A Trumpian Proposal to Conquer Cancer

On March 12, 1938, Germany invaded Austria.  Recognizing that war with the Third Reich was now probable and anticipating bombing raids on London, Admiral Hugh Sinclair, head of the Government Code and Cipher School (GCCS), set out to find property outside the city where the agency could relocate.  Unable to get funding from the government, Sinclair purchased with his own money Bletchley Park in Buckinghamshire.  This would be the site of the most spectacular cryptographic breakthroughs in history, made possible in part by the engineering of the world’s first programmable electronic digital computer.

Bletchley Park (photo credit: DeFacto)

In September of 1938, Neville Chamberlain returned from Munich to announce that he had achieved “peace in our time.”  Alexander Denniston, operational head of GCCS, was skeptical.  Deinniston, who had led the team that decrypted the Zimmermann Telegram, set out to recruit prospective cryptologists.  He dined at the high tables of most of the Oxford and Cambridge colleges and identified the most brilliant and creative problem-solvers among the young dons and students.  GCCS sleuths were mostly former scholars in the humanities, but Denniston recruited mathematicians, linguists, engineers, and others.  Some were keen chess players; several were accomplished musicians.  Many were eccentric.  There seemed to be a correlation

The story of Bletchley Park has often been told, sometimes (as in the films Enigma and The Imitation Game) with a great deal of creative license.  German ciphers were encrypted by the Enigma machine.  This electromagnetic device used as many as 8 rotors to encode and decode German text.  The settings were changed daily at midnight.  Using a model of the machine build by the Polish Cypher Bureau and smuggled out of the country, Alan Turing’s team first broke a code in January 1940.  But the operation was enormously time consuming.  Even a 3-rotor Enigma could produce nearly 159 quintillion (million million million) different settings.  A new machine had to be created to accelerate the process.  The first device was the electromechanical “bombe,” the second, the famous Colossus, the first digital computer, operational in February 1944. 

Ultra, the intelligence generated by Bletchley Park, was invaluable in winning the war.  Without it, the conflict might have claimed hundreds of thousands of additional lives and ended with the dropping of an atomic bomb on Berlin, or with the meeting of Soviet and American troops on the Rhine.  Historians have argued for worse outcomes, including the failure of the Normandy invasion.  Ultra was always credited to human agents.  “By Jove, you must have some very brave chaps,” Stewart Menzies, head of M16, was told.

***

Bletchley Park demonstrated that the collaboration of geniuses can produce quantum leaps in knowledge.  The term “genius” is streng verboten in an age of egalitarianism and cultural relativism, but the species exists.  As one of Alan Turing’s colleagues defined it, “What you realize when you get to know a genius well is that there is all the difference between a very intelligent person and a genius.  With very intelligent people, you talk to them, they come out with an idea, and you say to yourself, if not to them, I could have had that idea.  You never had that feeling with Turing at all.  He constantly surprised you with the originality of his thinking.  It was marvelous.”

Why not model a cancer research project on Bletchley Park?  Why not ask geniuses to decode the etiology of cancer, an enigma that kills over 600,000 Americans annually? 

Though they would work with oncologists, microbiologists, virologists, hematologists, biochemists, biophysicists, and geneticists, these individuals, specks trailing off the right side of the Bell Curve, would come mostly from disciplines in which enormously complex problems are solved—mathematics, physics, and computer science.

Cancer is a signaling disease.  Cells in the human body are in constant communication with neighboring and distant cells.  Cancer cells subvert the communications network.  They deregulate signals controlling their growth, disrupting multiple negative feedback mechanisms, while emitting their own signals.  Not only do they ignore commands to end mitosis and to commit suicide, but they avoid aging and death, conceal themselves from lymphocytes seeking to destroy them, generate capillaries to sustain their growth, penetrate epithelial walls to enter the bloodstream and lymphatic system, and invade tissue to form distant colonies, ignoring the barrage of signals telling them to cease and desist.

***

Our understanding of cancer has already benefited from a massive collaborative project, the Cancer Genome Atlas Program, undertaken by researchers at twenty institutions in North America.  Launched three years after the completion of the Human Genome Project, it wound up identifying the genomic changes in 33 different types of cancer, based on over 10,000 tumor samples. 

