tag:blogger.com,1999:blog-205797322024-03-12T19:11:22.969-07:00cargo cult scientistDedicated to the Cargo Cults of Biology Science, Biotechnology and the Pharmaceutical Industry.
"So we really ought to look into theories that don't work, and science that isn't science"
Richard Feynman,
Cargo Cult Science,
From a Caltech commencement address given in 1974Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.comBlogger500125tag:blogger.com,1999:blog-20579732.post-72888009052650416522024-03-02T17:45:00.000-08:002024-03-04T18:16:25.286-08:00Appealing to the Authority of Man <p><span style="background-color: white;">A<span style="font-size: medium;">t some point, if you are a Cargo Cult, you begin to realize that the Gods aren't going to step in. You are failing at getting the Cargo and the natives are getting restless. You must appeal to something more reasonable, something you can control. You find the highest ranking human in your group and begin to set up a new strategy. The big metal birds are not landing no matter how you reshape your runways. The headset made of coconuts and sticks cannot be made to summon the cargo planes. It has to be that the people are doing something wrong. They are not using the airport you have designed properly.</span></span></p><p><span style="background-color: white; font-size: medium;">The first step is to set up a new agency. Then set up a few more. Devote more resources towards the new groups. Let them define the issues and new terms to discuss said issues. Have meetings. Make claims that things are beginning to succeed, according to the new way of thinking...</span></p><p><span style="background-color: white; font-family: inherit; font-size: medium;"><span class="legendSpanClass" style="caret-color: rgb(29, 34, 40);"><span class="xn-location">BOSTON</span> and <span class="xn-location">LEXINGTON, Mass.</span></span><span style="caret-color: rgb(29, 34, 40);">, </span><span class="legendSpanClass" style="caret-color: rgb(29, 34, 40);">Feb. 15, 2024</span><span style="caret-color: rgb(29, 34, 40);"> /PRNewswire/ -- The Defense Threat Reduction Agency's (DTRA) Joint Science and Technology Office (JSTO) for the Chemical and Biological Defense (CBD) Program has awarded, through the Medical CBRN [Chemical, Biological, Radiological, and Nuclear] Defense Consortium (MCDC) requirement 22-05, "Adjuvant Activity to Vaccines Prototype," a 5-year contract totaling up to </span><span class="xn-money" style="caret-color: rgb(29, 34, 40);">$31 million</span><span style="caret-color: rgb(29, 34, 40);"> including program options to the team of Ginkgo Bioworks, Inc. (NYSE: DNA) and SaponiQx, Inc. (a subsidiary of Agenus Inc., NASDAQ:AGEN) to discover and develop next-generation vaccine adjuvants. Partners in adjuvant discovery and development since 2021, Ginkgo, which is building the leading platform for cell programming and biosecurity, and SaponiQx, developing a visionary adjuvant development platform, will use a combination of high-throughput empirical and artificial intelligence/machine learning approaches, including Generative Molecular Design (GMD), to develop superior novel saponin-based adjuvants.</span></span></p><p><span style="background-color: white;"><span style="font-size: medium;"><span><span style="font-family: inherit;"><span style="caret-color: rgb(29, 34, 40);">If you look at the SaponiQx website you see a rather sparse pipeline. QS-21 (available for supply) QS-7 and QS-X (R&D phase). At the inception of the company, which coincided with their partnership with Ginkgo, QS-21 was </span></span><span><span style="caret-color: rgb(29, 34, 40);">already</span></span><span style="font-family: inherit;"><span style="caret-color: rgb(29, 34, 40);"> "available for supply". Very little seems to have been done since 2021 in spite of the two powerhouses in the vaccine adjuvant </span></span></span></span><span style="font-size: medium;"><span style="caret-color: rgb(29, 34, 40);">space.</span></span></span></p><p><span style="background-color: white; font-size: medium;">What has been accomplished is a $31M 5 year contract to develop what the two companies said they were going to develop using their combined expertise. The final piece of the puzzle was this agreement from DTRA, JSTO, CBD through the DBRN, MCDC requirement 22-25. </span></p><p><span style="background-color: white; font-size: medium;">If all goes according to plan there will be cargo by the year 2029. </span></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-29971050755555486482024-02-23T17:56:00.000-08:002024-02-23T18:00:46.606-08:00So Many Collaborations<br /><br />I asked Gemini, "Who is The Cargo Cult Scientist?<br /><br />"The term originated from a famous speech by physicist Richard Feynman called "Cargo Cult Science." He used the analogy of cargo cults in Pacific islands, who built elaborate mock runways and control towers in hopes of attracting cargo planes. Similarly, "cargo cult scientists" might go through the motions of research, collecting data and conducting experiments, but their work lacks the underlying foundation of scientific rigor and ultimately fails to produce meaningful results or contribute to genuine scientific understanding."<br /><br />Okay then! Now let's look at a possible Cargo Cult Science project:<br /><br />The Defense Threat Reduction Agency's (DTRA) Joint Science and Technology Office (JSTO) for the Chemical and Biological Defense (CBD) Program has awarded, through the Medical CBRN [Chemical, Biological, Radiological, and Nuclear] Defense Consortium (MCDC) requirement 22-05, "Adjuvant Activity to Vaccines Prototype," a 5-year contract totaling up to $31 million including program options to the team of Ginkgo Bioworks, Inc. (NYSE: DNA) and SaponiQx, Inc. (a subsidiary of Agenus Inc., NASDAQ:AGEN) to discover and develop next-generation vaccine adjuvants. Partners in adjuvant discovery and development since 2021, Ginkgo, which is building the leading platform for cell programming and biosecurity, and SaponiQx, developing a visionary adjuvant development platform, will use a combination of high-throughput empirical and artificial intelligence/machine learning approaches, including Generative Molecular Design (GMD), to develop superior novel saponin-based adjuvants. -BOSTON and LEXINGTON, Mass., Feb. 15, 2024 /PRNewswire/ -- <br /><br />They are going to research and develop variants of naturally occurring compounds known as Saponins. <br /><br />This is an important concept because the current method for obtaining saponins is to extract the compound from tree bark. The process is not environmentally friendly. <br /><br />Back in 2021 "Vaccines are one of the most powerful tools we have to fight pandemics, but ensuring widespread access to efficacious vaccines continues to be a major challenge worldwide," says Jason Kelly, CEO of Ginkgo Bioworks. "We're proud that our platform is being used by companies across the vaccine supply chain to develop and manufacture the materials necessary for life-saving vaccines." <br /><br />Currently SaponiQx has one adjuvant available for supply (QS-21) and two in the R&D phase (QS-7 and QS-X. They have zero job openings. They have been working with Ginkgo since 2021.<br /><br />The problem with Cargo Cult Scientists, according to Gemeni, "their work lacks the underlying foundation of scientific rigor and ultimately fails to produce meaningful results or contribute to genuine scientific understanding."<br /><br />The collaboration touted in the recent press release by Ginkgo and SaponiQX has actually been ongoing since 2021. Where are the fruits of this labor? Meaningful results or advanced scientific understanding?<br /><br />Instead we have a word salad. Who is now involved in making SaponinQX successful?<br /><br />The Defense Threat Reduction Agency's (DTRA) Joint Science and Technology Office (JSTO) for the Chemical and Biological Defense (CBD) Program... through the Medical CBRN [Chemical, Biological, Radiological, and Nuclear] Defense Consortium (MCDC) requirement 22-05, "Adjuvant Activity to Vaccines Prototype," ...Ginkgo Bioworks, Inc. (NYSE: DNA) and SaponiQx, Inc. <br /><br />The Cargo? A 5-year contract totaling up to $31 million. Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-73763214308191234882024-02-23T17:20:00.000-08:002024-02-23T17:20:49.897-08:00Dying of Cancer<p>My mom died in 2023 from ovarian cancer. She was diagnosed in 2022, underwent surgery to remove a large tumor, underwent chemotherapy and died in July of 2023. There were no experimental drug trials offered as alternative therapies. There was no semblance of medical science advances. No antibodies against a specific protein on a cancer cell. No attempts to stop cancer cells from growing by targeting angiogenesis. No oncolytic viruses were injected into her body to take out cancer cells. No RNA anti-sense drugs, no RNA interference, no DNA gene therapy, no new anything. Just surgery, chemotherapy, death. </p><p>And it was not a very good existence. My mom became weak to the point we were ready to put her into a nursing facility. She lost her appetite often and simply had to force herself to eat something for energy. In the end we found her lying on the couch unable to get up. We called 911. She went to the hospital. The nurse told us that our mom would be released later that day. Nope, was our response. Two days later my mom passed away at the age of 77.</p><p>I suppose this is how we go. At 77 you are in danger of succumbing to a number of things. Our cells have kept us going for over 28,000 days. We wake up with renewed energy. We go to bed with the energy spent. We wake up recharged. Along the way we may do bad things regarding diet and exercise. We may breath in air pollution. We may challenge our systems with drugs, alcohol, and/or tobacco. When we feel something is wrong we go to the doctor and they diagnose the symptoms. </p><p>As each day comes and goes we are one day closer to the end. As we approach the age of 77 we are getting close. We don't know how long we have but that is for the best. A positive attitude can go a long way. </p><p>Sleep is biochemistry inside the brain. Our bodies need to sleep so our cells can be replenished. There is a cleansing process that occurs during stage 4 sleep. There is a pleasant dream phase called REM. If we drink too much the biochemistry shuts down the day in a sudden sleep. We call that passing out. We awake before the normal amount of sleep feeling poisoned. Food can also affect the sleep process. Too much Western society fast food or processed food will also cause trouble. A day of eating mostly vegetables and natural food with a fair amount of exercise that ends at the same hour (no drugs/alcohol/cigarettes) will lead to a pleasant nights sleep with an awakening with restored energy. </p><p>In the end my mom was not pleased with how she slept. She awoke with little energy. She made her way to the recliner where she would spend the day. Good Morning America was followed by Gunsmoke, Leave It to Beaver, Happy Days, The View... The last show made her an angry old person. The old time shows made her happy as if in a state of REM sleep. No mental challenges. The future was filled with chemotherapy and ultimately death. I don't mean to be depressing but for her it had become real. She did not have the energy to fight back. </p><p>So that is all. Cancer is wrapped up in the complexity of our DNA. It makes itself known when we can no longer stop the force it has on the overall system. We have little to show for our research. Just money spent and careers of the successful scientists. </p><p><br /></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-55218723879063228482024-01-09T10:26:00.000-08:002024-01-10T06:05:44.736-08:00Ginkgo Announces New Advisory Board! <p> January 8, 2024</p><p style="box-sizing: inherit; color: #585858; font-family: sofia-pro, sans-serif; font-size: 19px; line-height: 1.429em; margin: 0px 0px 40px;"></p><h3 class="wp-block-heading" style="box-sizing: inherit; clear: both; font-family: ivypresto-headline, serif; font-size: 30px; font-weight: 100; letter-spacing: 0.008em; line-height: 1.294; margin-top: 0px;">Today we’re thrilled to announce the formation of our new Biopharma Advisory Board!</h3><p style="box-sizing: inherit; color: #585858; font-family: sofia-pro, sans-serif; font-size: 19px; line-height: 1.429em; margin: 0px 0px 40px;">This council of experts from across the biopharmaceutical industry will provide critical insight into the development of Ginkgo’s core platform service offerings across target discovery, drug discovery, optimization, and manufacturing. The group, which will conduct regular meetings at Ginkgo and with its partners, includes (in alphabetical order) —</p><ul style="box-sizing: border-box; font-size: 19px; line-height: 1.429em; list-style: none; margin: 0px; padding: 0px;"><span style="font-family: times;"><i>How many of these CEO's have signed deals with Ginkgo Bioworks to provide Ginkgo with revenue rather than Ginkgo providing the CEO's with income? </i></span></ul><div><span face="sofia-pro, sans-serif" style="color: #585858;"><span style="caret-color: rgb(88, 88, 88); font-size: 19px;"><br /></span></span></div><div><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">“We try never to forget that medicine is for the people. It is not for the profits.”</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">– George Merck</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">I would like to focus on one of the members of the new committee. Previously I have talked about one of the new members of Ginkgos Advisory Board.</p><ul style="box-sizing: border-box; color: #585858; font-family: sofia-pro, sans-serif; font-size: 19px; line-height: 1.429em; list-style: none; margin: 0px; padding: 0px;"><li style="box-sizing: inherit; margin: 0px 0px 20px; padding-left: 40px; position: relative;">John Maraganore, PhD, served as the founding Chief Executive Officer and a Director of Alnylam from 2002 to 2021. Under his leadership, Alnylam helped lead the interventional RNA revolution by launching the first RNAi therapeutic medicine, ONPATTRO®, in 2018, followed by four more RNAi therapeutics through mid-2022. Dr. Maraganore was the chair of the Biotechnology Innovation Organization (BIO) from 2017 to 2019 and is an active mentor to leaders across the biotechnology industry. John is the principal of JMM Innovation, and also serves as a Venture Partner for Arch Ventures and Atlas Ventures, an executive partner for RTW Investments, a senior advisor for Blackstone Life Sciences, and as an advisor for M28.