I gave a talk to some folks at UBC's School of Music this past weekend, on biology, genetics and the odd reference to music. One of things I mentioned (with an auditary theme) was the interesting case of the use of Nude mice as vectors for the production of human ears (image below).
I usually talk about this, because it's a good example of how media can often coerse the reader/viewer to come to premature conclusions. You see, I find most of the audience will make one of two responses: either an "EEWWW" response, or a "THAT'S COOL" response. In any event, you would of gotten the sense from mainstream articles when this first went to press that perhaps this was a real human ear, and you could even whisper into the back of this poor mouse to garner a response.
Anyway, our Nude Mouse piece (showcased earlier) went over this a bit. The ear by the way is just a prosthetic.
(Nude mouse speaking) The media I can live without. We're fairly private creatures, so the whole publicity thing is not cool. Besides, they almost never get it right. One time, my uncle had a human ear prosthetic grow on his back, and well, Christ, with all the press that ensued, you'd think he was sleeping with Jennifer Anniston. Not only that, but if you picked up a newspaper, you'd see this picture of poor naked Uncle Orv with a huge human ear on his back, and you'd be totally thinking that he could hear out of this thing. Which, of course, is not at all true. A shame really - that experiment was pretty elegant in my view.
You're kidding me, right?
Not at all. Engraft a hollow polymer scaffold (shaped like an ear) on Uncle Orv's back, infiltrate it with tissue cells from a burn victim needing an ear prosthetic, and wait for growth. Unky Orv ends up doing good because he has no hair, and he also doesn't have the biology to reject the foreign ear tissue. How brilliant is that? (from the SCQ)
Of course, an inevitable question I always get regarding this, is "do they have to kill the mouse in order to get the ear prosthetic?" Maybe, we'll save that one for later...
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I attended a lecture at UBC during Jumpstart (international students orientation program) this year, where Professor David Ng talked about this mouse.
I believe that this is the exploitation of an animal as we are using this mouse without its consent for the betterment of human life. This will lead to more exploitation when people decide that their nose is to pointed and the mouse has a nose growing on it.
HUMAN EAR MOUSE
THE Confrontation with a potential Fellow Candidate with the Challengers
â In the past 10 years, Chinaâs â973â, â863â projects had injected enormous sum of 60 Million into the research team led by Prof Cao Yi Lin, and with other additional items, the total investment into the research projects is up to 300 Millions. â This level of importance and scale of investment is very rarely seen both inside China and Overseas.
Reporter of Oriental Outlook Li Wei in Shanghai.
Consultant Doctor Shanghai Jiao Tong University Cao Yi Lin âIf I were going after fame and fortune, I would not have come back to China. My return is based on a patriotic mind and I have more passion of my Country the more I was abroad in Foreign Country.â âTissue Engineering is my baby, I must raise him up, I hope my Country will have a place in this arena.â
25th May 2011, was elected as an effective Supplementary Fellow Candidate
This was a good news originally, but those suspicious scientists said to the Oriental Outlook that the Human Ear Mouse has placed Cao Yi Lin in the first Chair of the Tissue Engineering Arena in China, but in practice, this was â a fake earâ for deception of a 300 Million funding, also, the Man-made Skull as a Miracle in Life might also be a fake scam.
So what is really the truth? Our reporter began investigation.
The Huge Imagination of a âHuman Organ Factory â.
Cao Yi lin became famous in 2001 through the 15th Achievements Exhibition of the national â863â Project. His exhibit was a mouse bearing a âHuman Earâ on its back.
This flesh colored hairless mouse having a pair of red eyes and with long long tail , kept inside a sterilized transparent box, was actively moving around staring at the audience. The human ear on its back look very vivid and was almost the same size of the mouseâs body, and this caused excitements at the scene.
Because the large crowds of audiences, the exhibitors arranged a special independent hall for this exhibit and used this as the best exhibit to show to the Countryâs Leaders.
