In Carlo Caduff’s brilliant ethnography The Pandemic Perhaps, we enter a world of delayed apocalypse. The HnNn mutation of the influenza virus is on the radar of the WHO; scientists prognosticate the next pandemic; preparedness measures are put in place by public health organizations; a flu vaccine is ready to be shipped by the pharmaceutical company. But, once more suspended, the pandemic does not happen today. It will take place tomorrow. Caduff’s discussion of pandemic prophecy captures the strange exchange between influenza as a matter of scientific prognosis and of quasi-religious belief. His account thus reveals how fundamental uncertainties at the heart of the public health message are not only subject to reason, but also faith. In the genre of pandemic prophecy, scientific reason is augmented with faith, as scientists grapple with the ambivalent state of not knowing what will but suspecting that the worst might happen. Despite its sombre vision of the future, pandemic prophecy is not strictly speaking of the biblical apocalyptic genre, Caduff points out, as “it lacks the hope and desire for another world” and predicts “destruction without purification, death without resurrection […] dystopia without utopia” (7).

Part of what makes prophetic prognosis credible, in spite of its continued failure to predict, is what Caduff calls the “cosmology of the mutant strain” (80). Emphasizing its incessant mutability and volatility, scientists identify the virus as an erratic agent that constantly mutates and shifts shape, and is hard to pin down even in the lab. Showing how pandemic prophecy roots in the intricacies of research, Caduff powerfully describes scientists’ tireless efforts to define the elusive entity. How can a virus be defined in the dish, he asks, when even the tiniest of samples contains millions of mutations due to microbial instability? Vividly invoking scientists’ struggle with matter that is “constantly making itself different from itself” (88), Caduff shows how the conundrum is resolved in a statistical consensus. That is, the problem of microbial instability is overcome by a consensual agreement that indeed the dish contains a comprehensive entity. This makes the virus something scientists can work with, dealing with uncertainty by taking a leap of faith.

In my research about regenerative medicine in Scotland, the stem cell is the similarly, yet differently unstable agent that links scientific practice with public health millennialism. Like the virus, the stem cell is said to harbor an enormous capacity for shape shifting. Unlike the virus however, this capacity is not imminent apocalypse and doom, but instead nourishes visions of a glorious and hopeful future for human healing, where lab-grown replacement tissues for patients might become a salvational reality one day (Haraway 1997). Growing bodily tissues from stem cells is often perceived as a technical issue that can be overcome, once science is advanced. And yet, as I recently learned at a stem cell scientific conference, there is an element of “magic” to the salvation that stems from tissue regeneration. Stem cell science too depends on what, inspired by Caduff, might be called reason+. However, while microbial apocalypse adds faith, cellular salvation sums up with magic.

In September, I participated in the prestigious Hydra European Summer School on Stem Cells & Regenerative Medicine on the Aegean island of Hydra. As the meeting began, the participants set out to define the concept that had all brought them together. “What are stem cells?” asked one of the conveners, and at the time, it seemed like a provocative question. Nervous laughter, silence, reluctant replies, and at last heated arguments ensued. The discussion revealed the conceptual complexity of the question as well as its myriad array of possible replies. A common denominator, the group agreed, was that a stem cell is defined as the dormant cell in a bodily tissue that, once activated, has both the capacity to differentiate into varied resident cell types, repairing the tissue damage at hand, and also to self-renew, creating a copy of itself that goes back to dormancy as a backup system for future damage. Together differentiation and self-renewal are viewed as the baseline biological functions that assure the body’s ability to continuously repair and renew itself. This innate ability, stem cell biologists hope, might inform the regeneration of damaged tissues in patients suffering from a vast array of degenerative diseases.

In practice, the Hydra discussion revealed, differentiation and self-renewal make strange bedfellows. For instance in the bone marrow, the hematopoietic stem cell – that can give rise to all blood cell types – is surrounded by many other cell types. It is held in place by bony connective tissue, it is catered for by blood vessels, it is protected from harm by resident immune cells. Enveloped in this diverse environment, the dormant stem cell is activated when it receives signals to produce more of any one type of blood cell. Only then, the cell awakens and starts to divide, creating two daughter cells, one differentiating for the reproduction of blood cells and the other one self-renewing for future stem cell stock. But practically, the Hydra delegates debated, how can mere cell division be distinguished from differentiation and/or self-renewal? Is self-renewal just division? And, at what stage does differentiation initiate and consequently start to differ from self-renewal? These uncertainties were not abstract questions, but of vital practical relevance for bodily repair: It is, one eminent scientist highlighted, where the “magic” happens.

