Paul Nurse: Good afternoon, everybody. Seeing you all here at this Convocation reminds me of a definition of a convocation. It's -- a university event where a speaker informs rows of students dressed in identical caps and gowns, that the key to their future success is individuality.

So, we are all dressed up today, and we are dressed up for a very special occasion. And it's a real great pleasure that I welcome you all here today. The University will award today the Doctor of Philosophy Degree to 13 graduate students. We will also award the University's Honorary Degree, our highest distinction, to a leader of science who, I'm proud to say, also received his Ph.D. degree from Rockefeller University.

When John D. Rockefeller founded this institution in 1901, the emphasis was on biomedical research. It took 50 years before a formal graduate student training program was begun. And then, 50 years ago, when the Rockefeller Institute, as it was then called, was incorporated as a graduate university empowered to grant the degree of Doctor of Philosophy.

The following year, 1955, Rockefeller University -- some call it Rock Tech, of course -- enrolled its first graduate students, who, like the 13 students who will be awarded their degrees today, underwent advanced training in the sciences with a graduate curriculum very different to most other universities.

In this University, there are few formal courses. There are no formal examinations. There are no traditional departments. These are very different properties to most universities. Today's graduate students and their 860 predecessors have been part of a community of scholars pursuing their own independent research.

And they have learned that science by doing science. By doing science with the University's highly-distinguished research faculty, many of whom are here today with us at this ceremony. Leading this excellent graduate program today is one of its alumni, Dean Sidney Strickland. I'm going to ask Sidney now to come to the podium.

(applause)

INTRODUCTION

Sidney Strickland: Good afternoon, and welcome. Mr. President, Mr. Fisher, graduates, Rockefeller community and honored guests -- we have a unique tradition at Rockefeller in which we focus on the graduate. I now give my formal assurance to the President and the Board that these graduates have satisfied their obligations and are eligible to be conferred the Degree of Doctor of Philosophy.

Frederick R. Cross: It's my pleasure to present to you, on behalf of myself and Mike Rout -- we are co-advisors to Vincent Archambault, the first student to be presented to you today. Vincent is a great example of the kind of energy and abilities of a Rockefeller student. That's probably why he needed two advisors, to keep up with him.

After he came to Rockefeller, Vincent became interested in questions of how cell division is controlled. And he chose to study the simple (inaudible) carrier, bakers yeast, as a model system, combining proteomic[?] and genetic approaches to identify and study novel binding partners in proteins that control the cell cycle.

And this approach was somewhat unusual in that it required a number of different disciplines, and also, it required a major effort involving large-scale methodologies. These experiments are large scale, even on a simple physical measure, since they involve, among other things, hoisting about 40-liter flasks of yeast culture. And for the non-metrically minded, that's about 100 pounds-plus.

But Vincent is a very fit individual and had no problem with this aspect of the work. A much more delicate aspect of the project, for which simple muscle strength would not suffice, involved mastering the mass spectrometer techniques of Brian Chad[?].

I should say that Brian could certainly have been considered a third advisor of Vincent, except I guess there wouldn't have been room on the program. We are all working hard to keep up with him. The mass spec methods required a lot of delicate work. I'm not really sure about that because Brian doesn't allow me, personally, to do any more than look at his instruments from across the room.

But Vincent mastered this whole technically- and intellectually-demanding set of procedures to identify some specific and very interesting protein/protein interactions. In the course of this work, Vincent concluded that he would need genetic methods, in addition to proteomics and biochemistry that he had already become excellent at -- to characterize the significance of these protein/protein interactions.

And this transition in his project involved yet another step down in the size of muscle groups involved. Because the main instruments here are -- the toothpick, the micro-dissecting needle. And also, careful thought about the logic of genetic epistasis[?] and multiple mutant analysis. That involves some very small muscles inside the head, that are sort of hard to get at, but are very useful.

And then, these results then fed back to the larger-scale biochemical questions that Vincent started with. It made a closed circle.

So in addition to the outstanding job Vincent did on his thesis research, he's also proved to be a great colleague to others in the laboratory. Always happy to offer a helping hand and advice.

And so, we will certainly be sorry to see him go, but we are happy to see him launched on what we are sure will be a very successful career in the future.

Mr. President, Mr. Fisher and honored guests -- it is my pleasure to present to you Vincent Archambault.

