MIT Reports to the President 1999–2000
The Biotechnology Process Engineering Center (BPEC) is a multi-disciplinary body with faculty members from the MIT Departments of Biology, Chemistry, and Chemical Engineering, the Division of Bioengineering and Environmental Health (BEH), and the Whitehead Institute for Biomedical Research, along with the University of Toronto Department of Chemical Engineering and the Brown University School of Medicine Liver Center. The mission of BPEC is to carry out research and education combining engineering with molecular biology, emphasizing a strong relationship with industry in its various activities. The goals of the center are to perform cutting-edge, fundamental research in therapeutic gene and protein biotechnology based on contributions from, and interactions among, investigators from diverse relevant backgrounds.
While the mission of BPEC has remained unchanged since its inception in 1985, the central focus of BPEC’s research directions has now successfully completed a major transition from the previous Therapeutic Protein Biotechnology (TPB) thrust to a new Therapeutic Gene Biotechnology (TGB) thrust. The TGB thrust is now being primarily fostered by the National Science Foundation Engineering Research Center core funding, while support for the TPB thrust is provided by various governmental agency and industry grants. Central issues which are being addressed in the TGB thrust include problems associated with development of selective gene delivery vehicles for both ex vivo and in vivo approaches; the former emphasizes hematopoietic stem cells grown in culture and infected with viral vectors before implantation, whereas the latter emphasizes ligand-targeted synthetic or viral vectors with liver as a chief tissue objective. In the past year, we have added three new BPEC team investigators and one new collaborator, in order to address additional challenges as recommended by our Industrial Consortium Advisory Board and previous NSF review panel.
Educational programs of BPEC deal with the needs of undergraduates, graduates and industrial personnel. The goals of the educational programs are to provide integrated and broad bioengineering perspectives to the students; at the undergraduate level we now participate in the Biomedical Engineering Minor offered by BEH to students in all majors, while at the graduate level we likewise participate in the Bioengineering and Toxicology Ph.D. programs offered by BEH along with the traditional Ph.D. programs in Biology, Chemistry, and Chemical Engineering. In addition, NIH Training Programs in Biotechnology and in Genomics are administered from the BPEC office, leveraging the NSF ERC to broader educational opportunities at the engineering/molecular-biology interface. Undergraduate research is achieved through the Undergraduate Research Opportunities Program (UROP) for MIT students and the Research Experience for Undergraduates (REU) for non-MIT students. Special one-week summer courses are offered to industrial personnel.
Industrial activities and planning are coordinated through our new formally-constituted Therapeutic Gene Biotechnology Industrial Consortium Advisory Board (TGB ICAB), supervised by our BPEC team of Industrial Liaison (Matt Croughan) and newly-hired Associate Industrial Liaison (Jean-Francois Hamel). We are extremely pleased by the progress we have made this past year in beginning to reinvigorate our BPEC/industry partnerships following the difficult transition period; this progress can be seen in the highly positive industry SWOT analysis generated at our April 2000 ICAB meeting.
We have added to the BPEC administrative umbrella the new DuPont/MIT Alliance (DMA) in ‘Bio-Based Materials,’ as another facet of the BPEC mission to combine engineering with molecular biology. This Alliance provides $7 million year to MIT for a 5-year period, and nicely extends the impact of the BPEC engineering/biology collaborative spirit to even broader reaches of the MIT campus and industry.
Statistically reporting, 148 personnel took part in the center's research activities during fiscal 2000. This figure comprises of the following: 57 MIT Undergraduate worked as lab interns (I.e., UROP students), 12 non MIT undergraduates who participated in the center’s NSF Research Education for Undergraduates Program (REU); 26 graduate students; 21 postdoctoral associates/fellows; 16 visiting scientists, engineers, industry researchers, six administrative personnel, seven other director level personnel and 12 faculty (some faculty served as executive directors).
