed in the bath. But when it was still in her urine the next time she used the toilet, she went to her mother. Concerned, her mom called her dad, Richard Smith, and he took Jenna to the emergency room.

Richard was an ear, nose, and throat doctor in the University of Iowa’s school of medicine, a researcher who would become one of the world’s authorities on the genetics of hearing loss. His wife, Lynne Lanning, had worked as both a lawyer and a nurse. They had four young children: twins Jenna and Jessica, who were identical, and two boys, Luke and Rion.

At the ER, doctors ran tests on Jenna, but they couldn’t identify the cause of the blood. In the days that followed the bleeding intensified. At her parents’ urging, Jenna collected samples of her urine in Dixie cups for further testing. The doctors remained stumped, however, and after a while Jenna found the whole thing more annoying than worrisome.

The uncertainty was much harder on her parents. It wasn’t that doctors were misdiagnosing their daughter; they were unable to diagnose her at all. “It was horrible,” Richard said. “Imagine seeing your child and you know something is wrong, and you know the doctors treating her have no clue what to do.” Richard called a pediatric nephrologist he knew in Houston, where the family had lived previously. The nephrologist listed several conditions that could be causing the bleeding and said that, to determine which was to blame, Jenna’s parents should take her to Cincinnati Children’s Hospital Medical Center.

In July 1992, Richard, Lynne, and Jenna drove nearly 500 miles to get answers. Doctors in Cincinnati diagnosed Jenna with dense deposit disease, a condition in which proteins clog and damage the kidneys, leading to renal failure in many patients. There was no cure.

The hospital couldn’t tell the family much else—no one could. The disease was exceedingly rare, afflicting between one and three people in a million. Back home, Richard and Lynne spent hours inside the University of Iowa’s quiet medical library, poring over papers in search of information about their daughter’s illness. They could find no evidence that anyone was actively studying the condition.

Although many Americans—roughly one in ten—suffer from a rare disease, the experience can be lonely. Friends and relatives don’t understand the unique miseries such illnesses impose on daily life. Few doctors are likely to have encountered them before. And because there aren’t many patients, drug companies usually don’t invest in research for treatments.

Richard and Lynne feared that their daughter’s life might be tragically brief. Sometimes the mention of weddings would sink Lynne into melancholy; she couldn’t bring herself to watch the movie Father of the Bride. Richard agonized over what to do. His training compelled him to seek answers, but he wanted to be Jenna’s father, not the scientist charged with curing her. He kept his research focused on hearing loss. At first, anyway.

Stories of scientific discovery almost always celebrate individual researchers, consigning the contributions of loved ones, communities, and colleagues to footnotes. There are exceptions―the teams that built the first atomic bomb and deciphered the human genome, for instance. Science also has its share of famous families. Marie and Pierre Curie, along with their daughter Irène and her husband, Frédéric, won five Nobel Prizes between them for discoveries related to radioactivity. For the most part, however, the history of scientific progress has been mythologized as a succession of brilliant, driven individuals—often men—who chose the lab over the dinner table and competition over collaboration.

Some scientists have embraced the role of maverick. “You have to worry about your own work and ignore what everyone else is doing,” the physicist and Nobel laureate Richard Feynman is said to have told a colleague. The decades-long pursuit of a treatment for Jenna’s disease followed a very different path. There was no single hero, no lone scientist seeking glory. The biomedical quest required the efforts of a family and their neighbors in Iowa City, and the work of scientists around the globe. Together they changed an obscure area of medicine.

Richard and Lynne met in 1977, when both were working at Memorial Hermann-Texas Medical Center in Houston—she as a nurse, he as a medical intern. He noticed a run in her nylons and was smitten by her smile. She liked his down-to-earth manner and intelligence, his humor and kindness. They were working in the hospital’s burn unit when he asked her out.

The couple married in 1981, and except for two years in England, they remained in Houston until 1990. That December they moved to Iowa City, where Richard had a job waiting for him leading the pediatric otolaryngology division and running a research lab at the University of Iowa’s medical school. They had been there only a year when Jenna got sick.

Richard and Lynne learned that their daughter’s disease was caused by a malfunction in her complement system. Believed to have evolved long before other parts of our immune infrastructure, the complement system sends proteins to battle foreign invaders. Unlike antibodies, these proteins are not tailored to fight a specific virus or bacteria, but they kick into gear faster when a threat is detected. In people with Jenna’s condition, the complement system is like a runaway train: Proteins become overstimulated and then accumulate in the glomeruli, tiny filters the kidneys use to clear waste from blood.

Blood in the urine is one symptom of the disease. Others include swelling, high blood pressure, inflammation, and fatigue. When Jenna was in the first grade, her body struggled to make growth hormones. Her production of red blood cells slowed, and she grew increasingly tired. During rehearsals for The Nutcracker ballet around Christmas 1993, she’d finish her part and then lie down backstage, completely spent.

Doctors put her on a heavy dose of the steroid prednisone and on blood-pressure medication. The prednisone caused her body to retain water. She woke up each morning with her eyes swollen shut, then waited in bed until the swelling receded. She couldn’t fit into her clothes or shoes. She wore flip-flops and roomy jumpers Lynne sewed for her.

As twins, Jenna and Jessica had always been close. They played together, made up songs and dance moves, explored the woods near their home, and enjoyed pranking friends and family members. “She made a lot of things feel not so heavy,” Jenna said of her sister. Still, she sometimes thought that Jessica “got off scot-free” by not having dense deposit disease. Neither girl liked feeling different from the other. (Years later, Jessica would be diagnosed with type-1 diabetes; Jenna would not.)

The changes to Jenna’s appearance meant the girls were no longer identical. Once, according to Lynne, when a boy at school said that Jenna couldn’t be a twin anymore because of how she looked, Jessica slugged him. Lynne recalled sitting in the principal’s office, politely listening to a lecture—this is not the way we resolve things!—but understanding why Jessica had lashed out. Nothing was so frightening to her daughters as the idea that they’d stop being twins.

