Biology Reference
In-Depth Information
nome Sequencing Platform, a chemical engineer by training, had worked
previously as a project manager for the Fluor Corporation, “the larg-
est US-based, publicly traded engineering and construction fi rm.” Rob
came to MIT in 1999 as a fellow in the Leaders for Manufacturing
Program to conduct research on manufacturing systems and processes,
joining the Whitehead in 2001 in order to implement industrial process
design, control, and improvement techniques. 23
During the time I spent at the Broad Sequencing Center, the infl u-
ence of Nicol's manufacturing and industrial process design ethos could
be seen everywhere. Not only lean production, but Six Sigma (6
) and
a range of other manufacturing techniques had been put into practice
in biology. 24 First, a large amount of time and effort had been invested
in planning and streamlining processes and workfl ow for sequencing.
Space and materials were carefully organized to economize human and
sample movement around the labs. Beginning in 2003, the Broad re-
cruited a series of MBA students from the Sloan School of Management
(MIT's business school) to investigate the potential for improving the
manufacturing capabilities of the lab. As Matthew Vokoun reported,
“During the completion of the HGP in the 1990s and early 2000s, the
purpose of the Broad Institute's sequencing operation was to rapidly
scale-up or 'industrialize' the genome sequencing process. This indus-
trialization of sequencing refers to its transition from being a highly
skilled craft performed by a few very well-educated biologists to a
large-scale, coordinated production process involving over one hundred
technicians, engineers, managers, and scientists.” 25 This was achieved by
breaking the sequencing process down into small, repetitive steps that
could be performed quickly and accurately.
In 2003, Julia Chang was given the task of analyzing and improv-
ing the process of “picking” E. coli colonies for sequencing. 26 Picking
is an automated process through which E. coli colonies growing on
agar plates—each containing a distinct fragment of DNA—are trans-
ferred to 384-well plates for sequencing. Colonies used to be picked by
hand using a toothpick. At the Broad, a digital camera images the agar,
and a specialized software program analyzes the image to determine
the positions of colonies with desirable characteristics (size, roundness,
distance from other colonies). A computer arm fi tted with specialized
tips then transfers the suitable colonies to the wells. Chang's mandate
was to identify sources of variation in this process and suggest steps to
eliminate them. Working with the team responsible for picking, Chang
devised a series of experiments to determine what variables most infl u-
enced the yield of colonies successfully transferred to wells. Chang used
σ
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