Article 4: Wendy Chung

Wendy emits intensity, generativity, and depth of field. She moves easily from past to future. She has tremendous confidence in her vision and can articulate it boldly and humbly. Her presence is both receptive and awe-inspiring—how can this plain-spoken young woman be at the international pinnacle of futuristic scientific plans for our genomic hopes? - Rita Charon

Narratives of Discovery

 All non-referenced quotes are the words of Dr. Chung

Geneticist and pediatrician Wendy Chung has made her mark as a visionary scientist in genomic medicine, public perception and representation of science, medical education in genetics, and legislative and legal structures affecting the genomic enterprise. Her publications are influential, whether in Science on genetic predictors of autism, in JAMA on prospective risk cancer risk estimates in BRCA 1 and 2+ women, or in the genetics specialty literature on a vast range of genetic variants causing disease. Her labs have identified at least 25 genes and their phenotypes for neurodevelopmental and other diseases. Her genetic discoveries encompass autism, spinal muscular atrophy, congenital heart disease, congenital diaphragmatic hernia, pulmonary hypertension, cardiomyopathies, arrhythmias, breast and pancreatic cancer, rare inborn errors of metabolism, and common conditions of obesity and diabetes.

Kennedy Family Professor of Pediatrics (in Medicine), Dr. Chung leads the Precision Medicine Resource in the Irving Institute/CTSA and is Associate Director for Education of the Herbert Irving Comprehensive Cancer Center. She is Chief of the Division of Clinical Genetics in the Department of Pediatric and Medical Director of Columbia’s Genetic Counseling Graduate Program. Beyond Columbia, she advises NIH in Human Genome ELSI research, is clinical research director of the Simons Foundation Autism Research Initiative, has testified at the Supreme Court on genetics cases, and stars in the award-winning Ken Burns documentary “The Gene.” Finally and perhaps most importantly, she has a large pediatric practice in Children’s Hospital, following children and families for decades, while raising her own two boys at home.

Dr. Chung seems equipped with the metaphorical eyes of the dragonfly—360o vision with compound eyes having 28,000 lenses—and endowed with the range of the Hubble telescope. She inherited her mission as a dictate of time, starting medical school in 1990 as a biologist with a major in biochemistry. That was the year the Human Genome project and the Hubble telescope were launched. Wendy subscribes to a myth about herself that she and the Human Genome Project matured together, that they have a kinship, a twinship of sorts. Maybe she did not realize at the time that she had also inherited the Hubble Telescope’s ability to pierce spacetime too. She has arguably one of the most acute capacities within bioscience to see the present and the future of not just genomics but medicine tout court.

Even on a Zoom screen, Wendy emits intensity, generativity, and depth of field. She moves easily from past to future. She has tremendous confidence in her vision and can articulate it boldly and humbly. Her presence is both receptive and awe-inspiring—how can this plain-spoken young woman be at the international pinnacle of futuristic scientific plans for our genomic hopes? I can imagine what it must be like to be her patient or a patient’s parent, to be listened to with such attention, realizing that all these conversations are shared efforts in seeing reality together.

At the same time, she can question the most fundamental parts of her work:

"I do think that we're getting more into the ability to understand the complexities of heritable changes. There are also, as you know, changes that are going on over the life course, in terms of your genome, whether it's epigenetic or your environments and what you're exposed to. I'm not completely a genetic determinist or genetic nihilist and saying that everything is based on your genes." (7.14/2: 5:58-7:21)

With profound optimism, she cares for children with Chromosome 8 diseases and KIF1A Associated Neurological Disorder (KAND), all currently untreatable, and has organized a community of children afflicted with these conditions and their parents. Wendy’s message to this community is that the scientists and physicians and families are working toward knowledge that could, in turn, lead to something medically actionable.  

Knowing that it is unethical to screen for a condition for which there is no therapy or cure, she also knows that the sooner any patient or family know of a brewing condition, the more effective will be any intervention. Hence her leadership in executing mandated newborn  screening across the board for a growing number of genetic variants:

"It's really from an epidemiological point of view equitable, unbiased, and gives every baby a chance at the healthiest life possible. But, that comes with just incredible ethical questions about what [results] do you return, what do people want to know, does the child have a right to an open future? Are you robbing them of that?" (7.19/2 03:45).

Wendy is caught in paradoxes at the highest levels of science and technology.  She has graduated from the mission to figure out the genetics of rare diseases to the commitment to find and deliver treatments for the diseases she can diagnose. Why diagnose if that does not lead to improvement? It feels immoral to her to keep doing that.