Mr Shang Qing Xin, the then Head of operation of the Shanghai Tissue Engineering Research and Development Center, was responsible for bringing the mouse to Bejing to exhibit. He explained that the âHuman Earâ was made of the cartilage grown from cow cells on a human ear shaped template, and this was made a week before the exhibition. Firstly, the design of the human ear shape was done by a group of scientists, then the template based on the design was made using a polymer of glycolic acid. Then cow cells were implanted onto the template, and were programmed to divide and grow to form the required extracellular ground substances to construct the human ear.
After the âHuman Earâ had formed, Cao Yi lin himself transplanted the ear into the mouse body. The actual method was cut open the back of the naked rat whose immunity was suppressed, and the wound was sutured after the transplantation. After the polymeric template of the Human Ear was absorbed, the âHuman Ear and the mouse became a single entity.
The demonstration of the âHuman Ear Mouseâ has thus given birth to the unforeseen attention to the concept of âtissue engineeringâ, and the hope of a âHuman Organ Factoryâ.
This is how and when Cao Yi lin established his first Chair in the area of Tissue Engineering in China.
What is actually grown inside the back the this âHuman Ear Mouseâ ?
In 1998, and before this exhibition in China, Cao Yi lin was working as postdoctorate research in the USA, at that time, he was already become the Chinaâs chief Scientific Leader of the â973â major basic research Project âThe basic science of Tissue Engineeringâ, totally relying on the achievement of this âHuman ear growing on the back of a mouseâ.
Dr Shang QingXin told the Oriental Outlook after many years, : âThere was always a lot of doubt about this Human Ear Mouse, because we were always hoping that when Cao Yi lin was back to China, he could repeat the same experiment, especially when we all saw the photos. However, Cao always said, there was no meaning to repeat the experiment and , and it was a waste of time , therefore , the experiment was never repeated.â Shang earnestly said that â until the time of the 15th annual exhibition of the â863â Project, when the Secretary of the Shanghai Medical Department urged him that the experiment had to be repeated, Cao asked me not to get involved and gave me a mouse with a template implanted when I left.
Shang was the classmate of Cao as master student , he manage all the series of Cao âs events before he came back China and after he was back. But being the core people of the technology, Xang had no knowledge of the details about the experiment.
During the Bejing Exhibition, Shang had to bring the mouse back ever night to aspirate the fluid exdudated inside the mouse body with a syringe to keep the shape of the human ear. The fluid accumulation was due to the reaction against the transplanted materials.
Shang also said, due to the exceptionally exciting response from the public, the Secretary of the Shanghai Medical Department had directed him to ask Cao to extract the material inside the mouse to prove it was in fact ear cartilage as to show the long term result of the experiment . But Cao said to him, it was not possible. And without his knowledge, Cao ordered his research student to dispose of the mouse, and this famous human ear mouse was extinguished.
Shang said, : âFrom all the evidence up to date, the material implant into the mouse body is not cartilage, but most likely a glycolic polymer template.â
Our reporter made direct inquiries from Prof. Cao Yi lin about the details of the â863â exhibition, Cao explained that the little white mouse could not be kept for long period of time. When asked why not keep the ear cartilage only , Cao said ,:âAt that time, time was not enough, I had told the Secretary that we cannot do that in such a short time. They suggested that we make a sample to show in the Exhibition, but the literature of all the scientific basis of the experiment was completely published.â Our reporter followed up the query on the amount of time given by the Secretary, but Cao said : â He could not remember.â
About the importance of the saying ,: âHave to make a sample for the Exhibitionâ, Shang QingXin said that the Secretary put a lot of emphasis on this, because it was never intended tp be a sample only, but as a fact of an experimental result .
300 Million Invested in Total.
According to Shang QingXinâs understanding, the result of the experiment of Human Ear Mouse was published in America by Cao Yi Lin, in the Magazine, at that time the Impact factor of that Magazine was 1.697.
