Thyroid Cancer: History and Discovery

The story of thyroid cancer is, in large part, the story of how a single butterfly-shaped gland in the neck taught medicine some of its most important lessons. Because thyroid cells crave iodine, surgeons learned to remove the gland safely — an achievement that won Theodor Kocher the 1909 Nobel Prize — and physicists later learned to destroy malignant thyroid cells from the inside using radioactive iodine, one of the first treatments that could both find and kill a cancer (an early example of what is now called “theranostics”). The same iodine-hunger explains the tragedy of Chernobyl, where radioactive fallout caused a wave of childhood thyroid cancers, and it underlies today’s quieter controversy of overdiagnosis, in which ultrasound finds tiny, harmless cancers that may be better watched than cut out. This page traces that history honestly — the discoverers, the dates, the breakthroughs, and the hard lessons — for anyone who wants to understand where modern thyroid-cancer care came from.

Table of Contents

  1. The Gland and the Main Types of Thyroid Cancer
  2. Theodor Kocher and the Birth of Safe Thyroid Surgery
  3. Classifying the Cancers: Papillary, Follicular, Medullary, Anaplastic
  4. Radioactive Iodine: Hertz, Roberts, and the First Theranostic
  5. Seidlin 1946: Radioiodine Against Metastatic Thyroid Cancer
  6. Radiation as a Cause: The Lesson of Chernobyl
  7. The RET Gene, MEN2, and Inherited Medullary Cancer
  8. Overdiagnosis, Screening, and Active Surveillance
  9. Research Papers and References
  10. Connections

The Gland and the Main Types of Thyroid Cancer

Thyroid cancer arises in the thyroid gland, a small butterfly-shaped organ wrapped around the front of the windpipe (trachea) at the base of the neck. The gland’s ordinary job is to take up iodine from the bloodstream and use it to make thyroid hormone, which sets the pace of metabolism throughout the body. That iodine-hunger — a normal feature of healthy thyroid tissue — turns out to be the single most important fact in the entire history of thyroid cancer, because it is what makes the gland both treatable (with radioactive iodine) and vulnerable (to radioactive fallout).

Pathologists recognize four main types, named for how the cancer cells look under the microscope. Papillary thyroid carcinoma is by far the most common and usually the most curable; it grows from the hormone-making follicular cells. Follicular carcinoma also arises from follicular cells and, like papillary cancer, is called “differentiated” because the cells still behave somewhat like normal thyroid tissue — crucially, they still take up iodine. Medullary thyroid carcinoma is different: it grows not from follicular cells but from the calcitonin-producing parafollicular (“C”) cells, and a substantial fraction is inherited. Anaplastic thyroid carcinoma is rare, aggressive, and undifferentiated — the cells have lost their thyroid character (and their iodine uptake), which is why it does not respond to radioiodine and remains one of the most dangerous cancers known.

This four-way classification is not ancient; it was assembled piece by piece across the twentieth century, and each type carried its own discovery story. Understanding those stories — the surgery that made treatment possible, the radioiodine that made differentiated cancer treatable from within, the radiation exposure that causes the disease, and the genetics behind the medullary form — is the purpose of the sections that follow.

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Theodor Kocher and the Birth of Safe Thyroid Surgery

For most of medical history, operating on the thyroid was close to a death sentence. The gland is wrapped in large blood vessels and sits beside the nerves that control the voice and the tiny parathyroid glands that regulate calcium; nineteenth-century thyroid surgery was notorious for catastrophic bleeding and frequent death. The man who changed this was Emil Theodor Kocher (1841–1917), professor of surgery at the University of Bern, Switzerland, who brought to thyroid operations a meticulous, bloodless, antiseptic technique. Over his career he is reported to have reduced the mortality of thyroid surgery from roughly 18 percent to well under 1 percent — by 1912 he had performed thousands of thyroidectomies with a death rate below half of one percent. For this body of work he received the 1909 Nobel Prize in Physiology or Medicine “for his work on the physiology, pathology and surgery of the thyroid gland,” becoming the first surgeon ever to win the prize.

Kocher’s greatest scientific contribution was almost an accident of his own success. As he operated on more and more patients with goitre, he noticed that those whose entire thyroid had been removed often deteriorated afterward — becoming sluggish, swollen, and mentally dulled, a condition he described in 1883 and called cachexia strumipriva. He had, in effect, discovered what happens when the body loses its thyroid hormone entirely. This observation helped establish that the thyroid was an essential organ with a vital internal secretion, and it taught surgeons a lesson that still governs thyroid-cancer surgery today: how much gland to remove, and at what cost, is a decision with lifelong consequences.

