Howard Berg, Discoverer of Flagellum, Lives On

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Image: Bacterial flagellar motor, from Unlocking the Mystery of Life, Illustra Media.

Howard C. Berg (1934-2021) passed away on December 31, 2021 at the age of 87. More than any other scientist, he shed light on the complex biophysics occurring at the molecular level in living organisms, in particular the peritrichous (multi-flagellate) bacterium Escherichia coli. Of his 120 scientific publications, he was proudest of his 1973 article in Nature with the title “Bacteria swim by rotating their flagellar filaments”. It was the first known case of rotation in a biological organism, which other biologists had thought impossible.

At the end of this article, Berg and Robert C. Anderson state, “If, as existing evidence suggests, bacterial flagella rotate, the structures at the base of the flagellum deserve more attention than they have received. until now.” Since then, these structures have been found to contain rotors, stators, a universal joint, and other components made up of hundreds of proteins of twenty different types. Other examples of rotating biological motors have also been found: the archaeullum in archaea and ATP synthase in all living organisms.

Like it or not, Berg helped propel the intelligent design movement. Who could look at a mechanical outboard motor and say it was a lucky job? Michael Behe ​​could not. Some of the first electron microscope images of the flagellum, presumably from the Harvard lab, spoke for themselves: “It’s an outboard motor. It’s designed! Behe might well have thought. “It’s not an assembly of parts by chance.” The flagellum must have spoken to Berg itself to some degree. According to Scott Minnich in Unravel the mystery of life, Howard Berg called the bacterial flagellum “the most efficient machine in the universe”. But how enthusiastic was this scientist about a mechanical marvel he has spent his career observing?

“Death with His Boots”

Tributes to Dr. Berg, such as the one on the Harvard website and another posted on The scientist, describe him as a hard-working yet sympathetic character who “died with his boots on”, pursuing his research to the end. This was echoed by another tribute in Current biology. As a designer of observation equipment, Berg was without equal. To track small creatures, he designed a microscope with servomotors capable of following a bacterium along three axes.

Howard has continually modified and improved the tracking microscope over the years, giving him many reasons to visit the machine shop. He also built electrical and mechanical devices to perform various laboratory functions, including a foot-operated plate pourer and a Western blotting machine that had to be operated at its lowest setting lest it drive the proteins entirely. through the membrane. The machine shop was his refuge, perhaps to the disappointment of his family.

When cryo-electron microscopy was invented, allowing imaging of the flagellum at the molecular scale, Berg must have valued the high-resolution views over the blurry views he first saw in the 1970s.

Assuming an evolution

There is no evidence that Howard Berg ever departed from the standard materialistic dogmas of evolution so prevalent in academia. His latest article, a review article in Nature on bacterial motility published last year, assumes four-fold evolution:

  • ” … bacteria have evolved several motor mechanisms…”
  • “…various bacteria…each have evolved distinct molecular mechanisms…”.
  • “[two species] are not closely related, indicating convergent evolution….”
  • “The evolutionary success …is likely to follow from its generality…. (Emphasis added.)

To what extent these are his statements or those of his co-author, Navish Wadhwa, I do not know. I also don’t know what he thought of the intelligent design movement using the bacterial flagellum as a design icon – a fact that could hardly have escaped his notice. Berg’s views on evolution, however, do not change the reality that the bacterial flagellum is a sophisticated molecular motor displaying irreducible complexity. He was already there, waiting to be discovered. Berg simply found the right evidence, paving the way for many other scientists to watch and marvel, like the dozens of visitors who had come to Antony van Leeuwenhoek’s shop 300 years earlier to see the little ones “animalcules” (a pun on “molecules”). the Dutch merchant had discovered. What satisfaction Berg must have felt comparing his eyepiece to that of van Leeuwenhoek’s small hand-held device with which he became the first to see bacteria swimming in liquid.

Almost no inertia

Berg mentions Antony van Leeuwenhoek in a 30-minute bacterial motility video posted on the Harvard University website and YouTube, recorded in 2014. He even wields a replica of the tiny device and describes its excellent optics. In part 2 of his YouTube lecture, he gives more details about the structure of the flagellum and how it works. An interesting aspect of the flagellum that many ID advocates may not realize is that the bacteria-scale water viscosity is very high. The Reynolds number (a dimensionless number correlating inertia to viscosity) is extremely low, which means that a bacterium like E.coli experiences almost no inertia in the water. When the engine stops running, the bacteria stops moving. In order not to be shaken by the Brownian motion, the flagellum must overcome several physical constraints.

