Transforming Health: Fulfilling the Promise of Research

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Transcript

                  P R O C E E D I N G S

                    Opening Addresses

          MS. WOOLLEY:  Our program is Transforming Health, Fulfilling the Promise of Research. I am Mary Woolley, president and CEO of Research!America, and along with the Honorable Billy Tauzin, president and CEO of the Pharmaceutical Research and Manufacturers of America, we thank you for joining us today.

          We are particularly pleased to have Dr. Elias Zerhouni with us as our keynote.  Thank you for being with us, Dr. Zerhouni.

          We have a very distinguished group of panelists and moderators whom you will hear from shortly.

          PhRMA and Research!America are pleased to present today's conference because both our organizations are absolutely committed to the goal of fulfilling a promise of research.  Progress toward that goal means progress towards transforming health for the better.

          During our program today, you will hear a number of viewpoints as to what the future may hold, as well as suggestions on how we can overcome barriers in order to properly foster research and make our vision a reality.

          One of the keys to overcoming current barriers is collaboration, collaboration between the government, academia, and industry.  It is central to fulfilling the promise of research, and another key is earning and maintaining the public's confidence, trust, and support, and it is that topic that we are going to begin with.

          Research!America and PhRMA have commissioned a public opinion study to find out what Americans are thinking these days about medical and health research, to take a look at expectations, perceptions, concerns, and priorities.  The bottom line is this.  The American public wants research to succeed, and the sooner, the better.

          There is a rich pool of data in this new poll, data that has, in fact, a great deal in common with scientific data.  It reveals both the expected and the unexpected, and points us to topics that need further exploration, but public opinion poll data is unlike other scientific data in that public policy‑makers are more often going to pay attention to it, public opinion poll data, and that is another reason that we commission public opinion polls, to share our findings with the people whom we elect to help provide the environment and the resources we need to fulfill the promise of research to transform health.

          Our survey methodology is the standard public opinion poll, survey methodology, and we can provide additional details for anyone who is interested.  There is a quote here from President Lincoln who surely understood the value of public sentiment and public opinion, as do we.

          Now, research for health takes place, of course, in the broader context of health, and it is a frame for what should be our most effective messages.  So it is important to keep the public's view of current health issues very much in mind when we talk about the importance of a more robust environment for research.  We need to connect the dots for people about how research is going to help them not only in curing cancers and other diseases, but how research can help us drive down health care costs and help us find effective ways to assure that more people realize the benefits of research through accessible evidence‑based health care.

          One of the ways we, all of us in the research community, can better connect our enterprise to top‑of‑mind public concerns is by talking more about prevention, and I know we are going to be hearing more about that today.

          I said earlier that the American public wants research to succeed.  There is absolutely no question about that.  We have been seeing evidence of this in our polling for many years.  The public has very high expectations for research.  This level of confidence is, in fact, more broadly shared in the general populous than we sometimes hear in this city, at least judging from the current funding and policy environment that we are all faced with.

          Now, here we have asked an open‑ended question about what people feel are the most important health benefits of medical research, and you can see the way they talk, of course, about new cures and preventions, and that is pretty much what we would expect, but, again, this gives us clues in the words people use that we ought to be using in making our case.

          Given what respondents said about the benefits of research, we actually found it surprising that only 57 percent said that research has helped them or someone close to them.  This is an indication that we are not connecting the dots as well as we might when it comes to making it clear that everything in health care started out as a research question.  We have to talk about it over and over and over again, reinforcing that point.

          Now, in stark juxtaposition to that last slide, here we see that the overwhelming majority of Americans say they have benefitted from medical research over the last past year, they are just not seeing it that way.  We should consider the fact that we have a work assignment here.  If 90 percent of people say they purchase prescription drugs, they have benefitted from medical research, but they haven't made that connection.  We need to help.

          This is an interesting finding indicating that 57 percent of the public believe we are not making enough progress in medical research.  It is consistent with the high hopes and expectations we saw earlier, but it also raises a question as to what people think is standing in the way of more progress.  So we asked that question.

          Here is a list of five possible barriers to research, ranked according to whether or not people felt each of those barriers was, in fact, getting in the way of progress.  We have seen this ranking hold up quite consistently over time, and it gives us confidence that the public will resonate with calls for removing regulatory barriers, sustaining the R&D tax break, and spending more money for research.

          For the first time in this series, we asked about low participation of volunteers in clinical trials, and you can see that people aren't as convinced that this is a problem, but there is some concern.  The higher percentage of "don't knows" in that category, I think might actually be an under‑representation, since other work has demonstrated that most people do not, in fact, know much of anything about clinical research.

          One reason people don't know about clinical research is that their doctors are not talking to them about it, as is shown on this slide.  This only refers to participation in trials, of course, this particular question.  So it probably understates the percentage who have heard something about clinical trials, but even if we double the 7 percent figure, we can see that we have a long way to go in working with the medical practitioner community, as well as the public, in highlighting the importance to the future of health of more people being willing and interested to participate in research.

          Indeed, everyone has a stake in research, a health stake and also a financial stake.  The responses to this question show us that one way or often in more than one way, we all pay for research.  We pay for research as consumers of health care, including consumers of prescription medications, and we pay for research via our tax and philanthropic dollars, and you can see on this presentation that some of these overlap and can be combined.  The point is everybody pays.  Support for research comes across the full gamut of the public and their activities and their government.

          We also asked a question in the environment that we hear within the research community about clashes, potential conflict of interest and other issues, whether Americans think that the different kinds of institution that perform research should be working together, and overwhelmingly, that is exactly what people say.  They want all elements of the research community to work together because the simple equation there is if everybody who is smart and committed is working together, we will get the answer faster.

          I think that the public believes that the red flags that are sometimes raised within the community are the community's responsibility to resolve, kind of inside baseball issues.  The public just wants us to get the job done.

          One of the reasons we want to be assured of the public's continuing support of research is that we want their support to help grow investment in research.  You see here in this investment study how industry leads the way in its amount of funding for medical research with the Federal Government and other sources behind, but significant.  We are talking about a lot of money here, but it is plateauing out, and that has ramifications for the public's health, as well as for the health of the research enterprise.

          I believe that the findings in our poll today as well as the findings of our work over the past many years on these issues reveal that the public is actually ahead of our decision‑makers in wishing to make research for health a much higher national priority.

          For the most part, the public doesn't know about the problems caused on both a short and long‑term basis due to the current low‑priority status of research.  All of us in this room and our colleagues across the country have an obligation to speak out about this.

          One way we can all do that is to participate in getting the nation's leadership back on track in making research for health a priority and encourage candidates running for the Presidency to declare what they will do as President to assure a vibrant research enterprise in this nation.

          PhRMA is one of Research!America's partners in a new initiative to make the views of the Presidential candidates known to stakeholders and to the general population via this website.  You can help us, you can help the research enterprise, by contacting candidates and urging them to participate.  Please check it out.

          That concludes my remarks, and I am delighted to be able to turn over the platform to the Honorable Billy Tauzin, the president and CEO of PhRMA.

          [Applause.]

          MR. TAUZIN:  Thank you, Mary, and thank for all of you joining Research!America and PhRMA today in this very important question to focus on, indeed as this poll has shown, the importance of research to patients not only here in this country, but increasingly around the world.

          Secondly, let me really thank Dr. Elias Zerhouni for being with us today.  We are old friends, and we worked together for many years, me in my congressional role, he in his amazing scientific role on behalf of the patients of our country, and the work you do at NIH, Elias, it will live long after both you and I are gone for many, many years.  I want to thank you for all you do and thank you for being a part of this discussion today.  We look forward to it.

          Mary asked a question, talked about a question in the poll, about whether Americans felt a connection to research and whether they felt benefitted by the research that occurs in the health care communities of our country, and surprisingly, so few do.  Sometimes disease has to strike very close to you and very severely in your family before you begin to focus on that issue.  There are other things that, obviously, take your attention away, until that awful diagnosis.

          I went through that.  I got that terrible diagnosis.  I got that call from the doctors in Bethesda that, in the middle of a wonderful career in Congress, I had cancer.  The advice was to drop everything I was doing and go fight the battle for my life because I was given about a 5‑percent chance.

          Somewhere in that course of surgery and chemotherapy and radiation, they took the 5 percent away and basically said I was going to die.  I remember that extraordinary moment when Cecile, my care‑giver, my wife, an amazing moment, and I sat with the Dr. Wolf at M.D. Anderson and got that death sentence.  I remember looking at him and said, "I'm going to die, but not today, not now.  We're going to find something, aren't we?"  He said, "Yeah."

          So I was lucky.  I was very, very lucky because just two years earlier, Genentech had won approval for a drug called Avastin, and it wasn't approved for my cancer.  It had nothing to do with my cancer.  It was a colorectal drug, but Dr. Wolf and I and my wife, living in this country where we could make decisions like that, made a decision to take advantage of that amazing research and to try it.