(applause)

Robert G. Roeder: It's my pleasure to introduce Hwa Jin Baek. Hwa Jin was born and raised in Korea, received his undergraduate education at Seoul National University, where he developed his interest in molecular biology. After an additional two years as a research fellow at Samsun[?] Research Institute, where he undertook a project that employed yeast genetic approaches, he joined the Rockefeller University's graduate program.

Not being overly sold on a term you often hear in this field -- the awesome power of yeast genetics -- he joined my lab in 1999 to work on a gene regulation problem in animal cells. His problem involved the further characterization of a giant multi-protein complex, composed of about 25 individual polypeptides that we had earlier shown to facilitate activation of specific genes, by DNA-binding regulatory proteins.

In essence, by acting as a bridge between the gene-specific factors and the enzymatic machinery that actually copies or transcribes the DNA, in rigorous and demanding biochemical approaches, Hwa Jin identified and characterized a new component of this complex.

And more importantly, discovered additional mechanisms by which this so-called mediator complex stimulated transcription. This he did with remarkable skill and diligence, a great deal of independence; and on some occasions, a moderate amount of stubbornness.

This important work set the stage for an even deeper understanding of the very intricate gene control mechanisms of the cell. In this case, how a 25-subunit complex interfaces with another 50 or more proteins to turn on genes in a highly-regulated manner.

On a more personal level, Hwa Jin has been a very congenial and helpful member of the laboratory. Potentially related, he met and married a fellow graduate student -- Yun Kim Kang[?]. And despite long hours in the laboratory between both of them, there arrived a beautiful daughter, Michelle, who is their pride and joy, and perhaps, welcome relief from the exciting but demanding transcription work.

As you can see, Hwa Jin has been productive on several fronts . . .

(laughter)

. . . and will be remembered in the lab, both for his scientific ambitions and accomplishments, and for his personal achievements.

President Nurse, Mr. Fisher and honored guests, I am pleased to present Hwa Jin Baek for the Degree of Doctor of Philosophy.

(applause)

Ralph M. Steinman: Ladies and gentlemen, David Bonnyay has studied a basic property of the immune system -- tolerance. Tolerance has been as elusive in immunology as it has been in other spheres of life. Yet, in both instances, we know that tolerance can and must develop. So how does it happen?

How does the immune system charge into action to resist infection, but at the same time, remain silenced or tolerant of ourselves, our own proteins? David had a lead on how to silence the immune system to our harmless proteins, before infection strikes, so that the chance of an inappropriate auto-immune, or self-reaction, would not take place.

The lead he had involved a new approach from a student colleague, Daniel Holliger[?], in Michel Nussenzweig's lab. David adopted this new approach. He directed the toleragen to a select group of cells, dendritic cells. But he did this in the steady state.

Which means, in the absence of any other purdiment[?]. By quietly and specifically delivering the protein to dendritic cells, David could silence the immune response. In effect, tolerance requires a gentle interaction with dendritic cells, without provoking them.

This seems like a good strategy for tolerance in general, don't you think? David's signature feature is his wonderful disposition. Frankly, the kind every parent wants his or her child to bring home.

His personality really reflects his work. Remarkable tolerance, with all of its components. Since he helped us explain immune tolerance, I'd like to speculate a little bit about how his personal tolerance might have come about. It might have been due to the fact that he grew up in different parts of the world.

Going to school in the U.K. and Holland, and even having to learn to speak Dutch. Furthermore, he met a mate, Jennifer, with a demeanor that's equally warm to his own. So maybe a breadth of exposure and a good partner are pathways to tolerance. David is now pursuing a different track from most of our graduates.

He is already in the business world, dealing with exciting new pharmaceuticals for cancer. We are impressed with the zest and assurance that he is showing for this new activity. And we are sure he will continue to make us proud.

President Nurse, Mr. Fisher, honored guests -- it's a pleasure to present David Bonnyay to the Degree of Doctor of Philosophy.

(applause)

John D. McKinney: Among biomedical research institutions, Rockefeller University is regarded as something of a singleton. People use words commonly like "unique" and "unconventional" and even "eccentric" to describe our peculiar academic culture, and sometimes they apply these epithets to us personally.

There are a number of reasons for this, I think, including our small but very diverse faculty. Our near total lack of departmental structure, and our commitment and our enthusiasm for interdisciplinary studies. But if I personally had to single out the one attribute that I believe really defines us as an institution, I would say that Rockefeller is a place that believes and invests in the power of the individual.

