An Interview with Manuel F. Varela and Ann F. Varela: Jane Wright—The “Mother of Chemotherapy.”

Oct 10, 2021 by

[Dr. Jane C. Wright] never looked at things as obstacles.” She looked at them as challenges, and I think that she was a very ambitious person, and I think that she never let anything stand in the way of her doing what she wanted to do.”

—Alison W. Jones, Ph.D., daughter of Jane Wright

I know I am a member of two minority groups, but I do not think of myself that way. Sure, a woman has to try twice as hard. But—racial prejudice? I have met very little of it. It could be I met it—and was not intelligent enough to recognize it.”

—Dr. Jane C. Wright

I would argue that [Wright] was too busy being brilliant to give credence to opinions or beliefs that would stand in her way.”

—Ellen Elliott, Ph.D.

Michael F. Shaughnessy

1) Some female scientists come from a long line of parents/grandparents who were scientists. What do we know about the lineage of Jane Wright?

Dr. Jane C. Wright was a prestigious medical scientist who pioneered research dedicated to cancer treatment and prevention. She played a prominent role in revolutionizing medical research studies on cancer and changed the landscape of oncology.

Wright was a member of a prominent family of physicians and scientists.

Her father, Louis Wright, graduated from Meharry Medical College. He was one of the earliest African Americans to graduate from Harvard Medical School and practiced medicine at a municipal hospital in New York City. Dr. Wright became the first African American police surgeon in New York City in 1929. Harlem Hospital was where Dr. Wright established the Cancer Research Center.

Dr. Louis Wright’s father, Dr. Ceah Ketcham Wright, was born into slavery. Once the Civil War ended, he studied medicine and graduated from Bencake Medical College. Jane Wright’s step-grandfather, William Fletcher Penn, was the first African American graduate of Yale Medical College. Jane Wright’s uncle, Harold Dadford West, was also a biochemist and physician.

2) When and where was she born, and what we some early expectations of her?

Jane Cooke Wright was born on November 20, 1919, in New York City’s borough of Manhattan. Her parents, Louis Tompkins Wright and Corrine (Cooke), raised two daughters. Her mother, Corrine, was a public-school teacher.

Jane and her sister, Barbara, followed in the family tradition of becoming physicians. Jane Wright attended Smith College intending to earn a degree in art; however, her father convinced her to switch to medicine. Upon receiving her B.A. degree in 1942, Wright was awarded a full scholarship to attend New York College, where she graduated from an accelerated three-year medical doctoral program in 1945 with top honors. After earning the M.D., she interned at Bellevue Hospital from 1945 to 1946. In 1948, Wright performed her surgical residency at her father’s hospital, Harlem Hospital.

After completing her internship in 1947, Wright married an attorney, David D. Jones, Jr., on July 27. He died of heart failure in 1976. The couple’s two daughters, Jane and Alison, work in the medical fields of psychiatry and clinical psychology.

In 1987, Dr. Jane Cooke Wright retired as an emerita professor at New York Medical College after a 44-year medical practice and research career. On February 19, 2013, Wright died in Guttenberg, New Jersey, at the age of 93 from complications from dementia. Her contributions to cancer chemotherapy research have helped change the direction of medicine and continue to be used presently.

3) Wright’s research focused on what they then called the “Cinderella” of cancer research—chemotherapy. Why was chemotherapy scoffed at during that period?

Chemotherapeutic agents are chemical-based medicines that are used for the treatment of disease in humans. Such chemicals that have been used to treat cancers, i.e., anti-cancer agents, had been highly criticized for decades during the first part of the 1900s. The moniker “Cinderella” concerning cancer chemotherapy was coined by Dr. Jane C. Wright herself in a seminal review article on the topic, published in 1984. Wright was referring to the high potential of untried chemicals on the growth inhibition of cancer cells. She had realized that chemicals had medical promise, which had been hitherto unrealized. However, Wright was aware that toxic effects and the limited successes early chemical treatments had in effectively treating cancer were problematic. These early chemotherapies were highly varied. Such chemicals included agents like arsenic, clays, and leaves of violet, and material extracted from toads! Because these and other anti-cancer chemotherapies were ineffective and maybe even poisonous, not to mention expensive to develop, they were severely disparaged in favor of emerging radiation and surgical treatments. Thus, at the time, Wright was keenly cognizant of the failed opportunity that chemicals could address cancer treatment.

