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Biotechnology& Bioengineering

MauraC. Flannery DepartmentEditor

The longerI teach,the moreimportant not consider energy use withoutinvesti- organismswe choose to live with-the words become to me, the more I become gating topics all the way from the struc- on the windowsill and the cat in aware of how words influence the way ture of the atom and the geology of oil the backyard-are also pieces of tech- Downloaded from http://online.ucpress.edu/abt/article-pdf/60/6/464/48694/4450522.pdf by guest on 26 September 2021 we think. As , we have come deposits to the chemistryof oil refining nology, because they serve very useful to use the words and and the functioningof mitochondria. purposes: they bring beauty into our bioengineeringquite freely, often in ref- In TheAmericanHeritage Dictionary home, and companionshipas well. erence to genetic manipulations.I think (1992), bothengineering and both these words deserve more attention are defined in terms of : technol- because mixing the human-made and ogy is the application of science to in- natural worlds, as these words do, has dustry and commerce, and engineering WhatI've been referringto here are many implications.I am particularlysen- is the means used in designing and cre- not the ordinaryuses of the words bio- sitive to these words because I've been ating these applications.While both are technology and bioengineering-these teaching a course in science, technology characterizedin terms of and often refer to the molecular level or to and society for severalyears. I was asked processes, I find a intimate relationshipsbetween the liv- to develop the course for communica- broaderdefinition more useful.After all, ing and nonliving as in artificialjoints tions majors so they could come to ap- technology existed long before there or tooth implants. But before getting preciate how the relate to each were factories and was often developed into a specific example, I want to ex- other and to technology, and also to see with little relation to science. To me, plore a little furtherthe implications of how these relate to the larger culture. technology includes all human-madear- these words. I'll concentrate on the Puttingthis course togetherwas difficult tifacts that are in some way useful, and word engineering because a great deal for someone more interested in the in- engineering is the process of creating of the technology made in our world to- ner workings of and plants than such artifacts.When I ask my students day is createdby engineers, and though of locomotives and cameras, but it has to write abouta piece of technology that science and engineering are seen as re- been a lot of fun and I've learneda great does not requireelectricity and that has lated to each other, I think most biolo- deal. For example, I've come to appre- moving parts, they are paralyzed. Do gists see engineering as outside their ciate just how intertwined the sciences such things exist? But they end up real- ordinaryexperience. I know it was out- are with each other-you cannotdiscuss izing that spoons and rubberballs and a side mine until I started investigating a subject such as color without bringing lot of other very useful items fit the bill, technology issues, and then I discov- in everythingfrom the eye and the chem- so I think looking at the word technol- ered a number of authors who write istry of pigments to the of light ogy in broadterms makes a lot of sense. about engineering for the general pub- and the structureof a camera; you can- To my surprise, I've also learned lic and do a good job of making the something about from teaching practice and concerns of engineers ac- about technology.When we think about cessible to those outsidethe field. While Maura C. Flannery is Professor of Bi- technology we tend to envision ma- none of them writes about biotechnol- ologyand Assistant Director of theCen- chines; my students see an endless line ogy and bioengineering, their work is ter for Teachingand Learningat St. of TVs, cellular phones, computers,and relevant to issues involved in these John's University, Jamaica, NY CD-players. But we also use a great fields, and their neglect is not really 11439. She earneda B.S. in biology many living things as pieces of technol- surprisingconsidering that many of the fromMarymount College; an ogy. If technology is defined as some- people in these fields are not engineers M.S.,also in biology,from Col- thing useful, then watchdogs and to begin with. Biologists have comman- lege and a Ph.D. in science education and horses are included, to say nothing deered the words technology and engi- fromNew YorkUniversity. Her major of the we eat and wear. neering for their own purposes, with- interestsare in communicatingscience (Your out regardfor the fact thatengineers like to the nonscientistand in the relation- first thought may be that I'm referring to think of themselves as cer- shipbetween biology and art. to meat and furs, but plants too are liv- having ing thingsso this includesapples and cot- tain credentials,including an engineer- ton as well.) I would also argue that the ing degree. This is despite the fact that the word originally indicated those who plain how pieces