About half of those afflicted with Jenna’s disease progressed to kidney failure within a decade of diagnosis; it took her less than a year. She made it through the last day of first grade. Then, as other children departed for summer camp, she went to a clinic. While her classmates practiced archery and did arts and crafts, she learned about the catheter doctors would surgically insert in her body. Through that tube, a machine would pump fluid into her abdomen, where her peritoneum—her abdominal lining—would take over the filtering function kidneys usually perform.

She would take the peritoneal dialysis machine home with her and use it every day for the foreseeable future, possibly for the rest of her life. When a nurse tried to take Lynne aside to show her how to operate it, Jenna stopped her. “I’m the patient,” the seven-year-old insisted. “I’m learning how to run the machine.”

In such moments, Lynne was surprised at the strength she drew from her daughter. She needed it. Her grief could leave her feeling drained. One day she found herself crying into the soil as she gardened.

But Lynne and Richard were determined that sadness would not define their lives. For a long time, they didn’t have a TV in their house—they wanted the family to talk when they were together, and for the children to build forts, learn to sew, be creative. They had painting nights, creating portraits of one another. There were cooking contests, too. Richard and Lynne made sure to spend one-on-one time with each kid. Richard traveled with Luke to Japan, with Rion to the Grand Canyon, with Jessica to Italy, and with Jenna to England. Lynne took trips with the children to Brazil, England, and Guatemala. There were themed birthday celebrations: a James Bond party for Richard, where everyone was armed with Nerf guns, and one for Lynne where Richard dressed as the artist Bob Ross and the guests painted “happy little clouds.” Richard coached the kids’ hockey and soccer teams. He built harps and lyres from scratch, and Lynne played them.

Every day, Richard left for work at 5 a.m., while the children were still in bed. He returned around six at night. The family joked that they could hear him coming from half a mile away in his rust-bucket Isuzu Trooper with the bad muffler and a hole in the passenger footwell. When he wasn’t seeing patients or in surgery, Richard was in the lab. On Saturdays, Luke would go there with him. Sometimes the other kids joined. They liked to refill the communal candy jars and visit the mice used in experiments.

It seemed a wonder to the lab’s staff that Richard squeezed so much into a day. When they began using email to communicate, they received messages from him time-stamped three or four in the morning. “Why don’t you sleep sometime?” a colleague replied once. Indeed, Richard slept little. At night his mind kept running through the mysteries of his daughter’s disease.

Richard had read that it took 10,000 hours—the equivalent of working full-time for about five years—to achieve expertise in a subject. He believed it. In 1995, he began flying to conferences about kidney disease, where he talked to the few doctors who cared for patients like Jenna. Medicine was getting no closer to finding a treatment.

That year the owner of a ranch where Richard and Lynne’s children took riding lessons offered to host a fundraiser for kidney disease research. The family organized Dressage in the Heartland, which featured riding events, fiddle music, and bowls of chili. After raising upwards of $10,000 for the National Kidney Foundation, they held the event again the following year. There are hundreds of kidney ailments, however, and the foundation didn’t allow the money the family raised to be earmarked for the research of dense deposit disease. (The foundation said it now allows monetary gifts to be dedicated to specific conditions.)

Richard and Lynne ran into more disappointment during a visit to the University of Minnesota in early 1997. A specialist they consulted was blunt. “Nobody is looking at this disease,” he told them. “And barring something unforeseen, nothing will be done in the next twenty years.”

It was a four-and-a-half-hour drive back to Iowa City. In the car, Lynne brought up what the doctor had said. Maybe they would have to be that unforeseen something.

Over the next few years, Richard expanded his lab’s mission. As best he can recall, he told the staff “something along the lines of ‘Let’s study dense deposit disease and see what we can learn about it.’ ”

Not everyone felt comfortable with the change. “In science, we’re taught that you’re supposed to be dispassionate,” said Nic Meyer, a research associate. “There was some talk that this is a bad idea because, you know, it’s his daughter.” At the same time, she felt a strong pull in the opposite direction. Richard was a good boss, after all.

Jenna’s condition, Richard observed, was complex—the kind of medical puzzle scientists are drawn to because it’s challenging. The disease is sometimes inherited, but more often it isn’t. Either way a few genes are involved, including one called C3. This gene instructs the body to make a protein—also called C3—that’s crucial to the complement system. The lab’s staff learned that there were hot spots on the gene where certain mutations could interfere with the mechanisms that kept the body’s immune response from running amok.

Understanding the genes involved in Jenna’s disease was only the starting point. Further research—the kind that might lead to a treatment—would require the effort of more scientists and the money to pay for it. This is where Lynne came in. Using her legal expertise, and in collaboration with the Greater Cedar Rapids Community Foundation, she established a fund called Kidneeds in October 1997. Every penny raised would go toward research into dense deposit disease.

Two months after setting up Kidneeds, Richard and Lynn’s family were hunkered down at home one night as snow fell outside. It was Jenna and Jessica’s birthday. There was a knock at the front door, and Lynne let in a man covered in snow and holding two teddy bears. She recognized him as the twins’ school bus driver. His wife had died recently, leaving him to care for five boys on his own.

The teddy bears, he said, were for the girls’ birthday. He’d also heard about Kidneeds. He handed Lynne a check for a hundred dollars. “I wish I could do more,” he said.

Kidneeds soon began fundraising in earnest. It organized a chili dog cook-off that drew twenty teams representing, among other groups, the county sheriff’s department, local dialysis nurses, and a high school Spanish club. Along with the food, there was a silent auction and herding and agility contests for dogs. The event raised about $35,000—enough that Kidneeds decided to host it annually. For the next six years, it became part of Iowa City’s social calendar. There was also a Cinco de Mayo event at a local church. A grocery store donated ingredients to make enchiladas, and dinner was ten dollars a plate. Richard and Lynn’s children got involved in fundraising too, recruiting neighborhood kids to sell lemonade and cookies at a roadside stand where Rion also performed magic tricks. Jenna made and sold glass-bead jewelry.

