This time they went for 10 days. They flew to JFK and stayed in Brooklyn, where they enjoyed the hospitality of friends. Aunt Carol was away to her house in the countryside. Her house felt like their house for more than a week.

June is very hot, but the heat is only a prelude to the much higher temperatures and levels of humidity of July!

New York-Brooklyn

On our way to the boroughs near Brooklyn Bridge, we cross the lesser parts of this part of town. We ring Karin Levinson, who will provide the keys and show us around in our temporary house and the neighbourhood. Crossing Lafayette on Atlantic Street, we call her from our mobile phone. Where are you guys? She almost shouts in the phone. When she hears about our location, she really shouts ‘Close the windows, lock the doors’. The next ten days she takes some time off to guide us, tells stories about this part of town and at one point shows us from where on September 11 2002 she saw the second hijacked airplane crash into the other Twin Tower. She could see it right from the rooftop of her house.

The search for life went from New York to Baltimore and back. Then from New York to Cold Spring Harbour. Our final long trip went all the way to Boston. The final days we stayed in New York, mostly travelling by underground and on foot. We visit the Memorial Sloan Kettering Cancer Centre, to Rockefeller University and a number of departments founded and financed by the Ludwig Foundation.

We will meet 10 exceptional people. Four get added to our list on the fly, as we go about meeting all these remarkable people.

There is not one message this time. We meet ten characters willing to share their knowledge and experience, each with their own distinct passion. But not just passion! They all show absolute focus and admirable fortitude.

Bill Nelson

The first who we speak to is Bill Nelson. He invites us to sit down in his office with a broad smile. He is ready for the interview. We speak to a clinician who knows the forces of interest and the people that shape the landscape of oncology. His knowledge is almost encompassing.

The problem is certainly not that there are insufficient clinical trials taking place. It is a multi million-dollar business. The problem is what trials to single out as the most promising and relevant. Knowledge and access to relevant medical information is the key. What is required is more openness. Information of pathology is a key factor. Without it, assessment of treatment impact is insufficient. Getting the information accessible from one place, that is one of the biggest challenges. It can be done, but so far the engineering work that is required, still needs to be done. We lack infrastructure, he says.

Bill takes the way modern astronomy is done as example. In astronomy observations made from a multitude of points can quickly be combined. For example, if an exceptional cosmic event takes place and is registered in Chilli, it is possible to quickly check the observation from an observatory, say, in Australia

It is more fun to have impact than to be a star. That should drive the translational research, all the way from selecting trials to running them and making the right decisions along the way. We hear the clinician say what was earlier noted by the molecular biologist Ian Mattaj about biology: translational medicine will increasingly become an information science.

James Watson

This is the second time that we meet James Watson in Cold Spring Harbour. Jim is a real gentleman, albeit with strong opinions. He takes much time to show us around on the campus of Cold Spring Harbour Laboratories. After that he takes us out for lunch. His energy is unyielding. He is now 82, full of life. And only one objective counts: not being satisfied with marginal results. What counts is finding a treatment, prescribing a targeted drug that makes a big difference. To be able to do so, we must understand what a drug does or can do. 3 Months on a lifetime does not count. Saving a life for at least two years, that does count. But you need to know a lot more of each patient, biologically. This way, trials can be a lot faster and cheaper.

James the biologist finds most existing translational and clinical research too empirical. You take some medication; see whether it is not too toxic, then the question remaining is the dosage and the frequency and duration of deployment. And one does not have a clue what makes the substance effective.

Find the people who go for results. The people, who are deeply driven, often because of personal experiences, will go for the impact. And they are there, with excellent track records. I will make sure you meet two of them.

When we leave James promises us to call the office of Bob Weinberg, the next day in Boston. He wants us to meet Pier Paolo Pandolfi and Ragou Kuluri.

Bob Weinberg

What are the limiting steps? This is the basic question asked by Bob Weinberg. He receives us in style: he speaks fluent Dutch, takes us for a coffee to the restaurant in the Whitehead building and then invites us to his office. The office is filled with books; papers and the walls are filled with pictures from old students.

He points at one of the pictures. Look at that one he says. It is an informal meeting, no notes taken. People from all strands meet during a weekend. Young researchers, experienced scholars, people active in pharmacy, you name them, and they discuss research topics. Those kinds of meeting are crucial for creativity, he says. Superficially nothing comes out. But actually it is a breeding place for new developments. It is essential to keeping progress going in our field.

