The Differences: Multiple Myeloma - Vera Danchakoff and Geraldine Ferraro
Imagine human blood as products made in a factory. There are various types of products but they are all generated from the same raw material. This raw material is stem cells and in the factory, they are turned into three different types of blood cells — red blood cells (which carry oxygen), white blood cells (part of the immune system), and platelets (to assist in wound clotting). The factory produces all these different blood cell types (and subtypes) depending on demand. For example, when there is an infection the factory needs to produce more white blood cells to help assist the immune system. Blood cancers, however, dramatically change the rate of production, putting stress on the factory floor and creating chaos. The different blood cancers cause abnormal production of different cell types, causing an increase of one type of cell and not enough raw material to produce the others, resulting in an imbalance in blood composition and a dysfunction.
Mother of Stem Cells
The first scientist to describe stem cells’ ability to differentiate into various cell types was Vera Danchakoff, the first woman in Russia to become a professor. Dr Danchakoff officially proposed her theory in November 1915, during a lecture she gave before the College of Physicians and Surgeons at Columbia University where she worked as a visiting scientist. In her lecture titled “Origin of the Blood Cells”, she argued for the existence of hematopoietic stem cells – “hematopoietic” referred to the blood and “stem cells” referred to the original cells that develop into different cell types. She came to this conclusion after observing studies across various species. She suggested that these stem cells are not only capable of tissue regeneration in response to damage but also of abnormal development that causes diseases.
Her theory earned her the moniker “Mother of Stem Cell”. In fact, in 1916, Dr Danchakoff published the first English-language scientific paper to use the term “stem cell”, describing how different blood cells in the thymus of birds develop from one source cell. Scientists in the first half of the 20th century were divided in their support of Danchakoff’s theory until it was proven correct in 1961 through an experiment by scientists Till and McCulloch. The duo observed that injection of bone marrow cells (stem cells) led to the development of lumps (groups of cells) in the spleen of mice, and the number of lumps is identical to the same number of injected cells. Subsequent experiments confirmed that these lumps arise from the bone marrow cells. Unfortunately, Danchakoff passed away a decade before this discovery and so was not around to celebrate this confirmation.
Vera Danchakoff was multitalented and ambitious. However, as a young girl, she was discouraged by her family from pursuing medicine. Her family wanted her to become an artist such as a musician or a painter, as she exhibited talent as both. However, she decided to leave home due to this opposition. She attended university and became a professor, eventually obtaining the opportunity to move to America. It was a difficult decision as she was, in fact, a young widow with a small child. She decided to leave her young daughter behind temporarily with family members until she settled in America. Danchakoff is a rare early example of a scientist who managed to juggle work and motherhood.
While she became more well-known for her later work in graft-versus-host-disease, a condition where recipient rejects a transplanted organ, it is now widely recognised that she was ahead of her time with her stem-cell theory. Her two research focuses actually intertwine — graft-versus-host-disease is often a side effect of a stem cell transplant, a procedure commonly administered to treat blood cancers.
Multiple myeloma, more commonly known as just myeloma, is a type of blood cancer. Multiple myeloma begins in a type of blood cell called plasma cell, a subtype of white blood cell that is produced in the bone marrow (the spongy centre of the bone). Plasma cells produce antibodies, proteins that fight infections in your body, as part of their role in the immune system. Multiple myeloma causes excess production of abnormal plasma cells with abnormal antibodies — the factory is producing faulty products and a lot of them.
In its early stages, multiple myeloma is difficult to detect. At later stages, it can cause many problems such as a persistent dull ache or tenderness in the bones, fragile bones, anaemia (iron deficiency), recurring infections and kidney problems. Diagnosing multiple myeloma is a multi-step process. A GP will test for bone tenderness, signs of infections, and test your blood and urine. If they suspect myeloma, they will refer the patient to a haematologist, a blood disease specialist.
It is not clear what causes myeloma, but various risk factors have been linked to it. One of these is a condition called monoclonal gammopathy of unknown significance (MGUS), where there is an excess of protein molecules called immunoglobins in the blood. This condition itself doesn’t cause any symptom and doesn’t require treatment, but it is known that 1% of people with MGUS go on to develop myeloma. Myeloma is also more common in men than women, in adults over 60, and in the black population. Myeloma is not curable but is considered a highly treatable condition through combination therapy. Research is going strong worldwide in the effort to understand more and to cure this disease. There are also various clinical trials patients might be recruited into for potential treatments.