The translation of bodily topographies – where stem cells live in, and are sustained by, the company of other cells – into the petri dish is a difficult endeavor as cells’ mutual support is difficult to model in vitro. Consequently, if magic is needed to grasp the stem cell’s capacity for self-renewal and differentiation in vivo, it might be even more magical to make it happen in the lab. Then, how is the magic reproduced in the lab? I asked Robert, a postdoctoral researcher at the University of Edinburgh, the same question when on a rainy day during fieldwork he offered some advice on a cell culture that I had been growing for a few days. The first step was to assure that cells were content. As we took the cells from the incubator, Robert looked at the flask assessing the color of the medium. The medium looks orange-red when fresh and turns into yellow when the nutrients are used up, suggesting hungry unhappy cells, while it turns into purple when the O2-CO2 exchange in the flask is disturbed, suggesting that cells are asphyxiating, he explained. That day, I had screwed the lid of the flask on too tightly, and by now the bright purple of disturbed gas exchange was showing: an ominous sign. Even though the mishap could be corrected easily, it was a bad sign, cells were not too happy and Robert – knowing how to read the minutest of cellular signs – showed some concern.

Next, he peaked through the microscope to look at the cells, which were stuck at the bottom of the flask as translucent dots and surrounded by the gooey gel added to mimic the feel of connective tissue. He lamented: “They are too sparsely populated” and continued, that for stem cell populations in particular, it was essential to get the cell density right. In vitro colonies are often set up as monocultures, a dish with just stem cells. Compared with their bodily occurrence however, a monoculture fails to provide the support that stem cells would ordinarily receive from the cells in their vicinity as in the bone marrow. If the colony was too sparsely populated, the cells would die for lack of mutual support. If the cells were stacked on top of each other, they would cause each other to differentiate losing their valued stem cell state. The trick was, Robert suggested, to make a monoculture that wasn’t indeed a monoculture, where part of the cells spontaneously differentiated and part self-renewed.

Successful stem cell culture necessitated, in other words, the introduction of heterogeneity from within the cells, so the culture as a whole stayed in equilibrium between simultaneous differentiation and self-renewal. This balance could be struck – in spite of the stem cells’ lack of support from their neighbors – by regulating how densely seeded the cells were in their container. Having observed the minute intricacies of cell density time and again, Robert is proficient in the necessary conscientious care of ‘just getting it right’, a skill cell growers need to painstakingly acquire. This magic of care amplifies scientific reason about stem cell differentiation and self-renewal in order to deal with the uncertainties of cellular growth. If scientific uncertainties about the virus require reason+ that is augmented by faith, ambiguities about the stem cell are partly resolved by the addition of magic.

Taken forward into the realm of the public health message however, scientific uncertainties about the virus have an entirely different inflection than they have for the stem cell: While faith in the pandemic threatens with apocalypse, stem cell magic promises salvation, allowing for a peculiar relationship with the volatile and unpredictable entity at the heart of the public health project. With its spark of magic, regenerative medicine offers a vision of a better world with a capricious protagonist that is not threat, but hope; not death, but resurrection; not dystopia, but utopia. Just like pandemic influenza though, the bodily cures of regenerative medicine are in equal temporal deferral, not quite there yet. The cure will be ready tomorrow. To further think about the intersection of scientific uncertainty and its relationship to the millennial public health message Caduff’s The Pandemic Perhaps is just the right companion.

 

References

Haraway, D. J. 1997.  Modest-Witness@ Second-Millennium. FemaleMan [copyright]-Meets-OncoMouse [trademark]: Feminism and Technoscience. New York & London: Routledge.

 

Karen Jent is a doctoral candidate in the Reproductive Sociology Research Group (ReproSoc) at the University of Cambridge. Her PhD project explores benign and malignant growth in stem cell therapeutic development and regenerative medicine in Scotland. During her ethnographic fieldwork, she engaged in learning the magic of care for cells in the laboratory.