Without Kocher’s safe technique, none of the later history would have been possible — there would have been no reliable surgery to remove a thyroid cancer, and no foundation on which radioactive iodine could later mop up whatever surgery left behind. His work is the bedrock of the entire field, which is why a page on the history of thyroid cancer must begin in his Bern operating theatre.

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Classifying the Cancers: Papillary, Follicular, Medullary, Anaplastic

Once surgeons could remove thyroid tumours and pathologists could examine them, the work of sorting thyroid cancer into meaningful types began. The distinction between the slow-growing, iodine-avid “differentiated” cancers (papillary and follicular) and the deadly, undifferentiated anaplastic form emerged over the first half of the twentieth century as pathologists correlated what they saw under the microscope with how patients fared. The lesson was stark: a papillary cancer and an anaplastic cancer might both be “thyroid cancer,” yet one is among the most survivable of all malignancies and the other among the most lethal.

The clearest single discovery in this classification story is medullary thyroid carcinoma. In 1959, the Cleveland Clinic pathologists John Hazard, William Hawk, and the surgeon George Crile Jr. published the first clear clinicopathologic description of it, defining it as a distinct “solid” carcinoma containing amyloid in its stroma — a tumour that did not form the follicles typical of ordinary thyroid cancer. Earlier pathologists had glimpsed tumours of this kind, but Hazard and colleagues were the ones who named it medullary carcinoma and established it as a separate entity. It was later shown that medullary carcinoma arises from the calcitonin-secreting parafollicular C-cells — a completely different cell of origin from the common papillary and follicular cancers, which is why it behaves so differently and does not take up radioiodine.

This careful classification was not academic hair-splitting. Because the type of thyroid cancer dictates everything — whether radioactive iodine will work, whether the disease may be inherited, how aggressive surgery must be, and what the outlook is — the painstaking twentieth-century work of telling the four types apart is what made rational, type-specific treatment possible. The discovery that medullary cancer was its own entity, in particular, set the stage for one of the great genetic breakthroughs described below.

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Radioactive Iodine: Hertz, Roberts, and the First Theranostic

The most distinctive chapter in thyroid-cancer history is the discovery that you can destroy thyroid cells from the inside using radioactive iodine (iodine-131, or I-131). The logic is elegant: because thyroid cells — including the cells of differentiated thyroid cancer — naturally absorb iodine, a radioactive form of iodine swallowed by the patient travels through the bloodstream and is taken up almost exclusively by thyroid tissue, where its radiation kills those cells while largely sparing the rest of the body. The cancer, in effect, swallows its own poison.

The pioneer of this idea was Saul Hertz (1905–1950), chief of the thyroid clinic at Massachusetts General Hospital, working with the Massachusetts Institute of Technology physicist Arthur Roberts. The collaboration is often traced to a 1936 conversation in which Hertz asked whether iodine could be made artificially radioactive; Hertz and Roberts then carried out the foundational animal experiments showing that thyroid tissue concentrates radioiodine. On March 31, 1941, Hertz administered the first therapeutic dose of radioiodine to a patient with thyroid disease (hyperthyroidism) at Massachusetts General Hospital — the birth of radionuclide therapy and of nuclear medicine itself. (Other researchers, including Joseph Hamilton and the Lawrence brothers at Berkeley, were working on radioiodine in the same period; Hertz is generally credited with the first therapeutic application to thyroid disease.)

Radioiodine is now often called the first true “theranostic” — a portmanteau of therapy and diagnostic — because the very same substance both reveals the disease (a tracer dose lights up functioning thyroid tissue on a scan) and treats it (a larger dose destroys that tissue). This dual ability, discovered through the thyroid’s appetite for iodine, became a template that twenty-first-century oncology is still building on with newer radioactive drugs. For differentiated thyroid cancer, radioiodine remains a cornerstone treatment more than eight decades later.

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Seidlin 1946: Radioiodine Against Metastatic Thyroid Cancer

Hertz had shown that radioiodine could treat an overactive thyroid, but the dramatic demonstration that it could fight thyroid cancer that had already spread came a few years later, and it is one of the most celebrated case reports in the history of oncology. On December 7, 1946, the physician Samuel M. Seidlin (1895–1955), working with the physicist Leonidas Marinelli and Eleanor Oshry, published in JAMA the case of a patient whose thyroid cancer had metastasized — spread to distant sites such as bone — and who improved strikingly after treatment with radioactive iodine.