The power to explore, to discover, to create and ultimately, to change the world for the better. Rockefeller is an institution that supports innovative thinking and risk-taking, where individuals are actually encouraged to push the envelope rather than simply to stick to the safe and the sure path.

I think Katy Hisert's graduate career at the Rockefeller provides an excellent illustration of that peculiar philosophy. Katy came to us from Brown University, where she had acquired a solid background in basic immunology. Her undergraduate research project had focused on murine immuno responses to lymphocytic choreo meningitis[?] virus, which is a superb model system for studying basic immune responses during infection, but it's hardly of course, an important cause of global morbidity and mortality, unless you are a mouse, but no one is asking their opinion.

When she matriculated in our tri-institutional M.D./Ph.D. program, Katy was very keen to apply the knowledge and skills she had acquired at Brown to a more medically-relevant organism. But at the same time, she was reluctant to forego the tremendous advantages that model systems do have to offer.

Katy did a rotation in Coral Nathan's[?] lab at Weill Medical College, focused on the model organism salmonella typhemirium[?], which is probably the most-studied and best-understood of all bacterial pathogens.

She also did a rotation in my lab here at Rockefeller, focused on the pathogenesis of microbacterium tuberculosis -- the ideologic agent of TB, which is not so well understood as salmonella. Of course, ultimately she had to make a choice to go with the model or the real deal.

And in the end, she came up with a really gutsy and creative solution to this dilemma, I think. Basically she decided to have her cake and to eat it too. She realized that the fundamental questions that Coral's lab was asking in salmonella, and that my lab was asking in mycobacterium[?], were very closely related.

And she opted to pursue a dual thesis, working simultaneously in both labs. Now, this strategy of course, didn't make Katy's life any easier. Most students find it quite enough having to cope with just one project and one very demanding mentor, not to mention two.

But I'd like to think, and in fact, I would say I'm convinced, that Katy's training experience overall -- thanks to this unusual dual track -- was both broader and deeper than what either of our labs, mine or Coral's, could have provided to her.

Katy, it was not an easy path that you chose, but you have navigated it successfully to the end. And on the occasion of your graduation today, I salute you for your courage and creativity in defining your own path. I also salute Rockefeller University for allowing, and even encouraging actually, Katy to embrace that risk.

Of course, the story doesn't end here. And true to form, as we heard already from Dean Strickland earlier today, Katy has already bucked the trend and mapped out a rather unique path for herself in medical school, to which she is returning now.

She has already obtained permission to devote part of her first-year studies in medical school, to field studies on infectious diseases in impoverished communities in Southeast Asia and in Subsaharan Africa.

As a personal aside, Katy, I just want to say how very proud and enthused I am that you have taken this very unconventional choice and this very unusual path on your own, despite the considerable obstacles and risks that you face. And in that spirit, I would like to present you with one last small token of my esteem, which I hope you will find as inspiring as I did.

It's this book, which is modestly entitled How To Change The World.

(laughter)

What it is, it's a history, actually, of ashoka[?], which you may have heard of -- which is a philanthropic NGO which was founded a number of years ago by Bill Braton[?], the purpose of which was to identify and support so-called social entrepreneurs in all corners of the globe.

These are people you won't hear about on the evening news. But their ideas are already changing the human condition around the world, in 1000 very meaningful ways. They are, and I quote from the sleeve of the book -- "the driven, creative individuals who question the status quo, exploit new opportunities, refuse to give up and remake the world for the better."

Katy, I believe that you have all the right stuff to join the ranks of these successful social entrepreneurs, which includes of course, a newly-minted Ph.D. from Rockefeller University, which ought to be an asset. And I look forward to following the trajectory of what I fully expect to be a brilliant career in biomedical sciences devoted to the benefit of humanity.

Mr. President, Mr. Fisher and honored guests, it is my pleasure and privilege to present to you Ms. Katy Hisert.

(applause)

A. James Hudspeth: Jim Kappler has a very distinguished genealogy. He is the offspring of two world-renowned immunologists. And this has left its imprint, obviously, in this character; he has superior intellect and wonderful technical skills.

But those of you who know immunology recognize that if you ask an immunologist even the time of day or how the weather is -- you will get back a heap of Greek letters and symbols and acronyms. And this, being raised by two immunologists, puts Jim in the same category of children raised by wolves or other wild animals.