          I remember he told me, "This drug may kill you because it may interrupt all of the surgical healing.  It is going to interrupt the formation of capillaries, the structures the doctors created to put your gastric system together, but it just might save you, too.  It might starve the tumor of its capillaries, and we might get that thing, and I will show you a non‑identifiable screen of a liver cancer where we did it off label, and it worked.  So maybe it will work for you, because we got nothing else for you.  We can give you standard cancer therapy," and they did.  They gave me some great drugs from Sanofi, Oxaliplatin, and Xeloda from Hoffman‑La Roche, and I took all of that, obviously, but it was the Avastin I think that made the difference.  It really was.

          As a result, seven or eight months later, the cancer was gone.  I remember going to radiation, I said to the doctor, "Now, don't do anything we can't correct with surgery because we got to go back in.  Don't burn me so bad, we can't go back in."  He said, "Billy, if we sent a surgeon in right now, we couldn't find the thing."  It was gone.

          So was I lucky?  Yeah.  Was I extraordinarily lucky?  Yeah.  But was it luck that brought Avastin to the marketplace?  Was it luck that brought Avastin to the attention of Dr. Wolf?  Was it luck that brought Avastin to me?  No.

          I had traveled to California.  I met the team that worked for 14 years on Avastin.  I went to Nutley, New Jersey, and I met the 14‑year team that worked with the team in Genentech.  I heard their story about how they almost gave up two or three times on the drug because of how difficult it was to take it through that very extraordinary clinical process model we have constructed sometime in the last century here in America and how they persevered, and the stuck to it, and they eventually brought this amazing drug out.  It is being tested now in all sorts of cancers, as you know.

          I remember thanking them.  I remember they were crying.  I was crying.  We were crying there together, and one of them said, "Billy, nobody comes back and says thank you."  I said, "Yeah, but where I'm working now, I know where you live.  Most people don't know where you live, or they'd be here to say thank you, too, if they knew where you lived."

          So, Mary, I think the poll is right.  I don't think Americans yet understand how critical that 14‑year process was, but for all of us who benefitted from it, we not only understand it, we deeply appreciate it.  We deeply understand the message of what research can mean to families and lives and loved ones.

          Now, not only am I alive today and having a second chance at life, I remember John Breaux said, "Billy, when you were dying, did you see that white light?"  I said, "No. I felt a little heat around my ankles.  I figured I'd better come back and do something good."  Not only am I alive, but I got to see my two grandchildren born that I wouldn't have seen, and they got to see their grandfather.  We are going to have a good life together.  I got to walk my daughter down the aisle that I never thought I would get a chance to do.

          There are all kinds of amazing things that happen because research presents us with those opportunities that otherwise would have been lost, and the last 10, 20 years were being lost to so many people who now have the opportunity to see grandchildren and walk daughters and see their sons get married.  Those are the connection points that make the real understanding of how critical research is to Americans, and we need to make those stories real and make people understand how much we depend upon the researchers at NIH and all the 3,000 hospitals and institutions that receive the 50,000 grants a year that literally award 300,000 researchers in America with the tools and the assets they need to conduct basic research in this country on disease and on potential treatments.

          It is the connection between what we do at PhRMA, where we spent $55 billion last year in this country, out of $80 billion spent worldwide, $55 billion spent in this country, the only grant that has gone up.  That is why we do this in this country because at least here in America, we still have that connection.  We still understand it, not enough yet, Mary, but we still understand it, and it is still rewarded and supported.

          The question that Dr. Zerhouni needs to get an answer to is will we continue to support it.  I was in Congress when we fought to double the NIH budget.  We accomplished that.  The NIH budget with inflation factored in is going down again.  Thankfully, I saw the latest appropriation granted some increases, but we have got to be concerned that not only is the NIH budget relatively flat, but that it could continue to go down, and that is a dangerous signal for every patient who patiently waits for the next great discovery, and are they coming?

          Well, here is some good news.  Here is some really good news.  In our pipeline today, 650 new drugs being tested today for cancer, 140 for heart disease and stroke, 77 for HIV/AIDS, 185 being tested today for infectious diseases, 197 for mental illness, over 300 for rare diseases, and that is pretty new, by the way.  There is more and more research being done on the 6,000 diseases that affect 25 million Americans that don't ordinarily get a lot of attention, and PhRMA is proud to work with other organizations, NIH and their department, to, in fact, intensify efforts on those rare diseases.  There is a lot of great work going on.

          We are going to hear today from a care‑giver who has spent 11 years caring for a husband who suffers from Alzheimer's.  We are going to hear what that is like.  It is an amazing story.  Meryl Comer is going to give you a personal insight of what it is to witness that disease every day in your life.

          But here are the danger signals I see.  One, we are increasing life expectancy in America with all this great research, with all these new technologies, and we are bumping up to 78, 79, and pretty soon, we will top 80.  Most Americans believe they are going to live way past 74.  The sad truth is that if we as a couple live into our eighties, one of us will probably have Alzheimer's, unless we somehow find some solution to it.

          So, in the silly season of politics, when everybody is running for President, and Congress and the President are dueling it out over there on appropriations measures, let's think about that.  We are a country that is about to see an obesity explosion.  We are a country that is going to see a diabetic explosion, an explosion of asthma, an explosion of all sorts of diseases.  We are going to see it in our children right now because of the way in which we literally have allowed lifestyles to change in this country, and we haven't focused on prevention.  We haven't focused on early intervention.  We haven't focused on early disease management.

          We spend 85 cents out of every dollar today on treating the damage done by disease untreated, uncared for, undetected, when it should have been detected a long time ago and we should have dealt with it earlier.  That is why we helped with Dr. Ken Thorpe to put the partnership together on chronic disease and why we are trying to make that a center of this debate in the silly season, how we might reform health care in this country by focusing on that little simple tenet, that if you really focus on early intervention, prevention, and detection, you can save incredible dollars and untold suffering and amazing dollars to the U.S. economy in terms of productivity.  We can be a healthier and wealthier people if we have a good debate on how to change health care.

          But at the heart of it, we also have to think about will our health care system, will our government structure that is admired around the world, where we fund with government taxpayer dollars this amazing basic research through NIH and all of its affiliates and all the institutions that receive grants and the tools they need to conduct some of this research, and where our companies more and more do the research on applied sciences and really are taking those products to the point of approval and marketing, that combination is the envy of the world.  Will we see it sustained in this country?  Will we see those pipelines that I described to you begin to fail?  How do we make a connection that American really feel before they have to feel it, as I felt it and so many other patients feel it, on a personal level when someone they love or themselves are stricken with awful disease?  How do we get that message across?

          We at PhRMA have been thinking about that for the last three years, too, and we are working on several ideas.  One thing came to mind to me when I was thinking about all of this earlier.  As a kid growing up in rural Louisiana, if anybody came to me and said, "We want to build a new electric powerplant, and we want you to support it, but the wires are not going to reach your house," I would say, "Go away.  Leave me alone.  I've got no interest in your powerplant.  I've got no interest in your research on new efficient ways to deliver energy to people if you are not going to connect your pipeline to me and my family."  That simple thought helped us to put together the PPA program because you can't have people in America who don't have insurance and can't access medicines supporting research if you don't somehow make those medicines available to them, too, and the same thought has occurred to us internationally.

          You can't have people around the world supporting intellectual property and the development of new products and new discoveries in a system that rewards that research, you can't have them supporting that legal system of patents and intellectual property protections that reward the research that occurs if you don't somehow connect them to the medicines that that research products.

          So, today, we are working in Geneva with many other partners on new systems by which we can better serve people around the world who can't afford our medicines, particularly in those neglected diseases, how we might do research on diseases that nobody has paid attention to, collectively, and how we might create more accessible structures for people to get those medicines.  So there are some lessons there.  I think it is one of the things we have to focus on in this country is how we can make everybody understand that research is important to them; first, make sure they get the medicines they need; second, make sure they get the best health care they can.  That means you can't have anybody in this country without insurance, as simple as that.

          It is crazy, this insane subsidy system we have built in America where the people we are subsidizing to provide insurance to their employees are paying more to subsidize other people who don't have insurance.  That is what our system does.  Doctors provide $25 billion worth of free medicine in America.  Hospitals provide $25 billion of hospital care.  We at PhRMA provide something like 7 or 8 ‑‑ I'm not sure.  I can't, under antitrust laws find out, but it is something like 7‑, 8‑, $9 billion worth of free medicines through our discount programs and our free programs.  We are all doing that.  Who ends up paying for that?  It is the other people who buy insurance.  So we are discouraging them from having insurance because we subsidize those that don't have insurance through insurance costs that we are trying to subsidize insurance for.  Isn't that pretty crazy?

          If we want a good health care debate in America, a good policy debate, it ought to focus on how we can connect everyone in a system where they get the advantage of the best medicine available in this country through a good insurance program, that gives them a chance to get early interventions, preventive care, and care that literally gives them a chance to manage their disease before it damages and wrecks their body totally.  Those are the kind of things I think we ought to be doing, and then we ought to do something else.  We really have to somehow defend the system that continues to reward research and development in this country.  That is the reason so much occurs here.  It is the reason why research and development has left other countries.  It is the reason why Japanese pharmaceutical firms do their research in America and why more European firms do their research in America.  It is because in those countries, they are not awarded to do research.  They are rewarded to build generic products, but not to do basic research anymore.

