Culture Research

By Kristin Bratton Nelson

Vaccinations, now a cornerstone of public health programs worldwide, are one of science and public health’s most impressive success stories. Ironically, it is precisely because immunization is so effective at preventing disease that we take for granted our modern invulnerability to infections that plagued the generations before us. But vaccination coverage rates have fallen in recent years in the United States, and as a result, outbreaks of vaccine-preventable diseases increasingly make headlines. The Vaccine Race is a timely and vivid reminder of what came before, and what a remarkable human achievement it is to cheat nature—to outsmart a virus.

In her debut book, science reporter Meredith Wadman describes the pursuit of a rubella vaccine through a series of intertwined narratives about a bright young crop of ambitious scientists in mid-twentieth-century America. Wadman’s narrative spans nearly 50 years and several institutions and tells the story of several vaccine candidates. But it focuses primarily on three characters: Leonard Hayflick, a brilliant but stubborn cell culturist; Stanley Plotkin, a physician bent on discovering a rubella vaccine in time to stave off an impending epidemic; and Hilary Koprowski, their colorful, visionary boss and head of the Wistar Institute in Philadelphia.

Hayflick was instrumental in the birth of WI-38, the first human cell line derived from normal tissue able to be grown in a laboratory. Although scientists had previously been able to maintain human cells in the laboratory, the cells would often become cancerous, either by picking up genetic abnormalities as they replicated or as a result of harboring undetectable cancer-causing viruses. The advent of Hayflick’s new human cell lines represented a nearly infinite supply of “clean” cells for growing the viruses necessary to manufacture vaccines. Plotkin and Koprowski would do just that: in 1969, they developed the RA27/3 rubella vaccine, the first of many vaccines using WI-38 cells.

The importance of these discoveries is clear today, but they were hardly met with universal acceptance by the scientific community at the time. Hayflick’s cell culture research was consistently undervalued, and there was intense controversy over whether human cell lines should be used in vaccine development at all. But as the book’s subtitle suggests, Wadman’s central thesis transcends the science of the vaccine, focusing on a theme that continues to resonate today: the inevitable intersection of science, politics, and culture and the messy but remarkable process of scientific discovery.

Although the story doesn’t focus exclusively on Leonard Hayflick, he is perhaps its most memorable character. Extraordinarily bright but chronically underappreciated, his careful research would lay the groundwork for the development of vaccines that would protect hundreds of millions of people against polio, rabies, measles, varicella, hepatitis A, shingles, and adenovirus. But he was, first and foremost, a basic scientist, who was interested less in the finer points of vaccinology than the simple question of whether it was feasible to develop normal human cell lines for use in the laboratory. After establishing the WI-38 cell line, he would go on to forever change the field of cell biology. In 1965, he published a seminal paper describing what is now known as the Hayflick limit, an upper bound on the number of times a normal human cell population will divide. The paper had wide-ranging implications in a number of fields, including cancer biology and aging.

Hayflick’s career, however, was tarnished by his involvement in a protracted dispute with the Wistar Institute and the National Institutes of Health over claims to the WI-38 cells. Though Hayflick had been party to agreements stating that he did not have exclusive rights to the WI-38 cells, he insisted that their rightful ownership was in question. When he left the Wistar Institute for a professorship at Stanford University in 1968, Hayflick took matters into his own hands: he packed up his two children and drove to California, taking along his entire collection of WI-38 cells. Once at Stanford, Hayflick began selling the cells to pharmaceutical companies at a profit. In the lawsuit that ensued, Hayflick’s stubborn self-righteousness and general lack of cooperation irreparably damaged his career.

The episode showed Hayflick to be a bit too enterprising for the sensibilities of the scientific community at the time, which dictated that scientists be driven by passion for discovery rather than profit. (When Hayflick’s contemporary Jonas Salk was asked who owned the patent to his polio vaccine, Salk famously responded, “There is no patent. Could you patent the sun?”) The notion of developing biological products to be sold for financial gain was anathema to most in Hayflick’s field, and throughout the course of what turned out to be a very public dispute, Hayflick came to be regarded with contempt by many of his peers.

The controversy over ownership and commercialization of Hayflick’s WI-38 cells brought to the fore an issue that the scientific community would soon have to face head-on: that science and business are not, as many purists had long maintained, incompatible. Moreover, in the face of slowing growth of government funding for scientific research in the 1970s, commercialization represented an important source of financial support for the nascent but expanding field of biotechnology. Wadman paints the Hayflick case as a watershed event that raised important legal and ethical questions about who owns and can profit from biological products and, more broadly, about the role of scientists in bringing their discoveries to the market.