In 1999, Kidneeds began distributing the money it had raised. Scientists from around the world were invited to submit grant proposals, which were evaluated by three boards, including one comprising scientific advisers. The process helped raise the profile of dense deposit disease; suddenly, this ultra-rare condition was attracting research funding. Grants also served as seed money, helping researchers gather evidence that could lead to more sizable research support from the National Institutes of Health and other major funding agencies. “You cannot have a bonfire,” Richard said, “without an initial flame.” (To avoid conflicts of interest, his lab was excluded from applying for money from Kidneeds.)

Kidneeds also made Iowa City a hub for families of people coping with Jenna’s disease. At first one family at a time would visit. Richard and Lynne would take them out to dinner, and Richard would show them the lab and explain where the research stood. Within a few years, Kidneeds started hosting family conferences. People came for community support and to hear from researchers, psychologists, and even billing specialists, who offered insight on dealing with insurance companies.

Richard encouraged his staff to meet the families who visited Iowa City. In time, Nic Meyer changed her mind about science having to be dispassionate. “I think it’s a dumb idea,” she said. Knowing that people like Jenna were counting on her and her colleagues made their work feel all the more important.

“If I don’t do dialysis,” Jenna remembered thinking, “I die.” Still, she wanted so badly to be free of the machine.

Jenna’s disease was like a cloud that never lifted. One winter night, Lynne awoke and realized that the house felt cold. She crept into Jenna’s room and discovered that her daughter had left her window open. Jenna had taped a picture of a burning candle to the pane and placed a handwritten note nearby. It was addressed to angels, and it asked for them to watch over her. While doing pull-ups for a fitness test at school, Jenna had damaged her catheter. She was having surgery the next day to fix it.

Throughout elementary school, Jenna juggled doctors’ appointments, injections of growth hormones, and daily pills and shots to help her body make red blood cells. The treatments were little more than Band-Aids, however. Even the short walk uphill to the bus stop, one her siblings made with ease, left her winded. The swelling in her body shaped her interactions with people at school; she avoided the spotlight, keeping to herself.

More than anything else, dialysis dictated her life. Every night, she hooked herself up to the machine and ran it for eight hours. She couldn’t skip the procedure—a camping trip with friends was out of the question. When her sister went to sleepovers, Jenna rarely joined. If she did, she hauled the machine with her.

She felt her best the moment she finished dialysis, when her blood was at its cleanest. As the hours passed, she experienced a steady decline. There were long-term effects, too. She stopped producing urine entirely. High phosphorus levels in her blood left her with bloodshot eyes, making her self-conscious.

Jenna found it frustrating to be the object of constant worry or the reason for a family trip being canceled. One day, as a preteen, she turned to the internet to learn how long she could survive without dialysis. The answer was a matter of days, maybe weeks. “If I don’t do dialysis,” Jenna remembered thinking, “I die.” Still, she wanted so badly to be free of the machine.

An opportunity arrived in the summer of 2000, when doctors determined that Jenna, now 14, was healthy enough to undergo a kidney transplant. The procedure wouldn’t rid her of dense deposit disease, but a new kidney might work for a while—possibly for years. Lynne and Richard both wanted to donate and went through numerous tests at the University of Iowa. At first, Lynne appeared to be the best donor, because the biomarkers in her tissue were more compatible with Jenna’s. Doctors scheduled the surgery. Then a test revealed that Lynne’s creatinine clearance, a measure of kidney function, wasn’t optimal for donation. Lynne was devastated. “How can it be that I can’t even give my child my kidney?” she said.

Doctors did tests on Richard. They were concerned by the quantity of red blood cells in his urine, but determined that it was likely a side effect of exercise—Richard was an avid runner—and not a medical problem. Just a few days before the scheduled transplant, he was cleared to donate. The surgeon explained that he would make a single large incision in Richard’s flank, from front to back. “And when you wake up,” the doctor said, “you’re going to feel like you got hit by a Mack truck.”

The transplant took several hours. Afterward, Jenna was kept in the ICU for observation. That evening, Lynne was emptying the bag of urine from the catheter in her daughter’s bladder when a nurse told her the hospital staff would do that. “You don’t understand,” Lynne replied. “This is fun! Jenna hasn’t peed in seven years.”

When Richard woke the next day, he felt as if his abdomen was on fire. Even so, he rose from the bed, reached for a walker, and hobbled down the hallway to find Jenna. Lynne rushed after him; her husband had forgotten to close the back of his hospital gown.

As he entered Jenna’s room, Richard felt a wave of relief. She was resting in bed, apparently doing well. Her new kidney was large and felt like it had been squeezed into her abdomen, but she refused pain medication because it made her groggy. Richard told Jenna that he loved her, and she said it back.

A few days later, the family received an email from a friend. “What a true Independence Day this was for [Jenna],” the friend wrote, “to be free of dialysis for the first time in so many years and to be so full of hope for the future.” That hope was short-lived. Within a month, tests showed a dangerous buildup of proteins in Jenna’s urine. Two months after the transplant, doctors did a biopsy. The disease was already attacking the new kidney. It was only a matter of time until Jenna needed dialysis again.

One evening, she and her mother took a walk in the woods near their home after sunset. For most of Jenna’s life, nightfall had meant being tethered to a machine. She knew that being outside in darkness would seem like nothing to most people, but to her it felt profound. “I’m just grateful I got to see what life is like not being on dialysis,” she told Lynne.

Richard tried to downplay his disappointment about the transplant—he joked that his kidney turned out to be “a clunker.” In the fall of 2000, in an effort to prolong the organ’s function, Jenna began a blood-purifying treatment called plasmapheresis. She endured it as often as three times a week, three hours each session. It was hard on her body and usually left her vomiting.

