From SBS' President
Expanding SBS’ Scope & Purview
By Dejan Bojanic
When most of us think about SBS, the first thing that comes to mind is the annual conference, which has been held every September for the past decade. This meeting originally filled a need to bring the high-throughput screening (HTS) community together, and this in turn established the society, which is now well respected and has a healthy membership base.
But we are not just a one-conference society. SBS has also fostered scientific exchange through its peer-reviewed journal, the Journal of Biomolecular Screening (JBS) and has progressively become a wider resource for its members. We can comfortably say that the past 10 years have been successful and it is a job well done, thanks to the leadership of our founders and many other dedicated individuals.
So what will SBS do in the next decade? Plenty, and that’s a promise.
The annual conference will still be our flagship event. By virtue of its size and content, it will remain a cornerstone of the SBS calendar and will continue to provide a diverse program with presentations, posters, exhibits, tutorials, etc. It will provide companies the opportunity to roll out new products and technologies, and for breakthroughs in drug-discovery processes to be presented. Likewise, JBS will continue to be the leading journal in its field. But we want SBS to be associated with more than just an annual conference and a journal. We want it to provide further value to its membership, to help them build their careers, and to help bring in new blood. Thus, we are committed to diversifying further and providing a portfolio of products and services that are high quality, cost-effective, and valued. The diversification process has already started and our core focus areas are outlined below.
Regional Meetings
Recently, SBS organized a regional meeting in San Francisco entitled “Exploiting the Druggable Genome,” which attracted some 230 attendees. Last year, we had a very successful regional meeting at Harvard Medical School in Boston on “Academic and Industrial Approaches to HTS & Drug Discovery”
Although these started somewhat opportunistically, regional meetings are now part of a wider strategy for SBS to become more involved in drug discovery and, in effect, to evolve into a drug-discovery society. Our objective is to have more of these smaller meetings, which will cover a wide range of themes and be more convenient geographically. Some will address industry issues generally, but we are also considering in-depth meetings on specific topics, so don’t just expect mini-versions of our annual conference. We are constantly looking for additional subject matter, so please e-mail the chairperson of our Conference Committee, Ricardo Macarron (Ricardo.Macarron@gsk.com) if you have any suggestions. To reflect our commitment to provide more high quality meetings, the SBS Board recently approved a staff position within the SBS Office in support of this objective.
Partnerships
SBS sees itself as a supporting organization for its members and the drug-discovery community as a whole. To achieve this, SBS will operate independently or collaborate with sister societies as appropriate. An example of past successes include joint meetings held with SEBIOT and AAPS/ACS. We are in discussion with other groups for the future. Additionally, we do not want to reinvent the wheel and are very happy to endorse other non-profit organizations. For instance, the Laboratory Robotics Interest Group (LRIG) through its chapters has been very successful in setting up local meetings. This area is clearly in good hands and SBS and LRIG work together to cross-promote each other’s events.
Additional opportunities also exist where SBS could partner with societies not directly connected to drug discovery, thereby providing exposure to ancillary subjects and technologies and facilitating cross-fertilization. Overall, our objective is to provide the resources to help scientists and vendors become more effective contributors in their respective fields.
Education
The recent formation of the Education Committee was mentioned in a previous article of mine and Lisa Minor wrote about this in the April issue of SBS News. The team, which is now chaired by Doug Auld (dauld@mail.nih.gov), has been discussing several opportunities and is looking at assembling a course on drug discovery. This would be complementary to the virtual seminars that are available on our website (www.sbsonline.org).
Additionally, there has been interest expressed by departments from academic institutions spanning engineering to the life sciences that are keen to be more involved in drug discovery. This could open up possibilities for the creation of undergraduate or graduate drug-discovery curriculums that would provide vocational opportunities for students seeking a career in the industry. Again, the SBS Board has provided support by approving a dedicated staff position to support these initiatives. Thus SBS will be actively involved in continuing education as well as helping to introduce new talent into our industry.
Scope
The last key area I’ll cover here is the scope of SBS itself. Five years ago, our conference theme was “Targets, Compounds and Technologies”; this year it is “From Targets to Candidates”. This emphasizes the more integrated perspective that SBS now has of the drug-discovery process.
