# Presentation: 588460

## Review of the Department of Energy’s Genomics: GTL Program

**Notes:**
I’d like to thank Michael Flynn for the opportunity to speak about a new NRC report on Critical Needs for Research in Veterinary Science.

## Committee Members

**Jennie Hunter-Cevera**, Chair, University of Maryland, Biotechnology Institute
**Charles R. Cantor**, Sequenom, Inc.
**Wah Chiu**, Baylor College of Medicine
**Douglas R. Cook**, University of California, Davis
**Eric W. Kaler**, University of Delaware
**Thomas Kalil**, University of California, Berkeley
**David T. Kingsbury**, Gordon and Betty Moore Foundation
**Claudia Neuhauser**, University of Minnesota
**Gregory A. Petsko**, Brandeis University
**Mariam Sticklen**, Michigan State University
**Larry P. Walker**, Cornell University
**Janet Westpheling**, University of Georgia

**Notes:**
The study committee comprised 13 experts in different fields of veterinary science (food safety, biosecurity, laboratory animal medicine, comparative medicine, wildlife and conservation, just to name a few).  Experts were drawn from universities, private company, federal agency, and non-profit organization.  

## Committee Charge: To address the following three questions:

- 1.	Is the Genomics: GTL program, as currently designed, _scientifically and technically well-tailored_ to the challenges faced by the DOE in energy technology and development and environmental remediation?

**Notes:**
In the spring of 2004, the National Research Council has convened a panel of experts to identify the national needs for research in three fields of veterinary science: public health and food safety, animal health and comparative medicine.

## Committee Charge (cont’d)

- 2.	Does the proposed Genomics: GTL research and facility investment strategy _leverage_ DOE scientific and technical expertise in the most cost-effective, efficient, and scientifically optimal manner?
- 	Specifically, does the “business model” (i.e., number, scope, scale, order, and user operation plan) for the proposed Genomics: GTL facilities follow directly from the science case—should one exist—for systems biology at DOE?
- 	Are there alternate models for some of the proposed effort that could more efficiently deliver the same scientific output?

**Notes:**
In the spring of 2004, the National Research Council has convened a panel of experts to identify the national needs for research in three fields of veterinary science: public health and food safety, animal health and comparative medicine.

## Committee Charge (cont’d)

- In an era of flat or declining budgets, which aspects of the proposed Genomics: GTL program are _the most meritorious_?  Which appear to have the highest ratio of scientific benefit to cost?

**Notes:**
In the spring of 2004, the National Research Council has convened a panel of experts to identify the national needs for research in three fields of veterinary science: public health and food safety, animal health and comparative medicine.

## GTL

- -- “aims to understand biological systems well enough to predict their behavior accurately with mechanistic computational models” so that such knowledge can be used to engineer systems for bioenergy production and environmental remediation and to understand carbon sequestration.

## Study and Evaluation Process

- Two committee meetings were held, including one public meeting.
- Numerous teleconferences were held to gather information, draft the report and make final deliberations
- The committee heard from
- Representatives of DOE
- Academic, industry and national laboratories scientists, both funded and not funded by DOE
- Representatives of NSF, NIH, USDA, OMB, and OSTP

**Notes:**
The committee held five meetings, one of which was a community workshop, to gather information, draft report and make final deliberations.  The report was rigorously reviewed by 9 external reviewers and overseen.  The findings and recommendations represent consensus of the whole committee.

## Study and Evaluation Process (cont’d)

- The report was reviewed by 11 external reviewers.
- Report review process was overseen by report review coordinator.
- Final product is a consensus report of the committee.

**Notes:**
The committee held five meetings, one of which was a community workshop, to gather information, draft report and make final deliberations.  The report was rigorously reviewed by 9 external reviewers and overseen.  The findings and recommendations represent consensus of the whole committee.

## Report Structure

- Role of Genomics in Advancing Science
- Role of Genomics: GTL in Achieving DOE’s Mission Goals: Promises and Challenges
- Implementation of the Genomics: GTL Program Plans

**Notes:**
The report is laid out as follows:

Chapter 1 – provides background
Chapter 2 – discusses the progress that veterinary research has made and the many critical research areas that still need to be addressed.
Chapter 3 – suggests a agenda for how to carry out the critical research that are outlined in chapter 2
Chapter 4 – reviews the resources currently available for research
Chapter 5 – The committee made recommendations on the basis of the research needs and research agenda in chapters 2 and 3, and available resources in chapter 4.