One treatment that has been approved for multiple myeloma is the controversial drug thalidomide. Famously known for causing devastating birth defects worldwide in the 1950s-1960s, this drug strengthens the immune system and is believed to block the blood supply to cancerous cells. This ability to block the blood supply is also, ironically, what causes damage to unborn foetuses. One of the first patients to receive thalidomide as treatment was Geraldine Ferraro, a famous American attorney and politician.
Taking the Risk
Geraldine Ferraro was a prominent figure in American politics — she was most known for being the first female vice-presidential candidate to represent a major party in 1984. Before going into politics, she was a public school teacher who became a lawyer and eventually a district attorney. She was the first head of the Special Victims Bureau, a specialised unit dealing with abuse cases against women, children, or the elderly. She took this position in 1977, long before this unit was immortalised in popular media as Law and Order: SVU which started in 1999. She took this role seriously, often working long hours on difficult and emotionally charged cases, fighting for prosecutions on victims’ behalf. She knew every case was different and needed to be fought for with its own unique approach. Her experience made her realise that the justice system is far-too-often influenced by politics, convincing her to go into politics and make changes from the inside. She was a strong advocate for human rights, serving as the United States Ambassador to the United Nations Commission on Human Rights from 1993 to 1996.
Ferraro’s 1998 diagnosis came as a shock as it was discovered during a regular check-up — moreover, she had no family history of cancer. In the same year, researchers had started considering thalidomide as a treatment and Ferraro was admitted into a clinical trial. Yes, thalidomide — the drug that caused worldwide birth defects in the 1960s. Touted as a miracle drug to treat morning sickness, this drug disrupts blood circulation between mothers and their unborn babies and causes developmental abnormalities. This mainly happened because at the time no one actually understood how the drug worked – they were focused on the results and did not spend time looking at possible side effects. Medical science at the time also believed that embryos are protected by the placenta and what a mother consumed did not transfer through the placenta to the embryo. It was a misconception, and clinical trials nowadays are far more controlled when testing medications that may be consumed during pregnancy.
Thalidomide’s ability to disrupt blood circulation is believed to be the reason it is efficient in treating multiple myeloma. By disrupting blood circulation it is thought to stop the growth of abnormal plasma cells as well as limiting the supply of nutrients to these cells. Interestingly, thalidomide has an opposite effect on some other subtypes of white blood cells which leads to increased immune responses. With the help of thalidomide, Ferraro was able to continue working as a news commentator and a consultant until her death in 2011. She also used her fame and connection to raise awareness and campaign for multiple myeloma research. Thalidomide is now an approved drug for multiple myeloma treatment worldwide, used in combination with other therapy such as stem cell transplant or chemotherapy.
Observing the world and acknowledging differences were the key strengths of Vera Danchakoff and Geraldine Ferraro. Championing these ideas became their lifelong missions. They created controversies, faced oppositions, and in the end contributed to the betterment of the world.
References and further readings:
Al-Gailani, Salim, and Angela Davis. “Introduction to "Transforming pregnancy since 1900".” Studies in history and philosophy of biological and biomedical sciences vol. 47 Pt B,Pt B (2014): 229-32. doi:10.1016/j.shpsc.2014.07.001.
Danchakoff V. (1916) Origin of the blood cells. Development of the haematopoetic organs and regeneration of the blood cells from the standpoint of the monophyletic school. Anat. Rec., 10: 397-416. doi:10.1002/ar.1090100506
Danchakoff V. (1916) The Differentiation of Cells as a Criterion for Cell Identification, Considered in Relation to the Small Cortical Cells of the Thymus. J Exp Med. 1916 Jul 1;24(1):87-105.
Dwyer J. 19 June 2001. Ferraro Is Battling Blood Cancer With a Potent Ally: Thalidomide
Foerstel K, Foerstel HN, Foerstel KP. Climbing the Hill: Gender Conflict in Congress.
Getlin J. 20 June 2001. Ferraro Battles Cancer With Once-Barred Drug
Lichtman MA.The stem cell in the pathogenesis and treatment of myelogenous leukemia: a perspective. Leukemia (15):1489–1494(2001).
Loomis C. 28 March 2011. The Ferraro-Corman connection: Brought together by a killer disease. CNN money.com.
Raab S. 21 July 1984. Ex-colleagues Praised Rep. Ferraro As Lawyer.