The Jackson Laboratory KENNETH PAIGEN MEMORES AGENDA SIMUL AFFECTAMUS Jasup Memorial Library 34, AND University St. Bar Harbor, ME 04609 THE NEWCOMEN SOCIETY OF THE UNITED STATES In April 1923, the late L. F. Loree (1858-1940) of New York City, then dean of American railroad presidents, established a group interested in business history, as distinguished from political history. Later known as "American Newcomen," its objectives were expanded to focus on the growth, development, contributions and influence of Industry, Transportation, Com- munication, the Utilities, Mining, Agriculture, Banking, Finance, Economics, Insurance, Education, Invention and the Law. In short, The Newcomen Society recognizes people and institutions making positive contributions to the world around us and celebrates the role of the free enterprise system in our increasingly global marketplace. The Newcomen Society of the United States is a nonprofit membership corporation chartered in 1961 in the State of Maine, with headquarters at 412 Newcomen Road, Exton, Pennsylvania 19341, located 30 miles west of Center City, Philadelphia. Also located there is The Thomas Newcomen Memorial Library and Museum in Steam Technology and Industrial History, a reference collection open to the public for research in the areas in which the Society devotes attention. For educational and historical purposes the Society offers tours of its working models of original steam engines. Meetings are held throughout the United States, where Newcomen addresses are presented by organizational leaders in their respective fields. Most Newcomen presentations feature anecdotal life stories of corporate organizations, interpreted through the ambitions, successes, struggles and ultimate achievements of pioneers whose efforts helped build the foundations of their enterprises. The Society's name perpetuates the life and work of Thomas Newcomen (1663-1729), the British pioneer whose valuable improvements to the newly invented steam engine in Staffordshire, England brought him lasting fame in the field of the Mechanical Arts. The Newcomen Engines, in use from 1712 to 1775, helped pave the way for the Industrial Revolution. Newcomen's inventive genius preceded by more than 50 years the brilliant work in steam by the world-famous James Watt of Scotland. The Newcomen Society of the United States is affiliated with The Newcomen Society for the Study of the History of Engineering and Technology, with offices at The Science Museum, South Kensington, London, S.W.7, England. The Society is also associated in union with the Royal Society for the Encouragement of Arts, Manufactures and Commerce, whose offices are at 6 John Adam Street, London, W.C.2, England. Members of American Newcomen who visit Europe are invited to visit the home of Thomas Newcomen at Dartmouth in South Devonshire, England and to see a working model of a Dartmouth Newcomen Engine. e "We sit today, here in Bar Harbor, in the center of a very profound scientific revolution which is making possible the application of genetics to medicine and to improving the quality of our lives, in ways that have never been possible before." - -Kenneth Paigen, Ph.D. This address, dealing with the history of The Jackson Laboratory, was delivered at a "1997 Maine Meeting" of The Newcomen Society of the United States held in Bar Harbor when Dr. Kenneth Paigen was guest of honor and speaker on October 3rd, 1997. The Jackson Laboratory KENNETH PAIGEN DIRECTOR THE NEWCOMEN SOCIETY OF THE UNITED STATES NEW YORK EXTON PORTLAND 1997 Newcomen Publication Number 1506 Copyright, 1997 THE JACKSON LABORATORY Permission to abstract is granted provided proper credit is allowed The Newcomen Society, as a body, is not responsible for opinions expressed in the following pages First Printing: September, 1999 SET UP, PRINTED AND BOUND IN THE UNITED STATES OF AMERICA FOR THE NEWCOMEN SOCIETY OF THE UNITED STATES BY CRWGRAPHICS. INTRODUCTION OF DR. KENNETH PAIGEN, IN BAR HARBOR, ON OCTOBER 3RD, 1997, BY MR. DAVID SHAW, CHAIRMAN OF THE BOARD, THE JACKSON LABORATORY. It is a pleasure to be here today and to introduce my good friend and colleague Ken Paigen, as well as to participate in this event honoring one of the world's great scientific institutions. Ken Paigen has gained international recognition for his distinguished career-over 47 years in the field of genetics. In 1946, he