The program revealed that a significant number of genes are mutated, as many as 80 in breast and colon cancer, 60 in pancreatic cancer, and 50 in brain cancer.  There appears to be a correlation between the number of mutated genes in the cancer and its resistance to chemotherapy:  acute lymphoblastic leukemia (ALL), the first cancer to be checked by drugs, has fewer than 10 alterations.  Researchers have also identified some of the pathways, the signaling sequences, disrupted by the mutant genes.  But the problem remains, as Siddhartha Mukherjee put it before the completion of the project, “We will soon know what the mutant genes are.  The real challenge is to understand what the mutant genes do.”

A 2020 Cancer Act could meet that challenge by funding research to utilize the massive amount of data generated by the Cancer Atlas project (nearly 2.5 petabytes, 1015 bytes).

Can mathematicians help?  One of the nation’s foremost cancer researchers thinks so. 

After “every signal-transducing protein will have been put in its place on a large chart describing how cells receive and process the signals that influence their growth and differentiation,” writes Robert Weinberg, “a new set of talents will be brought to bear on the cancer problem.  Mathematicians with expertise in analyzing complex multicomponent systems will explain to biologists how the minicomputers inside cells actually function.  They will tell us how the mind of the cell works, and how it becomes derailed during the tumor progression.”  As Weinberg explains further, “at present, cancer geneticists focus their energies on understanding the roles of single genes and how each of these influences the creation of a tumor.  But the great majority of tumors arise from the combined actions of a constellation of genes, not single ones operating in isolation.  In the future, new kinds of mathematics will make it possible to understand the origins of polygenic cancers, in which cohorts of genes act in combinatorial ways to favor the appearance of cancers.”

In the most widely cited paper in oncology since its publication, Weinberg and Douglas Hanahan conclude that “we still know very little about the release of these mitogenic signals [stimulating mitosis].”  They express the hope that “the signaling circuitry describing intercommunication between…various cells within tumors will be charted in far greater detail and clarity, eclipsing our current knowledge.  And…we continue to see cancer research as an increasingly logical science, in which myriad phenotypic complexities are manifestations of a small set of underlying organizational principles.”

Future cancer researchers must be cryptographers, decoding communication among cancer cells and between those cells and normal cells.

***

Who would be invited to join the Bletchley Park II task force?

In 1938, Alastair Denniston relied on something like the old boy network to identify and recruit participants in the deciphering programs.  Those planning 2020 Cancer Act will have better options. 

Winners of the Fields Medal would be good candidates.  This prestigious award is presented every four years to the most original mathematician under the age of forty.  (The only woman to win a Fields Medal, Stanford professor Maryam Mirzakhani, died of breast cancer at age forty.)  Potential nominees might include as well winners of the Salem Prize, awarded every year to a subset of young mathematicians.  There are, in addition, about eighty-five prizes awarded exclusively to American mathematicians. 

There are also about eight-five prizes presented annually to computer scientists by the Institute of Electrical and Electronic Engineers (IEEE) and the Association for Computing Machinery (ACM).  The most prestigious prize is probably the Turing Award, given by the latter.  Recipients of the IEEE’s John von Neumann Medal, Internet Award, and Medal of Honor could also be approached.

In physics, winners of the Breakthrough Prize in Fundamental Physics and especially the New Horizons in Physics Prize would be obvious candidates.  There are also about forty prizes awarded annually to American physicists. 

Nobel laureates could be solicited as well, though the prize is sometimes awarded decades after the achievement for which the recipient is recognized, and original work in math and physics is often done by individuals in their twenties and thirties. 

***

A few takeaways from two earlier cancer acts, Nixon’s 1971 “War on Cancer” and Obama’s 2016 “Moonshot Initiative.”  

1.  Despite the many put-downs, partly because of its association with Nixon, partly because of the hype accompanying the declaration of “war,” the 1971 Act was a success.  “The ultimate impact has been extraordinary,” according to Fred Applebaum, deputy director of the Fred Hutchison National Cancer Center.  “It turned out money did buy ideas,” Vincent DeVita, former director of the National Cancer Institute and the Yale Cancer Center, concludes.  “Putting brilliant people to work on a problem broad enough to give wide range to their imaginations generated ideas aplenty.”