Numerous research milestones were accomplished during fiscal 2000. Listed below are the following "top 10":
Value-added for industry can be categorized as follows: (a) a multi-investigator, multi-disciplinary academic research unit combining engineering with molecular biology for solving fundamental, generic basic problems posing severe obstacles to the long-term growth of a broad-based therapeutic gene biotechnology industry; (b) an inter-disciplinary academic unit combining engineering with molecular biology in training of the young investigators who will become the foundation of the developing therapeutic gene biotechnology industry; (c) a multi-disciplinary center stimulating dissemination of forefront biotechnology and bioengineering activities into the traditional science and engineering disciplines, bringing new problems and approaches toward their enrichment. A crude under-estimate of the magnitude of the value-added to the United States can be obtained by realizing that approximately 1—2% of pharmaceutical/biotechnology industry revenues is devoted to basic research of the sort fostered by BPEC research efforts and undertaken by researchers of the sort exemplified by BPEC graduates. Accordingly, given that the inter-disciplinary BPEC research activities and BPEC graduates are at the leading edge of what is sought by industry, the roughly $3 million yearly investment from government and industry in BPEC activities can be considered to be leveraged perhaps 50-100 fold into ultimate industrial productivity.
Our objectives remain to impact the education of undergraduate students, graduate students, and industrial personnel in their ability to work at the engineering/biology interface on important problems in biotechnology.
At the undergraduate level, our goal is to ensure the students are integrated into our research thrusts for both MIT (UROP) students and students from other institutions (REU and high schools). To expose the students to cross-disciplinary activities and teamwork, the projects are selected carefully and critically. BPEC provides initial experiences to undergraduates and encourages students to work in industry as internees. Our Industrial Liaison and Education Coordinators contact companies associated with BPEC for summer undergraduate internships and the replies are then matched with BPEC’s undergraduates for summer employment.
The Division of Bioengineering and Environmental Health (BEH) has now further enhanced its undergraduate curriculum aimed at integrating molecular cell biology with engineering, by developing a new 5-year SB/MEng program in Bio/Medical Engineering to accompany the onging Bio/Medical Engineering SB Minor program. The BME Minor is MIT’s first inter-departmental minor degree, available to undergraduates taking any BS Major degree at the Institute. The program comprises 4 subjects in Bio/Medical Engineering–2 core subjects and 2 electives. These subjects require substantial preparation in science and engineering, and thus the minor is structured in the form of a Science Core (3 subjects) and an Engineering Core (2 subjects) which serve as prerequisites for the Bio/Medical Engineering subjects. The goal of the degree program is to educate students in how to apply fundamental engineering principles to solve challenging problems in biology and medicine. A common theme is the integration of individual components of a biological system to describe both the spatial and temporal organization of the system as a whole. The scale of this integration may be as small as molecules and cells or as large as organ systems or whole organisms. Students gain an appreciation of how to solve problems at these different scales by taking two core biomedical engineering courses. They can then pursue particular interests through the two restricted electives in bio/medical Engineering.
More than ever, cutting-edge research combining engineering with molecular biology concomitantly requires analogously novel educational programs, and BPEC is at the heart of a radical new academic unit created at MIT this past year: the Division of Bioengineering and Environmental Health (BEH). BEH is a departmental structure within the School of Engineering charged with creating and administering educational and research programs that forge engineering with modern biology. Rather than focusing on a particular application field like most ‘biomedical engineering’ departments being created across the country, BEH is focused on fostering a new discipline of biological engineering that will educate engineers to create technologies based on molecular biology whether the application area is medicine, environment, agriculture, materials, manufacturing, or so forth. BEH has initiated a new Bioengineering Ph.D. program with a novel core curriculum aimed at training this type of next-generation biotechnologist, alongside students trained in inter-disciplinary fashion in the MIT Departments of Chemical Engineering, Chemistry, and Biology–with all these programs intertwined through the NIH Training Programs in Biotechnology and Genomics also administered by BPEC.
At the graduate level, one of the goals of BPEC is to provide research experience related to the Center's research thrusts. We ensure that the research is conducted with a spirit of teamwork and inter-disciplinary input. This is achieved by joint faculty advisors on the doctoral thesis and/or thesis committee members from different departments and disciplines. To provide industrial perspectives on the students' training program, industrial personnel are often members of doctoral thesis committees. In addition, our industrial collaborators have also participated in course lectures, both for undergraduates and graduates. To further integrate our graduate students into the industrial environment, our students are part of our technology transfer activities to industry. In this capacity, the students obtain valuable perspectives on industrial research and development and, at the same time, act as the conduit to testbeds at industrial sites. Our graduate students also actively participate as teaching assistants (TAs) in the courses which are related to the Center's research thrusts. This training provides experience in teaching in case the students are planning careers in academia.
Through the efforts of the BPEC, the Interdepartmental Biotechnology Training Program successfully completed its 11th year. Twenty-four Training Faculty participate from the Departments of Biology, Chemistry, Chemical Engineering, and Mathematics, and the Division of Bioengineering and Environmental Health. This training grant is funded by NIH (NIGMS) with a total of 20 pre-doctoral trainees and recently received a new award for an additional five years.
