A Life Everlasting (20 page)

F
ive years after Thomas's death, a lot had changed. What started as a broken heart blossomed into a sense of pride in my son's accomplishments. His donation exposed me to a world of scientific and medical advancements I would not have even imagined before. I had the privilege of meeting brilliant and kind professionals who are changing the field and saving and improving lives on a daily basis.

Thomas led me to a new career, and his deeper purpose gave me one, too.

At the end of October 2015, the National Disease Research Interchange (NDRI)—the organization that facilitated the donation of Thomas's cornea to Harvard and his retina donation to the University of Pennsylvania—celebrated its thirty-fifth anniversary with a symposium at the Union League of Philadelphia: “
From Donation to Discovery: The Critical Role of Human Tissue in Research.
”

Since its founding three and a half decades earlier, not only had NDRI become a leader in the world of recovering and
distributing human organs and tissue for research—what they call “biospecimens” in the profession—they had also developed a number of specialized programs to help researchers in specific ways.

The first panel of the day was called “Advancing the Nation's BRAIN Initiative.” BRAIN stands for “Brain Research through Advancing Innovative Neurotechnologies,” and the initiative was launched by President Barack Obama in April 2013 to support further understanding of the human brain and uncovering new ways to treat, prevent, and cure brain disorders like autism, epilepsy, schizophrenia, Alzheimer's, and traumatic brain injury. And the government wasn't fooling around: the National Institutes of Health invested more than $130 million in BRAIN in the first two years alone.

Why so much interest in the brain? Because every year, approximately one in eighty-eight children in the United States is born with autism or a related disorder, and more than five million older people will be diagnosed with dementia—a number that's likely to rise as the boomer generation moves into old age. Also on the rise are ALS, or amyotrophic lateral sclerosis (a.k.a. Lou Gehrig's disease); Parkinson's; and progressive supranuclear palsy, a degenerative neurological disorder that affects about twenty thousand Americans and for which there is no effective treatment or cure.

Suicide is a significant public health issue as well. It remains one of the leading causes of death in this country: it's tenth overall, fifth for ages forty-five to fifty-nine, and second for ages ten to twenty-four. Suicide among young Native Americans is nearly twice the national average. Women are three times more likely than men to attempt suicide, but men are four times more likely than women to actually kill themselves.

Here are some of the other sobering statistics for suicide
in the United States, according to the American Foundation for Suicide Prevention: a million people attempt suicide every year, and forty thousand are successful. Veterans account for more than 22 percent of suicides. (U.S. Department of Defense guidelines make it very difficult for researchers to gain access to the brains of deceased veterans for the purpose of research, whether death was from suicide or traumatic brain injury.) And 90 percent of people who commit suicide have a diagnosable psychiatric disorder.

Given these upsetting numbers, researchers are keen to investigate the physiological aspects of brain function that might help explain why suicide is such a big problem.

So here's the big challenge that medical science faces: We all learned in school that the brain is the most complicated organ in the body, which means it remains—even with all our advancements—one of the least understood. There are something like one hundred billion neurons sending about one hundred trillion messages to one another, which makes the brain “one of the greatest mysteries of science and one of the greatest challenges in medicine,” according to the BRAIN Initiative. Given the ambitiousness of the project, NIH is collaborating with scientists and engineers from other government agencies, such as the Defense Advanced Research Projects Agency (DARPA), National Science Foundation (NSF), U.S. Food and Drug Administration (FDA), Intelligence Advanced Research Projects Activity (IARPA), and private partners. It's a huge undertaking, and these studies require donated whole brains.

On the dais for the first panel at the NDRI symposium were Mark Frasier, senior vice president of research programs at the Michael J. Fox Foundation for Parkinson's Research; Richard D. Hasz, vice president of clinical services at the Gift of Life Donor Program; John Madigan, vice president for public policy
at the American Foundation for Suicide Prevention (SPAN/ USA); Dr. Daniel Perl, a man with many titles including director of the Neuropathology Care Center for Neuroscience and Regenerative Medicine; and Thor D. Stein, a neuropathologist with the U.S. Department of Veterans Affairs.

