by Sarah Gray
Mara came home from her first day of tenth grade exhausted. By the time she went to bed that night, she realized she had spent her entire evening doing treatments and hadn’t touched her homework. Sadly, it was clear to her that she wouldn’t be able to keep up, so her parents eventually withdrew her from regular high school and enrolled her in Keystone National High School, an online, self-paced high school program for students with unique scheduling needs. Her mom and dad also checked in with Mara’s doctor to see if there was anything they could do to stop the rapid decline in her health, and asked about a new clinical trial that was backed by the Cystic Fibrosis Foundation. It was still looking for participants, and Mara fit the criteria to join.
And so, in July 2013, at the age of sixteen, Mara, together with her parents, decided that she would become what Mara calls “a human guinea pig,” and registered her for the experimental drug trial.
The trial involved taking five pills in the morning and four pills in the evening. In Mara’s mother’s lay terms, “DNA makes RNA. RNA makes protein, and the proteins are defective. They don’t allow for the processing of water and salt. So this treatment corrects the defective protein.” This kind of treatment is called a “protein assist” or “protein correction.” Instead of treating an infection, this would prevent an infection.
Gradually, over the course of months, Mara began to notice an improvement. She stopped getting sick as frequently; her energy level increased; she didn’t feel as run-down as she had before; and some of her lost lung function returned. Her rapid decline not only stopped; it reversed direction. This was almost unheard-of.
There is a coda to Mara’s story.
In 2001, when Mara was four years old, she lost her comrade: her nine-year-old brother, Ian. Though he had CF, he died from something else. After what seemed like a bad case of stomach flu, he lapsed into a coma, and a week later he died. Ian was diagnosed with viral encephalitis, an inflammation of the brain that can start with flu-like symptoms. His parents, Sharon and Mike, were asked about organ, eye, and tissue donation by their local OPO, Gift of Life, in Philadelphia.
Ian was thoughtful and sensitive, and lived “like he knew he didn’t have much time,” said Sharon. He wrote a sixteen-chapter book about a fantasy world, with themes surprisingly sophisticated for someone who was only nine years old. The book was about self-sacrifice, saving other people, and what it means to be heroic. “He liked to think of himself as someone with a sword and a shield,” said Sharon. The preface to his book reads, “I want something to happen to me. Something strange. Something different. . . . I want to go to a different world. I have a feeling that one day I’ll get my wish.” Mike and Sharon thought that donating Ian’s body for the benefit of others was the right choice.
Initially, Mike and Sharon thought that his having CF would preclude Ian from being a suitable donor, but they learned they were wrong. Ian was a candidate to donate for research as well as transplant. His kidneys, corneas, and heart valves saved and changed lives through transplants. His liver was donated to NDRI for research on drug toxicity and metabolism. His lungs, trachea, and pancreas were donated to the University of North Carolina for CF research. (Fourteen years later, the UNC researcher still remembers receiving this donation. It was unique because the lungs had such little CF damage compared with the ones that are donated after a lung transplant.) Ian’s gallbladder was also donated for medical and scientific research.
The bottom line is: The donation of Ian’s organs, eyes, and tissue for research may very well have contributed to the studies that could lengthen or save Mara’s life—as well as the lives of thousands of other CF patients around the world.
Today, Mara’s prognosis is good. As of 2015, she takes the commercially approved dose of the drug Orkambi, the direct result of the trials she participated in. Her energy is high enough that she’s consistently completing her high school classes and is scheduled to graduate from high school as part of the class of 2016. In the past, she could rely on getting a lung infection every six months or so, which would put her out of commission for two to three weeks. So far, it’s been eighteen months with no infection. This kind of freedom allowed her to do something she would have never attempted in the past: she has two part-time jobs—one at a bakery, where she bakes wedding cakes, cupcakes, and pastries; and one at a health club, teaching tennis to children. She is healthy enough that she recently traveled to Washington, DC, to speak on a panel before Congress. The panelists reminded Congress of the importance of funding basic research. Maybe Ian’s little sister has a sword and shield of her own.
Mara says that she was born at a good time to have CF. In the last twenty years, great strides have been made in treatment thanks to momentum in research. And she is now on the cusp of what was once an impossible-to-imagine adulthood.
“I keep reminding myself to calm down,” she says. “You’ve got time.”
EPILOGUE
Dreamworld
December 2015
During the first week of the last month of 2015, as part of my job with AATB, I attended the International Summit on Human Gene Editing in Washington, DC.
Jointly hosted by the National Academy of Sciences and the National Academy of Medicine’s Human Gene-Editing Initiative—alongside the Chinese Academy of Sciences and the U.K. Royal Society—the meetings brought together experts from all over the globe to talk about the many issues surrounding research that’s currently being conducted to alter human genes.
Specifically, the discussion centered on a revolutionary new gene-editing technique called CRISPR, which stands for “clustered regularly interspaced short palindromic repeats.” These short DNA sequences are a key component in the immune systems of bacteria.
