Editor Li Xinyi
September was originally the autumn harvest season, but for elizabeth holmes, the female version of Jobs and the founder of Theranos, an American blood testing company, winter came early.
Recently, the media reported that Holmes would be tried to pay for the "scam" he had set up before, which cost investors more than 700 million dollars. On September 2, the news rushed to the hot search list.
It is understood that from 2065438 to March 2008, Holmes and Theranos were accused of fraud by the US Securities and Exchange Commission (SEC) and faced fraud charges as high as 12. If convicted, Holmes will face up to 20 years in prison.
In fact, cancer detection through blood is a liquid biopsy technique. Liquid biopsy is a diagnostic technique to detect biomarkers and analyze tumors by collecting samples of human body fluids such as blood, effusion, urine and saliva. This technology has the advantages of convenient and fast sampling process, low invasion to human body, good compliance, non-invasion and high efficiency.
In recent years, there are more than 3.5 million new cancer cases and more than 2 million deaths in China every year, and the prevention and control situation is grim. Liquid biopsy technology makes it possible to screen cancer at an early stage. "The significance of early screening is that it can greatly improve the cure rate, greatly reduce medical expenses and improve the quality of life of patients." Ye Dingwei, Chairman of the Committee of Urogenital Oncology of China Anti-Cancer Association and Vice President of Fudan University Cancer Hospital, said in an interview with the media.
Blood drop cancer detection scam
In 20 14, Theranos, a star biotechnology company in Silicon Valley, spent nearly 60 billion yuan to create the myth of "blood test", which once sensationalized the whole country. The company claims to have invented a breakthrough and innovative technology. By collecting one or two drops of blood from fingertips, it can complete more than 240 tests that can only be completed by professional laboratories, ranging from cholesterol to cancer detection.
In its heyday, Theranos's valuation once reached 9 billion US dollars (nearly 60 billion RMB), and Holmes was also on the cover of the 20 14 issue of Forbes magazine. His bold remarks and black high collar made the media call him "female Jobs".
However, on 20 15 and 10, some media revealed that Theranos's "blood test causing cancer" was a shocking scam. The company bought Siemens instruments for testing and passed the test results off as its own products. The subsequent investigation results also show that the detection machine "Edison" invented by him is full of loopholes, and the related technology can't support the good wish of "drop blood to detect cancer".
20 18 In March, Sherlock Holmes and Theranos were accused of fraud by the US Securities and Exchange Commission (SEC) and faced fraud charges as high as 12. If convicted, Holmes will face up to 20 years in prison. The prosecutor said that she deliberately misled patients in the test and exaggerated the company's performance to investors.
Theranos also closed at 20 18. According to the latest news, Holmes' opening statement will be held on September 8, 20021year, and the trial is expected to last for 13 weeks.
In sharp contrast, in 20 16 1 year, Grail Company, the first American company to detect cancer with appearance technology, was established and immediately became popular. Both Google and Bill Gates participated in the investment. The person in charge of the above-mentioned enterprise pointed out that Grail was able to develop the corresponding technology because of its clear methodology in academics. Epigenetics can be used for tumor screening, which has been proved by many scientists' research and experiments, and has been recognized in the field of biology. Sherlock Holmes' so-called "blood test to prevent cancer" has never explained its scientific principle clearly, nor has it been recognized by professionals.
"Scientists' cognition is not determined by media and public evaluation, but by academic achievements. Without academic accumulation, even business geniuses can't make innovations, which is disrespectful to science. "The person in charge of the above-mentioned enterprises said.
Can blood test cancer?
In fact, the accusation against Theranos, an American blood test company, and its founder, elizabeth holmes does not mean that blood tests cannot detect cancer, but that the concept of blood tests for cancer itself is not scientific enough.
What is the principle of blood test screening for early cancer?
Generally speaking, the human body is composed of countless cells, all of which release DNA and protein into the blood, including mutated cancer cells. The DNA and protein mutations contained in cancer cells can be found by blood test after entering the blood, thus identifying early cancer.