completed his undergraduate studies in biology at Johns Hopkins University, and earned a Ph.D. in biochemistry at the California Institute of Technology in 1950. Dr. Paigen's career in genetics began at Roswell Park Memorial Institute in Buffalo, New York. Following a 27-year tenure at Roswell Park-ten as Chairman of the Department of Molecular Biology-Dr. Paigen accepted a position as Professor and Chairman of the Depart- ment of Genetics at the University of California at Berkeley in 1982. He has authored more than 100 scientific papers and is well-known for his pioneering work in the field of biochemical genetics. Throughout his career, he has kept a very strong interest in knowing the possible medical applications of his work, and he has used his knowledge to improve the diagnosis of birth defects and studies of genetic factors contributing to cancer of the lung and of the bladder. Dr. Paigen was appointed Director of The Jackson Laboratory in 1989. As some of you may remember, that was the year of a disastrous fire from which the Laboratory has since recovered, thanks to his great efforts and the efforts of the staff. As Director, Dr. Paigen has taken The Jackson Laboratory in some exciting new directions during the most active period of scientific discovery and knowledge expansion in his- tory-and a very important part of that has been the biotech and genetics revolution. The Laboratory's exciting new directions include the con- struction of a state-of-the-art research facility in 1992 and the addition {5} of 18 new research groups to the Laboratory's scientific staff, for a total of over 100 Ph.D.s. During Dr. Paigen's tenure, the Laboratory has also expanded its Genetic Resources function, providing tens of thousands of researchers worldwide with tools, information, mouse models and other resources for genetics research. And he has helped the Laboratory get involved in the emergence of bioinformatics, which is a new research field pioneered by the Laboratory uniting computer technology-one of the great technological revolutions of all times-and the genetics revo- lution. Dr. Paigen's guidance has helped The Jackson Laboratory successfully recover from the 1989 fire; in the intervening years, the Laboratory's employee base has expanded from 500 people to over 800 people. Throughout his tenure as Director, it has been my privilege to serve on the Laboratory's Board of Governing Trustees, and now to serve as its Chairman. Please join me in welcoming Dr. Kenneth Paigen. DR. KENNETH PAIGEN DIRECTOR THE JACKSON LABORATORY {6} Good Afternoon: We are clearly very privileged to receive the Newcomen Award, and it is always reassuring when a group as significant as this recognizes the Laboratory's accomplishments; it gives us confidence that perhaps we really are on the right track. So, in the name of our 800-plus employees- who have made the institution what it is-thank you very, very much. It is indeed an honor. I would also like to formally acknowledge several people this afternoon whose support made this event possible: First is Tim Healy and his colleagues from the First National Bank of Bar Harbor; another is Jack Kelley of Nickerson & O'Day; also Vern Sprague of Irving Oil Corporation; and finally, Randy Searles of Ariel Creative. They have contributed to the Laboratory over time, and, especially, made possible today's meeting. I LIKE TO TALK FOR A FEW MINUTES ABOUT THE RELATIONSHIP The Jackson Laboratory has with the rest of the world. We are citizens of a very small town-Bar Harbor, Maine, with a wintertime population of 3,500 people-and at the same time, citizens of the rest of the world. What is it like to live in a relationship in which I know almost as many people in Paris, or Novosibirsk, or Montpellier, France, as I do in Bar Harbor? It is an unusual and interesting lifestyle. Let me illustrate this for you: Last year, the Laboratory distributed 1.6 million mice to research labs in 50 different countries. At the same time, we taught a course in bacteriology to the second-graders at Conners- Emerson School here in Bar Harbor. We're very proud that the bacte- riology course has been honored with its own award and is now used as a model statewide for primary school education. Another example, a local point: In the last five years, we've contributed over $180 million to Maine's economy, all of which has come from