“Playing God in Biology” by Brian Klaas

Playing God in Biology

Author: Brian Klaas

Translator: Aref Ebadi

The following text is a translation and abridgment of a short section from the book “Fluke: Chance, Chaos, and Why Everything We Do Matters” (2024) by Brian Klaas. The central theme of Klaas's book is the impact of small, seemingly invisible events in shaping large-scale trends. The excerpt below concerns one of the longest-running biology experiments, in which scientists, by studying tens of thousands of generations of the bacterium E. coli in a laboratory environment, attempt to demonstrate how much of the variation in twelve strains of this bacterium is the result of chance and how much is the result of convergence.

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Our understanding of human history is a struggle between convergence and contingency. That is, are it the ancient and fixed currents that drive changes, or does history hinge on the smallest details? Since we cannot empirically test the past, we have no choice but to speculate about these two worldviews.

But what if we could create various worlds and, within each of them, control not only events but also time itself? Imagine having the position of God, able to stop time whenever you willed and sometimes rewind it to replay important moments. This way, one could observe the hidden secrets of cause and effect with unprecedented precision and understand how change and transformation occur – and ultimately, whether contingency or convergence prevails. This is an intoxicating thought experiment. But is it feasible?

A few decades ago, a scientist named Richard Lenski realized this could be done without the need for science fiction stories. At the time, Lenski, who also sports a distinguished Darwinian beard, was an evolutionary biologist conducting field research on the aggressive behavior of Southern ground beetles in the countryside of North Carolina. Lenski enjoyed working in the lap of nature, but his study progressed slowly; there were many venomous snakes to watch out for, his target beetles sometimes drowned in downpours, and most importantly, the complexity of the real world introduced so many variables into the research that it practically made testing his most intriguing ideas impossible. Lenski thought to himself how good it would be if he could conduct experiments on evolutionary changes not in the untamed, untouched wild, but in the controlled environment of a scientific laboratory. Thus, in 1988, Lenski began one of the most important and, at the same time, longest-running experiments in the history of science.

Lenski's experiment is as beautiful as it is simple. Take twelve identical flasks or laboratory containers, add twelve identical strains of the bacterium Escherichia coli (E. coli) to them, feed them exactly the same glucose soup, and let them evolve. Since E. coli reproduces rapidly, 6.64 generations are produced each day. Each generation among humans takes roughly 26.9 years, meaning one day in the world of E. coli is equivalent to 178 years in our human time. It may be hard to believe, but since 1988, Lenski has personally witnessed the evolution of 70,000 generations of E. coli, which equals 1.9 million years of change in its human equivalent. In 2004, another extraordinary scientist named Zachary Blount joined Lenski's lab. Together, they have long overseen twelve microbial worlds, each spinning on its own within a flask.

I went to meet these scientists and was therefore able to glimpse their controlled worlds. The laboratory of Lenski and Blount, located at Michigan State University, is not particularly remarkable. The lab shelves are filled with beakers, graduated cylinders, Petri dishes, and white bottles of chemicals. Lenski pointed to a square incubator near the entrance, set to 37 degrees Celsius—the temperature of the human body. As the incubator hummed, it gently rotated and shook the flasks of microbes.

Blount explains the experiment with enthusiasm. Each day, the bacteria grow in the same glucose soup, which contains sugar and citrate—the latter known to us as “the acid that gives orange juice its sharp, tangy taste.” Our tiny test organisms swim in citrate but can only eat the sugar. To reproduce, E. coli bacteria divide into two nearly identical cells, rather than having sex. Thus, the diversity we witness in the flask is mostly the result of mutation, or errors that occur when copying DNA.

The essential feature of the experiment is that twelve different populations, from a common ancestor, evolve freely under identical conditions. The experiment therefore removes sex, environmental changes, and predators from the equation, allowing scientists to study evolution in its purest form.

Thus, Lenski and Blount can test whether convergence or chance prevails. If change is the result of convergence, all twelve flasks should remain nearly identical even in the long term, with only negligible variations. Each of these flasks might have its own evolutionary path, but ultimately they would all arrive at roughly the same place. But if chance holds sway, the twelve populations in question should eventually diverge in significant ways, because random accidents would create strange microbial creatures that forever alter the evolutionary trajectory.

