by Christoph Weigel
The perspective paper by Margaret McFall-Ngai and colleagues was recently featured by Elio in this blog, strongly emphasizing its Chicxulub-like impact on microbiology. Here I offer a postscript, a few loosely connected thoughts from a historical perspective about its impact on biology and life sciences in general.
Until the 50s of the last century, advancement in biology was largely the product of three overlapping generations—students, active scientists, and emeriti—laboring over methods, paradigms, concepts, and theories. With few exceptions, these were European and North American men. Theories put forward by the emeriti during their active time tended to be overthrown by their former students who now become active scientists themselves: a spiral of slow progress. Since experiments were tedious and methodological progress slow, scientists were inclined to heated debates regarding concepts and theories. Few theories held for more than one generation, notable exceptions being Darwin's insight of evolution, Mendel's concept of inheritance, and the cell theory by Schleiden and Schwann. Collecting thousands of different mosses or pinning thousands of insects for a museum collection was considered at least equally important as experiments, the lattermost often designed to prove an existing theory rather than to generate a new testable hypothesis. Nevertheless, Louis Pasteur's experiments disproving the spontaneous generation of life and Robert Koch's postulates for proving disease causation can be considered to have ushered in the dawn of experimental biology.
By the late 20th century, biologists were diligently striving to disprove Ernest Rutherford's famous dictum that “...science is either physics or stamp collecting.” As molecular biology emerged, it was hoped—and rigorously asserted by its practitioners—that living systems could be completely understood in terms of the properties of their constituent parts (fundamentalist reductionism), and biology ultimately would be reduced to physics, as according to James Watson: “... there are only atoms. Everything else is merely social work” (cited here). Evolution research was dismissed because, being in essence historical, it could not be reduced to physics. Instead, the fitting approach was to solve the structures of biomolecules, which would thereby reveal their function. Likewise, the road to increased understanding of biology was the falsifiable working hypothesis, itself derived from previous experimental results (empirical reductionism).
Influenced to some extent by the New Age idea that our planet is most fittingly perceived in toto as a single living organism, a growing number of biologists in the 80s began to argue for a holistic approach. The reductionist approach then in vogue could not explain the emergent properties of complex biological systems, or, as Steven Rose phrased it: “...watch a flock of birds, startled by a noise, take off from the field on which they have settled—see them wheel and turn in formation, and try to explain or predict the behaviour of the group merely from a knowledge of the wing-musculature of each individual and aerodynamic theory.” However, there was a flaw in this argument: no holistic concept at that time was able to propose meaningful experiments.
At about the same time, a second criticism was put forward by biologists concerned that reducing biology to physics could in the end strangle scientific creativity. They favored curiosity-driven research over technology-driven research. Or, as Elio put it during a meeting in '87 in memory of Luigi Gorini: “On the planet Krypton every experiment works. As a consequence people quickly run out of ideas and so they spend their time sequencing the human genome. With Luigi, experiments did not always work, but he never ran out of ideas.” (quoted here).
Now, early in the 21st century, the situation is dramatically different. Never before were the life sciences explored by so many researchers from diverse cultural backgrounds, both men and women. Due to the ever increasing speed of technological development, research now spans about five rather than three contemporary generations. Cutting-edge technology of the 80s is at best of historical interest today—who remembers Maxam-Gilbert sequencing? Experiments have become less tedious but they now produce so much data for analysis that hardly any time is left for any of these multiple generations to debate what it all means. When the human genome sequence was published, biology hit a wall of biological complexity. Many biologists saw that fundamentalist reductionism was failing and the spiral of progress arrested as biology was drawn in various directions. Its central narrative seemed lost—almost.
At this point, enter the paper by McFall-Ngai et al., just in time, adding umami flavor to Carl Woese's call for 'New Biology for a New Century'. That call was paraphrased elegantly by Freeman Dyson: “... postulating a golden age of pre-Darwinian life, when horizontal gene transfer was universal and separate species did not yet exist. Life was then a community of cells of various kinds, sharing their genetic information so that clever chemical tricks and catalytic processes invented by one creature could be inherited by all of them. Evolution was a communal affair, the whole community advancing in metabolic and reproductive efficiency as the genes of the most efficient cells were shared. ... But then, one evil day, a cell resembling a primitive bacterium happened to find itself one jump ahead of its neighbors in efficiency. That cell separated itself from the community and refused to share. Its offspring became the first species of bacteria—and the first species of any kind—reserving their intellectual property for their own private use. With their superior efficiency, the bacteria continued to prosper and to evolve separately, while the rest of the community continued its communal life.” Although Margaret McFall-Ngai and her co-workers refrain from expressing it explicitly, I can easily imagine them adding to this narrative: ...In separating itself from the community, refusing to share everything, this first species did not end communication with its siblings and the rest of the bunch, but rather increased its specificity, as witnessed by the ubiquitous communication among and direct interactions—even gene swapping—between the extant prokaryotes and eukaryotes, viruses, and a plethora of mobile genetic elements.
To come full circle—or more precisely to reenter the spiral—Karl Popper had suggested already in 1986 that by adopting 'active Darwinism' biology would avoid the teleological trap and eventually come into accordance with his scientific method of reductionism. Instead of the prevailing view in which selection was the imposed driving force of evolution, Popper’s 'active Darwinism' proposed that: “...the organism itself is not passive and neutral, waiting to be selected, but instead actively participates in its own selection, by choosing appropriate environments and modifying inappropriate ones; organism and environment interpenetrate and modify one another in ways which are determined in part by their own mutual history.” (cited here). I assume Margaret McFall-Ngai and her colleagues would prefer the plural here: organisms and environment interpenetrate and modify one another... This added complexity can then be tackled by the approved methodologies of empirical reductionism without the danger of reverting to "stamp collecting,," as pointed out by Carl Woese.
This is where we stand today. Biology has its 21st century narrative, which is just another word for an extended to-do list for biologists. The good news (for Elio, in particular): acute observation and curiosity have regained their pivotal role in finding out what life is all about. As we move forward, we eventually can teach computers one of the most precious, though enigmatic, of human traits—pattern recognition—so they can help us to cope with the approaching tsunami of data, help us visualize biological complexity.
Christoph is a lecturer in Life Science Engineering at the Hochschule für Technik und Wirtschaft, Berlin, Germany.
Woese, C. (2004). A New Biology for a New Century Microbiology and Molecular Biology Reviews, 68 (2), 173-186 DOI: 10.1128/MMBR.68.2.173-186.2004
Rose, S. (1988). Reflections on reductionism Trends in Biochemical Sciences, 13 (5), 160-162 DOI: 10.1016/0968-0004(88)90138-7