Her condition only worsened. She struggled to eat, and searing cramps wracked her stomach. Soon doctors diagnosed Jenna with a rare, life-threatening complication of peritoneal dialysis called encapsulating peritoneal sclerosis. An inflammatory response had caused the lining of her abdomen to thicken and scar, forming a membrane that grew and squeezed around her intestines like sausage casing, affecting her bowel function. Without intervention, she could deteriorate into profound malnutrition. Her intestinal wall could tear, allowing stomach acid and bacteria to leak into her abdominal cavity. Up to half of patients with the complication die within a year of diagnosis.

In early 2001, Jenna, who had just turned 15, underwent surgery to try to remove the membrane. It was performed by Anthony Sandler, a family friend and surgeon with expertise in complex intestinal problems. He had never operated on encapsulating peritoneal sclerosis but had the skill and confidence to try. In the operating room, when he saw the extent of the complication, he stopped the procedure and went to consult with Jenna’s parents. “Richard, her entire small intestine is encapsulated in a cocoon,” Sandler said. If only a section were affected, he explained, he could cut it out and rejoin the remaining parts, preserving the continuity of Jenna’s bowel. But the membrane was wrapped around the whole thing.

Richard knew how serious this was—he had read about the mortality rate for peritoneal sclerosis. Lynne watched her husband’s head roll back as if struck by a bullet. He closed his eyes. The couple held on to each other.

“Let me try something,” Sandler said. “We’ll see how it goes.”

Back in the OR, with exquisite care, Sandler made a few cuts along the length of the membrane, gradually freeing the intestinal tract from its grasp. When he was done, Sandler briefed Jenna’s parents. According to Richard, before the surgeon said a word, his smile indicated that the procedure had worked. Richard grabbed his friend in a hug and began to cry, then collapsed into a chair, emotionally exhausted.

The scarring in her peritoneum meant that, when her kidney function finally declined to the point that she required dialysis, Jenna had to use a different method than before. She started hemodialysis: A machine drew blood from her arm, passed it through a filter, then pumped it back into her body. Jenna felt conflicted. The effort to break free of life on dialysis had ended in defeat, but after completing her first session, she felt better than she had in a long time.

Dialysis was “a weird blessing,” she said. “Good, but not natural. Helpful, but hard work.” It wasn’t the problem; her mysterious disease was.

In 2004, more than 1,000 miles east of Iowa City, in the hamlet of Chappaqua, New York, a financial trader and manager named Sean Tully discovered that his four-year-old daughter’s urine had turned the color of Coca-Cola. In April 2004, a doctor reported that she had red blood cells and abnormal protein levels in her urine. She was diagnosed with dense deposit disease.

The doctor gave her parents little hope. There was a good chance their daughter would go into renal failure and require dialysis by the time she was 14 or 15. Tully read online that relatively few people lived more than twenty years on dialysis. The doctor explained that only one organization seemed to be doing anything about the girl’s condition. It was called Kidneeds, and one of its cofounders was a researcher at the University of Iowa.

Tully called Richard, and the two hit it off. On the advice of friends, Tully also watched the movie Lorenzo’s Oil, based on the true story of a family who’d successfully pushed medical researchers to investigate their son’s illness, another rare disease called adrenoleukodystrophy. Sean contacted the boy’s father, Augusto Odone, and drove to meet him in Washington, D.C. How, Tully asked, had Odone spurred action for his son? “You need to get all the doctors and scientists who know anything about the disease in a room together,” Odone told him. It was crucial that experts curb their competitive instincts and work as a team.

Tully asked Richard why he hadn’t organized such a meeting. Richard explained that the funds Kidneeds raised went to research—nothing else. Even the people who attended the family conferences paid their own way. He and Lynne didn’t have the money to fly scientists in from around the world, put them up in a hotel, and rent a meeting venue.

“You’ve got the money,” Tully assured him. “I’m the money.”

Tully, who had worked for Citibank and then a German bank, flew out to Iowa City a few weeks later to meet Richard and Lynne. He brought a $25,000 check. There was more where it came from.

Richard had never organized this kind of conference before. He asked the advice of a friend who recently became dean of the newly launched Olin College of Engineering in Needham, Massachusetts. The dean unexpectedly volunteered space at Olin for the conference, solving one major challenge. A date was set for August, when the college would still be on summer break.

Richard began contacting scientists, doctors, and experts in kidney failure and the complement system. He told them their expenses would be covered. They would even receive a small stipend for attending. Once he had commitments from a few prominent researchers, he used their names to persuade others to attend—he knew that scientists didn’t like to be left out of an important meeting. In all, twenty experts agreed to attend. Richard, Tully, and Tully’s brother picked them up at Boston’s Logan Airport and drove them to Needham.

Experts at the Olin meeting discussed what little was known about dense deposit disease. Gerald Appel, a kidney expert at Columbia University, reported that prednisone, prescribed to Jenna and to Tully’s daughter, did not actually help patients. There was discussion of a mouse model of dense deposit disease developed in 2002 by researchers at Imperial College London. (A similar model had been discovered by chance in a Yorkshire pig almost a decade earlier.) Animal models are essential in research because they allow scientists to study how a disease progresses and test potential treatments—a process that can lead to clinical trials in people. There was also consensus at the meeting that the only way to definitively diagnose the disease was with a kidney biopsy. Researchers agreed that they needed to find a way of regulating a branch of the complement system known as the alternative pathway, where the C3 protein plays a central role. If they could find a way to block the activation of C3, they might be able to stop dense deposit disease at its source.

Richard was particularly encouraged by the work of a conference participant named John Lambris. Born in the scenic village of Rodavgi in the mountains of northwestern Greece, Lambris was a highly regarded immunology researcher at the University of Pennsylvania. He had been studying the complement system for thirty years, seeking to understand its basic biology. As part of this effort, Lambris’s lab had screened a library of more than 200 million peptides―molecules made of short chains of amino acids. They looked for ones that could attach to C3 and control its activation, thus functioning as a complement inhibitor. The team had found only one. When it passed repeated tests in the lab, Lambris later said, “we realized we had found something special.” In 1996, he named the molecule compstatin.