Bob warns of illusions. He wants to express a word of caution. Do understand, he says, that the biggest gains are yet to come from prevention!

And then what could have been a lecture begins. His seminal book Cancer Biology is opened and he points to s set of graphs. This is his point: for long some claimed results were actually illusions. Beware of those he says. Make sure you don’t sell illusions for progress. DON’T!

Bob looks at research from the perspective of Academia. He wants to shield researchers off, let people work on their data without pressing for publication. It is obvious that there is a tension between our wish to move fast and the desire to supervise young researchers and give them the time to develop their own ideas.

Despite his professional caution, he is frank about a number of good chances for certain progress. First, he says, get rid of the 60-year-old mouse xenographic model of predicting drug effects. It is based on implanting tumour tissue in mice. It is a very poor predictor of drug effects. There are much better ways of working. For example you implant two samples of a tumour in a specially prepared mice, having right genetic make up. By comparing effects, you can have way better data regarding the intended and unintended effects of a new drug or a combination of drugs. Do this properly, and you have results in five years!

It should be possible to make way better stratifications of morbidity versus mortality. Improved stratification will bring the number unnecessary operations down.

He expresses that the much-desired improved communication between lab and clinic is genuinely required, but he is extremely sceptical about actual improvements. He wants us to look very critically at the celebrated comprehensive cancer centre models that are heralded.

There is another limiting step, which is easily overlooked: recruitment. Right now getting the people who will eventually do the work, after many years of training, puts you off. This must change.

WORK on Lung cancer and Pancreatic cancer! These are the killer ones.

Pier Paolo Pandolfi

After meeting Bob Weinberg, we are transferred to Harvard Medical School: the Beth Israel Deaconess Hospital. First we meet Pier Paolo Pandolfi. Busy earning his third Nobel Prize, says his colleague Ragou who we are going to meet after him. In the evening we have supper with Pier Paolo and Ragou. It was James Watson who arranged it this way.

Pier Paolo is a discovery machine. He proudly explains about his recently published article in Nature. He proves that specific regions in the junk DNA (the parts of the DNA that were long thought to be junk, i.e. to have no meaning at all) do not code for proteins, but have a regulatory function at higher levels of the regulation of the growth of the cell. His discovery will vastly complicate the determination of the role of gene malfunctioning in generating cancer in the body. He is clear about this. BUT now that we know this, we can take it into account, which is a lot better than having no idea what perturbations form at the heart of the cancer that one tries to grasp.

And he is clear about something else. Yes, he believes he can make a huge difference regarding the treatment of cancer in the next ten years. Pier Paolo lost both parents due to cancer. No tears in his eyes. What we see is a man full of energy and ready for the next discovery.

About leadership in the lab, Pier Paolo thinks it is different from how it used to be. He thinks present day leaders have a more facilitating role. You don’t need generals. People work differently these days.

Ragou Kuluri

We leave Pier Paolo and enter Ragou’s lab. After listening to us for about 10 minutes, he starts an exposition that is both philosophical and specific on the finest details of molecular cancer biology at the same time. A sign on the wall says we are in the department of matrix biology!

First, we should learn to distinguish between clinical cancer and ‘just’ cancer. Most cancers, he says remain in the body, unnoticed. According to his view, which he is now finding supportive evidence for, many if not all people have cancer lesions, but the cancer usually does not become critical or malign. He wants to know what kind of environmental aspects, and interactions between the body environment and a tumour lead it to become malign and in some cases lethal.

Consider this, he says. Only a fraction of the tumour tissue is malignant. This portion may be less than 5%. Tumour tissue is not homogenous and a bigger portion may actually a way of the body to encapsulate the malign parts. Now, if you destroy the tumour as a whole, both the bad and the good parts, you may in fact worsen the situation. The body lost its means to defend itself against the uncontrolled growth of cells.

Here speaks a holist. He looks at the body as a system of interacting parts that together create a balance. By operating a person or treating a person with medicine it is possible to do more harm than good, in case the balance is broken. We need to find out more about this balance.

Lloyd Old

Lloyd Old meets us in the Zuckerman building, just opposite of the Memorial Sloan Kettering Hospital. His secretary invites us in.

