Paul A. Marks is the president emeritus of Memorial Sloan-Kettering Cancer Center. After completing postdoctoral research at the United States National Institutes of Health and at the Institut Pasteur in France, he joined the faculty at Columbia University. Marks served as dean of the Medical Faculty at Columbia University from 1970 to 1973.
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The book is a memoir of Paul's life, and it goes through the journey he had in becoming an influence in the growing world of cancer research. It makes a great account of the road blocks that characterized the "war" on cancer.
Memoirs are a very special kind of book in that it's impossible to summarize it without re-writing the whole book, simply because it's event based, not in the strict historical sense, but in a memory based sense. This would be like trying to watch a movie with 2/3rds of the scenes deleted, which inevitably deletes out key characters from the story. However, I will attempt to outline the overarching themes in the book (namely the historical context). It's the best one can do without compromising the integrity of the book.
On The Cancer Frontier was published in 2014.
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He starts the book by describing how a cancer diagnosis was in the 1940's. Frankly, it was not good. Getting diagnosed with cancer at that time was the equivalent of obtaining a death sentence. The question was, how long are you going to live? And probably even more gruesomely, when will the pain start? Quite evidently, this means that there was no extensive knowledge on the workings of cancer. The analogy he used in the book accurately captures the response you would get as a medical practitioner in the 1940's. He said that if you were a medical prodigy at the time, one would go into cardiology, surgery, or internal medicine. However, working on oncology and studying cancer was like being a biologist and dedicating your entire career to the study of "bigfoot".
The statistics were in fact gruesome:
"In addition, cancer rates rise with age. In fact, aging may be one of the strongest risk factors, so as life expectancies go up, so does the number of cancer cases. About 40 percent of Americans born today will be diagnosed with cancer at some time during their lives, according to the National Cancer Institute (NCI). The more remarkable statistic, though, is the increase in survival rates. The five-year survival rate from all cancers has risen from 35 percent in 1950-1954 to 70 percent in 2002-2008, according to data from the National Cancer Institute. As a result, cancer victims are dying at later ages, and for a growing number of patients, cancer has become a manageable, chronic illness and not a death sentence."
The discovery of DNA in 1953 by James Watson and Francis Crick was the first spark that marked the birth of molecular biology. In fact, the birth of molecular biology became probably the single most important event for the fight against cancer. So through the second half of the 20th century, cancer research boomed.
"The key to these successes has been breakthroughs in basic science rather than a single-minded focus on producing a "cure." That may sound like a simple distinction, but it has been at the heart of a long battle within the medical community and between researchers and lawmakers in Washington. Often, biologists have pursued research, making remarkable discoveries about obscure enzymes or gene sequencing without knowing how the findings might open doors to new treatments. The applications came later or, frankly, sometimes not at all. That frustrates those who believe that finding cures is the only appropriate task of cancer research and the rest is a distraction. The truth is that basic research has been the engine for most of the successes in the war on cancer."
On MSKCC:
"Memorial Sloan-Kettering pioneered what are called disease-management teams, in which different specialists work jointly to care for a patient. These teams provide for much better communication among the diagnosticians and oncologists who are focused on a patient's particular cancer. We developed the first cancer pain-management program, the first freestanding breast cancer center, the first adult outpatient clinics for administering chemotherapy, and a psychiatric program for helping patients, relatives and friends manage the shock and depression that can be produced by a cancer diagnosis. These programs contributed to increases in survivorship rates and have been adopted by cancer centers across the countries."
So during the 50's onwards, Marks got into research, and describes some of it below:
"Soon after I joined his laboratory, Kornberg left the NIH for Washington University in St. Louis, but he was replaced by Bernard Horecker, an outstanding biochemist. By studying cells in a simpler organism, in this case, spinach leaves, we discovered three new sugars and three new enzymes in a metabolism pathway called the pentose phosphate pathway, through which cells burn sugars. In the first step along the spinach-cell pentose phosphate pathway, an enzyme called G6PD, we discovered, was the catalyst.
I returned to Columbia in 1955 and began my own independent research career as a junior faculty member. I decided to try to determine if human cells had the same chemical pathway as spinach leaves and used the enzyme G6PD. I chose to look at human red blood cells. It was a pragmatic choice, as I could draw blood from my willing colleagues or use leftover blood samples that had been sent to the hospital's laboratory for diagnostic purposes.