Back then, Lambris didn’t envision compstatin as a possible treatment for a specific disease, and he knew it was a long way from being able to serve that role. For one thing, unless it was continually infused into the bloodstream, its effectiveness was very brief. Although there were methods for improving the molecule’s staying power, employing them and then developing compstatin into an actual drug would likely take years of work and millions of dollars.

There was something else: Obtaining grants would mean defying his peers. At the time there was a strong belief in Lambris’s field of study that blocking C3 could cripple a vital arm of the immune system and put patients at risk of infection. Lambris thought the risk was overstated, but many other scientists didn’t share his view, and some of them would be evaluating his grant proposals.

His first application to the National Institutes of Health was denied. So was the second. And the third. And the fourth. And the fifth. Each application took weeks or sometimes months to put together. Each rejection had to be overcome. “When you hear the news, you have a glass of wine and then the next day you start thinking,” Lambris said. He found inspiration in the words of the Greek writer Nikos Kazantzakis, who said the right path goes “uphill.” With his latest defeat still fresh, Lambris would pore over the criticism from grant reviewers and use it to devise a new set of experiments. If successful, the experiments would bolster the case for compstatin.

On his seventh grant application to the NIH, in 2001, Lambris finally received approval. This time he had wine to celebrate. Then, with $2 million in funding spread over five years, he and his colleagues set out to make a better formulation of compstatin. After exploring several strategies, the team attached a polymer to the molecule that slowed its removal from the body. They also strengthened the way compstatin bonded to C3 and improved the molecule’s structure and stability.

When it came to testing compstatin in animals, nature made the researchers’ work difficult. Mice and rats are the most common animal subjects in clinical tests used to determine a drug’s safety, dosing, and metabolism, but rodents wouldn’t work for compstatin—their C3 structure was too different from humans’. Instead, the scientists had to use long-tailed macaques. The monkeys, primarily raised in Southeast Asia, China, and Mauritius, cost several thousand dollars apiece―many times the cost of a rat or mouse. Despite the financial obstacles, Lambris and his team managed to create and test hundreds of versions of compstatin.

The Olin conference in 2004 marked the first time Lambris began thinking of compstatin as a possible treatment for dense deposit disease. In talking to Richard, he realized that the success of his research could change lives like Jenna’s.

By 2006, Lambris’s team had boosted the binding strength of the original formulation by a factor of more than 250. The new generation of compstatin remained active in the bloodstream much longer and did a better job of restraining the complement system. Lambris licensed a version of the molecule to a company called Potentia Pharmaceuticals, which was later acquired by Apellis Pharmaceuticals. He hoped that compstatin would complete the rare journey from the lab to actual patients.

So did Richard and Tully. Two years after the Olin meeting, they organized a second conference on dense deposit disease, this time in England. Richard gave an opening talk entitled “Moving Towards a Cure.” In truth, however, the progress he described felt slow to him. There was still a great deal scientists didn’t understand about the disease. For instance, why did roughly half of patients go into kidney failure within a decade while half did not? No one knew what explained the split—which biological mechanism fated some people to a life on dialysis or worse. It felt like a coin toss, one Jenna had lost.

In many respects, she had adjusted remarkably well to hemodialysis. In high school she played tennis, and her shyness lifted. In the summers, she and two of her siblings worked in their father’s lab. She learned to sequence DNA samples and search for mutations, painstaking tasks that demonstrated the slow and deliberate pace of scientific research. She went to the University of Iowa and then to the University of Oregon, where she got a master’s degree in architecture.

Along the way, she grew more accepting of her chief burden: the dialysis machine. She even named it—Jamal—and came to feel a grudging respect for it. “He does one thing,” Jenna said, “He does it really well, and he knows nothing else.” Still, the longer she was on dialysis, the greater the risk of serious infection and heart problems. Upwards of 45 percent of long-term dialysis patients die of cardiovascular disease.

The story of Tully’s daughter took a different turn. After several years, the blood in her urine became less frequent. Then, in the summer of 2011, when she was 13, it went away entirely. Her doctors ran tests every six months, then every year. Eventually they determined that, for unknown reasons, the disease had simply stopped afflicting her. Her family was relieved that she seemed to be in remission, but Tully was left with another mystery that science had yet to explain: Was his daughter’s disease gone for good, or lying in wait?

As the quest for answers continued, grants from Kidneeds allowed scientists in the U.S. and abroad to investigate basic aspects of the disease’s machinery. Researchers illuminated the important roles played by autoantibodies, which sometimes mistakenly switch on the complement system, and factor H proteins, specialized molecules that can trigger disease by failing to regulate complement activation. “Kidneeds-supported research was important because it helped define why complement becomes uncontrolled in C3G,” Lambris said.

That term—C3G, short for C3 glomerulopathy—represented another important development. The term was adopted at a meeting in 2012, where experts, including Richard, agreed that dense deposit disease belonged under the same diagnostic umbrella as a condition called C3 glomerulonephritis. Both afflictions shared the same driving force—dysregulation of the complement system—so going forward, they would be considered subtypes of a single disease.

In Iowa, Richard and his colleagues developed clinical guidelines for evaluating a patient’s complement system—an important tool for doctors, especially those unfamiliar with C3G. The lab identified a dozen genetic mutations linked to the condition and observed how the disease progressed in different animal models. The Iowa team also discovered the mutation that had caused an eight-year-old boy to suffer from another disease of the complement system, known as atypical hemolytic uremic syndrome (aHUS). They determined that he might benefit from a drug called eculizumab. Although eculizumab wasn’t yet approved for treatment of aHUS, doctors received permission to try it, and the boy responded well. A year after Richard and his team published their findings, the FDA granted accelerated approval for patients with aHUS to take eculizumab, now known as Soliris.