Simply because of this published result, Cao Yi Lin won the most honorable international price in Plastic Surgical Science, the James Barrett Brown Award, and had thus added this most honourable page to his CV. He was also the only Asian who was awarded this honour until today.
But according to Shang, this Award is equivalent to an award to a Thesis in China. The content of Cao âs Paper âTransplantation of Chondrocytes Utilizing a Polymer-Cell Construct to Produce Tissue-Engineered Cartilage in the Shape of a Human Earâ showed that innovative part of his paper was on the application potential in Plastic and Cosmetic Surgical usage of a reconstructed Ear in the shape of a Human Ear Structure.
26th February 2001 âHuman Ear Mouseâ became famous in the 15th Annual Achievement Exhibition of the â863â Project
April 1997 Cao Yi Lin experimenting in vitro cellular replication in Shanghai
Oct. 2000 The reporting at that time showed Cao Yi Lin leading team was successful in the subject of using tissue engineering technology to replicate Goat Skull Bone, Chicken Muscle Tendon, and Pig Joint Cartilage
Our reporter searched the main page of the American Society of Plastic Surgery , found that James Barrett Brown Award was the one of the 8 awards delivered by that Society in that particular year, and it was in fact an Award for Thesis.
In 1999, a year before Cao Yi Lin went back to China, he was consecutively awarded the âExcellent Youth Academic Awardâ of the Society of Truth Inquest Scientific Technology Foundation, the Elite of Scientific Technology of Shanghai City, 3 hourorable awards of the major young specialist contributors of the Human Resource Department of the PRC, and thus he was pushed to the top of the leading Persons of the Tissue Engineering Scientific Arena.
âOne fake Human Ear, deceiving 300 Millionsâ, was the comment to our reporter from one of Cao âs subordinate, high level member of the Shanghai Tissue Engineering National Engineer Research Team Center Yuan Jun Sen (Traniteration) .
He explained that in the past 10 years, due the enormous attention attracted by the Human Ear Mouse, our Country had invested into Cao Yi Linâs Scientific Research Team funding of at least 60 Million through â973â, â863â projects. If adding other investments from other sources, the total cumulative invested research funding would reach to about 300 Million. Such an emphasis in the importance and the enormous investments is very rarely seen both in the National Level or the International Level.
Suspicion of Exaggeration in the âMiracle of Lifeâ
There is another item appearing very suspicious, and that is the so called â Miracle of Lifeâ --- Man made Skull Bone.
In 2001, there were a number of Media Reporting on the success of Cao Yi Lin in the reconstruction of deficient Skull bone of a Child patient Jin Lin using tissue engineering. This achievement changed the traditional way that we can treat defective bone and shocking new discovery to the world.
In a traffic accident, Jin Lin bumped onto a concrete wall which caused one sixth of his skull bone macerated leaving with only a thin layer of Dura Mata (the membrane of the Brain).
According to traditional method, the big âholeâ can only be repaired by metal and / or synthetic materials. But the then 7 year-old Jin Lin, whose skull bone would still be continuously growing for ten and more years, would need to have such materials replaced surgically every few years to adjust to the growing skull because these reconstructive materials cannot grow at the same time as the other areas of the skull bone.
Cao Yi Lin suggested the Man Made Bone Method for treatment in this case. The process was to extract the mesenchymal stem cells from the bone marrow of the patient himself, incubating these stem cells in an environment to induce them to differentiate into bone cells, and then transplanting and attaching these bone cells onto a structured template made of biological material and then growing the complex in vitro to such a stage, and then transplanted to the skull. After the metabolic degeneration and resorption, excretion of the template structure, the Man Made Skull Bone would replace the entire defect of the patientâs Skull.
It was claimed after 4 months observation and followed up, the replaced Man Made Skull bone was exact match for the skull of the patient and it was a perfect fit.