2.  An administration whose #1 priority was the health of American had little interest in cancer research until its final year.  President Obama added nearly $8.6 trillion to the national debt, which rose from 52% to 77% of GDP.  But funding for the National Cancer Institute declined each year in constant 1998 dollars until 2016, when there was a small uptick.  In inflation-adjusted dollars, the Moonshot Initiative provided over a seven-year period just a fifth of what Nixon’s War on Cancer allocated over a three-year span.  Putting Joe Biden in charge revealed a certain lack of seriousness.  Prior to the drafting of the Act, the Vice President didn’t bother meeting personally with a team from the American Association of Cancer Research to discuss the state of cancer research. 

Obama spoke frequently about his mother who died of uterine cancer at age 52. 

“I remember just being heartbroken, seeing her struggle through the paperwork and the medical bills and the insurance forms.  So, I have seen what it's like when somebody you love is suffering because of a broken health care system.  And it's wrong.  It's not who we are as a people.” 

Ann Dunham was not suffering from a broken health care system.  At Memorial Sloan-Kettering Cancer Center, she received the most advanced treatment available in the world, covered by her insurer.  Dunham was suffering from a cancer for which the chemotherapy regimen (cisplatin and pacilitaxel, the same as today) is not very effective at stage IV.

3.  Both cancer acts enjoyed bipartisan support.  The great majority of Republicans voted for the Moonshot Initiative, which passed in the House 392 to 26.  Would their pathological hatred of Trump compel Democrats to oppose any cancer legislation bearing his name?  If so, the message to voters is unambiguous:  the elimination of private insurers has a higher priority than the elimination of cancer.

***

A panel of geniuses solving the riddle of cancer is a Trumpian idea -- big, bold, courageous.  It has something of the aura of a reality TV show.  But the project would be in deadly earnest.

Over 1.8 million Americans will be diagnosed with cancer this year, 4,950 each day, and around 606,520 will die of the disease.  Nearly 40% of Americans will receive the bad news during their lifetimes.  Over 17 million Americans have been diagnosed with cancer, and are currently battling the disease or living with the fear of its return.  They and their friends and relatives are waiting for answers that the brightest men and women in America should be invited to help provide.

*****

For a longer version with references and footnotes, please contact the author at jeff@jefflipkes.com

On March 12, 1938, Germany invaded Austria.  Recognizing that war with the Third Reich was now probable and anticipating bombing raids on London, Admiral Hugh Sinclair, head of the Government Code and Cipher School (GCCS), set out to find property outside the city where the agency could relocate.  Unable to get funding from the government, Sinclair purchased with his own money Bletchley Park in Buckinghamshire.  This would be the site of the most spectacular cryptographic breakthroughs in history, made possible in part by the engineering of the world’s first programmable electronic digital computer.

Bletchley Park (photo credit: DeFacto)

In September of 1938, Neville Chamberlain returned from Munich to announce that he had achieved “peace in our time.”  Alexander Denniston, operational head of GCCS, was skeptical.  Deinniston, who had led the team that decrypted the Zimmermann Telegram, set out to recruit prospective cryptologists.  He dined at the high tables of most of the Oxford and Cambridge colleges and identified the most brilliant and creative problem-solvers among the young dons and students.  GCCS sleuths were mostly former scholars in the humanities, but Denniston recruited mathematicians, linguists, engineers, and others.  Some were keen chess players; several were accomplished musicians.  Many were eccentric.  There seemed to be a correlation

The story of Bletchley Park has often been told, sometimes (as in the films Enigma and The Imitation Game) with a great deal of creative license.  German ciphers were encrypted by the Enigma machine.  This electromagnetic device used as many as 8 rotors to encode and decode German text.  The settings were changed daily at midnight.  Using a model of the machine build by the Polish Cypher Bureau and smuggled out of the country, Alan Turing’s team first broke a code in January 1940.  But the operation was enormously time consuming.  Even a 3-rotor Enigma could produce nearly 159 quintillion (million million million) different settings.  A new machine had to be created to accelerate the process.  The first device was the electromechanical “bombe,” the second, the famous Colossus, the first digital computer, operational in February 1944. 

Ultra, the intelligence generated by Bletchley Park, was invaluable in winning the war.  Without it, the conflict might have claimed hundreds of thousands of additional lives and ended with the dropping of an atomic bomb on Berlin, or with the meeting of Soviet and American troops on the Rhine.  Historians have argued for worse outcomes, including the failure of the Normandy invasion.  Ultra was always credited to human agents.  “By Jove, you must have some very brave chaps,” Stewart Menzies, head of M16, was told.