          How do we maintain that system when Americans are increasingly upset because they seem to be the only ones paying for this research?  Tough questions.

          And the most important one, how do we continue the enormous amount of money we spend in research and development when pipelines are beginning to fail, when this process that now takes about 14 years, much too long, and spends about a billion dollars per drug, knowing that 7 out of 10 won't capture that cost in the marketplace once they get approved, and after they approve more and more, obligations are placed upon them because of safety concerns?  How do we maintain that structure when we will be dealing with personalized medicines in a world where science teaches us that we can build medicines for smaller and smaller patient populations?

          Think of what I just said.  The current model focuses on broad clinical trials and is designed for us to spend a billion dollars over 14 years to produce a new medicine for the broad population, and we try to know everything we can about it in 14 years.  Hopefully, we won't be surprised.  Three percent of the time, we are.

          The new science tells us that very soon, we will be able to identify smaller and smaller patient classes for whom a medicine is specifically designed.

          Now, we know in rare diseases, it is hard to put a billion dollars worth of research and development behind a disease with only a thousand patients.  How are we going to have research and discovery conducted in this country at a billion dollars a clip for smaller and smaller patient populations, and is 14 years, is 14 years satisfactory to anybody?  Is 14 years satisfactory to anybody who is waiting for that new medicine who might not be as lucky as I was because it didn't quite come out in time for them to save their mother, their father, their daughter, their son?

          We got some huge challenges.  So, while we are thinking in this silly political season about who's got the best health care plan and who knows what is best politically to gather enough votes to be elected President or Senator or Congressman or whatever they are running for, why don't the rest of us be thinking those deep thoughts.  How can we build new models that are much more efficient than the current model?  How can we convince Americans, more and more Americans, Mary, on how important research and development is before they get that ugly diagnostic call?  How can we make sure that no one in our country is left out of this process, so that they all support it, and how can we make sure that in the ugly contest for scarce taxpayer dollars that we never, ever forget how important it is to continue to fund National Institutes of Health, and how we keep that extraordinary cooperative spirit going between the private and the public structures that do research in America?

          Now, I was one of the lucky ones.  The Cancer Society tells us that there are more and more lucky ones like me.  Cancer deaths are finally going down in this country, successively for several years, at an accelerating rate, but there are tens and tens of thousands of new diagnostic cases every day, and what we see in the future is an ugly, ugly situation where America gets sicker and poorer unless we answer some of these deep questions I have asked you to think about today.

          So today is a good day to begin thinking and talking about them, and today we have assembled in this room some pretty good people who can help us think it through, starting with Dr. Zerhouni.

          Before I bring him up, Mary and I would love to answer any questions we can right now, if you want to take a moment or two to ask us a couple of questions, and then I will bring up the real story, and we will hear from the guy at the point, as the Marines call it, in this effort to battle disease at every element.

          Any questions, anyone?  Yes, sir.

          ATTENDEE:  You had talked about personalized medicine and how that is going to transform the way we think about that.  So, from the organization that you represent, do all of the members of your organization embrace personalized medicine and all of the implications that are associated with it in terms of the cost and how they would be able to change the patterns of health care that we provide to all of our citizens?

          MR. TAUZIN:  Absolutely.  The one thought in their mind, however, is will they do that here in America, or will some other country come up with some models that work much better.

          For the first time this year, more than 50 percent of the market for America's pharmaceutical companies will be outside of the United States.  The markets are growing abroad as more and more people can afford and take advantage of newer medicines as they come out.

          The real question is whether some country, rich with oil revenue, loving to do a great economic incentive program, might invite all our countries to go over there and do the research there because they are going to set up models that work in a personalized medicine world.

          I did something this year that didn't get a lot of attention, but let me tell you about it.  I got associated with a group called the X PRIZE Foundation.  You may remember them from Space Launch.  They are interesting people.  Their theory is the theory that brought Lindbergh to Paris.  He didn't go to Paris to see the girls, although that would have been okay.  He went to Paris to win a prize, and that is when he flew across the Atlantic.  It made history.

          The X PRIZE Foundation is built around that notion.  If you create prizes, you can incentivize people to do some interesting things.  So they offered a $10‑million prize for the first people that could launch a commercial space vehicle, and the Mojave group did it.  They spent about $150 million to win a $10‑million prize.  It's the glory of it, the excitement of it.  Now their commercial development is around it.

          They came to me and said, "Billy, you served as chairman of the Commerce Committee, Telecommunications, Health, Energy.  Give us some ideas."  So I gave them a bunch, and one of them we came up with was we really needed a genetic prize.  If you did a personal genetic screen, it would take a long, long time and cost about $2 million when we started this.  It is coming down rapidly now.  If you did 100 of them, it would take 12 years.  That is coming down, too.  We said how can we really drive it down, how can we drive it down to where a personal genetic screen, a total screen, could cost less than $1,000.  So we offered $10 million.  We found a diamond mine operator in Canada who had a lot of money to give away, and we got $15 million from him.  We offered a $10‑million prize to the first team that could put together a system that would do 100 personal genetic screens in 10 days, that will drive it down to under $1,000 cost, and they have to do it twice.  They have to do it on their first team and then on a team of so‑called personalities.  I am one of those.  I am a personality.

          [Laughter.]

          MR. TAUZIN:  Hawkins is another one who volunteered.  Larry King, "Larry King Live," is another volunteer.  A hundred of us volunteered to be the second guinea pigs, and that is a little interesting because there is on protection for us.  There is no privacy protections or anything right now, but we are going to do it.  We think it is worthwhile.

          But what happens when we get to that point?  Do you see where I'm going?  When we really get to the point where we can do individual personal genetic screens and we understand a great deal more about the way in which those genes work together and pathways to either create or defend against disease, we are going to be down to that question.  Do we have a model that allows us to do research in that world?  We don't.  We do not.  The current model will break.  It will shatter.  New discoveries will be thwarted, and I suspect some country is going to be looking to pick up the pieces if we don't pick them up ourselves.  All of our companies are thinking about that.

          Anyone else?  Yes, sir.

          ATTENDEE:  You see now most of us who advocate for research are essentially licking our wounds this morning from the House failing to override the President's veto of the Labor‑HHS bill.

          Having served in Congress ‑‑ and you have sort of alluded to this ‑‑ how do legislators square the fact that many of them stand up and give very moving, passionate speeches, as you have done, for medical research, but when push comes to shove during the votes, they just don't support the bill that will carry that research?

          MR. TAUZIN:  Don't misinterpret that.  The people that voted against it, this is a political fight going on.  It is not about the dollars or what is in the bill so much as a political fight or the priorities in the bill.

          I can tell you that 99 percent of them, if you give them a choice among things to support, they will want to fix the roads in their district.  They want to do what they call "earmarks," all those things that make a difference for their constituencies, and then they want to do some nice broad things and help the country.  Most of them are good people.

          I have been Democrat.  I have been a Republican.  John Breaux called me a "Transvesticrat."

          [Laughter.]

          MR. TAUZIN:  I have been one of each.  Winston Churchill switched parties three times.  They asked him about it.  He said, "To rat is difficult.  To re‑rat is very difficult."  I haven't re‑ratted.

          But the bottom line is they are both good people.  They are going through political warfare right now.  They are not interested in accomplishing a lot, so much as they are trying to affect the results of the next election round.  That is sad, but that is true.

          Inside that, however, is a lot of support for NIH and for medical research.  We have just got to somehow get them past the nasty politics they are caught up in, and it is nasty.  I miss Congress a lot.  I don't miss that part.  I really don't.

          So don't misinterpret that.  You will have a lot of those "no" votes who really support NIH.  They are just playing politics right now.

          Yes, sir.

          ATTENDEE:  I am trying to develop a new message campaign to drive NIH funding.  I am curious if you would comment briefly on the viewpoint that says that grass‑roots campaigns are difficult and unnecessary, that you just need to get to the subcommittee chairman and then you are done.  Could you comment on that?

          MR. TAUZIN:  Well, I think that might have been true at some point.  I don't think that is true today.  I think more and more, you have to have a combination of both grass‑roots messaging and organizations and work done with key players in the bodies.

          The contest for funding is huge.  There is never enough money, no mater how much taxes you collect, to do everything everybody wants to do.  There never will be.  That is why, if I can put a plug in, these government‑run systems in Europe make bad decisions about new medicines because there just isn't money to fund them.  So they leave them out of the formulation.

          The truth is you have got to have both.  Members have to feel that they are hearing something from their constituents.  Whatever you think about Members ‑‑ and Congress' reputation is pretty low right now ‑‑ whatever you think about them, most of them have pretty good standing in their own constituencies, in their own districts.  Everybody hates the other congressman, but they pretty well get along with their own.