(laughter)

There's been a very definite effect on his pattern of speech, which ranges from reticent to mute.

(laughter)

When I first encountered Jim, I was a bit worried about this, but it turns out that it makes him a delight to advise because, obviously, the responsibility of all the faculty is dealing with students' problems and helping them along. So when we would meet periodically, I would ask if everything was going okay.

And he would say -- "Yes."

"Do you need anything? Is there anything I could do?"

"No."

And this has continued for four or five years, to my delight. He's done extremely well, for which I can take very little credit. Now, the one thing that does bring Jim alive, and even make him slightly loquacious, is sports. He's heavily into athletics himself. He's the only person here on an athletic scholarship today.

(laughter)

He is a serious lacrosse player and also is interested in all kinds of other sports. And in fact, it's the one thing that really galvanizes his activity are various athletic tournaments -- the NCAA finals and the like -- which make him appear hawking bets on various office pools for these sporting events.

And this attitude has also carried over to being really the mainspring of Jim's research career. We are interested in hearing. Our lab works on how hearing works normally, what goes wrong with it. And in the long run, what might be done to deal with that.

And one of the approaches we've taken, with a great deal of help from Jim, is a genetic approach. We use zebrafish, which are mutagenized and then examine the fish for those that have hearing problems -- as clues to what happens in problems in human hearing.

Now, genetics is in fact the application of sophisticated reasoning, statistical reasoning, really -- to problems having to do with animal behavior. In essence, it's very much like horse racing or betting on any other kind of athletic event.

The great advantage of genetics over, say, betting on horses, is twofold. First, when genetics works, it's for the benefit of mankind and in fact, we can find useful things about hearing problems in humans from the sort of work that Jim and others in his group have done.

The other really nice thing about it is that, while both activities cost tens or hundreds of thousands of dollars -- in genetics, you use somebody else's money.

(laughter)

Specifically, Mr. Fisher's.

(laughter)

So Jim has really spearheaded, in our group, the development of all the statistical tools for the analysis of genetic alterations in zebrafish. He's been a wonderful asset to us all and has really helped, not only the other undergraduate students, but numerous post-docs in our group.

He's succeeded himself, already, in cloning one very interesting gene. And he is well on the way, and probably has located a second. So it's been a great pleasure having him with us, and we will look forward to his career in other areas of science.

So, Mr. President, Mr. Chairman, distinguished guests, it's a great privilege for me to present to you James Alexander Kappler, for the Degree of Doctor of Philosophy.

(applause)

Ralph M. Steinman: Ladies and gentlemen, I am an immunologist.

(laughter)

My student, Kang Liu, never stops talking. Actually, Kang retraced a characteristic path, I feel, in our graduate program. A lovely path that I quickly came to respect when I arrived here. At that time, there were three graduate students, who very much remind me of Kang, in the lab.

And I was struck by the fact that they were far from classical apprentices. Each was developing new methods, new areas of research within the lab -- rather than pre-existing ones. If these students were apprentices, then they were learning the trade of discovery.

All three went on quickly to professorships in major institutions, after leaving here. So Kang Liu walked into the lab and declared that she wanted to better understand how the immune system deals with tumors.

"Kang," I said, "tumors are demanding enough, but they are different from our usual lab interests, which is infectious diseases." So Kang just went out on her own. She took apart the tumor problem, literally, by asking what transpires if a tumor cell dies and is captured by dendritic cells?

Dendritic cells are sentinels. And normally, they have to alert the body that an infection is taking place. But Kang figured out how to study the sentinels during their capture of dying tumor, and in an intact animal.

Together with colleagues from Kyoto, she demonstrated the remarkable efficiency with which dendritic cells deliver proteins from tumor cells to the immune system. And then following this delivery, she documented two very different outcomes. On the one hand, she showed that the immune system could be silenced to the tumor.

And on the other hand, she was able to induce strong resistance to tumors by properly activating the dendritic cells. The latter findings on tumor resistance, I feel, are worthy of pursuit in patients.

So Kang Liu really made things happen. And I can't overlook what happened on a trip home to China, early in her graduate school career. She sat next to a young faculty member from Hunter College -- not a tourist, but an expert in Chinese history.

Well, the skies were very friendly. Love bloomed. Marriage to Richard ensued in Central Park, and a charming son, Leo Belsky[?], has joined the lab family. Kang Liu begins her post-doctoral work on another area of immunology with Michel Nussenzwieg, I suspect, shortly after this ceremony. We confidently await the future fruits of her ingenuity.