***

Bletchley Park demonstrated that the collaboration of geniuses can produce quantum leaps in knowledge.  The term “genius” is streng verboten in an age of egalitarianism and cultural relativism, but the species exists.  As one of Alan Turing’s colleagues defined it, “What you realize when you get to know a genius well is that there is all the difference between a very intelligent person and a genius.  With very intelligent people, you talk to them, they come out with an idea, and you say to yourself, if not to them, I could have had that idea.  You never had that feeling with Turing at all.  He constantly surprised you with the originality of his thinking.  It was marvelous.”

Why not model a cancer research project on Bletchley Park?  Why not ask geniuses to decode the etiology of cancer, an enigma that kills over 600,000 Americans annually? 

Though they would work with oncologists, microbiologists, virologists, hematologists, biochemists, biophysicists, and geneticists, these individuals, specks trailing off the right side of the Bell Curve, would come mostly from disciplines in which enormously complex problems are solved—mathematics, physics, and computer science.

Cancer is a signaling disease.  Cells in the human body are in constant communication with neighboring and distant cells.  Cancer cells subvert the communications network.  They deregulate signals controlling their growth, disrupting multiple negative feedback mechanisms, while emitting their own signals.  Not only do they ignore commands to end mitosis and to commit suicide, but they avoid aging and death, conceal themselves from lymphocytes seeking to destroy them, generate capillaries to sustain their growth, penetrate epithelial walls to enter the bloodstream and lymphatic system, and invade tissue to form distant colonies, ignoring the barrage of signals telling them to cease and desist.

***

Our understanding of cancer has already benefited from a massive collaborative project, the Cancer Genome Atlas Program, undertaken by researchers at twenty institutions in North America.  Launched three years after the completion of the Human Genome Project, it wound up identifying the genomic changes in 33 different types of cancer, based on over 10,000 tumor samples. 

The program revealed that a significant number of genes are mutated, as many as 80 in breast and colon cancer, 60 in pancreatic cancer, and 50 in brain cancer.  There appears to be a correlation between the number of mutated genes in the cancer and its resistance to chemotherapy:  acute lymphoblastic leukemia (ALL), the first cancer to be checked by drugs, has fewer than 10 alterations.  Researchers have also identified some of the pathways, the signaling sequences, disrupted by the mutant genes.  But the problem remains, as Siddhartha Mukherjee put it before the completion of the project, “We will soon know what the mutant genes are.  The real challenge is to understand what the mutant genes do.”

A 2020 Cancer Act could meet that challenge by funding research to utilize the massive amount of data generated by the Cancer Atlas project (nearly 2.5 petabytes, 1015 bytes).

Can mathematicians help?  One of the nation’s foremost cancer researchers thinks so. 

After “every signal-transducing protein will have been put in its place on a large chart describing how cells receive and process the signals that influence their growth and differentiation,” writes Robert Weinberg, “a new set of talents will be brought to bear on the cancer problem.  Mathematicians with expertise in analyzing complex multicomponent systems will explain to biologists how the minicomputers inside cells actually function.  They will tell us how the mind of the cell works, and how it becomes derailed during the tumor progression.”  As Weinberg explains further, “at present, cancer geneticists focus their energies on understanding the roles of single genes and how each of these influences the creation of a tumor.  But the great majority of tumors arise from the combined actions of a constellation of genes, not single ones operating in isolation.  In the future, new kinds of mathematics will make it possible to understand the origins of polygenic cancers, in which cohorts of genes act in combinatorial ways to favor the appearance of cancers.”

In the most widely cited paper in oncology since its publication, Weinberg and Douglas Hanahan conclude that “we still know very little about the release of these mitogenic signals [stimulating mitosis].”  They express the hope that “the signaling circuitry describing intercommunication between…various cells within tumors will be charted in far greater detail and clarity, eclipsing our current knowledge.  And…we continue to see cancer research as an increasingly logical science, in which myriad phenotypic complexities are manifestations of a small set of underlying organizational principles.”

Future cancer researchers must be cryptographers, decoding communication among cancer cells and between those cells and normal cells.

