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the intellectual
the intellectual
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Editor’s note
This is an old article published by "Intellectuals" on May 4, 2017. The original article was ruled inappropriate by the court in four places. It has now been deleted and pointed out for infringement. content and then re-publish it, leaving readers with a problem-free version of the article. For details about the judgment, please see the apology statement released on March 19.
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2017 Holidays, CCTV News, People's Daily and CCTV "Economic Half Hour" program also released a news "major breakthrough! A drop of blood can test cancer, which has been approved for clinical use! Made in China! !" Unexpectedly, the news report with these three exclamation marks was a success, causing many professionals and media to question it for "misleading the public" and "false propaganda."
In fact, the heat shock protein 90α quantitative detection kit, regarded as a "major breakthrough", was approved by the State Food and Drug Administration (cfda) as early as 2013. However, it was only approved by multiple CCTV columns on this Labor Day. Pay attention, and especially emphasize that this technology is "Made in China". Can this result detect cancer and truly benefit patients? Who is Luo Yongzhang who made the "historic breakthrough"?
CCTV’s report received a large number of forwards and comments, and some commentators said that the report should be more rigorous.
"People's Daily" has a high popularity, which makes this news have a high degree of attention.
"Blood drop cancer test" has been questioned
On November 28, 2013, Science Network blogger Dr. Wang Shouye expressed strong doubts about the news that "Tsinghua professor discovered that a new tumor marker development reagent can detect cancer."
A few years later, the news of "blood cancer test" was once again reported on CCTV. Wang Shouye, who is now the president of the Chinese Antibody Association, couldn't help but feel deeply. He posted an old article and did not want to comment anymore. He just reiterated that he takes responsibility for the article.
's so-called "blood drop cancer test" heat shock protein 90α quantitative detection kit uses enzyme-linked immunoassay technology (elisa), which is already a very mature technology. It uses a highly specific antigen-antibody reaction to detect the Only a small amount of tumor antigens in the blood can also be detected using this method. Wang Shouye believes that bleeding is just a gimmick to promote the technology.
An industry insider who did not want to be named told Intellectuals that the real drop of blood test is to prick your fingertip just like measuring blood sugar, put a drop of whole blood on the fingertip on the test paper, and immediately insert it into the blood glucose meter for testing. , the blood glucose reading is displayed immediately. The hsp90α product of Yantai Proji Biotechnology Development Co., Ltd. uses enzyme-linked immunoassay. The operation must first draw a few milliliters of venous blood, then centrifuge to separate the serum/plasma, and then take out 50-100 microliters from it and put it in The reaction wells of the microplate plate can be placed in the microplate reader for detection after repeated incubation and washing. To describe such a complicated testing process as "a drop of blood" is to change the concept and mislead people to accept it.
A Weibo account suspected to be that of Professor Luo Yongzhang made a special reply to this news on the evening of May 1st. The statement that "a drop of blood detects tumors" is very inaccurate. To be precise, it should be called "monitoring tumors."
Limited diagnostic significance
Although "monitoring" and "detection" are the same word, their clinical significance is far different. Monitoring is just an assessment concept, while detection is a diagnostic concept, emphasizing the detection of tumors.
It is worth noting that the heat shock protein 90α quantitative detection kit (enzyme-linked immunoassay) obtained the registration certificate in 2013. The registration approval document of the State Food and Drug Administration clearly states that the scope of use is "This product is used to quantitatively detect heat shock protein 90α in EDTA-K2 anticoagulant plasma of non-radiotherapy lung cancer patients. This indicator is used to monitor the condition of patients with confirmed lung cancer and Efficacy evaluation.” It means that the clinical trial subjects of this product when it was registered and approved were only diagnosed and untreated lung cancer patients.
Professor Sun Yan, a senior academician of the Chinese Academy of Engineering, had a direct conversation with Luo Yongzhang in the article "Serum markers are not recommended for lung cancer screening in asymptomatic or high-risk groups" published in February 2016, saying: "I am A friend from Tsinghua University found that the positive rate of heat shock protein in tumor patients is more than 80%, while the positive rate in normal people is about 10% to 20%, so he vaguely claimed to have found a good early diagnosis indicator of tumors. It just confuses the concepts of monitoring indicators and diagnostic indicators. Maybe this heat shock protein is useful, but there are both false positives and false negatives in its experimental results, so it has no diagnostic value. "
In fact, in 2013. On November 17, 2019, the School of Life Sciences of Tsinghua University announced that Professor Luo Yongzhang had made a major breakthrough in discovering a new tumor marker for the first time in the world - heat shock protein 90α (hsp90α). He had to clarify that he did not say that the hsp90α quantitative detection kit he developed could screen various cancers, but emphasized that the correct statement should be "the hsp90α quantitative detection kit is the world's first to use hsp90α protein in the 24 years since its discovery." Its clinical products play an important role in improving the condition monitoring and efficacy evaluation of cancer patients and realizing personalized cancer treatment. "How did
hsp90α obtain the national third-class (highest category) medical device certificate?