Wright had written that a notable milestone in successful cancer chemotherapy had its origins in the mid-1860s with the advent of the so-called Fowler’s solution, a form of potassium arsenite, for leukemia treatment. See Figure 1. The anti-cancer and general chemotherapeutic potential of arsenic derivatives was an unexplored field.

File:Potassium arsenite.png

Figure 1. The potassium arsenite chemical structure.

During the following decades, however, bacterial toxins were also used for cancer treatment. Unfortunately, these toxin-based avenues suffered from inconsistency in their levels of improvement from clinical conditions and toxicities in the patients treated.

Additional chemotherapies were based on hormones that had been developed for improving treatments of various tumors. This hormone-based development occurred during the same era as the onset of anesthetics, which provided a much-improved surgical means of treatment. Then, in the latter part of the 19th century, William Roentgen’s discovery of the rays named after him and Marie Curie’s discovery of radium ushered in the new era of radiation therapy for cancer treatment.

Interestingly, throughout the first half of the 20th century, new varieties of anti-cancer therapies were developed based on organic- and immuno-based agents. However, they were considered failures because of their low success rates in improving patient outcomes or disease prevention. Surgery and radiation became the medical treatments that had all of the attention of both clinicians and researchers. Wright had invoked the Cinderella effect here. That is, primarily, these chemical modes of cancer treatment were considered failures—chemotherapy was Cinderella. Surgery and radiation treatments were considered the popular treatment modes—Cinderella’s sisters. However, the chemical-based agents as effective treatments ultimately triumphed in the face of widespread disparagement and outright vilification by the medical community.

Part of why chemotherapy ultimately prevailed (Cinderella phenomenon) had to do with research conducted by Dr. Wright in this area. In 1949, Wright had started a collaboration with her famous father, Louis Tompkins Wright, who was one of the first African Americans educated at Harvard Medical School. At Harlem Hospital, Dr. Jane Wright and her father firstly examined different groups of anti-cancer chemical agents. Together, Wright and Wright (daughter and father) established the utility of tissue cultures as venues for testing anti-cancer agents in vitro, i.e., in the test tube or “in a glass.”

The Wright team then tested various chemical candidate therapies in live patients in the clinical wards to measure treatment efficacy. Jane Wright was known to have treated patients amid despair as they had all been rejected by other medical doctors. The patients had cancers that were deemed incurable, and their physicians had given up on them. Such patients were sure to die from their cancers. However, they were given new hope when they arrived in Wright’s ward. In an unprecedented move, she considered these rejected patients candidates for new experimental “last resort” medical treatment. Wright had chosen to conduct a well-designed experiment, an extensively performed systematic analysis of specific chemicals and collection of clinical cancer data, a virtually untried practice on other humans in medical history.

Secondly, Wright and her father became pioneers in the so-called combination chemotherapy for the treatment of cancer. Their pioneering novel idea held that cancer treatment could be attained by using more than one chemical agent at a time and, importantly, in proper sequential order of their administration to the cancer patients. Wright had established that combination therapy was successful if the chemical therapies were given to patients in a specific order, as first established in vitro, then in vivo, i.e., in the patient. These two sorts of experimental approaches to chemotherapies (i.e., cell culturing first, then patient administration) showed substantial improvements in the survival rates of her cancer patients. Wright had demonstrated chemotherapeutic efficacy, and Cinderella now prevailed because of her research-based approaches to medical treatment.

Wright studied several clinically successful chemotherapies for cancer patients in the Cancer Research Foundation ward at Harlem Hospital in New York City. One of these chemotherapeutic agents dealt with the so-called antimetabolites, such as folic acid antagonists. Folic acid in humans is essential for making the building blocks of DNA, RNA, and protein. Pregnant women are often provided with folic acid supplements, as many new cells are produced during pregnancy. Without folic acid, healthy cells (and cancer cells!) cannot reproduce. Perhaps a lack of folic acid could result in little or no cancer cell growth. Thus, it was necessary to block the folic acid function in cancer cells. Such folic acid inaction could stop cancer cell growth and treat clinical cancer in an efficacious manner.