</li></ul><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">A quick search of ONPATTRO: </p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;"><b><u>Wikipedia</u></b></p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">Onpattro is a medication used for the treatment of polyneuropathy in peop[le with hereditary transthyretin-mediated amyloidosis, a fatal rare disease that is estimated to affect 50,000 people worldwide.</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">The per-patient cost is between US $451,430 and $677,145, depending on the number of vials needed. As of 2020, there were 1050 people globally receiving parisian, generating $65.5M in net revenues. </p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;"><b><u>The <a href="https://www.biospace.com/article/fda-questions-efficacy-of-alnylam-s-patisiran-in-attr-cm-ahead-of-adcomm-meeting/" target="_blank">FDA</a></u></b></p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">Alnylams Pharmaceuticals push for parisian to be expanded to a much larger pool of patients...</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">In a briefing document released ahead of the Sept. 13 meeting of the FDA's Cardiovascular and Renal Drugs Advisory Committee, the agency called into question the efficacy of the drug in treating that pool of patients.</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;"><i>Remember, medicine is for the people, not the profits. </i></p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">Patisiran was already approved by the FDA in 2018 for the treatment of hereditary ATTR amyloidosis polyneuropathy, which made it the first-ever RNA interference therapeutic approved by the regulator.</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">Nevertheless, vutrisan - sold under the brand name Amvuttra - still represents the company's most lucrative product. In its second-quarter 2023 financial update, net revenues for the drug were $132 million, versus $91 million for Onpattro. <i>In the fourth quarter Onprattro sales were down to $79M.</i></p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">For the full-year 2023 net product revenues of $1.24B were reported. The revenues come from sales of its four marketed products Onpattro, Amvuttra, Givlaari and Oxlumo.</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">Onpattro: $355M</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">Ambuttra: $558M</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">4060 patients worldwide were receiving commercial Onpattro and Amvuttra as of year-end 2023.</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">Givlaari: $219M</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">Oxlumo: $110M</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">650 patients were receiving Givlaari as of year-end 2023</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">430 patients were receiving Oxlumo as of year-end 2023</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">So roughly 5140 patients are generating $1.24B. </p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;"><u><b>Yahoo Finance</b></u></p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">In October 2023, Alnylam experienced a massive setback after the FDA issued a Complete Response Letter (CRL) in response to the company's supplemental new drug application (sNDA) for the label expansion of Onpattro to treat the cardiomyopathy of transtheyretin-mediated (ATTR) amyloidosis. </p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">However, following this development, the company shifted its focus to the phase III HELIOS-B label-expanding study of Amvuttra in the treatment of cardiomyopathy of ATTR amyloidosis. </p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;"><b><u>CCS</u></b></p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">John Maraganore has long struggled to get dubious RNAi drug products on the market. From the perspective of the market, he has succeeded. But then again, so did the Covid vaccine. Safety and efficacy can be dealt with best under emergency conditions. John Maraganore has succeeded. He is a hard working man. Long listed here as a Cargo Cult Scientist he has created over $25B in market capitalization. </p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">Alas, only 5,140 patients are receiving treatment. Those patients are already very sick people. They get results only a professional statistician working in the Cargo Cults can detect. We have to wonder what it is like for the patients receiving the RNAi drug product. Do they feel a difference? Are they less sick?</p><p style="box-sizing: inherit; font-family: Invention, sans-serif; font-size: 16px; line-height: 1.75rem; margin: 1rem 0px;">In the Cargo Cults the natives still look to the skies. They believe what they are doing will one day provide results. Ginkgo Bioworks has said that John Maraganore has produced results and he will now advise them on how they too can see the massive returns on their investments. Although the expertise of John Maraganore was in RNAi drugs, he seems to have now moved on to biotechnology capital. He is an investment strategist. He advises on money. Ginkgo does not do RNAi drugs. Nonetheless, they have found an ally. A man who knows that medicine can make great profits even if the people don't need them. </p><p style="caret-color: rgb(32, 33, 34); color: #202122; font-family: sans-serif; font-size: 14px; margin: 0.5em 0px 1em;"><sup class="reference" id="cite_ref-9" style="font-size: 11.2px; line-height: 1; unicode-bidi: isolate; white-space: nowrap;"></sup></p></div>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-68263833981900513742024-01-09T08:28:00.000-08:002024-01-09T08:28:56.753-08:00Book List<p> <span style="font-family: inherit; font-size: medium;">1. <b>Betyrayers of the Truth - </b>William Broad and Nicholas Wade</span></p><p><span style="font-family: inherit; font-size: medium;">The lures of careerism and big money, the pressures of huge research factories, the repeated failure of supposedly fail-safe mechanisms of scientific inquiry to detect and correct fraud - <i><b>Betrayers of the Truth </b></i>is about how science really works and why scientists are tempted to cheat. </span></p><p><span style="font-family: inherit; font-size: medium;">2. <b>On Bullshit</b> - Harry G Frankfurt</span></p><p><span style="background-color: white; caret-color: rgb(15, 17, 17); color: #0f1111;"><span style="font-family: inherit; font-size: medium;">Most people are rather confident of their ability to recognize bullshit and to avoid being taken in by it. So the phenomenon has not aroused much deliberate concern. We have no clear understanding of what bullshit is, why there is so much of it, or what functions it serves. And we lack a conscientiously developed appreciation of what it means to us. In other words, as Harry Frankfurt writes, "we have no theory."</span></span><br style="box-sizing: border-box; caret-color: rgb(15, 17, 17); color: #0f1111; font-family: "Amazon Ember", Arial, sans-serif; font-size: 14px;" /></p><p><span style="background-color: white; caret-color: rgb(15, 17, 17); color: #0f1111;"><span style="font-family: inherit; font-size: medium;">3. <b> Innumeracy</b> - John Allen Paulos</span></span></p><p><span style="background-color: white;"><span style="font-size: medium;"><span style="color: #0f1111; font-family: inherit;"><span style="caret-color: rgb(15, 17, 17);">Mathematical Illiteracy and It's Consequences. Innumeracy - the mathematical counterpart of illiteracy- is a disease that has ravaged our </span></span><span style="color: #0f1111;"><span style="caret-color: rgb(15, 17, 17);">technological</span></span><span style="color: #0f1111; font-family: inherit;"><span style="caret-color: rgb(15, 17, 17);"> society.</span></span></span></span></p><p><span style="background-color: white; caret-color: rgb(15, 17, 17); color: #0f1111;"><span style="font-family: inherit; font-size: medium;">4. <b>A Drunkards Walk</b> - Leonard Mlodinow</span></span></p><p><span style="background-color: white; caret-color: rgb(15, 17, 17); color: #0f1111;"><span style="font-family: inherit; font-size: medium;">How Randomness Rules Our Lives. </span></span></p><p><span style="background-color: white; caret-color: rgb(15, 17, 17); color: #0f1111;"><span style="font-family: inherit; font-size: medium;">5. Predictably Irrational - Dan Ariely</span></span></p><p><span style="color: #0f1111; font-size: medium;"><span style="background-color: white; caret-color: rgb(15, 17, 17);">Challenging assumptions about making decisions based on rational thought. No amount of education can reliably prevent us from making mistakes. We can be, </span>because of our biases, the easiest person for us to fool. </span></p><p><span style="background-color: white; caret-color: rgb(15, 17, 17); color: #0f1111;"><span style="font-family: inherit; font-size: medium;"><br /></span></span></p><p><span style="background-color: white; caret-color: rgb(15, 17, 17); color: #0f1111;"><span style="font-family: inherit; font-size: medium;">A healthy dose of skepticism is necessary when looking at information. Be it the modern day media to science to technology, we all must have the ability to separate the truth from everything else. Our bias is our biggest enemy. We will prefer certain truths over others. </span></span></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-28973377455342365742024-01-06T07:39:00.000-08:002024-01-06T07:48:42.756-08:00Wax On Wax Off<p>It is assumed, in science, that a true genius comes along once and a while. All of the people in between are just stewards of the collective knowledge given to us by the geniuses. They teach the new generation about the work. As Richard Feynman pointed out in Cargo Cult Science. "<span style="font-family: Times; font-size: 16px; text-align: justify;">That is the idea that we all hope you have learned in studying science in school—we never explicitly say what this </span><i style="font-family: Times; font-size: 16px; text-align: justify;"><b>is</b></i><span style="font-family: Times; font-size: 16px; text-align: justify;">, but just hope that you catch on by all the examples of scientific investigation." In the process of learning the thing that was discovered long ago we hope to learn how to think as well. </span></p><p>What is "what this<i><b> is</b></i>"? It is not the fruits of the labor that matter most in science. It is the scientific method that we learn, teach and practice (as scientists) that matters. The journals Cell, Science and Nature all insist that the fruits of the labor defines the level of genius of the scientist. They do not seem to value the labor of thought, experimental design, execution and proper conclusions as much. This leads to the individual scientists focusing on their narrative more than their methodology. </p><p>The Cargo Cult Scientist believes that the method is what matters. The scientific politician focuses on the fruit. Think of it like Ginkgo Bioworks laboratory <a href="https://www.ginkgobioworks.com/case-studies/the-future-of-food/" target="_blank">produced meat</a>. Technologists can produce meat-like substances. They cannot produce the biologically produced meat that evolved over billions of years. Would you prefer cutting into a steak or scooping up the pooding produced by a biotech company?</p><p>Think of that disgusting meat the same as the miracle molecules we put into peoples bodies. We find individual proteins the are part of a complex system. We manufacture them because that is within the complicated paradigm of our understanding. Then we take the final product and use it in our simple understanding.</p><p>Indeed Ginkgo Bioworks seeks to replace your companies research team. BIOLOGY BY DESIGN! I suppose, unlike nature, Ginkgo will design biology to do what you want it to do. The problem is in the understanding of the scientific method. We don't design biology. We seek to understand it. </p><p>As always, we return to the problem of Simple-Complicated-Complex. Ginkgo Bioworks programs cells to "make everything from food to materials to therapeutics". Programming a cell is complicated. So the biotech or biopharma company hires Ginkgo rather than hiring a research staff. They get the cell line they want. They have the product that comes from a bio-engineered cell. Now what? </p><p>I ran into this problem at every biotech company. One example was producing a library of peptides that could be screened to find that one magical peptide that would deliver RNA to specific cell targets. RNA interference won two scientists the Nobel Prize in 2006. It was all the rage in knocking out gene products in biotechnology. But it didn't work in most situations. Why? It was assumed that the laboratory staff were doing something wrong. When this square peg couldn't be hammered through the round hole people began looking for a peptide or protein to deliver the RNA to the cell target. The narrative was in place. The project failed. We were all let go. The project was turned over to a prestigious professor at a European University. He too produced nothing to support the narrative. The narrative was simply changed. The science was working! Occasional reports were put out via company press releases that the scientist was making progress.</p><p>The project was most likely doomed from the start. Yet if, in an alternative universe, we had been allowed to fail we could have learned. Had we been given years of exhaustive research we may have made some valuable discoveries in our failures. We would have advanced our knowledge in the process/methodology. Instead we all went on to the next attempt to maintain employment in biotechnology. Most of us failed to do so. </p><p>The future of Ginkgo Bioworks is no different. They are pursuing the idea that understanding complicated biotechnologies will lead to the kind of discoveries that make science work. There is a disconnect there. Like Mr. Myagi in the Karate Kid taught, wax on, wax off. Why? It was a Hollywood creation based in dubious reality but the concept is real. In science, the method is the thing. Learn how to conduct research and the results will teach you new things. Unfortunately, in business, there is not enough time to wax on and wax off until the time comes to apply the knowledge. People in offices who mostly attend meetings need data. They need charts and claims of near future riches. Ginkgo promises you they can help. In time you will end up with a few fish but no understanding of how to fish. </p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-23331539179476797552023-12-02T04:48:00.000-08:002023-12-02T04:48:39.147-08:00When You Have to Succeed<p> Ginkgo Bioworks will help you succeed. They have a stake in your success. So much so that you will have to pay them in perpetuity if you get a drug approved. Not so much if you hire a staff of scientists to be your R&D.