But according to insiderâs information given to our reporters, Jin Linâs operation was in fact unsuccessful in that : the replaced material was absorbed. The insider people of the said hospital in Shanghai searched the records and found no related record of Jin Lin, no patient record nor any admission records.
Prof Cao Yi Lin admitted to Oriental Outlook reporter that in the later days, some of the replaced materials was absorbed, but then Jin Lin was very difficult to be contacted.
In the reported 2008 recommended documents of the National Second Class Award for Technological Inventions in the Tissue Engineered Tissue Reconstruction Key Technological Scientific Research and Application, there were 23 Cases of Clinial Application of the Osteogenic Tissue developed by Tissue Engineered Bone Marrow Mesenchymal Stem Cell . In all the 23 cases of maximum human skull defect reconstruction involved 1/6 total human skull area, (from age 6 to 27 years old), the followed up rate was 100%, the longest followed up time period was 2 years. With the result of the external examination, and 3 D CT scanning for all the long term followed up patients, the treatment results were very good.
However, what our reporter found out is that in these 23 cases of operations, there were many cases similar to Jin Lin, there were no proper admission hospital records, no patients records,. From 2001 to 2006, there were only 5 cases having complete patient history records.
Prof. Cao Yi Lin told our reporter, : â At that time and environment, we could carry out experiment when we obtained the hospital ethical committeeâ permission and the patientsâ informed permission. But later, we have new regulations, we will need to pass the tests, therefore we stopped the experiments.â
Our reporter ask what the new regulations were, Cao said it was not a new regulation, but it was because of the increased complexity between doctors and patients. Later on, whether there were other people doing the experiments, he did not know about them.
Shang Qing Xin said, : â For any Scientific research Records, they must be kept long term. If we cannot trace the records, how can we prove that we have done these operations? Even if really 23 cases were done, this lack of records also violated the very basic principles in Researchâ
After exploring in multiple directions, Oriental Outlook reporters contacted two patients that have received such Skull Bone Reconstruction using Autologous Bone Marrow Mesenchymal Stem Cell Man Made Bone, a 15 year old girl Cao Ren Yue of Liao Ning Province, Ying Kou City, had the surgery in 2003 at the age of 7, her condition was similar to Jin Lin, also with skull defect after injury. Her father Cao Ying Feng told Oriental Outlook : âthe surgery was a failure, the wounded place was still soft, and we must wait for her to grow up to repeat the reconstructive surgery.â
Shi Chao Hui of Jin An County , Zhe Jiang Province received the same skull repair surgery in 2003, his mother told Oriental Outlook : â Not Successfulâ.
Prof. Cao Yi Lin replied : â At present there cannot be a 100% guaranteed success, the success rate is around 70%.â
Shang also said, due to the exceptionally exciting response from the public, the Secretary of the Shanghai Medical Department had directed him to ask Cao to extract the material inside the mouse to prove it was in fact ear cartilage as to show the long term result of the experiment . But Cao said to him, it was not possible. And without his knowledge, Cao ordered his research student to dispose of the mouse, and this famous human ear mouse was extinguished.
Scientific things are more difficult than thought
Despite the omnipresent promotion, Shang Qing Xin still expect the concerned Government Department to start investigating, to check the âSuccessâ and why was there only reporting but not any literature published. Usually, a research can only be accredited when it is published and the result can be repeatedly done by other laboratories.
Yuan Jun Sen said, there are published literatures on the application of osteogenic tissue derived from bone marrow mesenchymal stem cells by tissue engineering in foreign countries, : â If you want to publish literature, you must have patient records as basis for examination, the source of the materials must be formal.â
Our reporter has obtained a copy of raw materials used for power-point slides for exhibition of the operation, in the repairing of a child skull defect, the templates shown were 3 pieces of triangular bone tissue. After Shang Qing Xin and Yuan Jun Sen saw the slides, they definitely identified the bone pieces were only pigâs decalcified bone and not human bones. Pigâs decalcified bone are bigger in sizes and the structure is different from that of humanâs.