***Question 1:****  Is the Genomics: GTL program, as currently designed, scientifically and technically well tailored to the challenges faced by the DOE in energy technology development and environmental remediation?*
**Answer 1: ** **Yes**, **the use of systems and synthetic biology approaches** in the Genomics: GTL program to address some of the most pressing issues in microbial genomics relevant to DOE’s mission in energy security, environmental remediation, and carbon cycling and sequestration **is not only appropriate but necessary**.

**Answers to the Charge**

**Notes:**
This statement by Virchow is as wise today as it was over a century ago.  Knowledge gained from one species benefits all.  Research in veterinary science affect human health either directly through biomedical research and public health or indirectly by addressing domestic animal, wildlife, or environmental health.   

**Answer 1 (cont’d): ** The study of individual components only does not provide knowledge on systems integration at the level of pathways, organisms, and microbial consortia --for example, on the effects of introducing new metabolites or new or engineered organisms to a community; or on organism or community responses.
- Systems biology research is needed to develop models for predicting the behavior of complex biological systems, to engineer microorganisms for bioremediation and energy-related needs, and to understand carbon cycling.** **

**Notes:**
This statement by Virchow is as wise today as it was over a century ago.  Knowledge gained from one species benefits all.  Research in veterinary science affect human health either directly through biomedical research and public health or indirectly by addressing domestic animal, wildlife, or environmental health.   

## 	Question 2:  Does the proposed Genomics: GTL research and facility investment strategy leverage DOE scientific and technical expertise in the most cost-effective, efficient, and scientifically optimal manner?  Specifically, does the "business model” (i.e. number, scope, scale, order, and user operations plan) for the proposed Genomics: GTL facilities follow directly from the science case—should one exist—for systems biology at DOE? Are there alternate models for some or all of the proposed effort that could more efficiently deliver the same scientific output?

**Notes:**
Public Health and Food Safety
Prevention of the recurrence and reduction of the effects foodborne illnesses associated with livestock and poultry.
Protection of food-animals from intentional introduction of biological agents or related products that can cause disease or death in humans and animals.

## 	Answer 2:  The committee enthusiastically endorses the goals of the Genomics: GTL program and acknowledges the need for infrastructure, but it believes that DOE’s current plan for building four independent facilities for protein production, molecular imaging, proteome analysis, and systems biology sequentially may not be the most cost-effective, efficient, and scientifically optimal way to provide this infrastructure.  

	As an alternative, the committee suggests the construction of up to four institute-like facilities, each of which integrates the capabilities of all four of the originally planned facility types and focuses on one or two of DOE’s mission goals.

- 	**As an alternative, the committee suggests the construction of up to four institute-like facilities, **each of which integrates the capabilities of all four of the originally planned facility types and focuses on one or two of DOE’s mission goals.

**Notes:**
Comparative Medicine
Improvements in human and animal health research through comparative studies in many disciplines, including hematology, immunology, vaccinology, virology, genetics, transplantation and gene therapy. 
Reduction of the risk of transmission of zoonotic and other emerging agents between wildlife, domestic animals, livestock and humans.

## 	Question 3:  In an era of flat or declining budgets, which aspects of the proposed Genomics: GTL program are the most meritorious?  Which appear to have the highest ratio of scientific benefit to cost?

	Answer 3:  The Genomics: GTL program’s research has resulted in and promises to deliver many more scientific advancements that contribute to the achievement of DOE mission goals.  The committee proposes the initiation of facilities that integrate the four capabilities of protein production, molecular imaging, proteome analysis, and modeling and analysis of cellular systems because they are all necessary for achieving a predictive understanding of microbial systems through systems biology.  

**	****Answer 3:  **The Genomics: GTL program’s research has resulted in and promises to deliver many more scientific advancements that contribute to the achievement of DOE mission goals.  **The committee proposes the initiation of facilities that integrate the four capabilities of protein production, molecular imaging, proteome analysis, and modeling and analysis of cellular systems** because they are all necessary for achieving a predictive understanding of microbial systems through systems biology.

**Notes:**
Veterinary research faces a critical personnel shortage that is not limited to biomedical sciences. We cited a lot of evidence of personnel shortage in many disciplines of veterinary science in the report.  But we received most data on personnel for biomedical sciences and for veterinary colleges.  Researchers with veterinary expertise are needed to fulfill the organizations’ roles in public health and food safety, animal health, and comparative medicine.