          For the most part, most of them pay a lot of attention to what they are hearing from home folks.  I remember my rule was when anybody showed up at my office, even Dr. Zerhouni, if there was somebody from my district in the outer office, they came to see me first.  You take care of your local constituents first.  So you can't miss that, but you can select what districts you are working in.  Obviously, if you are trying to influence the decision of some key players, work in their districts.  That is where your grass‑roots campaigns ought to go.

          While we are at it, don't forget the FDA.  Funding NIH is critically important, but FDA is woefully underfunded.  PhRMA is putting up 70 percent of their budget today.  That is too high.  Realistically, that ought to be under 50 percent.  I would feel much better ‑‑ we all would ‑‑ if we saw more congressional funding of the FDA as well.

          So those are messages that resonate with Members when they hear from people at home, "Hey, don't forget to fund these agencies.  They are critical to food safety.  They are critical to research and my health and my family's health."  When they hear that, then when you go in their office, it resonates better when they talk.  Don't forget grass roots, very critical.

          I want to bring Dr. Zerhouni up.  So I will take one more.  Go ahead.

          ATTENDEE:  I am John Reichard with Congressional Quarterly.

          I just want to take another crack at that question that was asked earlier.  You emphasized the importance of funding NIH.  Was it a mistake for the President to veto the Labor‑H bill?

          MR. TAUZIN:  I don't know all the reasons why he vetoed it.  He may have vetoed it for other reasons.  I don't think he vetoed it because of the level of NIH funding.  I would be surprised if that was his reason.  I suspect there are other reasons why, including some political reasons, but I know him and I know his administration well enough to know that they value medical research, and Dr. Zerhouni will verify that, that they support very heavily.

          In Texas, for example, where the President comes from, the people of Texas just approved a $3‑billion bond issue to study cancer and to research cures from a State government level.  So I know the President comes from a State where there is a strong emphasis.

          We just did a fund‑raiser for NIH last night in this city with Tom Hanks who is playing the role of Charlie Wilson in the new movie.  Go see it.  It will be fun.

          So my guess is that it wasn't NIH funding that was in his mind when he vetoed the bill, but in the end, obviously, the Congress and the President are going to have to come to some agreement on the total funding in the bill and a place where the President can sign it because it is a critical bill.  It has to get signed.

          I am going to take one more, and then we will finish.  Go ahead.

          ATTENDEE:  [Inaudible.]

          MR. TAUZIN:  Well, a couple thoughts.  Let me tell you.  Just recently, I think it was Bob Eisner who was talking about the concern that he had that FDA was turning down new drugs because there were other drugs that were nearly as effective or as effective in a disease class.

          That is a bad decision.  Let me tell you why.  One, it enforces monopoly.  One of the good things we have is that we have got a lot of companies competing in the same disease class, trying to find a lot of drugs that serve patients in that area, and the idea that they are all competing and that they are offering drugs in the same disease class from whom doctors and patients can choose, that is good for patients.  It is bad for patients when you only got one drug in a disease class.  That is a monopoly, and that is not going to lead to the kind of marketplace competition that leads to hopefully lower prices and more affordability in drugs.

          Secondly, I don't have to preach this to people in this room ‑‑ I think you well know it ‑‑ that all drugs operate very differently in the human body, and they all have different side effects for the human body.  You may have two or three drugs that are in a disease class that are very useful for some patients, that are very unuseful for another.

          I was surprised to learn more about that when I went through cancer treatments, how when they read me the list of all the side effects, I said, "My God, I don't want to do this."  Listen to some of the ads on television that recite all the side effects.  Why would I take that drug?  They don't all happen.  They happen for some.  Some happen for others.  Most of the patients who took the drugs I took lost hair.  I grew hair.  I am trying to figure that out.  Maybe it is in my Cajun heritage or something.  I don't know.  But the bottom line is you can't make a judgment that you ever have enough drugs in a class until you got 100 percent of the patients in that class getting the best treatment from those drugs.

          What traditionally happens is an evolution in discovery.  We discover a drug that is good for 10, 20, 30 percent of the patients in a class.  Then another company comes out with a slightly different version of the drug, but it takes care of another 10 or 20 percent that were not serviced by the first drug or couldn't take it because of the side effects, and then we come up with another one in the class that takes care of the next 20 or 30 percent.  Eventually, you get to 80, 90 percent of the patients who have a drug that works for them, that they can tolerate, and then the next effort in evolution is to find out how to take that drug in a pill instead of an infusion, how to take it once a month instead of once every three hours.  You get user friendliness innovations in drugs, and to forget those things is really to harm patients.

          I will be very specific to you.  When you build a drug that, for example, an alcoholic has to take every day, you are probably not going to help that fellow that way.  They are going to forget to take it, and then they are going to take a drink instead.  But if you build a drug that they can take every week and tolerate or every month and tolerate, you can really go after alcoholism in that patient, and that is repeated across the spectrum of diseases.

          So keep that in kind when you talk about that.  Do you ever have enough choices when it comes to getting the right medicine for the right patient?  Of course, you reach a point at some point.  When you got 100 percent covered, it should be there, but should you stop when you are just taking care of 50 percent of the patients of a class and say we have got enough generic drugs available, we don't need a new drug?  Ask the other 50 percent.

          I will give you another great example.  Xigris is a drug made by Lilly for sepsis.  It will take care of a third of the patients with sepsis.  It doesn't work for the other two‑thirds.  We don't know why.  One day, we will find out, but in the meantime, if somebody comes up with a drug that works for another third or another third, God bless them.  It will save some lives.  Is it satisfactory that Xigris is around?  No.  We still need to take care of the other two‑thirds.

          Thank you very much.

          Ladies and gentlemen, let me bring in the star performer here.  I want to hear from him.

          MR. TAUZIN:  He has really brought the institution into the modern age.

          He has obviously got a huge background himself in radiology and medicine.  He spent his career in clinical and scientific administrative leadership.  He was at Johns Hopkins I know where I got my surgery, that doctor and where the brilliant work they did.  He is credited with developing the imaging methods used for diagnosing cancer and cardiovascular disease.  He is one of the world's premier experts in magnetic resonance, the MRIs.  He has extended the role of the MRI in taking snapshots of gross anatomy, visualizing how the body works at the molecular level, not just the gross level, and he has pioneered magnetic tagging which is a non‑invasive method of watching the heart in action, which is pretty cool, and he is renown for refining an imagine technique called ‑‑ and this is a tough one ‑‑ computer tomographic densitometry ‑‑ is that pretty close? ‑‑ which really helps designate or discriminate between non‑cancerous and cancerous nodules in the lung.  How cool is that, that you can tell that just by imaging.

          He has done some amazing work.  So he is a visionary.  His role is seeing things more clearly and allowing science to see things more clearly.  Isn't that a beautiful metaphor for what NIH does and for what Dr. Zerhouni does?  His work, his background is in helping us see through science what disease looks like and how we can find an answer to it.  He is a champion, a pioneer, a warrior in the fight against disease, running the institution that helps us all find those answers.

          Please welcome Dr. Zerhouni.

          [Applause.]

                     Keynote Address

          DR. ZERHOUNI:  Well, thank you, Billy, and thank you, Mary, for having me today.  I always marvel, really marvel about the ability of Billy to weave together in the same speech the most humane consideration about patients and himself and the human dimension of what we do with the highest strategic insights and how to really crystallize together the hope of research and the delivery of the research results to the people.

          I really cherish the moments we worked together.  You were a great champion of the doubling of the NIH when I became director.  You remember the 2001, 2002, 2003 were the last three years, and there were lost of questions then because the Federal budget had gone into deficit.

          I remember in 2002 when I became director, something unique in the history of the budget committees of Congress.  I was called to come back and testify, basically after the fiscal year was already ongoing, and in a testimony that I had to give about why should we not slow down the doubling of the NIH budget, and in 2002 ‑‑ this is a little secret history ‑‑ there was a proposal to slow it down to about 5 or 6 percent a year.  I would say that at that time, his committee and many Members of Congress came forward and said, "No.  We committed," and the President himself said, "We committed to finishing the doubling," and they finished the doubling.  It was a 16.5‑percent year, the last good year of my tenure.

          [Laughter.]

          MS. WOOLLEY:  So far.

          DR. ZERHOUNI:  So far.

          But it has been an exciting, exciting time, and I think I could not really agree more with what Billy said, and that is, never underestimate the power of innovation and imagination because if you do you are going to miss what I think we are all about.  We are not the National Institutes of Health.  We are the National Institutes of Hope to millions of patients who are really counting on that, and at the end of the day, after five and a half years in this job where I have had pretty much a unique perspective about what is really being done both here in the United States and worldwide in medical research and knowing the state of the research, I come with the absolute conclusion that unless we speed up our understanding of biological systems and unless we do that and succeed at it, the risk is that 25 years from now, we will practice medicine in the same context, with the same concepts that we do today, and that will be an unmitigated disaster for mankind, not just for the United States.