President Nurse, Mr. Fisher, honored guests -- it's a great delight to present Kang Liu for the Degree of Doctor of Philosophy.

(applause)

[END OF SIDE A]

Albert Joseph Libchaber: Frank Vollmer is an undergraduate who studied in Germany, Bayreuth University. When he came to my lab, a young biologist lost among physicists, he had some difficulties from which he recovered. He also recovered from his passion for motorbikes, which led to some bones broken.

Frank was interested in new techniques. He learned optics from Steve Arnold[?] (inaudible) and built an optical center to study the optical resonance of a glass sphere[?]. The glass sphere is much larger than the wavelengths of light. It is a remarkable resonator for a mode trapped inside by total internal reflection and no losses, of course, in the glass.

Absorbed proteins or virus or bacteria, absorb on the surface within the optical evanescent field of the light, and shift the resonance frequency. This leads to an optical detection of any biological object. The ultimate sensitivity of this detector is that of one protein.

The response is linear[?] in concentration for what are called (inaudible) particles -- particles smaller than the wavelength of light. The response is quite (inaudible) for particle (inaudible) and the wavelengths of light.

This unique detector is Frank's own work. He will pursue his research as a fellow with the (inaudible) Institute at Harvard[?] University.

Mr. President, Mr. Fisher -- I am glad to present Frank Vollmer for the Degree of Doctor of Philosophy.

(applause)

Paul Nurse: As President, it is my honor and privilege to confer the Degree of Doctor of Philosophy upon you. Graduates, please rise. By the authority of the regents of the University of the State of New York, which they have vested in the trustees of the Rockefeller University, and is by them delegated to me, I confer upon you the Degree of Doctor of Philosophy, which admits you to all the rights and privileges thereunto pertaining.

(applause)

Please be seated. It is now my great pleasure to recognize the contribution of Rockefeller's alumnus and former President, David Baltimore, who began his career at this institution and rose rapidly to become the most influential biologist of his generation.

A Rockefeller education certainly played a role in David's success, but his formidable intellect, his leadership abilities, his uncanny eye for scientific talent -- were all well developed long before he arrived here. He first encountered Howard Temin, with whom he would one day share a Nobel Prize, at a summer program for high school students at the Jackson Memorial Laboratory.

Inspired to pursue a career in science, David chose chemistry as his major at Swarthmore College. And he was accepted as a Ph.D. candidate in biophysics at M.I.T.

But another summer exploration would change the direction of his career. At a course in animal viruses at Cold Spring Harbor, he became friendly with Dr. Richard Franklin of the Rockefeller University, and decided in 1961, to come to Rockefeller.

David completed his thesis work in a blazing 18 months. He had already begun post-doctoral studies by the time his Ph.D. was awarded in 1964. A short time later, David overturned a central assumption about how nature operates.

In back-to-back papers published in 1970, David and Howard Temin reported their independent findings that certain RNA viruses contain a previously-unknown enzyme that enabled these retroviruses to transcribe genetic information from RNA into DNA.

In recognition of their work, Baltimore and Temin shared the 1975 Nobel Prize in Medicine with their colleague, the distinguished virologist Renato Dulbecco. David was then 37 years old.

Like all important discoveries, his early findings have continued to reveal a fundamental significance. Over the years, it has become increasingly clear that the flow of information from RNA to DNA is much more than an unconventional survival strategy practiced by certain retroviruses.

When cells divide, for example, reverse transcription plays a vital role in maintaining teleneres[?] during chromosome duplication. The newly-discovered retroviral enzyme, reverse transcriptase, rapidly became an essential research tool. Molecular biologists could use it to copy messenger RNA to DNA -- a feat that helped to launch the biotechnical revolution of the 1970s.

It was a controversy surrounding biotechnology that first propelled David into the public policy arena. In 1975, the year of his Nobel Prize, he was a key organizer of a conference, an important conference that recommended the first ethical and safety standards for the use of recombinant DNA technology.

When the retrovirus that causes AIDS emerged as a major pathogen of the twentieth century, the scientific community and the world at large turned, once again, to David. As a leader of a pioneering study of the AIDS epidemic in the '80s, he emerged as a passionate advocate for greater federal investment in HIV research.