outside the state. At the same time, in those five years, our researchers have gained international recognition for innovative genetic approaches that have opened up for medical exploration fields like heart disease, glaucoma, osteoporosis, autoimmune diseases like lupus, even gall- {7} stones. In fact, there is a major front-page story in today's Bangor Daily News describing the recent epilepsy work at the Laboratory, which is groundbreaking in what it has been able to achieve. So we sit today, here in Bar Harbor, in the center of a very profound scientific revolution which is making possible the application of genetics to medicine and to improving the quality of our lives, in ways that have never been possible before. The question is, why is that so? What has brought this about? Why do we read about the latest genetic advance almost daily in our newspapers? The technology may be complicated, but the underlying reasons are not. Our bodies are the product of our genes. Our genes carry the set of instructions that makes us. The extent to which we understand those genes and what they do provides us a window, an ability to understand our own physical entity: who we are, what we are. Most of us see this as the key to 21st century medicine; this is where the dramatic advances are going to come from. To gain that understanding, we need experimental models-we need a place to do the research, a means to carry out the experiments. And the scientific world's consensus is that, by far, the best available model we have is the mouse. That has come about primarily because of work that was done at The Jackson Laboratory. There are three people here today who contributed very significantly to that: Thomas Roderick, Chen Chai, and Nathan Kaliss, all of whom are emeritus senior staff scientists of The Jackson Laboratory. For decades, The Jackson Laboratory has been the world center for the study of mammalian genetics-mouse genetics. Very simply, there is nothing else in the world comparable; nothing else like us anywhere. We have played a major role in creating many of the experimental tools that are used for genetics research, and we've not only made those tools available, we've made the mouse strains possible for others to use as well. And on the research side, over the years our own work has led to a number of important advances. In addition to the epilepsy work which is on the front page of today's paper, bone marrow transplants-and our ability to carry out organ transplants-was based on George Snell's research at the Laboratory. In fact, George Snell's work on the immune system, which made transplants possible, won the Nobel Prize in 1980. The original experiments that ultimately led to an understanding of what cancer is at a cellular/molecular level were done at The Jackson Labora- {8} 1980: DR. GEORGE D. SNELL RECEIVES THE NOBEL PRIZE, COMMEMORAT- ING HIS VISIONARY WORK WHICH LED TO LIFE-SAVING ADVANCES IN ORGAN TRANSPLANTATION. tory. A much better understanding of diabetes, and with it new prospects for treatments, have come out of the Laboratory. In vitro fertilization resulted from work at the Laboratory: it was done first in mice, and that technology transferred over to humans. And right now we are conduct- ing pioneering work in gene replacement therapy for birth defects and for developing immune therapy as a new medical modality-and those two have tremendous implications for the cancer problem. It's a problem which remains unsolved, in large part, and if we are going to solve it, it's going to require completely new kinds of therapy, not simply chemo- therapy and radiation and surgery. On that basis, it is easy to understand the widely held view that the Laboratory is one of the key institutions in national/international efforts to develop 21st century medicine. I realize that's a very bold statement to make, SO I'll buttress it with some reality. There are a set of strategic programming meetings going on at the National Institutes of Health; it's been an honor on my part to participate in several of those. And what has come out is the clear declaration by the leadership at NIH-both the Director of NIH, Dr. Harold Varmus, and the Director of the National Cancer Institute, Dr. Richard Klausner-that the mouse will be the key research platform technology for the next decade, and that the Labora- tory will play an essential and central part