Gu Jianren (1932–2022) He is a pioneer in tumor molecular biology, Academician of the Chinese Academy of Engineering, and lifelong Honorary Director of the Shanghai Cancer Institute. He established foundational frameworks for cancer-related gene research and gene therapy in China.

         Introduction

For generations of molecular oncology researchers, “Office 505” at the Shanghai Cancer Institute was more than just a workspace. Behind its time-worn oak door, where faded diagrams of DNA helices adorned peeling walls, Gu Jianren spent decades conducting a symphony of scientific discovery. This cramped room, perpetually redolent of aging paper and laboratory solvents, became a crucible where the complex language of cancer genes was gradually decoded.

Here, under the dim glow of a desk lamp that often burned past midnight, Gu transformed abstract genetic sequences into tangible hope for millions. His journey was defined by the relentless pursuit of a single question: What hidden script within human cells commands them to betray their own existence?

The Genesis of a Genetic Detective

Born in 1932 in the ancient, cultured city of Suzhou, Gu Jianren enjoyed a carefree childhood. His father was a renowned physician and one of the founders of the Second People’s Hospital of Suzhou. Growing up in this medically rich environment, Gu developed an early passion for medicine, aspiring to become a skilled surgeon dedicated to saving lives.

Gu did not consider himself a naturally gifted child. He often struggled with arithmetic, puzzled by classic logic problems, and found it difficult to grasp the nuances of language, barely passing his Chinese exams. However, he firmly believed that diligence could compensate for a lack of innate talent. If he didn’t understand something after reading it once, he would read it repeatedly until he grasped it.

In 1948, at just 16, Gu was admitted to the prestigious Shanghai First Medical College, embarking on his dream path. Alongside medicine, his love for classical music, particularly the symphonies of Beethoven and Mozart, was a constant companion, helping him mature throughout his long career.

In 1953, a national directive shifted Gu’s career toward basic medical research. Fate led him to pathology, where he found his calling. He moved to Guangzhou to study under two masters, Liang Boqiang and Qin Guangyu. Even in his later years, Gu vividly recalled his first cadaver dissection, a meticulous seven-hour exploration that left him with a profound reverence for life. He believed the essence of pathology was to “save the living, honor the deceased, and serve the people.” He had found his mission.

In 1954, Gu joined the pathology department of the Shanghai Cancer Hospital. Through his deep friendship with Professor Gu Suiyue, he learned a fundamental truth: “To be a good pathologist, one must not only explore the world under the microscope but also go to the wards, listen to patients, and connect with clinicians.”

Just as Gu thought he would dedicate his life to pathology, the course of his career changed again.

In 1958, the Shanghai Cancer Research Institute was established. As a leading pathologist, Gu was selected to join, with a mission to apply pathology to the study of tumor genesis. He realized his knowledge needed to expand. He began to ponder: If morphology alone couldn’t reveal how tumors develop, what could? Around this time, Chargaff’s work “Nucleic Acids” was published. Gu devoured the book, realizing that the malignant behavior of cancer cells must be linked to their genetic material. The newly proposed double helix theory and the nature of the four bases—A, G, C, and T—piqued his intense interest.

At 28, Gu embarked on a new academic quest. He joined the Institute of Cell Biology at the Chinese Academy of Sciences, working as a lecturer but learning as a student for four years. Under the guidance of Professor Lü Jiahong, he began to explore the world of biochemistry and molecular biology. During this period, he worked in the lab by day and prepared for his future research at night.

It was here that a series of experiments offered a glimpse of hope. When he transferred the RNA of normal mouse liver cells into liver cancer cells, not only was the cancer’s growth inhibited, but its metabolism also began to revert to a normal state. This discovery suggested the possibility of reversing cancer’s malignant behavior. From that moment on, the study of tumor nucleic acids became the focus of his lifelong career.

Over the next half-century, Gu came to understand that while completely reversing solid tumors was unlikely, their “evil” behavior could be suppressed with the right therapies. This could lead to a harmonious coexistence between the tumor and the host—a state of “living with cancer.” This hypothesis painted a new picture of hope.

In 1978, Gu went to the UK as a state-sponsored student to study at the Beatson Institute for Cancer Research in Glasgow under the renowned molecular biologist Professor John Paul. He felt as though he had sailed into the vast ocean of molecular biology, witnessing its boundless expanse.

After three years of intense study, armed with a deep understanding of gene expression and regulation, Gu returned to China. It was from this point that he began his new journey: researching the oncogenes and related genes of primary liver cancer.