          There is no doubt that life sciences and the breakthroughs that we want and we need in life sciences are going to be a determinate for the history of modern civilization, just like physical sciences in the 20th century.  Make no mistake about it.  It is the absolute frontier of knowledge that will determine whether or not we are successful in health, but also whether or not we are successful in environmental remediation, environmental strategies, and creating alternative sources of energy.

          The evolution of 4 billion years has developed systems which we do not yet understand, and yet, they contain the solution to many of the ills that we as a civilization are confronted with.

          So what I would like to do is share with you some of the strategic visions.  I am going to try to emulate Billy here and try to really give you the major forces that are driving both our thinking at NIH and where I think we fit in the total picture because it is a total picture.  You cannot succeed from any one component of the system ‑‑ innovation, pharmaceutical, biotech, government, academic ‑‑ without understanding the total system.

          So let me just start by saying that transforming health and fulfilling the promise of research is going to require new thoughts, new concepts, new methods.  What we have today is just not efficient enough, and I think you heard it from my friend.

          The question there is how, how do you go forward, what is the shape of things to come, and how do you then strategize the total investment of the NIH budget to advance that.

          First, I think we have to look at the track record and where we have been, and there is no doubt that the investment in biomedical research has paid off enormously.  I think you just heard the statistics about cancer death in the United States.  This was starting in 1991, '92.  There was a trend in the rate, but people said, "That is just a fluke, that is just people stopping smoking which is a major reason for that, but in absolute numbers, cancer deaths are not going do."  Well, for the past three years, they have.  Not only they have, but they have gone down in an accelerating rate, and there are many reasons for it.  Much of it is due to our early screening and prevention strategies, but a lot of it is also due to advances in our understanding of the disease process.

          What is the investment in this war on cancer that we have conducted now for about 30 years as the Cancer Act, 1971?  About $9 per American per year.

          If you look at heart disease, we have had a 60‑percent drop in mortality.  In fact, if we had not had the advances we have witnessed over the past 30 years, there would be 1.3 million people dying abruptly today, instead of today we have 500,000, 500,000 too much, but think about the economic impact of saving the lives of so many young people who then remain productive.

          Economists have shown that this value per year is anywhere between 1.5‑ and $2.5 trillion; investment, $4 per American per year.  So the investment you as an individual have made in the past 30 years from your own pocket to not have the risk of acute heart failure and heart disease, coronary heart disease, has been about that much.

          There is no doubt that return is there.  If you look at disability, it is obvious that we are aging, but also, we are living longer younger because the disability rates have been dropping for the past 20 years to about 30 percent for Americans over the age of 65.  What that means is that we have made advances that are able to maintain the quality of life for much longer with a life expectancy that has gone up by one year every five years.  The total NIH investment over the past 30 years averaged, per American for all of this, $44 per American per year.

          So it is not like we are talking about breaking the bank here.  We are really talking about probably the best ratio between investment and return that I can think of in terms of government activities.

          So let me just say that the track record of biomedical research and research in general has always been at the core of the advances of this country and in maintaining its preeminence, and I think the public knows that through Mary's pose.  There is a sense that unless you advance in your knowledge of the physical world, it is very hard for you to implement policies that will be of service to the entire nation, but also to the world.

          And it is what I said about, for example, the telephone.  If you had frozen telephone innovation 50 years after the beginning of the research on the telephone, remember that when Alexander Graham Bell proposed the telephone, he was turned down.  Western Union turned him down.  They thought the telegraph was going to be the answer to that.  Everybody predicted that it would be eight people who could afford that telephone.  Fifty years later, this is 50 years later now.  This is about the same amount of length that I am describing here, 50 years of molecular research that we have done at the NIH, 50 years hence is about 1925, 1930.  Imagine that some smart person said, "You know, it is too expensive, this telephone."  At that time, you had the connectors, and it cost you about $75 in 1930 dollars to make a one‑minute phone call to Europe.  $75 then is about $1,000 a minute today.  Suppose we had come in and said, "You know, this is going to break the bank.  This telephone is crazy.  Why do we need to talk to each other?  Let's stop this innovation.  Let's not have it."  That is exactly the conversation we are having here.  Let's not make a mistake.  This is fundamentally what is being discussed, the freezing of innovation for years and years to come, and I think it is clear that if we don't respond to this in a very clear way, the picture of having computers and then better communications and then cell phones that everyone can get in the middle of India ‑‑ I was just in India ‑‑ in the middle of India where there is absolutely nothing, everybody has a cell phone.  So Graham Bell was absolutely a visionary, but more importantly, we did not stop the innovation.  That is the key to this message.

          So we have made advances.  There is no question that we have funded scientists across the U.S.  If you look at the productivity of this, there has been between 1998 and 2004, 3,114 new technologies that have been brought to market.  What that means is that they have been marketed, licensed.  Somebody has said these are valuable enough to spend dollars on.  This had a huge impact on biotechnology with the whole biotechnology industry created.

          Now, having said that, let's just look at the other side which is the challenge.  I don't believe that we are making the progress and the speed and effectiveness and productivity that I would hope to see, clearly.

          So, having said that, everybody can say that, public polls included, and say we are not making progress fast enough, and it's like, "Okay.  So what do you propose?  Do you have a better idea?"

          I had a talk one time with some advocates who are famous, who have developed computer systems and understand a lot about engineering, computer systems, and software and so on, and one of them was telling me how they felt absolutely outraged that NIH had not yet developed an HIV vaccine, and that every time we try, it fails, and we go on for 20 years and it didn't work.  It worked for drugs, and yet in 1985, everybody predicted that a vaccine would work and drugs would not, and the opposite has happened.

          I was flabbergasted that someone so experienced, so successful in life would tell me that, and I turned back, and I said, "You know, when I use your computers, I have viruses and bugs in my software that you have not been able to eliminate.  I am so worried about the viruses that come from the system that you designed.  I have to figure out the virus from the system that was designed by God knows how and when and has evolved for 4 billion years."  So the difficulty should not be underestimated.

          There is a tendency to underestimate the difficulty of biomedical research and poopoo it and say, "If we just had better this or better that, the disease processes would not impact us as much as they are," and there is a good reason to be prodded to make progress, but I think there is also a good reason to look analytically about where the challenges are and what we need to do about it.

          No doubt, biomedical health expenditures are going to be the dragon or is going to drive public policy, the growth of Medicare much higher than the GDP growth, and we are going to face a real challenge.  Biomedical research must be part of the answer.  We must help somehow find a way to deliver more effectively than we have.

          The cost of health care is going to reach $4.1 trillion.  It will double in 10 years.  No one can really sustain and afford that in any form, even if we improve the delivery system, and God knows how much we know that our delivery system is not as efficient as it could be.  Even if you did that, you still would have a problem.

          So some real breakthroughs, innovative breakthroughs are going to be needed, and that really needs to be understood in the concept of what are the real challenges we are facing.  The first and foremost is chronic diseases.  We have had a shift from acute to chronic diseases.  Eighty percent of our expenditures are in chronic diseases.  Of those, five conditions make up 80 percent of those expenses, and you know which they are.  Often today, the same patient may have multiple diseases at once.  So that even the concept of diseases and institutes that study this and not that starts to meld together at a time when there is scientific convergence as well between diseases and our understanding of the different diseases.

          Aging of the population, health disparities remain a problem both within countries and between countries.  I think emerging and reemerging infectious diseases are going to be a huge challenge.  They are reemerging for good reasons, because there is an unsettled situation worldwide in terms of human population and its relationship to its environment, and obviously, we are seeing also emerging noncommunicable diseases, obesity being the primary example, but we are seeing a rise in mental health conditions, for example, that will reduce, in fact, the quality of life in one of the most important populations, 25 to 44, worldwide.  This is actually one of the fastest rising cause of disability worldwide, as identified by the WHO.

          So obesity clearly is the shape of things to come.  We do not wish to see this happen.  It is obvious that we have to respond to these rising threats.

          So these major factors will force a transformation, whether we like it or not, and I always remind myself of Billy when he was in Congress always tried to build bridges, I would say, and maybe a transvesticrat is what you need to do that, but he did it.

          The thing that was interesting to me is that these factors were there.  They are there today.  They are going to be there, the Medicare cost, the entitlement cost, the pressure on discretionary budgets, the choices you have to make.  Clearly, everybody knows that whether we like it or not, whether it be a revolution or a good evolution, something has to change, not just something, but a lot of things have to change, and I think when you look at that, you need to have some sort of driving strategy.

          The driving strategy that I have tried to come to is this one, and that is that we need to change the paradigm of health care.  You have heard it, and people say it in different ways, but I have been talking about this since 2003 where, in fact, a very simple econometric analysis will tell you that today, as we know it, there are very few diseases that occur overnight that you could not predict were there before.  Infectious diseases, you catch a bug, that is not predictable, but most of the other diseases, we find markers, biological markers, years before the disease strikes, so that you can see that there is a preclinical phase, the phase that is existing in our population that we do not detect, and the disease becomes obvious.  You have high blood pressure or high cholesterol, and we start to take care of that, but more often than not, the patients come at the last stage.