In 1996, he chaired an NIH blue ribbon committee that set an ambitious new agenda for the development of an HIV vaccine. David continues to make valuable contributions to the important discourse between scientists and the public, on complex scientific issues such as the sequencing of the human genome and stem cell research.

In 1892, David was approached to head a bold experiment. The creation of an independent research institute associated with MIT. Just as he had expanded his own laboratory, to integrate studies in virology, immunology and molecular biology, David designed the Whitehead Institute as a new kind of research environment that would build bridges across disciplinary boundaries.

Under his leadership, as founding director, the Whitehead Institute achieved renown for the brilliance of its faculty, and the opportunities it provided for young investigators. When he returned to the Rockefeller University as President in 1991, David brought this zeal for excellence and commitment to young scientists, with him.

Drawing on his experiences as a student, as a young researcher, as an institutional leader, he introduced many ideas here that took hold and prospered. In particular, his emphasis on nurturing the careers of junior faculty members, helped to build the vital Rockefeller University of today.

In 1997, David Baltimore took on another challenge when he accepted the Presidency of the California Institute of Technology. Cal Tech's faculty and trustees recognize that David could help that institution to expand its role in the life sciences by encouraging intellectual ties between biology, chemistry, physics, math and engineering.

His current job has literally given David a whole new universe to discover. Right now, Cal Tech's world-renowned department of astronomy and astrophysics is planning to build the most powerful telescope on earth, capable of gathering light that began travelling to our planet 14 billion years ago.

Actually, today is not only a special day for us and for David, it's a special day for astronomy. There was a transit of Venus across the sun, which I observed from the University with my telescope, a few hours ago. And that only occurs every 100 years or so.

Anyway, the University President charged with leading this exploration of the cosmos, is now sitting just a few feet away from the place where he stood to defend his doctoral thesis. This is the 40th anniversary of David's Ph.D. -- an occasion in which we are very proud to share.

It is only fitting that David Baltimore should be the first alumnus to receive an honorary doctorate from Rockefeller. Because he has brought this University great honor throughout his remarkable career, as researcher, educator, leader in science policy and master builder of scientific institutions.

Today we are privileged to celebrate the homecoming of Rockefeller University's most distinguished alumnus. Mr. Fisher, graduates, faculty and honored guests, I'm pleased to present David Baltimore for the Degree of Doctor of Science, Honoris Causa.

(applause)

Paul Nurse: By the authority of the regents of the University of the State of New York, which they have vested in the trustees of the Rockefeller University, and is by them delegated to me, I confer upon you the degree of Doctor of Science, Honoris Causa, which admits you to all the rights and privileges thereunto pertaining.

(applause)

We now have the pleasure to hear David speak on a topic, "The Politics of Science." David?

David Baltimore: First of all, let me thank Paul and everybody else here, for this extraordinary honor. Rockefeller Institute first came into my ken many, many years ago, when I was growing up in the suburbs of New York. And when I graduated from college, I had a difficult choice to make, of whether to follow a couple of other people who had come from Swarthmore the year before, and come here as a graduate student; or go to MIT.

And I chose to go to MIT. That only lasted a year, as Paul has noted, before I realized that there were opportunities at Rockefeller, particularly with Richard Franklin, that were beyond anything that I saw anywhere else in the world. And it worked out that way.

Richard was a wonderful mentor. He left here many, many years ago and is now retired in Switzerland. But I owe him an enormous amount for the very things that you heard about from the wonderful presentations of the various students here.

The freedom that Rockefeller can provide for a young person to follow his or her own nose, into the things that ultimately matter to the individual. Science is an individual enterprise. It's an enterprise that's very much about people finding their passions.

And the Rockefeller is one of the rare places where you can do that. I'm reminded again, of the beauty of this ceremony. No where else, I think, in the world does each individual get the kind of attention that an individual does in this ceremony. And each of these students -- and of course, students elsewhere deserve it, but this is the only place that really is in the position to do it.

Now, I presented a pretentious title for a very simple reason. And that is that -- politics and science are tightly interwoven all the time. And we are now seeing aspects of that relationship that are of central importance to the future of the biomedical enterprise and the future of this country. And I thought I would focus on three. Three are many others that could be considered.

One is -- the general issue of the reputation of science or the position of science and the thinking of the federal government.

The second is -- the need for trained personnel, if we are going to maintain our strength as a scientific powerhouse in America.

And the third comes not so much from the political realm, as from the progression of science. The need to structure science around more focused questions, as we move forward with our ability to use the basic knowledge we've developed, to deal with disease.