The NIH Genome Training Grant was administratively transferred from the Whitehead Institute to the BPEC. The objective of the Genome Training Program continues to be the development of cross-disciplinary studies in informatics and functional genomics. However, additional emphasis on functional genomics technologies and toxicogenomics is supported by new faculty from the Media Arts and Sciences, EECS, and BEH. Additional changes to the program include the addition of new training faculty, new training courses, and a pared-down advisory committee. A total of 25 Training Faculty from the Departments of Biology, Chemical Engineering, Mathematics, Electrical Engineering and Computer Sciences, the Division of Bioengineering and Environmental Health (BEH), Laboratory of Computer Sciences, and the Media Arts and Sciences participate in the Training Program. There are currently 10 predoctoral training slots being requested for the next five years and three postdocs, due to an increase participation of training faculty and increased interest in genome sciences
An especially important and exciting development during this past year has been the introduction of a new Ph.D. program in Bioengineering (BE) within the Division of Bioengineering and Environmental Health (BEH), beginning in Fall 1999. The mission of BEH is to educate leaders, and generate and communicate new knowledge, at the interface between engineering and biology. The central premise of BEH is that the science of biology will be as important to technology and society in the next century as physics and chemistry have been in the one now ending. Therefore, engineers and scientists must be educated who: can apply their measurement and modeling perspectives to understanding how biological systems operate, especially when perturbed by genetic, chemical, mechanical, or materials interventions, or subjected to pathogens or toxins; and can apply their design perspective to creating innovative biology-based technologies in medical diagnostic, therapeutic, and device industries, or in non-health-related industrial sectors such as agriculture, environment, materials, or manufacturing. That is, we must educate a new generation of people who can solve problems using modern biotechnology, emphasizing an ability to measure, model, and rationally manipulate biological systems. Hence, a key function of BEH is to create and support curricula in which biology and engineering are taught as synergistically as possible, and the new BE Ph.D. program is aimed directly toward accomplishing this function. The new program is designed to bring together engineering and biology in as fundamental a manner as possible. Stated broadly, it will educate students to use engineering principles in the analysis and manipulation of biological systems, to solve problems across a spectrum of important applications. Accordingly, the curriculum will emphasize fundamental concepts more than particular applications. By learning to advance both engineering and biological knowledge, it is anticipated that the graduates will be well positioned to contribute to many areas of research in both academic and industrial settings.
In this initial year of its operation, 1999—2000, 11 outstanding 1st-year Bioengineering graduate students were brought in; our goal for the foreseeable future is to recruit ~10—15 new graduate students per year. The typical entering students hold a B.S. (or M.S.) degree in an engineering discipline (typically Biomedical, Chemical, Electrical, Mechanical, Materials Science, or Computer Science). During their first year the students pursue a unified core curriculum, in which approaches from the various engineering disciplines will be used to examine biological materials and organisms over a wide range of length and time scales. The core curriculum, which will consist largely of subjects not offered previously at MIT, will be the hallmark of the new program. The program will have its own Ph.D. qualifying exams, the written part of which will be based on the core curriculum. To enhance depth and breadth, the core subjects will be supplemented by electives in the biological sciences and engineering. A student's research will ordinarily begin near the end of the first year, leading after approximately five years of total residence to a completed Ph.D. thesis.
There are many indicators noting how BPEC is recognized and respected as a national center to the professional communities. One measure on the outreach and leadership of the ERC faculty is the invited presentations to the various biotechnology communities. The 11 faculty members in the BPEC during 1999—2000 participated in the following categories:
Number of seminars at universities = 44
Number of seminars at industry = 25
Number of presentation at national and
international conferences and symposium = 34
Number of workshop/short course participation = 91
A second indicator of BPEC’s faculty leadership and achievements is the honors, awards and professional leadership services bestowed during fiscal 2000. A significant number of the BPEC faculty have been recognized by invited distinguished lectureships across the country, major awards and prizes, and fellow election in professional societies. It is our opinion the data presented above demonstrates the Center’s outreach and leadership in the field of biotechnology.