In particular, Wright had focused on newly developed anti-folic acid chemicals like aminopterin, A-ninopterin, and A-methopterin, which later became known as methotrexate, and all showed promising improvements in the clinical outcomes of a significant number of patients. Some patients had better outcomes when treated with a combination of a folic acid antagonist and the so-called citrovorum factor, a then newly discovered biologically active form of folic acid thought to help reverse the toxic effects of specific anti-folic acid compounds. It was known then that folic acid itself could not undo the harmful effects of anti-folic acid chemicals on healthy cells. Thus, the citrovorum factor was a good candidate for combination therapy. It was a significant finding.

Specifically, Wright and her colleagues showed that administration of A-methopterin alone decreased the mass size of metastatic anaplastic carcinoma cases. The A-methopterin treatment also reduced skin ulcerations in cases of adenocarcinoma of the breast tissue. The skin lesions had showed improved healing. The citrovorum factor alone had increased the white blood cell count in a few cancer cases. These experimental data represented a suitable control group to compare with the set of patients receiving combination therapy.

Interestingly, however, they showed that with a combination of A-methopterin and citrovorum factor, the white blood cell counts returned to normal healthy levels, improved ulcer healing in several patients, and reduced metastasis to the bone tissue in cases of breast cancer. Importantly, Wright would be recognized as having established the clinical efficacy of methotrexate (A-methopterin) in patients with inoperable cancers of the skin and breast. That is, Wright clinically demonstrated remission in these patients with methotrexate. This new finding was a significant breakthrough in the chemical treatment of solid tumors.

Overall, conducting clinical research on these and other chemical-based agents, Wright had ushered in a triumphant Cinderella effect by discovering new methods for cancer treatments to improve patient outcomes. Thus, Wright had played a prominent role in regaining the respect that chemotherapy had lost in the early and mid-20th centuries.

4) Nitrogen mustard or nitrogen gas—how does this work to fight cancer?

An alkylating agent called mechlorethamine or nitrogen mustard is a derivative of nitrogen gas. This agent was discovered in 1854 and produced in 1886. In 1917, during the Great War, it was reported that military personnel exposed to nitrogen gas exhibited an immunosuppressive effect in the form of lowered white blood cell counts. Shortly afterward, to find new and improved war gases, nitrogen mustard agents were developed as potential chemical warfare weapons. During the so-called Great War, the Germans used the mustard gases called “Yellow Cross” as blistering agents to attack the British. The war gas was called “Yperite” by the French, who were also targeted for chemical attacks by the Germans.

Interestingly, in 1942, a mustard gas-harboring U.S. naval vessel was sunk by accident. During that disaster, medical officials noted that sailors exposed to the mustard gas had developed lowered counts of white blood cells, a circumstance called pancytopenia. Thus, a systematic study of sulfur- and nitrogen-mustards was invoked to examine the phenomenon more closely. During the analysis, it was discovered by Cornelius Rhoads that some of these chemical agents induced lymphoid tumors in laboratory animals. However, it was also discovered that nitrogen mustards could kill specific forms of cancer cells in human patients. Thus, beginning in the 1940s, during World War II, nitrogen mustard was studied for its ability to treat cancer.

Wright’s work with these mustard-like agents began in the late 1940s. She focused on studying one of the alkylating agents as a clinical chemotherapeutic candidate to mediate efficacious anti-cancer properties. A promising anti-cancer agent was a member of the mustard-like ethylenimines, a nitrogen mustard breakdown product called triethylenemelamine (TEM). See Figure 2. The chemical name of TEM was officially known then as 2,4,6 tris-ethyleneimino-1,3,5 triazine. In modern times, the IUPAC (International Union of Pure and Applied Chemistry) name is 2,4,6-tris (aziridin-1-yl)-1,3,5-triazine.

File:Triethanolamine 3D ball.png

Figure 2. Ball-and-stick molecular model for triethanolamine (TEM).