For example, the team of researcher Chen Xingdong of Fudan University found that for five common malignant tumors, colorectal cancer, esophageal cancer, liver cancer, lung cancer and gastric cancer, the early cancer signal-micro-tumor methylation exists in the blood circulation and can be detected non-invasively.
In addition, the research team also found that in the early stage of disease development, even a few years before asymptomatic diagnosis, there will be cancer signals in the blood. Using samples from Taizhou prospective cohort, Fudan research team proved that DNA methylation sequencing can detect cancer earlier than traditional diagnostic methods.
Based on the methylation characteristics of ctDNA, researchers of Yao Yuan Gene designed a set of machine learning methods-Panseer. The specificity of the training set is 94.7%, and the sensitivity to the patient samples collected after diagnosis and the samples collected before diagnosis reaches 88% and 9 1% respectively. In an independent test sample set, the research team achieved 88% sensitivity in 1 13 patient samples collected after diagnosis on the premise that 207 healthy control samples reappeared 96% specificity. In addition, the detection sensitivity of 98 samples collected 1-4 years before diagnosis reached 95%.
Dr. Rui Liu, the correspondent of the above research and co-founder and chief technology officer of Yao Yuan Gene Company, believes that the biggest technical breakthrough of this research is to construct a targeted sequencing library of plasma free DNA by using semi-targeted PCR technology, which greatly improves the enrichment efficiency of methylated targets and solves the problems such as the scarcity of ctDNA in the plasma of early cancer patients, the high loss rate of DNA by conventional methods and the limited detection sensitivity.
Chen Xingdong said that at present, some foreign detection methods similar to various cancer early screening studies are very expensive. This study confirms that it is effective and economical to extract a small amount of DNA from a single tube of blood for detection as an early screening method for potential first-line cancer.
It's actually a liquid biopsy.
Cancer detection through blood belongs to liquid biopsy technology. Liquid biopsy is a diagnostic technique to detect biomarkers and analyze tumors by collecting body fluid samples such as blood, effusion, urine and saliva. The workflow of liquid biopsy includes sample collection, logistics and transportation, sample detection and inspection report.
Although tissue biopsy is the gold standard for tumor diagnosis and can be used for morphological and molecular evaluation, studies show that due to the heterogeneity within and between tumors of the same patient, tissue biopsy can not capture the genome panorama of all tumor loads of patients; In addition, tissue biopsy also has some shortcomings, such as invasive, unable to provide enough pathological samples, not suitable for dynamic monitoring, and not suitable for puncture in some tumor sites.
Liquid biopsy technology has the advantages of non-invasive and high efficiency. The sampling process of liquid biopsy is convenient and quick, with little trauma and good compliance. At the same time, the detection process is simple, the dependence on medical resources is low, the sample accessibility is high, and it is convenient for multiple sampling. The detection period is usually 1-2 weeks.
However, liquid biopsy technology also has some problems, such as poor capture ability, low detection rate and great individualization difference, and its technology is still being further improved.
According to the analysis of Toubao Institute, there are three main analytes in liquid biopsy technology. The first is the detection of circulating tumor cells (CTCs). This is a tumor cell that falls off from the solid tumor focus and enters the peripheral blood circulation spontaneously or due to diagnosis and treatment. Because it carries a lot of information related to the mechanism of tumor generation, metastasis and drug resistance, it can be used to monitor tumor dynamics and clinical treatment effect, and also to detect drug sensitivity.
At present, the clinical application value of CTC detection technology in judging the prognosis of patients with metastatic colorectal cancer, breast cancer and prostate cancer has been confirmed.
The second is the detection of circulating tumor DNA(ctDNA). CtDNA refers to the circulating DNA fragment released by tumor cells into human blood system, which comes from necrotic or apoptotic tumor cells, CTC and tumor exosomes, and contains gene mutations unique to tumor genome. It can be used to detect small residual lesions and occult metastatic lesions and monitor the therapeutic effect of tumors, and can also be used to analyze the changes of genetic information such as mutation, amplification and deletion of tumor cells. CtDNA detection can detect tumors before clinical symptoms appear, which has the application potential of assisting early diagnosis.