There was also Deborah C. Mash, director of the University of Miami Brain Endowment Bank, which is one of just six designated brain and tissue biorepositories in the country. They're supporting research into ALS, multiple sclerosis, Huntington's disease, traumatic brain and spinal injury, developmental disorders like autism and Down syndrome, and mental-health issues like depression and bipolar disorder. Founded in 1987, the bank holds more than two thousand brains, with another five hundred people on the list to donate.

As the experts convened to discuss challenges in acquiring tissue to study, it became clear that recovering brains for research was rather different from acquiring other organs and tissues. For instance, the medical/social interview, now called the Uniform Donor Risk Assessment Interview, wouldn't have covered the kind of information that scientists looking at the brain need. A person can donate a kidney or skin without anyone needing to know if he or she ever heard voices, but not so the brain. Trying to come up with a uniform list of questions for potential brain donors and their families was a challenge.

In addition, families need to feel comfortable with the decision to donate, since they also make a decision about what kind of funeral to have. Some family members may wish to see the decedent one final time at an open-casket funeral. Facing the death can help some people believe it and come to terms with it. Initially, there was concern from both families and funeral directors that a brain-recovery incision would alter the appearance of the decedent and force a difficult decision on a family
in this position: “Do we donate a brain for research, or do we have an open-casket funeral?” OPO professionals wanted to make it possible to do both.

Rebecca F. Cummings-Suppi, L.F.D., C.T.B.S., is manager of tissue recovery and preservation at Gift of Life Donor Program in Philadelphia and is also a licensed funeral director and embalmer. She spoke about this challenge at the 2014 American Association of Tissue Banks annual meeting. Becky and her team developed a brain-recovery technique that involved making an incision from ear to ear at the back of the head where the skull meets the spine. I was touched by the pride she took in caring for both the needs of a grieving family and the research protocol.

“I don't believe in putting anything of value in the ground. Whether it's a diamond ring that can be passed down to another generation, or if it's tissue for transplant or for research,” she told me. “That's how cures happen.”

The second panel that day focused on research for rare diseases—which, generally speaking, don't have relevant animal models such as mice. (Even common disorders, like age-related macular degeneration, have this problem, because mice don't get this disease, so there's no way to study it in them. That's why researchers like Patricia D'Amore at Schepens Eye Research Institute at Harvard need human tissue to complete their work.)

NDRI's Rare Disease Initiative collects donated tissues, organs, and blood as well as DNA and cell lines for more than one hundred rare conditions. Some of these include amyotrophic lateral sclerosis, or Lou Gehrig's disease—a progressive degenerative disease that targets nerves in the brain and spinal cord and causes progressive muscle weakness and paralysis until the patient is no longer able to breathe on his or her own. (Perhaps the most famous sufferer, aside from the New
York Yankee great after which it gets its nickname, is physicist Stephen Hawking, who has managed to survive for many years beyond the usual life expectancy for this brutal disease). Also included is Lewy body dementia—also known as dementia with Lewy bodies—a disease named after scientist Friedrich H. Lewy, who identified the abnormal protein deposits in the brain that disrupt normal functions such as perception, thinking, and behavior. (The late comedian Robin Williams was found to be suffering the early stages of this disease when he took his life in 2014.) Another disease included is sickle cell disease, a genetic condition characterized by abnormal hemoglobin in the red blood cells. (At the moment, only a stem-cell transplant can cure this otherwise lifelong condition, and life expectancy is between forty and sixty years in the United States, which is nevertheless up from fourteen years just forty years ago.)

Notable among the veteran scientists on the dais for this second panel was the smiling face of a teenage girl. That's because the discussion centered in particular on NDRI's partnership with the Cystic Fibrosis Foundation and Vertex Pharmaceuticals, which together have developed the first-ever medications to treat the underlying cause of cystic fibrosis rather than just its symptoms. The young woman's name was Mara Cray; she was a patient.