Decoding the Oncogene Constellation

In the 1980s, the prevailing international view held that cancer was caused by mutations in just one or two genes. Gu Jianren challenged this dogma, becoming the first to report that liver cancer involves the activation of multiple proto-oncogenes and growth factor receptor genes. He argued that cancer isn’t the result of a single gene’s failure, but is driven by a constellation of genes that collectively fuel its development and progression.

In 1981, Gu led a national research project under China’s “Sixth Five-Year Plan” focused on isolating liver cancer oncogenes. He explained that these oncogenes originate from normal “proto-oncogenes,” which serve vital functions in embryonic development and cell regeneration. Gu’s theory was that these genes are kept in check in healthy cells. However, when triggered by environmental factors like carcinogens, radiation, or viral infections, they can become activated. This activation leads to the overproduction of cancer-causing proteins, resulting in abnormal cell metabolism, uncontrolled proliferation, and ultimately, cancer.

Throughout the 1980s, the idea that a single gene alteration could induce a tumor remained dominant. After years of research, however, Gu and his team identified the abnormal activation of seven specific oncogenes and related genes—including N-ras, c-myc, and c-est2—in liver cancer. This created a distinct “oncogene profile” for the disease, reinforcing Gu’s conviction that its development is not due to one or two genes, but a whole set of abnormally activated genes. These findings were crucial in paving the way for the now widely accepted multi-gene model of carcinogenesis.

Gu also made significant strides in linking the hepatitis B virus (HBV) to liver cancer. He pioneered the use of HBV DNA as a key marker for infection, developing a diagnostic platform using dot blot hybridization. In collaboration with others, he also identified the critical role of the HBV X gene in tumor formation. These achievements profoundly advanced the scientific understanding of how liver cancer develops and improved strategies for its prevention and treatment.

By the late 20th century, the international focus in tumor genomics was largely on cDNA expression profiles, which measure gene activity. Gu, however, saw a limitation in this approach, believing that only a fraction of expressed genes are actually involved in cancer development. He innovatively designed a high-throughput screening platform based on cell growth, which could directly identify genes at the genomic level that either promote or suppress tumor growth. This novel strategy accelerated the discovery of valuable new genes, advancing cancer diagnostics, drug development, and gene therapy.

After more than six years and over 90,000 transfection experiments, Gu’s team identified 3,814 genes that either promoted or inhibited cell growth. These included 2,836 known genes, 372 entirely new genes, and 598 novel gene sequences. While analyzing the known genes, Gu made an unexpected discovery: a class of genes related to environmental factors, nutrition, redox processes, immunity, and neurotransmitter receptors, all linked to cell growth. He classified these as “systemic regulatory gene clusters.” This data provided a groundbreaking new perspective on the mechanisms of cancer.

Gu recognized that while genetic defects are central to cancer, environmental factors like chemicals, viruses, and nutrition also play critical roles. He argued that research should not be confined to the tumor itself. This led him to redefine cancer as a “systemic disease characterized by the abnormal growth of local tissue cells.” In his view, tumorigenesis is the result of a systemic regulatory imbalance. This work, published in the prestigious journal PNAS, was met with high international acclaim, with experts stating he had “opened a new field.”

If cancer is a systemic disease, Gu argued, then its treatment must be fundamentally rethought. He emphasized that therapy must not compromise the body’s own regulatory and repair systems. For early and intermediate-stage cancers, he believed that surgical or local interventions should not just remove the lesion but also facilitate the restoration of the body’s overall function. This requires a new focus on repairing and rebuilding the body’s regulatory balance. Discovering new biomarkers in the nervous, endocrine, and immune systems to detect and restore this equilibrium, he concluded, would be a critical direction for future research.

The Gardener of Scientific Ecosystems

Gu Jianren believed that scientific research thrives on teamwork, often likening his research team to a symphony orchestra. He emphasized the importance of unlocking each member’s potential and fostering collaboration to achieve the best possible outcomes.

In 1985, in recognition of its pioneering work in oncogene research, the Shanghai Cancer Research Institute was approved to establish the State Key Laboratory of Oncogene and Related Genes, becoming the first local research institute to receive such a prestigious designation. Gu Jianren was appointed as the laboratory’s inaugural director.

For 18 years, Gu led the laboratory with a blend of vision and pragmatism. He balanced long-term strategy with hands-on execution, promoting interdisciplinary collaboration and collective problem-solving to keep the laboratory at the forefront of scientific innovation.

He once told his colleagues and students, “Only about one-tenth of the ideas I propose may be correct. Even if I occasionally make mistakes that lead to failed experiments, I will take full responsibility.”