An indicator of outreach from BPEC is its collaborative efforts with other universities in education and/or research. In education, we have had invited guest lecturers in our graduate and undergraduate courses from not only other universities but also from biomedical and biotechnology companies, including representatives from CytoTherapeutics, Dyax, Advanced Tissue Sciences, Genzyme, Entelos, and Circe Biomedical. In research, we sponsored seminar series in both ‘Bioinformatics’ and ‘Stem Cells’ with invited speakers again from other universities and from industry. Research collaborations of BPEC faculty with colleagues at other universities are numerous, including projects with investigators at Dartmouth Medical School, Brown University Medical School, Harvard Medical School, University of Delaware, Purdue University, Odense University (Denmark), University of Copenhagen (Denmark), and University of Toronto, not exhaustively.
BPEC has entered into a partnership with the bioengineering-related ERCs at Georgia Tech and University of Washington to co-sponsor an annual Workshop; in February 2000 it was held at Hilton Head, SC, and was entitled ‘Workshop in Computational Modeling in Biology and Physiology.’ This partnership is fostering positive interactions among these three bioengineering-related ERCs, and indeed MIT and Georgia Tech are developing plans to identify new collaborative research projects under joint ERC auspices.
On the industrial interactions front, we are exceedingly pleased to officially have a new Therapeutic Gene Biotechnology Industrial Consortium in place, with ten companies who have participated enthusiastically in our October 1999 Fall Retreat as well as our April 2000 Spring Board Meeting. This Consortium is largely the result of extraordinarily effective work by our Industrial Liaison, Dr. Matthew Croughan, a BPEC alumnus and former Senior Scientist in cell culture technology at Genentech. Furthermore, we have added Jean-Francois Hamel in the position of Assistant Industrial Liaison and Laboratory Supervisor, to focus on student and facilities interactions with industry as well as day-to-day operation of the core laboratory.
Accordingly, a plan for an intermediate-level consortium in therapeutic gene biotechnology was written and distributed to the TGB IAB members for their review. Many responded favorably and soon sent in signed consortium agreement forms and fees. Thus, we now have a substantial Industrial Consortium in our new TGB Thrust, and have held a first meeting of our Industrial Consortium Advisory Board (ICAB), in April 2000. The ICAB’s conducted analysis of the Center was gratifyingly favorable–clearly, our new industry partners view BPEC as having regained a sound footing in its new strategic direction.
Regarding infrastructure advances, we have reconfigured our BPEC core laboratory space in MIT Building 16 to increase the coherence of BPEC-related research activity, and have consequently observed an enhancement of social as well as technical interactions among our students, postdoctoral associates, and research staff.
BPEC’s objectives remain to impact the education of undergraduate students, graduate students, and industrial personnel in their ability to work at the engineering/biology interface on important problems in biotechnology. In order to carry out these objectives, BPEC plans to continue its outreach involvement in education through the BEH, NIH Training Grants, UROP and NSF REU programs, and industrial internships. In addition, through collaborative and team efforts continue its research focus in gene therapeutics. The goal for BPEC’s Industrial Consortium Advisory Board is to expand its membership to 15 firms in the coming year.
Four new investigators were added to BPEC research teams. Three serve as lead investigators on particular projects: in the Targeted Delivery Vehicle Sub-Thrust: Dr. K. Dane Wittrup, Professor of Chemical Engineering and Bioengineering at MIT; Dr. Jack Wands, Professor of Medicine and Director of the Liver Research Center at Brown University Medical School; and, Dr. Shuguang Zhang, Principal Research Scientist in the Center for Biomedical Engineering at MIT. Wittrup and Wands bring expertise in human therapeutic applications focused on antibody-targeted adenoviral vectors for liver cancer therapy, and Zhang adds expertise in novel, peptide-based synthetic delivery vehicles to complement our ongoing organic polymer-based synthetic vehicle work directed by Robert Langer. Dr. Ihor Lemischka, Professor of Biology at Princeton University, has joined as a collaborator on a project directed by Harvey Lodish in the Stem Cell Vehicle Sub-Thrust, providing additional expertise on stromal factors that regulate hematopoietic stem cell function.
Mr. Jean-Francois Hamel transferred 25% time from the Department of Chemical Engineering to serve in two capacities: Core Facility Lab Manager and the Associate Industrial Liaison.
Ms. Patricia Reilly transferred 100% time from the Department of Biology to assume of the role of Program Manager for the DuPont MIT Alliance.
More information about this center can be found on the World Wide Web at http://web.mit.edu/bpec/.
Audrey Jones Childs
MIT Reports to the President 1999–2000