</p><p>I was somewhat to surprised to see a drug that came from a biotechnology company I worked for, being advertised during a streaming sports event. I did not know what they named the drug but I could tell they were selling the narrative my former employers had developed from day one. I looked it up and there it was. The one and only drug ever approved from an employer of mine in my 13 years in biotechnology.</p><p>The technology was standard stuff. Make an antibody against a target protein. Sort through the B-cells and make a list. Test the antibodies on the list, pick one, viola.</p><p>After our first project failed to get past a milestone with a big pharma partner we were in trouble. We had to move on to the next drug in the pipeline fast. We revived an abandoned project... long story short... I saw the drug on a commercial while watching UFC fights.</p><p>What happened to the guy who cloned the antibodies and sorted through them? He has been out of the business for many years. I haven't talked to him but I see from LinkedIn a curious lack of progress in his career. </p><p>What would the difference have been had Ginkgo Bioworks done the work of finding the antibody that became the drug? Firstly there would be a considerable ongoing cost. My co-worker has long since cost anyone in biopharma a dime. Secondly, Ginkgo would have had to learn a new skill. The system of cloning and manufacturing came from a specialized yeast system. So specialized was this system, it had not been done before. The standard CHO cell system was, in the narrative of the company, subpar. They had a better system. Yeast! They had the same expression and yield results. The truth was that they expressed about 1/10th the antibodies of the standard CHO cell system and the yeast extract needed created a nightmare for downstream process development. </p><p>The problems that came with using yeast cells were not insurmountable. They had to be handled however by far superior minds at contract manufacturing organizations (CMO's). The antibody selection was simple. The laboratory work was complicated. The manufacturing issues became simple to complicated thanks to the experience of the CMO options. </p><p>Ginkgo Bioworks did not exist at the time my former employer could have considered them as a partner. We went with a company that had many decades of experience developing manufacturing methods that resulted in drugs that could be sold. </p><p>Ginkgo is attempting to be your laboratory professionals. Sit in your cubicle/office and make decisions based on your needs for success. Like Donald Trump, who worked as a biotech CEO in developing the Covid vaccine, you lay out the plan. Vaccine, now, go! But the people who work in the labs have to actually produce something. It could be Ginkgo or it could be the people you hire and dress in white lab coats. Either way, you tell them your narrative and they provide you with the data you need or they go away. Even when they have succeeded, they go away. </p><p>The difference with Ginkgo Bioworks? You have to keep paying them as long as the drug makes money. My ex co-worker and all of the people who developed the drug advertised on the UFC stream... gone. </p><p><br /></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-50292673063803697952023-10-21T06:18:00.005-07:002023-10-21T06:31:58.244-07:00Ginkgo Bioworks<p><span style="background-color: white; font-family: inherit;"> </span></p><h1 class="quoteText" style="caret-color: rgb(24, 24, 24); color: #181818; font-weight: normal; line-height: 21px; margin: 0px 0px 15px; padding: 0px;"><span style="font-family: inherit; font-size: medium;"><i style="background-color: white;">Ginkgo Bioworks, Biology by Design</i></span></h1><div><span style="background-color: white; font-family: inherit;">We begin with the very first statement on the Ginkgo Bioworks website. THEY design biology. Something goes wrong in a biological system? They, like auto mechanics, fix what went wrong. </span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span style="background-color: white; font-family: inherit;">Once again, The Cynefin method of thinking leads us to the fundamental flaw. </span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span style="background-color: white; font-family: inherit;">Simple, Complicated and Complex.</span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span style="background-color: white; font-family: inherit;">Biology is complex. Biotechnology is complicated. Some laboratory techniques are kind of simple.</span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span face="ivypresto-headline, serif" style="letter-spacing: 0.24px; text-align: center;"><i><span style="background-color: white; font-family: inherit; font-size: medium;">Biology is the most advanced manufacturing technology on the planet. We program cells to make everything from food to materials to therapeutics.</span></i></span></div><div><span face="ivypresto-headline, serif" style="letter-spacing: 0.24px; text-align: center;"><i><span style="background-color: white; font-family: inherit; font-size: medium;"><br /></span></i></span></div><div><span style="background-color: white; font-family: inherit;"><span face="ivypresto-headline, serif" style="letter-spacing: 0.24px; text-align: center;"><span>There it is. Biology is not a manufacturing technology. It is a branch of science. We must return to our basic understanding of how we </span></span><span face="ivypresto-headline, serif"><span style="letter-spacing: 0.24px;">perceive the world. </span></span></span></div><div><span face="ivypresto-headline, serif"><span style="background-color: white; font-family: inherit; letter-spacing: 0.24px;"><br /></span></span></div><div><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="background-color: white; font-family: inherit;"><span style="box-sizing: border-box;">Science is a</span> system of knowledge. It is concerned with the physical world and its phenomena. It entails unbiased observations and systematic experimentation. In general, a science involves a pursuit of knowledge covering general truths or the operations of fundamental laws.</span></p><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="background-color: white; font-family: inherit;"><br /></span></p><span style="background-color: white; font-family: inherit;"><span class="marker p1" style="box-sizing: border-box;"></span><span class="marker AM1 am-inline" style="box-sizing: border-box;"></span><span class="marker MOD1 mod-inline" style="box-sizing: border-box;"></span></span><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="background-color: white; font-family: inherit;">Science can be divided into different branches. The physical sciences study the inorganic world and <a class="md-dictionary-link md-dictionary-tt-off mw" data-term="comprise" data-type="MW" href="https://www.merriam-webster.com/dictionary/comprise" style="border-bottom: 2px dotted var(--blue); box-sizing: border-box; color: var(--link-color); text-decoration: none;">comprise</a> the fields of astronomy, physics, chemistry, and the Earth sciences. The biological sciences such as biology and medicine study the organic world of life and its processes. Social sciences like anthropology and economics study the social and cultural aspects of human behavior.</span></p><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="background-color: white; font-family: inherit;"><br /></span></p><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="background-color: white; font-family: inherit;">Science is a system of knowledge. We have to apply our version of The Scientific Method in order to advance our knowledge. We used to think the <a href="https://sites.nlm.nih.gov/exhibition/shakespeare-and-the-four-humors/materials/HS-Four_Humors_Primary_Sources.pdf#:~:text=The%20four%20humors%20theory%20was%20developed%20in%20ancient,were%20thought%20to%20result%20in%20specific%20personality%20types." target="_blank">Four Humors</a> regulated our health. We have changed our minds on that one. We have added more and more understanding to the point where we know what we are made of and to a small degree, how it happens. DNA codes for chains of amino acids that form proteins. The proteins do the work.</span></p><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="background-color: white; font-family: inherit;"><br /></span></p><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="background-color: white; font-family: inherit;">What then makes Ginkgo Bioworks different among the herd of biotechnologies? They offer a variety of services and technologies. Each is there to help the customer speed through their research without the need to establish their own laboratories. Let's look at one offering.</span></p><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="font-family: inherit;"><i style="background-color: white;"><br /></i></span></p><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="caret-color: rgb(88, 88, 88);"><span style="font-family: inherit;"><i style="background-color: white;">Whether you’re looking to discover and synthesize a novel functional protein, optimize your protein production, or enhance processes to scale up your protein manufacturing, Ginkgo’s best-in-class capabilities empower your protein R&D.</i></span></span></p><p class="topic-paragraph" style="box-sizing: border-box; line-height: 1.6; margin-bottom: var(--paragraph-margin-bottom); margin-top: 0px; overflow-wrap: break-word;"><span style="background-color: white; font-family: inherit;"><br /></span></p></div><div><span style="background-color: white; font-family: inherit;">Is Ginkgo a manufacturing organization? Do they have decades of experience successfully developing and executing upstream and downstream manufacturing processes? </span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span style="background-color: white; font-family: inherit;">No matter what you want to do, Ginkgo claims they can do it all. Fermentation, strain optimization, scale up your manufacturing processes... they got you covered.</span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span style="background-color: white; font-family: inherit;">How does this compare to the CCS concept of The Empowered Laboratory? Ginkgo will help you develop the shape of your molecules. They will help you make them and manufacture them. The Empowered Laboratory work force will challenge your assumptions. They will test your theory. They will employ </span><span style="background-color: white;">unbiased observations and systematic experimentation.</span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span style="background-color: white; font-family: inherit;">To be fair and honest, Ginkgo is real. It exists and has put its money where its mouth is. They make their claims and they invite you to use their services. On the downside, they are in business to make money. They do not care if your drug stands a chance. They are taking your money to do what you want done. While your success is their success, they have also taken the low road of shielding themselves from the standard biotechnology pitfalls of research. Some things just don't pan out. Ginkgo will take that journey with you but it is you who ultimately stands alone at the end of the wrong path. Ginkgo simply cashes your checks and goes back to their business.</span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span style="background-color: white; font-family: inherit;">George F. Merck famously said: "<span style="caret-color: rgb(51, 51, 51);">We try to remember that medicine is for the patient. We try never to forget that medicine is for the people. It is not for the profits. The profits follow, and if we have remembered that, they have never failed to appear. The better we have remembered it, the larger they have been."</span></span></div><div><span style="caret-color: rgb(51, 51, 51); color: #333333;"><span style="background-color: white; font-family: inherit;"><br /></span></span></div><div><span><span style="background-color: white; caret-color: rgb(51, 51, 51); color: #333333; font-family: inherit;">I don't make the claim that Ginkgo Bioworks doesn't care about the medicine or the patient. I will admit that they are indeed about the technology. They are certainly better at many aspects of biotechnology than most new companies. A new company, or a new group within an established company, has to develop. Ginkgo will put you ahead of the curve in getting started. Ginkgo is there to help you advance your technology, not your science. </span></span></div><div><span><span style="background-color: white; caret-color: rgb(51, 51, 51); color: #333333; font-family: inherit;"><br /></span></span></div><div><span style="background-color: white; font-family: inherit;"><span style="caret-color: rgb(51, 51, 51); color: #333333;">If you think of science as the </span><span>unbiased observations and systematic experimentation employed in the pursuit of knowledge covering general truths or the operations of fundamental laws... Ginkgo Bioworks is not concerned. Science would be up to the customer of Ginkgo. Once you, the customer, has got your science right the profits will come. Ginkgo will assist you in maximizing </span>your<span> profits by helping you design the physical biological products you seek. </span></span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span style="background-color: white; font-family: inherit;"><span>What is missing? Science. We do not design biology, we study biology. With our current understanding we can attempt to make interventions that disrupt the path our biology has put us on. If we have </span>cancer<span>, we can attempt to stop the cells from dividing out of control. If we have protein imbalances that cause disease, we can make antibodies to fight excessive protein concentrations. But what we are fighting is not well understood. By employing the scientific method, we can get to a greater understanding. We can see how our behaviors involving diet and exercise </span>effect<span> our health. </span></span></div><div><span style="background-color: white; font-family: inherit;"><br /></span></div><div><span style="background-color: white; font-family: inherit;"><span>As the pharmaceutical industry strays </span>further and further away from science and focuses more and more on single protein interventions (biopharmaceuticals) we can expect little value to come from them. </span></div><div><span style="font-family: inherit;"><i><b style="background-color: white;"><br /></b></i></span></div><div><span style="caret-color: rgb(32, 33, 34); color: #202122;"><span style="font-family: inherit;"><i><b style="background-color: white;">So they've arranged to imitate things like runways, to put fires along the sides of the runways, to make a wooden hut for a man to sit in, with two wooden pieces on his head like headphones and bars of bamboo sticking out like antennas—he's the controller—and they wait for the airplanes to land. They're doing everything right. The form is perfect. It looks exactly the way it looked before. But it doesn't work. No airplanes land. So I call these things cargo cult science, because they follow all the apparent precepts and forms of scientific investigation, but they're missing something essential, because the planes don't land.