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The Leukemia "Shanghai Protocol" Should Be Renamed the "Harbin-Shanghai Protocol"

发布时间：

2026-09-26

The Leukemia "Shanghai Protocol" Should Be the "Harbin-Shanghai Protocol"

Sun Zuodong

Disclaimer: This article is compiled based on published papers, publicly available media materials and the author’s personal experience at the 2018 National Technical Invention Award defense hearing. It is intended solely for historiographical deliberation and does not constitute any legal finding of "plagiarism". Some claims circulating online remain uncorroborated. Readers are invited to form their own independent judgments.

Today I choose to speak out, hoping to reconstruct the full account of a collective research breakthrough in Chinese medicine. Records of scientific contributions ought to duly acknowledge the efforts of all participants. There should be room for debate over the historical attribution of academic achievements. That said, content involving fabricated facts or defamatory remarks falls outside the scope of legitimate discussion.

Acute promyelocytic leukemia (APL) was once a deadly hematological disease. Combination therapy with all-trans retinoic acid and arsenic trioxide has drastically boosted cure rates and represents a world-renowned Chinese medical achievement. Internationally, this therapeutic regimen is widely referred to as the "Shanghai Protocol". Nevertheless, a thorough review of research trajectories shows that the pioneering early-stage clinical work by the Harbin team must not be overlooked. From the perspective of complete Chinese scientific historiography, it should rather be documented as the "Harbin-Shanghai Protocol". This is not to negate the established name, but to restore a chapter of history that has been obscured by narratives in international academic publications.

I. Origins in Harbin: From Folk Remedy to Clinical Validation

Folk practices using arsenic-containing prescriptions to treat tumors existed early on in Lindian County, Heilongjiang Province. In 1971, Han Taiyun, a pharmacist at the First Affiliated Hospital of Harbin Medical University, adapted these topical formulations into an intravenous preparation: Injection-713 (Ailing-1). Led by Zhang Tingdong, the Department of Traditional Chinese Medicine carried out systematic clinical validation. Researchers progressively isolated components of the compound preparation and confirmed arsenic trioxide as its core active ingredient. This intervention focused on eliminating existing malignant leukemia cells in the body, constituting a symptomatic treatment targeting pathological manifestations. Zhang Peng completed large-sample clinical studies on purified arsenic trioxide, and Sun Hongde conducted long-term follow-up of patient cases. Both were key members of the Harbin research team.

According to certain public application documents and media reports, discussions regarding author attribution once took place within the Harbin team. Sources state that when filing the patent for arsenic trioxide injection in 1995, only Zhang Tingdong was listed as inventor. Zhang Peng and Sun Hongde argued that they had made core contributions which were inadequately reflected in the patent record. Disputes over attribution repeatedly thwarted the team’s applications for the National Technical Invention Award. Debates over the historical contributions of this work persisted within academic circles through Zhang Tingdong’s later years.

II. Mechanistic Breakthroughs by the Shanghai Team

In the 1980s, Wang Zhenyi’s team established differentiation-induction therapy using all-trans retinoic acid and published corresponding clinical outcomes in 1988. Research groups led by Chen Zhu and Chen Saijuan later collaborated with researchers in Harbin. They elucidated the molecular mechanism whereby arsenic trioxide degrades the PML-RARA fusion protein, developed the combined-drug regimen, and promoted its global roll-out. This therapy consequently became known in international literature as the "Shanghai Protocol".

The Harbin team was the first to verify the clinical efficacy of arsenic trioxide in eradicating malignant leukemia cells. At the molecular level, the root cause of the disease lies in mutations generating the PML-RARA fusion protein. Two fundamentally competing causal hypotheses once existed regarding the pathogenesis of APL: whether genetic mutations trigger leukemia, or leukemic progression gives rise to genetic alterations. According to collations from online self-media sources, Zhu Yuejun, then a doctoral candidate, arrived at experimental inferences contradicting the mainstream stance of the research group and subsequently left the team. Scientific breakthroughs often hinge on a thin margin; once articulated, many critical academic insights can serve as cornerstones for subsequent research. This episode has for years fueled online debates concerning the attribution of academic credit.

One core principle of the Nobel Prize in Physiology or Medicine is to trace the origin of original scientific ideas.

This life-saving therapy is the product of successive collective endeavors spanning generations of researchers. Judged against Nobel Prize assessment criteria, credit ought to be allocated to those who first made clinical discoveries, those who clarified molecular mechanisms, and those who refined therapeutic protocols. While the Nobel Prize is not awarded posthumously, medical historiography should preserve the pioneering work of trailblazers.

The therapeutic value of this regimen stems from its dual-level synergistic effect: arsenic trioxide directly eliminates diseased cells, whereas genetic-level research explores the root origin of the illness. The Harbin team paved the clinical path for treatment; researchers in Shanghai refined the understanding of its molecular mechanisms.