***

Who would be invited to join the Bletchley Park II task force?

In 1938, Alastair Denniston relied on something like the old boy network to identify and recruit participants in the deciphering programs.  Those planning 2020 Cancer Act will have better options. 

Winners of the Fields Medal would be good candidates.  This prestigious award is presented every four years to the most original mathematician under the age of forty.  (The only woman to win a Fields Medal, Stanford professor Maryam Mirzakhani, died of breast cancer at age forty.)  Potential nominees might include as well winners of the Salem Prize, awarded every year to a subset of young mathematicians.  There are, in addition, about eighty-five prizes awarded exclusively to American mathematicians. 

There are also about eight-five prizes presented annually to computer scientists by the Institute of Electrical and Electronic Engineers (IEEE) and the Association for Computing Machinery (ACM).  The most prestigious prize is probably the Turing Award, given by the latter.  Recipients of the IEEE’s John von Neumann Medal, Internet Award, and Medal of Honor could also be approached.

In physics, winners of the Breakthrough Prize in Fundamental Physics and especially the New Horizons in Physics Prize would be obvious candidates.  There are also about forty prizes awarded annually to American physicists. 

Nobel laureates could be solicited as well, though the prize is sometimes awarded decades after the achievement for which the recipient is recognized, and original work in math and physics is often done by individuals in their twenties and thirties. 

***

A few takeaways from two earlier cancer acts, Nixon’s 1971 “War on Cancer” and Obama’s 2016 “Moonshot Initiative.”  

1.  Despite the many put-downs, partly because of its association with Nixon, partly because of the hype accompanying the declaration of “war,” the 1971 Act was a success.  “The ultimate impact has been extraordinary,” according to Fred Applebaum, deputy director of the Fred Hutchison National Cancer Center.  “It turned out money did buy ideas,” Vincent DeVita, former director of the National Cancer Institute and the Yale Cancer Center, concludes.  “Putting brilliant people to work on a problem broad enough to give wide range to their imaginations generated ideas aplenty.”

2.  An administration whose #1 priority was the health of American had little interest in cancer research until its final year.  President Obama added nearly $8.6 trillion to the national debt, which rose from 52% to 77% of GDP.  But funding for the National Cancer Institute declined each year in constant 1998 dollars until 2016, when there was a small uptick.  In inflation-adjusted dollars, the Moonshot Initiative provided over a seven-year period just a fifth of what Nixon’s War on Cancer allocated over a three-year span.  Putting Joe Biden in charge revealed a certain lack of seriousness.  Prior to the drafting of the Act, the Vice President didn’t bother meeting personally with a team from the American Association of Cancer Research to discuss the state of cancer research. 

Obama spoke frequently about his mother who died of uterine cancer at age 52. 

“I remember just being heartbroken, seeing her struggle through the paperwork and the medical bills and the insurance forms.  So, I have seen what it's like when somebody you love is suffering because of a broken health care system.  And it's wrong.  It's not who we are as a people.” 

Ann Dunham was not suffering from a broken health care system.  At Memorial Sloan-Kettering Cancer Center, she received the most advanced treatment available in the world, covered by her insurer.  Dunham was suffering from a cancer for which the chemotherapy regimen (cisplatin and pacilitaxel, the same as today) is not very effective at stage IV.

3.  Both cancer acts enjoyed bipartisan support.  The great majority of Republicans voted for the Moonshot Initiative, which passed in the House 392 to 26.  Would their pathological hatred of Trump compel Democrats to oppose any cancer legislation bearing his name?  If so, the message to voters is unambiguous:  the elimination of private insurers has a higher priority than the elimination of cancer.

***

A panel of geniuses solving the riddle of cancer is a Trumpian idea -- big, bold, courageous.  It has something of the aura of a reality TV show.  But the project would be in deadly earnest.

Over 1.8 million Americans will be diagnosed with cancer this year, 4,950 each day, and around 606,520 will die of the disease.  Nearly 40% of Americans will receive the bad news during their lifetimes.  Over 17 million Americans have been diagnosed with cancer, and are currently battling the disease or living with the fear of its return.  They and their friends and relatives are waiting for answers that the brightest men and women in America should be invited to help provide.

*****

For a longer version with references and footnotes, please contact the author at jeff@jefflipkes.com