HOW DAVID BERRY’S INVENTIONS WORK
dFGF2: Protein to Treat Stroke
This invention resulted from Berry’s thesis research into
compounds called glycosaminoglycans, which are complex sugar polymers.
The best-known of these molecules is the anticoagulant heparin.
Heparin-like glycosaminoglycans, formally known as heparin/heparan
sulfate-like glycosaminoglcyans (HSGAGs), are present on the surface
of every cell in the body. HSGAGs have 48 building blocks –
compared to DNA, which has four, and proteins, which have 20. They
can interact with a number of important proteins because of the
significantly higher number of possible HSGAG sequences.
Berry investigated the way heparin interacts with a particular
type of fibroblast growth factor protein called FGF2, which is involved
in the formation of new blood vessels. He discovered a way to optimize
FGF2 to treat stroke.
For FGF2 to have an effect on cells, it needs to form a dimer,
where two FGF2s come together. Heparin and other HSGAGs facilitate
this dimerization process. The dimerized FGF2s form a complex with
two cell surface receptors. This entire five-member complex is brought
into the cells, leading to the cellular response.
The new protein Berry et al. created, called dFGF2 or dimerized
FGF2, functions as the two FGF2 molecules brought together by heparin.
It thereby serves as three components of the five-member signaling
complex. This entirely eliminates the need for the heparin component.
Cells therefore respond to dFGF2 at a lower dose than they do for
FGF2. Cells can also respond more to dFGF2 than to FGF2.
The dFGF2 protein reduces the variability in obtaining a cellular
response. For the treatment of stroke, dFGF2 has a stronger effect
than FGF2 and can produce its effect at a lower dose, reducing the
chance for side effects.
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Internalized Heparin for Cancer
Berry discovered another use for heparin as a treatment for cancer.
He discovered that when heparin, which is negatively charged, binds
to a biodegradable polymer called a poly(B-amino ester), it results
in a positively charged complex, about 200 nm in diameter.
Cells have a tendency to take up positively charged substances
of ~200 nm or less in diameter through a process called endocytosis.
Cancer cells have a faster rate of endocytosis than most normal
cells. As a result, the polymer-heparin conjugate is selectively
taken up by the cancer cells and the heparin is delivered to them
without affecting the other healthy cells. This eliminates the side-effects
common in treatments such as chemotherapies, which attack both healthy
and cancerous cells.
Certain varieties of the poly(B-amino ester) polymers are better
for certain types of cancers, so they can be matched for maximum
In addition to its use as an internal delivery mechanism for heparin,
Berry developed a new procedure to use heparin externally, as well.
His self-described “cancer Band-Aid®” is a surface
coating made from various complex sugars, including heparin. Although
different coatings can have different functions, two specific sugars
can cause cancer cells to bind to the surface, where their growth
is prevented and from which they do not metastasize. Berry envisions
this device being used after a surgery, such as the type used to
remove melanoma, to ensure any “leftover” cancer cells
are extracted from the body.
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Hydrogen gas is currently produced on an industrial scale, primarily
for petroleum refining, using two techniques: electrolysis and steam
methane reforming. Two techniques have been developed to produce
hydrogen biologically from bacteria. The two biological hydrogen
processes reduce the pollution and costs associated with steam methane
The first biological technique uses water to convert carbon monoxide
to carbon dioxide and hydrogen. This reaction is currently part
of steam methane reforming and is known as the water-gas shift reaction.
In the current technique, a high-temperature environment and certain
metal catalysis, such as a zinc-oxide, are required. This reaction
has been estimated to consume up to 15% of the total operating costs
of steam methane reforming, or between $0.76 and $1.70 per gigajoule.
The replacement technique Berry helped develop involves engineering
specific bacteria to readily consume carbon monoxide from their
environment. These bacteria have an enzyme complex that can undergo
the same reaction as occurs in steam methane reforming, and are
limited only by how much carbon monoxide they can consume. Estimates
for a “biological water-gas shift” suggest operating
costs of only $0.52 per gigajoule, with low capital costs of only
$0.14 per gigajoule per year.
The second technique uses several engineering steps to replace
the entire steam methane reforming process. Ten times more efficient
than the biological processes, it could greatly undercut the costs
of steam methane reforming techniques used today.
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