Cell Language Theory, The: Connecting Mind And Matter

Applications of the Cell Language Theory to Biomedical Sciences 297

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biologists to measure rates of gene expressions (denoted as TR, transcrip-

tion rates [315]) by measuring mRNA levels (denoted as TL, transcript

levels [315]). In other words, they have created the scientific atmosphere

in which it is deemed legitimate to accept a simple one-to-one correspond-

ence between TL and TR. The following quotations reflect such a lax

attitude in the microarray field (emphasis is mine):

“... Microarrays prepared by high-speed robotic printing of comple-

mentary DNAs on glass were used for quantitative expression mea-

surements of the corresponding genes....” [308]. (7.4)

“Oligonucleotide arrays can provide a broad picture of the state of the

cell, by monitoring the expression level of thousands of genes at the

same time....” [312]. (7.5)

“... DNA microarrays, permits the simultaneous monitoring of thou-

sands of genes....” [313]. (7.6)

These statements would be correct if the term “genes” (in italics) were

replaced by “mRNA levels” or “transcripts”. In other words, workers in this

field routinely conflate “genes” with “gene transcripts” and Transcription

Rate (TR) with Transcript Level (TL), leading to numerous false-positive

and false-negative conclusions in interpreting microarray data. Most inves-

tigators in the field seem to think that there is no harm in using the terms

“gene expression” and “mRNA levels” interchangeably, but the investiga-

tions by Garcia-Martinez et al. [315] and Fan et al. [316] have now clearly

demonstrated that the mixing of these two terms can lead to erroneous

conclusions [317–319].

Because of the experimental difficulties involved in measuring TR, it

was not until 2004 that J. Perez-Ortin and his colleagues in Valencia, Spain,

succeeded in measuring both the TR and TL values simultaneously of the

whole genome of budding yeast subjected to glucose–galactose shift [320–

322]. It is well known that when budding yeast cells are deprived of glu-

cose, they undergo a profound metabolic transition from fermentation

(converting glucose into ethanol) to respiration (converting ethanol to car-

bon dioxide and water) known as the diauxic shift [322]. When these TR

values are plotted against the TL values, highly nonlinear trajectories were

obtained as shown in Figure 7.5. Previously investigators routinely assumed

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