          Then if you look at the cost curve, in our system, there is an exponential growth as you wait in terms of intervention.  So, if you can catch hypertension early at age 30, it is basically a dollar a day, go to exercise and diet and you will fix it.  If you don't catch it, it is $10,000.  If the patient has a real infarction and you need to treat that, it is $100,000 for a bypass, and if that fails, you need to go to a transplant, a million dollars.  So it is 1, 10, 100, 1,000.  You see the growth is really fast.

          So there is no doubt that if you look at the strategy that we have been following because of our lack of knowledge primarily, it is the curative treatment.  It is the worst part of the curve to intervene.

          Over the past 30 years, the progress that I have described to you has been primarily related to our ability to do symptom management, understanding that a symptom drives a particular disease process like high cholesterol or smoking or high blood pressure, and then we treat that symptom.  So we manage the symptom down, and sure enough, there is a result that you see in the fact that by moving the curve back, you are able to achieve some cost savings, both in terms of disability, quality of life, and cost, real dollars, but at the end of the day, you realize that if this is the model, that there is a long preclinical phase, that you don't develop Alzheimer's disease overnight, that you do it 25 years before diabetes or Parkinson's disease, then you need to put your research at the very early stages of that disease, and that is what we call "molecular preemption."

          In other words, you need to understand the molecular pathways that are really determinant in this disease in that individual and intervene at that point.  Well, let me tell you, the bad news is we don't have that knowledge.  The good news is we have tools that are emerging that tell me that we have never had better opportunities to have that knowledge than we do today.

          So it is the simple, straightforward approach to go from a curative paradigm to a preemptive paradigm.  It will require quite a bit of research, quite a bit of development, and I show you this in a real disease process.

          This is rheumatoid arthritis.  When you look at this hand, you can see what, in fact, has happened.  We did not know the immunoresponses that were involved and the damage to joints in rheumatoid arthritis.  So we had symptomatic treatments that just took care of the pain, but the hands would end up being deformed, as you see on the right‑hand side.

          With the new class of antirheumatic drugs, the TNF‑alpha inhibitors and specific agents that were active, the progression has been dramatically slowed and in some cases actually reversed.  It is unbelievable.  This had never happened in a disease process, but in the past two years, we have discovered three genes, and I can tell you all the efforts we are making right now are focused on these three genes.  It is almost like you have lamp posts that are lighting up, and all your researchers are going there and looking at that, and the hope is that you will be able to intervene, no longer after joint damage has started, but before joint damage started.

          That is the picture of the future.  This is what we call P4 medicine or Four P's of medicine.  First and foremost, you need to be more predictive.  If you have no knowledge of the behavior of a biological system, all of the talk we have about side effects or personalized medicine, when we say is that going to destroy the business model of PhRMA, maybe yes, maybe not.  Why not?  Because you could have personalized approaches that affect different populations.  One molecule could be at play with different disease processes.

          The example is Avastin being used not in colon cancer, but in your particular condition, or Avastin being used by a thermologist for macular degeneration today, same molecule, three different diseases, and it is something that may happen, but it will not happen unless we have an understanding, predictive understanding of what is going on.

          This means also personalized preemption.  What is the difference between prevention and personalized preemption?  The difference is that if I today give statin drugs to 100 million people, I know statistically that only 10‑ to 15 million of those will eventually develop a heart attack.  I am using statins in 85 percent of that population with not a real shred of strong evidence that that patient in that disease will suffer.

          On the other hand, if I knew the 15 percent that did, I would go after those, and then instead of treating 100 million because they have insurance, I will treat 15 million times 100 worldwide because I know those are the ones at risk.  That is the difference between general prevention and personalized preemption, much more cost effective and at the same time much more productive in terms of being able to have the health impact that you need.

          Then you need to develop preemption.  A cancer vaccine this past year on cervical cancer is a good example of that, and the fourth P is that you will not be able to deliver that medicine if it succeeds in any way, shape or form without a complete reform of the health care delivery system because patients will not be as sick or will not be sick at all.  They will not be patients.  They will be normal, and because of that, you will have to redeploy the way we pay for and we encourage people to and how we train our health care professionals to deliver this care.

          Having said that, let me tell you it sounds like a great idea, but what is the scientific challenge?  I am going to try to crystallize it because, at the end of the day, we can make very long speeches about what is happening in different diseases and different approaches to disease, but at the end of the day, I have come to the conclusion that there is one fundamental challenge, and the challenge is as follows.

          If you look on the left‑hand side of the slide, what you are seeing there is just one little part of a response pattern for a cell that has been damaged, either by x‑rays or ultraviolet light or an infection, whatever it is.  It seems like the cell responded in a very prototypical way, except that in this case, you find over 150 molecules that seem to be involved and interrelated in how the cell responds.  That is 150.

          Now, when I was Dean of Research at Johns Hopkins, we were expecting that there would be about 140,000 genes in the Human Genome, and then it was 60,000 and then 40,000 and now 25,000.  We know there are 25,000 genes.  We also know that there is about 300,000 proteins that are coded by this genome, and the forms of these proteins are about three times greater, to about a million.  So what I am showing you here is 150 of a million different kinds of proteins interacting or molecules interacting.  That is the challenge.

          The challenge, we didn't know that in 1971.  In 1971, there was a sense that cancer was one disease that you could find the magic bullet, that perhaps Alzheimer's is one disease that you will find a magic bullet.  This concept is just what is misleading.  I don't think the reality is that simple.  It is more complex, and we need to realize it, and we need to admit with humility that we may not know 90 percent of what we need to know.  We may know 10 percent of what we need to know when you look at the complexity that has been unraveled over the past 20 years in terms of the advances we have made, but that doesn't mean we will not be able to overcome that.  How do we overcome that?

          So, on the right‑hand side of the slide I am showing you, a chip, and I betray my scientific background in physics and engineering and mathematics.  That is pretty much where I come from.  I am a systems person.  When you look at that chip, let me just get you into a thought experiment for a second.

          Let's suppose you are a martian.  You are coming from Mars, and you are a scientist.  You have never been on earth before, and one of your researchers brings you this chip out of the computer that we are using today and says, "You know, this civilization, they were using that chip.  I don't know what that is.  I don't know what it does."  Well, you look at it and you say, "Well, let's study it."  How would you study it?

          First, you would study the components of the chip, the transistor, and the resistance and whatever else there is, and the wires, but at some point, even if you had that knowledge, you wouldn't know that that chip was used to make a PowerPoint presentation by the director of NIH.  You don't know that by looking at that.  You would need another class of research strategies to be able to do this, and this is what I mean.

          I said over the past 50 years, science has been involved in looking at the components of biological system,s just like you would look at the components of a newly discovered integrated circuit, but we do not understand who they are all interrelated and how they interact in health or disease.  That is, in one word, what I consider the core challenge, the central challenge of life sciences in this century.

          So we need to move from the hardware of life, which has been the sort of historical period we have gone through over the past 50, 60 years.  We are still in there.  We are still going to do that.  We don't understand all of the components in cell biology, but we are getting there, to the software of life component where we need to understand molecular pathways in the regulation, their interaction in health and disease.

          Is there hope to do that?  Yes.  I think one of the first things that I was convinced of was we could not advance scientifically unless we had a different roadmap, a different conceptual understanding of what needed to be done to advance the science, and we did and came up with these three‑legged roadmap for medical research at the NIH.

          One is what we call New Pathways to Discovery, which means what are the tools, what are the resources, how do we implement the breakthroughs to understand this complexity.

          The second is Research Teams of the Future.  Research is no longer something you can do in a small lab with two people and three pipettes.  You really need very powerful resources.  A $1,000 genome capability will be a huge breakthrough for us, proteinomics capabilities, analytical capabilities, computers.  You need people to come together in ways they have not come together before.

          So my role at NIH has been to break those barriers between disciplinary fields, so that they can collaborate together.  We have created a new grant mechanism, so that scientists from physical sciences can work with biological scientists and researchers in cancer, if need be.  That is the key to it.

          In a period of rapid innovation, the most important thing you need to do as a leader is remove the barriers to interactions, whether it be regulatory barriers or be because we grant things in a certain bureaucratic way or because we have no vision of where it needs to be, and to me, that is the second leg of this roadmap.  It forces the agency to try new things that would not have been tried otherwise.

          The third one is something that is right in line with the surveys, and that is that people do not participate in medical research to the extent that we need them to, and that means we have to change the way academic institutions interact with industry, interact with government, to be able to make sure that patients do get asked to participate.

          We were always criticized at one point and said, "Well, you don't have enough participation," except for the cancer patients who participated at a high rate.  Parkinson's disease patients don't participate.  Why?  Because they are not asked.  When you do the surveys, you find that the great majority do not get asked to participate.  That means we need a reengineering of our clinical research engine.  We cannot keep doing what we have been doing at the cost we have been doing it and ultimately end up with the rate of failure that we are ending up with.  So that is the third leg of the vision, if you will.

