Dean's World

A few months ago my blood-brother Jerry Kindall forwarded the following rather beautiful video to me: The Inner Life of the Cell, by a group of Harvard. I've attached a YouTube version below.

It's a quite lovely video but parts of it bothered me. So I asked Professor Gerald Pollack if he would like to comment upon it for Dean's World readers. And indeed he was interested. The below are his thoughts on the matter. --Dean

Dean Esmay found the following video quite compelling:

But after having read Cells, Gels and the Engines of Life, Dean thought I might have some comment. And indeed I do.

The video depicts a multitude of cellular processes, all artfully choreographed as a series of molecular dances. The dances are charming, and surely worth viewing. One feels a sense of purpose, and even a kind of intimacy with the players.

But the play misleads. The detail of action implies that the activities keeping the cell abuzz are understood to a gnat’s eyebrow, affirming the air of confidence coming from cell-biology books — the sense that the essential mechanisms of the cell are well understood and completely in hand, and that all that remains is to fill in a few missing links.

But that is not at all the case. Even many of the fundamentals remain questionable.

Over the past half-century the predominant view of how cells function has been based on a framework that may be familiar even to those with only a low-level biology course. It goes like this: Surrounded by a membrane, the cell cytoplasm contains organelles and molecules such as the nucleus, mitochondria, RNA, proteins, ions, etc., all bathed in a sea of water. Traffic in and out of this water compartment is controlled by pumps and channels lodged in the cell membrane — each one specific for a particular type of molecule. The membrane, then, is the site of much of the critical action.

What you may not know is that this foundational framework is merely a hypothesis, and not a fact. Its essence is challenged by an increasing number of researchers, led initially by Gilbert Ling, Ludwig Edelmann, Miklos Kellermayer, Carlton Hazlewood and others, and the challenge is rapidly gaining support worldwide. Even Nobelist Albert Szent-Gyorgyi questioned central aspects of this hypothesis. Some have argued that membrane pumps are impossible – that they violate basic principles of chemistry and physics. Others have questioned whether membrane integrity itself is essential for cell function. Why? Because it turns out that even when the membrane is torn asunder, the cell continues to function.

Indeed, you might stop and contemplate that for a moment: even when the membrane is torn apart, the cell often continues to function. Many examples of this can be found. For example, when a muscle is sliced like a sausage, the region near the slice is injured as you might expect, but the regions distal to the cut survive quite well despite the absence of an enclosing membrane. The same has been shown true of nerves. And, when single cells grown in a culture dish are sliced in half with the fine tip of a tapered glass probe, half the cell dies after a day or so, while the other half continues to live, and even divides to produce progeny. All of this without a continuous membrane.

Another point that has been argued is that the inside of the cell is not merely a collection of molecules floating in water; rather, the cytoplasm is more like a gel — something akin to the inside of a raw egg.

This last point is particularly far-reaching. Even though the cell’s gel-like character is broadly acknowledged, it has also been broadly ignored. Virtually every cellular mechanism understood by contemporary biologists today rests on the assumption that the cytoplasm is an aqueous solution and not a gel. Under this presumption, constituent molecules float in a sea of water. They are entirely free to diffuse from place to place — from highly concentrated zones to less concentrated zones. It’s much like throwing a pinch of salt into the chicken soup: the salt diffuses to regions of lower concentration and the soup becomes uniformly salty. Likewise, in the cell, diffusion of various molecules from high to low concentration is implicitly figured to be a central protagonist governing numerous cellular mechanisms.

But, if the cell is a gel rather than a collection of molecular machines sitting in water and enclosed by a taut membrane, such a scenario cannot be. Molecules may diffuse easily through water, but they cannot diffuse very easily through a gel. Placing a suspension of molecules on one side of a blob of Jell-O, and waiting for the molecules to appear on the other side will require undue patience. Diffusion therefore is not likely to be a central player in cell dynamics — which instead require fast, responsive action.

Thus, biologists following orthodox approaches cannot hope to develop mechanisms that are valid, for the basic foundational presumption is wrong: molecules cannot diffuse easily. But if they cannot diffuse easily, then something else must be driving them, and that is the challenge. This situation harks of Galileo. The pre-Galilean notion of an earth-centered solar system was in good confluence with the belief system of the day, but it led to horrendously complicated planetary orbits with cycles upon epicycles — which of course turned out to be erroneous. Once the real foundation was established, the orbits became a lot simpler — and perhaps even correct.

Here's how planetary orbits looked when we thought the sun and the planets all revolved around the Earth:

But then Copernicus suggested that the sun should be in the center and not the Earth, and the orbits suddenly looked like the below. --Dean

And so it is with the cell. Building upon an invalid foundation has brought biological mechanisms to a level of complexity rivaling pre-Copernican epicycles. The beautiful video with which we started this discussion. That complexity can be appreciated by perusing the relevant chapters in any standard cell-biology book. The mechanisms they describe are extremely complicated — probably too complicated. Properly set, the video’s delicately choreographed molecular dances would turn into clumsy orchestrations of the cell’s many themes, each one out of tune with the others. The real-world result if this were all true would be a cacophony of noise.