Pigâs decalcified bone belongs to Class 3 implanted Medical Instruments, clinical use of which has to pass the test of National Drug Administration Department, to avoid any potential rejection problems, and viral antigen contamination and spread. But in the 23 cases of operation, there were no such application found.
Cao Yi Lin told Oriental Outlook , â At the early stage, the pigâs decalcified bone had been used, there were parts of human bone also. But the early parts (Pigâs decalcified bone) had passed the application and was approved for clinical use, and they were approved products.â
But according to insiders, the surgical template was supplied by a plastic surgeon, Pan Yin Gen of Qi Dong City Peoples Hospital, Jiang Su Province, he was engaged in long term Pigâs Skin and Pigâs Decalcified Bone Research.
Pan Yin Gen established Shanghai Dong Ci Medical Technology Co. Ltd. on his research basis.
Our Reporter telephoned Pan Yin Gen under the pretense of enquiries on their business, to understand the situation of the clinical application of their products. Pan Yin Gen said, â Cao Yi Lin and his tissue engineer research center used his decalcified bone, and their experiment was in fact carried out by his company.â But speaking the opposite of Caoâs saying, Pan Yin Gen admitted that their product was applying for the license only, and in fact it was not yet approved for the clinical use.
Same as the omnipresent reported success included the Goat Skull Bone, Chicken Muscle Tendon, Pig Joint cartilage, etc anti-immunity high level Mammalian animal organ replications. Shang Qing Xin involved in the majority of the experiments, but he cannot believe that there was the so called âBreakthroughâ.
âI had personally performed many cartilage replication experiments, the long term result of these experiments were all failures. When just having a structure, the materials were extracted from the animal after killing it, this cannot prove the success of the experiment, at least we must wait for a year or two for observation. If really it was successful, we could have used it for clinical applications already, every result would be a potential productivity of Billions. At the end of the day, the researchers all did not further continue the experiment, this is very worthy our attention.â
April 1983 Dr Shi Yao Shun of the Shanghai Ninth Peopleâs Hospital was applying a silicone ear prosthesis on a patient. Due the large human population in China, the demand of organ defect replacement were very great
Prof Cao Yi Lin said in response to the inability to transform the results of the experiments in all these years into productivity, â we originally thought that there were many experiment would be converted to clinical applications, but Scientific things are much difficult than our thoughts, we must work practically.â
The Top Scientist has too many jobs to take care of.
Being the Chair Scientist of the most important National â973â Basic Scientific Research Program âTissue Engineering Itemsâ, Cao Yi Lin has many other jobs to take care of, he was the Superintendent of the Plastic Surgery Hospital of the China Medical Science Academy, the Chief of Shanghai Tissue Engineer Research and Development Center, the CEO of Tissue Engineer (Shanghai) of the National Tissue Engineer Center, etc. Moreover, he also was the Superintendent of the Hang Zhou Plastic Surgery Hospital .
Too many administrative duties often caused the Top Scientist incapable of taking care of all the jobs. This also happened on Cao Yi Lin. Bejing and Shanghai Colleagues all reflected to Oriental Outlook that Cao Yi Lin is not present in the research projects all the time.
Mo Yu (Transiteration), Vice Superintendent of the Plastic Surgery Hospital of the China Medical Science Academy said to Oriental Outlook that, â we could see him often in 2006 and 2007, but in 2010 the whole year, he was not even there for 2 months, but only this one jobâs annual salary was at least 500 -600 K.â
Cao Yi Lin consecutively acted as âTen â Five â and âEleven-Fiveâ Two years â863â Tissue Engineer Projects Specialists Assessment Team Head. During this period of time, his team members consecutively won 4 major special items in tissue engineering, which was in total a 30 Million â863â Research Funding.
Facing with the criticism and the suspicion, Prof Cao Yi Lin felt being deeply wronged, : âTo achieve something, one must offended some others, history will prove the facts.â