of technology change Flormandeal more with results,Vincenti were skilled, though often with little over time. His basic thesis is that arti- gets down to the nitty-grittyand shows schooling, such as railroad engineers. facts continue to be changed, to be im- how these results are actually created. The word is still often commandeered proved, until they become particularly by those in such fields-one of my stu- well-suited for the job they must per- Polymerase Chain Reaction dents informed me that there is such a form, and then the rate of change slows thingas a cosmetic engineer(A. Duncan, or even stops. To prove his point, he uses But where is the biology in all this? personal ,March 1998), not the sophisticatedtechnology of the I've just been discussing technology and and the refuse collectors in late 20th century-what my studentssee engineeringand haven't touched the bio like to referto themselves as sanitaryen- as real technology-but rather,such ev- part, but I'm getting there. I think the gineers. eryday items as the fork, the paperclip, ideas. I've gleaned from the books I've Engineers are seen as very practical, and the Post-itTM.In ToEngineer Is Hu- mentionedare relevant to biotechnology down-to-earth people. They are very man, Petroski (1985) arguesthat failure and bioengineering.A good example of goal-oriented.Usually, they have a rather is an essential and unavoidable part of this is the development of PCR, poly- clear vision of what they are to create, the process of engineering,that it is im- merasechain reaction, in the early 1980s. though how they would get to that goal possible for an engineer to know all the This technique was the subject of a ma- may not be nearly as obvious. This in- implications of a particulardesign. Of jor biotech development effort and then terest in the practical and the serious course, engineers work hard to avoid became a tool in a greatmany other such Downloaded from http://online.ucpress.edu/abt/article-pdf/60/6/464/48694/4450522.pdf by guest on 26 September 2021 gives the impression that engineers are failure by taking into account what they efforts. This technique is the brainchild not very exciting people and are rather know aboutphysical forces, the proper- of Kary Mullis, a molecular narrowin their interests: today they en- ties of materials,and the stresses of use, who was working for Cetus, a biotech joy spending time working with their and if they kept doing the same thing firmnin California. Though he had a computers;as in the past theirslide rules over and over, creating the same build- Ph.D. in , he was do- occupied their attention. The engineer ing or the same bridge design, then the ing the ratherroutine job of synthesiz- Samuel Florman has written several failure rate would drop to nearly zero. ing oligonucleotides, relatively short books to try to counteract this impres- But as new materialsbecome available nucleotidesequences, for otherresearch- sion. I read The Existential Pleasure of and new challenges arise, the old solu- ers in the company.While drivingout of Engineering(1976) long before I started tions are abandoned,and it is through town one weekend, it struck him that teaching about technology; it was the movement into new, unchartedwaters there was a way to synthesize large title that attracted me. In this book, that failures are most likely to occur. amounts of a particular nucleotide se- Florman argues that engineers are not Thus failure and progress are two sides quence, any particularsequence in a ge- emotionless automatons who think of of the same coin, and it's impossible to nome. This could be done by separating nothing but numbers and graphs. They have one without the other. the two strandsof DNA, addingprimers derive a great deal of emotional as well WalterVincenti is another engineer that were complementaryto the begin- as intellectual satisfaction from their who sees failure as intimately involved ning sequence of one strand of the tar- work. Creating something out of form- in the design of new technology. His get sequence and to the ending sequence less material,making peoples' bet- book, WhatEngineers Know and How on the other strand.If DNA polymerase ter, and working on large awe-inspiring They Know It: Analytical Studiesfrom was added, both strands of the target projects are all sources of pleasure. In AeronauticalHistory (1990), is wonder- would be synthesized. These new The CivilizedEngineer (1987) he shows ful, but I'm not sure why I bought it. I double-strandedmolecules could thenbe that engineering is not separate from think it was the first partof the title that heatedso the strandswould separate,and other endeavors, and he contends that it sold me, because it couldn't have been the same process could be run again and is "the main business of humankindto the subtitle;I not only have no expertise again, with each iteration doubling the build, to be technologically creative"(p. in aeronautics, but don't really desire numberof strands;in other words, as its 14). He sees literatureas a commentary any. Despite this handicap,I enjoyed the name implies, PCR is a chain reaction. on , but engineering is "the stuff of book; Vincenti arguespersuasively and Theoretically at least, a mere 30 cycles