"Everything starts with the patient and it goes back to a patient, right? I started thinking back to the 20 years that I've been doing this and thinking about all of those people, families that I've come to know over the years, and we're great pals, but at the end of the day, we still want something more than just being able to support these individuals. I guess seeing them passing on and still being frustrated. [She pauses.] You know, to me being able to give reproductive options and even preimplantation genetic diagnosis is great and that's wonderful. That's still not helping the generation of folks that we have around now." (7.14, 2nd transcript, 20:28).

It is as if Wendy is attuned existentially to the afterlife, as if the ghosts of her dead patients are instructing her. It reminds me of a scene in W.G. Sebald’s novel Austerlitz where Evan the cobbler tells Austerlitz of the veil between this life and the next:

Evan the cobbler . . . had a reputation for seeing ghosts. . . . Hanging from a hook on the wall above Evan’s low workbench, said Austerlitz, was the black veil that his grandfather had taken from [a] bier . . . [Evan] once told me that nothing but a piece of silk like that separates us from the next world.[1] (53–54)

Wendy’s ghosts have led her to join George Hripcsak in Columbia’s Department of Biomedical Informatics in the eMERGE (Electronic Medical Record & Genomics) study, an NIH-funded project that combines data from multi-institutional DNA biorepositories with electronic medical records to assemble predictive combinations of signs and symptoms of common diseases (breast cancer, prostate cancer, ischemic heart disease, etc.) and then to scan electronic medical records for matches of patients with any of those combinations. The hope is to equip doctors to better predict if and when a patient might develop a particular disease: 

"We don't want to leave [our adults] behind. And so a cutting-edge thing that we're doing right now is about genomics and the electronic medical record. What we're doing is hair-raising for me because we're right at the precipice, we're right at the edge of where we should be pushing clinical implementation."  (8.3, 09:37).

Wendy thinks in systems—social, ethical, legal, political, economic, cultural, global—and has developed skills to predict, communicate, persuade, model, and endure. Gifted with fluency to interact with the scientific community, the lay press, network television, social media and caring for patients ranging from Washington Heights neighbors to clients who fly her to the Mideast to perform diagnostic work-ups on newborns, her work embroils her in ethical, religious, and economic quandaries. An awareness of psychological complexity governs her clinical actions, registering her patients’ hopes and fears, what they can and cannot bear to know. She wants more clarity so that clinicians can be straight with patients instead of talking in code:

"Everyone should feel good about their decision at the end of the day. [We need]  information to inform those decisions. That helps the communication between our healthcare teams and the families, because there's more certainty. We're not talking about hypothetical things. It's not this amorphous sort of discussion where I'm saying this, but I really mean this. Very straight-forward discussion adds a huge level of clarity and honesty and transparency."

As I listen to Wendy discuss her work, I appreciate the onion layers of responsibility she accepts—regarding the unborn, the adults who cannot be left behind, the general public, the physicians, the science. While the therapeutic capacities of medicine widen by day, she foresees the need to face “not one rare disease at a time. It's the infrastructure for 7,000 conditions at a time, right?” (8.03, 15:31). Selecting among therapeutic approaches—an ASO (antisense oligonucleotide), gene replacement, or gene editing, or non-genetic interventions—is but the beginning. Recruiting patients who might benefit from an emerging therapy, setting up clinical trials, selecting outcome measures, the organization and payment for all those things have to be foreseen and worked out.

Our conversation veers inevitably to money. Wendy asks pointedly, “How do you build the plane while you’re flying it?” (8.3, 06:01). If experimental treatments are developed by industry who stand to gain should they be found effective, ought not the cost of experimental treatment be borne by pharma? Even if that comes to pass, the eventual price of these treatments may well be exorbitant, unless fundamental changes are made in health care coverage. The wealth/health gap increases, Wendy realizes. She tells of wealthy older men seeking to father a child who come to her for genetic screening of their sperm or pre-implantation embryos against the possibility of autism. We agree that the unacceptable but seemingly inevitable outcome of these practices is that ill children are born to poor families while the privileged can afford to screen them away.

Wendy hopes that the Biden-proposed ARPA-H will be one answer to health inequity. Defined by the NIH as “building high-risk, high-reward capabilities (or platforms) to drive biomedical breakthroughs that would provide transformative solutions for all patients,” such “cancer moon-shot” funding may a more equitable distribution of the fruits of our scientific work.

Physical chemist and philosopher Michael Polanyi describes how “responsible choices made in the course of scientific inquiry. . . are made by the scientist; they are his acts,” but these acts “stand under the judgment of the hidden reality” the scientist hopes to uncover. “In these intensely personal acts, therefore, there is no self-will. Originality is commanded at every stage by a sense of responsibility for advancing the growth of truth. . . . Its freedom is perfect service.[2]

            Wendy Chung stands as a model of discovery, originality, responsibility, and freedom.