Cystic fibrosis (CF) is a life-threatening genetic disease that affects thirty thousand children and adults in the United States and seventy thousand people worldwide. CF causes a buildup of thick, gluey mucus in the lungs, pancreas, and other organs. The mucus in the lungs clogs air passages and traps bacteria, which can lead to severe infections that damage the lungs. In the long run, the damage can be such that the only option is a lung transplant. Today, the life expectancy of a person with CF is under forty years. In the 1950s, it was fewer than six.

The Cystic Fibrosis Foundation was founded in 1955 by a group of parents whose children had the condition. At the time, CF kids were not expected to live long enough to enroll in grade school. In 1980, the Cystic Fibrosis Foundation created a research development program to speed up the search for a cure. That move contributed to the discovery, in 1989, of the CF gene, the first major step in understanding the disease at its root. The Cystic Fibrosis Foundation has been behind just about every drug invented to treat the disease.

In the mid-2000s, clinical trials began on the first oral medication that targets the mutated protein responsible for CF. In 2012, the FDA approved ivacaftor (Kalydeco) for certain CF patients over age five. In 2015, the FDA approved Orkambi, a two-drug combo of ivacaftor and lumacaftor, for about one-third of CF patients over age twelve. It was a huge breakthrough for the treatment of this disease, presenting the possibility for the first time of CF patients living out something closer to the life span of someone without CF.

This most recent milestone occurred in large part thanks to an effort begun by the Cystic Fibrosis Foundation with an assist from NDRI. In 2006, NDRI began receiving donations of diseased lungs from CF patients who received transplants. The donations were transported to Vertex, a global biotechnology company that studied the tissue to develop two new drugs designed to combat the disease at its biological root. Since CF, like other rare diseases, has no correlative in the animal world, to really make advances in treatment, researchers needed human tissue.

“We needed a relevant pharmacology model to assess our drugs,” said Eric Olsen, Ph.D., Vertex vice president and CF franchise leader. “Airway cells derived from the native tissue provided by NDRI allowed us to better understand” how the drugs might work in patients with CF, he told the panel.

Chris Penland, Ph.D., director of research at the Cystic Fibrosis Foundation, has said: “The most important contribution that NDRI makes is their ability to reach out into the community and acquire tissues to help drug discovery efforts. Almost every primary cell used in the research to make these discoveries was from a lung NDRI acquired.”

You could draw a direct line between the donation of those lungs by people who had no choice but a lung transplant and future CF patients who may be saved from ever needing one.

For example, Mara Cray. She has been just one direct beneficiary of those sixty years of research and about two hundred donated CF lungs.

In parallel to all this research using donated lungs, in 2014 NDRI launched a five-year initiative called the Molecular Atlas of Lung Development Program (LungMAP), which is funded by the National Heart, Lung and Blood Institute and the NIH. For this project, NDRI is looking specifically for pediatric lungs in order to study pediatric lung diseases—ones that develop in utero and in early childhood.

That's a tall order, but had it been available when Thomas died, he might well have been eligible to donate. It would have been a privilege to be a part of this project.

Perhaps the most ambitious program that NDRI supports by providing human tissue is the genotype-tissue expression (GTEx) program, which was launched in October 2010 by the National Institutes of Health's Common Fund.

As I learned from the Duke study, gene expression has a huge impact on a person's health. The federal government decided to create a massive data bank to study how that expression affects genes and correlates to various genetic diseases.

The National Human Genome Research Institute (NHGRI) described it in terms even I could understand: “Each
cell in the human body contains a complete set of genes, yet not every gene is turned on, or expressed, in every cell in the body. To function properly, each type of cell turns different genes on and off, depending on what the cell does. For example, some genes that are turned on in a liver cell will be turned off in a heart cell.”