“When viruses attack bacteria, the bacteria mobilize CRISPRs to neutralize the attack by destroying specific DNA sequences in the invading virus,” said biochemist Sam Sternberg, Ph.D., who studied in one of the labs credited with making the discovery, the Doudna Lab at U.C. Berkeley, and is the author of an upcoming book about CRISPR’s discovery. “By transplanting CRISPR into other kinds of cells, though, scientists have developed a new way to alter the genome.”
The technique makes it possible to make specific changes in DNA—in plants, animals, and, yes, humans. Harnessed by science, CRISPR could change everything we know about medicine. CRISPR was named “2015 Breakthrough of the Year” by the American Association for the Advancement of Science, and key players in the discovery of CRISPR were nominated for the 2015 Nobel Prize for Chemistry.
Since CRISPR is so powerful and so accessible, scientists from all over the world agreed to meet to establish some ground rules for how it should be used.
This particular conference was considered the descendant of a 1975 meeting called the International Congress on Recombinant DNA Molecules, which was held at the Asilomar Conference Center in Pacific Grove, California. In 1975, biochemists and geneticists and ethicists argued about whether research into manipulating DNA was a good idea.
The concern in 1975 arose from work that Paul Berg, a renowned biochemist at Stanford and one of the meeting’s organizers, was doing with simian virus 40, which could be made to cause cancer in rodents. Some scientists worried that the bacteria might escape and cause cancer in people. The meetings ended with an agreement that scientific inquiry could continue, but with restrictions to limit “unforeseen and damaging consequences for human health and Earth’s ecosystems,” as Berg wrote many years later in an opinion piece in the journal Nature called “Meetings That Changed the World.”
Today, it’s gene editing that’s become a controversial subject. Gene editing is exciting because it has the potential to cure fatal genetic disease. Normally, a development like this would be celebrated, since it could hold the answer to many patients’ prayers and stop suffering. However, gene editing might also be used for less noble purposes, which is where the controversy comes in.
A month before the summit, doctors were able to cure a little girl
with previously incurable leukemia “by removing immune cells, editing them so they’d go after cancer cells while also resisting a chemotherapy drug, and then injecting them back into her,” as Ed Yong wrote in the Atlantic. Elsewhere, researchers are working on taking cells from HIV sufferers, “deleting a gene the virus needs to stage its invasions,” and putting the cells back inside the patient. This kind of application of the technology is called somatic cell therapy; it changes cells inside a person’s body, and that’s as far as it goes.
Many new medical advancements are met, at first, with fear. In the 1970s, along with Berg’s simian virus 40, in vitro fertilization, a.k.a. the making of “test-tube babies,” was perceived by some as a threat to the fabric of our society. Cloning faced the same fears in later years; stem-cell research, the same. Some experts fear that gene-editing technology will to lead to eugenics, or to breeding humans to have specific characteristics. CRISPR could be used to edit the human germ line (i.e., genes inside eggs, sperm, or embryos). If genes are changed at this level, those alterations can be inherited by future generations. Maybe that sounds ominous, but what if it’s harnessed in a good way—say, to get rid of deadly and debilitating genetic diseases like Tay-Sachs and Huntington’s forever?
Panelist Hille Haker, the Richard McCormick, S.J., Chair of Moral Theology at Loyola University Chicago, recommended a two-year ban on basic genetic-editing research while the experts figure out “if we should” be doing this. She also recommended that the scientific community hold off on using CRISPR to find cures for disease for those two years, arguing that we need to consider the freedom of choice of the embryo.
When I heard her comments I thought, Freedom to have cystic fibrosis? To suffer and die as a child? The unspoken point seemed to be: if you have a disease, it’s because God wants you to have one. Patient voices were noticeably absent from the agenda.
For example, nobody was asking Jeff Carroll, an assistant professor in the Department of Psychology at Western Washington University, whose lab is looking at symptoms of Huntington’s disease, what he thought. It’s a subject close to his heart, since Jeff inherited the mutation. The thirty-eight-year-old knows that sometime in the next couple of decades, he’ll “lose control over his body and slowly go mad, just like his mother did,” wrote Antonio Regalado in the MIT Technology Review when he wrote about the conference.
During the Q & A, the organizers had put microphones in the audience, and I couldn’t help myself—my blood was boiling from listening to all this speculation and theorizing in the face of suffering—so I decided to speak.
“I’m the mother of a child who died because of a fatal birth defect. He was six days old and he suffered every day. The look on his face was like, ‘Mom, what’s going on?’ He had seizures every day. We donated his body for research. If you have the skills and the knowledge to fix these diseases, then freaking do it! That’s it.” And with that, I sat down.
NPR called me the next day to ask if I said “fricking,” “frigging,” or “freaking.”
What Is the Answer?
Most of the people on the organ-transplant waiting list are there because of a disease—a disease that could have an alternative treatment, or even a cure. Giving a kidney to a researcher could extend the already years-long waiting list, but how much longer does the list grow if researchers cannot access the organs, eyes, or tissues they need in order to find a cure?