## 	Answer 3 (cont’d):  Therefore, the question of which facility with a distinct capability is the most meritorious is irrelevant.  If DOE were to set up vertically integrated facilities, it would have to select which of its mission foci should be the targets of the first integrated facility.  The committee suggests that bioenergy be its first choice given the pressing concern of energy security. 	

**Notes:**
Veterinary research faces a critical personnel shortage that is not limited to biomedical sciences. We cited a lot of evidence of personnel shortage in many disciplines of veterinary science in the report.  But we received most data on personnel for biomedical sciences and for veterinary colleges.  Researchers with veterinary expertise are needed to fulfill the organizations’ roles in public health and food safety, animal health, and comparative medicine.

## Recommendation 1

**	****The committee recommends that DOE and the nation give high priority to genomics research aimed at achieving DOE’s mission goals.**

**Notes:**
Here are a few examples of opportunities in veterinary research in improve human and animal health.  

Prevention and control of infectious, toxicologic and parasitic diseases of food producing animals will help maintain maintain herd health and economic viability of industries that supply meat, milk, eggs and other animal products.
Improvement of the longevity and quality of life of companion animals, which in turn will have favorable effects on their caregivers.
Determination of optimal care for laboratory animals and prevention, detection, and management of their diseases.  
Prevention of population declines in wildlife species that are of interest for ecological balance, recreation, tourism, or conservation. 

## 	DOE should revise its plans for creating four single purpose and technique-driven facilities in sequence.  Instead, DOE should create up to four institute-like facilities that each contains all of the capabilities of the original planned facility types—protein production, molecular imaging, whole proteome analysis, and systems biology—in a vertically integrated manner.  

	Each facility could focus on one or two of the DOE mission objectives and develop short, medium and long-term goals to chart a course for the program.  Short-term milestones should be used as a metric for independent evaluation.

- 	Each facility could focus on one or two of the DOE mission objectives and develop short, medium and long-term goals to chart a course for the program.  Short-term milestones should be used as a metric for independent evaluation.

**Recommendation 2**

**Notes:**
For each of the example of opportunities in veterinary research, the committee set a research agenda that includes short, medium and long term research needs.  In doing so, the committee found that there are some overarching strategies for implementing research agenda that apply to most, if not all fields of veterinary research.

Implementation of interdisciplinary research
The need to expand our knowledge, detection, and control of infectious diseases
Expand the study and use of bioinformatics.  Develop databases and other resources 
Quantify scientifically based animal health and welfare characteristics to optimize sustainable and socially responsible food-animal production and laboratory animal research
Expand research on the human-animal bond and the overall role of animals in society

## Merits of Vertically Integrated Facilities for Genomics: GTL Program

- Establish the Genomics: GTL program in a leadership position to launch a world-class, comprehensive, integrated research and training program in systems and synthetic biology.
- Research programs of the facilities would be built on overarching biological themes relevant to the DOE missions
- New technologies would be developed in the facilities on the basis of well-justified scientific problems.

## Merits of Vertically Integrated Facilities for Genomics: GTL Program

- Attract investigators around the country to use them –leverage DOE’s ability to manage complex integrated research programs.
- New computational approaches and tools would be developed in the facility to promote synergy between modeling and experimentation at both bench and field level.
- First facility serves as a pilot to validate the hybrid approach and identify roadblocks – not be outdated.
- Have staged investments with expandable bases, flexibility to shift directions without losing prior investments, leverage and open-source positioning.

## Recommendation 3

- 	DOE should consider locating user facilities on private land off DOE reservations to allow an open-access policy and in close proximity to research institutions that have established programs or centers of excellence in biosciences and biotechnology.
- 	The locations for the user facilities should be selected via an open and all-inclusive competitive process that provides ample opportunity for universities and industry to partner with DOE and its national laboratories.
**	**

**Notes:**
Based on the research needs outlined in chapters 2 and 3, and the assessment of resources available in chapter 4, the committee came up with 8 findings and recommendations.

The committee found that veterinary research has interfaces with human and animal health so that it is interdisciplinary by nature.  Collaborative and interdisciplinary research is crucial in translating scientific advances from one traditional discipline to another.  However, administrative or cultural barriers and lack of economic resources may hamper such research.

## Recommendation 4

**	**DOE should consider partnering with universities and other federal agencies to develop programs that employ Genomics: GTL institute-like facilities as training grounds for the next generation scientists.