Efficient drug discovery cannot be compartmentalized into silos and SBS cannot operate in a silo. Instead, we will be a greater part of the integrated whole that is drug discovery and we aim to become the go-to society for the drug-discovery professional. This means even greater expansion into those areas that were previously considered upstream or downstream of HTS and that is why we are considering changing our name, as discussed in the June issue of SBS News.
We clearly still have a way to go and there are many opportunities available to us. SBS is committed to serving the needs of its membership and in the present climate, where drug discovery is getting harder and more expensive, SBS will directly and indirectly work to help improve productivity. Our vision is for SBS to be perceived as an organization that caters to the many needs of its members, contributes to more efficient drug discovery, and thus to society as a whole.
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Conference Keynote
Chris Austin Explores & Clarifies the Promise of NIH Molecular Libraries
Interviewed by Marilynn Larkin
In the June 2005 issue of SBS News, we presented an overview of the NIH Roadmap,
including the Molecular Libraries Initiative. In his keynote address at the
SBS 11th Annual Conference & Exhibition, Chris Austin, MD, Director of
the NIH Chemical Genomics Center (NCGC) and co-Principal Leader, NIH Roadmap
Molecular Libraries and Imaging Implementation Group, will describe how the
various parts of the initiative fit together to advance the science of small
molecule screening and biology, focusing particularly on the role of the newly
formed Molecular Libraries Screening Center Network (MLSCN; see box, p.7, and
SBS/NIH Connections on the SBS website: www.sbsonline.org). Opportunities for
SBS member participation will also be explored. In this Q&A, Austin offers
highlights of his presentation.
Just what is meant by the "molecular libraries" initiative?
CA: I've noted
that the "molecular libraries" name is potentially
confusing because it does not indicate the class of molecule being studied,
and suggests that the purpose is solely to create libraries. The initiative
is actually a set of 12 integrated programs that together aim to facilitate
the use of small molecule compounds to understand biology in the public sector.
It is part of the NIH Roadmap for Medical Research, a set of ambitious new
initiatives in translational science begun by the current NIH Director Elias
Zerhouni after his appointment in 2002.
Where does molecular imaging come in?
CA: Originally, molecular libraries and
molecular imaging were two different roadmap initiatives. They were subsequently
merged for the purpose of implementation,
because it was clear that each of them had components that were analogous
to the other: each has a database component, a technology development component,
and a production component. Certainly, part of what limits our ability to
identify and use small molecules is the ability to detect them. As you know,
people who do screening are constantly thinking "how do I detect this
event?" Often, that is an imaging question, which is why the two were
put together.
You've described the various molecular libraries initiatives as both screening
and "what goes into it and what comes out of it." Would you elaborate?
CA: Yes.
For a "roadmap" to this Roadmap initiative, check out http://nihroadmap.nih.gov/molecularlibraries,
but let me summarize here. The "production", or screening, components
are the MLSCN and the repository of chemical compounds screened by the MLSCN
centers. The "what goes into screening" components are technology
development initiatives in chemical diversity, assay development, and HTS instrumentation,
and the MLSCN assay selection initiative. On the output end there is PubChem
(http://pubchem.ncbi.nlm.nih.gov/) , which provides public access to assay,
screening, and chemistry data from publicly available and donated sources,
and will provide access to MLSCN assay, screening, and chemistry data as well.
PubChem is designed to be a "Genbank for small molecules"; data donated
from researchers and projects outside the Molecular Libraries initiative, such
as the National Cancer Institute Developmental Therapeutics Program and the
new Nature Chemical Biology journal, are already in PubChem. By analogy, Genbank
is populated by data from many labs around the world in addition to the NIH
funded genome sequencing centers. We hope that PubChem will, in the end, be
as useful to the research community as Genbank is. But it's intended for data
accessibility, integration, and presentation; it's not a research component
of the MLI.