Lloyd lives in New York and for him New York is the place to be. You have everything you need right here, he says; I don’t travel anymore these days and nor do I need to.

Otmar Wiestler from the Deutsche Krebs Forschungs Zentrum in Heidelberg introduced us to Lloyd Old, referring to him as his old mentor and now friend. Dressed in style, with a beautiful flower in front of the window right next to him, we are received with grace.

We get a detour through the last 20 years of research. His interest in immunology is obvious. He sees the alllogenic blood transplant of Peter as a success of an extreme form of immunotherapy.

Translational medicine is not the right concept for the practice of research and development of new therapies that we want to support. Lloyd argues that a different model is more appropriate. He speaks of clinical discovery, as the better model.

This is not facile idiom. In the later discussions the wording of Lloyd gets gradually more meaning. It is not appropriate any more to develop drugs first, to discover their clinical relevance not for mice but for real patients later. No! By taking the observation and tracing of the development of a tumour together with discovering what happens biologically, can we determine new uses for existing medicine and the need for developing new drugs.

The conversation takes a turn, half way. He acknowledges that we take our ambition very seriously. He repeats the phrase used by Otmar Wiestler: Do the right thing! He speaks of the 5 (maybe 7) P’s:

-       Take the right People.

-       Have a strong and robust Program.

-       Go for aggressive Patenting.

-       Make sure that Production trials are part of your program and you control these. Control phase 1, 2 and 3.

-       Anticipate on your results becoming part of Protocols. It must be integral in your clinical trial management.

-       Make sure that you have your Public relations in order.

Do the P’s right and you are in control. You should not be satisfied with less!

Charles Sawyers

Charles is serious about his work. All of the people we speak are. In his case determination is self-defining. He is co-developer of Gleevec, and he knows what he is talking about. He knows cancer research and drug development, from beginning to end. This is a doctor and a researcher in full.

Charles is making a number of points. You need teams of ten, he says. It should contain at least a pathologist, a surgeon, a medical oncologist or a haematologist, an endocrinologist and in many cases a neurologist. The fields you have to be absolute master of are pathology, endocrinology, imaging and DNA sequencing. Indeed, the availability of the best technology to support you is crucial.

The bottleneck that requires much attention is to train the right kind of professional. This is expensive. At least 5 years of lab experience is required, before clinicians can be left on their own as researchers, and be fully active researchers in a lab environment. In Sloan Kettering a limited group steps into a program of 2 years training. Often it stops for them at that point, and their main occupation remains clinical work. But, part of them go on and work for another 3 years in the lab. They will become the new generation of clinical researchers. They will do the clinical discovery in teams.

We scribble down some statements:

Know your enemy. It is gene mutation. Develop a drug that blocks this.

Sub classifies the patient to define the drug. You do this based on Molecular Profiling. Based on DNA. You need infrastructure and people to do this properly. This is crucial.

There are a lot of drugs but that we (still) don’t know how to use them.

Harold Varmus and Paul Nurse

The meeting with Harold and Paul is a rejoinder. Harold smiles and says, after a brief exposition of our plans; you guys have actually listened to us! It is said with some well-meant irony. He is positively surprised, and so is Paul. For us it is like getting clearance. We are in. We have passed an examination!

Harold is busy moving. He is newly appointed head of the NCI: the National Cancer Institute. While he is teasing us a little bit by saying that he just got Charles Sawyer, now you will see that Sloan Kettering will loose him to you after I’m gone…ha ha! Harold offers to be of service at any point, most likely behind the scenes. He has clout.

After Harold leaves, Paul takes over. He is doing his utmost best to support us. We will have to make a number of big decisions and he guides us through them. Who will take part in the committees? Who will bring in what? Is the time frame appropriate? What institutes should we commit? He is very precise and leaves no room for vagueness. And we make notes.

Paul moves to London, in December, to become president of the Royal Academy. He is eager to help and to become involved in a way that allows him to give maximum support, given all the restrictions he has to live and especially work with.

Richard O’Reilly

He does not say so, but this is Richard O’Reilly: He wants to know what he is doing with and to patients.

Richard is a Paediatric Cancer specialist, in particular of blood cancers. He starts by listening carefully. For almost ten minutes he only looks, almost stares at us.

Then it is his turn.