in making that possible. {9} 1930s: ENTRANCE TO THE ORIGINAL JACKSON LABORATORY BUILDING. Now, all of this had to have its beginnings somewhere, and The Jackson Laboratory began with Clarence Cook Little, who was quite an extraordinary man. As a graduate student at Harvard, he established mammalian genetics as a science, with the goal of understanding the cancer problem. He became the country's youngest college president in 1922, when he assumed the presidency of the University of Maine. Little was quite a brilliant administrator as well as a brilliant scientist. While at the University of Maine, he established a summer science program: way back in 1924, he brought students to Bar Harbor in the summertime on field trips to study biology. From Maine he went to the University of Michigan, and then in 1929 he came back to Maine to found The Jackson Laboratory. It's very interesting to go back in the archives and see why Little chose Bar Harbor as the site for the Laboratory. One primary reason was that the coastal climate was ideal for raising animals. Nowadays we have air conditioning and central heating, but in 1929, the climate was a very important factor. The second important factor is that the local residents were capable and loyal employees, with a strong work ethic. And I have 10 } 1920s: ROSCOE B. JACKSON, HEAD OF THE HUDSON MOTORCAR COMPANY AND A MAJOR SUPPORTER OF DR. C.C. LITTLE'S EARLY RESEARCH EFFORTS. MR. JACKSON'S UNTIMELY DEATH IN 1929 LED TO THE NAMING OF LITTLE'S NEW VENTURE: THE ROSCOE B. JACKSON MEMORIAL LABORATORY. TODAY, IT IS SIMPLY CALLED THE JACKSON LABO- RATORY. to compliment this community: that is still very, very true. Third, ample space had been donated to build the Laboratory by George B. Dorr, who was also essentially the creator of Acadia National Park. The original intent was to name the Laboratory after George Dorr's father, Charles H. Dorr. But Roscoe B. Jackson, one of the early and very generous donors who helped establish the Laboratory, died in 1929. The decision was made to name the Laboratory in Mr. Jackson's honor. Little considered the then-relatively low cost of living and the relaxed pace of life in Bar Harbor as a plus. And he also believed that the isolation and quiet of Bar Harbor in the winter was good for creative thinking and the pursuit of scientific ideas, a statement that I'm not sure all of us would quite agree with at the end of April or the beginning of May. A number of wealthy families from the Detroit area-the Fords, the Webbers, the Jacksons-supported C.C. Little's vision of the Labora- tory. They provided major funding which was used to construct the original facility and pay staff members' salaries. Now, Little's timing was absolutely impeccable. He began the Laboratory within months of the start of the Great Depression-so you can imagine that the first years of the Laboratory were really quite a struggle. We began with 16 employees and a $56,000 budget. (Our budget now is almost 1,000 times that sum quite a change.) Little served as Managing Director of the American Cancer Society as well as Director of the Laboratory, and in 1938, he was instrumental in Congress' { 11 } 1930: THE ORIGINAL STAFF OF THE JACKSON LABORATORY. FOUNDER C.C. LITTLE IS IN THE CENTER OF THE BACK ROW. creation of the National Cancer Institute (the first of the National Institutes of Health). The Laboratory received the second grant that NCI ever awarded in its history. It was in those very early years, in the 1930s, that the Laboratory's mission really crystallized and has remained SO ever since. The first element is our research program-what I have talked about and what you see on the front page of the Bangor Daily News today, the staff and their inquiries. We now have 36 active research groups at the Laboratory, over 100 Ph.D.s, and many technical support staff members. Providing genetic resources to scientists worldwide is the second element of our mission. Over these 68 years the Laboratory has become not only a center for research, but the place for experts in mammalian genetics to come to work and to learn, and especially the place to obtain the dozens, later the hundreds, and I have to say now the thousands of genetically different mice that are used as models to study various diseases. And all of that is backed up by the knowledge of the staff. We are a Cancer Center, one of 11 designated