Ryan Emptage and Cole Davis
Dr. Alber
Biocomplexity Seminar
The Future of Molecular Biology
Following the discovery of the structure of DNA by Watson and Crick, the
scientific horizons for biotechnology and molecular biology became limitless. Once the
structure of the blueprint of life was unlocked, scientists everywhere could start to study
and manipulate DNA. In this paper, we will discuss some of the most current
developments in the study of molecular life and explain how some of these new
developments will most certainly be affecting us in the near future.
With the advent of computational biology, the field of genetics has evolved at an
astounding rate. Not only can supercomputers encode the human genome (and others),
but we can now do something with that data. The idea was that the DNA from
prokaryotes (simple cellular organisms, like bacteria) and eukaryotes (complex
organisms) behaved similarly. One gene creates one protein and those proteins do the
“work,” which still holds true for prokaryotes. Problems arise in the analysis of
eukaryotic DNA. The archaic viewpoint was that the DNA was made up of exon (codes
for protein) and intron (junk DNA) strands. The intronic DNA composes the majority of
eukaryotic DNA, yet it was thought to be junk. Recent research has led to new theories
that will revolutionize genetics.
One theory is that in prokaryotes some of the non-coding intronic RNA and even
some of the non-coding exonic RNA might have vital functions in regard to genetic
sequences. It is thought that they control the DNA-cleaving proteins which cut DNA.
RNA strands have other functions. For example, several types of RNA strands arise:
short interfering RNAs (siRNA), MicroRNAs (miRNA), Tiny non-coding RNA’s
(tncRNA), and RNA interference (RNAi). SiRNA’s are only 21 or 22 nucleotides in
length and interfere with the replicating process to silence genes. MiRNA’s silence genes
at the stage of protein syntheses. TncRNA’s are 20 to 22 nucleotides in length, and their
function is unknown. RNAi is the silencing of gene expression by double-stranded RNA
molecules. Now what is the significance of these tiny RNA strands? Perhaps all of
complex life makes use of them. A couple of plant biologists, Jorgensen and Mol,
injected multiple copies of a purple pigment gene into petunias, did not make the flower
more purple, but in fact had the opposite effect. The transgenes interfered with the
original genes and silenced the effect, resulting in “albino” flowers. This opens up a
huge frontier in medicine. Now it is technically possible to silence genes with RNA.
One of the men studying the functions of life is Norman Packard, CEO of a
company called ProtoLife. Unlike other companies studying the mechanisms of life,
ProtoLife is attempting to create a new form of living being from non-living chemicals in
a lab. The first issue for this type of project is to define life. ProtoLife has determined
life to be contained within something that replicates and can evolve through a process
similar to Darwinian evolution which operates by natural selection. What are the
requirements of such an organism? Packard, who has chosen to take the most simple of
routes, has boiled the requirements down to containment, heredity, and metabolism. The
organism they are trying to create, nicknamed the Los Alamos Bug due to ProtoLife’s
collaboration with Los Alamos National Laboratory in New Mexico, will be contained
within a droplet of fatty acids whose hydrophilic heads create a membrane. Heredity will
by handled by the A,T,C, and G nucleotides in a DNA-like molecule called PNA. PNA
is engineered so that its backbone is uncharged, letting it dissolve in the fatty acid glob.
At a certain temperature, the double-stranded PNA molecule separates and the strands
migrate to the surface due to the slight charge in the PNA nucleotide bases. At the
surface, certain primers will be provided to help replicate the PNA and the replicated
PNA molecule will travel back into the fatty acid membrane. Metabolism will occur
when the “food” of the Bug, fatty acids with a light sensitive mask on the hydrophilic
head to keep these molecules inside of the membrane, is struck by light. When light is
able to penetrate this “mask”, the light sensitive molecule will be removed and the now
normal fatty acid will join the membrane causing the globular organism to grow. At a
certain size, surface tension on the membrane will be high enough to cause the mass to
split into two separate droplets, thus fulfilling the replication requirement. ProtoLife is
hoping that these molecules will one day perform many useful functions. These
simplistic organism could one day be synthesized to break down toxic chemicals,
produce hydrogen fuel, administer drugs to the body while sensing how much of the drug
it needs, and check for problems in the human body as it roams through the blood stream.