</b></i></span></span></div><div><span style="font-family: inherit;"><i><b style="background-color: white;"><br /></b></i></span></div><div><span style="background-color: white; font-family: inherit; font-size: 30px; letter-spacing: 0.24px; text-align: center;"><br /></span></div><div><span style="background-color: white; font-family: inherit; font-size: 30px; letter-spacing: 0.24px; text-align: center;"><br /></span></div><div><br /></div>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-62269266717448096632023-06-04T06:43:00.005-07:002023-06-04T06:48:05.847-07:00Is Ginkgo Bioworks a Cargo Cult Biotech?<h1 class="quoteText" style="caret-color: rgb(24, 24, 24); color: #181818; font-weight: normal; line-height: 21px; margin: 0px 0px 15px; padding: 0px;"><span style="font-family: times; font-size: small;">Biology By Design. Biology is the most advanced technology platform on the planet. We program cells to make everything from food to materials to therapeutics. - Ginkgo Bioworks</span></h1><h1 class="quoteText" style="caret-color: rgb(24, 24, 24); color: #181818; font-weight: normal; line-height: 21px; margin: 0px 0px 15px; padding: 0px;"><span style="font-family: times; font-size: small;"><br /></span></h1><h1 class="quoteText" style="caret-color: rgb(24, 24, 24); color: #181818; font-weight: normal; line-height: 21px; margin: 0px 0px 15px; padding: 0px;"><span style="font-family: times; font-size: small;">The CEO of <a href="https://www.ginkgobioworks.com" target="_blank">Ginkgo Bioworks</a>, Jason Kelly, has a very clever introduction to biotechnology. He presents a slide with a picture of an Apple computer, an iPhone, a camera, and a metal watch on a gray desk decorated with a potted plant back lit with a lamp. "What's the most complicated device on this table?" he asks. His answer is the plant. He is incorrect. </span></h1><div><span style="font-family: times; font-size: small;">Here at the Cargo Cult Scientist, we have covered this logical error.</span></div><div><span style="font-family: times; font-size: small;"><br /></span></div><div><a href="https://www.mindtools.com/atddimk/the-cynefin-framework"><span style="font-family: times;">https://www.mindtools.com/atddimk/the-cynefin-framework</span></a></div><p><span style="font-family: times;">The Cynefin method of thinking describes simple, complicated and complex systems. The process of creating a slide presentation is simple. The iPhone is complicated. The plant is complex. </span></p><p><span style="font-family: times;">The technology products are complicated. The plant is not a complicated device. It is a complex living organism. </span></p><p><span style="font-family: times;">In<a href="https://www.technologyreview.com/2021/08/24/1032308/is-ginkgos-synthetic-biology-story-worth-15-billion/" target="_blank"> this article</a> from MIT Technology Review by Anthony Regelado, the author points out a an inconvenient truth. "<span style="background-color: white;">Given Kelly’s spiel, it is surprising that 13 years after it was founded, Ginkgo can’t name a single significant product that is manufactured and sold using its organisms."</span></span></p><p><span style="background-color: white;"><span style="font-family: times;">It is the Cargo Cult looking to the skies for that magical cargo. It has not yet arrived.</span></span></p><p><span style="background-color: white;"><span style="font-family: times;">The ceremonial practices of the biotech cargo cults are studied here at the CCS. We must look at the science and then back at the ceremonies of the biotech executives. There are plenty of real science and technology concepts employed at Ginkgo. As is true with all bullshit, the truth is a valuable tool. The difference between real science and cargo cult science however is in how the truth is employed. Is the truth employed in generating new scientific avenues and technologies? Is the truth used to convince people of things that aren't so? </span></span></p><p><span style="background-color: white;"><span style="font-family: times;">In my next post I will tackle just one claim from Ginkgo Bioworks. I will pick it randomly and discuss the issues from the perspective of the empowered laboratory workforce. I am not Bill Gates or Cathy Wood sitting in an office receiving a sales pitch. I am a guy who knows how to do the work. </span></span></p><p><br /></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-62554079989294437472023-03-25T06:48:00.003-07:002023-03-25T07:14:20.805-07:00Desperate Things <p> </p><h1 class="quoteText" style="caret-color: rgb(24, 24, 24); color: #181818; font-family: Merriweather, Georgia, serif; font-size: 14px; font-weight: normal; line-height: 21px; margin: 0px 0px 15px; padding: 0px;">“The mass of men lead lives of quiet desperation. What is called resignation is confirmed desperation. From the desperate city you go into the desperate country, and have to console yourself with the bravery of minks and muskrats. A stereotyped but unconscious despair is concealed even under what are called the games and amusements of mankind. There is no play in them, for this comes after work. But it is a characteristic of wisdom not to do desperate things..” - Henry David Thoreau</h1><div><br /></div><div>Is the modern day life science professional wise? Does s/he go to work each day with a purpose to discover new things or have they found employment that they desperately need? In my 13 year career in Biotechnology I was merely employed. During that time I learned many important things but they were learned on the periphery of my official work. </div><div><br /></div><div>Biotechnology is a wonderful thing. What most biotech employees do is not. They can employ the technology but does it result in scientific advancement? They turn on the machines, fill out the paperwork and go home as early as they can. Many of these employees are fully aware that their work is not science. </div><div><br /></div><div>Take, for example, an employee at Theranos. At the high point there were nearly 700 people working at Theranos. 2 (CEO and President) went to jail, 2 (laboratory technicians) were whistle blowers. In between were a whole lot of people engaged in "desperate things". </div><div><br /></div><div>Thought experiment: You have been working at Theranos for a few months. You are driving to work. The sun is coming up and it is going to be a beautiful day. But you are worried. You have to give a presentation soon and the results you need are just not coming in. You know what needs to go up on that PowerPoint slide. You have a meeting with your technicians. Will they have the data you need to please your superiors? </div><div><br /></div><div>The desired outcome IS the only instruction. Those above you have given you instructions on what they need from you. You have then given instructions to your group. They must now go into the laboratory and achieve the desired outcome. The problem is that they are using a machine designed by other people. The machine cannot achieve the desired outcome. They turn on the machine, inject the sample, and await the results. They show up to the meeting with the results. </div><div><br /></div><div>As you drive to work you imagine a genius has arrived at Theranos. He knows that the samples are not properly biochemically presented to the machine. He makes the adjustments that only a true biochemist can make. The results come in easily. Eureka! The machine works! Anyone can now prepare the samples, inject them into the machine and get accurate results. With great pride and joy you will stroll into your presentation with results sure to please all in attendence. You acknowledge and thank your staff. You finish the presentation by laying the ground work for full bonuses and future promotions. </div><div><br /></div><div>But you are not the genius who can make everything work. Even worse, you are just smart enough to know that the project was doomed from the start. Why? Bad science. The finger prick sampling of blood introduces factors that destroy accurate testing. You know this. You know your technicians can't overcome this reality. You need the job however. You have kids, a mortgage, a new car. Everyone thinks you are a success. As you drive to work on a beautiful day, you are living a life of quiet desperation. You must throw your technicians under the bus. </div><div><br /></div><div>If you read Bad Blood you will remember the story of George Shultzs' grandson. He was a technician at Theranos who was not getting the desired results. His superiors were threatening him to get those results or else. He became a whistle blower by talking to a reporter at the Wall Street Journal. His superiors, those who drove to work on beautiful days with worried minds, began to suspect the technician would spill the beans. He went to visit his grandfather only to find two Theranos attorneys awaiting his arrival in a room on the second floor. It was an ambush. He needed to sign the nondisclosure contract or face dire consequences. He bravely became a whistle blower rather then live a life of quiet desperation. </div><div><br /></div><div>This is of course the extreme. But most scientists face unpleasant consequences when the desired results are not forthcoming. True science will overcome this dilemma eventually. True science works and will provide the path to making things work. True science will only allow for it's proper application. This is known as technology. You can keep trying but only proper application produces useful predictable technology. You must use the scientific method. If not you must live a life of quiet desperation. </div><div><br /></div><div><br /></div><div><br /></div><div><br /></div>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-12178519689217765652023-03-12T06:47:00.006-07:002023-03-12T08:08:38.757-07:00The Value of An Empowered Laboratory Professional<h1 class="quoteText" style="caret-color: rgb(24, 24, 24); color: #181818; font-family: Merriweather, Georgia, serif; font-size: 14px; font-weight: normal; line-height: 21px; margin: 0px 0px 15px; padding: 0px;">“The trouble with the world is not that people know too little; it's that they know so many things that just aren't so. ”</h1><p><br style="caret-color: rgb(24, 24, 24); color: #181818; font-family: Merriweather, Georgia, serif; font-size: 14px;" /><span style="background-color: white; caret-color: rgb(24, 24, 24); color: #181818; font-family: Merriweather, Georgia, serif; font-size: 14px;">― </span><span class="authorOrTitle" face="Lato, "Helvetica Neue", Helvetica, sans-serif" style="color: #333333; font-size: 14px; font-weight: bold;">Mark Twain</span></p><p><br /></p><p>The main reason some believe Sars-Cov-2 was man made is the Furin Cleavage site. It is found in the new virus as four amino acids P R R A. There is a reasonable probability that this could happen in nature. What reduces the probability is that the R's (Arginine) are coded for by the nucleotides CGG. </p><p>In the genetic code there are 6 codons that code for R. In human beings the codon CGG is the most frequently found. 21% of the R codons in the human genome are CGG. In Sars-Cov-2 CGG however it is the least used codon. Only 3% of R codons in Sars-Cov-2 are coded for by CGG. <i>See the article below: </i><span style="font-family: Calibri;"><i><b>SARS-CoV-2 origin: an affair of codons?</b> </i></span></p><p>Occam's Razor posits that the answer with the least amount of assumptions is the most likely to be true. </p><p>It is simply a fact that the natural evolution theory of Sars-Cov-1 to Sara-Cov-2 requires more assumptions than does the man made theory. Considering the improbable Arginine inclusion in the improbable Furin Cleavage site insertion, the lab leak theory is the Occam's Razor choice. </p><p>The logical fallacy Appeal To Authority: The <a href="https://www.logicalfallacies.org/" style="color: black;">fallacy</a> of appeal to authority makes the argument that if one credible source believes something that it must be true.