Wright’s famous cancer remission project, now considered a classic experiment in the history of cancer research, involved experimental administration of the mustard-like agent TEM to 14 hospital patients with incurable and terminal cases of cancer. Overall, the cancerous ailments were called neoplastic diseases. These patients’ cancers included one case of a so-called anaplastic sarcoma, three carcinomas, a fibrosarcoma case, three lymphosarcomas, one case of reticular cell sarcoma, an osteogenic sarcoma, two Hodgkin’s disease cases (Figure 3), a chronic myelogenous leukemia case, and one case of mycosis fungoides. Before the experimental TEM treatment was given, all patients were tested by histopathologic analysis to confirm their cancer diagnoses.

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Figure 3. Histopathology of Hodgkin’s lymphoma.,_Reed-Sternberg_Cell.jpg

Wright conducted the famous experiment in the following manner. Each patient was given a tablet of 5 or 10 mg of TEM once a day for two to four days. If the patients exhibited no toxicity after 30 days, the TEM treatment regimen would be repeated. The patients were examined by white and red blood cell counts, repeated biopsies of cancer and normal tissues, tissue culturing, blood chemical composition, bone marrow sampling, and X-rays during the study. The clinical experiment headed by Wright was exhaustive and, thus, labor-intensive.

At the end of the study, the results were striking. Nine of the 14 terminally ill patients (with incurable cancers) continued to live after receiving the TEM chemotherapeutic agent! Sadly, three of the 14 patients who had improved somewhat after receiving TEM later died from their cancers. In the end, five of the 14 patients showed no clinical benefits from TEM and died. Nevertheless, the nine patients who were quite likely to die from their cancer diseases were saved by the TEM. The mustard-like derivative saved a significant number of patients from an all but definite death!

Dr. Wright, her father, and two colleagues (Drs. Aaron Prigot and Solomon Weintraub), who conducted the famous study, used the medical terminology remission to indicate that their TEM saved nine cancer patients’ lives who otherwise faced certain death. Wright’s preliminary TEM clinical cancer study was published in the 42nd volume of the Journal of the National Medical Association in 1950. Derivatives of the deadly war gases, the mustards, would now be used instead to save lives by killing cancer cells. Wright’s publication would be a groundbreaking study in the efficacious treatment of cancer.

5) The time factor—and early intervention—what do people need to know about this?

Each tumor is a unique mass of tissue, consisting of a cell mixture, with individual cells differing in their appearance, biochemical or physiological behaviors, and molecular structures of their genomes. This diverse population of individual cells in a tumor mass represents a genetically diverse, heterogeneous set of non-normal cells. As tumors progress, their cells become even more heterogeneous with each subsequent cell proliferation event. That is, new generations of cancer cells produce new variants. These assorted cells in a tumor are constantly multiplying their numbers, mutating their genomic DNA, competing with each other and with healthy cells, evolving, adapting, and diversifying their cellular nature. By so doing within their patients, tumor cells can exploit their local environments, permitting them to react to anti-cancer agents used to kill them.

The diverse nature of the cells inside a tumor mass can allow some of them to convert from a relatively harmless benign state into a cancerous one. An official cancer is a tumor that has become malignant, which is the ability of cells in a tumor to break loose from the original primary tumor mass and move about, invading new tissues elsewhere in the body and forming new secondary tumor masses. This malignant ability, breaking away and invading new places to generate secondary tumors, is called metastasis. Tumors that metastasize are considered malignant and, therefore, cancerous. Thus, the cancerous nature of tumors makes it difficult to treat diseases caused by them effectively.

Suppose tumors can be detected early, in their primary stages, when they are still small masses, and before they metastasize and become secondary cancerous tumors, then it can be possible to cut them off at the pass with surgery or radiation therapy. If, however, the tumors are detected later in their growth stages of progression, when they have become cancerous, i.e., malignant, then anti-cancer chemotherapy will be necessary.

Cancer research has three focuses of scientific investigation: diagnosis, prevention, and treatment. If a diagnosis is made early, before carcinogenesis has been established, it may be possible to use surgical intervention or radiotherapy to remove small tumors to achieve a cure. Thus, much cancer research has been devoted to developing exact and sensitive molecular tests for early diagnosis.

