As the human body replaces millions of dead cells every day, it relies on a process of cooperation between cells that evolved as a way to guard against cancer, according to newly published research from a UA biologist.
This cooperation, which would seem to run contrary to natural selection, was a key development in the evolution of multicelled organisms, said John Pepper, an assistant professor of ecology and evolutionary biology. Pepper and colleagues at the University of Pennsylvania and Wistar Institute in Philadelphia published the research in PLoS Computational Biology.
"The problems may have been so big that there were no workable multicelled organisms until this was solved," Pepper said.
The presence of cooperation in nature — whether between animals or at the cellular level — has been a bit of a puzzle for evolutionary biologists because competition is the hallmark of natural selection, Pepper said. In the case of multicelled organisms, the cooperation was necessary so that one particular type of cells didn't proliferate at the expense of the whole.
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"How can they cooperate so intensively that they stop being an organism and start being part of an organism?" Pepper said. "The organism made of cooperative cells will leave more descendants than organisms made of uncooperative cells."
The simplest way for cells to reproduce would be to duplicate themselves, Pepper said, but in that manner natural selection within the body would lead to cells that reproduce faster and thwart any obstacles to their own proliferation. However, ruthlessly selfish cells that divide as fast as they can would be disadvantageous to the body, leading to cancerous growth.
"A lot of cancer biologists observe that cancer happens when cells stop cooperating with each other," he said.
Using what is known as an agent-modeling approach, Pepper creates virtual cells using a computer. While it's hard to program real cells, this approach allows total control over the conditions. The researchers could create a whole population of virtual cells and turn them loose under a certain set of rules designed to test a particular hypothesis.
Pepper said the vast majority of the cells are simply worker cells, carrying out the mission of whatever tissue they comprise but unable to duplicate themselves, which would be the simplest way to replace dead cells.
"It might seem more efficient, more straightforward, but it would lead to reproductive competition," he said. The competition would have cells reproducing endlessly, leading to cancer.
The reproductive duties are instead handled by a very small number of specialized cells — the stem cells — which can divide to reproduce themselves, as well as produce what scientists call daughter cells, or the descendant cells that replace those that die off.
The computational biology approach that Pepper uses is a relatively new field that has developed rapidly over the past decade. It started at the Santa Fe Institute, where Pepper worked as a postdoctoral researcher before coming to the UA. The field has seen sharp changes as the idea of virtual experiments has caught on as a way to accomplish what can't be done in normal wet labs.
Pepper himself is interested in building bridges between disciplines by applying basic ideas of evolutionary biology to cancer or other disease-related research. Pepper said that although the research paper he just published has no immediate implications in cancer treatments, he hopes his research can get people thinking about cancer in new ways.
"There's been a lot of attention on what happens when people do get cancer. We're asking what happens when people don't get cancer — what happens when things go right, not just when they go wrong," Pepper said. "The basic philosophy here is if you want to know how to fix something that's stopped working right, you have to know how it's supposed to be working."
"The organism made of cooperative cells will leave more descendants than organisms made of uncooperative cells."
John Pepper, University of Arizona assistant professor