My dream is not to make all organ-procurement organizations and eye banks go bankrupt by recovering tissue for research. The system is set up to provide organs, eyes, and tissue for patients who need a transplant. Supplying these donations for researchers is an afterthought: many OPOs refer to these donations as “research-only,” as if this were some kind of second-place or consolation prize. But the researchers may need these tissues to find a treatment or a cure for the very diseases that put those patients on the transplant waiting list. In most cases, OPOs have a monopoly on recovering organs, and they can choose not to recover an organ for research. In many organizations, this would be seen as a sound financial decision. OPO leadership might report that they cannot afford to recover organs or tissue for “research-only” donations. What can be done to change this? Researchers need tissue to conduct life-saving research, and in some cases they cannot get it, or they have to wait years.
Perhaps the processing fees for both transplant and research could be exactly the same, taking away the incentive to recover for transplant only. Perhaps this might lead to better treatments and cures, and the transplant list might decrease naturally because of this.
My Dreamworld
My dreamworld: A step toward a cure for deadly diseases like retinoblastoma, urea cycle disorder, cystic fibrosis, and anencephaly. A new treatment for cervical cancer. A medical device that can save the sickest and smallest patients through innovative intraosseous access. Training for paramedics to find an infant’s airway. Cornea studies that may help restore lost vision.
Like millions of others before them, these discoveries were made possible through organ, eye, tissue, blood, and whole-body donations. In many cases, the decision to donate was made by grieving families on the worst day of their lives. Why shouldn’t they ultimately know the impact of these donations? I wanted to know, and now I want to help others find answers that may give them meaning and peace, as my journey in learning about Thomas’s donations did for me and my family.
Fortunately, things are changing. The National Disease Research Interchange is in the early stages of launching a program to keep donor families informed about research that involves their loved ones’ donations.
In addition, OPOs across the country are learning more about neonatal donation, communicating with one another, and developing new processes. The OPO in Dallas, Southwest Transplant Alliance (STA), performed their very first neonatal donations for research in 2015, per the request of Michelle Seyl, mom of baby Alex, who was born with trisomy 18. Trisomy 18, also known as Edwards syndrome, is caused by an extra chromosome and is life-threatening. Michelle told me that because of the Philly.com story, she reached out to STA to facilitate research donations of her son’s body: his brain went to the Brain Endowment Bank at the Miller School of Medicine for the study of trisomy 18 and other neurodevelopmental disorders; and his lungs went to the International Institute for the Advancement of Medicine, which matched the donation with a request from researchers investigating new treatments for cystic fibrosis.
Eversight, one of the largest consortium eye banks in the United States, has launched a donor family–researcher program to help donor families and researchers meet. This is how Eversight describes its work: “Through research, we seek to have a maximum impact on finding new cures and better therapies for those with blindness and vision loss—giving hope to millions. This program would offer a previously untapped potential and fulfill a new mission of Eversight; to provide a greater source of healing and pride for families experiencing loss. We not only help to restore and preserve sight, but we offer families hope through eye donation as an opportunity to allow their loved ones a lasting legacy. The researcher would greatly benefit from gaining a deeper understanding of the gift that makes their efforts possible. Our program would shed light on the inseparable bond between donation and finding the next cure.”
In my dream world, there would be an established process for a donor’s family to be more informed, if they want to be, about the research projects to which their loved one contributed. The donor’s family would have the right to be notified if a study is published; they would be invited to attend events, tour facilities, and correspond with the researchers. Organ, eye, and tissue donors would be recognized with a memorial plaque in every lobby. This would go both ways: researchers would be invited to write a letter to the donor’s family about their research, and they could meet if they want to. Researchers and organizations would be accustomed to this kind of interaction—the same way medical schools are now inviting donor families to deceased-donor recognition cerem
onies. Alex Solomon, a student at Georgetown Medical School, explained that students there are told before the beginning of the full-year anatomy lab that the deceased donors they will be working with will be “the most valuable teachers we’ll ever have in our medical career,” and that students are expected to treat them with the utmost respect. At the end of the course, eight months later, the students create and conduct a remembrance ceremony complete with readings and songs for the families of the donors, which is held in the school’s largest auditorium. Students, faculty, and extended family are then invited to mingle—an invaluable opportunity for the students to thank the donor families for their loved one’s final gift.
If you are a researcher or work in an organ-procurement organization and are approached by a family, as I approached the facilities that received my son’s gifts, here’s why you don’t need to worry about this: it’s completely legal within the parameters of HIPAA and may even improve the experience of your employees and researchers, as well as bring comfort to the donor family. (Also, in my experience, PR teams are glad for the opportunity to tell a positive story about what their organization does.)
In July 2013, Bethany and Eric Conkel founded Purposeful Gift after having lost their son, Amalya, the previous year. This is how they describe their effort: “The goal of Purposeful Gift is to make the donation process easier for families in the future by offering accurate information in regards to various types of donation, as well as providing resources and support to families as they walk through their journey.” Purposeful Gift has helped parents around the world learn about research donation options, and helps educate OPOs around the country. Thanks to Purposeful Gift, multiple OPOs have completed their very first neonatal research donation.