Medical and biomedical scientists think that cancer prevention is preferred over attempting a cure, an outcome that is not always guaranteed. Many cases of cancerous tumors are preventable, especially if one does not smoke—tobacco smoke is one of the most common causes of cancer worldwide—tobacco smoke contains potent DNA mutating chemical carcinogens. Thus, avoidance of smoking can result in a significant reduction in the incidence of cancer cases.

Interestingly, it is widely thought by scientific investigators that simple lifestyle changes would go a long way towards preventing cancers, in addition to steering clear of tobacco, if one wishes to avoid cancer. A healthy diet and avoidance of overeating would prevent the overweight and obese condition, two factors associated with cancer. Surprisingly, environmental exposure to cancer agents is much less significant than factors associated with tobacco and obesity. Experts in cancer biology have unequivocally stated that roughly half of the cancers are preventable with these two changes in lifestyle: avoidance of both smoking and obesity.

The successful treatment of cancer is a highly complicated endeavor. The molecular machinery of a normal healthy cell is an exceptionally complex instrument. If such a normal cell undergoes carcinogenesis, the molecular cell mechanisms become even further intricate. If one considers the hundreds of distinct types of cells and tissues that can turn into cancerous masses, one can appreciate that “cancer” represents an exceedingly complex collection of diseases. Cancer is not one disease, but preferably, it is a constellation of many distinct ailments. Each cancer patient has a disease unique to that individual.

Cancer researchers have likened the curing of cancer as analogous to killing weeds in a garden. Though anti-cancer agents, radiation therapy, and surgery remove cancerous cells, not every cancer cell is eradicated in the process. Surgery can remove the original mass but not every one of the metastasized tumor masses. Problematically, anti-cancer medicines and radiation that are used can also kill normal healthy cells. Lastly, cancer cells can adapt, mutate, or evolve into new forms resistant to radiation and chemotherapy.

Nevertheless, despite these difficulties addressing cancer treatment, there have been successful chemotherapeutic agents that have been used to treat specific cancers. Dr. Jane Wright was a key investigator who found some of these effective anti-cancer chemical agents. She studied TEM and methotrexate, for instance. Wright’s scientific work made it possible to treat Hodgkin’s lymphoma, leukemias, and other cancers with specific anti-cancer chemotherapeutic agents. Thus, Wright and other cancer investigators have helped find cures for cancer despite the difficulties that cancerous cells devised.

Wright was a prominent investigator whose work was key to discovering that aminopterin and methotrexate were efficacious anti-cancer agents. These agents are known as folate analogs. The methotrexate molecule inside a living cell inhibits the enzyme called dihydrofolate reductase. See Figure 4. The enzyme typically converts the substrate dihydrofolate into a product called tetrahydrofolate, which can be used as a coenzyme to synthesize thymine for making needed DNA. When methotrexate inhibits dihydrofolate reductase, the cell cannot make DNA, which stops the cell from growing into abnormal clumps or masses of cells typical of cancer.

File:Methotrexate ball-and-stick model.png

Figure 4. Ball-and-stick model of methotrexate—an antimetabolite and antifolate drug.

Recently, various forms of cancer cells have evolved to develop a mutant in which the dihydrofolate reductase enzyme no longer gets inhibited by methotrexate. In the enzyme’s biochemical active site, a leucine amino acid at position 22 was altered into an arginine residue in one notorious case. The leucine-22-arginine mutation within the enzyme changes its structure just slightly enough to make methotrexate unable to bind and obstruct the protein. The result of the cancer cell’s resistance to methotrexate is that cancer can proliferate into large masses once again, potentially leading to disease and enhanced mortality.

6) Leukemia—how is it different from treating this cancer from, say, lungs, kidney, brain, and other parts of the body?

Wright’s discoveries involved the unprecedented remission of specific cancers like Leukemia with the TEM anti-cancer agent. In general, Leukemia is a form of cancer that involves abnormal growth or proliferation of white blood cells in the body. See Figure 5. Leukemia cancers can also involve cellular precursors of the white blood cells, such as hemopoietic cells.