And I will deal with those three briefly. In February, I got one of those requests that come to Nobel Laureates -- would you support my issue? And I usually file such letters because I can't take on everybody's issues, and usually they are things I don't know enough about to be useful.

But in this case, I rapidly signed the petition that had been put in front of me because it resonated with my own concerns that had developed over the last few years.

It was a petition from . . . actually, a statement ultimately . . . from the Union of Concerned Scientists, a group I don't necessarily always agree with -- that said that in this administration, we've seen too many cases in which science has been put aside, of activities being put aside in the name of politics.

And the Union of Concerned Scientists actually did a whole study of this, and it's all published and available on their website. But it had an interesting resonance in the press. The press covered this event the way few petitions in science are ever covered.

And I think the reason is because the press knew that this was a problem, but hadn't been able to write about it themselves because they didn't have anybody to say it that they could quote -- and now there was somebody they could quote.

The statement, actually, is a wonderful one. It starts off with a quote from President Bush, Sr. in which he touts the importance of objectivity in thinking about public issues. It goes on to say that in the present administration, a lot of that seems to have been put aside, and asks that we go back and listen to what George Bush, Sr. said.

Very soon thereafter, two members of the federal panel on bioethics were dismissed, who had opinions about stem cell research that were not in line with the chairman's opinions. Really underlining the need for political correctness, if one is to even give advice to the federal government -- just exactly the kind of thing that the UCS statement was talking about.

More recently, in the last couple of weeks, we've seen the FDA not allow the morning-after pill to be sold over the counter. Again, countering the advice that they had gotten from scientific panels, that this was an appropriate thing to do.

The thing that strikes me strongest, given my background as Paul has so wonderfully recited, is in AIDS -- where the government took down a website that supported condom use and replaced it with complicated statements how condoms work and sometimes don't work other times. How abstinence is the only thing which will really work. And that there is a sort of truth about that, but in the real world, it's not particularly helpful. What really bothers me is that in the less-developed world, where AIDS is the most serious health challenge that we face, we should be doing everything we can to support countries like Uganda and Thailand, that are seriously educating their populace about the importance of condom use.

And who have been able to reduce the spread of AIDS, the spread of HIV in very effective ways -- in some cases, up to 80 percent. So, there are things we could be doing, if we are willing to go back and look at what really does work, to take an objective approach.

What we need to do is to go back to choosing people who are on panels for their scientific abilities, for their knowledge and objectivity -- not for their political positions. We need to publish uncensored reports. And we really need to recognize that what science does, when it meets public policy, is to set ground rules.

You can't change the facts of nature. Now, they may be hard to determine and there may be an uncertainty in them -- there often is. But given all of that, you can't simply ignore important challenges. The challenge of global warming, being one of those that we, in particular, have to take seriously.

The work force issue is, of course, a very different issue. America has had many great scientists that were born here. Our Oppenheimer's and our Ben Franklin's. We've had many scientists who have come here from abroad -- the Von Carman's[?] and Fermi's and Zallard's[?]. That mixture has made American science great.

But today we are seeing increasingly fewer people being trained in science in the great American universities. And an increasing need to bring our scientific talent from abroad. And just at that time, of course, the response to the 9/11 terrorist attack has led to a closing down of our openness to the outside world.

A set of restrictive policies, some of them seemingly arbitrary; some of them certainly not likely to increase our security at all. But very hard to get around. And the response that we are seeing from abroad is people saying -- it's just not worth trying to come here for training.

And we saw it in just this year, a really severe drop in the applications to graduate schools around the many universities in America. We certainly saw it at Cal Tech.

So, enormous damage has been done already. This kind of thing is very hard to reverse. Many other countries are walking into the breach, saying -- come here, we'll make it easy for you, we have good training to provide.

Of course, with the globalization of science, there are many places that can provide strong training. We'd like to believe that it's not as good as we can do here, but it's not bad. And so we are going to find ourselves in the position where neither are we training sufficient people here, nor are we bringing people in from abroad. And that has to be a problem for our economy and for our national security itself.

Finally, let me turn to a different focus. I started in molecular biology here, in 1961. And at that time, the general public didn't know molecular biology existed. It's actually a bit of a curse at Cal Tech because those of us who are old enough, remember that Cal Tech was the center of so much of molecular genetics. Max Delbrook[?], in particular, being the focus of that.

