A Cell’s Life

Here’s a simple statement most Americans would agree with. If tissue removed during an operation is about to be thrown out with the garbage and has no identifying information, it should be permissible to use it for research without the patient’s consent.

This isn’t just a sensible idea; it’s the law of the land. In fact, the federal regulations don’t even consider this to be research involving human subjects. It is exempt from the federal rules, requiring neither review by an institutional review board (IRB) nor consent from the patient.

If this all seems straightforward and uncontroversial, then you have not read Rebecca Skloot’s remarkable book, The Immortal Life of Henrietta Lacks. Skloot spent the past decade exploring one such research study, which mushroomed into one of the most important discoveries in the history of science: the development of an immortal line of cells known as HeLa cells that have played a central role in tens of thousands of research projects, with incalculable benefits to humankind. Their popularity is related to their ability to reproduce rapidly and easily, their immortality, and their familiarity, because thousands of studies have allowed their biologic characteristics to be known in great detail.

That’s the good news. But while scientists, entrepreneurs, and patients have been enjoying the many benefits of HeLa cells, the extended family of Henrietta Lacks, the woman who was the source of the cells, has endured nearly 60 years of anguish directly related to the success of the HeLa cell line. They remain mostly impoverished and without access to health insurance, unable to share in many of the benefits made possible by Lacks’s contribution.

Skloot’s book tells two parallel stories, reminiscent of Anne Fadiman’s influential The Spirit Catches You and You Fall Down, the celebrated account of one Hmong family’s encounter with the U.S. health care system, interwoven with the history of Hmong civilization. In Skloot’s book, researchers at the Johns Hopkins Hospital discovered one of the holy grails of in vitro cell biology: a human cell line that could propagate itself forever, defying Hayflick’s dictum that every cell has a limited number of times it can reproduce itself. In the other story, a poor black woman dies in a segregated ward with excruciating pain from untreatable cervical cancer, and her family grapples for decades with the consequences of being excluded from any meaningful information about her death and her immortal progeny. It is only in an afterword that Skloot begins to explore a third story: the problem with the “simple” concept that research with unidentifiable residual human tissue should be outside the regulatory structure of human subjects research.

The story of the HeLa cells alone is sufficient for a book and has indeed been the subject of a BBC documentary and numerous other accounts. The numbers alone are mind-boggling: An estimated 50 million metric tons of cells; 60,000 scientific studies; the generation of immeasurable profits; and the saving of untold numbers of lives.

But it is the other two stories that demand our attention. Because informed consent was not required for the development of the HeLa cells, neither Henrietta Lacks nor her impoverished family, including her husband and five children, knew the cells even existed until 20 years after they had become “celebrities” in the world of science. The family was contacted at that time by researchers at Hopkins who wanted blood samples to help them better define the genetic characteristics of the HeLa cells, in part because the cells were so prolific that they were contaminating and dominating cell cultures all over the world, making it difficult for scientists to determine whether they were studying HeLa cells or those from another source. But the inadequacies of the consent process for a simple venepuncture planted the seeds of confusion, leading some of the family to believe they were being tested for cancer.

This was the first of several fantasies and nightmares that came to dominate the thinking of the Lacks family. Words such as “immortal cell lines” that were mundane in the world of science were interpreted as a suggestion that Henrietta herself was still alive, decades after her reported death, held captive at Hopkins as a research subject. The word “cell” supported this fear, as its sole meaning for an impoverished, largely illiterate black family evoked images of a prison.

Skloot pulls off a remarkable tour de force in reporting by maintaining a dispassionate perspective in writing about these events, despite becoming a character in the story. Over the course of 10 years, she developed a personal relationship with several key family members, particularly Henrietta’s daughter Deborah, as she built the trust required for them to begin talking with her and over time to share critical archival material and reveal their deepest feelings.

You won’t often see a passage like this in a book of this quality. It follows an angry accusation by Deborah that Skloot is a spy for Hopkins, part of the conspiracy that has been exploiting Henrietta and the family for 50 years:

“Then, for the first time since we met, I lost my patience with Deborah. I jerked free of her grip and told her to get the fuck off me and chill the fuck out. She stood inches from me, staring wild-eyed again for what felt like minutes. Then suddenly, she grinned and reached up to smooth my hair, saying, ’I never seen you mad before. I was starting to wonder if you was even human cause you never cuss in front of me.’”

Despite the page-turning force of both stories, it is the third story, the ethics and regulation of research involving residual samples, that makes the book required reading for those involved with policies and practices in this area. I have been arguing for 15 years that human research is wildly over-regulated in the United States, dominated by inflexible interpretations and the application of rules with little or no relevance to protection of human subjects. There is a growing consensus that the bureaucracy is discouraging innovation and discouraging students from entering the field. All that is true, but the Lacks family story forces us to ask whether the least risky category of research, on unidentifiable residual tissue, is under-regulated.

One part of the problem is the vanishing relevance of the concept of identifiability. Henrietta Lacks’ immortal cells had a code name so meaningless that they were long believed to have come from an unknown source given a made-up name such as Helen Larson. But 20 years after Henrietta’s death, when the eminent geneticist Victor McKusick had a scientific reason to track down the real source in order to obtain more samples from Henrietta’s descendants, he had little trouble finding them.

The ability to do genome-wide analyses on microscopic samples, coupled with ever-growing databases and repositories (such as the results of genetic research that the National Institutes of Health require to be made public and the collection of blood spots from newborns) has reduced confidence that any sample can be truly “unidentifiable.” Breakdowns in physical security measures, whether thefts of laptop computers or hacking into “protected” databases, have further eroded confidence in the confidentiality of stored samples or data derived from them.

A second problem is the limited value or meaning of consent when many of the most important projects cannot even be imagined at the time when the samples are obtained. Henrietta Lacks might have gladly consented to George Gey’s request to use part of her discarded tumor for studies in his lab. But no one could have anticipated at the time that this small experiment would lead to 50 million metric tons of cells that would transform the practice of medicine or that many of the medical benefits would be beyond the reach of Henrietta’s children. Their mother is buried in an unmarked grave in a town that no longer exists. It is not at all clear that she would have agreed to contribute to that kind of system.

At the least, the Lacks family experience should lead to a reexamination of the current policy of exempting such research from the federal regulations. The DHHS Secretary’s Advisory Committee on Research Protection is the appropriate group to review this issue. In my view, technology has made the concept of “unidentifiable” almost obsolete when human cells are involved. To better protect individuals and families such as the Lacks will require higher standards of consent or stricter rules for sharing access to such materials. The recent settlement with the Havasupai tribe over unconsented use of donated tissue tells us that this issue is not unique to the HeLa story.

If Skloot’s book does not cause you to rethink your position on these issues, then you have missed its most important point. But it is still a page-turner of the first order.