On the other hand, carcinoma cancers are derived from epithelial cells of the body. Several organs of the body, like the kidneys, lungs, and brain, contain specialized epithelial cells. Because of their widespread presence in many body areas, carcinomas account for most human cancer cases. Lastly, sarcomas represent a third type of cancer. Sarcoma cancers arise from cells of the muscle or connective tissue.

A cancer mass is often derived from a single rogue cell that has undergone a new change in its genetic state. A well-known carcinogen is a molecule called benzene, a chemical that mutagenizes DNA molecules and can cause acute Leukemia. Primary cells with mutated DNA maintain the altered genetic state such that new generations of cells in the reprobate cell’s lineage harbor the same abnormal growth properties. All subsequent generations of the parental cell’s descendants are cellular scoundrels, too, growing inappropriately and causing dangerous disease states in an individual’s life and possibly leading to death.

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Figure 5. Normal blood versus the abnormal cellular state of Leukemia.

Leukemia also has a microbial cause. For instance, in the case of the virion called human T-cell leukemia virus type I (HTLV-1), a member of the Retrovirus family, the microbe is known to cause both Leukemia and lymphoma, the latter of which is another form of cancer involving aberrant white blood cells.

Methotrexate, a well-known drug studied intensively by Wright, is used to treat acute Leukemia, a rapidly growing tumor. The anti-cancer drug can kill cells that rapidly divide. However, methotrexate can kill non-tumor cells that also happen to undergo cell replication rapidly, whether such target cells are normal or cancerous. Thus, the clinical administration of methotrexate can affect bone marrow stem cells, epithelial cells of the gastrointestinal tract, and hair follicles. Therefore, the patient undergoing chemotherapy with methotrexate for Leukemia can often experience weakened immunity, nausea of the gut, and hair loss as side effects.

Other chemotherapeutic agents can be used for Leukemia. Clofarabine comes to mind, a known purine analog. This medicine can inhibit an enzyme called ribonucleotide reductase, preventing the conversion of ribonucleotides to the production of deoxyribonucleotides. Thus, inhibiting deoxyribonucleotide synthesis prevents DNA formation and cell growth. Clofarabine has been used to treat pediatric patients who have acute myeloid Leukemia.

Similarly, another analog of the purines, called cladribine, inhibits the target enzyme ribonucleotide reductase, preventing the production of all four types of deoxynucleotides and, thus, preventing DNA synthesis. Cells that lack building blocks to make DNA cannot proliferate further and are prevented from producing cancerous cells or masses of tissue. Cladribine is used to treat several types of so-called chronic lymphoid leukemia cases.

7) Wright worked on getting certain drugs to very hard-to-reach or difficult-to-reach places in the human body—why is this important?

Indeed, one of the most considerable difficulties in cancer treatment using anti-cancer chemotherapeutic agents entailed the need for new ways of administering such chemotherapy in patients so that their proper cancer targets in the body could be reached. One of the principal reasons the mode of anti-cancer drug administration was problematic was that many of the agents were toxic. Thus, if the chemotherapies were given to patients intravenously (I.V.), the drugs could extensively damage non-cancerous tissues, like the gastrointestinal tract or the bone marrow, both tissues needed for normal body functioning, especially in patients already compromised by their cancers. Further, if the anti-cancer drug were provided at reduced levels during I.V. administration (to address toxicity), then the lowered amount given would be ineffective in defeating the cancerous tissue in any meaningful way. Therefore, too much toxicity and too little anti-cancer efficacy were both serious problems when clinicians considered chemotherapy. These conditions proved to be grave problems in cancer wards worldwide.

In the early 1960s, Wright was entirely devoted to developing improved techniques for appropriately directing effective chemotherapies to cancer patients, especially in individuals already deemed hopeless by their physicians. Of Wright’s first keynote research projects, one of the experimental approaches she considered concerned a technique called perfusion. The medical procedure involved first isolating the tumor’s circulation away from the rest of the patient’s body, then introducing the anti-cancer agent into the closed circulation circuit. The isolated circuit perfusion technique was invoked in 48 of Dr. Wright’s otherwise hopeless patients—those whose various cancers were already too far gone for any hope of surgery or radiation—experimental chemotherapy with Wright’s perfusion method would be their only and last hope.