In 2020, the Future Science Prize in Life Science was jointly awarded to Wang Zhenyi and Zhang Tingdong. The official award recognized their respective decisive contributions: Wang Zhenyi for all-trans retinoic acid and Zhang Tingdong for arsenic trioxide in treating APL, formally acknowledging the historical accomplishments of the Harbin team. Scientific progress relies on continuous new propositions from researchers. Wang Zhenyi himself has repeatedly stated publicly that the "Shanghai Protocol" was not an individual invention. He underscored the unique value of research on arsenic compounds carried out by Professor Zhang Tingdong’s team at Harbin Medical University starting in the 1970s, noting that all parties had invested tremendous effort.

III. A Chance Encounter at the 2018 Award Defense

In 2018, I attended the defense for the National Technical Invention Award at the Harbin Science and Technology Building. Outside the venue I chanced upon Zhang Tingdong: he was leaving after completing his defense while I was about to enter for mine. Our projects were scheduled for the same session. President Yang Baofeng and other individuals were also present. Academic communities can be small. This brief encounter gave me a tangible sense of the hardships endured by older-generation researchers striving amid difficult conditions, and spurred my sustained interest in this chapter of medical history.

IV. Practical Reflections: Who Should Adjudicate Academic Disputes?

The merits of scientific claims should be judged by the scientific community itself. The historic Scopes Trial a century ago delivers a profound lesson: courts may rule on whether conduct violates the law, yet they have no jurisdiction to pass judgment on the truth or falsity of scientific theories. Religion and science should each abide by their own boundaries; using judicial power to intervene in scientific controversies hinders the advancement of human civilization.

Disentangling credit for intellectual contributions falls within the domain of the history of science. Clashes among divergent viewpoints are normal in research. When major unresolved controversies surround an academic episode and parties interpret its background and sequence of events in radically different ways, resorting to criminal compulsory measures demands extreme prudence. Should factual misjudgments occur, subsequent correction and remedy for infringed rights will prove extremely difficult — as the saying goes, it is easy to summon a spirit but hard to send it away.

Public authority must observe clear boundaries: distinguishing debates over academic viewpoints from illegal infringements. Criminal instruments should not be readily deployed against speech limited to sorting out historical facts and exchanging scholarly critiques. Legal sanctions shall apply only in cases involving proven fabrication of facts, malicious personal attacks and other explicit illegal acts. It is hoped that space for science communicators to objectively reconstruct history can be safeguarded, so that people are not penalized merely for holding alternative academic perspectives.

Academic discourse should embrace pluralistic viewpoints. When disputes over intellectual ownership arise, all parties should have equal channels to file appeals. The judicial system is not tasked with determining whether science is right or wrong. If people dare no longer express dissenting views, science can hardly evolve.

Every link in the research chain deserves to be seen: inspiration derived from folk herbal prescriptions, Han Taiyun’s formulation development, clinical validation by Zhang Tingdong’s team, long-term case studies by Zhang Peng and Sun Hongde, Zhu Yuejun’s experimental explorations back then, as well as mechanistic interpretations by the Shanghai team. Major medical achievements are mostly fruits of collective collaboration; pioneering front-line explorations ought not to be omitted from historical narratives.

V. Historical Reflections

The clinical discovery of arsenic-based therapy took place in Harbin; mechanistic elucidation and standardization of the combined therapeutic regimen were accomplished in Shanghai. Their work represents relay-style scientific exploration.

International academic papers name it the "Shanghai Protocol". From the full perspective of Chinese scientific history, it deserves to be called the "Harbin-Shanghai Protocol".

Harbin delivered clinical validation of the drug; Shanghai clarified its molecular mechanisms and formulated the combination regimen. Historical narratives that record only the Shanghai contribution leave a vital fragment untold in China’s medical history.

Medical historians may continue to discuss multiple themes: the clinical starting point in Harbin, mechanistic research and combination-therapy development in Shanghai, and questions of attribution within research teams. Discussion, however, does not equal accusatory judgment. Legitimate deliberations over credit belong to medical scientists and historians of science. Accusations of plagiarism, personal humiliation and organized online harassment cross the line of reasonable debate. This regimen has saved hundreds of thousands of patients worldwide and stands as a source of pride for Chinese medicine. How research contributions can be fully documented remains a topic worthy of continued reflection by future generations.

Closing Note: This article is compiled based on published papers, publicly-available media materials and the author’s personal observations from the 2018 award defense. Some claims circulating online await further verification. It is intended exclusively for historiographical discussion.

Appendix: Personal Reflection

First they came for the Communists, and I did not speak out — because I was not a Communist.

Then they came for the Jews, and I did not speak out — because I was not a Jew.

Then they came for the trade-unionists, and I did not speak out — because I was not a trade-unionist.

Then they came for the Catholics, and I did not speak out — because I was a Protestant.

Then they came for me — and there was no one left to speak for me.

— Martin Niemöller