          So let me just give you one example of how this vision, if you will, is playing out in real terms.  When I became director, we knew the Human Genome was going to be completed, but it was very important not to stop, even though the budgets were flattening, not to stop the exploitation of that.  It is not enough to have one sequence.  You really need to have the sequence of many, many different people, and so even though it was very expensive, we went ahead and created the HapMap with collaborations around the world with the leadership of Francis Collins.

          What was very interesting is that that advance was very controversial.  A lot of people criticized us for it.  They said, "That is not part of what you should do, and you should let people come up with their own small grants and ideas," but unless you have that tool, your own researchers get stymied.  They would not develop insights because they would know that they could not really test them.

          So this has made it possible, and I am just going to show you why I believe that we have never seen as many opportunities in science as we have in this decade.

          In 2000, there was one gene that I knew about that had something to do with diabetes, PPAR gama.  It is an enzyme.  I was waiting for the discoveries.  In 2001, there were two discoveries that were made that related to Crohn's disease, inflammatory bowel disease, two genes.

          When I became NIH director, I kept asking.  I said, "Please tell me what is happening that will tell us that we are delivering on our doubling."  The legislators were every day asking me, "We have doubled your budget.  What have we gotten for it?"  So I really was around the NIH asking them to show me what the breakthroughs were.

          2002, none.  2003, one major one, which was the discovery of a master gene in diabetes.  2004, nothing.  It is hard to be NIH director and report nothing, and then 2005, age‑related macular degeneration, all of a sudden, there was a spat of discovery in April of 2005.  Remember that month because it came within two weeks of each other, and they discovered basically two genes and then a third one that showed that macular degeneration was actually an inflammatory disease and not a degenerative disease, as we called it, so, again, a complete rethinking of the disease process.

          2006, it gets better, five.  Prostate cancer, all of a sudden, there is a possible discovery about why African Americans have a high rate of cancer.

          2007, the first six months of 2007, an enormous influx of new discoveries.  The second six months, look at the diseases where we have made what I call lighting up lamp posts where we didn't know there was any discovery to be made before, not that those discoveries are going to be the key, but I have to tell you between 2001 and 2002 where I can count on the fingers on my hand, the discoveries that relate to common diseases now.  I am not talking about rare diseases, and then you have this, and actually, it continued.

          This is 2007.  This is the sort of harvest of what we have been saying all along, that investment at the basic level is key to making this progress.

          So, for example, multiple sclerosis, there has not been a factor discovered in multiple sclerosis for 30 years.  Until the HLA discovery of the '70s, nothing had been discovered, and all of a sudden, two, then childhood and adult obesity and then host control of HIV‑1, we are finding why some people are resistant to HIV, and then Type 1 diabetes and on and on.  This is obviously an enormous harvest, but an enormous harvest also posted some logistical problems, how are you going to study all of this, because remember an association is not a causation.  We need to really prove this.

          So we are really coming to a point where I as a director find that we have enormous opportunities, but enormous needs at the same time to really make that progress.  So it is a long and treacherous road.  It is not going to be overnight, but ultimately, what we are doing will allow us to develop the tools to understand that chip that I was telling you about at the software level, not at the component level, and that is where we are reengineering in the clinical research.

          We have basically phased out the 55‑year‑old clinical research system of the United States, which was based on general clinical research centers, and phased in a new, completely different system called the Clinical and Translational Science Awards, and it has been received with a lot of enthusiasm.  Why?  Because for the first time, it allows you to train a next generation with completely novel methodologies, completely different ways of looking at a human population or human samples.  This is something that to me is what the agency should do.

          It was difficult.  It was a lot of political pushback because you are changing something that has been three for 60 years, but ultimately, 24 institutions bought into it, the best institutions, but they agreed to work in a different way.  They will collaborate in an open environment with all of the partners that we need to have, and this is really my message here.

          There is an ecosystem of science and biotechnology.  You cannot look at any one actor and think that that actor will make it happen.  Public organizations, patient organizations, universities, Congress, FDA, all of this is an ecosystem that is envied in the rest of the world.  Everywhere I go, I get asked about this system.

          So preserving this and the energy of that will require proactive steps and a balanced national portfolio of research, and what I mean by that is if you look at what NIH spends, it is like a pyramid.  We spend 55 to 60 percent of our research on basic research, and the reason for that is because no one can sustain 30 years of basic research in something that may or may not work, except the government, and 40 percent is in translational clinical research, especially rare diseases or diseases where there hasn't been really fundamental progress.

          Industry spends more than we do, $59 billion.  You are double our size.  In fact, when we doubled, industry almost quadrupled since 1991, and that may be a reflection of the productivity issue, that $1 billion per drug, but it also shows that we do most of the R and industry does most of the D, and the two together is the balanced portfolio that I talk about.  So you never can look at one at the exclusion of the other, and that is why we believe that there is a strategy we need to follow, and that is a strategy of defining what I call a precompetitive world where industry, academia, government need to build databases of knowledge that are available, openly available, that we don't just restrain in terms of access to it.

          For biomarkers, for example, biomarkers will be key to progress, and I think you are going to hear more during this program.  Having databases where the scientific information is not hidden, but made open to the public, so that when we do a gene sequence ‑‑ and we are going to do more and more and more ‑‑ that it is available to companies, to scientific institutions, academia, all of it, because it is not competitive.

          The complexity of what we are dealing with is such that I don't believe that it is going to be one magic bullet for one disease at a time.  It is going to be a network of different approaches that will be balanced according to individual variability.  You cannot approach that unless you build an infrastructure of information that allows exchanges, very quick exchanges, so you don't spend your time duplicating something, as someone else has already done and already wasted millions of dollars on and knows it is not working.

          So NIH wants to be that glue of information and the broker, if you will, and last but not least, despite all of my entreaties, if you will, despite the sense that I have that we are at the edge of a real revolution, that we have made progress, that only research can really bring the breakthroughs, what is also important is I don't think that we can just rest on our laurels and things are going to happen just by itself.  We need to encourage new pioneers, new investigators, new scientists thinking differently, because we are just blocked and stuck in the way of thinking which I think can only be broken by pioneering young scientists encouraged to come into the system.  Right now, we are discouraging them.  If they think that this is not a career choice for them, the 300,000 scientists that we have, the average age has increased by 10 years.

          If you look at the curves, we will have more scientists funded that are older than 65 than scientists that are younger than 35 in 10 to 15 years time.  This is not sustainable.

          So one of my passions is to take money from existing programs and putting it into what I call "new innovators," "new pioneer programs," "new pathways to independence," because trust me, new ideas come from people who have not been indoctrinated in old ideas.

          So the Pioneer Award Program is something that works.  I will give you one example which I like to cite.  This is Karl Deisseroth, who is an M.D., Ph.D. from Stanford, applied three times to NIH in the regular process and couldn't get funded.  Why?  Because he had this crazy idea of taking the human neuron, a neuron in the brain, and going to a discovery that was made in Germany in an algae.  This is a plant that had a receptor that changed colors when there was a certain wavelength of light, and he said, "You know, I am going to take that algae receptor.  I am going to mix it with a human ‑‑ mice neuron at the time, but my goal is to do it in human neurons by having sort of a genetic engineering technique, and I am going to be able to activate the neuron just with light.  So think of it, a series of brains, and you would create essentially a light‑activated brain.  How is that for an interesting idea?"  Well, turned down, turned down, turned down.

          So he came to this process, the Pioneer Award Program, which is a bold program, sort of a very, very far out idea, and he proposed this idea.  He said, "If I succeed, I will then use a jellyfish molecule that has been shown to turn off neurons."  Well, two years later, he is on the cover of Nature.  He is one of the most successful scientists.  He has been able to devise a system whereby through genetic engineering, you can make neurons anywhere in the brain on demand, to be activated or deactivated, and he sent me a movie of a worm, a C. elegans worm, which is sort of an experimental animal.  He said, "Doctor, let me show you the worm is going to go from right to left," and he flashed the lights, red‑blue, red‑blue, red‑blue, and the worm went right to left, and then he said, "I am going to make him reverse," and then he went blue‑red, blue‑red, blue‑red, and the worm reversed.  That is the only way you are going to be able to study the complexity of the brain, but you cannot think of studying that complexity unless you make breakthroughs like this.

          So the last message I have is the greatest risk for innovation is to stop taking risks, and this is my message.  We are at the edge of exciting times.  I cannot tell you how exciting they are, but we will have the duty of implementing and encouraging breakthroughs that you can I cannot describe today.

          Thank you very much.

          [Applause.]

          DR. ZERHOUNI:  I will be happy to take a few questions if you have time.

          MR. TAUZIN:  Doctor, what is the political implication of a worm that turns right or left, depending upon red or blue?

          [Laughter.]

          DR. ZERHOUNI:  I think it is a transvesticrat on demand.

          [Laughter.]

          DR. ZERHOUNI:  I would be happy to answer a few questions.  Yes, sir.

          ATTENDEE:  You have alluded to the health care system, as did Mr. Tauzin when he spoke, and I wanted to address that in terms of prevention and ask this question.