As I began my search, I made two interesting discoveries: one, I found G6PD in human red blood cells, suggesting that the spinach leaves and human blood used the same pathway, and two, some of the blood donors were deficient in the enzyme.
One of these donors was, as it happened, my laboratory technivian. Further testing showed that her son had a G6PD deficiency, too. I also found that blood from several members of a Greek family we tested had low G6PD levels, which produced what I determined was a type of anemia. Our findings strongly suggested that this medical condition was hereditary. Testing three generations of the Greek family, the pattern of the G6PD deficiency indicated that the inherited trait was passed on from parent to child by a defective gene located on the "X" chromosome, the sex chromosome. This confirmed that the path to the anemia could be traced directly back to an abnormal gene. It was an epiphany for me, as relatively little was known about the genetic causes behind certain diseases."
Where the "war" of cancer actually begins however, is during the second year of Nixon's presidency:
"When he turned to cancer, Nixon was very specific. 'I will also ask for an appropriation of an extra $100 million to launch an intensive campaign to find a cure for cancer, and I will ask later for whatever additional funds can effectively be used.' He was proposing to nearly double the National Cancer Institute's budget. 'This can be the Congress that launched a new era in American medicine.' That was it. The "war" on cancer had begun."
He then talks about the experimentation he has done with leukemia and DMSO in mice, and how leukemic cells turned into hemoglobin cells via inducing globin through an addition of DMSO. The DMSO itself was refined into something called HMBA (or Hexamethylene bis(acetamide)) It was the first time research has uncovered a way to stop the "unlimited proliferation of cancer cells in test tubes with a chemical that did not kill healthy cells."
Expounding on research, he talks about the ever-growing research on viruses, such as HIV and HPV which was ground breaking information at the time, especially since they know how HIV were mediated through reverse transcriptases.
By the time the 1980's rolled around, The New England Journal of Medicine released an article titled "Progress Against Cancer?" which did not yield favorable numbers. Partly due to reckless and passive government policy on smoking, lung cancer rates soared. Cancer deaths in the United States had risen from 151.0 per 100,000 populations to 188.8. When the cancer mortality rate was adjusted to reflect patterns in different age groups, it too had gone up, from 170.2 in 1962 to 185.1 in 1982. Incidence of cancer also rose. On a light note however, survival had gone up as well.
"A year later in his article "Rethinking the War on Cancer," Bailar further stressed this idea, urging that "treatment must come to be seen as a second line of defense." He concluded, "If we take the beginning of the modern era of cancer research to be the early 1950's, we have had 35 years of unfulfilled promises." These are the types of harsh criticisms that were rolling around by the 80's.
By that time, Memorial Sloan-Kettering replaced a grand majority of its research team, as well as its doctors, to filter out and keep those who were undoubtedly dedicated to providing the best care possible.
By the late 1980's they had done clinical trials for HMBA. A woman in particular who took HMBA, had gotten rid of her cancer with the HMBA therapy. It was the first time they saved a life through an alternate therapy that did not include surgery. After a couple of months of the therapy she was in total remission.
Around the same time, a psychiatrist in Sloan-Kettering by the name of Jimmie Holland made a significant innovation, namely that is the field of psycho-oncology. The idea was that the psychology of the patient was just as important as their physiology. It was evident that when diagnosed with cancer (especially in those times), patients automatically gave up right away. The idea of good care started to mend with not only body, but mind as well.
Through this paradigm shift, along with generous donations from Rockefeller and others, Sloan-Kettering developed an integrative medicine program that catered to a wide array of patient needs. This was crucial in persuading patients to stick with their cancer regimes, because it provided personalized incentives.
"Memorial Sloan Kettering's integrative medicine program now offers touch therapy, mind-body therapy, acupuncture, creative therapy, reiki massage, and nutrition counseling, as well as exercise programs to improve strength and promote relaxation. The services are available to anyone receiving cancer care at Memorial Sloan-Kettering or elsewhere and to the general public as a whole."
"When patients who are interested in these methods have access to them, we have found, they often comply with their medical treatment regimens better and are less likely to turn to what I regard as quackery, drugs or dubious herbal treatments that, in many instances, do not work and can be harmful, especially if they pull the patients away from proven medical therapies."
This largely in part helped improve patients' quality of life.
In 1992, Memorial Sloan-Kettering opened its first ever exclusive breast cancer center. And later in 2009, a new one subsequently opened.