Moreover, Lenski and Blount possess something most scientists lack: a time machine. E. coli bacteria can be frozen without harm. This means the freezers act like a “pause” button on a movie player. To press “play” again, you simply take the bacteria out of the freezer. Since the beginning of this experiment, Lenski and his team have frozen the populations from each flask every five hundred generations. This means they can “replay” any part of the experiment from any time they wish. Want to replay the bacteria from the day the Soviet Union collapsed or from 9/11? No problem. In these twelve worlds, it is Lenski and Blount who rule over time.

For over a decade, the experiment seemed to support the hypothesis of evolutionary convergence. Of course, since change and transformation are inevitable, the twelve cultures did differ to some extent. But they all appeared to be changing along similar paths. Each of the bacterial lineages was getting better at eating sugar every day, gaining more “fitness” in Darwinian terms. Everything was perfectly orderly, and the mutations that occurred did not seem to matter much. It was as if all twelve populations were traveling on a single rail track toward a similar destination.

But one day in January 2003, Tim Cooper, who was a postdoctoral researcher at the time, went to the lab to check on the twelve populations. It was something he had done hundreds of times before, but this time something was different. Eleven of the bacterial populations looked normal, “just like blue flasks with a drop or two of milk dissolved in them. The only sign that millions of bacteria lived inside was a slight cloudiness.” But the twelfth flask was entirely different from the rest. This flask was somewhat dark and turbid, when it should have been relatively smooth and clear. Cooper told me, “I thought there had been a mistake, but I was sure something interesting was happening.”

Cooper calls Lenski.

Lenski said, “I thought it was a lab error. To avoid contamination, our lab motto is ‘When in doubt, dump it out.’” Thanks to their microbial time machine, correcting errors is easy, so Lenski decided to restart that bacterial line from the last frozen sample. A few weeks later, that flask turned cloudy again. It was clear it wasn’t an error—something was going on.

The baffled scientists decided to sequence the DNA of the bacteria in that particular flask, and in doing so, they stumbled upon something astonishing. Among the bacteria, an ability had evolved that allowed them to eat the citrate they were floating in—a capability that should not have been possible. In the twentieth century, there was only one recorded instance of E. coli digesting citrate. That such a thing had happened by chance was, in itself, a major discovery. But this was just the beginning of the story.

For this line of “weird” bacteria to be able to digest citrate, they had to undergo at least four unrelated mutations that offered no clear benefit to their population—in other words, seemingly meaningless errors. But if these four errors did not occur in a specific order, the fifth mutation, which grants the ability to eat citrate, would not be possible. Five random mutations had accumulated on top of one another, which was entirely improbable. That is to say, pure chance.

But just how random were these mutations? To answer this question, Blount spent years studying the population of weird bacteria. He thawed samples from various stages of the mutated lineage to see, using these frozen bacterial fossils, whether the ability to eat citrate would reappear. After analyzing nearly 40 trillion cells over three years of experiments, Blount was able to replicate the citrate-digesting mutation only seventeen times. But if he went too far back in the bacteria’s evolutionary history, the citrate mutation never occurred. The whole affair was pure chance.

To this day, after 70,000 generations—equivalent to 1.9 million years of evolution from a human perspective—only one of the twelve lineages is capable of digesting citrate. For the bacteria in that one sample, a small change meant their entire future was altered, and all of it resulted from a random mutation made possible by four unrelated accidents. The other eleven bacterial worlds continue to eat sugar and, oblivious to it all, swim peacefully in what Lenski calls “lemon dessert.”

Blount argues that the long-term evolution experiment provides us with a sophisticated and rigorous logic for thinking about turning points in human societies. For example, some historians believe the key to the Allies’ success in World War II was D-Day. If this claim could be tested empirically, historians would implement the same research design as Lenski and Blount. Suppose you had a thousand identical Earths that you could pause at different times during World War II. If the number of worlds where the Allies win after D-Day is higher, historians could logically conclude that D-Day was a turning point in their victory in World War II. But if the Allies win in 75 percent of cases regardless of whether the world starts in June 1942 or June 1944 (i.e., D-Day), then it would be obvious that the historians were mistaken. D-Day wasn’t that important, and the Allied forces were more likely to win in any case.

But unfortunately, we only have one Earth, and we cannot turn back time. Experiments on convergence versus chance are only possible in scientific laboratories and on microbes. Nevertheless, it seems that for now, Lenski and Blount—and the large team of researchers who have worked on the long-term evolution experiment—have resolved the issue of convergence or chance: the world appears convergent to us, until one day we discover, to our surprise, that it is not.

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