## Epilogue

**	****DOE has done an exceptional job in leading the country in many areas of research that were at the cutting edge, in particular the Human Genome Project.  **
**	****DOE now has an opportunity to become a world leader in systems biology through the Genomics: GTL program and by integrating or connecting fundamental research data to other programs within DOE and other national and international agency programs****.  **

**Notes:**
To alleviate the scientific needs and meet societal needs, additional veterinary researchers must be trained.  A debt repayment program similar to the NIH clinical research loan repayment program should be initiated to address the concerns about the large debt burden faced by graduates of Colleges of Veterinary Medicine.  Training programs modeled after NIH’s Center for Cancer Research Training Initiative or USDA-ARS PhD training programs.  

## Epilogue (cont’d)

- 	**The committee commends DOE for its forward development of the Genomics: GTL program and encourages the DOE administration to consider the committee’s proposed alternative plan for the Genomics: GTL facilities.  **
**	**
**	****The recommendations in this report, if implemented, will enhance DOE’s potential for success in their three critical mission areas: bioenergy, bioremediation and carbon sequestration. **

**Notes:**
To alleviate the scientific needs and meet societal needs, additional veterinary researchers must be trained.  A debt repayment program similar to the NIH clinical research loan repayment program should be initiated to address the concerns about the large debt burden faced by graduates of Colleges of Veterinary Medicine.  Training programs modeled after NIH’s Center for Cancer Research Training Initiative or USDA-ARS PhD training programs.  

## AND........

**March 28, 2006**
**DOE OFFICE OF SCIENCE TO REVISE PLANS****FOR GENOMICS:GTL FACILITIES**
**Plans to Issue New Solicitation ****for GTL Bioenergy Research Centers **

## The Department of Energy’s Office of Science announced today that it is revising its plans for the deployment of new research facilities to support its Genomics:GTL program. 
The decision to reshape plans for the new GTL research facilities comes in response to the President’s recently announced Advanced Energy Initiative and a review of the GTL program by the National Research Council (NRC) of the National Academies. 
Begun in 2000, the Office of Science’s GTL program supports advanced research in systems biology aimed at harnessing the powers of the microbial world to produce abundant and clean energy, absorb carbon dioxide, and transform radioactively contaminated waste.

**The decision to reshape plans for the new GTL research facilities comes in response to the President’s recently announced Advanced Energy Initiative and a review of the GTL program by the National Research Council (NRC) of the National Academies. **
**Begun in 2000, the Office of Science’s GTL program supports advanced research in systems biology aimed at harnessing the powers of the microbial world to produce abundant and clean energy, absorb carbon dioxide, and transform radioactively contaminated waste.**

## The specific goal of the new facilities plan will be to accelerate GTL systems biology research in the area of bioenergy, with the objective of developing cost-effective, biologically based renewable energy sources to reduce U.S. dependence on fossil fuels. 
The Office also said the new facilities plan, to be based partly on recommendations from the NRC panel, should be able to accomplish the GTL program’s objectives more rapidly and at reduced cost. 

**The Office also said the new facilities plan, to be based partly on recommendations from the NRC panel, should be able to accomplish the GTL program’s objectives more rapidly and at reduced cost. **

## As part of the reassessment, the Office of Science has cancelled its Funding Opportunity Announcement (FOA) for a planned GTL Facility for the Production and Characterization of Proteins and Molecular Tags, issued in early January. 
The Office of Science plans to issue a new solicitation in the coming months for one or more centers for bioenergy research. 

**The Office of Science plans to issue a new solicitation in the coming months for one or more centers for bioenergy research. **

## Centers focused on systems biology research into carbon sequestration and bioremediation are also being considered for future years. 
The NRC committee recommended that the GTL facilities should be focused not on particular technologies, but on research underpinning particular applications – bioenergy, carbon sequestration, or environmental remediation. 

**The NRC committee recommended that the GTL facilities should be focused not on particular technologies, ****but on research underpinning particular applications – bioenergy, carbon sequestration, or environmental remediation.**** **

## Drawing on the NRC recommendations, the Office of Science is formulating a plan for one or two vertically integrated centers with a focus on bioenergy research.
The Office believes that these centers can be operational at a date earlier than the originally planned Facility for the Production and Characterization of Proteins and Molecular Tags. The Office of Science plans to issue the new solicitation soon. 

**The Office believes that these centers can be operational at a date earlier than the originally planned Facility for the Production and Characterization of Proteins and Molecular Tags. ****The Office of Science plans to issue the new solicitation soon.**** **

## Thank You

- for your time
- and attention.