Testimony

Statement by
Emanuel F. Petricoin, Ph.D.
Senior Investigator
Office of Cell Tissue and Gene Therapies
Center for Biologics Evaluation and Research
on
NIH Ethics Concerns: Consulting Arrangements and Outside Awards
before the
House Investigation and Oversight Subcommittee

May 18, 2004

Mr. Chairman, I am pleased to be here today so that I may provide answers, to the best of my ability, to any questions that you may have and share with you any relevant insights. My name is Dr. Emanuel F. Petricoin III, and I am a Senior Investigator, in the Office of Cell, Tissue and Gene Therapies in the Center for Biologics Evaluation and Research, within the US Food and Drug Administration. I have been a US Government employee since 1993, and have been honored to spend the entirety of my post-graduate career in the Public Health Service.

I understand from the news coverage and your letter of invitation that you are investigating NIH ethics concerns, consulting arrangements and outside awards. I appreciate the seriousness with which you are taking this investigation. I hope that I can provide information that will help you. I believe that my outside activities, all of which were submitted, reviewed and approved according to the procedures in place, were performed to the highest ethical standards. I believe I followed, to the best of my ability, not only the instructions but also the intent of the ethics guidelines. On May 7th, 2004, I was informed that Biospect, with whom I had an approved outside activity, had been recently and now considered, based on a re-review, to be a significantly regulated entity. As a result of this new classification, this approval had been revoked. Upon notification of that decision, I immediately and without hesitation ended this outside activity. I want to note that my approved activity with Biospect was listed on all of my filed OGE 450 forms (Executive Branch Confidential Financial Disclosure Report), and that even as of the last review cycle, this activity was found not to be in question.

BACKGROUND REGARDING MY CAREER

Ever since I can remember, I have wanted to be a scientist. My family always jokes with me about how they can never recall me wanting to do anything else. From the time I won my first science fair ribbon in the 4th grade until today, I have never envisioned myself doing anything else. Mr. Chairman, I am a Washington DC local. I remember as a child, driving by the NIH and the Naval Hospital and staring in disbelief at the size of the buildings where everyone inside were all scientists!! I stand before you today as an individual who I believe, has been trying to make a difference in the public health, especially in light of my father's death from a sudden heart attack when I was 21 and my mother's battle with breast cancer. My time spent in high school and college working first as a patient transporter, then in a microbiology and clinical laboratory, solidified my decision to work in an area of science that could directly affect people's lives.

I could not wait to go to college. While many of my friends and dorm mates waited until their sophomore years to declare a major, at the University of Maryland I charged headlong into the Microbiology major, received my degree in 3 years, and received my PhD in Microbiology in five years in 1990. My PhD research focused on the analysis of genes, proteins and surface molecules for gonorrhea vaccine development. I was immediately drawn to a project that didn't seem esoteric, but might allow me to contribute to work that could actually lead to a vaccine some day. During my thesis work, I gained expertise in pathogenic microbiology and infectious disease analysis, immunology and cell biology, biochemistry and protein chemistry, protein separation and fractionation methodologies, and mass spectrometry analysis of molecules within complex biological and bacterial samples. I successfully identified and characterized the first gene for a gonorrhea surface molecule that later became considered for a potential vaccine target. We employed a variety of protein analytical techniques, and were one of the first scientific groups to successfully employ mass spectrometry to analyze the sugars attached to lipids on the surface of disease-causing bacteria. Moreover, as a consequence of my PhD studies, I became facile in the handling of clinical specimens and body fluids as well as diagnostic testing methods for bacterial characterization. During my part-time employment at Southern Maryland Hospital, I gained valuable expertise in tissue and body fluid collection methods, clinical sample handling and storage methods, and clinical diagnostic technology. Moreover, I became adept and fully trained using a variety of robotic and microfluidic technologies. This combined experience in research and diagnostic practice was the basis of my choice to seek a post-graduate career in translational medicine- on my continuing journey for bench-to-bedside applications.

POST-DOCTORAL CAREER

From 1990 until 1993 I was a National Research Council Fellow in a post-doctoral position in the Division of Cytokine Biology, CBER/FDA. I was very interested in cancer-based applications, and because of my PhD training, realized that new classes of molecules and proteins were being developed which may really have an impact someday. However, the scientific community lacked knowledge about the way these proteins communicated with cells and what really caused cells to grow, die and spread uncontrollably. I was drawn to a laboratory which was focused on trying to understand how a widely known protein, interferon, actually worked and caused cancer to die or quelled viral infections. As icing on the cake- I was able to work at an FDA facility that was at the NIH- the Nation's premier research institute and my childhood fantasy. During my post-graduate work, I gained valuable expertise in signal transduction biology, protein-protein interaction methodologies, protein phosphorylation, and cytokine biology. For the first time, our laboratory identified and characterized members of a signaling pathway that later became the well known "JAK-STAT" pathway. This pathway is now thought to regulate and be involved in viral disease, inflammation, and cancer. Additionally, during my post-doctoral fellowship, I was able to extend my graduate expertise using mass spectrometry and protein separation methods by employing new proteomic technologies. Using these tools, I identified and sequenced a new protein, produced by many different cancer cell lines. This protein was experimentally demonstrated to interfere with interferon activity.

