By Jason Socrates Bardi
"Or whether shall I say,
mine eye saith true,
And that your love taught it this alchemy,
To make of monsters and things indigest
Such cherubins as your sweet self resemble,
Creating every bad a perfect best,
As fast as objects to his beams assemble?"
Shakespeare. Sonnet 114, circa 1600.
One of the most famous photos of 1953, taken by Antony Barrington
Brown, shows future Nobel laureates James Watson and Francis
Crick discussing some of the finer details of the antiparallel
double helical structure of DNA, which they had just described
in the journal Nature.
Towering over the heads of the two scientists is a massive
physical model of DNA that was built using rods, clamps, flat
pieces of metal, and other bits of laboratory detritus. Building
the monstrous model was integral to the understanding of DNA's
structureas model building often is.
"Having a physical model is extremely valuable," says Professor
Arthur Olson, who is a member of the Department of Molecular
Biology at The Scripps Research Institute (TSRI). "A physical
object in a social situation promotes interaction and discussion,
and it enables one to see physically the implications of some
From the Virtual to the Tangible
A crystallographer by training himself, Olson remembers
how he built his first protein structure by hand in a "Richards
box"which resembled something that you would expect
to find as a professional magician's illusion rather than
as a professional scientist's tool. A contraption with a physical
model of a molecular structure made out of metal rods and
a half silvered mirror that reflected hand-traced images of
electron density, a Richards box revealed the molecular structure
as a stick model (brass) of all of the protein atoms.
Having such a physical model always provided easy access
to the biology of molecules, but biologists didn't always
have easy access to the physical models. They were hard, often
impossible, to build by anyone except the most patient and
steady-handed individuals. This all changed a few years later
when computers became powerful enough to represent molecules
"Building physical models was tedious," says Olson. "Computers
allowed you to do it much better and much faster."
So, for a while, physical models went the way of the dinosaur
and computers reigned. Software designed to display molecules
improved along with the power of the computers themselves,
and other features were added, such as virtual reality gloves
that allowed researchers to move the image around by "hand"
and special head sets that simulated a three-dimensional feel
to the flat images.
But in the end the images were still flat and displayed
on a computer screen. Something was lost in not being able
to touch, hold, and manipulate a model physically.
Today, technology is turning a corner. It is now possible
to fabricate physical (or "tangible") models automatically
with the click of a button on a computer. Scientists like
Olson are making these tangible models and starting a renaissance
that marries these models with the power of computers.
Fabricating Objects Automatically
Olson uses a whole new class of inkjet printer to make tangible
models. The printer basically lays down layer after layer
of a special fine plaster powdereventually filling a
well about the size of a gallon of ice cream.
The printer builds the model as the layers are laid down.
On top of each layer, the printer puts down colored water
in a pattern resembling the cross-section of the physical
model on that plane. A fresh layer of powder goes on top of
that, and the printer lays down the pattern in colored water
for the next cross-section. As the thousands of layers are
built up, the printer sprays different patterns on each layer,
and the water acts as an adhesive and sets the plaster for
In this way, the layers are built up with the colored water
binding each layer together. When the process is finished,
the volume of powder contains the physical three-dimensional
models, which can then be lifted out, dusted off, and finished
Olson uses one of the models regularly when he is discussing
his research related to the human immunodefficiency virus
(HIV) protease. Olson directs a large NIH-funded project that
seeks to establish a drug design cycle aimed at developing,
testing, and refining novel approaches to making specific
inhibitors of HIV protease that are capable of limiting or
eliminating drug resistance.
"We're not just looking at a protease," says Olson. "We're
looking at the mutational range due to drug resistance and
[seeing] what we can predict about it."
As part of this work, Olson meets frequently with his co-investigators
at TSRI and at other institutions, and he finds that tangible
models of HIV proteases help to facilitate discussion.
"People see different things in three dimensions than they
do on a computer screen," says Olson. "I've had people look
at physical models of proteins they have studied for years
and say, 'Gee, I never saw that before!'"
Last year, Olson was awarded grants from the National Science
Foundation and the National Institutes of Health to pursue
a project called Tangible Interfaces for Molecular Biology.
This project entails building models and using them as interfaces
for a computational environment. Rather than simply making
such tangible interfaces as a proof-of-principle, Olson has
sought collaborations with other investigators at TSRI who
can apply such tools to their immediate research.
"We're making models for a number of people around Scripps
working on various projects," he says. "People really
do appreciate these physical models, and they use them in
collaborations and in the examination and exploration of structure."
This is not a service but a mini-collaboration and an exchange.
So far Olson has provided 10 scientists at TSRI with such
models. The other scientists give him feedback, providing
him with case studies of what the model is good for and what
it is not good for. This feedback is valuable for Olson's
goal of determining how tangible models can be used and how
they can be enhanced.
The point of the grant is to determine how people can use
physical models to understand complex structuresespecially
if they are not experts in structural biology themselves.
At the moment, Olson is building a "vocabulary" of molecular
representations to see what is possible and what is useful
He is exploring possibilities such as fabricating physical
models and inserting small point magnets into them as a way
of simulating hydrogen bonding and other non-covalent interactions.
And he is experimenting with attaching pieces of models to
wire and other flexible materials as a way of representing
For instance, he models single DNA strands with tiny magnets
inserted into the individual bases, which represent the hydrogen
bonds. One such model, which he keeps on his desk, readily
forms a double helix with the magnets clicking together as
the bases pair.
Olson is also trying to further enhance his physical models
by using them as computer interface tools with a new technology
called augmented reality.
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