Larry Norton, MD, thinks that the cure for cancer is within reach but will require developing a better business model to get there.
During last month's American Association for Cancer Research annual meeting in New Orleans, Norton -- deputy physician-in-chief for breast cancer programs and medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center -- sat down with 鶹ý for an exclusive interview.
Reflecting on what he had observed at the meeting and elsewhere, he discussed the steps he thought should be taken to solve the cancer puzzle.
Step Back to See Solution
Norton -- who co-developed with the NCI's Richard Simon, ScD., the Norton-Simon Hypothesis -- is widely know for his contributions to the mathematical understanding of tumor growth and drug administration, as well as causes of treatment resistance, and development of therapeutic regimens that increase benefit while decreasing toxicities.
The hypothesis states that the rate at which a cancer will shrink in response to treatment is directly proportional to the tumor's growth rate.
Norton told 鶹ý that he thinks cancer is a disease of how cancer cells relate to other cells and tissues in their vicinity.
"It's a disease of relationships and relationships are the easiest things to target if you know they exist. But we are not doing quite enough work in defining those relationships and defining those mechanisms by which these relationships carry out their biological activities."
He explained that about 10 years ago he realized that cancer cells will die or occasionally go into dormancy if left alone, and that nothing he has seen or heard since then has dissuaded him from that thought.
The cancer cells have to be rescued through cell-to-cell contact by something in their vicinity, he said, adding that he is convinced that cancer growth is directly proportional to the contact of the cancer cells with other cells in their vicinity.
"Finding out what those mechanisms of rescue are is all that we need to do to cure cancer. And when it happens my prediction is that it may be obvious and simple and we'll all say 'we could have done that 30 years ago,'" he said.
According to Norton the various components of cancer cells are being studied individually, "... but not as much time [is devoted to] pulling them together into a very cohesive model of cancer," he said. "The overarching model might be staring us in the face and we're not seeing it."
He said that we need different kinds of scientists looking at cancer from 30,000 feet. "We need mathematical models. Basic mathematical discovery is essential but we also need people who are good at looking at systems and not dissecting them into separate parts but putting them together."
Change the Approach
He said that we also need a different scientific approach and noted that the National Cancer Institute, the Breast Cancer Research Foundation (which he co-founded with Evelyn Lauder and where he remains scientific director), and some other foundations are beginning to collaborate on supporting mathematicians' involvement in cancer.
"We need to develop another area of scholarship where people go from room to room [at conferences such as AACR] and start connecting the dots. We have too much splintering and not enough gluing in the field."
A better model, he said, can be gleaned from physics, which often pulls together disparate parts as the basis for laws or principles to guide research such as the law of universal gravitation, or the law of electromagnetism, or Faraday's principles.
"And that's where we are with cancer. We know the models exist because of the regularity of normal life, and just how similar we look," he said, noting that any two humans are more phenotypically and genetically alike than any other known species.
Norton said that his overall view is that cancer is simple and there are probably already enough facts to start formulating overarching models that make sense, which is what he thinks will help solve the cancer problem.
To that end, he said that think tanks are developing mechanisms for funding innovative, collaborative grants. Too many areas of intellectual activity do not have mutual respect for other areas, he said, citing quality-of-life researchers who complain that those involved in clinical trials don't seem to respect them, and basic scientists who think that clinicians are a lower order of intellectual activity.
And Those Journals ...
Scientific journals also have to change, according to Norton.
"The high-prestige journals are interested in publishing masterpieces, and in the museum world there is a role for museums where painting after painting is a masterpiece." But these museums are archival and tend to respect past periods in history.
What is needed, said Norton, are journals that are similar to more contemporary museums that showcase not necessarily masterpieces, but art in evolution of an artist's life of work.
As it now stands, according to Norton, if a researcher has a good scientific idea and conducts the first two experiments, it will require a minimum of 3 years before it can be published in a major journal.
"They [journal editors] will reject it right away unless I have every conceivable control and when it goes to the reviewers they will provide criticism about not what I've done wrong, but suggestions for additional experiments."
His solution would be journals that publish hypothesis-generating research and opinion pieces and where researchers could publish what they've done so far and where they think it is going.
Norton has some skin in the journal game: Nature Publication Group plans a new journal called Breast Cancer in partnership with BCRF. Not surprisingly Norton said that journal will meet his living document model.
Best Ideas
The other major area that needs to be addressed is filling the "big hole between academic early discovery and big pharma research leading to commercialization."
"Some of the best ideas I've heard at this meeting [AACR] will never reach the level of consciousness to be developed as commercialized products, even though they may have great promise."
He said that some might reach the level of small biotech companies, which can then be acquired by larger companies, and he was totally supportive of that; however the barriers to get from really innovative discovery to a small biotech operation were so huge that only a very small percentage of true innovation could be able to make it over that hurdle.
But Norton added that the problems are identifiable and often deal with intellectual property.
Often projects get started without enough money to go to completion and after products are acquired the scientists who were responsible for the early discoveries can't participate in future development.
Conflict of interest rules can prevent clinicians who have a vested financial or intellectual interest from being involved in projects, "so they rip the baby out of your arms at a very early stage," said Norton, who also cited distrust as another inhibiting factor.
"We don't need anything other than the genius business minds of our world to identify this as an issue, and it could be different kinds of people who are willing to lose money because they want to save the world. Remember," he said.
"I just want cancer cured, and I don't care who gets the credit," he said.