As director, Gu made it his mission to open the lab to nationwide collaboration, making it a partner for the broader academic community. Under his leadership, the lab achieved remarkable results. For instance, a partnership with West China University of Medical Sciences established an Rb tumor suppressor gene expression system in E. coli—the second such system globally. The lab also independently designed and synthesized peptide fragments to produce antibodies, confirming expression defects in all 19 cases of Chinese retinoblastoma studied. Furthermore, a graduate student from Zhejiang Medical University completed a groundbreaking study in Gu’s lab, demonstrating for the first time the integration of HBV DNA in fetal liver cells.

As a doctoral advisor, Gu led by example, creating a supportive environment for young researchers. He was dedicated to nurturing emerging scientific talent and took great pride in watching his students grow into leaders in their respective fields.

For Gu, learning was a lifelong pursuit. After turning 70, he refreshed his knowledge by studying updated editions of biochemistry and embryology textbooks. In 2004, he began teaching himself neurobiology. In the vast realm of scientific research, his footsteps never ceased.

The dream of “conquering cancer” drives every medical professional. In his later years, Gu remained motivated by a deep desire to heal and a profound curiosity about the human body. He often said, “If my health permits, and I can continue to solve key problems in cancer research, then my time on this earth will not have been in vain.” These words reflect the dedication of a true scientist, an inspiring legacy that continues to resonate.

Gu’s students span the globe. He mentored 42 doctoral and 23 master’s graduates, most of whom have become leaders in their fields. This is his legacy: a generation of medical leaders and a profound contribution to the advancement of medical science.

With remarkable strategic vision, Gu Jianren’s career was marked by significant milestones. Over his lifetime, he published more than 500 academic papers and obtained 58 Chinese patents. His body of work stands as a testament to his enduring impact on science and medicine.

The Unfinished Symphony

Reflecting on his decades-long scientific journey, Gu Jianren approached his numerous achievements and honors with a sense of humility. He remained deeply grateful to his mentors, friends, leaders, and family.

Throughout his life, Gu often reminisced about the mentors who had shaped his path. Professor Gu Suyue from the Tumor Hospital introduced him to oncology and pathology. Professors Lü Jiahong and Yao Zhen from the Chinese Academy of Sciences guided his major transition from pathology to cell biology and nucleic acid biochemistry. And Professor John Paul in the United Kingdom welcomed him into the realm of molecular biology.

He also expressed gratitude to Zhu Ruiyong, the former director of the Cancer Institute, for the opportunity to help establish a national key laboratory in Beijing.

His extensive experience led Gu to champion the integration of medicine and biology, the intrinsic link between morphology and function, and the unity that spans from molecules to cells, tissues, organs, and the entire organism. Reflecting on his path in cancer research, he once remarked with emotion, “It seems I have returned to the starting point, but perhaps it is a higher starting point.”

Gu once shared his personal philosophy: “In my life, I have studied pathology, seen outpatients, and conducted research. In any position, I have held fast to one belief: to be dedicated and to be happy. Being dedicated means doing the work at hand well and not letting time slip by idly. Even when my position changed, I had no regrets, because every experience is a precious life asset. And happiness comes from not being overly attached to gains and losses, for they are constant companions in life. This is a truth of the past, the present, and the future. We cannot change the timing or the circumstances, but everyone has their own sky above their head. Once you have chosen a path, you must walk it firmly and happily.”

In Gu’s view, the ultimate pursuit of science was to elevate it to the realm of art, to create a soul-stirring symphony. In his own words: “For everyone, science is an unfinished symphony.” Even in his nineties, his pursuit of science and truth never ceased.

Gu Jianren passed away on September 27, 2022. During the period of mourning, he received condolences from Party and state leaders, as well as from people across all walks of life. His words, “I am just an ordinary scientific worker with few accomplishments in my life,” continue to resonate deeply with many today.

“From earth’s embrace, the fragile sprout appears,

Defying tempest, conquering winter’s tears.

A spirit forged, in purpose strong and deep,

To fill the world with fragrance, secrets keep. ”

—Thus lived Gu Jianren, while silent ages sleep.

Editor: Chen Qing @ ShanghaiDoctor.cn

Note: Chinese Sources from “The Path of Benevolent Medicine” which was published in 2024. It records 90 important medical figures in the history of Renji Hospital. Yewen Renyi (ShanghaiDoctor.cn) team was one of the major writers of the book and is authorized by Renji hospital to create English version on the website of ShanghaiDoctor.cn