By contrast, gel foundation yields a more satisfying framework, on which one can build for the future. It yields mechanisms that are not only in harmony with each other, but also in accord with a wealth of evidence — at least as much as the textbook views. I know I cannot hope to convince you of this in this short overview, but you might consider a few features:

- The gel foundation explains why the cell survives breaches in its membrane; Jell-O sliced in half remains Jell-O;

- It implies that a single generic mechanism (a gel phase transition) explains varied cellular actions;

- It shows how this simple generic mechanism can account for essential cellular functions (motion, division, secretion, etc.) — and can even explain the rapid movement of molecules through the thick gel-like cytoplasm.

For a more in-depth look, I believe you will find that the best information is conveyed simply and straightforwardly in my book (Cells, Gels, & the Engines of Life: A New, Unifying Approach to Cell Function), which has become something of a best seller and is being used as a classroom text in an increasing number of universities. Although it is technical, it is designed for the non-expert. You may read it and judge for yourself.

In closing: as charming as the video may be, it deceives. It depicts processes that seem simple, elegant, even graceful; but when the essence of each process is modified to fit the experimental evidence, and all processes are then melded together into what ought to be a functional cell, they add up to a confusing jumble. The cell is anything but a confusing jumble. The cell must function as a well-orchestrated ensemble — something akin to the delicately interwoven themes of a Bach fugue.

For any of you who may be interested, I encourage you to have a look at the gel/cell foundation (www.cellsandgels.com) and compare its functionality with the vaunted complexity of “authoritative” textbook mechanisms.

Do let Dean know what you think. I won’t be taking part in any "flame wars," but Dean promises to forward to me any rational and thoughtful inquiries, and if the number is a sufficient, a followup piece might be forthcoming.

Gerald Pollack is Professor of Bioengineering at the University of Washington. His home page is available here: Gerald Pollack--Dean

In that final phase, one of the entangled photons will be sent through a slit screen to a detector that will register it as either a particle or a wave — because, again, the photon can be either. The other photon will be sent toward two 10-kilometer (6.2-mile) spools of fiber optic cables before emerging to hit a movable detector, he said.

Adjusting the position of the detector that captures the second photon (the one sent through the cables) determines whether it is detected as a particle or a wave.
...
Because these two photons are entangled, the act of detecting the second as either a wave or a particle should simultaneously force the other photon to also change into either a wave or a particle. But that would have to happen to the first photon before it hits its detector — which it will hit 50 microseconds before the second photon is detected.

George Monbiot takes on the widely acclaimed debunking of climate change by Christopher Monckton. Real Climate also weighs in.

The Scientist says that many National Institutes of Health employees are complaining about the ethics requirements of working there.

Cry me a river. It used to be simply understood that if you work for the government you're a public servant in a position of deep trust to the taxpayers. You don't get rich but you do have respect, reasonable wages, and excellent benefits (including excellent job security).

It is despicable that we now allow people with direct financial investments in the drug companies and other biotech firms to be in prominent positions within the NIH hierarchy. That is, bottom line, a huge conflict of interest, and if people don't like it they shouldn't get into government service.

I'm tired of my tax dollars being treated like a trough that people from private industry can belly up to.

(Thanks to Dave D. for forwarding this to me.)

More U.S. blacks attempt suicide than previously thought, according to a landmark study appearing in today's Journal of the American Medical Association that could help explode the myth that black suicides are rare because of cultural and religious views against it. The first nationally representative study to look at attempted suicide among blacks found that about 70,000 blacks try to kill themselves each year and 4%, or roughly 1.4 million, attempt suicide at least once in their lives. That lifetime rate is similar to that of whites but higher than the 2.8% found among blacks in previous surveys. Other research has shown that the actual suicide rate in whites is about twice as high as in blacks, though rising rates among young black men have narrowed the racial gap.

The study is the first to look at suicidal behavior among the two leading ethnic groups within the U.S. black community — black Americans and Caribbean Americans. The lifetime prevalence of suicide attempts was much higher among Caribbean-American black men, at 7.5%, suggesting that about 53,000 try at least once to kill themselves. The reasons for that relatively high rate are uncertain.

Suicide attempts in the study were least common among blacks in the South. While depression is strongly tied to suicidal behavior in whites, anxiety disorders were more common than depression in blacks who attempted suicide in the study. That is an important racial difference that could alert doctors to black patients who might be contemplating suicide, said Alvin Poussaint, a Harvard University psychiatry professor and race relations specialist.

My response: When I read this story, I thought of the recent controversy surrounding whether football star Terrell Owens recently tried to kill himself with those pills. About this study, I say: slow down. They added folks of Caribbean immigrant descent into the mix, whose higher rate in turn jacks up the overall black stats. Would the rate of native black Americans (for lack of a better term) be significantly lower minus the addition of these black immigrants and the children of recent black immigrants? Perhaps blacks of Caribbean descent have a different cultural viewpoint toward suicide than native black Americans do. And it should be noted that most blacks live in the U.S. South, where the study showed the black rate was the lowest.