          We have an employer‑based private sector health care system in this country, and I have often asked myself this question as an economist.  What incentive does the employer have to offer preventive benefits when we have such a high turnover rate and mobility rate of the work force, when that person will benefit maybe 10 or 15 years in the future, when the average time with a firm is less than four years in this country?  So the small coffee shop on the corner, should they offer preventive benefits?  That person is going to be gone in three years working for a competitor who will reap those benefits.

          You did allude to the health care system, and so did Mr. Tauzin.  I ask you, perhaps we ought to examine our employer‑based and maybe do something with it.  It is a little bit out of your scientific area perhaps, but I know you think often of these issues as well.

          DR. ZERHOUNI:  Well, fundamentally, the question you are posing is to the extent that we know what to do that we didn't know in 1965 or before, how adaptable is our system to knowledge and that is developing.

          I mean, frankly, an employer didn't know 30 years ago that if you control hypertension and cholesterol, you are going to have a healthier patient, or diet.  That was not in the cards.

          On the other hand, I think this idea of life cycle management ‑‑ because when I talked about the fact that today, a disease should not be looked at as the last event, but as a process that takes 25 to 30 years, and you have to manage or recycle, I can see a world ‑‑ because remember we have aging of the population.  We have a 17 million qualified job deficit coming in front of us, nurses, doctors, software engineers, you name it.  There is not going to be a problem to employ and find qualified employees and employers are going to compete on the availability of employees, but you would want them to be healthy and not disabled and so on.

          First of all, you are posting a right problem, we are not managing the life cycle of the disease.  Our system is not designed for that.  It has never been designed for that.  There is a lot of gridlocking going on and a one‑size‑fits‑all approach.  I don't think that is the way the American system works.  It is usually you let the genius of the best practices sort of be tried, and it is very hard to do in our system, but at the end of the day, that issue of taking into account the total cycle of the disease is the only solution.

          Yes, sir.

          ATTENDEE:  [Inaudible.]

          DR. ZERHOUNI:  Yes.  It is actually interesting because prioritization is always multifactorial.  So we started, first and foremost, with the 10 most common diseases ‑‑ it makes sense, right? ‑‑ than the ones that have the largest impact, and then we said where are we in many, many other diseases in terms of having the populations that are already studied.

          Remember that the fundamental strategy is if you have a genome, that is not enough.  You need to understand the environment of that individual.  Right?  So, over time, you really need to study patient cohorts that have a particular disease over years and years and years, and we have 119 of those at the NIH.  The most famous one is the Framingham Study since the '50s.  So, by having these cohorts already available, we knew 5, 10 years ago that it would be really important to look at the DNA.  So we preserved the DNA.

          So a lot of these studies are done on populations that were already studied by our researchers before.  So the priority is done on, A, the target of opportunity.  You have the patients.  You have the ability to take a thousand patients, a thousand controls, collaborations with other countries.  In the diabetes research, we found 12 genes.  Do you remember I started with one in 2002?  We have 12 today.  It is all because of collaboration between the Welcome Trust, the NIH, and Finland because they have a high incidence of this.  So it is target of opportunity towards understanding population cohorts in the most common diseases that we can study practically in a context of having the material, having the ability to do those studies.

          MS. WOOLLEY:  Can you take one more?

          DR. ZERHOUNI:  Okay.

          ATTENDEE:  Without minimizing the challenges, the scientific challenges that you talked a bit about here, can you talk a little bit more about the cultural and institutional barriers to kind of speeding things up, building the kind of collaboration that you clearly see as necessary in breaking down these barriers, and what the NIH's role in doing that sort of thing is?

          DR. ZERHOUNI:  So you are pointing your finger on the most important thing.  Academia is portrayed as being very resistant to change, and I happen to disagree and agree at the same time.

          Let me give you an example of why.  If you look at the 100 top governments in the world in 1900 and if I asked you the question how many of them have survived intact in 2007, the answer is two, Britain and the U.S.  Every other government has gone through revolutions, destruction, rebirth.

          If you look at academic institutions and I ask you the same question, the top 100 universities in the year 1500 ‑‑ not 1900, but 1500 ‑‑ and I ask you the question of those, how many are currently active and viable, do you know what the number is?  75.  So there is the ability to adapt.  They don't adapt fast, but they do adapt.  It has arrived.  That survivability is the proof of adaptation.

          So what I think we need to do is a little bit of what I try to accomplish with this roadmap.  It is to sort of show where there is a consensus and there is a need, and then create the programs that incentivize that behavior, and it is happening.  I can tell you it is happening.

          There is a new department at Harvard that was created four years ago called the Department of Systems Biology.  Now, creating a new department at Harvard is harder than solving the Middle East crisis.

          [Laughter.]

          DR. ZERHOUNI:  So trust me, it is a revolutionary change.  I am seeing that happening around the country because we are encouraging also interdisciplinary research funding.  So, in these grants that we have generated, there is one reform that we have implemented, which is sort of under the radar.  People don't appreciate that, but we work with the Office of Science and Technology.  We had a lot of support from the White House.

          The President, with all the criticism that people get when they are in political life, has come five times to the NIH.  This is the President that has visited the most, and he helped us in changing the Federal rules that says that for any grant, there should be only one principal scientist investigator.  So we have changed the rules in the Federal Government to allow what we call multi‑principal investigators from different institutions being able to work on the same problem.  Before, it was impossible.  You had to give it to somebody at Harvard or Hopkins or in physics or in biology, but not all four.  Today, we can do that, and it is changing the behavior of institutions, but again, you are absolutely correct.  When you observe it, you feel like it is unchanging, but it does change.  It takes a generation almost, but it will happen.  It is happening.

          ATTENDEE:  [Inaudible.]

          DR. ZERHOUNI:  And the other thing that is driving it, too, it is like what we say in terms of institutions.  People in the field, scientists in the field, are noticing that science is converging, that to solve a problem today, you cannot just stick to your discipline.  You really have to use different approaches, different tools, different methods, and because science is converging, departmental structures are going to blow up, and they are going to be different than what they are today, and already, you are seeing that.  So there is a fundamental movement because of the problem being redefined and the approach being different.

          Thank you very much.

          MS. WOOLLEY:  Are you willing to do one more?  We had a lady who was overlooked.

          DR. ZERHOUNI:  I'm sorry.

          MS. WOOLLEY:  In the light, it is hard to see.

          ATTENDEE:  My question to you is regarding emerging and reemerging infections.  What do you think the NIH wants to see come out of that area?  What kind of research questions, I think it is better asked, that you would want to see derived out of that area?

          DR. ZERHOUNI:  Well, first of all, we need to have a global view of this issue, and let's face it, it is going to be probably the number‑one cause of public health risk worldwide and probably the number‑one cause of public instability worldwide, and we need to make investments at the global level.

          Actually, NIH has been probably one of the most proactive in this domain.  We quadrupled our investment globally, and we are now present in 110 countries.  You need scientific capacity in those countries who are collaborating with scientists across the world.

          In fact, the scientist that discovered SARS was an NIH‑funded scientists in Hong Kong, and we need to keep that going and collaborate with WHO and create a capacity for analysis and research in the fields where this whole issue can come up.

          By the way, it is not just in Africa that it happens.  It happens right here.  So the multidrug‑resistant Staph. aureus problem is not a problem of someone else's.  It is our problem, too.  It is happening right here.  So capacity‑building is one.

          The second is to build a complete understanding of the microbial world.  So the two major programs launched this year through the NIH roadmap, one is the Epigenome which is an understanding of regulations of the genome, and the other is the Microbiome, and the Microbiome is going to give us probably the best ID card for every organism that exists, both in ourselves and interacts with ourselves worldwide.  So you need to have the tools developed, and you need to really be strategic about that.

          The third is remember that we have an issue in terms of developing vaccines, antibiotics and so on, an issue that is economic for vaccines, and antibiotics is also becoming an economic issue, and we need to really be proactive in that.  So we are going to develop the capacity of understanding in a different way the immune response and the ability to interact with that.

          That is a comprehensive plan.  It is not one thing, but it is clearly something that is reemerging as a major issue, not just because of diseases of poor, but also because of resistance in our own environment, drug resistance.

          MS. WOOLLEY:  Thank you.

          [Applause.]

          MS. WOOLLEY:  Thank you so much, Elias.  Aren't we privileged to have you as the director of the National Institutes of Health, what extraordinary leadership, and your remarks about risk‑taking is something that we did a little of here this morning.  We took the risk of getting behind schedule just a few minutes in order that we all could benefit from this extraordinarily rich set of remarks and challenges that Dr. Zerhouni has provided.  So thank you for that, Elias.  Thank you for all you do.

          We are going to take a brief break and ask that you come right back here in 10 minutes, which would be five minutes to 11:00 on my watch.

          [Break.]

                         Panel 1

Transforming Health:  How Will Research Shape the Future?

          MS. COMER:  We are short‑circuiting introductions.  I was in television for 30 years, and that means it puts me somew