The key insight was that some metastatic thyroid-cancer deposits, scattered far from the neck, still behaved like thyroid tissue and still took up iodine. That meant radioiodine could seek them out wherever they had lodged in the body and irradiate them selectively — a genuinely new idea in cancer treatment, where most therapies of the era could not target disease that had already spread. The case attracted enormous attention, helping to establish radioiodine as a standard treatment for metastatic differentiated thyroid cancer and cementing the thyroid’s special place in the early history of nuclear medicine.

It is worth noting, in the interest of accuracy, that Seidlin himself was carefully cautious in print: he wrote that despite the remarkable clinical improvement it could not be concluded that the tumours had been completely destroyed. That honesty is part of why the report endures — it captured both the real promise of radioiodine and the appropriate scientific restraint about it. The treatment Seidlin reported is, in refined form, still used for metastatic thyroid cancer today.

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Radiation as a Cause: The Lesson of Chernobyl

The same biology that makes thyroid cancer treatable with radioiodine also makes the gland uniquely vulnerable to radioactive iodine in the environment — and the most dramatic proof of this came from catastrophe. When the Chernobyl nuclear reactor in present-day Ukraine exploded on April 26, 1986, it released large quantities of radioactive iodine-131 into the air. That fallout settled on pastures, was eaten by cows, and concentrated in their milk; children who drank the contaminated milk absorbed the radioiodine straight into their growing thyroid glands, where its radiation damaged the cells’ DNA.

Beginning roughly three to four years after the accident, doctors in Belarus, Ukraine, and the contaminated regions of Russia observed a sharp and unmistakable rise in thyroid cancer in children and adolescents — far above the normally very low childhood rate. The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) concluded that this surge of childhood and adolescent thyroid cancer is the clearest documented health consequence of the disaster, with many thousands of cases attributed to it among those who were young at the time of exposure. Children proved especially susceptible because their thyroids are small, growing, and metabolically active, and because of their high milk intake.

Chernobyl provided, in the most painful way, definitive human evidence for something researchers had long suspected: ionizing radiation, especially in childhood, causes thyroid cancer. This lesson reshaped public-health practice. It is why potassium-iodide tablets are stockpiled near nuclear plants — flooding the thyroid with ordinary, non-radioactive iodine blocks it from absorbing the radioactive kind — and why radiation exposure of the head and neck in children (including, historically, certain medical X-ray treatments) is now recognized as a major risk factor and avoided whenever possible.

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The RET Gene, MEN2, and Inherited Medullary Cancer

While radioiodine and radiation dominate the story of the common follicular-cell cancers, the medullary form opened an entirely different and equally important chapter: the discovery that some thyroid cancer is inherited, and that it can be predicted — and even prevented — by reading a person’s genes. Medullary thyroid carcinoma had long been known to run in some families, sometimes alongside tumours of the adrenal and parathyroid glands in syndromes called multiple endocrine neoplasia type 2 (MEN2). The question was why.

The answer arrived in 1993, when two independent research groups reported that inherited (germline) mutations in a single gene — the RET proto-oncogene on chromosome 10 — were the cause of the MEN2 syndromes and of familial medullary thyroid carcinoma. (The gene had already been mapped to chromosome 10 by linkage studies in the late 1980s; the 1993 work pinned down the specific causative mutations.) RET is a gene whose normal job is to help cells receive growth signals; certain mutations leave it stuck in the “on” position, driving the C-cells toward cancer. This was one of the era’s landmark demonstrations that a hereditary cancer could be traced to specific, identifiable mutations in one gene.

The clinical impact was profound and is one of the clearest success stories in all of cancer genetics. Because a simple blood test can now reveal whether a family member carries the dangerous RET mutation, at-risk relatives can be identified before cancer ever appears, and surgeons can remove the thyroid pre-emptively — preventing a cancer rather than merely treating it. More recently, the discovery that RET drives these tumours has led to targeted drugs that block the overactive RET protein, an approach that also benefits some patients with non-inherited, RET-driven thyroid cancers. The path from a 1959 microscope slide to a 1993 gene to a modern targeted therapy is a model of how understanding a cancer’s root cause transforms its care.

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Overdiagnosis, Screening, and Active Surveillance

The most modern chapter in thyroid-cancer history is, paradoxically, about finding too much cancer. As high-resolution neck ultrasound became widespread, doctors began detecting very small papillary thyroid cancers — some only a few millimetres across — that would likely never have caused symptoms or harm in a person’s lifetime. Detecting and treating such cancers is called overdiagnosis, and it can lead to overtreatment: surgery, lifelong hormone replacement, and anxiety for a “cancer” that was never going to threaten the patient.

