ISHPSSB

Microbial ecology offers case studies to think through the boundaries of the concept of regenera-
tion. One example is the human gut microbiome, that is, the community of microorganisms that


is harboured in the human intestinal tract. In healthy human adults, the activities of this microbial
community are integrated into fundamental physiological processes of the human host, such as
the metabolic functions of digestion and vitamin production. Antibiotic treatment can disrupt the
functions of this microbial community, which can be detrimental to the health of the human host.


Following treatment, and in a healthy adult human, the microbial community returns to its previ-
ous state, and once again provides vital functions. This process looks like a candidate for regen-
eration—the system is disturbed and returns to a previous state in a way that resembles limb re-
generation—but is this how we should think about this kind of system change?


I will focus on two issues. The first is about defining function. The taxonomic profile of
the gut microbial community (who’s there) is quite variable across individuals and through time,
whereas its functional profile (what they’re capable of doing) is relatively stable. The outcome of


regeneration will thus be a return to a previous functional state. But function is arguably sub-di-
vidable, for example, we might choose to characterize the function of the system broadly, such as


carbohydrate metabolism, or more specifically, such as one form of glucose utilization. Our deci-
sion will determine whether regeneration has occurred. Should regeneration be decision-relative


in this way? The second issue is about the importance of host control. A return to a previous
functional state is in part controlled by the human host, whether intentionally (e.g., by eating
probiotics) or unintentionally (e.g., by producing mucus layers on the gut lining that encourage
certain microbes). Is this host control necessary for regeneration? For example, bromeliad leaves
harbour microbial communities that also have stable functional profiles across individuals, but
with no host control: does the recurrence of such communities count as regeneration? What does
this say about other examples of ecological regeneration, such forest regeneration?

The use of the concept of regeneration spans across scales of organization, from the cell, to


ecosystems. The capacity to regenerate also widely diverges at each scale. For example, planari-
ans can regenerate both their head and their tail, salamanders can regenerate limbs, and mammals


have only very restrictive regenerative abilities in some of their tissues like the liver or some ep-
ithelial tissues. One aim of this symposium is to build a framework that allows (1) comparing


regeneration across scales and (2) better characterizing the regenerative abilities of any system of
interest.


In this talk, I will apply a multidimensional framework for understanding regeneration at multi-
ple scales to cancer. Cancer is recurrently compared to regeneration, with claims that fall mainly


in two categories:
• Cancer is a regenerative process that went awry.


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• Cancer mutations hijack regenerative processes leading to the expansion and progression of
the disease.


Using this multidimensional framework, I will first characterize the regenerative potential of var-
ious cancers, highlighting their similarities and differences with more canonical regenerative


processes. Second, I will explore the benefit of applying this framework and show how these


similarities and differences can be therapeutically meaningful. Third, I’ll argue that the regenera-
tive potential of cancers relies on stem cells identity.

Historically, the bodies of metazoans have been divided into two different kinds of cells:
germline and soma. Germline refers to the reproductive cells (sperm, ova) and all the cells in the
lineage that leads up to these gametes (i.e. primordial germ cells, germline stem cells, etc.), and
soma refers to all other cells in the body. Whereas soma is understood to be mortal, germline is
often deemed immortal, and constitutes the basis of heredity and evolution. It is commonly held
that once the germline is specified during development, somatic cells cannot become a part of the
germline cell lineage. This is called the Weismann Barrier, and it is held to be universally and


dogmatically true. One of the consequences of the Weismann Barrier is that germline, once re-
moved, should not be able to regenerate. And yet, we see instances throughout metazoans where-
in germline regeneration is commonplace. How, then, should we interpret (1) regeneration of the


germline, and (2) the relationship between germ and soma?


Beginning with the regeneration framework proposed for this session, I will lay out a se-
ries of cases in which the germline regenerates in metazoans, highlighting similarities and differ-
ences between the cases. Next, I will explore the ways in which we can interpret regeneration


within the germline—at the level of the cell lineage and at the level of the individual cells—and
reflect on what thinking about regeneration at these different levels means for our understanding
of germline regeneration. Penultimately, I will discuss how the cases of germline regeneration
that I present require a revision in our understanding of the relationship between germ and soma.
Finally, I will argue that understanding germline regeneration, particularly the processes that
govern it and the cells involved, have important and broad implications for science policy and
research related to genome editing.

Humans have significant impacts on the rest of the living world. In few areas are such impacts as
obvious as coral reef systems. Bleaching events, disease and altered ecosystem dynamics are but


a few of the multiple threats coral systems face. As such, descriptions of coral as ‘dying’, ‘de-
graded’ or ‘damaged’ are frequent. Attempts to regenerate degraded coral reefs, both the organ-
isms themselves and the associated ecosystems, are now common. Language extolling the value


of coral accompanies these descriptions and regeneration strategies. The value of coral can be
considered from multiple angles: affective value (Braverman, 2018), financial value (Costanza et
al., 2014) and ecological value (Knowlton, 2001) are three notable forms. These various forms of
value attributed to coral systems are presented as reasons for us to take action to regenerate them.
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Here I will argue that this role for value attribution is only part of the picture. First, I
show that the value attributed to coral systems determines which changes to them are seen as


damaging and which as regenerative. Describing a change in a coral system as regenerative re-
quires the prior attribution of value to some entities (over others) within it. Second, I argue that


value attribution, in terms of what form of value is attributed to which entities and functions, also


induces different regeneration strategies, shaping the future of coral systems. Given the role hu-
mans now play in dictating the future of coral (both through unintended influences and active


regeneration strategies), the reasons why different actors value coral become increasingly impor-
tant. This is more than saying humans save corals because corals are valuable. It is to say that the


different ways humans attribute value to coral shape the actions humans take to regenerate coral.
The regenerated system is not identical to its predecessor: some aspects are sacrificed and new
aspects introduced.


As a way of supporting my argument and exploring its consequences, I draw on an anal-
ogy between coral regeneration and urban regeneration. This demonstrates that value attribution


plays a much larger role in understanding and inducing coral regeneration than is currently sup-
posed—and the way actors in coral regeneration attribute value to coral is much more important


than previously recognized.

Discussions of regeneration often start with the god Prometheus. As punishment for helping man,


Prometheus was chained to a rock. Every day an eagle plucked out his liver; every night it regen-
erated to be plucked again the next day. Current researchers often point to this example as


demonstration of the marvellous powers of regeneration. Biologists began to marvel at the re-
generative powers of hydra, planarians, and earthworms in particular, recording phenomena and


offering explanations through the 18th and 19th centuries. Thomas Hunt Morgan provided a
summary of the topic in 1901 to provide a foundation for modern experimental interpretations.
These early studies focused on organisms and their functional parts, then in the early 20th century
began to look also at regeneration in cells. Only much more recently have the same terms been


applied to ecosystems and microbial systems, as well as to sub-cellular and multi-cellular sys-
tems. To understand regeneration in a complex adaptive system, we need clarity about the system


and what makes it “work” functionally and structurally. Then we need to understand what kinds
of factors cause disruption or even system failure. And what responses result in regeneration of
the parts of functions. This talk will look at these larger issues, drawing on historical examples to
illuminate larger issues about system failure and regeneration.