Richard had made an important contribution to medicine, but it wouldn’t help his daughter. He and his colleagues had high hopes that Jenna’s condition might be treated with another molecule, known as soluble CR1, and the FDA granted compassionate-use permission to test it on an eight-year-old girl with C3G. She had reached the end stage of kidney failure and had no other options. The girl received seven doses, suffered no health problems, and experienced some short-term benefit. Based on those results, Richard and his colleagues received permission to test soluble CR1 in six more patients. The first was a teenage boy who came to Iowa from New Jersey with his mother. His kidneys seemed to function better on the drug, but after six weeks the effect waned. Doctors opted not to test soluble CR1 in the remaining five patients, and the drug never entered clinical trials.

There were other disappointments. A drug called avacopan had worked well in animal testing, and when it was given to patients, they reported feeling better. But tests showed no improvement in their kidney function and no decrease in proteins in their urine.

Richard seldom talked about the challenges in his work, but Jenna always knew when one appeared. Her dad would lie quietly on the couch, hands folded on his lap, thinking. At work he kept an IV bag at his desk that once held soluble CR1; it was a reminder that failure is part of science, a painful but often necessary step toward success.

When news at the lab was encouraging, Richard came alive, popping into everyone’s offices to chat. Sometimes he stood outside meetings and pressed his face against the glass to make his colleagues laugh. During a truly great week, he would take out a small commuter bicycle he kept in his office and pedal through the hallways.

Richard also kept close tabs on C3G research happening outside his lab. John Lambris had founded his own company, Amyndas Pharmaceuticals, and in 2016 its latest iteration of compstatin, known as AMY-101, received orphan-drug designation from both the FDA and the European Medicines Agency for treatment of C3G. (The designation offers companies incentives to develop treatments for rare diseases, including tax credits and a period of market exclusivity that frees them from competition with generics.) Meanwhile, the version of compstatin licensed to Apellis Pharmaceuticals was advancing through the research gauntlet.

Initially, Apellis wasn’t interested in compstatin as a rare-disease treatment. But evidence suggested that the complement system played a role in retinal disease, raising the possibility that a complement inhibitor could treat a form of age-related macular degeneration. The leading cause of vision loss in people over 60, macular degeneration affects about twenty million Americans and 200 million people around the globe. Compstatin, in other words, could be a blockbuster drug. Its development for the treatment of a common eye disease could provide valuable information about its formulation, stability, and safety in humans. And this knowledge, in turn, could help later efforts to adapt the drug for the treatment of C3G and other diseases.

According to Dick Harrison, a former scientist and project adviser at the company, the Swiss pharma giant Novartis also recognized that a complement inhibitor could be “a potential money spinner.” But when early research results on macular degeneration were disappointing, the company did something unusual: It continued to explore the possibility of using complement inhibitors to treat other conditions—obscure ones. This was unusual for Novartis, Harrison explained, because it didn’t have a reputation as a “a rare-disease company.”

Novartis scientists took a different approach to taming the complement system. Rather than trying to block C3, they targeted its partner in crime, a protein known as factor B. Together the two proteins produced an immune response that Richard likened to “a guy blowing a bugle, telling everybody to come out and fight.” Stop either protein and you stop the whole system. The runaway train comes to a screeching halt.

Leading the Novartis team was Nello Mainolfi, an Italian-born scientist then in his thirties. Using a high-speed screening system, Mainolfi and his colleagues went through Novartis’s collection of 1.1 million lab-made compounds seeking one that could bind to factor B. They narrowed the possibilities to a pool of 250,000, then screened those using a test that employed a protein found in cobra venom. Eventually, they settled on a molecule called LNP023. Just as Lambris had done with compstatin, the Novartis scientists then spent years laboring to improve their molecule. They increased its potency more than a thousandfold and ensured that it could maintain its hold on factor B without affecting other systems in the body.

Mainolfi left Novartis in 2015 but tracked the progress of LNP023, now called iptacopan. “These drugs are like your babies,” Mainolfi said. At roughly the same time, iptacopan and Apellis’s version of compstatin, now called pegcetacoplan, reached the moment of truth: They were cleared for clinical trials for treatment of C3G. (As Apellis had hoped, pegcetacoplan also proceeded to clinical trials for the treatment of retinal disease.)

Richard’s lab in Iowa City would play a major role in what came next. As the capital of the C3G research universe, it would be tasked with recruiting patients for the trials. Jenna, though, would not be one of them.

Jenna accompanied her dad to medical appointments, watched him grow weaker, and worried about his future―a reversal of the roles they’d played for most of her life.

By 2019, Jenna had spent more than half of her thirty-four years on dialysis. Three hours of hemodialysis, performed five to six days a week, kept her alive. But the toll was heavy. Sometimes blood clots pressed against her arteriovenous fistula, the surgical connection between an artery and a vein in her arm that enabled hemodialysis. This threatened to prevent the blood-filtering process entirely. Clots could also cause problems for the heart, brain, lungs, and circulatory system. Fond as she’d become of Jamal, Jenna was once again ready to be done with dialysis.

Nineteen years after her first kidney transplant, Jenna committed to another one. Saying yes was the easy part. Then came the medications to prevent rejection, regular blood draws to test their effectiveness, and prescription adjustments with unpleasant side effects. Jenna wrestled with anxieties about what could go wrong. Journaling helped, she recalled, “to let go of the me I had known up to that point” and “to be whomever this new person was going to be.”

Lynne once again offered her daughter an organ. Her creatinine clearance wasn’t an issue this time, but her kidney was no longer a good biological match for Jenna. Doctors determined that the antibodies Jenna had developed in response to the failed transplant from Richard meant that her body would reject kidneys from more than 90 percent of donors. Still, Lynne was able to help. She gave a kidney as part of what’s called a donor chain: Her organ went to a patient waiting for a kidney in another state. In exchange for that donation, Jenna received a compatible organ from a stranger. (According to the National Kidney Registry, a donor chain “can facilitate anywhere from two to thirty transplants.”)