And yet, no one in the outside world, outside of the internal coterie of people in the field, knew what was going on, that miracles were happening. And so, even today, everybody says -- well, isn't Cal Tech a physics school? And we probably have more Nobel Laureates in biology than we have in physics.

Anyway, that's all beside the point. I remind us of this though, to say that things have changed enormously. That today, molecular biology is so much stronger in its abilities to handle problems than it ever was before. And if you say to yourself, one of the goals of biomedical research is to deal with disease . . . and I say one of the goals, because one of them is to learn about nature . . . then there has to come a point at which you've gotten enough basic information, that you can begin to think in a focused way about disease processes.

And we find ourselves today, I think, in that position relative to certain problems and not others. A problem like AIDS is a very focused problem. It's caused by a virus of 10,000 nucleotides[?]; we know every one of them. We know all the proteins that are made.

We may not know what they all do and we may have a lot to learn in that regard, but we can also formulate a lot of problems, in quite exact ways that need focused attention.

Cancer is reaching that point because we've been so successful in defining the oncogenes, the tumor suppressor genes, the mechanisms by which cancer even metastases are becoming clearer, or will soon, I think.

So we can, again, focus our attention on the specific answers. After all, cancer really is hundreds of diseases. And see what we can learn about them, and what we can do about them. What kinases[?], to go back to one of the degrees here, underlie their activities.

Nervous system diseases -- I wouldn't say the same thing. We really do not understand how the nervous system works. We don't understand how it codes information. We don't understand how it integrates information. We don't really understand what information is in that context.

So we've got a long way to go there. So I think we need to pull out those things that we really can focus on -- and focus on them. Well, the National Institutes of Health is very poorly set up to do that. They have bought the litany, which I helped drum into them over the years, that RO1 grants are the most important things.

That you have to give the investigator total freedom to follow his or her nose, wherever they want to go. And all of you who got degrees today, we talked about how you did follow your noses -- and that's terrific.

But that's not how you get problems solved. And I think we need to take problem-solving mode more seriously. Now, part of my concern about that comes from the fact that, at Cal Tech, we manage for NASA the jet propulsion laboratory. So we have 5,000 people -- all of them are Cal Tech employees -- whose job it is to make satellites.

And those satellites go up and investigate Mars and Saturn. And at the end of this month, we will go into orbit around Saturn with a Casini[?] launched six years ago; and it started being built probably 20 years ago. And nothing can go wrong with those satellites.

Because if any little thing goes wrong, the whole thing is over. So this is the most focused kind of activity you can imagine. And it works. People devote their lives to doing this. The remarkable thing is, of the 5,000 people -- none of them have tenure and many of them spend their whole life at JPL. So there are different ways of doing science.

Very challenging, very satisfying, with a goal very well-defined, to be met. Where I had personally been most frustrated about this is in the development of an AIDS vaccine. Because I've seen huge amounts of money going from the National Institutes of Health, to study AIDS in this way or that way; and very little attention being put to how you are going to build a vaccine that's going to make a difference.

Now, that's changing and it's changing mainly because the committee that I worked with, and Harold Varmus in particular, when he was Director of NIH, saw the need for an NIH-sponsored institute that would focus on an AIDS vaccine. And in fact, that has been built just in the last couple of years. It's the first attempt by the federal government to respond to a particular health need -- one that was being picked up poorly, to some extent, but not enough by the pharmaceutical industry.

And so, the vaccine research laboratory now has a $90 million budget at NIH, and is really making vaccine candidates; this was something that NIH was incapable of a number of years ago. And which, basically no basic research laboratory . . . sorry, no university-based or institute-based laboratory around the country is able to do.

So I think that we need to think carefully about what problems can be solved. We can't be sure they can be solved, but you can say -- the probability is high enough that we really ought to focus our attention on it. With a $27 billion or $28 billion NIH budget, there is room for these kinds of activities.

So I've run over a wide range of things. How science is treated as an enterprise. How we keep it going at the incredible rate it has been going, with the really wonderful people that we have; we've seen many of those people here today. And thinking about how we reorganize our structures to take into the account the need to have focused research on focused problems.

These are agendas for the future. I thank you very much for your attention.

(applause)

Paul Nurse: Thank you, David, for those remarks. Dr. Baltimore, Chairman Fisher, graduates, faculty, staff and students -- this concludes the 46th Convocation of the Rockefeller University.

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