life itself." It is difficult to readFlorman interestinglythat engineering is a body would produce over a billion copies of and not see machines and bridges and of knowledge engineers add to by de- the target sequence. buildings as the products of exciting sign and experimentation, and as this This idea was so simple and the com- challenges to the human mind. body of knowledge grows, designs im- ponents of the system so commonly Henry Petroski, another engineer/ prove andfailure becomes less common. available, Mullis figured that someone writer,is less interestedthan Florman in He uses a wealth of examples from air- else must have come up with it long be- the pleasure of engineering. Petroski is plane design to make his point. In each fore him. But a search of the literature more concerned with the process of en- case, problems and failures sent engi- and talks with colleagues convinced him gineering: whvatit means to design a neers back not so much to the drawing thatthis was, in fact, somethingnew. He bridge or a paper clip; how the work of boardbut to experimentationand analy- and his techniciandid experimentsto see One engineer influences that of those SiS of existing data to comeup Withzso- if the techniquewould work,but it turned who come after, how engineers contend lutions. Here are examples of problem out to be difficultto converta simple idea with the problemsof their profession. In solving at a very sophisticatedlevel that into a reality. Paul Rabinow (1996) has The of Useful Things( 1992) give a clear picture of how engineering writtena book on the discovery and de- he uses a biological concept to help ex- really works. While Petroski and velopment of PCR in which he tells how this conversion was finally achieved. tury, this was a new experience for bi- how does a company make money on a The path from idea to reality was nei- ologists, and that may be why it still technique?Cetus hadpatents on the pro- ther straight nor smooth, much as the makes many biologists a little uncom- cess and made money by selling re- story of airplane improvements that fortable.And thereare legitimate reasons agents-DNA primers and poly- Vincenti chronicles. The path to effec- for this unease. There continue to be merase-as well as thermocyclers, in- tive PCR says a lot about how science is problems with the ownership of infor- strumentsthat automatically control the done within a commercial context, and mation and the free flow of information various repeating steps in the chain re- about the relationship between science from employed by such com- action including the cyclical warming and technology, about turning science panies. But in the case of PCR, the com- and cooling of the samples. While Ce- into technology.In reality,Mullis did not mercial development of this technique tus was also involved in the develop- discover anything new about the living provideda powerfultool thathas slurred ment of a number of other products, world in coming up with the idea of many lines of researchin both academic PCR-which had started out as of pe- PCR. Instead, he conceived of a new and commercial settings. It also made ripheralimportance to the company'sfu- way of using what was already known possible the synthesis of the large ture-became its most valuable asset aboutDNA polymeraseand primers and amounts of DNA sequences needed in when it was bought by the pharmaceu- restriction ; he used them as the HumanGenome Project. tical giant Hoffmann-LaRoche in 1991. tools, as useful pieces of technology, in As with many discoveries and inven-

In describing the history of PCR, it Downloaded from http://online.ucpress.edu/abt/article-pdf/60/6/464/48694/4450522.pdf by guest on 26 September 2021 a new manufacturingmethod, a way to tions, this one was not developed to its is impossible to separatebusiness from make large amounts of specific pieces full potentialby the person who had first biology. From its inception, it was inex- of DNA. conceived of it. Mullis did do the first tricablylinked to a commercialenviron- Not being at all involved in the bio- experimentsthat indicatedthe potential ment, but this may have had the posi- technology world, I found Rabinow's of PCR but he didn't carry the develop- tive effect of speeding its development. description of how companies such as mentefforts very far.This storyis a good If Mullis had been working in the aca- Cetus developed in the 1970s and 1980s exampleof why scientificresearch is dif- demic world and had dragged his feet fascinating.Cetus, foundedin 1970, was ficult to do and why everything takes as he did at Cetus, it is unlikely that one of the early biotechnology compa- much longer than might be expected. someone else in the same university nies. Like most of them, it was long on Nothing works right the first time, or would have taken the project over as scientific expertise and short on prod- even the fiftieth. Mullis' results, after happened at Cetus; in all likelihood, ucts, since it proved more difficult than months of work, indicatedthat PCR had some form of the techniquewould have anticipated to identify the lines of re- possibilities, but these results were no been developed elsewhere, but at a later search most likely to create commer- where