</p><p>When the funding of "gain of function" research became an issue Dr. Fauci needed to clarify what he knew he had been funding. "...gain of function is a very nebulous term...", he stated in a hearing with Rand Paul. In his defense he discussed <a href="https://www.phe.gov/s3/dualuse/Documents/p3co.pdf" target="_blank">PC3O </a>which was developed between 2014 and 2016 and officially codified in 2017. Gain of function can be good or bad for us. Whenever we are altering DNA sequences in living organisms however, we run the risk of "a dangerous situation". We must always proceed with extreme caution. </p><p>The question Dr. Fauci now had to answer was whether or not he violated the man made guidelines defining "gain of function". His defense is that the research at The Wuhan Institute of Virology would not reach the criteria of "research that might lead to a dangerous situation". He is most likely correct. He did not sign off on inserting the Furin Cleavage site into a viable version of Sars-CoV-1. The research he funded did involve gain of function but not in a genome that encoded for a dangerous virus. What happened after they approved the grant is unknown hoewever. </p><p>Quantity vs quality is part of the problem. In 2017 2,442,608 science and engineering articles <a href="https://www.nsf.gov/statistics/2019/nsf19317/overview.htm" target="_blank">were published</a>. The NIH/NIAID does not have the ability to validate the mountain of work done with their grant money. The NIH has a<a href="https://www.nih.gov/ABOUT-NIH/WHAT-WE-DO/BUDGET" target="_blank"> budget</a> of $45B. 10% of that money is used in its own laboratories. </p><p>Test the tests. Use that $4.5B spent on NIH labs to test our investments. Once the recipients of the grants have submitted their narratives of what took place in their laboratories... CHECK THEIR WORK. It is not sufficient to peer review in carpeted offices. Check in the lab by an empowered laboratory work force. Invest in people who wear white lab coats because they need to keep bad things off of their civilian clothing. Cultivate their careers. Develop specialized laboratory professionals though continuing education. Make that work force a deterrent to faulty thinking from PhDs who find laboratory work beneath them. </p><p>People do not know that Dr. Fauci and most scientists with whom he communicates NEVER set foot in a laboratory. Sars-CoV-2 most likely escaped from The Wuhan Institute of Virology in the body of a laboratory technician. We will never know the truth by combing through grant proposals. The truth lies in the notebooks and databases used by the laboratory staff. </p><p>In the case of Sars-CoV-2 there might have been a clue left in the RNA. Laboratory manipulations leave clues. An experienced laboratory work force would be a powerful tool in identifying manipulations or clues. Currently we have the authority of Dr's Fauci and Collins vs the Furin Cleavage site with CGG Arginine codons. </p><p><span style="font-family: Calibri; font-size: xx-large; font-weight: 700;">SARS-CoV-2 origin: an affair of codons?</span></p><div class="page" title="Page 1"><div class="layoutArea"><div class="column"><p><span style="font-family: Calibri; font-size: 12pt;">Antonio R. Romeu</span><span style="font-family: Calibri; font-size: 7pt; vertical-align: 5pt;">1 </span><span style="font-family: Calibri; font-size: 12pt;">and Enric Ollé</span><span style="font-family: Calibri; font-size: 7pt; vertical-align: 5pt;">2<br />1</span><span style="font-family: Calibri; font-size: 12pt;">: Chemist. Professor of Biochemistry and Molecular Biology at the Rovira i Virgili University.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">Tarragona. Spain. </span><span style="font-family: Calibri; font-size: 11pt;">Corresponding author. </span><span style="font-family: Calibri; font-size: 12pt;">Email: </span><span style="color: navy; font-family: LiberationSerif; font-size: 12pt;">antonioramon.romeu@iubilo.urv.cat<br /></span><span style="font-family: Calibri; font-size: 7pt; vertical-align: 5pt;">2</span><span style="font-family: Calibri; font-size: 12pt;">: Veterinarian, Biochemist. Associate Professor of the Department of Biochemistry and</span></p><p><span style="font-family: Calibri; font-size: 12pt;">Biotechnology of the Rovira i Virgili University. Tarragona. Spain. Email: </span><span style="color: navy; font-family: Calibri; font-size: 12pt;">enric.olle@urv.cat</span></p><p><span style="font-family: Calibri; font-size: 12pt; font-weight: 700;">Abstract</span></p><p><span style="font-family: Calibri; font-size: 12pt;">The furin cleavage site, with an arginine doublet (RR), is one of the clues of the SARS-CoV-2 origin. This furin-RR is encoded by the CGG-CGG sequence. Because arginine can be encoded by six codons, in a previous work we found that in SARS-CoV-2, CGG was the minority arginine codon (3%). Also, analyzing the RR doublet from a large sample of furin cleavage sites of several kinds of viruses, we found that none of them were encoded by CGG-CGG. Here, we come back to the core of the matter, but from the perspective that in the human genome, in contrast, CGG is the majoroty arginine codon (21%). Here, we highlighted that the 6 arginine codons provide genetic markers to a traceability on the RR origin in the furin site, as well as, to weigh the probability of the theories about the origin of the virus.</span></p><p><span style="font-family: Calibri; font-size: 12pt; font-weight: 700;">Key words</span></p><p><span style="font-family: Calibri; font-size: 12pt;">SARS-CoV-2 origin, Furin Cleavage Site, Arginine Codon Usage, Bioinformatics.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">As it is known (1,2,3) and we have also addressed (4), the origin of SARS-CoV-2 could be reduced to the origin or acquisition of the furin cleavage site in its S protein. This was a gain of function: there had been an insertion in the S gene that had caused the S protein to gain more capacity for human infection. SARS-CoV-2 belongs to the group of Betacoronaviruses, Sarbecoviruses (Lineage B). It was surprising that it was the only Sarbecovirus species with such furin site. At present, still nobody knows how and when it got to the virus. this is a key point in the controversy over the origin of the virus pandemic.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">Before going ahead, some basic concepts of biology need to be absolutely clear. Based on the universal genetic code and in the protein sinthesis, when the sequence of a gene is read in frames of three, the combination of the 4 letters taken three by three, results in the existence of 64 triplets or codons. Since there are only 20 protein amino acid, there are more than enough codons to go around, allowing some amino acids to be specified by more than one codon. The arginine (whose symbol is R), can be encoded by any of the 6 triplets: AGG, AGA, CGA, CGC, CGG, CGT.</span></p></div></div><img alt="page1image41469360" height="0.700000" src="blob:https://www.blogger.com/797c1680-f094-469d-8282-59cf2822a0e6" width="175.200000" /> <img alt="page1image41480176" height="0.800000" src="blob:https://www.blogger.com/1f15685f-8f8d-4c1f-8e04-259020949c79" width="89.300000" /></div><div class="page" title="Page 2"><div class="layoutArea"><div class="column"><p><span style="font-family: Calibri; font-size: 12pt;">In SARS-CoV-2, the furin site is characterized by the insertion of a 4 amino acid sequence (PRRA), which corresponds to the insertion of 12 nucleotides (3 x 4). In SARS-CoV-2, the RR doublet of the furin site is encoded by the CGG-CGG codons. It is worth bearing in mind that furin cleavage site, with RR doublet, is common in the world of viruses (5) (including Coronaviruses, but excluding Betacoronaviruses). Recombination with other viruses is the most plausible explanation for the acquisition of this site in SARS-CoV-2 (6). However, to analyze the likelihood of such virus recombination, we screened the databases, and analyzing the RR doublet from a large sample of furin cleavage sites of several kinds of viruses. We found that there were no RR doublets encoded by the CGG-CGG codons (4). We observed that AGA triplet was the majority codon involved in these viral RR doublets. In all genetic recombination, there is always a donor and an acceptor of genetic material; and the donor code is passed to the acceptor. If the SARS-CoV-2 has acquired the furin site by recombination with another virus, at the moment, from the information available in the genomic databases, we can't know what it may have been.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">With these results, we were interested in determining the arginine codon usage in SARS-CoV-2. Studying the composition of all its proteins, we found (4): AGG (13%), AGA (45%), CGA (5%), CGC (10%), CGG (3%), CGT (24%). The AGA triplet was the majority, and interestingly, CGG was the minority. In the specific case of S protein, of the 42 arginines it has, 20 are encoded by AGA, and only 2 by CGG (4). It was surprising that CGG-CGG codons, were those that encoded the RR doublet of the SARS-CoV-2 furin site.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">Since each species has its own codon usage. Regarding the amino acid arginine in Homo sapiens, the frequency of use of triplets is (7): AGG (20%), AGA (20%), CGA (11%), CGC (19%), CGG (21%), CGT (9%). This pattern of the human genome contrats with that of the virus. In the human species, the CGG triplet is the majority (21%) and in the virus it is the minority (3%). It is surprising that in SARS-CoV-2, the furin site RR doublet uses the arginine majority codon of the human genome.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">Circumstance like this fuels the great dilemma on conflicting theories about the origin of the virus: natural or laboratory (biotechnological).</span></p><p><span style="font-family: Calibri; font-size: 12pt;">The theory that supports a natural origin of SARS-CoV-2, should consider that two independent events have occurred in time: (i) the insertion by mutation or recombination of a 12 nucleotides sequence, encoding the furin site, in a strategic site of the S gene; and (ii) such inserted sequence must contain the majority human arginine codon: CGG. Both events already have a low probability, however, since they are independent and had had to be simultaneous, the probability would be even lower.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">The theory that supports a laboratory origin of SARS-CoV-2, should contemplate that the insertion of the furin site in the virus genome had been in a controlled way. Considering the current applications of genetic engineering, genes of certain human proteins are now inserted (cloned) into microorganism genomes suitable for their commercial manufacture. A typical example is the insulin production obtained from the yeast </span><span style="font-family: Calibri; font-size: 12pt; font-style: italic;">Sacharomyces cerevisae</span><span style="font-family: Calibri; font-size: 12pt;">. In these circunstances, human genes are biotechnology optimized with the majority codons of the recipient microorganism. In the case of the SARS-CoV-2 furin cleavage site, it gives the impression that a 12-nucleotide sequence had been cloned into the genome of a given virus originating the SARS-CoV-2. Of course, this cloning sign can only be glimpsed since arginine has 6 triplets in the universal genetic code. In the impossible case that arginine had 2 codons, such as lysine (by the way, lysine is also a positive</span></p></div></div></div><div class="page" title="Page 3"><div class="layoutArea"><div class="column"><p><span style="font-family: Calibri; font-size: 12pt;">amino acid and present in viral furin sites), that traceability does not it would make sense and, there would be no doubt about the natural origin of the virus.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">This is the state of the art on the origin of SARS-CoV-2, from the genetic perspective. The issue must also be approached with a forensic genetic mindset. Results based on genetic markers are always expressed in stochastic or probabilistic terms. In genetics, there are no absolute certainties, but there are evidences so highly probable that allow sentencing of guilt or the determination of paternity and/or maternity relationships. Thus, under the umbrella of the sequence analyses, the origin of SARS-CoV-2 cannot be proved as a mathematical theorem. However, between two theories, which have the same consequences, the simplest explanation is usually the most probable: Occam's razor.</span></p><p><span style="font-family: Calibri; font-size: 12pt; font-weight: 700;">Acknowledgements</span></p><p><span style="font-family: Calibri; font-size: 12pt;">This work has not been awarded grants by any research-supporting institution.</span></p><p><span style="font-family: Calibri; font-size: 12pt; font-weight: 700;">Competing interest declaration</span></p><p><span style="font-family: Calibri; font-size: 12pt;">All authors declare that they have no conflicts of interest.</span></p><p><span style="font-family: Calibri; font-size: 12pt; font-weight: 700;">References</span></p><p><span style="font-family: Calibri; font-size: 12pt;">1. Britt Glaunsinger. Coronavirus biology. The second lecture in the COVID-19, SARS-CoV-2 and the Pandemic Series. University of California, Berkeley. 2020. Accessed June 2, 2021. https://www.youtube.com/watch?v=r2mOU2qOCYs.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">2. Nicholas Wade. Origin of Covid — Following the Clues. Accessed June 2, 2021. https://nicholaswade.medium.com/origin-of-covid-following-the-clues-6f03564c038.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">3.Kristian G Andersen, Andrew Rambaut, W Ian Lipkin, Edward C Holmes, Robert F Garry. The proximal origin of SARS-CoV-2. Nat. Med. 26:450-452, 2020. PMID: 32284615. doi: 10.1038/s41591-020-0820-9.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">4. Romeu, A.R.; Ollé, E. SARS-CoV-2 and the Secret of the Furin Site. Preprints 2021, 2021020264 (doi: 10.20944/preprints202102.0264.v1). Accessed June 1, 2021..</span></p><p><span style="font-family: Calibri; font-size: 12pt;">5. Elisabeth Braun, Daniel Sauter. Furin-mediated protein processing in infectious diseases and cancer. Clin. Transl. Immunol. E1073, 2019. PMID: 31406574. doi.org/10.1002/cti2.1073.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">6. William R Gallaher. A palindromic RNA sequence as a common breakpoint contributor to copy- choice recombination in SARS-COV-2. Arch. Virol. 165:2341-2348, 2020. PMID: 32737584. doi: 10.1007/s00705-020-04750-z.</span></p><p><span style="font-family: Calibri; font-size: 12pt;">7. GenScript Codon Usage Frequency Table(chart) Tool. Accessed June 2, 2021. https://www.genscript.com/tools/codon-frequency-table.</span></p></div></div></div>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-7246319829584314042023-03-05T06:54:00.037-08:002023-03-05T07:07:21.910-08:00By What Authority?<p>The Jews closed the canon of The Old Testement in 100 AD at the Synod of Jamnia. At that time they decided which were the canonical books of the Hewbrew scripture. The books of The New Testament were decided upon at the Senate of Rome under Pope Damasus in 382 AD. The recipients of the message of the old and new testaments were already in place. The authorities were selected, the message was selected and then canonized in the Bible. </p><p>In science we don't close the books. We leave room for improvements or complete reconstruction. </p><p>We don't talk about "the science" so much here. We talk about the scientific method, which is what Feynmans CCS was all about. "But there is one feature I notice that is generally missing in cargo cult science. That is the idea that we all hope you have learned in studying science in school--we never say explicitly what this is."