Berg describes these counterintuitive properties of water at the molecular level and shows how the spiral shape of the filament is optimized for motility under such conditions. It also explains why the run-and-tumble strategy is best for following a concentration gradient at this scale. The flagellar motor itself, as we know, has sufficient irreducible complexity, but it is also regulated by a signal transduction system composed of other machines that monitor concentrations of desirable or undesirable substances and guide the motor to or away from them by changing the direction of its rotation. (The way it works in peritrichous bacteria with bundles of flagella working together sounds like a good research project for design scientists.)

Additional Optimization Perfections

Dr. Berg describes additional optimization perfections, such as how protein building blocks are injected through the hollow filament to the tip when the flagellum is built or repaired. These molecules barely pass through the filament, like pistons in a cylinder, but move quickly and efficiently toward the tip, he explains, due to the time intervals between their insertion. The tribute in Current biology mentions a final callback to his work:

At the age of 87, he received a grant from the NSF to experimentally test the prediction that the stator that drives the rotation of the bacterial flagellum is itself a rotating machine. This work will be continued by the remaining members of his laboratory under the supervision of a former student of Howard, Aravinthan Samuel, now professor of physics at Harvard.

All of these properties of the flagellar motor cry design, but in the videos Berg talks about them in a subdued tone, sharing his graphs and experimental results in the academic vernacular. He ends by saying, with only a modest and calm minimum of joy,

E.coli has a large number of turns; it’s been going on for billions of years. And we keep finding these things, and they’re amazing, because we didn’t imagine they were happening, but E.coli is smarter than us.

It was probably his normal disposition as a scientist to exercise restraint, or maybe he was a little shy in front of the camera while recording for the iBiology channel. But it’s hard to imagine a scientist so close to an excellent example of bioengineering not being enthusiastic about it. Curiosity must have driven him to devote much of his life’s work to this biological marvel, but who knows why he didn’t jump out of his eyepiece and shout “It’s an outboard motor!” There’s also a slight possibility that he didn’t want to express too much passion for what had become an icon of smart design.

He could have outsourced his own exuberance to van Leeuwenhoek, whom he quoted at the start of Part One. In a translation by biographer Clifford Dobell, the Dutch merchant said:

It was for me, among all the marvels that I discovered in nature, the most marvelous of all; and I must say, for my part, that no more pleasing sight has yet presented itself to my eyes that these several thousand living creatures, seen all alive in a drop of water, moving one among the other, each having its own proper movement.

So even with his sober and pragmatic manner, Howard Berg may have shared this sentiment internally with his predecessor.

Further reading

You want to know more ? Howard Berg has written two books available on Amazon:

Random Walks in Biology (1993) has five stars on Amazon by laymen. It seems devoted to physical concepts related to bacterial motility, not questions of origin.

E. coli on the move (2004) is a more technical (and expensive) book. Springer-Link gives the table of contents and this summary of the epilogue:

I have told you some things about a free-living organism only one micron in size. It is equipped with sensors which counts the molecules of interest in its environment, coupled with a reading device this calculated whether these numbers increase or decrease. The output is an intracellular signal which modulates the direction of rotation of a set of rotary motorseach turning one Helix variable pitch. Each motor (or engine) is driven, in turn, by several force-generating elements (like pistons), powered by a transmembrane ion flux. In addition to a gear change(labeled front and back but likely to move on its own) there is a stator, rotor, drive shaft, bushing and universal joint.

The site also displays part of its Chapter 12, “Rotary Motor”, where it calls the flagellum motor “a nanotechnologist’s dream (or nightmare).” There are additional excerpts from other chapters, such as “Flagellar Motion” and “Optimal Control”.

Some of Dr. Berg’s 120 scientific papers can also be viewed. His 1973 article is behind a paywall at Nature.

Or check out the website for Berg’s lab at Harvard, with a statement about his research goals.

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