Since data from assays and primary screens have not generally been
available in the public sector before, our advisors early on told us that there
needed
to be a research component to the "output", or cheminformatics, part
of the MLI. There is reason to believe that there will be a great need for
cheminformatics with the advent of MLSCN data, just as there was a need for
bioinformatics with the advent of genome sequencing. This is where the Cheminformatics
Research Centers (http://grants1.nih.gov/grants/guide/rfa-files/RFA-RM-05-012.html)
come in. These centers will do data crunching on the screening data that comes
out of the MLSCN. They will also develop data analysis algorithms and programs
that will be made publicly available as a product of the MLSCN, the same way
that the chemical probes themselves will be made available.
In sum, what will
come out of the MLI are not only the screening data, but novel chemical libraries,
novel assays, novel instruments, novel chemical probes
of biology, and informatics algorithms to enable to community to broadly
deal with the data. What distinguishes the extramural and intramural components
of the initiative?
CA:
About 90% of the NIH budget goes to extramural research, which is the funding
of grants and contracts that go to universities, medical schools, companies,
etc. About 10% of the budget goes to intramural activities-that is, labs
physically at NIH. The NCGC, PubChem, and the Imaging Probe Development
Center (one of the Molecular Imaging Initiatives) are intramural; all the other
parts of the MLI are extramural.
On a programmatic level, the intramural program
is distinguished by a couple things. Intramural research programs go through
peer review posthoc - after
the research is done - rather than as a prerequisite to the research as is
the case with extramural grants and contracts. In this way, the intramural
program operates somewhat similarly to research programs in the private sector.
The quid pro quo of this arrangement is that intramural researchers must
be willing to jump onto new scientific opportunities quickly, and they must
be
willing to take greater risks in their research. The NCGC-the first of the
MLSCN centers-started operations June 9, 2004, whereas the extramural MLSCN
centers were just announced in June of this year. Similarly, PubChem went
from conceptualization to a presence on the web in less than 12 months, giving
a
great jump-start to the MLI.
It was decided to have both intramural and extramural
components in the MLI since we knew that the initiative would be challenging
to get going on every
level. So the intramural components were used to get the MLI up and running
quickly, and to work out some of the kinks that we knew would arise in
setting up such a new program.
What question about the initiative do you find yourself answering over and
over?
CA: I'm most frequently asked "How is this different from pharma?" The
answer is that the MLI is different in every way from pharma, except for some
of the technologies used. We are doing bimolecular screening utilizing the
same state-of-the-art technologies that are being used in the most technologically
advanced pharmas and biotechs. But the purposes for which these technologies
are used are distinct from pharma. I should say that through visits to many
pharmas and biotechs, we have learned a great deal about what works and what
doesn't, and that has helped enormously in getting the MLI started on the right
foot.. One of the wonderful things about this process has been how open and
sharing our pharma and biotech colleagues have been. Since this initiative
is positioned so firmly pre-competitively, our private sector colleagues generally
want the MLI to succeed, and want us to learn from their experiences rather
than repeat them. There is a wonderful collaborative sense that if the MLI
succeeds, pharma and biotech will know more about their targets and hopefully
will also succeed.
Beyond the technologies, the questions we are asking are
different, and the products are different. First, since the MLSCN assays are
coming from academic
researchers looking for probes of their experimental systems, the palette of
assays submitted to the MLI is the reciprocal of that in pharma. So the HTS
technologies will be applied to a very different set of targets, most of which
fall into the traditionally "nondruggable" genome or are targets
for rare diseases. Second, the products of the MLSCN screening will be probes,
not drugs, the MLI will produce and screen a broader range of compounds than
pharma - e.g., known toxic compounds, metabolites, non-Rule-of-Five compliant
compounds, and natural products.
We define a probe as a chemical compound with adequate potency and aqueous
solubility to allow it to be used in in vitro experiments. We have purposely
designed the MLI to stop at this point since producing a compound with the
selectivity, pharmacokinetic, and toxicological properties required in a drug
is difficult, expensive, and time-consuming. These probe compounds will be
very useful as tools to understand biology, and to the degree that researchers
use them with therapeutic intent we expct they will be used mainly as target
validation tools. Researchers who use them as starting points for therapeutics
will have a great deal more work to do; our own analysis shows that >95%
of the time and expense of making a drug comes after this "probe" stage.s
Austin Explores & Clarifies the Promise of NIH Molecular Libraries.
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Advancing The Science of Drug Discovery
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