Over 70% of the children survive cancer.

Regarding paediatric cancer treatment and research, the US knows 3 excellent hospitals: Memorial Sloan Kettering Cancer Centre, St Judes and Dana Farber.

In St. Jude they invested 65 million dollar in defining the genome that is responsible for developing cancer in kids.

This is upbeat. Then he looks worried, and says that he finds it surprising how parents choose for their kids to participate in trials, which has helped paediatric cancer research forward. But as adults, who could be parents, people are very reluctant to participate in trials. This is a big problem! Germany is better; The Netherlands is also difficult…just like here.

1.3 million people in the USA develop cancer each year and only 65.000 of them are on a trial. ‘How does one change the mentality from patients and institutes that don’t want to participate on a trial into patients and institutes that join trials enthusiastically and make the results known to all the institutes in the world?’ People have to get the mentality of the trial!

Then an astounding fact is given. In Memorial Sloan Kettering they cure 65% of the children with Neuroblastoma, with Tumour Targeted Antibodies. Elsewhere Neuroblastoma is a killer. The Pharmaceutical Industry is not interested in the required medicine, therefore we make here. We don’t deliver it to other centres, we don’t have a scalable production facility. This is the only place where it is done!

Beware that all the successes with drugs that are at least 20 years around!

Give people direct access to all the trials. If no other option is available, do it virtually. In Europe you got the history, the infrastructure and the centres. GO!

Natural Killer Cells, T-Cell Depletion is hot at the MSKCC (O’Reilly also spoke about T-Cell Depletion in Amsterdam at the Pinedo prize).

He ends with a puzzle for us:

‘How do you rearrange things so that the light that’s in there comes out?’

Richard was fantastic.

People are pivotal!

We see right away that the next generation or researchers and leaders will also be a crowd of distinct characters. They will grow up in an environment in which information and communication devices dominate the scene. Yet they will show the same passion, the same focus and the same fortitude. All ten people we spoke to were in their own way fabulous. After ten days in New England, the three boys return to the Netherlands, as if reborn.

‘We have to go on with research but in a different way. Different and better. That’s our goal and that will solve our problem with cancer’. That was the most important message we got from them.

The British emphasized the setup of a new kind of hospital with diagnostics and treatments from the bed back to the laboratory and vice versa.  A new type of doctor is needed: a doctor-researcher with respect from the researchers as well as respect from the doctors.

The French spoke about a new culture. It’s not one researcher or doctor that’s the most important girl or boy. Cancer treatments are done in teams. Everybody plays its part and is of the same importance. That’s a mind shift!

The Germans advised us to set up a Biobank with all the details about patients and their treatments. Because of the individual nature of cancer you need patterns between thousands of patients to know how to treat each patient as an individual. A paradox but true!

12, 13 and 14th of january 2011 we bring all these beautiful scientists together in Amsterdam for the Conference Understanding Life! They will discuss all the subjects that are spoken of above and will agree upon the Programme Understanding Life! This programme is written by The Three Boys with input from all the scientists and doctors that they have spoken. It’s reviewed by them as well. We all work together to make cancer a disease that all the people around the globe can live with. With a good quality of life.

Our promise to the cancer patients and its loved ones is crystal clear: ‘ We will get cancer in control within 10 years.’

The Three Boys,

21st of July 2010.

Stephen worked with Lee Hartwell and James Watson. Both Nobelprize Laureates.

He started his second life after his period as a MD and PhD and after he heard of a father AND a son who had eye-tumor. He started Sage.

Sage Bionetworks is a young nonprofit research organization linking academic and commercial biomedical researchers through the Sage Commons; a progressive new paradigm for cooperation.

There is a great need to share all the information that is risen out of all the patients. That’s what Sage does.

Stephen Friend: ‘It’s never the data of the scientists! It’s the patients data.’ Statements like ‘It’s my study’ are outdated. You are never allowed to make money out of things that are from nature.

Our talk with Stephen was so inspiring on both sides that he decided to open an Amsterdam office of Sage next to Seatle, San Francisco and Beijing. Inspire2Live will support this initiative with great enthusiasm. All the patients data from Europe will be collected and made available this way. Patients will benefit from this initiative.

Paris 2010

We travel by Car. It is easy to park the car near St. Denis Station and to travel to the Quartier Latin by subway. Right in the middle of the Quartier the Marie Curie Centre can be found.

