Embracing the Integrative

I wrote this about the meaning of “integrative” biology. It was just published, but with open access so here it is for your information.

Published in 2013,  Journal of Integrative Biology  55: 890 -891.

My invitation to join the editorial board of Journal of Integrative Plant Biology (JIPB) brought back fond memories. In the early 1980’s when I was a Ph. D. student, the library subscribed to Acta Botanica Sinica (as JIPB was then titled) and would put out current issues in the reading room. When I had finished reading each issue, I remember checking off my name on the strip of paper stapled to the cover. In those days, the journal published in Chinese, with English abstracts, and I saw papers that I wished I could read in full.

Fast forward to today and the modernization of the journal. At the annual editorial board meeting, held in picturesque Lijiang, I was awed by the statistics heralding the improvement of the journal, and inspired by the energy of staff and editors, transforming the journal from a repository of acta to a place for the sharpest cutting-edge articles. Readers wishing to learn more about the history of JIPB and its current status may read two recent articles (Cui et al. 2012; Liu 2012).

I was also struck by the choice of the word integrative. Using this word in the journal’s title is brave. The word sounds a little vague; what does it mean, really? However, as I argue here, the fuzziness of integration does not imply fuzzy thinking but is inherent in its meaning. This is both the challenge and promise of integration.

Consider calculus: When we differentiate we lose information; when we integrate, we have to add information. Sometimes it can be inferred, sometimes guessed, but most often it has to be assumed. This is the famous ‘constant of integration’, a measure of ignorance. The derivative tells us the relationship between two neighboring points; in contrast, the integral starts with the relations between a set of points and tries to find something global, namely the area of the curve. It does not always succeed and this is one reason why hoisting the banner of integration is brave.

There are other reasons. Continuing with the calculus metaphor, let’s imagine the Journal of Differential Biology. This would be a journal devoted to the instantaneous forces impinging on the current state of the system and its infinitesimal changes toward the next state. Although a caricature, this reminds me of the reductionist attitude currently dominating biology.

There can be little doubt that in today’s biology, the molecular is the privileged level. Often, studies of molecules are called “mechanistic” while studies of organisms are called “descriptive”. But biology is a hierarchy, and it seems questionable to single out one level. In a hierarchy, all levels count. That is in fact how a hierarchy is defined. It might be that being so familiar with the levels of organism and ecosystem—those of daily experience, we inevitably find the molecular level alluring. But what is interesting about hierarchies is not that they have nested levels—those self-enclosing Russian dolls are curious but little more—but how the levels are connected. Integration is important because it connects levels.

Let’s look at a different hierarchy, and think about how we might analyze Herman Melville’s great whaling novel, Moby Dick. In a novel, at least two levels can be distinguished: words and stories. We might run an analysis of word juxtapositions and produce a map of the frequencies with which any word lies next to another. This network could indeed provide insight about how Melville deployed words. But most of us would reject the notion that such a “word hairball” on its own constitutes a deeper analysis than an exposition of an aspect of the story—for example, why the great whale is white. Even those of us who seldom read fiction and never read literary criticism can recognize that to analyze a novel effectively one needs to attack both the words and the story.

 Returning to biology, we can consider the gene. For many, this is the ultimate level of life and has the most privileged position of all. It is indeed among the most delicious facts of our biosphere that deep inside each cell resides a digital information store—the genome. Perhaps because their similarity to the written word resonates, genes captivate the attention of scientists. Rightly so, genes contain a truly tremendous amount of information and they are inherited. But we should remember that genes do nothing on their own—they work inside a cell. No gene can be expressed without cellular machinery. Even with its genome, a cell cannot construct endoplasmic reticulum (ER) without the pre-existing structure. The cell can enlarge its ER but it cannot build the organelle de novo. The same is true for most cellular organelles. This underscores the fact that information resides not only in the genome but also in the cytoplasm. Analog information to be sure, but essential nonetheless for the living system to function. No organism reproduces by naked DNA—at least one complete cell is always involved.

 Molecules of interest to the biologist—genes, proteins, or lipids—do not interact in an infinite dilute solution—they interact in a cell. And cells reside in organisms, which reside in ecosystems. The cell is more than a sum of its parts. Poke a hole in a cell, all the parts are there but they no longer function as a cell. The unity of the cell constitutes the system, provides the boundary condition for the behaviors allowed to the molecular components. And so too upward to organism and ecosystem. We cannot neglect the boundary conditions if we are going to understand life.

We err to disparage an integrative study because it lacks the precision of differentiation. Instead, we should embrace integration because it unites levels of biological hierarchy. Would-be contributors to JIPB who are good reductionists needn’t worry. Integration is not required by the journal, but rather welcomed. JIPB, through its choice of title, signals its belief that the dominance of the molecular level will eventually fade as we gain a more profound understanding of life. I predict that, once this deeper understanding arrives, JIPB will be said to have led the way.

 

REFERENCES:

 Cui J, He P, Liu F, Tan J, Chen L, Fenn J (2012) 60 years of development of the Journal of Integrative Plant Biology.  J. Integr. Plant Biol. 54: 682–702.

Liu CM (2012) From Acta Botanica Sinica to JIPB: Connecting Chinese plant science with the international community for 60 years. J. Integr. Plant Biol. 54: 678–681.

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