After surgery, Jenna’s hair fell out, a response to medication. She could live with temporary side effects, though, because tests showed that the donor kidney was working. Jenna named it Jasmine―Jazzy, for short. Life with Jazzy was not a night-and-day change. It took getting used to. Jenna had surgical scars, and she kept the fistula in her arm in case she ever had to go back on hemodialysis. However, Jazzy let her escape the regimented “dialysis life”―not just the daily sessions on a machine, but the parade of necessary medications and doctor appointments. Jenna could accompany friends on a road trip, try yoga, go hiking. In her words, she could “spend time learning what Jenna likes, not just doing what Jenna has to do.”

Her family’s joy over the new kidney was tempered by some disturbing news. Shortly before the transplant, Richard noticed an ache in his right shoulder when he performed surgery. Thinking that he’d injured his rotator cuff, he got an X-ray. It showed that his shoulder was fine, but his doctor noticed a lesion the size of a grain of rice in the lower lobe of his right lung. It was cancer.

The news stunned Richard. Fortunately―or so it seemed―there was very little cancer. He wouldn’t need chemotherapy or radiation. The story could have ended there, but out of an abundance of caution, doctors had recommended removing the lower lobe of his right lung during the biopsy. That part of the procedure did not go as planned, and the middle lobe was removed as well.

Over the next seven months, Richard developed persistent complications. What remained of his right lung was beset with infections. He was tired. He lost about forty pounds. There were days when walking from one office to another left him out of breath. For four months, he had a chest tube that drained fluid from his failing lung.

His lab needed to draw up a succession plan for its management in case the worst happened. Richard would always say, “I know, I know,” then put off doing it. “Our entire lab felt it,” said Jori Hendon, the operations manager. “There were many of us who were so scared.”

Although Richard sometimes referred to his lung issues as “a hiccup,” the problem dragged on for three years. He kept working. Once, after a procedure, his staff expected him to take time off for recovery. But the university hospital where he was being treated was connected to the lab, and he snuck over to check on things, pulling an IV stand with him. “He was the epitome of the saying ‘doctors make the worst patients’ back then,” Hendon recalled.

Jenna accompanied her dad to medical appointments, watched him grow weaker, and worried about his future―a reversal of the roles they’d played for most of her life. Eventually, Richard had to give up his work as a surgeon; he performed his last procedure in August 2022. Three months later, doctors removed what remained of his right lung. This left the affected side of his torso looking hollowed out, as if a grapefruit had been scooped from it. Shortness of breath became his default condition.

Still, he insisted on reporting to the lab each day. His family and colleagues knew why: Even if Jenna no longer needed it, Richard didn’t want to retire before there was a treatment for C3G. He wasn’t about to set aside his career with clinical trials for two promising drugs just around the corner.

Carla Nester, an internist and nephrologist, had been the first kidney expert to join Richard’s lab, and she now took on a key role in the clinical trials of iptacopoan and pegcetacoplan. Like Richard, she had seen C3G up close and felt a sense of urgency. Early in her career, she treated a young woman in her thirties who had received a second kidney transplant after the first was destroyed by C3G. “We were trying to save her next transplant, and it wasn’t going well,” Nester recalled. “We just didn’t have anything we could do.” The woman agreed to undergo plasmapheresis, the treatment that had made Jenna vomit. The patient died anyway.

C3G became Nester’s nemesis. While many doctors go their whole careers without seeing a single C3G patient, she would treat dozens. When the time came to recruit people for the clinical trials, she secured twenty—the most by any participating institution in the world.

In early-phase testing, both drugs proved safe. Only with the studies’ phase three trials, however, would researchers resolve the question at the core of drug discovery: Does it work better than a placebo? Iptacopan began its crucial trial in July 2021. Pegcetacoplan’s commenced less than a year later. The measure of success was the same for both: a reduction of the harmful buildup of proteins in patients’ urine. The iptacopan trial involved seventy-four patients—a relatively small number, reflecting the rarity of C3G. The pegcetacoplan trial drew 124. There were a few differences between the studies. Iptacopan, for instance, was tested in adults with C3G who still had their own kidneys. Pegcetacoplan was tested on adults and children with C3G or a similar kidney disease known as IC-MPGN, and some of the participants had received kidney transplants.

The first twenty-six weeks of the phase three trials were the double-blind period, when no one—not even the researchers—knew which patients received the drugs and which got a placebo. It wasn’t an easy time for Nester. She was eager to know if the treatments were working for her patients. Then again, if she knew they weren’t, “it’s not like I could take patients out of the study and put them on something that would fix them.”

There were promising signs. C3G often makes patients’ urine foamy, and some noticed this effect lessen. Nester’s youngest patient in the iptacopan trial reported feeling healthier. “I’m kind of back to doing what I was doing before,” they said, referring to life before their C3G diagnosis. Still, less foam in the toilet and a patient feeling good were not conclusive results. And what if the patients experiencing the improvements were on the placebo, not a drug? Nester tried not to get her hopes up.

At the end of the double-blind period in the iptacopan trial, her youngest patient’s results were the first she examined. On the page was a list of biomarkers—indications of disease or health. Anything abnormal would be indicated with a box shaded pink. All Nester could think as she scanned the list was, Wow. There were no pink boxes.

Later, when the pegcetacoplan data came in, she saw a similar result in one of her younger patients, a little girl. “Her urine protein was gone,” Nester said. “It was just completely gone.” Not every patient had such a profound outcome, but Nester knew: The drugs worked.

When the trials finished, there was no immediate announcement of the results. Nester and other researchers had signed nondisclosure agreements with the pharmaceutical companies that prohibited them from saying anything. Nester couldn’t even talk to Richard about her patients’ data. And no one knew what the FDA would do when presented with the findings. The agency could request more information or longer patient follow-up. It could deny approval of either or both drugs for any number of reasons. All anyone could do was wait.