</p><p>The "idea we all hope you have learned" is the scientific method. How do we get to the truth? How many times have we, as individuals, gotten something wrong? We argue and we shout and we point our fingers at the other guy. The bitterness in our online debates demonstrates something the psychologists should be studying. What is road rage? What is cyber bullying about? Why are we so different in different situations? I will suggest that we are different because there is a place in all of our minds where opposition to our thoughts is never encountered. It is a safe space.</p><p>It is here, this place inside our minds where we can find the scientific method. The Bible is questioned by Atheists, just not in church while the preacher is giving his sermon. We all must go out into he world where our thoughts are questioned. We must first develop our narrative so we can survive and evolve. </p><p>When we find ourselves alone and we choose to sit and think, it is there where we can explore without fear or interruption. Our minds can roll on freely getting it right and wrong. Recognizing when we are wrong is good. Others publicly recognizing how wrong we are can hurt our feelings. Therefore we must think alone and allow ourselves to make mistakes. We must also thrive to correct our wrong thinking with truths.</p><p>Biotechnology has failed to nurture the right people. The industry has evolved selecting those who best cave to authorities like Dr's. Fauci and Collins. When the Covid vaccine was introduced where were the experts asking about the MOA of mRNA vaccines? How could we introduce a paradigm shift to vaccinations when faced with a pandemic? Why was there so little emphasis on treatment? What was our understanding of how viruses pass through the human race? Did we really think we could just hide in our homes while the virus waited for us just outside the front door? There were some left to ask questions, but they too learned the powers of authority and dogma. </p><p>I won't talk about the origins of the pandemic at this time. I will simply say that the pandemic showed us the problem with dogmatic science. Fauci created the NIAID bible during the HIV/AIDS era. Koch's postulates were ignored. Ineffective and harmful solutions, such as AZT, were allowed. Using the same authority (Fauci) and the same NIAID bible, we simply went through the pandemic with minimal resistance to it's destructive path. We learned nothing and we saw what happens when Cargo Cult Science takes center stage. True science will not canonize the Covid 19 book however. We must all go to that safe space in our minds and think about the many aspects of the pandemic. Never stop thinking and asking questions. Just be aware of whom you may be offending and why they take offense. </p><p> I'll end with another Feynman classic quote that sums up the problem of thinking in a public place, not in that safe place in your mind where the scientific method thrives. </p><h1 class="quoteText" style="caret-color: rgb(24, 24, 24); color: #181818; font-family: Merriweather, Georgia, serif; font-size: 14px; font-weight: normal; line-height: 21px; margin: 0px 0px 15px; padding: 0px;">“I would rather have questions that can't be answered than answers that can't be questioned.”</h1><p><br style="caret-color: rgb(24, 24, 24); color: #181818; font-family: Merriweather, Georgia, serif; font-size: 14px;" /><span style="background-color: white; caret-color: rgb(24, 24, 24); color: #181818; font-family: Merriweather, Georgia, serif; font-size: 14px;">― </span><span class="authorOrTitle" face="Lato, "Helvetica Neue", Helvetica, sans-serif" style="color: #333333; font-size: 14px; font-weight: bold;">Richard Feynman</span></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-2157555733570498322022-05-15T06:43:00.002-07:002022-05-15T06:43:21.241-07:00One Such Narrative<p> I once made a phage display library. The CEO of the company had a narrative he wanted to push. We find a peptide that binds to a protein and we can deliver drugs to specific targets. Making the library was in the realm of complicated. It required a background in many laboratory techniques but most people should be capable of learning how it is done. The narrative on the other hand required a Cargo Cult Scientist. </p><p>After my cohorts and I had been sacked the Cargo Cult Scientists set themselves to work. They published a paper. They patented the library and the idea behind it. They sent the library to a professor in a far away land who reported back that everything was going well. Nothing specific was ever reported but the company renewed the professors contract and sent out a press release stating that all was going according to plan.</p><p>Then the company failed. The CEO had been fired. The President of the company had been sent forth to sell the narrative. I last saw him on a stage presenting our research. He knew they fired the technicians. The whole idea failed to produce results but the narrative still had legs. The Presidents voice faltered as he told the tale. No one believed the technology was going to work. What magical pixy dust was being sprinkled on the phage display library in that far off land by the esteemed college professor? </p><p>The President seemed to disappear. I hoped he hadn't done anything rash. He was a good person. His involvement with the Cargo Cults of Biotech had put him in a tight spot. What was his future?</p><p>Fast forward. The Chief Scientific Officer under the CEO and President had moved on to a new Cargo Cult selling a similar narrative. This company specialized in drug deliver systems. The former President now needed a job and was hired to push the narrative of the new company. He was hired in 2016. The company filed for bankruptcy in 2018. They were purchased for less than my old Seattle house sold for recently. </p><p>In the word "Biotechnology" is technology. It is not science to produce or discover molecules that bind to other molecules. There are technologies such as phage display that one can use to find such molecules. Technology is real. Phage Display can find you a peptide that binds to a protein. Then what?</p><p>That is the point where most technologists lose their jobs. THEY are supposed to now make the technology fit the narrative. The narrative is the purview of the PhD. The narrative is what the C-level executives are selling. </p><p><br /></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-13721945423512048072022-03-13T11:12:00.001-07:002022-06-21T10:42:09.707-07:00A New Alzheimers Drug<p> The FDA <a href="https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease" target="_blank">approved a drug</a> for the treatment of Alzheimers on June 6, 2021. </p><p><br /></p><blockquote><p><span style="background-color: white; caret-color: rgb(51, 51, 51); color: #333333; font-family: Georgia, Times; font-size: 18px;">Today FDA approved </span><a data-entity-substitution="canonical" data-entity-type="node" data-entity-uuid="ef338c96-fdd8-41db-a8bc-8ac436fd4dd8" href="https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/aducanumab-marketed-aduhelm-information" style="box-sizing: border-box; color: #001871; font-family: Georgia, Times; font-size: 18px;" title="Aducanumab (marketed as Aduhelm) Information">Aduhelm (aducanumab)</a><span style="background-color: white; caret-color: rgb(51, 51, 51); color: #333333; font-family: Georgia, Times; font-size: 18px;"> to treat patients with Alzheimer’s disease using the </span><a data-entity-substitution="canonical" data-entity-type="node" data-entity-uuid="082c98db-46dd-4b0c-ac2a-68d9b0fc7766" href="https://www.fda.gov/drugs/information-health-care-professionals-drugs/accelerated-approval-program" style="box-sizing: border-box; color: #001871; font-family: Georgia, Times; font-size: 18px;" title="Accelerated Approval Program">Accelerated Approval</a><span style="background-color: white; caret-color: rgb(51, 51, 51); color: #333333; font-family: Georgia, Times; font-size: 18px;"> pathway, under which the FDA approves a drug for a serious or life-threatening illness that may provide meaningful therapeutic benefit over existing treatments when the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients and there remains some uncertainty about the drug’s clinical benefit.</span></p></blockquote><p><br /></p><p>In all of my experience with biotechnology, I have never worked at a company or research laboratory that did not have an amyloid beta project underway. Aduhelm is an antibody that binds to amyloid beta. In my core belief in the cynefin method of thinking (simple, complicated, complex), this approach has always been simple. Alzheimers, the human brain and aging are complex. Amyloid beta as a drug target is simple using complicated research and complicated methods of developing an antibody. Clinical trials are also complicated. BUT... to merely hire scientists to develop an antibody against Amyloid Beta is simple. Telling doctors and clinical trial specialists to hammer that square peg through a round hole is simple. </p><p>But it didn't work. At least that was the conclusion in: </p><p>https://www.health.harvard.edu/blog/a-new-alzheimers-drug-has-been-approved-but-should-you-take-it-202106082483</p><p>Once again, we really should look into science that isn't science. What prompted the powers that be to approve the drug? The need to fill the gap was too great. They needed to offer something even though that something doesn't work. </p><p>What happens next? The answer is well known in the pharmaceutical industry. If the patient gets better... claim responsibility. If they get worse... they came too late. If they stay the same... up the dose. </p><p><br /></p><p><br /></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-85156858489129749402022-01-09T07:31:00.004-08:002022-01-09T07:45:26.907-08:00Elizabeth Holmes Enters the Cargo Cult Hall of Fame<p>Elizabeth Homes was on trial for <a href="https://techcrunch.com/2022/01/08/theranos-elizabeth-holmes-startup-friends/" rel="nofollow" target="_blank">fraud</a>. She intentionally lied to people to enrich herself and maintain her multi-billion dollar biotech empire. But remember, biotechnology has a substantial cargo cult science branch of science and technology. What Ms. Holmes did was not unusual. Her crime against the good name of science is the same as most biotech/pharma companies. Fake it til you make it.</p><p>Biotechnology is good. It is real. I once argued with a distant family member over the existence of DNA. His church had put on a seminar by someone who argued that DNA is a man made construct. How then did I use it to do my work? How could I order a piece of DNA and end up with a protein that I could purify and use to do specific things?</p><p>Science is about the truth. Cargo Cult Science <a href="https://www.amazon.com/Bullshit-Harry-G-Frankfurt/dp/0691122946" rel="nofollow" target="_blank">is about BS</a>. A bullshit artist prefers the truth when they can use it but the narrative is of utmost importance.</p><p>Elizabeth did not create a blood testing device that provided accurate results. If you had a concentration of glucose in your blood of X you could not expect Theranos technology to ever know what X is. Theranos boasted that their blood testing device could perform 273 tests. No longer would a patient have to go into a hospital and pay the exorbitant cost of their tests. Using a device the size of a toaster one could get a pin prick, have the blood sucked into the Theranos "Nanotainer", insert the "Nanotainer" into the device and within an hour have the results sent to their doctor. The only problem was that the results were not accurate. The tests did not work</p><p>Now... to Elizabeth Holmes, this did not pose a big problem. She most likely assumed that scientists could be hired to sort out those pesky details. Her mission was go raise capital to hire the scientists and provide them with what they needed. What they all needed however was the scientific method. It's not for sale in the Sigma catalog. </p><p>Any and all of the biotechnology companies that I worked for could have simply been a branch of Theranos. We all had the same problem. We began with an outcome that we would prefer. We then hired lower level "scientists" and forced them to provide evidence that the narrative is the truth. </p><p>Perhaps Elizabeth Holmes did not know how science and technology works. Perhaps she believed that one begins with a narrative based on preference. Once the narrative began to fail she was too far into a lifestyle that was wildly exciting. Sitting on stage with Bill Clinton, face on the cover of Forbes, name on list of 30 (billionaires) under 30... must of have been intoxicating. She was in a place where she wanted to be. Science/technology would be her savior. She believed in science. She had faith. She did not understand that science is not about faith. </p><p>Her story is a cautionary tale of how science can devolve into Cargo Cult Science. It costs people money, careers and freedom. As Elizabeth settles into her jail cell, many more will begin their careers in the life sciences. They too will begin pushing narratives that are not true. The world of life science, biotechnology and medical science is wrought with fraud. We do not have a sure fire way of weeding out the CCS folk from the good. It is only through the study of such cases as the Theranos fraud that we can advance our understanding of what is science and what is not. </p><p>We have a long way to go. The scientific method remains in the same quandary as it did during Richard Feynman's day. </p><p><b>"Most people believe so many wonderful things that I decided to investigate why they did." "So we really ought to look into theories that don't work, and science that isn't science." -Richard Feynman. </b></p><p><br /></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-67257105628000772432022-01-09T06:40:00.001-08:002022-01-09T07:36:57.868-08:00Rogan and Gupta<p>Recently there was an <a href="https://nypost.com/2021/10/14/joe-rogan-takes-on-sanjay-gupta-over-cnn-lying-about-covid-treatment/" target="_blank">exchange</a> between Joe Rogan and Sanjay Gupta on Joe's show. It involves the controversial subject of Covid 19 treatments. Let us explore the use of language in this story and how it applies to the Cargo Cult belief system. </p><p><span style="caret-color: rgb(36, 36, 36); color: #242424; font-size: 17px;"><span style="font-family: inherit;">Stromectol is an anti-parasite human medication. DuraMectin is an anti-parasite horse medication. Both have, as the active </span></span><span style="color: #242424;"><span style="font-size: 17px;">ingredient, Ivermectin. Each drug has a name. They each have distinct ingredients. They are produced in separate locations by separate companies. They both use Ivermectin as the active ingredient. </span></span></p><p><span style="color: #242424;"><span style="font-size: 17px;">Was it accurate that Joe Rogan took a horse medication versus a human medication? Did CNN lie?