We are most gracefully received and soon we sit in a conference room with Daniel Louvard (Head of the Research Department of the Curie Institute), Sergio Roman-Roman (Head of the Translational Department), Francois Doz (Pediatric Oncologist), Jean Nicolas Munck (Head of the Hospital) and Olivier Aycard (Pedestrian Geneticist).

We introduce ourselves and within minutes after our introduction, Daniel takes us on a trip through the history of the Centre. Most remarkably it is Marie Curie herself who figures prominently in the presentation. With love and admiration he tells about her work and life and shows how her presence is still a source of inspiration and guidance.

When one visits a number of countries in a row, one feels tempted to search for distinctions. What distinguished these engaged people from all other groups that we met? Let us be frank. Daniels views and the contributions of his team resonate well with our findings so far. There is a committed and strong common understanding among the different dedicated researchers and clinicians that we meet.

What we find distinctive is Daniels insistence that creativity is essential. His presentation commemorates how creativity can survive and even thrive in an institutionalised world. And while one cannot tame creativity, one can organise creativity. Often Marie Curie is used as an example. Why did she make the connection between radioactivity and curing cancer? For her it must have been a leap in the dark or maybe a leap of faith, and yet looking back, it all seems so natural.

The rationale

Innovation springs from the interface between disciplines. In the case of cancer research, this is most certainly the case. This is true for translational medicine in particular. Here the research cannot rely on pre-existing routines.

What makes it all the more daunting –and challenging– is that the research does not consist of adapting existing protocols, but on making a series of disciplined choices. It should be clear that our rationale requires Comprehensive Cancer Research and Treatment Centres as drivers of the research. Why? In the sense, the answer is given most poignantly a few weeks after this meeting, by Otmar Wiestler, head of the Deutsche Krebs Forschungs Zentrum: (because) it is easy to cure a mouse, and very difficult to treat a human patient. And as Daniel Louvard and his colleagues are keen to point this out, without the reference to the mice: research, discovery and invention will be proven right at the end point of translation: the patient.

The proof of the pudding is in the eating. This is most certainly true for translational medicine. It is at the site of the patient that the value of the work and cooperative efforts of several disciplines is proven.

Hence the rationale of setting up a network of comprehensive cancer centres: the patient needs the lab, and the lab needs the patient. And it is this ongoing and painstaking process of information flowing back and forth between laboratory and patient that will ultimately result in major improvement of cancer treatment.

The culture

At Marie Curie, many disciplines work together closely. All research is joint research and the question who is the main author often does not make sense. It has become customary to have an alphabetical list of authors. It is more important to focus on what some author has contributed, than to rank their relative importance.

So the research culture is one of cooperation and competition. Both are crucial. But one element of the culture is, curiously enough, easily forgotten: the patient. He and she also must have a voice in the debate. It is from their experience, from their fate, that the network medical biologists, bio-informaticians, lab researchers, clinicians and blends of these, learn to know what works.

The culture question is pivotal. The willingness to share, listen, accept and give criticism, listen to an exegeses of an expert on a seemingly unrelated topic will determine the success that the patient will profit from.

The ingredients

We are the ingredients, you are the cooks, says Daniel Louvard. Being Dutch, we are flattered. The French kitchen is superior to ours, no doubt about that. But his point is clear. Novel research requires disciplined creativity. Lasting change in cancer treatment requires committed attention and the willingness to test new ideas, incorporate new technologies, stick to common goals, drop research line which proves unsuccessful, or redundant. Committed organisers and people willing to spend large portions of their working lives on meeting with, listening to and sometimes directing researchers, clinicians and their institutions are also needed. The Curie Institute works with young scientists. An average age of 34! Young people because: ‘They take risks and dare to make mistakes. They are naïve and creative. And moreover; you have to be in the lab on a daily basis for science work. Older scientists travel a lot and can’t be in the lab for to long’.

When we leave we see something that elevates all of us: the passion to look for and go for better treatment of cancer for all of us who get cancer.