The synthesis of such an organism is currently in the early development phase as
researchers are still devising a way to limit the Bug to one round of PNA replication per
droplet division to facilitate evolution. The Protolife team is hoping that the Bug will be
operational within five years.
In another area of study, scientists are finding the increasing importance of intron
segments of DNA, which were once thought to be quite useless. In classic gene
expression, the introns were simply excised by a cellular technique called splicing before
the DNA was translated to make proteins. Now, scientists are finding that there are many
alternative ways to splice DNA which cells use regularly. These newfound methods can
skip introns and splice a single exon, retain small pieces of an intron, or separate exons so
that each is on a different piece of the two resulting pieces of DNA. Put simply, the DNA
once thought to be just taking up space and disposed of upon splicing is being shown to
have significant importance. With all these methods of splicing, each gene which was
once thought to code for only one type of protein has been shown in some cases to be
able to code for up to three or four proteins, making each segment of DNA, both introns
and exons, increasingly critical.
With all of the new technology being developed, there is increasing focus being
given to ethical questions. The new field of synthetic biology, in which entire genomes
are created from scratch, has caused many to worry about the potential consequences of
such a technology, and these worries are well substantiated. In 2002, Eckard Wimmer
and his team of scientists from the State University of New York at Stony Brook
synthesized a poliovirus from mail-order DNA. In 2003, Craig Venter and his Rockville,
Maryland team did the same with a virus that infects bacteria in just three weeks. Why
even take the risk of inciting biological warfare or releasing a deadly virus? Most
scientists would agree that the benefits are far more substantial than the risks.
Synthesized biomolecules could treat certain diseases, repair damaged body cells, or
create alternate fuel sources. What are some methods which keep the benefits of genetic
technology while reducing the risk? Some scientists suggest that a license should be
required in order for a research group to conduct genetic experiments. Others suggest
that individual companies should take matters into their own hands by crosschecking
suspicious businesses for possible misuse of such a power. One DNA synthesis
company, Blue Heron, has taken this step to help reduce the risk of technological abuse.
Still others suggest that companies should be part of an “honor code” and report
potentially dangerous technologies directly to the government. An additional safety
mechanism in the synthesized organisms would be to include a “self-destruct gene”
which could be triggered if any populations of experimental organisms got out of hand.
None of these safeguards have been implemented yet, but no one argues with leading
researcher George Poste when he states, “Biology is poised to lose its innocence.”
The future of molecular biology promises to be one full of advance but danger as
well. As we make the steps toward the artificial creation and manipulation of life’s
processes, we must be careful to not endanger our own. The human genome has less
genetic material than both rice and corn, showing that our complexity arises from the
many ways we read our comparatively fewer amount of genes. This fact proves that we
are just scratching the surface of knowing our genetic potential and the genetic potential
of the genomes we synthesize.
Bibliography:
Gibbs, W.. “The Unseen Genome: Gems among the Junk.” Scientific American.
November 2003: 48-53.
Mattick, John S.. “The Hidden Genetic Program of Complex Organisms.” Scientific
American. October 2004: 60-67.
Novina, Carl D. and Sharp, Phillip A.. “The RNAi Revolution.” Nature. Vol. 430,
8 July 2004: 161-164.
Ast, Gil. “The Alternative Genome.” Scientific American. April 2005: 58-65.
Ball, Phillip. “Starting from Scratch.” Nature. Vol. 431, 7 October 2004: 624-626.
Holmes, Bob. “Alive!” NewScientist. 12 February 2005: 28-33.