Every day, we hear of another breakthrough using gene testing and DNA to identify a new target, new treatment, new combination or novel pathway that will lead to the cure of cancer, or so it has been hoped for over two decades.
Unfortunately, the reality has been somewhat less inspiring. In an article in the August 11th , 2018 Wall Street Journal entitled "IBM Has A Watson Dilemma" the authors examine Big Blue's effort to apply the most powerful computer in the world to solve the most vexing medical problem in the world. The question: "Can Watson Cure Cancer?"
What the people at IBM and their collaborators at major universities around the country hypothesized was that cancer could be reduced to its genetic elements, that these could to be examined through pattern recognition and that treatments could be selected to match the patterns.
This reductionist thinking suggested that the complexities of human biology could be dissected and reassembled by smart doctors, or in this case, smart computers like one big jig-saw puzzle. After Big Blue won Jeopardy in 2011, it was assumed that it could solve any problem.
Unfortunately, those expectations have not been met.
In a quote from the article, "More than a dozen IBM partners and clients have halted or shrunk Watson's oncology-related projects." They go on “Watson cancer applications have had limited impact on patients”. The explanations provided include Watson being "tripped up" by a lack of data or treatments evolving faster than the trainers can update the system, but the picture gets gloomier when we realize that there has been no published research to show that Watson actually works in cancer: None.
Where did this go wrong? It is a dictum in business that failures that occur late in the stage of development for any new product line demand that one goes back to the original "premises and assumptions."
This is where IBM and their academic colleagues confront a dark reality, one that these scientists have been unwilling to accept. The “third rail” of medical oncology is the very real possibility that cancer isn’t a collection of mutations, amplifications or gene rearrangements.
Put simply, cancer may be more complex than its genes. For those who argue that cancer has not been solved because we haven’t applied enough crunch power, the current analysis puts that to rest. The concerning reality for those wedded to genomics is that cancer refuses to obey the dictates of data managers.
The complexities of cancer’s response to nutrient deprivation, hypoxia, hormone and growth factor withdrawal, alterations in the micro-environment, cell-cell communications, immune interactions and the cancer cell's indomitable desire to stay alive provide a labyrinth that even Big Blue can’t navigate. Where to from here?
One answer is that we must be humble enough to be instructed by cancer, not the other way around.
In my laboratory, we study cancer biology as systems biology.
We study how cells talk to each other and to their micro-environment.
We expose cells to drugs and combinations to induce injury and then gauge the degree of programmed cell death, one form of which is apoptosis. In our laboratory, we can identify active drugs, combinations, sequences, and synergistic interactions that dance circles around even the most powerful computers. Thomas Kuhn, in The Structure of Scientific Revolutions, said "Each paradigm will be shown to satisfy, more or less, the criteria that it dictates for itself."
We see in the recent IBM data the abject failure of genome-based scientists to satisfy even those criteria that they set out for themselves. The most powerful computer in the world cannot solve a problem if tasked with erroneous information; the biologic equivalent of “garbage in garbage out”.
Is it not time to have an honest discussion about the sacrosanct cancer-gene connection? More time, energy and effort should be put into in the study cell biology, the cancer phenotype and biosystematics.
Though there is no shortage of commercial entities, prepared to charge handsomely for genomic analyses, we should be careful not allow our patients to become the victims of contemporary scientists’ faulty premises and assumptions.
As always, I appreciate your thoughts and comments.
Dr. Robert Nagourney, has been internationally recognized as a pioneer in cancer research and personalized cancer treatment for over 20 years. He is a TEDX SPEAKER, author of the book OUTLIVING CANCER, a practicing oncologist and triple board certified in Internal Medicine, Medical Oncology and Hematology helping cancer patients from around the world at his Nagourney Cancer Institute in Long Beach, California. For more info go to NAGOURNEYCANCERINSTITUTE.COM
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