On the website of the Tsinghua University Academy of Sciences, the report stated that the product has obtained the highest level of Class III certification from the State Food and Drug Administration. However, in fact, as long as the relevant product involves cancer, it must apply for Class III registration application with the State Food and Drug Administration. (For more information, please see cfda: http://www.sda.gov.cn/ws01/cl0053/103757.html) An obvious fact is that there are more than tens of millions of production and sales companies that have obtained Class III registration certificates nationwide.
In 2013, Professor Luo Yongzhang released scientific research results to the outside world.
In vitro diagnostic reagent registration management measures. Picture taken from cfda website
hsp90α How valuable is it in tumor screening? The
Heat Shock Protein 90α Quantitative Detection Kit can currently be used to quantitatively detect heat shock protein 90α in EDTA-K2 anticoagulated plasma of non-reflective lung cancer and liver cancer patients, as a way to monitor the condition and evaluate the efficacy of patients with lung cancer and liver cancer. In the recent "Economic Half-Hour" program, Cheng Jing, an academician of the Chinese Academy of Engineering, also said that heat shock protein 90α can predict distant metastasis in the lungs and can help doctors determine whether tumors have metastasized remotely, which will help their clinical judgment and diagnosis. helpful.
The above-mentioned industry insiders said that heat shock protein 90a is indeed a useful new product for prognosis assessment and efficacy monitoring of lung cancer. It is not easy to promote it in hospitals all over the country recently. It provides doctors with a new weapon to diagnose and treat patients with lung cancer, which is a good thing. However, criticism from the academic community is that it is wrong to exaggerate the use of this new product for cancer screening. Industry experts have pointedly pointed out that abusing tumor markers such as 90a for health check-ups is " tantamount to murdering money and killing people!" "We are in vitro. I have worked in the diagnostic circle for many years and have learned a little bit about the truth. I am writing this to my colleagues, relatives and friends because I am afraid that you will be encouraged to spend money unnecessarily."
The currently clinically recognized liver cancer biomarker is the clinically recognized liver cancer marker alpha-fetoprotein (afp). According to reports, heat shock protein 90α can detect liver cancer patients with negative afp test results, with a detection rate as high as 94%. , and can play a role in the early detection of liver cancer.
As of now, there are three ongoing clinical trials related to heat shock protein 90α, calling it a broad-spectrum tumor marker. Further research and confirmation are needed. If the use of this new product is exaggerated and its broad spectrum is promoted, Using it for cancer screening is contrary to the facts.
Currently, there are dozens of different types of tumor biomarkers, and heat shock protein 90α is just one of them. It has certain value in the early diagnosis of cancer, but it is emphasized that it has a major breakthrough and is a global problem. It's obviously an exaggeration.Appropriate tumor markers can detect tumor progression earlier, but CT and B-ultrasound are still the gold standards for detecting tumors. Biomarkers are only an effective auxiliary detection method, and their role and value should not be exaggerated.
It is worth mentioning that although the heat shock protein 90α quantitative detection kit was approved for production by cfda in 2013, according to the management of Yantai Proji Biotechnology Development Co., Ltd., which is responsible for producing the kit, revealed on the "Economic Half Hour" program , which has yet to resolve production issues.
Luo Yongzhang’s story
After holding a press conference at Tsinghua University in 2013 to announce a “major breakthrough,” Luo Yongzhang was questioned by academic circles at home and abroad.
Wang Shouye summarized in a subsequent blog post that Professor Luo Yongzhang only published the first paper on hsp90α in 2009, and there is no evidence that he "discovered hsp90α as a brand-new tumor marker for the first time in the world". Many researchers have studied heat shock protein 90α before him. Professor Luo Yongzhang is neither the pioneer nor the most influential scholar in this field.