This was explicitly the message they got from Pier Paolo Pandolfi and Raghu Kalluri. Both MD’s and PhD’s from Harvard Medical School in Boston. They are young and enthousiastic scientists who are certain about the possibility of curing cancer. They are very much influenced by James Watson. In his laboratory in Cold Spring Harbor The Three Boys had a wonderful 4 hour talk and lunch with this grandfather of the Double Helix: the structure of DNA that was discovered by him and got him the Nobelprize. James Watson arranged the meeting with Pandolfi and Kalluri and gave The Three Boys the assignment to cure cancer.

Bob Weinberg who is the director of MIT in Boston and delivers brillant science that results in new and better treatments for cancer was very enthousiastic about our initiative. He will attend the conference Understanding Life! in Amsterdam on the 12, 13 and 14th of january 2011 and will also advise the programme plan that will be written the next months. This programme plan which is also called Understanding Life! contains projects for getting cancer in control. First getting it in control then cure it.

In Baltimore was a good talk with Bill Nelson from the Johns Hopkins. One of the best hospitals from the USA. Mr Nelson is a specialist in bringing science to the bed and back. He gave some good new ideas on diagnostics based on DNA sequencing. Probably the biggest revolution in cancer treatments for the next years. In the Netherlands this form of diagnostics will also be set up with money from the Alpe d’HuZes foundation.

A very good advice for the organization of Understanding Life! came from Lloyd Old. A very experienced scientist who owns a research fund of 2 billion dollars: The Ludwig Fund. Loyd Old emphasized the Public Relations. ‘Let people and scientist always know what you do and for whom’. We will mr Old. Thank you for your advice.

At The Memorial Sloan Kettering the boys learned from Richard O’Reilly that science in some hospitals is not exported to all the hospitals in the world. In this excellent hospital they cure 60% of the children with Neuroblastoma where in most countries this is a deadly disease. Also at the Memorial Sloan Kettering Charles Sawyers showed us that this hospital has made much progress in the field of Prostate- and Lungcancer and also in Melanomas. This knowledge and experience should be exported. Inspire2Live is inspired to do this.

Finally The Three Boys visited Paul Nurse and Harold Varmus. Both Nobelprize Laureates. They loved the programme plan and when asked to give advice at certain moments they both agreed enthousiasticaly. They will attend the conference in januari.

Watch for the extended version of the search for life by The Three Boys. It will be published within days.

Heidelberg 2010

We are guests at the EMBL: the European Molecular Biology Laboratory. The General Director is Iain Mattaj. He and his colleague Silke Schumacher receive us with much enthusiasm. We are way too early, but we are invited to come into Iain’s office immediately after being served a fresh and delicious cup of coffee.

We have entered the hall of biological molecules. Here we enter Wonderland, where nothing is what it seems. In swift strokes Mattaj sketches the meaning of the biology of cancer, how his field may contribute to solving cancer and how one can keep seeing the system through the networks of interacting pathways from gene to cancer: From Genotype to Phenotype. This network is a miraculous interconnected and yet highly organised system of molecules. One tends to grant these molecules all kinds of roles: messengers, mailboxes, delivery services, repair shops, etcetera. Some molecules do repair and delivery, depending on what other molecules they meet.

Mattaj listens carefully, before he provides information. We want to know what cancer is from the viewpoint of biology and systems biology in particular. What is cancer, really, if it is not in our genes, not in the cells, and cannot be identified with malfunctioning body parts, while we do speak of lung, breast, or colon cancer?

The problem

Mattaj is not a cancer specialist. Nevertheless he is prepared to share his view on cancer. The fact that cancer research is not his speciality makes his outlook all the more interesting.

One of the first remarks he makes is that while cancer is a problem for those who suffer from it, is not at all clear what kind of problem it is. It was hoped for initially, by scientists, to identify types of cancers with corresponding patterns in the genes of people.

But while the genes have a very important role and bringing gene sequencing to the clinic is a must, the genes are just one crucial station in a myriad of interacting pathways.

Mattaj offers us the following picture. Just like water as we feel and drink it is not a direct expression of the bonding of two atoms of Hydrogen, and one atom of Oxygen, cancer is not a direct expression of a (malfunctioning) gene. Hence the notion of systems biology. Zillions of interacting H₂O molecules give rise to what we know as water. Vast numbers of interconnected pathways of generative molecular processes form a system that we know as life. Breakdowns in the system, or generative molecular pathways that outrun other pathways may lead to cancer.

