Biology Reference
In-Depth Information
significant problems. First, how to deal with the enormous
signal-to-noise challenges intrinsic to all large data sets,
and second, how to convert data into knowledge. Solving
these problems is the role of systems medicine. The key for
systems medicine in the future will be to ascertain and
deconvolute the 'network of networks' for each individual
and to be able to follow its dynamics in response to various
types of biological information, providing fundamental
insights into wellness and disease.
Looking back in history there were four paradigm
changes that led directly to systems medicine: (1) auto-
mated and high-throughput biological technology, (2) the
Human Genome Project, (3) the creation of cross-
disciplinary biology institutes, and (4) the creation of
systems biology as an area of research
[22,23]
We will
spend some time focusing on one of these, the Human
Genome Project, to describe the revolutionary effect that it
has had on biology.
The first meeting on the Human Genome Project was
held in the spring of 1985. Twelve 'experts' had been
invited to Santa Cruz to consider whether sequencing the
human genome was advisable. This committee came to two
conclusions: (1) the project was feasible albeit technically
difficult; and (2) the group was split 6 to 6 on whether it was
a good idea. In the mid and late 1980s perhaps 90% of
biologists were opposed to the project, as was the National
Institutes of Health (for reasons such as: big science is bad;
the genome is mostly junk, so why sequence it? no good
scientists would participate in such a mindless endeavor,
etc.). A committee of the National Academy of Sciences
with both opponents and proponents was convened to
consider this possibility, and their unanimously favorable
report turned the tide. The project was initiated in 1990 and
finished in 2004
4.
It made mass spectrometry-based proteomics possible
by providing the sequences of proteins and their
corresponding tryptic peptides.
5.
It brought computer scientists, theoretical physicists,
software engineers and mathematicians into biology to
deal with the exponentially increasing data sets,
thereby providing new software and mathematical
tools for converting data into knowledge.
6.
By requiring that genomic data be made public as soon
as it was determined, it pioneered the idea of open
data, rapidly published and available to all.
7.
It also pioneered the importance of assessing data
quality and the software necessary for this assessment.
8.
It made the genomes of microbes, plants, and animals
accessible to all biologists, transforming many fields
of biology (e.g., microbiology, virology, immunology,
etc.).
9.
It revolutionized our understanding of molecular
evolution.
10.
For medicine, it made possible new approaches to
genomic diagnoses; it enabled personalized medicine;
and it is forging new approaches to assessing proper
drugs (therapies) for differing kinds of cancer.
11.
It brought biology into the realm of big science and
initiated a big science/small science debate that
continues even today. Big and small science can be
beautifully integrated, and each plays an important
role in deciphering biological complexity [1].
The Battelle Memorial Institute has recently estimated that
the Human Genome Project has led to almost $800 billion
in benefits for an initial investment of about $3.5 billion. It
is clear from skimming though these benefits that the
project enabled and enriched systems approaches to
biology and medicine in many different ways that go far
beyond genomics itself.
Many people use the term 'genomic medicine' to
denote the medicine of the future, yet in principle genomic
medicine is one-dimensional in nature, only encompassing
nucleic acid information. Systems medicine, in contrast, is
holistic and utilizes all types of biological information,
including DNA, RNA, protein, metabolites, small mole-
cules,
under budget and ahead of schedule.
Many have argued that the genome project did not fulfill
its promise, but the truth is quite the opposite. The Human
Genome Project has transformed both biology and medi-
cine in several important ways:
e
1.
It made systems biology possible by providing
a complete parts list of all (most) of the genes (and by
inference their corresponding proteins) in the human
and several model organisms. This parts list was
essential
interactions,
cells, organs,
individuals,
social
for
global
and
integrative
systems
networks and external environmental signals
integrating
them so as to lead to predictive and actionable models for
health and disease.
e
approaches, not
to mention all subsequent human
biology research.
2.
It 'democratized' all genes (and indeed any region of
the genome) by making all genes available to all
biologists.
FIVE SYSTEMS' STRATEGIES FOR DEALING
WITH BIOLOGICAL COMPLEXITY
To develop predictive and actionable models we need to
tease apart the complexity of health and disease. Systems
medicine employs five strategies to deal with biological
3.
It pushed high-throughput biology to the next stage by
driving technologies to increase the speed and accu-
racy of DNA sequencing to pioneer other genomic
technologies,
such as DNA arrays and parallel
sequencing.
