Par­a­digm Shifts, Par­a­digm Drifts

The orig­i­nal ver­sion of this es­say ap­peared in a 2009 is­sue of ASM's mag­a­zine, Mi­crobe. I thank Mark Mar­tin for res­ur­rect­ing it.

by Elio

In 1962, Thomas Kuhn wrote a book of sem­i­nal im­por­tance, The Struc­ture of Sci­en­tific Revolu­tions, wherein he in­tro­duced the con­cept of "par­a­digm shift." Kuhn pro­posed that sci­ence ad­vances through a "se­ries of peace­ful in­ter­ludes punc­tu­ated by in­tel­lec­tu­ally vi­o­lent rev­o­lu­tions," in which "one con­cep­tual world view is re­placed by an­other." Par­a­digm shifts oc­cur rapidly; other sig­nif­i­cant in­sights take their time in de­vel­op­ing and are the stuff of "nor­mal" sci­ence. Bor­row­ing from the lan­guage of in­fluenza vi­rol­ogy, I will call the lat­ter "par­a­digm drifts." How do these con­cepts ap­ply to the mi­cro­bial sci­ences?

The rabbit–duck il­lu­sion. Source

A par­a­digm shift, in the Kuhn­ian view, must have these at­tributes: un­prece­dented, open-ended, broad, sim­ple, and fruit­ful. The de­f­i­n­i­tion does not read­ily lend it­self to quan­titative analy­sis, and I will use a per­sonal read­ing of Kuhn's terms. I present here ex­am­ples of what in my mind consti­tute par­a­digm shifts and drifts in mi­cro­bi­ol­ogy. Each of them can be re­duced to a gen­er­al­iza­tion that, let us hope, is both grace­fully sim­ple and ex­ceed­ingly far-reach­ing. I rea­lize that mak­ing such choices may be au­da­cious, but it is meant to be merely a per­sonal state­ment. My pur­pose here is pri­mar­ily to elicit dis­cus­sion.

Surely, read­ers will want to add to or sub­tract from this list since, since, as I im­plied above, there is con­sid­er­able room for opin­ions. Here I will posit that many of the most ex­cit­ing cur­rent develop­ments in mi­cro­bi­ol­ogy qual­ify as par­a­digm drifts be­cause they are dis­tinctly work in progress. I have no doubt but that even­tu­ally they will lead to im­por­tant gen­er­al­iza­tions, but not quite yet. This view does not di­min­ish their grandeur and lus­ter.

The Plan­e­tary Preva­lence of Mi­crobes  It has been known for cen­turies that mas­sive rock de­posits such as lime­stone, bio­genic sil­ica, and coal are of bi­o­log­i­cal ori­gin, much of it mi­cro­bial in na­ture. Still, it came as a sur­prise some years ago when it was cal­cu­lated that the Earth's ex­tant bio­mass is hugely mi­cro­bial, the mi­crobes com­pris­ing per­haps one tenth the to­tal weight of all liv­ing things. Much of this enor­mous global cargo is found in un­der­ground wa­ter oc­cu­py­ing the spaces within the rocks. Here, me­tab­o­lism is thought to be slow and un­hur­ried, yet the to­tal flux con­tributes mean­ing­fully to geo­chem­i­cal ac­tiv­i­ties. In the oceans, mi­crobes carry out about as much photosyn­thesis as all land plants com­bined. Prokary­otic and eu­kary­otic mi­crobes share the work, per­haps al­most equally.

Metage­nomic tech­niques al­low a cen­sus of the mi­crobes present in al­most any habi­tat. We can se­curely con­tend that ge­o­logic and at­mos­pheric trans­ac­tions can­not be en­vi­sioned with­out in­cluding the ac­tiv­i­ties of mi­crobes. Both quan­ti­ta­tively and qual­i­ta­tively, much of the planet's me­tabolism is mi­cro­bial. And I haven't even men­tioned the viruses!

What Do We Know Of Bac­te­ria As Or­gan­isms?  What a ques­tion! Given the enor­mity of the mi­cro­bial world, we can only re­duce it to a few par­a­digms. Fore­most in our ac­quain­tance is a species that most of us carry in our gut, Es­cherichia coli. So much is known about its struc­ture and meta­bolism that our knowl­edge of it (and its close cousin Sal­mo­nella) was cov­ered in 1996 in two fat vol­umes called 'Es­cherichia coli and Sal­mo­nella', to­tal­ing over 3000 pages (Mamma mia!). We pub­lished an up­date in 2000 and now there is a jour­nal EcoS­alPlus, ded­i­cated to pub­lish­ing our grow­ing knowl­edge of these bac­te­ria along with oth­ers. It's fair to say that we know more about these species than about any other bac­te­ria, per­haps more than about any other liv­ing things.