The aforementioned industry insiders recently told Intellectuals that the entire family of heat shock proteins, including 90α, has long been confirmed by domestic and foreign scholars. In 1989, Weber's research group reported the full-length gene sequence of human hsp90α for the first time, confirming the identity of the protein. In 1992, Ferrarini's research group discovered that human hsp90α can be secreted extracellularly by tumor cells and can be used as a tumor marker. In 2002, Neckers Research Laboratory published a paper proving that hsp90α levels are increased in the blood of patients with metastatic cancer.
Luo Yongzhang is the director of the National Engineering Laboratory of Anti-tumor Protein Drugs. The honorary director of the laboratory is jointly served by Zhou Guangzhao, an academician of the two academies, and James D. Watson, one of the discoverers of the DNA double helix structure. In media reports, there are many expressions of Watson's appreciation for Luo Yongzhang's work.
In fact, at a press conference held in Tsinghua University in 2013, Watson did write to Luo Yongzhang to express his congratulations: "You have firmly established the concept of hsp90α as a tumor marker and successfully developed a quantitative detection kit for this protein. , used for clinical monitoring in China. Congratulations to you, your team and Tsinghua University for achieving such great achievements in such a short period of time!"
Luo Yongzhang takes a photo with Watson. Picture from tsinghua.edu.cn
The aforementioned industry insiders reminded that Watson is sure of the clinical value of hsp90α as a tumor marker. As for whether the hsp90α kit can widely detect various cancers, it obviously requires more clinical data. Only with support can a conclusion be made. He further emphasized that in 2009, Watson also recommended a mouse study that Professor Luo Yongzhang participated in when he was a visiting scholar in the United States. The paper was published in the Proceedings of the National Academy of Sciences (pnas). The study was conducted through in vitro Cultured lung adenocarcinoma cell lines and mouse metastatic lung cancer models were used to study the mechanism and role of hsp90α in the secretion of metastatic cancer cells. This is a basic study based on mice and does not have any clinical data.
In Luo Yongzhang's research career, another work that was questioned was the national first-class new drug he developed, also known as the "world-class new anti-cancer drug" - Endu.
American scientist Judah Folkman was the first discoverer of angiotensin (angiostatin) and endostatin (endostatin). He discovered the two proteins in 1991 and began developing them through the company he founded, entremed.
In 1999, Luo Yongzhang returned to China and began to develop new drugs based on endostatin, and founded Medezin Bioengineering Co., Ltd. in Yantai as the chief scientist. He knew that endostatin was unstable and stabilized it by adding a few amino acids. In 2003, he successfully developed Endu, a new drug that inhibits blood vessel growth, and was later named one of the "Top Ten Science and Technology News in China in 2005".
folkman did not know at first that Luo Yongzhang was studying the protein endostatin he discovered until he learned about it in a report. Then he contacted Luo Yongzhang through a Chinese scientist in the laboratory and asked for some drug endostatin. He found that endostatin was indeed more effective than endostatin.
According to a report in the Wall Street Journal in 2005, because the cost of developing endostatin was too high, and its properties were unstable in vitro and easy to decompose, and most importantly, it did not bring much benefit to patients, entremed later had to gave up and transferred the patent to Boston Children's Hospital.
Luo Yongzhang intends to enter the US market, but if the drug wants to enter the US market, it will obviously face patent disputes. "Because the structures of Endostatin and Endostatin are very similar, Boston Children's Hospital owns the patent for Endostatin, which involves protein preparation methods, tumor treatment, etc. If Endostatin intends to enter the U.S. market, it needs a patent license." Leslie Grushkin-Lerner, intellectual property manager at Boston Children's Hospital, said. The endostatin patent applied by
folkman.
Endu’s Chinese patent.
Endo applied for a U.S. patent, but it was still filed under the name of modified endostatin. It only took 4 years for
Endo to go from phase I clinical trial to CFDA approval for production, which is amazing. At that time, Endo received full support from the country. In September 2006, Simcere Pharmaceuticals acquired 80% of Medezin Biological shares for only 200 million yuan, and Endo was subsequently put on the market by Simcere Pharmaceuticals.
Although Endo holds patents in both China and the United States, its entry into the U.S. market is still limited by the patent restrictions of endostatin.
Currently, this drug is approved for the treatment of non-small cell lung cancer. According to reports, its combined use can extend the median survival time of patients with advanced NSCLC to about 17 months. However, some experts said that its single drug has an objective response to lung cancer patients. The rate is only about 3%, which is almost equivalent to the "vitamin effect".
An industry insider commented that this is by no means the first and there is no innovation in technology.
