December 2021 BOC Newsletter | Page 6
MOLECULAR BIOLOGY CERTIFICATION: RECOMBINANT DNA
TECHNOLOGY TO MOLECULAR DIAGNOSTICS - TODAY’S
TECHNOLOGY INSPIRED BY PAST DISCOVERIES
by Lela Buckingham, PhD, MSc, MB(ASCP)
CM
DLM
CM
Nucleic acid testing techniques used in the
clinical laboratory are based on momentous
discoveries leading to what was called re-
combinant DNA technology. Even with their
futuristic visions, early scientists may not
have predicted what we take for granted as
routine work today. Imagine the reactions
of historical scientists to our current pro-
cedures. The Greek physician Hippocrates
(400-377 BC) is credited with the initiation
of diagnostic testing of patient body uids.
He may not have realized the true wealth of
information in these materials, stored inside
of nucleated cells in the form of deoxyribo-
nucleic acid (DNA), carried by ribonucleic
acid (RNA) to be translated into protein and
ultimately the phenotypes he observed. We
can only wonder how prescient his vision of
the information held in body tissues and u-
ids actually was.
The form of genetic information was rst
proposed in 1866 by Gregor Mendel as dis-
creet units of inheritance. Mendel would
likely be gratied that his theories have
been the basis of molecular genetic testing.
Fredrich Meischer, who rst isolated nucleic
acid from cells in 1869, would be intrigued
by automatic nucleic acid isolation systems
currently used and our ability to obtain his
“nuclein” from unlikely sources such as pre-
served tissue and touched objects. Walther
Flemming would certainly appreciate the in-
tricate uorescent imaging technology that
allows medical laboratory scientists to ob-
serve and study the mitotic chromosomes
that he rst described in 1882.
Scientic interest in nucleic acid analy-
sis grew through the late 1940s to early
1950s. After their experiments in the 1940s
on DNA as the genetic material, Oswald
Avery, Frederick Grifth, Maclyn McCarty,
and Colin McCleod might still be fascinat-
ed with its use for detection and identica-
tion of microorganisms and how disease
risk could be traced through DNA. Study of
DNA was highlighted by the rst descrip-
tion of its molecular structure published by
James Watson and Francis Crick in 1951.
Rosalind Franklin’s famous X-ray diffrac-
tion images were key to the solution of the
double helix. What would she think of the
use of computerized sequence analysis to
instantly predict effects of amino acid sub-
stitutions on protein structure and function?
Who among the many contributors to the
discovery of messenger RNA 10 years lat-
er would have predicted the use of a modi-
ed RNA as a therapeutic vaccine? Werner
Arber, Daniel Nathans and Hamilton Smith,
who rst described restriction enzymes in
the mid 1960s, may eventually have con-
sidered the potential use of the Cas en-
zyme and clustered regularly interspaced
short palindromic repeats (CRISPR) for
gene therapy. After the demonstration of
semiconservative DNA replication in 1958,
Matthew Meselson and Frank Stahl would
certainly be intrigued by the discovery by
Kerry Mullis leading to the nucleic acid am-
plication methods routinely performed by
laboratory scientists today. As high com-
plexity tests using nucleic acids evolved,
single target hybridization techniques gave
way to multiplex arrays and cytogenetic im-
aging as well as nucleic acid amplication
and sequencing methods.
The American Society of Clinical Pathology
(ASCP) recognized the importance of cer-
tied knowledge and skills in molecu-
lar biology and, in 2003, implemented the
Technologist in Molecular Pathology (MP)
Certication Examination, which is now
the Technologist in Molecular Biology
(MB) Examination. Certication in molecu-
lar biology initially offered by the National
Credentialing Agency for Laboratory
Personnel (NCA) in 1997 was recognized
by ASCP in 2009. Medical scientists with
ASCP certication have realized preferred
hiring by medical and industrial laborato-
ries developing and utilizing DNA and RNA
analysis for nucleic acid testing, as well as
development of diagnostic products and
instrumentation.
Molecular diagnostics as a key aspect of
patient care has also led to opportunities for
administrative and management positions
in this area. In medicine, molecular pathol-
ogy has become a valuable component of
diagnostic and prognostic interpretation for
physicians. This requires laboratorians who
have developed specialized skills, not only
in performance of molecular protocols, but
design and interpretation of nucleic acid
testing methods for diagnosis and charac-
terization of acquired and inherited diseas-
es. Bioinformatics for clear communications
with physicians and other health profession-
als is of tantamount importance. In keeping
current with the evolution of the profession,
ASCP introduced the Specialist in Molecular
Biology (SMB) Certication Examination in
2018. This examination addresses skills re-
quired for supervisors, managers and direc-
tors of molecular diagnostics laboratories
including advanced molecular testing, bio-
informatics, novel clinical applications and
laboratory management, including method
design and test development.
To establish eligibility for the MB examina-
tion, there are sets of minimum prerequisites
(routes), depending on education, training
and experience. These include combina-
tions of a baccalaureate or higher degree
from a regionally-accredited college/univer-
sity. In addition to formal training, full time
experience in a molecular biology laborato-
ry that offers molecular methods including
nucleic acid isolation, amplication, detec-
tion, sequencing, hybridization techniques,
and data analysis is required. The time of
experience (six months to one year) de-
pends on the level of education completed.
Routes of eligibility for the SMB examina-
tion include successful completion of the
MB examination and a baccalaureate or
higher degree and full-time experience in
molecular biology laboratory (one to three
years). Detailed descriptions of the routes to
eligibility for testing and subject content for
the MB and SMB can be found at ascp.org.
As in other elds of study, technology is
rapidly advancing. Keeping current with on-
going developments through classes, as-
sociation and society meetings, original
articles, texts, new product development
and electronic sources can not only ben-
et those wishing to become certied in
this area, but enhance existing laboratory
skills. Scientists of the past would marvel at
what is possible in the molecular diagnos-
tics laboratories today. And we have not yet
imagined the wonders of the future for this
technology, using nucleic acids for predic-
tion, diagnosis, treatment, and eradication
of disease.