Wadman takes an even-handed, journalistic approach to tackling several thorny ethical issues around vaccine development and testing. The quest to find young cells to supply Hayflick’s cell culture experiments saw one of the first uses of human fetal tissue for research. Since fetal tissue was difficult to obtain for research in the United States, Hayflick turned to Europe, where countries operated under slightly more relaxed rules. Wadman chronicles the long journey of the tissue that would eventually give rise to WI-38, from the fetus of an unnamed woman in Sweden to Hayflick’s laboratory in Pennsylvania. The Swedish woman who donated the tissue after undergoing an abortion—she is referred to as “Mrs. X” in the book—did not know until many years later of its eventual whereabouts or its use. Wadman draws the apt comparison to the story of Henrietta Lacks, whose tissue was used without her consent to create the HeLa cervical cancer cell line around the same time.

Although none of Hayflick’s work was illegal, it was done with an air of secrecy to avoid unwanted attention from anyone who might look askance at his experiments. Though research involving fetal tissue is now highly regulated, it remains a lightning rod for controversy. Beyond whether the research itself is acceptable, the issue of exactly how far an individual’s ownership of his or her tissue extends—for example, whether donors should have any financial claim to biological products produced using their samples—remains a contentious one.

Once researchers developed potential vaccine formulations, they had to test them. In the absence of regulations governing consent of research subjects, a range of institutions—women’s prisons, orphanages, and homes for the mentally disabled—became testing grounds for the safety and efficacy of several potential rubella vaccine candidates in the 1960s. Wadman recounts disturbingly little regard for the strict informed consent procedures so critical to the integrity of biomedical research today. (Legislation governing consent in research studies, resulting from revelations involving gross misconduct in the Tuskegee Syphilis Study, did not emerge until the mid-1970s.) Although Wadman’s descriptions of these studies are enough to make a modern-day scientist cringe, her tough but balanced treatment of these issues is commendable. She applies a highly critical lens to these practices, noting that they were reprehensible irrespective of their legality. To this day, these episodes remain a shameful stain on the eventual success of the rubella vaccine.

In Wadman’s telling, the human costs of the pursuit of a rubella vaccine take several forms. The first is the many individuals who volunteered their bodies, knowingly or unknowingly, to develop the WI-38 cells and to test the vaccine. The second is the self-sacrifice of the many scientists—some recognized by history, others not—who spent entire careers seeking to keep the rubella virus at bay. The third may be more abstract: the children for whom the rubella vaccine, because of the political roadblocks it encountered, was heartbreakingly too late.

During the 1950s in the United States, rubella caused epidemics every several years that were met with generalized terror among pregnant women. Rubella infection could not be diagnosed, but was almost certain to cause severe birth defects if an expectant mother contracted it in the first trimester of pregnancy. Wadman recounts vividly the story of Steven Wenzler, born to a mother who contracted rubella during her pregnancy only a short time before the vaccine was available, who suffered serious cognitive and physical deficits that would profoundly influence the course of his life. She reminds us how truly frightening it is to be defenseless against a disease that we cannot detect or treat. With the emergence of several disastrous pandemics over the past few years, perhaps we have a sense of what this fear may have been like. And as the scientific and public health communities scramble to develop and responsibly test vaccines for new viral threats, including Ebola and more recently Zika, Wadman’s commentary on the “human costs” of similar previous efforts is particularly resonant. One thing is certain: we will continue to confront threatening epidemics of diseases, old and new, and it will be incumbent upon us to have learned from our past experiences.

Wadman’s writing is what makes the book a standout, and it’s a testament to her skills as a storyteller that it reads considerably more like a detective novel than nonfiction science history. Wadman is as adept telling a story set at the lab bench as she is about the trials of Steven Wenzler and his family, and this makes for a dramatic and highly engaging story. The book is meticulously researched, and though the story has an almost overwhelming number of characters, a helpful glossary in the back ensures that readers can always track backward to refresh their memories if needed. Wadman balances her more dramatic flourishes with clear, jargon-free descriptions of cellular biology and immunobiology, managing to make accessible even the most technical of concepts.

The Vaccine Race tells a compelling and highly accessible story about the extraordinarily hopeful but fiercely contentious nature of scientific research. At its core is a story about the profound impact that passionate and brilliant—but, to be sure, flawed and often biased—scientists can have on the human condition. We don’t see this nuanced portrayal of scientists enough, especially in a manner artfully tailored to appeal to a wider audience. It acknowledges that science is done by humans, and therefore it will never be perfect. In fact, the scientific process is in many ways a reflection of both our most industrious, inventive selves and our many shortcomings, but it also serves as an objective measure of our immense capacity for progress.