In Wright’s hands, cancerous tissues in the pelvis, arms, legs, head, chest wall, head, or the brain were isolated and perfused with anti-cancer drugs. The cancer medicines that were found to be most efficacious in her patients included triethylenethiophosphoramide (an organophosphorus agent), Dihydro E-73 (an antibiotic derivative), nitrogen mustard, actinomycin D (an antibiotic), methotrexate, and mithramycin (antibiotic). Many of the patients treated showed dramatic improvement in their outcomes. Before, their doctors had given these patients no hope. Now their cancers reduced in size, and for as long as the study was conducted, they stayed that way!

In other study patients, Wright used the circulation isolation and perfusion methods to perform combination therapy with two anti-cancer drugs. In two patients tested, Wright combined a new drug phenylalanine mustard (PAM), called by its experimental code CB-3025 (now called melphalan), plus the triethylenethiophosphoramide agent. In one of these individuals, patient number 45, her leg melanoma had shrunk and then disappeared, but later returned in three weeks after her surgery had been performed to excise the cancer mass. However, in the second patient, number 52, her leg melanoma also shrank but did not return, even five weeks after her surgery. In 1962, Wright published these results in a medical journal called Cancer. The research group, led by Wright and including Frederick Golomb, Allen Postel, Alden Hall, Stephen Gumport, and Kenneth Cox, concluded in their publication that perfusion therapy worked well in treating various severe cancer cases, especially if combined with surgery and in one exemplary case, with more than one medicine.

Afterward, Wright continued working with Golomb to focus on cancers of the head and neck. They tried a combination of local perfusion with isolation of affected lymph nodes but combined the treatment regimen with surgery to excise the bulk of the cancerous tissues. In these cases, the cancers were operable. Importantly, Wright and Golomb paid strict attention to technique and proper drug dosing levels. The cancer researchers found that their newly modified clinical method worked well when performing the surgery, and the perfusion simultaneously had worked significantly better towards inducing cancer tissue necrosis (cell death) and towards healing the surgical wounding. Wright and Golomb published their findings in The American Journal of Surgery in 1964, concluding that their new method was not only efficacious against head and neck cancers, but it was also safe and simple.

8) Using a catheter to deliver anti-cancer drugs—was this a new approach, and is it still used today?

Working with Dr. Billy Sammons, Golomb and Wright made a significant discovery in 1964 while using a catheter for anti-cancer drug delivery into the major arteries of cancer patients. They combined newly made polyethylene catheters with a new method to visualize the tip of the inserted catheter using a fluoroscope which helped control its direction of movement through the vessel to arrive at the target cancer mass. They astutely took arteriograms using the ends of inserted catheters to visualize the effectiveness of the delivered anti-cancer drugs at the tumor mass locations. Indeed, their catheter method is commonly used in many tissue-specific cancer cases even in modern times.

In their new study, the trio of cancer clinicians devised a method to deliver high doses of anti-cancer drugs to tumors in the body using a so-called percutaneous visceral intra-arterial infusion catheter. The new catheter infusion method sent the anti-cancer medications directly into the major blood vessels of the patient. Wright and her team of physicians focused their attention on inserting external catheters into the celiac, femoral, brachial, hepatic, splenic, iliac vessels, as well as the carotid arteries. They even placed catheters into renal, mammary, and mesenteries. They could flood cancer tissues hiding in the colon, cervix, kidneys, skin, rectum, and pancreas. The groundbreaking work was published in the 20th volume of the prestigious Journal of the American Medical Association.

9) Like many others on the proverbial front lines, she never really got the recognition she deserved. Your thoughts?

Although Wright felt that she did not experience sexual or racial discrimination and was widely regarded among her cancer research peers, she did not receive the typical accolades that many of her non-African American male counterparts did. Often, white male researchers were given (or took) credit for cancer studies that Wright previously initiated.

