“Anger Is Awesome”: Martin Moran’s Quest to Find Where Rage Meets Compassion
“Born This Way” or “Choice”?: Understanding the Development of Sexual Identity

Tales from the Frontier of Genomic Medicine

A Q&A with Steven Lipkin, MD, PhD and Jon L. Luoma

DNA Lab. Photo credit: University of Michigan School of Natural Resources & Environment

We are living in an age that promises to be a watershed in the history of health and medicine. Genetic testing is experiencing the kind of exponential growth once seen with the birth of the Internet as the plummeting cost of DNA sequencing makes it increasingly accessible for individuals and families. In The Age of Genomes: Tales from the Front Lines of Genetic Medicine, which went on sale this week, geneticist Steven Lipkin, MD, PhD and science journalist Jon Luoma explore the transformative potential and risks of genetic technology through the true stories of patients facing devastating neurological diseases, cancer, and other maladies. Physician Siddhartha Mukherjee, author of The Gene: An Intimate History, called The Age of Genomes “a thrilling and deeply relevant book” that “remind[s] us how profoundly the new science of genomics and will impact all of us in the future.” Our blog editor Christian Coleman caught up with Dr. Lipkin and Luoma to ask about the implications of genome sequencing we should consider, medical and sociological, as well as the possible side effects to look out for.

Christian Coleman: What are some of the benefits of having access to the stores of genetic data we have now?

Steve Lipkin, MD, PhD: Genetic information has become an important part of preventative health. About six percent of the American public belongs to a family that carries a genetic disease, and this number is likely to rise with likely improvements (albeit also increased costs) in quality of life and lifespan. If a person has no diseases that run in their family and has no personal medical issues, then the chances that they will learn something interesting from genetic testing is low. One exception to this rule is when couples are planning to start a family, because many serious genetic diseases are recessive (e.g. mutations from both parents contribute), and so don’t usually have family history. For example, I found that I carry four known recessive disease mutations. While they don’t obviously affect me, this information is useful for my daughters if and when they want to start families.

CC: Speaking of starting families, advances in genetic medicine will impact women’s reproductive options. Tell us what kind of relationship a patient should have with her geneticists and what she can expect from her appointments. 

SL: The availability of in vitro fertilization and pre-implantation genetic diagnosis (PGD) has changed the landscape for couples who want to use genetics to improve the lives of their children for serious childhood diseases. PGD for pediatric genetic diseases—and there are thousands—has helped alleviate a tremendous amount of suffering for children.

The newer thing is that in the United States, Europe, and Japan, PGD for adult genetic disorders is widely available. There is currently great variance of opinion among the general public, different medical specialties, and individual medical providers about whether the potential risks of PGD outweigh the benefits of preventing a serious disease that a person may or may not develop over a lifetime.

The Ethics Committee of the American Society for Reproductive Medicine (ASRM), whose members provide these services, concluded in 2013 that “PGD for adult onset conditions is ethically acceptable as a matter of reproductive liberty.”  The precise number of parents having ART (advanced reproductive technologies)/PGD performed for adult-onset conditions is not well known, and this procedure is not regulated in the United States at the state or federal level. Anecdotally, it is increasing a lot.

In the next decade, we will likely see effective gene editing techniques that allow correction of gene mutations without side effects for embryos.

CC: You write about the “knowledge imperative,” the patients’ desire to know as much as possible about their genes for the sake of health and planning for old age. While generally beneficial, in what ways can the knowledge imperative be harmful to them? 

Jon L. Luoma: Lydia (not her real name), a patient who appears in the book’s second chapter, “The Unactionables,” originally visited Steve’s clinic because she was deeply worried that she might have inherited genes linked to the terminal ovarian cancer that afflicted her mother. On that score, she got some good news: her family’s medical history suggested no unusual risk for that disease. But the family history also raised a red flag: that she might instead be at risk of inheriting genes linked to Alzheimer disease, which had afflicted both her father and an uncle.

A careful examination by a neurologist, following by genetic screening, could improve her knowledge about whether she was at increased risk for this devastating malady. But since Alzheimer disease can’t be cured, was it knowledge this patient—or any patient—wanted to have?

Lydia had been fully prepared to pursue testing for cancer, where aggressive screening and early detection can mitigate known risks. But she wound up deciding that she didn’t want to further pursue knowledge about the risks she might bear for incurable Alzheimer disease. Other patients might have preferred to proceed with testing in order to plan their lives accordingly. Yet even that might be a fraught decision—the presence of deleterious genes might only increase the probability, rather than certainty, of suffering a related disease, raising the risk of unwarranted anxiety and depression.