Ours is the Age of Imag­ing  Cur­rent bi­ol­ogy has ren­dezvoused with its vi­sual ori­gins. For much of its re­cent his­tory, the chem­i­cal way of look­ing at things bi­o­log­i­cal pre­vailed. Enor­mously contribu­tory as it was, vi­sual it was not. How things have changed! Now, every as­pect of bi­ol­ogy has bene­fited from tech­ni­cal de­vel­op­ments in mi­croscopy, from the abil­ity to vi­su­al­ize sin­gle mol­e­cules, of­ten within liv­ing cells, to the dis­cov­ery of bac­te­r­ial cy­toskele­ton-like struc­tures, to the abil­ity to "crawl" in­side cells to see what they are made of. Op­ti­cal tweezer tech­nol­ogy per­mits the study of sin­gle mol­e­cules in ac­tion – poly­mer­iz­ing, stretch­ing, pulling, twist­ing. The op­ti­cal mi­cro­scope is now tran­scend­ing the bar­rier of phys­i­cal res­o­lu­tion, thanks to an ar­ray of fancy meth­ods with acronyms such as SI, PALM, STORM. The elec­tron mi­cro­scope has not been left out, with progress in cry­oto­mog­ra­phy and other tech­niques, plus var­i­ous scan­ning probe mi­cro­scopes. New views are grad­u­ally re­plac­ing old ones re­gard­ing the be­hav­ior of in­di­vid­ual mol­e­cules and the struc­ture of cells and viruses. But, de­spite all these mag­nif­i­cent de­vel­op­ments, few gen­er­al­iza­tions are yet pos­si­ble in this field.

Evo­lu­tion  Two rad­i­cal find­ings char­ac­ter­ize the mod­ern view of evo­lu­tion: the ex­is­tence of three do­mains of life and the lat­eral trans­fer of genes be­tween species. Both are fun­da­men­tal con­cepts, and both arose abruptly. Con­cep­tu­ally, both leave key ques­tions open such as, what is the ori­gin of the three do­mains? Dis­cus­sions abound, es­pe­cially about the an­ces­try of eu­kary­otic cells. Of equal con­cern is the ex­tent and im­por­tance of lat­eral gene trans­fer. To what de­gree does it incon­venience the very con­cept of the Tree of Life? And is it mainly rel­e­vant to the lower taxa? Strongly held views ex­ist on all these ques­tions. Are today's tools ad­e­quate to re­solve them? Will more genome se­quenc­ing and in­for­matic analy­ses fur­ther our un­der- stand­ing of how mi­crobes, and in­deed all of life, have evolved? Or must we await a new method­ol­ogy?

Mi­cro­bial So­ci­ol­ogy (or So­ciomi­cro­bi­ol­ogy)  For most of the his­tory of bac­te­ri­ol­ogy, bac­te­ria were thought to carry on as in­di­vid­u­als, with only a few sig­nif­i­cant in­ter­ac­tions be­tween them. The few cel­e­brated in­stances of col­lec­tive be­hav­ior, such as seen in cer­tain dif­fer­en­ti­at­ing bac­te­ria, were con­sid­ered to be spe­cial cases. We now know that bac­te­ria and ar­chaea build com­plex and inter­active com­mu­ni­ties (e.g. biofilms), the re­sult of in­tri­cate con­ver­sa­tions be­tween them. But be­yond that, even "plank­tonic" prokary­otic cells com­mu­ni­cate with one an­other. Much like in­sects, they use spe­cific chem­i­cal com­pounds as their com­mu­nity or­ga­niz­ers. These act to turn on and off genes, di­rect the mak­ing of biofilms, and trig­ger a re­sponse to in­im­i­cal in­flu­ences such as antibio­tics. Gen­er­ally speak­ing, bac­te­ria and ar­chaea act in ways akin to those of the so­cial in­sects. They are in­deed "su­per­or­gan­isms." Not only must we treat mi­crobes with greater re­spect, we can also pre­sume that the be­hav­ior of all liv­ing things evolved from that of the "sim­ple forms of life."

Cel­lu­lar Mi­cro­bi­ol­ogy  (I con­sider this a thorny term, as all mi­cro­bi­ol­ogy is cel­lu­lar, but it seems to have trac­tion, so I will use it here. It stands for "path­o­genic mi­cro­bi­ol­ogy.") Pre­vi­ously, hosts and sym­bionts, ben­e­fi­cial or oth­er­wise, were be­lieved to go their own sep­a­rate way. The ex­cep­tion to this had al­ways been the viruses, while path­o­genic bac­te­ria, fungi, and pro­tists were thought not to have such a close in­ter­de­pen­dence with their hosts. We now know that hosts and par­a­sites in­teract ex­ten­sively at a mol­e­c­u­lar level, each us­ing mol­e­c­u­lar and struc­tural con­stituents of the other for their own pur­poses. Of course, the kinds of mu­tual ap­pro­pri­a­tions and em­bez­zle­ments dif­fer be­tween spe­cific pair­ings, re­flect­ing the skills and com­pe­tency of each mem­ber. But, in each case, the give and take is ex­ten­sive and has pro­found con­se­quences. Our think­ing has shifted from view­ing sym­bio­sis and par­a­sitism in terms of pairs of or­gan­isms en­gaged in a com­plex cho­reography to a more uni­tary view in which the two con­sti­tute a new whole, a "holo­biont".

Now, how about the ad­vances in such ex­panses as the reg­u­la­tion of gene ex­pres­sion, the an­i­mal mi­cro­biome, the evo­lu­tion of sym­bioses, and many, many more? I would like to leave their sta­tus open to dis­cus­sion. You might add to this list or ar­gue about my in­di­vid­ual choices. Whether your choice of shifts and drifts matches mine or not, no mat­ter. Let us re­joice in liv­ing at a time when the list of mi­cro­bi­o­log­i­cal con­tenders is grow­ing at such a rapid pace.