by the National Cancer Institute. At the time of our last review, when we were describing our Genetic Resources program, we realized with a shock that the three people who guide that program had over a hundred years of experience among them. And in the last few years, we have moved to providing { 12 } information systems-the world's computer databases for mammalian genetics sit in Bar Harbor and are accessed thousands of times a day from Web sites all over the world, twenty-four hours a day. Our third mission has been to educate and to train the next generation of scientists, ranging from second-grade grammar schoolers on up to postdoctoral interns (currently, there are 45 interns at the Laboratory). If those were our beginnings, what has happened over these interven- ing 68 years? We have endured two fires: 1947, which completely destroyed the Laboratory, and 1989, which destroyed a large piece of it. Since the '89 fire, we have invested $72 million in new facilities and new programs-a good part of that money was raised through a Capital Campaign. David Shaw, Chairman of our Board of Governing Trustees, led the charge and raised $20 million. We've grown from 500 employees to over 800, and I expect that in the next two years, we will employ over 1000. Our budget now stands at over $50 million a year. 1947: C.C. LITTLE CONTEMPLATES THE DESTRUCTION OF THE JACKSON LABORATORY. FRENCHMAN'S BAY CAN BE VIEWED BEHIND HIM; THE DEFORESTATION THAT MADE THAT VIEW POSSIBLE PROMPTED DR. LITTLE'S OFT-QUOTED, OPTIMISTIC COMMENT: "NOW WE CAN SEE THE SEA." { 13 } MEMORIAL 1947: THREE VIEWS OF THE FIRE THAT LEVELED NOT ONLY THE JACKSON LABORA- TORY, BUT MUCH OF BAR HARBOR AS WELL. { 14 } 1960s: AERIAL VIEW OF THE JACKSON LABORATORY CAMPUS, INCLUDING THE THEN-NEW MORRELL PARK FACILITY AT FAR RIGHT. 1989: FIREFIGHTERS BATTLE THE BLAZE THAT DESTROYED THE LABORATORY'S MORRELL PARK PRODUCTION AND DIS- TRIBUTION FACILITY. { 15 One of our major concerns is the quality of what we do-not just the quantity of what we do. It's important that we seek objective measures, and the clearest objective measure that we have is our ability to compete nationally for research grants from the National Institutes of Health. We are proud that, compared to a national average of about 14 percent of applications to NIH being funded, our success rate is now 55 percent. This has got to be one of the highest batting averages in the country, if not the highest. What does the accelerating pace of genetics research mean for us? What is the future ahead of us as an institution, and even more so, what does it mean to you personally, to each and every one of you? Let me deal with the institution first. We're faced with the necessity of dealing with very rapid growth, and we have to manage this constructively. We're coping with tremendous opportunities that are presented to us, at the same time that we are seriously constrained by finding funds for the facilities that it takes to house those programs. As one grows, there's a continuous challenge to maintain the quality of what you're worth, and the Laboratory has three essential principles for keeping that quality up. Number one is that you've got to hire the very best people possible. Number two, you have to give them the ability and the freedom to carry on their work. And number three, you must never accept anything less than the very best. Those are the things that we strive for. As an institution, we also recognize that since our mission is to improve the quality of life for humanity, then we have to begin at home with our own employees. And home means not only our employees, it means the communities that we live in: Bar Harbor, Hancock County, and the state. We have a strong "buy Maine" policy: 83 percent of our annual operating expenses are spent within the state of Maine, and 99- plus percent of our money comes from outside the state of Maine. The income and sales taxes that our employees paid last year contributed $1.8 million to the state treasury. And as a research institution that has worldwide visibility, we feel the responsibility to do whatever we can to promote the growth of biotechnology and research in the state-and we take that responsibility quite seriously. So if that's what it means to us as an institution, what does it mean to you, personally? Where is the science going? When I talk about 21st century