near convincing enough for pub- date. The significantresources available cially viable products. This was despite lication,let alone for commercialexploi- at Cetus meant that development oc- the fact that Cetus had relatively large tation.Cetus executives, once convinced curred rapidly and continued until sat- amountsof money at its disposal. Com- of PCR's value, became impatientwith isfactory results were achieved. While panies like Cetus used some of this Mullis' seeming inability to do further there have been cases of researchersin money to hire famous molecular biolo- researchefficiently. Reading between the businessbeing preventedor discouraged gists as advisorsin orderto increasetheir lines, it appears that Mullis, like many from publishing their results, this was credibilityand thus attractstill more ven- innovators, was good at creating ideas hardly the case here. In fact, manage- ture capital. This also made it easier to but not at making them a reality, so an- mentpushed Mullis to publishand when attractrising young scientists to head re- other group of researcherswas assigned he continued to stall, the development search projects. to work with Mullis. group published a paper on the tech- Though many academic scientists This second group was eventually nique, with his name included in the list would see doing in a commer- able to hone PCR into an effective tech- of authors. Needless to say, because cial setting as less "pure"science, it does nique, though it took them a couple of Mullis was not the only one responsible have its advantages.Because it was well years to do this. It requireda great deal for the successful developmentof PCR, financed, Cetus could provide research- of the trial and error Vincenti and some who had worked on the project ers with state-of-the-art facilities and Petroski write about. For example, be- were less thanthrilled when Mullis, and equipment.Working in this setting also cause the double-strandedDNA must be Mullis alone, received the 1993 Nobel freed researchers from teaching and heated after each round of synthesis in Prize for for inventing PCR. committee work-two often heavy bur- order to separatethe strands,the DNA This isn't the first time that such con- dens of the academic world-and per- polymerase used in the process needed troversyhas arisenover the Nobel Prize, haps more importantly,from the need to to be resistant to destruction by heat. but it is interesting that such problems get grants, something that consumes a Finally a polymerasecalled Taqwas re- of attributionare as likely to take place great deal of time for those mounting coveredfrom the thermophilicbacterium in a commercial setting as in an aca- majorresearch efforts. Thus biotechnol- aquaticus, and it remained demic setting. ogy firms were involved in more than stable through repeatedcycles of heat- just technology, with making useful ing andcooling. This increasedthe yields Metaphors products, they were also changing the from a PCR synthesis several ordersof way biological researchwas done. While magnitude.It was improvementssuch as Having discussed a particularex- chemists have been doing this in the synthesis system that finally ample of biotechnology-engineering a in industrialsettings since the 19th cen- made PCR an attractivetechnique. But synthesis process using the stuff of liv- ing things, enzymes, nucleotides, DNA complexityinvolved not found in the non- trendin biology,a majorshift fromstudy- sequences-I now want to get back to living world.And in dealing with human ing the living world to manipulatingit, to the word bioengineering. I think it is a beings, thereare ethicaland social issues remakingit. There is an exhilaration,in fitting wordfor the developmentof a pro- that are of a differenttype from those in- the senseFlorman describes, for biologists cess such as PCR, which involved the volved in dealing with the inanimate who have moved from being observersof design of a process, just as an industrial world. Using mechanisticmetaphors has natureto being builders.Also, it may be engineer might design a process for the advancedour understanding of the human thatbiologists would like to be engineers, manufactureof soap or tires. It involved body in many ways. Jonathan Miller to have the power to design from scratch decisions about temperatureconditions, (1978) has argued,for example,that Wil- ratherthan to just acceptthe designsof na- ingredient concentrations, and reaction liam Harveywould not have been able to ture.Talking in termsof engineeringand times that chemical engineers deal with figureout thecirculation of bloodthrough technologymakes it seem thatbiologists in synthesizing pharmaceuticalsor pet- the heartwithout comparing it to thefunc- have a certaincontrol over life, perhaps rochemicals. So the word engineering, tioningof a pump.But comparing the heart morethan they reallydo, andthis is a level as used by Petroski and Florman,seems to a pumpor the eye to a cameracan also of control that at least some biologists to be appropriately used in describing lead to the errorof lookingat the body as would like to have. PCR. But I thinkthat this appropriateness a collectionof partsthat can be almostend- In closing, I should say however,that