"The innovative clinic, named for Evelyn Lauder to commemorate her energy and generosity, opened in 1992. It was the first of its kind and a trendsetter for the world of cancer care. It has since been replicated around the United States and in other countries. The center has not just led to better treatment, but also brought a new level of awareness and public engagement with cancer. The stigma was lifting, though it would be a long process."
"Memorial Sloan-Kettering subsequently opened a new Evelyn H. and Leonard Lauder Breast Center in October 2009, as part of a sixteen-story breast and imaging center, financed by a $50 million gift from the Leonard and Evelyn Lauder Foundation. It is a long way from the East Side garage where our idea first took root."
"The model of a dedicated facility is also being applied to other forms of cancer at Memorial Sloan-Kettering, including prostate cancer, colon cancer, melanoma, and gynecological cancers."
During the late 90's and early 2000's, epigenetic therapy spawned a new medical industry. Through the discovery of HDAC's, or Histone Deacetylases, specific cancers can be targeted if the person had the right genetic makeup. The problem however, is that if the cancer mutates to resist HDAC drugs, all of a sudden the effectiveness of it goes away completely. Cancer is a genetic Darwinian disease in that sense. One drug in particular, SAHA (or Vorinostat), started to become very popular in the pharmaceutical market. This is exactly around the time where numerous pharmaceutical industries started to take a tremendous interest in developing cancer drugs to help treat the disease.
He also talks about how, although funding research for personal treatment is crucial, the other crucial have would be cancer prevention. This of course would be achieved through preventive medicine and public policy.
"Given that long history, and research into more contemporary carcinogens, the issue in prevention is not knowledge so much as the will to limit or prevent exposure. These are questions for politicians and government policy makers. Many offending agents, including asbestos, coal tars, and certain fungal toxins such as aflotoxin, have been reduced, producing fewer incidences of mesotheliomas, cancer of the lining of the lungs, and forms of leukemia. The question is not whether preventive measures would be effective—we know cancer rates would fall—but the cost: whether the public could be persuaded to give up certain habits and, perhaps most important, where the funding for prevention programs would come from.
Such measures would save countless lives. It would, however, be a grievous error if they were funded by cutting back on research into better cancer treatments. No matter how many cancers are prevented, there will still be many tens of thousands of people diagnosed with cancer every year. They deserve the best possible care and the promise of improved therapies, which can come only from continued investments in basic science and new drug development.
Those investments were being made and, by the end of the 1990's, proving their benefits. From a rate of 184 out of every 100,000 Americans dying from cancer in 1980, the figure had declined to 164 in 1997. The five-year survival rate for all cancer patients had increased from 51 percent in the 1974-1976 period to 64 percent in the 1995-2000 period. That was, however, just a down payment on the payoff from the research spending we were to achieve over the next decade."
Cancer screenings as a preventive measure is also talked about near the end of the book.
"Memorial Sloan-Kettering recommends that women begin annual screening for cervical cancer with Pap smears at age eighteen and get regular mammograms starting at age forty. From age fifty on, people should have a colonoscopy or a "virtual" colonoscopy with a CT scanner every four to five years."
In collaboration with the IBM Watson computer program and the health provider Wellpoint, Sloan-Kettering will bring national screenings, diagnosis, and treatment standards, and ultimately the outcomes, closer to those achieved at Memorial Sloan-Kettering.
"When this computerized database is operating properly, an oncologist will be able to provide a cancer patient's complete diagnosis and record to the system, and it will come back with advice on a treatment program using the most advanced techniques and drugs available. The computer's advice will also reflect the accumulated experience and judgments of top oncologists who have treated similar cases.
The process starts with an accurate diagnosis. There will be an estimated 1.6 million new cases of cancer detected in 2013; roughly 20 percent could be diagnosed incorrectly or incompletely, based on projections by the American Cancer Society. Because a correct early diagnosis is crucial to successful treatment, a poor diagnosis can contribute to higher cancer mortality rates. The new computer program should be able to reduce these errors.
So far, Watson has cross-correlated more than 600,000 diagnostic reports, 1 million pages of medical journal articles, and 1.5 million patients records. On top of that, Memorial Sloan-Kettering's experts in various cancers have tutored Watson in the complexities of diagnosis and treatment. The computer is also absorbing the latest in genetic and molecular research, enabling individually tailored treatments. This program gives physicians across the country access to the best information on almost every cancer. It is online and accessible instantly. Watson is a could-based adviser that never forgets.
Watson may also become an important tool for patients, providing clear data on treatment methods, drug side effects, survival rates, and alternative treatments."
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