Anything abnormal would be indicated with a box shaded pink. All Nester could think as she scanned the list was, Wow. There were no pink boxes.

In March 2025, Richard and Lynne were vacationing in St. Augustine, Florida, with friends. On a hot Friday morning, they’d just left a museum and were sitting on a bench when Richard received an email from Anirban Bose, the medical director for nephrology at Novartis. Bose asked if he had time for a call about “some exciting news.”

Richard replied right away, trying to hold his emotions in check. He’d had a good feeling about the Novartis trial, but the FDA’s decision about iptacopan, now branded Fabhalta, had been delayed. At first he expected the news to arrive in the spring of 2024. Then the decision was pushed back past summer. When 2024 turned into 2025, Richard felt as if he’d been waiting forever. Now, in St. Augustine, he put his phone on speaker as Bose finally delivered an answer: Fabhalta had received FDA approval.

It had been more than thirty-three years since the blood appeared in Jenna’s bathwater. Lynne sometimes imagined that, when this moment came―if it came―it would be punctuated by the sound of champagne corks popping. Instead, there was just the warmth of the Florida sunshine and an overwhelming feeling of gratitude. “There were so many, many people who contributed in different ways who made this happen,” Lynne said later. “The news felt like a stained glass window made of thousands of pieces of kindness, each side by side, the little and big acts of kindness all coming together to support and make this one beautiful accomplishment, and each piece necessary.”

Richard typed an email to his lab staff 1,200 miles away in Iowa City. “Yesterday,” he wrote, his heart beating faster, “Fabhalta was approved by the FDA as the first drug available worldwide specifically for the treatment of C3G.” It was a “huge step,” he continued, that had come about in large part “because of you.”

Richard wanted to tell Jenna but wasn’t sure he had permission from Novartis. She learned the news the next day, when she saw an article posted to the Facebook page of a C3G group. She read it, reread it, then read it a third time, almost in disbelief. “This is a drug. It’s not still in trials. It’s actually available,” she recalled thinking. “Holy cow.”

Four months later, there was more good news: The FDA approved pegcetacoplan for the treatment of C3G under the commercial name Empaveli. The results from both drugs’ clinical trials had been strong. On average, Fabhalta reduced protein in the urine by 35 percent. With Empaveli the reduction was even greater: 68 percent. This signaled that patients’ kidneys were repairing themselves, though some damage from C3G, such as scarring, would be permanent. Patients helped by the medications also reported having more energy and less swelling in their bodies.

Not everyone improved. Some patients did not respond to either drug; researchers would have to determine why. Still, after decades without a single effective treatment for C3G, there were now, incredibly, two.

To patients with severe rare diseases, the drugs that target their conditions can mean life itself. They must take the medications daily, weekly, monthly, or whatever is required, year after year, forever. It’s often said that you can’t put a price on life, but drug companies do just that. In 2010, Soliris, the drug that Richard’s lab helped advance for the treatment of aHUS, set an industry record when it was priced at more than $400,000 for a year’s supply. Soliris has since been eclipsed. Lenmeldy, a one-time treatment for metachromatic leukodystrophy, an often fatal genetic disease affecting the brain and nervous system, costs an estimated $4.2 million. The breakthroughs in C3G research introduced two more examples of sky-high drug prices: Fabhalta, an oral medication taken twice daily, costs nearly $600,000 for a year’s supply. Empaveli, which C3G patients receive through twice-weekly injections, clocks in at more than $500,000.

Novartis stressed that Fabhalta’s price does not reflect the actual amount the patient pays, which depends on many factors, including insurance coverage. “We price our medicines to reflect the value they deliver for patients, healthcare systems and society,” the company said in an email statement. Apellis did not respond to several requests for comment about the price of Empaveli. John Lambris, whose compstatin molecule provided the basis for Empaveli, was blunt about pricing. “The cost is unacceptable,” he said. “My hope was always that this invention would make a meaningful contribution to society by reaching and benefiting as many patients as possible.” (Lambris’s pharmaceutical company, Amyndas, hasn’t pursued clinical trials for the version of compstatin it calls AMY-101, though it may do so in the future. It is also working on complement inhibitors that could be administered less frequently, more conveniently, and at a substantially lower cost.)

Jenna has been healthy since her second transplant seven years ago. A stranger’s kidney has made it possible for her to stay up until three in the morning perfecting her brush stroke—painting is one of her hobbies—and to throw herself into learning agentic program development, which uses artificial intelligence to build and test software. “Never in a million years would I have done some of the things I have since the transplant,” Jenna said, “simply because my routine wouldn’t allow it.”

If the health of her kidney changes—and it could—she might be prescribed Empaveli or Fabhalta. “I would hope my insurance would cover the costs,” she said. “I can’t pay for a half-million-dollar medication out of pocket.” If the drugs proved unaffordable, her only option would be a return to dialysis.

Richard hasn’t heard any reports of insurance companies refusing to cover the medications. The treatments have been available only a year, however, and coverage decisions can change. Plus, there’s the question of cost throughout the world. If a poor couple in a poor country found themselves in the situation Richard and Lynne faced back in 1992, with a little girl who suddenly got sick with C3G, treatment would now be available. But what if they couldn’t afford it?

There’s only one thing Richard can do. “I can continue to push the science forward,” he said. Luckily, it’s what he knows best—and what Lynne does, too. Kidneeds, which has distributed more than $2.75 million in grants since it was founded, continues to raise money for C3G research. Lynne is gearing up for the organization’s twenty-first family conference. Participants will learn about the FDA-approved treatments and where new research is heading. Richard’s lab is part of that research—he and his colleagues continue to seek new and better treatments for C3G that can create competition, drive down prices, and save lives.

Richard has slowed his relentless pace—but only a little. He still arrives at work every morning by seven or eight. He’s seen the difference his lab can make. “I am having too much fun to retire,” he said.

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