hides a problem,and the problem is that lessly replaced,rather than as an organic the engineeringmetaphor also has some bioengineeringinvolves a metaphoricaluse whole with limits to its being "fixable." connotationswhich biologistsmight well Downloaded from http://online.ucpress.edu/abt/article-pdf/60/6/464/48694/4450522.pdf by guest on 26 September 2021 of the word engineering.By this I mean Theability to "engineer"-to cut attendto. One is failure;as Petroskinotes, thatthe wordhas been takenout of its usual and rearrangeand paste much as you failure is an essential ingredientin engi- context and used in a very differentand would pieces of wood or metal-leads to neeringadvances. This means thatbiolo- even alienone. Engineeringusually refers the assumptionthat almost any "design" gists cannotexpect a smooth road ahead to the human-made.Bioengineering does you might want can be created.Making and must be preparedto deal with conse- too, butit alsoinvolves living things or their such an assumptionis an incredibleact of quencesof bioengineeringthat may be un- products,and thinking about living things hubriswhich our use of the wordbioengi- pleasantif not dangerous.This is some- in termsof engineeringcan changeour at- neeringsomehow makes more feasible. It thingmany observers have warnedof, but titudestoward the living world. neglectsthe fact thatbioengineers are not a closer look at engineeringhistory might In his analysisof metaphor,Max Black startingwith simple raw materials as more be a good way to sober some of the more (1978) writes that when a word is used traditionalengineers often do, raw mate- radicalpredictions of thebiotechnologists. metaphoricallysome of its meanings,con- rialwhose properties have been studied for notationsand "entailments"remain valid years. Instead,bioengineers are working References while others do not. In the case of using with materialsthat are ordersof magni- engineeringto describe the manipulation tudemore complex. I readsomewhere that TheAmenicanHeritage Dictionary (3rd ed.). of living things,it is truethat such manipu- the most sophisticated composite (1992).Boston: Houghton, Muffin. lation involves design, trial and error, materials-that is, materials produced movementtoward a practicalgoal, just as from two differentsubstances with very Black,M. (1978).Metaphor. In J. Margolis engineeringdoes. But engineeringalso has different properties-are not fiberglass (Ed), PhilosophyLooks at theArts (pp. otherimplications that are not as appropri- andnew-age ceramics, but bone and wood. 451467). :Temple Univer- ate. Engineeringbrings with it thoughtsof Yet with these materialswe are still deal- sityPress. machines,of life-less processes, of mak- ing withrelatively simple systems relative Forman,S. (1976).The Existential Pleasures ing thingsfrom scratch,and none of these to the whole genome or to an intactani- of Engineering.New York:St. Martin's. connotationsquite fits when considering mal or . Florman,S. (1987).The Civilized Engineer. living things. A mechanisticview of life I am hardlyan enemy of biotechnol- New York:St. Martin's. waspopular with some biologistsat theend ogy in the mold of such outspokencritics Miller,J. (1978). The Body in Question.New of the 19thcentury, and Philip Pauly (1987) of genetic engineeringas JeremyRikfkin York:Random House. has writtenof JacquesLoeb's verymecha- (1991),butl do thinkit is importantto keep Pauly,P. (1987). Controlling NewYork: nistic view of life. But other lines of re- in mind the impact of the subtle entail- Life. search at the time and later clearly indi- ments of words,the host of connotations OxfordUniversity Press. cated that living things are much more each carrieswith it. Talkingabout genes Petroski,H. (1985).To Engineer Is Human: complex than machines and thatlikening in termsof engineeringsomehow makes TheRole ofFailure in Successful Design. themto machinescan leadto simplisticand themseem simplerthan they are;they be- New York:St. Martin's. inaccurateexplanations of biologicalpro- come ribbonsof chemicalsthat can easily Petroski,H. (1992).The Evolution of Useful cesses. I thinkthis same dangerexists to- be cut and moved aroundand, if neces- Things.New York:Knopf. day. sary, replaced.That genes only Rabinow,P. (1996). Making PCR:A Story of Metaphorsare powerfultools thatcan withina complexcellular environment and Biotechnology.Chicago: University of makenew conceptsmuch clearer by relat- are very much influencedand controlled ChicagoPress. But ing them to already existing ideas. by thisenvironment fades from view when Rifkin,J. (1991). BiospherePolitics. New metaphorsdo have dangers.It is impor- the emphasisiS on engineering. York:Harper Collins. tantto always keep in mind thata similar- But if wordslike engineeringand tech- ity is not an identity,that while there are nology are so problematicin termsof bi- Vincenti,W. (1990). WhatEngineers Know similarities between engineering and ology, why arethey so commonlyused by andHow They Know It: Analytical Stud- bioengineering,the factthat the latterdeals biologists?I thinkin partthis is because iesfromAeronauticalHistory. Baltimore, with living thingsmeans there is a level of theseterms have been used to signala new MD:Johns Hopkins University Press.