The starkest illustration came from South Korea. After thyroid ultrasound screening was widely added to routine health check-ups, the rate of thyroid-cancer diagnoses soared — reported in a widely cited 2014 New England Journal of Medicine analysis (Ahn, Kim, and Welch) as roughly fifteen times the rate two decades earlier. Yet the number of people dying from thyroid cancer barely changed. That combination — an explosion of diagnoses with flat mortality — is the classic signature of overdiagnosis: screening was finding a huge reservoir of tiny, harmless cancers without saving more lives. The finding prompted Korean physicians to publicly discourage indiscriminate screening, after which diagnosis rates fell substantially.

The response to this problem produced one of the gentler revolutions in oncology: active surveillance. Rather than immediately operating on every small, low-risk papillary cancer, doctors carefully watch it with periodic ultrasounds, stepping in with surgery only if it actually grows or spreads. The pioneering work came from Akira Miyauchi and colleagues at Kuma Hospital in Japan, where a clinical observation program for low-risk papillary microcarcinoma was proposed in 1993. Over decades of follow-up, the great majority of these tiny tumours stayed stable, very few progressed, and patients on surveillance did not die of thyroid cancer — evidence strong enough that active surveillance is now an accepted option in major guidelines. Together, the overdiagnosis story and the rise of active surveillance mark a hard-won maturity in the field: the recognition that, for thyroid cancer, the wisest treatment is sometimes patient, watchful restraint.

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Research Papers and References

The references below combine landmark peer-reviewed papers and authoritative historical reviews with curated PubMed topic-search links into the primary literature. Where a stable DOI or a specific paper could be confirmed, it is cited directly; otherwise a PubMed topic search is provided so readers can reach the underlying studies. Each link opens in a new tab.

  1. The Nobel Prize in Physiology or Medicine 1909 — Emil Theodor Kocher, “for his work on the physiology, pathology and surgery of the thyroid gland.” — NobelPrize.org — 1909 Prize summary
  2. Tan SY, Merchant J. Emil Theodor Kocher (1841–1917): thyroid surgeon and Nobel laureate (biographical review). — PubMed: Kocher thyroid surgery Nobel history
  3. Hertz S, Roberts A. Radioactive iodine in the study and treatment of thyroid disease (foundational radioiodine work, Massachusetts General Hospital / MIT). — PubMed: Hertz Roberts radioactive iodine thyroid
  4. Fahey FH, Grant FD, Thrall JH. Saul Hertz, MD, and the birth of radionuclide therapy. EJNMMI Physics. 2017;4(1):15. — doi:10.1186/s40658-017-0182-7
  5. Seidlin SM, Marinelli LD, Oshry E. Radioactive iodine therapy: effect on functioning metastases of adenocarcinoma of the thyroid. JAMA. 1946;132(14):838–847. — doi:10.1001/jama.1946.02870490016004
  6. Hazard JB, Hawk WA, Crile G Jr. Medullary (solid) carcinoma of the thyroid — a clinicopathologic entity. Journal of Clinical Endocrinology & Metabolism. 1959;19(1):152–161. — doi:10.1210/jcem-19-1-152
  7. Mulligan LM, et al. Germline mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993;363(6428):458–460. — doi:10.1038/363458a0
  8. Donis-Keller H, et al. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Human Molecular Genetics. 1993;2(7):851–856. — doi:10.1093/hmg/2.7.851
  9. Ahn HS, Kim HJ, Welch HG. Korea’s thyroid-cancer “epidemic” — screening and overdiagnosis. New England Journal of Medicine. 2014;371(19):1765–1767. — doi:10.1056/NEJMp1409841
  10. Ito Y, Miyauchi A, et al. Active surveillance of low-risk papillary thyroid microcarcinoma: the Kuma Hospital experience. — PubMed: active surveillance papillary microcarcinoma (Kuma / Miyauchi)
  11. UNSCEAR assessments of the Chernobyl accident — childhood thyroid cancer and iodine-131 exposure. — PubMed: Chernobyl childhood thyroid cancer iodine-131
  12. Williams ED. Cellular origin of medullary thyroid carcinoma in the parafollicular C-cells (historical). — PubMed: medullary thyroid carcinoma C-cell origin
  13. History of radioactive iodine theranostics in differentiated thyroid carcinoma (review). — PubMed: history of radioiodine theranostics in thyroid cancer
  14. RET-targeted therapy (selective RET inhibitors) in RET-altered thyroid cancer. — PubMed: selective RET inhibitors in thyroid cancer

External Authoritative Resources

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Connections

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