</span></span></p><p><span style="color: #242424; font-size: 17px;">As you know, The Cargo Cult Scientist is interested in the truth and how we get at it. What we know in this case is that Joe took an Ivermectin drug prescribed by his doctor. We know that CNN people said that Joe took a horse medication. If (and we don't know this) Joe took Stromectol, we could ask CNN a different question. Is Stromectol a horse medication. If they say yes, then the onus is upon them to prove that point. The argument they will make will be that Ivermectin is the active ingredient used to treat horses for parasites. We would then be arguing whether or not an active ingredient is the same as a drug. </span></p><p><span style="color: #242424;"><span style="caret-color: rgb(36, 36, 36); font-size: 17px;">Why does it matter? We human beings have different ways of dealing with the truth. If it suits our narrative we eagerly accept the truth and use it to make people think positively about our narrative. If it does not suit our narrative we downplay the truth. We find ways to discredit the truth. If we are clever we can fool people into focusing on the positive nature of our narrative while ignoring the negative impact the truth has upon our narrative</span></span><span style="caret-color: rgb(36, 36, 36); color: #242424; font-size: 17px;">.</span></p><p><span style="color: #242424;"><span style="font-size: 17px;">This is a major factor in the Cargo Cult thought process. If the positive aspects of the narrative outweighs the negative aspects of the truth, people will accept the narrative. </span></span></p><p style="text-align: left;"><b><i><span style="font-size: 17px;"></span></i></b></p><blockquote><p style="text-align: left;"><b><i><span style="font-size: 17px;">"I think that there's a lot of people more concerned about being precisely, factually, and semantically </span><span style="caret-color: rgb(36, 36, 36); font-size: 17px;">correct than about being morally right." -Alexandria Ocasio Cortez</span></i></b></p><p style="text-align: left;"></p></blockquote><p style="text-align: left;"><span style="color: #242424;"><span style="font-size: 17px;">There is a reason why the scientific method has provided the world with so much. Human selfishness gets some people more than their fair share. It can also lead to a lifetime of unhappiness. Science only seeks to know the truth. Facts are used as tools to learn, not to manipulate the understanding of others. Being concerned about what is "morally right" is the purview of scoundrels. </span></span></p><p style="text-align: left;"><span style="color: #242424;"><span style="font-size: 17px;">Joe Rogan put Sanjay Gupta on the spot. He didn't ask Gupta if CNN had lied. He told Gupta that CNN lied and he asked if that bothered him. Gupta finally had to admit, "They shouldn't have said that." In other words, a news agency should not intentionally lie. True.</span></span></p><p style="text-align: left;"><span style="color: #242424;"><span style="font-size: 17px;"><br /></span></span></p><p><br /></p>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-76927409371099702812021-10-24T06:59:00.001-07:002021-10-24T06:59:28.769-07:00Covid 19<p> It has been a long time since I have turned to this blog to get some thoughts put into words. The blog was always a way of venting to myself. I didn't care if anyone read the blog. I was only trying to put into words the torment of working in a group think environment. Within this a handful of failed biotechnology companies and our industry I was always thinking... just the wrong thoughts. </p><p>Today I am tormented by the pandemic and the conversation around the virus. The first thing to point out is the virus itself. It is a Corona virus. It is called SARS-Cov-2 and is related to SARS-CoV (Sever Acute Respiratory Syndrome Corona Virus). SARS-CoV was the virus that led to the SARS pandemic in 2003. Here is a chart that compares the two:</p><p><br /></p><table border="1" cellpadding="0" cellspacing="0" style="border-collapse: collapse; border-spacing: 0px; box-sizing: border-box; caret-color: rgb(51, 51, 51); color: #333333; font-family: open-sans, sans-serif; font-size: 16px;"><tbody style="box-sizing: border-box;"><tr style="box-sizing: border-box;"><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 178px;"><p align="center" style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"></p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p align="center" style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"><strong style="box-sizing: border-box;">SARS-CoV</strong></p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p align="center" style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"><strong style="box-sizing: border-box;">SARS-CoV-2</strong></p></td></tr><tr style="box-sizing: border-box;"><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 178px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"><strong style="box-sizing: border-box;">Transmissibility R<span style="bottom: -0.25em; box-sizing: border-box; font-size: 12px; line-height: 0; position: relative; vertical-align: baseline;">0</span></strong></p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">2·4</p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">2·5</p></td></tr><tr style="box-sizing: border-box;"><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 178px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"><strong style="box-sizing: border-box;">Incubation period</strong></p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">2 to 7 days</p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">4 to 12 days</p></td></tr><tr style="box-sizing: border-box;"><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 178px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"><strong style="box-sizing: border-box;">Days between symptom onset and maximum level of infectivity</strong></p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">5 to 7 days</p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">0 days</p></td></tr><tr style="box-sizing: border-box;"><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 178px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"><strong style="box-sizing: border-box;">Amount of patients with mild illness</strong></p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">Low</p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">High</p></td></tr><tr style="box-sizing: border-box;"><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 178px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"><strong style="box-sizing: border-box;">Amount of patients needing hospitalization</strong></p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">Most patients (over 70 percent)</p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">Few patients (20 percent)</p></td></tr><tr style="box-sizing: border-box;"><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 178px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"><strong style="box-sizing: border-box;">Amount of patients needing intensive care</strong></p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">Most patients (40 percent)</p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">1 in 16,000</p></td></tr><tr style="box-sizing: border-box;"><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 178px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;"><strong style="box-sizing: border-box;">Risk factors for severe illness</strong></p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">Increased age, underlying illnesses</p></td><td style="box-sizing: border-box; line-height: 1.58em; padding: 0px; width: 195px;"><p style="box-sizing: border-box; line-height: 1.58em; margin: 0px 0px 25px;">Increased age, underlying illnesses</p></td></tr></tbody></table><br /><div>The RNA sequences that have been published all seem to be in agreement. A complete genome sequence from Ranjit Sah et.al. https://mra.asm.org/content/9/11/e00169-20 was >99.99% identical to two previous published sequences. How does this sequence compare with SARS-CoV?</div><div><br /></div><div>The SARS-Cov sequence was published in 2003 by the CDC. It is 29,727 bp (29811 bp in SARS-Cov-2) in length. Using the BLAST (<span face=""helvetica neue", helvetica, arial, sans-serif" id="yui_3_10_0_1_1606676151048_135" style="caret-color: rgb(82, 82, 82);"><span style="color: #525252; font-size: 14px;">Basic Local Alignment Search Tool</span><span style="background-color: white;"><span style="color: #525252; font-size: 14px;">)</span> on the NIH page we come up with 82% homology.</span></span></div><div><span face=""helvetica neue", helvetica, arial, sans-serif" style="caret-color: rgb(82, 82, 82);"><span style="background-color: white;"><br /></span></span></div><div><span face=""helvetica neue", helvetica, arial, sans-serif" style="caret-color: rgb(82, 82, 82);"><span style="background-color: white;">The beginning of thinking about a problem is to gather the facts. We have lived with Covid 19 for a long time now. We have several vaccines. We have known knowns and known unknowns. And we have the problems associated with Cargo Cult thinking. </span></span></div><div><span face=""helvetica neue", helvetica, arial, sans-serif" style="caret-color: rgb(82, 82, 82);"><span style="background-color: white;"><br /></span></span></div><div><span face=""helvetica neue", helvetica, arial, sans-serif" style="caret-color: rgb(82, 82, 82);"><span style="background-color: white;">The unknown origin: Why does it matter? The normal genetic drift that leads to strain variations is useful information. In the chart above we see a few of the consequences of genetic changes. Should we be worried? What can we do to prevent negative outcomes (?) and so on. </span></span></div><div><span face=""helvetica neue", helvetica, arial, sans-serif" style="caret-color: rgb(82, 82, 82);"><span style="background-color: white;"><br /></span></span></div><div><span face=""helvetica neue", helvetica, arial, sans-serif" style="caret-color: rgb(82, 82, 82);"><span style="background-color: white;">The known danger: We know that most people who die from Covid 19 exceed the age of a normal life span. The sickest are mostly obese. The danger is not great among healthy younger people. We are therefore attempting to protect the vulnerable by not getting and spreading the virus. </span></span></div><div><span face=""helvetica neue", helvetica, arial, sans-serif" style="caret-color: rgb(82, 82, 82); color: #525252;"><span style="background-color: white;"><br /></span></span></div><div><span style="background-color: white; caret-color: rgb(82, 82, 82);"><b>HOW DO WE BEGIN TO UNDERSTAND SARS COV 2? </b></span></div><div><span style="background-color: white; caret-color: rgb(82, 82, 82);"><b><br /></b></span></div><div><span style="background-color: white; caret-color: rgb(82, 82, 82);">The problems of Cargo Cult Science among our professional science class had come home to roost. We are told to get vaccinated and to social distance. Wear masks and avoid crowds. It appears as though our highest ranking scientists have never thought about viruses before. They are ubiquitous. We need viruses to survive. How then do we now expect to eliminate the viruses we don't like? </span></div><div><span style="background-color: white; caret-color: rgb(82, 82, 82);"><br /></span></div><div><span style="background-color: white; caret-color: rgb(82, 82, 82);">Like everyone else, I don't have the answers. I have questions and those are considered taboo in the Cargo Cult. We should be using science to debunk claims that seem wrong. We should reject the main stream media sources and we should not take NIH/NAID/CDC... scientists to be any better than ourselves. Seek knowledge. </span></div>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com1tag:blogger.com,1999:blog-20579732.post-69722966928110547532019-10-20T10:07:00.001-07:002020-02-16T10:08:16.150-08:00Theranos's Bad Blood No one thought to test the tests.<br />
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The company depicted in John Carreyrou's Bad Blood was indeed a Cargo Cult Biotech. A sociopath CEO gathers a group of highly educated individuals who pledge allegiance to the narrative. Step one was the narrative. Theranos had a good one, replace highly regulated laboratories and their skilled technicians with with a machine the size of a toaster. Step two was to hire people who will work backwards to provide the product and supporting details. As in all bullshit narratives, the truth is preferable. If the truth does not support the narrative, fake til you make it. The narrative will be altered only as the last straw.<br />
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Theranos began with a blood testing device called The Edison. The narrative was that Theranos would provide cheaper, faster and equally accurate blood tests. Hitherto people had to go to their doctor or the hospital to have blood drawn. The blood is sent off to the lab for whatever tests the doctor requires to make decisions on a persons health. The ground breaking technology at Theranos was going to change all of that. The patient would go into the pharmacy and enter a room where the Theranos technology would produce results within an hour. </div>
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The blood testing device replaced the hospital laboratory and highly trained/regulated staff. Hospital labs are ran by Medical Laboratory Scientists <a href="https://en.wikipedia.org/wiki/Medical_laboratory_scientist">(MLTs)</a>. These individuals often get a bachelors degree in a life science then apply to an MLT program. The programs last a couple years and produce specialized hospital personnel. Errors in blood testing can lead to serious outcomes including death, thus the need for the highly educated and regulated staff.<br />
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At one point in the Theranos saga an executive from Walgreens was at Theranos for a meeting. He had a plan. He was going to have Theranos do a test on his blood that day. Then he was going to go to Stanford Hospital and get the same test done with them. It is about as simple as one can design an experiment. Someone makes the claim that they can do something better, faster and cheaper. Have them do that thing and compare it to the thing it is replacing. So what happened?<br />