JOINING FDA/CBER

As I entered the twilight of my post-doctoral training, I was intent on being a research scientist working directly for patient benefit. My postgraduate work on the NIH campus made me realize that the unique environment provided by a vibrant scientific community all striving for translational medical benefit was the place I wanted to stay. My time as a post-doctoral student in an FDA facility revealed a different but equally important aspect to the translation and delivery of medical benefit to the bedside that I had not recognized before. I was intrigued and impressed by the FDA scientists I interacted with. I was intrigued by their unique combination of bench-side research talents as well their understanding of what it took to get a biologic approved for clinical benefit. I decided that I could blossom in such a role and was ecstatic that in 1993, I successfully competed for a publicly advertised tenure-track US Government position. I was tenured in the Center for Biologics Evaluation and Research in 1998, and am proud that my entire post-graduate career has been spent as a US Government scientist working at the US Food and Drug Administration.

FDA/NCI COLLABORATION ESTABLISHED

In 1997, as a result of a series of highly cited scientific publications from the laboratory of Dr. Lance A. Liotta of the NCI, I contacted Dr. Liotta to discuss potential collaborative opportunities to use proteomic analysis of laser capture microdissected human cancers. This discussion resulted in the first joint Interagency Agreement (IAG) between the FDA and the NCI. The focus of this IAG was to work jointly together to develop and test new proteomic technology for clinical and translational applications. I had finally realized my dream job. Working at the FDA and learning about the process of delivering safe and effective medicine to the public let me explore and expand my scientific talents which linked back to my times as a college freshman working in a hospital lab.

Based on our combined research and clinical expertise, we embarked on a variety of research projects that employed a variety of emerging proteomic technologies for discovery of diagnostic biomarkers and therapeutic targets. The overarching goal was to develop and evaluate methods for personalized medicine and early detection of cancer as a means to provide translational public health impact with a high degree of scientific rigor and an eye towards rapid patient benefit. This goal has been a consistent cornerstone of our joint collaboration. During the past 6 years, our program has successfully developed a number of new exciting proteomic technologies, with over 90 publications to our credit. These publications are the direct result of a talent pool of highly creative scientists both within the program itself as well as our fantastic set of scientific collaborators outside the program. We have entered into several documented US Government Material Transfer Agreements (MTA) and US Government Cooperative Research and Development Agreements (CRADA) that have proved highly successful. Within each of these agreements and arrangements we sought a clear path to facilitating and translating our work to public benefit without constraining our ability to maintain the necessary independent and creative freedom that has served us so successfully. In addition to the need to maintain creative freedom to operate, we are driven by a transparent process of proteomic data dissemination into the public domain. We are proud that as US Government scientists, we were the first group to offer all of our mass spectral data in the public domain, and continue to provide all of our data to the entire scientific community as a public service. This public dissemination of data and transparency has been commended by the National Cancer Advisory Board. We are also proud that while we were the first group to demonstrate the use of mass spectrometry based protein fingerprinting for cancer applications in the spring of 1999, recently hundreds of scientists at the latest meeting of the American Association of Cancer Research (April 2004) are reporting independent success using a variety of different approaches. Our raw data has been downloaded over 500 times in the past two years, and scientists, from around the world, including a 2002 National Medal of Science Winner, named by President Bush as one of the nation's leading scientists, have published extremely exciting results using our raw data as the basis of their own pattern recognition methods and tools.

Our ongoing work continues to accelerate. We have recently invented new technology that is wholly owned by the Government and has been advertised in the Federal Register. This has allowed us to identify thousands of new biomarker molecules that may be useful for cancer and disease diagnosis. We believe that this new diagnostic information archive, never before known to exist in the blood, may contain important information for the detection of many diseases - not just cancer. We hope that this information can translate into broad public health benefit.

I certainly receive many outside activity requests every year. Almost all of these I dismiss immediately because they are invitations, which directly relate to my official duties as an FDA employee and my ongoing US Government scientific research. I consider only those requests that invite me to participate not because of my US Government position, but because of my general scientific expertise which encompasses my lifetime as a scientist, and whose activities are directly unrelated to my government job. In those instances where I chose to pursue the opportunity I always submit an HHS 520 form for approval. This approval form is approved or declined after due diligence under current established procedures. I would never knowingly pursue any activity which I felt would run counter to this process, and I certainly would never knowingly pursue or continue any outside activity which I felt was in conflict with a career spent as a scientist in the pursuit of public and patient benefit.

In closing, Mr. Chairman, I wish to express my gratitude to CBER, the FDA and PHS for providing for me a working environment and research funding support for a body of work which I believe is highly successful and is one that I am extremely proud of. I will answer, as best I can, any questions you may have for me.

Last Revised: May 19, 2004