medicine, I mean several things. First, identifying entirely new 16 } targets for developing drugs that we can use to treat disease. Second, developing entirely new therapies: some based on modulating the immune system, others based on our knowledge of how genes function in tissues. These are important for many diseases; as I said earlier, they are particularly important for the cancer problem. Third is something that we've never had before, personalized medicine. What is good for the average individual is not necessarily good for every one of us. Can we have a medicine which is tailored to our individual differences? Our needs are different; we respond differently to drugs. The reasons for those differ- ences lie in our genes, and if we can understand those, can we respond sensibly? (The image that always comes to my mind is from Star Trek: Dr. McCoy with his tricorder, waving it over the patient. For years I wondered what it was that this tricorder recorded, until I realized one day that one of the things it had to record was the patient's individual DNA sequence, displaying that patient's potential responses to therapy.) And finally, prevention. This has always been the ultimate dream of medicine. As we come to understand more, can we intervene earlier? Can we intervene before symptoms, before overt illness, rather than waiting until the patient comes to tell us? I and many others believe that that can be done, and that we will see it happen. There's a caveat: all of this is going to come slowly and incrementally. A good metaphor is that we all know what it's like to watch the tide come in-it's a very slow process. The first and most obvious thing that will happen is improved diagnosis. The second is entirely new kinds of therapy. Some will be drug therapies that look conventional but are based on new targets; others will be entirely new kinds of therapy that never existed previously. We will move to individualized medicine, and all along the way, we will increasingly seek new ways to cope with the concept of prevention, to begin to reduce the incidence of disease. So what are my final messages? First, The Jackson Laboratory's history began as a small summer study program for biology field students; 68 years later, we are the world's center for mammalian genetics. My second message is simple: we are citizens of Maine, this is where we work, this is where we want to be, this is where we live. Thirdly, the research at the Laboratory has led to breakthroughs in understanding and treatment of { 17 } human disease. Concomitantly, the scientific community relies on us for the information, the tools, the knowledge they need to make greater advances in human health. IfI had a single message to convey, it would be that our history is really only just beginning, because the application of genetics to human health is only just beginning, and we intend to be there all the way. So in the name of everyone at The Jackson Laboratory, I would like to thank you again, and to give the promise that we will do all we can to justify the honor that's been bestowed on us. Thank you. { 18 } 1950: THIS GROUP OF HIGH SCHOOL SUMMER STUDENTS INCLUDES FUTURE PH.D. HOWARD TEMIN, KNEELING AT LEFT. TEMIN WENT ON TO RECEIVE THE NOBEL PRIZE IN 1975 FOR HIS WORK IN UNDERSTANDING THE ROLE THAT VIRUSES PLAY IN THE ONSET OF CANCER. 1990s: HIGHSEAS, THE LABORATORY'S SUMMER STUDENT RESIDENCE. { 19 } WESTERN - UNION 38002 SPJ052 SP0212 *MP1200 SP1208 SPONSAGE GOVT ML POW THE UNITS HOUSE WARRINGTON DC to 1954 * FRANK 8 13418, PRESIDENT Rescort $ JACKSON MEMORIAL LABORATORY= BAR KARBOA BE= AM DELIGHTED TO LEARS or THE TWENTY PIFTE ANNIVERSARY OF THE ROSCOE . JACKSOS MENORIAL LABORATORY AND of THE TRIEUTE WHICH 18 BEING PAID TO ITS DIRECTOR, or CLAIMER c LITTLE. THIS NATION, WITH ITS RAPIDLY GROWING POPULATION ORGANIZED INTO IN INCREASINGLY COMPLEX SOCIETY. DEPENDS IN 0000 MEASURE ON THE INGENUITY of PHOSE WHO DEPOTEDLY AND PATIENTLY TOIL is its RESEARCH LIBORATORIES BROIGH THEIR EFFORTS OUR ECO NOMY IS REGILARLY STIRULATES. THROUGH THEIR EFFORTS OUR PEOPLE ARE ABLE TO FIND MORE AND BETTER JOSE TO ELJOY EVER GREATER COMFORTS OF LIVING. TO EXTEND TO THE JACKSON MEMORIAL LABORATORY MY BEST MISHES FOR CONTINUED SUCCESS # THEREFORE TO EXPRESS - HOPE #HOSE FULFILLMENT WILL ADVANCE THE GENERAL we NY WARN CORSPATERATIONS go TO DR LITTLE AND MY GREETINGS TO N.L. was ARE HONORING HIS