CC: The price of DNA testing and genome sequencing has come down considerably, but how do you see the influence of class and socioeconomics playing out in genetic medicine? It seems as though upper-middle-class patients and celebrities have the access to the most rigorous testing. 

SL: We live in an age of wealth disparity, with the wealthiest segment of the population owning an ever-growing, oversized slice of the world’s riches and financial assets. Over the longer term, differential availability of genetic services has the potential to create an underclass with high burden of disease and a wealthier class that has a lower burden, and possibly enhanced attributes. This is very concerning to me. Genomic knowledge for family disease prevention can have powerful effects, whether positive or negative, on the “fairness gap” between the genetic haves and have-nots across the planet, and this will likely reverberate across generations.

What is striking about emerging treatments for genetic diseases is how dramatic the inequalities could turn out to be, with the potential for some patients to be left with little access to relevant care, others to have limited access because they are fortunate enough to have the right insurance, and a third group, the very wealthy, having complete access: the medical corollary of “the haves, have nots, and have yachts.”

CC: Our country has an unsavory history with eugenics. How much of a risk do we run revisiting genetic discrimination when seeking genetic counselling or, as you noted in a few cultures, choosing a life partner or to have a child based on DNA testing? 

JLL: Genetic discrimination is another matter. As noted in Chapter 8, “Generation XX/XY,” two sets of studies, one from as recently as 2014, revealed that as many as forty percent of people who might benefit from genetic testing avoid it because of fears of genetic discrimination. Their fear isn’t so much that some sort of eugenics regime is going to be imposed on them, but rather that genetic data might be turned against them in the job market or by health insurers.

In fact, the chapter highlights a number of cases where the risk of genetic discrimination was real, including what turned out to be a hapless attempt to identify employees at risk for repetitive stress disorders by one major company, and a preposterous but persistent denial of health insurance to two children who could not possibly have inherited their mother’s recessive genetic disease, because their father was not a carrier.

Some of the worst of this may be behind us. In 2008, Congress overwhelmingly passed, and President George W. Bush signed, the Genetic Information Non-Discrimination Act (GINA), which prohibits genetic discrimination in employment and health insurance. However, there are some notable gaps, including the fact that GINA does not ban discrimination related to life, disability, or long-term care insurance. Further, as with, say, age- or race-based discrimination allegations, claims can be difficult to win. (There were some 700 such claims outstanding in the U.S. as the book was nearing completion.)

As one bioethicist puts it, “Discrimination can be implicit, indirect, and subtle…and be hard to prove. Patients may be treated ‘differently’ and unfairly, raising questions of how to define “discrimination.”

CC: What current developments in genomics are you most excited about? 

SL: There’s a lot going on! I anticipate that improvements in gene editing technology will have major impacts on many areas. These will likely increase the rate of genetic testing in terms of disease correction for children. Many families will be able to benefit from this and will drive the burden of genetic disease down. This will likely come in as being expensive, but hopefully costs will come down as the technology increases in scale.

There are new ideas about synthetically constructing animal genomes and placing them in cells. This is a very bold and innovative idea, and is becoming more topical. However, as the gene editing technologies improve, this synthetic approach may well be more cumbersome. Clearly, this area needs regulation as the ability to introduce new animal species or cross speciation can have effects on the environment that we may not be able to predict and result in unintended consequences.

In the cancer space, gene editing technology is being used to generate exciting new therapies that use the immune system to attack cancers, and to kill cancer cells directly. There are many labs and companies pursuing these, which so far has worked better for leukemias and lymphomas because they may be more immunogenic.


About the Authors 

Steven Monroe Lipkin, MD, PhD, FACMG, has been a practicing clinical geneticist for almost twenty years. He directs the Adult and Cancer Genetics Clinic and is the vice chair for Translational Research at the Sanford I. and Joan Weill Department of Medicine at Weill Cornell in New York City.

Jon R. Luoma’s writing about science and the environment has appeared in National Geographic, GQ, the New York Times Sunday Magazine, and Audubon, where he was a longtime contributing editor. He is the author of three previous nonfiction books: The Hidden Forest, A Crowded Ark, and Troubled Skies, Troubled Waters.