The third is foreign body detection. Exosomes are vesicles shed by tumor cells and distributed in body fluids such as blood, saliva and urine. Exosomes are usually produced and released in large quantities, and maintain the stability of vesicle components under the protection of outer lipid membrane, and the quantitative information they carry can predict the existence of malignant tumors.
At present, in the early screening market of liquid biopsy, start-up biotechnology companies such as Firestone Medicine and Pan Zi have made extensive arrangements. Recently, Grail, a cancer screening startup that American gene sequencing giant Illumina plans to acquire for $8 billion, is also developing liquid biopsy technology, hoping to screen cancers such as ovarian cancer at an early stage.
The market potential is huge
It is understood that there are more than 3.5 million new cancer cases and more than 2 million deaths in China every year, and the prevention and control situation is grim. In recent years, the incidence of lung cancer, breast cancer and colorectal cancer has obviously increased, while the incidence of liver cancer, gastric cancer and esophageal cancer remains high.
Taking liver cancer as an example, according to the research report of Southwest Securities, the market space for early screening and early diagnosis of liver cancer in China is as high as 200 billion yuan without considering the market penetration rate. Liquid biopsy technology makes it possible to screen cancer at an early stage. Whether in the field of tumor diagnosis, treatment or monitoring, the advantages of liquid biopsy make it the most potential non-invasive diagnosis method for tumors, with high clinical application value and market prospects.
"The significance of early screening is that it can greatly improve the cure rate, greatly reduce medical expenses and improve the quality of life of patients." Ye Dingwei, Chairman of the Committee of Urogenital Oncology of China Anti-Cancer Association and Vice President of Fudan University Cancer Hospital, said in an interview with the media.
The capital market is enthusiastic about the early screening technology of liquid biopsy. According to incomplete statistics, in the first half of this year, there were 15 major financing projects in the global liquid biopsy industry, with a total financing of more than 640 million US dollars. According to the data of Evaluate Medtech, half of the 10 financing companies before 2020 are start-ups in the field of liquid biopsy.
Among the 15 liquid biopsy companies that raised funds in the first half of the year, 14 rounds of public financing. Judging from the financing rounds, it is mainly concentrated in the A round, with 6 companies. Followed by round B and round C, there are three respectively. There is still much room for growth in this market in the future.
It is understood that at present, more than ten listed companies such as Huada Gene, Dean Diagnostics, Berry Gene and Kangmei Bio have included early tumor screening and liquid biopsy in their business scope. The blood test products of Exact Sciences Company in the United States for early hepatocellular carcinoma (HCC) obtained the breakthrough medical device certification granted by FDA on 20 19. In the early screening of pan-cancer fluid biopsy, Grail and Guangzhou Burning Stone are also actively developing. There are also many research institutions in China to carry out this research. At present, many biotechnology companies are actively involved in the field of early screening and early diagnosis of cancer, and their products are transformed.
The national level also attaches great importance to early screening of tumors. The outline of Healthy China 2030 points out that it is necessary to strengthen the screening and early detection of chronic diseases, carry out early diagnosis and treatment of key cancers in high-incidence areas, and promote opportunistic screening of chronic diseases such as cancer stroke and coronary heart disease. It is also proposed that by 2030, the health management of chronic diseases in the whole life cycle of the whole population will be realized, and the overall five-year survival rate of cancer will be improved by 15%. Under the dual influence of policy and market, early screening and early diagnosis of tumor has become a hot research field at home and abroad.
Huaan Securities predicts that although it is still in the early stage of development, with the continuous breakthrough of technology and the strong support of national policies, China's early tumor screening market based on liquid biopsy is expected to reach 1000 billion in 2030.