Wright pioneered the rigorous clinical testing of anti-cancer agents in cell culture systems and then comparatively measuring the clinical responses to these agents in cancer patients. Wright developed drug combination therapies for cancers, devising novel means for proper sequential administration of drugs to effectively minimize cancer mass sizes in patients considered all but terminal. She had developed the means for determining the proper dosing of anti-cancer drugs, first in vitro, then in vivo.

Wright’s cancer research investigations were used to develop general treatment guidelines for oncologists nationwide, if not worldwide. Wright’s studies demonstrated the importance of analyzing the effects of drugs on cells in culture before treating patients. As a result, Wright discovered the first steps of what may be considered personalized medicine, where each patient’s clinical circumstances were taken into consideration and used to treat cancer. Furthermore, Wright first developed the reliable and straightforward perfusion method to supply needed anti-cancer medicines directly into affected organs. Before Wright’s invention, such cancers required major surgery or were deemed inoperable. With Wright’s perfusing method, however, such cancers were now effectively treatable with drugs.

Wright revolutionized the medical research studies on cancer and changed the landscape of oncology. Wright was able to enjoy a highly successful career with accomplished academic appointments. At one point in her career, in 1967, Wright became an associate dean and was, thus, the highest-ranked African American female in a national medical institution.

However, she was never made a member of the U.S. National Academy of Sciences, nor would she ever garner a Nobel Prize. She was not even a recipient of the prize that many consider as a precursor to the Nobel, the Louisa Gross Horwitz Prize. She was bypassed for the Szent-Györgyi Prize for Progress in Cancer Research. There was no nod to Wright by committees for the Harvey Prize, the Breakthrough Prize in Life Sciences, the Wolf Prize in Medicine, the Massry Prize, the Lasker-DeBakey Clinical Medical Research Award, the Paul Ehrlich award, the Ludwig Darmstaedter Prize, or the Warren Alpert Foundation Prize, to mention a few. All of these are prizes given to investigators for breakthroughs in cancer research.

Perhaps it might have seemed that Wright was a widely respected scientific investigator amongst her cadre of colleagues in the cancer research field. Nevertheless, Wright was bestowed even by this community with very few of its honors specific to cancer research. As far as we know, Wright was awarded only one award specific to this wide-ranging research area: the American Association for Cancer Research, in 1975.

Nevertheless, in 1964, President Lyndon B. Johnson appointed Dr. Wright to his presidential Commission on Heart Disease, Cancer, and Stroke. The committee’s charge was devoted to devising new recommendations for a network of cancer treatment centers throughout the U.S. The commission established a new network called the Regional Medical Program (RMP), which provided cooperative agreements between various research-oriented institutions, schools of medicine, and clinically based cancer treatment centers. The RMP soon became a nationwide organization. In 1971, Wright was elected president of the New York Cancer Society, the organization’s first female physician-scientist. These efforts would prove to have long-lasting and endearing ramifications towards influencing the effective treatment of cancer nationwide.

In 2011, an award was created in Wright’s honor, the Jane C. Wright Young Investigator Award, established by the Conquer Cancer Foundation and the American Society of Clinical Oncology. Another accolade named after Wright, created by the American Association for Cancer Research in 2006, is the Minorities in Cancer Research Jane Cooke Wright Lectureship.

10) What have I neglected to ask or say about this brilliant scientist? (I guess I should add in a postscript that she was African American—so she was a stellar individual who accomplished a great deal during her lifetime.) 

In 1949, Dr. Wright and her father, the eminent Harvard-educated Louis Tompkins Wright, collaborated on evaluating the therapeutic potential of chemical agents towards cancer in the clinical wards at Harlem Hospital. Many of their collaborative works, mentioned above, included the famous folic acid antagonist, methotrexate. Sadly, however, the Wright-Wright collaborative association was short-lived because the elder physician passed away in 1952. Consequently, however, the younger Dr. Wright, at the age of 33 years, became head of the Cancer Research Foundation after her father’s passing.

Dr. Jane Cooke Wright was a prolific writer known to have published over 130 scientific articles dealing with the fight against cancer. She also wrote and published nine books during her career. In February of 2021, Wright was featured during the celebration of Black History Month as a prime example of the heights that African Americans could achieve. Indeed, as a cancer researcher extraordinaire, indisputably she was of the “Wright Stuff.”

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