Cancer, Mataj says, is literally a amalgam of 1000nds of diseases, whose etiology (underlying causes) may vary widely. Breakthroughs may be achieved for particular cancers, yet may be out of reach in other cases of cancer. He agrees that curing cancer is not what one should be striving for, overall. Making it a chronic disease is a more viable aim, in line with the character of the disease.

The strategy

We want to know from the biologist what our strategy should be in order to treat an illness that we cannot and may not ever fathom completely. While we do not understand turbulence, we can make aeroplanes. What to do with cancer?

Here speaks the biologist of the future:

Biology is an information science. The reason why biology will remain productive, the next several decades is because many new methods and techniques are created and adopted that show us how the biological dynamics of our bodies and in particular of cancer takes place. Sequencing and imaging techniques become robust, accurate and cheap. New ways of simplifying (modelling) complex interaction are sought and found. Cancer may very well be the first domain from which we learn how the disease, and how life itself functions and spreads. Biology attracts bio-physicists, bio-informatics specialists, et cetera. We do not know yet what combination of techniques and knowledge will bring the next break through. We do know that in the case of cancer no neat and clean solution will be awaiting us.

According to Mattaj the exploitation of databases that store our (disease related) biological biographies and make combinatoric research possible, will be increasingly important. He also points out many caveats: The British NHS oversees one of the biggest and most refined databases of disease-related biological information on the human body. But privacy laws prevent its use. Moreover, the database is not structured in a way that is conductive to research.

He agrees with us that the patient could have a leading role here. Because, the patient is the main beneficiary.

The plan

We love it when the plan comes together.

Mattaj envisages a network of co-operating research institutes and clinics. Biological and clinical information should be shared from the lab to the bed and back. But he stresses that while the best research institutes should become involved in a coordinated effort to deal with cancer, making cancer a chronic disease is as much a matter of cunning as it is a matter of scale: more information should become available for each individual case of cancer. It is of course critical that the information is correct, relevant and well structured. And just like our systems biological knowledge of cancer will evolve, the cancer itself will evolve as well.

We love it when the plan comes together. In this case, the coming together is part of the plan. The web, its open structure, its possibilities to bring people and biological information seamlessly together, is a crucial ingredient in breaking the barrier from incurable to chronic. It is the expertise of some, the wisdom of the crowd and specialised information exchange that come together on the web.

The story is unfolding. The Understanding Life conference in January 2011 is a hallmark in the story, which has only just begun. Cunning and strength will be needed to translate a molecular systems biology of cancer into viable clinical practices. We are lead to believe that systems biology will be the frontier of scientific discovery for the years to come. Cancer research will be a pivot in this novel and extremely challenging domain. But it will also be a science lead by a deep value: contributing to living a life in harmony with cancer.

We are invited to the CRUK Cancer Research Institute, located in the Li Ka Shing Centre. The very polite taxidriver drops us off right at the gate, and she wishes us good luck. We are again looking for the remnants of the impossible. Cambridge is a good place to continue our search for life.

Bruce Ponder’s secretary planned two meetings, one after the other. The first is with Carlos Caldas, who heads the Breastcancer lab. Then we meet Bruce Ponder and David Lane.

Carlos Caldas is head of the Breast Cancer Research Group of the Cambridge Research Institute of Cancer Research UK. Professor Caldas is educated in John Hopkins Medical Centre.

Sir Bruce Ponder was appointed Professor of Oncology, University of Cambridge in 1998 and appointed Li Ka Shing Professor of Oncology, University of Cambridge in 2007. In 2008 he received the Knighthood for ‘Services to Medicine’. From 2005 till present he is the Director of Cancer Research UK Cambridge Research Institute

Sir David Philip Lane is a Britisch Oncologist. He is best known for his work on the P53 tumour suppressing-protein. He was made a Knight Bachelor in 1999. In April 2007, Cancer Research UK has appointed Professor Sir David Lane as its first Chief Scientist. He is currently serving his 2 year sabbatical from the University of Dundee as the Executive Director of Singapore’s A*STAR Institute of Molecular and Cell Biology (IMCB) where he was appointed from 1 August 2004.

What follows is an intense debate, lead by Lane and Ponder, and intermittently clarified or illustrated by Caldas. The Brits are very conversational and the more we probe, the more enthusiastic they become. And we concur, of course.

