Notes
on Panel Session: MEWG
Workshop, 3 Feb 2005
The
Panel was asked to address three areas concerning the future of
Metabolic Engineering (ME):
- What
directions for ME were foreseeable?
- What
societal concerns could be addressed by ME?
- What
common themes pervaded ME research?
These
were put in context with last year’s panel conclusions.
Directions for ME included the area of plant genomics, which was a
priority for development by the previous panel. Little progress has
been made. Only two plant genomes are available. Another high priority
area was the use of ME for development of new products, new chemistries
and new pathways. A final area was enhancing the availability of
results from genomics studies in general.
Why is progress in ME slower than expected? Frost agreed with
Stephanopoulos that ME is "hard stuff" that requires an
inter-disciplinary effort. This often involves having people transition
from their native discipline into something else, for example, to move
from training in Chemical Engineering to Genetics to
Biochemistry. Development of these people resources requires
something akin to Centers-of-Excellence.
Roberts focused on a need for more genomics information on higher
organisms, especially plants, as indicated last year. Analyses are
being stymied due to a lack of data input from such genomes, which have
been fully sequenced. There is also a need for tools to evaluate
metabolic flux both experimentally and mathematically in order to study
issues such as compartmentalization.
Frost indicated that these problems are compounded when one tries to
study multiple gene manipulations simultaneously due to a lack of
appropriate tools. Good high throughput methods are not available.
Peoples indicated that we are moving into the post-genomics era. There
should be more focus on systems biology. Therefore, multidisciplinary
approaches are emphasized. What separates us from apes is gene
expression, more so than just sequence.
Several panelists then moved on to a focus on commercial issues. Kinney
addressed developments of biopolymers, pharmaceuticals, etc. The
questions has become, "How do I produce my product more cheaply, more
efficiently?" Competition from other countries like China is pushing
this. In the pharmaceutical arena US companies are relying on
biotechnology, to come up with new syntheses, to give them an
advantage. But Frost indicated that industry must drive the need for
biotechnological approaches by having a broader outlook. The chemical
industry suffers from me-too-ism. Companies are
buying each other, rather than developing new products through
R&D. This inhibits research and suppresses need for new
scientists coming from academia. Lack of foresight in chemical
industry management is slowing down product development. Poor decisions
for marketing Poly Lactic Acid (PLA) have had a chilling effect on the
development of other products targeted in a similar fashion. Poor
economic performance by companies that develop products through
metabolic engineering has a chilling effect on progress in the
discipline because of the lack of a consumer of the research at the end
of the pipeline.
Other shortcomings of industry were discussed. Much industrial organic
synthesis is semi-synthetic. We need organic chemists who can work with
aqueous solutions. Classic organic chemistry is way behind. ME can
take over where classic organic chemistry falters.
How do we deal with the issue of getting the training for those in
different disciplines since ME is interdisciplinary? In the area of
antibiotic production, most is now done offshore: fermentation
engineering is no longer taught in US. Students are interested in
medical
microbiology or more glamorous bioinformatics, not the biochemical
engineering end use side of things. If there is no perception of a job
at end of pipeline, one can’t attract people.
The discussion moved to the cart-horse issue of doing metabolic
engineering because it is interesting or because there is a specific
goal in sight. Which approach is most appropriate for
industry? Does interesting research lead to viable products,
or must one focus on a specific product goal to ensure that the best
research is done? Frost answered that one needs some product to buy to
drive
research. But there are societal needs that government may wish to see
addressed and government can help fill some gaps that industry cannot
or chooses not to do independently, indicated Valerie Reed of DOE.
Too focused an approach, however, can lead one down the wrong path, as
mentioned by David Nes of NSF and Frost. One can work hard to engineer
the wrong pathway and still not end up with a product at the end.
The panel moved to a discussion of the significance of ME in the public
mind. Erickson had indicated that ME was below the public radar. Is
that good or bad?
Erickson saw this as a bad thing. If we were more visible we could make
industrial biotech more understandable to the public and move the focus
away from being exclusively on the more controversial agricultural
biotech. Industry associations can feed stuff to the press
who are hungry for information. What about government’s (e.g. MEWG)
role? It was pointed out that MEWG supports disparate sets of
researchers and the word gets around that way, because local press can
pick up stories from universities, etc. If there were Centers of
Excellence, this could be enhanced. It appears that MEWG may be having
an effect through its research support. Stephanopoulos indicated that
the significant increase in papers in the Journal of ME track with our
Announcements of Opportunity.
Have we made progress? Frost said there is much more progress compared
to first ME conference. We can look at all genes in cell at once.
Bioinfomatics permits analysis of the data generated in a way not
thought of 10 years ago. We can now think in systems concepts.
Investigators are now frustrated because they can’t get the high
throughput
they want to generate the data that they can now handle. They must
resort to models and better analytical tools to compensate.
After much discussion of the deficiencies of the US chemical industry
Stephanopoulos offered a Silver Lining. The Chemical industry is not
innovative. To get innovation one needs R&D funding!
This creates intellectual property, e.g. sequences, which have value.
At the end the question was asked whether the research direction
supported by MEWG was still appropriate?
It was suggested that there be an added focus on isolation and
characterization of single cells. There was considerable discussion of
the amount of modeling that should be included in the next MEWG
announcement. How to get high throughput synthesis and implementation
of gene constructs appears to be a bottleneck for research progress.
Therefore Stephanopoulos suggested a new item; “Molecular biological
and high throughput cell screening methods for combinatorial Metabolic
Engineering.” Jeffries offered a variation: “High throughput molecular
biological and downstream screening methods (for single cells) to
facilitate recombinatorial approaches.”
Background
on the Panel Session