As in the US, we ask four questions:

• How to proceed with cancer research?
• How to improve cancer research?
• How can we speed up to bring the knowledge from the laboratory to the clinic?
• How to judge the quality of cancer research?

We need not ask the questions. All they need is a signal, beginning with the how… questions.

The Cambridge turn
The conversations did not go as they went in the US. There is the platitude that Brits are more concerned with tradition than the Northern Americans are. And there is truth in this platitude. Not only do Lane and Ponder recount the stories of discovery, they converge on a set of interrelated themes:

• Education: a new breed of scientist-clinicians must be shaped. This is done so far in just a few places in the world. In the CRI of Cambridge, the Memorial Sloan Kettering Cancer Centre, Dana Farber Cancer Institute in Boston and The John Hopkins Hospital in Baltimore.

• Status: the future breed of professionals will need adequate support, to gain status and influence regarding both the direction that research should take, and to initiate new forms of patient-oriented treatment.

• Environment: Ponder, Lane and Caldas speak of a stable environment that enables the new breed of professionals to deliver new forms of high quality care (a hospital within a hospital, so to speak). In fact, they see that this environment permeates to publicity as well. Publishing ones work in the top notch Academic Journals is insufficient. What is needed is an outpour of research reports that tell the story from the lab to the bed and back!

At some point in the conversation, the remark is made that cancer research and treatment will require a different sociology. Hence the idea that we should focus on education, status and the working environment, including publishing about ones work.

The Brits love scandals-for the good!
Another element in the conversation did not turn up so far in the US conversations. It turns out that there are examples of treatment that show dramatic improvement compared to existing forms of treatment. But the way of working is so different from current clinical standards, that acceptance is low. Now comes the punch line: once you have shown that this new form of treatment (involving a more intense collaboration between patient, clinician and lab) is feasible, you cannot withhold it from the patient. Or you will risk severe criticism from the public! As Sir David Lane put it: ‘If we don’t execute what we already know, it’s a scandal!’

A cost paradox
What can be done now was virtually impossible 5 years ago (Lane). And what is crucial is that with more knowledge of the patient itself, treatment can be way more targeted. And very often, no new medication is needed! All you need is a detailed picture of biology of the cancer in one particular patient. This is complex, but with the present means, it can be done. Apart from the fact that you cannot withhold new forms of therapy that definitely benefit the patient, if the costs/benefit ratio goes up, there is little reason to keep working the old way. However, there is a paradox. At the beginning of the treatment, costs will definitely rise. The diagnosis and impact monitoring will be much more knowledge intensive. But the results are based on knowledge of the individual, not based on the effect-seizes determined by statistical samples, with little knowledge of the responsible biological processes in the individual.

Molecular management of cancer
A point made often and not to be missed is the following: the current breed of clinicians thinks in terms of Randomised Controlled Trials. Very few have sufficient understanding of the molecular networks of interaction that give rise to and feed the cancer. Remember this: unless the molecular basis of the cancer of an individual is understood, there is no way we will get cancer in control. This is exactly why the convergence of research and clinical practice is so crucial. No two cancers are the same and no two patients are the same. Its expression is different from patient to patient. Lane: ‘And your timing is fabulous: we have now very strong reasons to believe that cancer is becoming a manageable illness.’

The funding umbrella
Ponder makes one point with much force. Lane and Caldas reinforce his point several times. Put the funding of the research and the related treatment beneath one funding umbrella. Moreover, make sure that no funding substitution takes place. This is common anywhere. Some charity brings in money and next the traditional sources of funding are removed. The net effect is that the innovation does not benefit the patient, because all that happens is a systematic shift of costs to charities.

Conference Understanding Life!
We leave the gentlemen with an invitation for our conference Understanding Life! In januari 2011. Ponder, Lane and Caldas are pleased to be invited, express their support and say they will attend.

Never Ever Quit! is their motto. They want the impossible and they are looking for its beginning. They are that practical, after all. Where the impossible starts something new may be in reach.

They start with cancer. Too many people are dying of cancer each year. In total 8 million all over the world. The three boys carried with them two big questions :

1. Is it possible to get cancer in control and can it be made a chronic disease? A disease that allows people good quality of life even when they are forced to live with the cancer?
2. If so, how can we stimulate the scientific research so that this will happen and we will be able to tell to people: ´Yes you do have cancer but it is under control´.

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