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Elizabeth Holmes told the Walgreens executive that there was no machine available to do the test. The experiment was abandoned and never attempted at a later date. How, you ask, did a company like Walgreens, the FDA and $10 billion dollars worth of investors not do this test? Select one of the 272 blood tests and compare that test to the hospital version of the test. Never happened.<br />
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The reason the test was never done was because cargo cults do not understand the scientific method. In Elizabeth Holmes the investors, partners and fellow executives had a superstar. She was pretty, young, smart, charismatic and a great spokesman for the narrative. It was, after all, her narrative. She started the company with the narrative and began working her way backwards. When the obvious experiment was proposed, she nipped it in the bud. She did not even think such an experiment would ever be done.<br />
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In my Biotech experience, on two occasions, I had been tasked with improving a protein purification yield. If I was getting 1 gram per liter, I was to get more than 1 gram per liter. Pretty simple. The only problem was no one above me knew what the yield was. They told me to improve something without knowing what that something was. That is precisely the problem of Theranos. All of that money, all of those high powered board members, all of those employees and no one thought to test the test. </div>
Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com2tag:blogger.com,1999:blog-20579732.post-67611797604304996472018-09-16T03:26:00.002-07:002018-09-16T03:26:23.270-07:00Juno Sold for $9,000,000,000Long ago, when I first began working in biotechnology, I read a book called, <a href="https://www.amazon.com/800-Million-Pill-Truth-behind/dp/0520246705">"The 800 Million Dollar Pill"</a> It was a book that told the story of an industry gone mad. The cost of bringing a drug to market was out of control and something needed to be done. The book came out in 1998. Twenty years later Juno, a company that has yet to get a drug approval, sells for nine billion dollars.<br />
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How does this happen?<br />
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Juno has a promise. As usual in our cargo cult companies, Juno provides an <a href="https://www.explorecarttherapy.com/">animated illustration</a> on how their technology works. Their pipeline page shows 11 candidates. Eight are in phase 1 and three are in phase 1/phase 2. The promise is the cargo that we look for up in the sky. We've heard about the cures for cancer. When do they arrive?<br />
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For the investors and higher ups at Juno, the cargo has already arrived. $9 billion is a big deal. And they never even got to phase three with any drug candidate.<br />
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Another company that is on our list as a cargo cult is Serepta. I discussed how they got their first drug approved from a trial with only 12 patients <a href="http://cargocultscience.blogspot.com/2016/09/sereptas-cargo-plane-has-landed.html">here. </a> The company has since gone on to improving their stock price by releasing a new study that only has 3 patients. AAVrh74.MHCK7.micro-dystrophin (that's the name of the drug) was shown to have increased micro-dystrophin and reduced serum creatine kinase. As you can see from their handling of data from the previous trial, they have a way of making data fitting into the preconceived narrative. Does it help the young boys in their daily struggle with the disease? We do not hear from the parents. Since the studies are done on only a few kids, why not follow them as the disease progresses? What do the drugs do besides change the numbers on the charts submitted to the FDA?<br />
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Since beginning this blog, the Cargo Cults of Biopharma have evolved. They no longer need to spend $800M and get a drug approval. They have improved their ceremonies. The man in the watch tower with a coconut headset now looks more like a real air traffic controller. The deals continue to be made and money continues to flow into companies like Juno and Serepta. What do we the consumers get in exchange? Cures for cancer? Treatment for DMD?<br />
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It's about money. Science is losing. Before we leave the planet our money will be spent on these useless products. Currently our money is funding research that will one day become another biotech start-up. Are we getting our moneys worth?Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-14446370223951499162018-05-26T10:39:00.000-07:002018-05-27T15:39:56.022-07:00The Narrative These Days - Theranos<div class="separator" style="clear: both; text-align: center;">
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We all live by a narrative. Our narrative is the reality that we perceive. It is the explanation we have for why things happen. It is the world we think everyone is experiencing just like us. The only difference between us and our neighbors narrative is that ours is correct and theirs is not.<br />
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Take for example, how people behave "these days". My aging relatives often talk about how the kids today are rude. Apparently things were not so back in the day. In my narrative that is exactly what older people said about my aging relatives when they were young.<br />
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Take for example, our political turmoil "these days". In the first half of last century we experienced two world wars. There must have been turmoil. The leaders managed to get the people behind the idea of fighting an enemy. Currently we are breaking down internally. We see our fellow Americans as enemies. We are also breaking down in our relations with Iran and North Korea. Are we any worse or better than previous generations on how we live in peace? Are we marching towards war overseas or even here in our own country?<br />
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The place to be intellectually is in between or off to the side of the battles. We need to be on the outside looking in. We need to witness events as if a Martian studying planet earth. Are you a Trump fan or a lefty? What if there were a third option where you stand back and watch the two sides make their arguments? What if you took note of the arguments, not the conclusions? Where is that place where you are a journalist gathering information to tell a story.<br />
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That is the subject that I have been working on. Before we can present our narrative to the world however, we have to learn how to make the presentation. Anyone, these days, can share their narrative. YouTube, Twitter, and Facebook are a few ways of annoying people with your thoughts. Rarely does someone intrigue you enough to make you take notice. I certainly never went viral. But I still think of my narrative here on the CCS. I think about the bad science that goes into the life sciences and how it effects our lives. I think how food is our medicine yet we still cling to pills. I think of the scientific method and it's counterpart, the cargo cult scientific method. I think of how to present an argument against it.<br />
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<a href="https://en.wikipedia.org/wiki/George_P._Shultz">George Shultz</a> was a life long "fan" of science. When he heard the arguments presented by Theranos' Elizabeth Holmes he was sold. Once Shultz was on board Theranos <a href="https://www.mercurynews.com/2018/03/25/letter-george-shultz-played-key-role-in-the-rise-and-fall-of-theranos-it-wasnt-just-elizabeth-holmes/">took off</a> financially. It turns out that G. Shultz was a life long fan of the cargo that science provides. Nonetheless, a man with his power can make a cargo cult airport into a hub as well funded as LaGuardia. He was not aware of the simple tests one could do to verify Holmes' story. See <a href="http://cargocultscience.blogspot.com/search?q=theranos">here </a>for a link to the simple test, second to last paragraph.<br />
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Theranos is an interesting story. It has been told, will continue to be told and may even one day made into a Hollywood movie. The CCS version will not be the same. It is not a story about a perceived scam by one or a few people. It is about an industry based on promising the cargo. It will be about leadership who promise anything under the sun because they honestly think they can facilitate the landing of the planes. They know what the cargo should be and they will assemble their airport just right... some day. Yet they are missing something. The shape of the antenna on the coconut headphones. The arrangement of fire along the runway perhaps.<br />
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Theranos has the same problems all cargo cults have. The narrative is too simple. The explanations of how it will all work are too complex. The complicated pieces can be sussed out by low paid highly educated nerds with no power within the organization. The leadership has all of the power, but no real technology solutions. They specially in the narrative.<br />
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Before I end we must remember <a href="https://cargocultscience.blogspot.com/search?q=atossa">Atossa,</a> a small breast cancer biotech in Seattle. They did exactly what Theranos did. They promised a simple test. They did not have one. They lied. They are still in business. The leadership are from the finest schools. They make wonderful promises about the best cargo we can hope for. The planes do not land.<br />
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The narrative these days continues to pile up the loss of billions of dollars in investments. Just as the narrative did in 1985, 95, 05 and 15, the planes have not landed. We need to get to the heart of the matter. We need to talk about why we fail. How does one present the argument that our great leaders are merely Cargo Cult Scientists?<br />
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Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-22963770409779354102017-02-26T10:20:00.003-08:002017-02-26T10:20:36.301-08:00One of My HeroesGary Taubes has a new book out. I love what he does. <a href="http://www.slate.com/articles/news_and_politics/hey_wait_a_minute/1997/10/nobel_gas.html">Here</a> is an early piece he wrote on one of my old bosses.<br />
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<span class="clsDropCap" style="color: #281b21; font-family: sl-Apres, helvetica, sans-serif; font-size: 16px;">P</span><span style="background-color: white; color: #281b21; font-family: sl-Apres, helvetica, sans-serif; font-size: 16px;">rusiner's proposition has been controversial from the get-go. The researcher who did Prusiner's lab work at the University of California at San Francisco quit over the publication of Prusiner's very first prion paper in 1982, arguing that Prusiner was overinterpreting the available data to push the prion hypothesis.</span></blockquote>
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After three years in Prusiners lab I came to same conclusions as Gary and the above researcher. Prusiner and his minions were hammering a square peg through the round hole of the prion narrative. Only information supporting their narrative was offered up to the public. It was during my time at this laboratory I first read Feynmans Cargo Cult Science speech and it hit me like a ton of bricks.<br />
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Quick story: To grow cells that express proteins, we sometimes use spinner flasks. The flasks hold media with growing cells. In the flask is a magnetic rod. The flasks sit on a spinner plate that spins the rod thus stirring the growing cell culture. One day the plate stopped spinning. I took it to the repair shop and had it fixed. When I brought it back the ladies using the plate complained that their cells were no longer growing as well. I suggested they adjust the speed at which the cells were spinning. My supervisor informed me that the plate was perfect before I put my hands on it. "Take it back and get it fixed right!" When I explained that the speed is adjustable and that it is up to us to set the proper speed, she doubled down. "Take it back!" I unplugged the plate and walked on down the hall with it. Down in the basement repair shop I told the guy what I was up against. He volunteered to explain the mechanics to the boss lady. I said no. I was defeated by then. I brought it back up, set the speed to where I knew it would work. I let her think we had fixed the problem in the repair shop. She has since been promoted to laboratory manager at Dr. Prusiners <a href="http://ind.ucsf.edu/welcome-ind">Institute for Neurodegenerative Diseases. </a><br />
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Gary Taubes pointed out in his opening remarks at the Seattle Town Hall (see video below), he was obsessed at how hard it is to do science right. How do we do it right? How do we know if the science we have been given is right? Experimentation? Reproducible results? Is that how professional scientists operate? That has not been my experience.<br />
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Gary Taubes went on to the most important work of his life, correcting the bad science behind nutrition. We have been handed a load of crap from nutrition science in the western world. Our diet is the leading cause of our poor health. Our health care professionals and their prescriptions are not the solution.<br />
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People believe what they want to believe however. What sets Gary Taubes apart is that he has let his research guide him to his beliefs. You can disagree with his message but not his method. The research leads, the scientist follows.<br />
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<iframe allowfullscreen="" frameborder="0" height="315" src="https://www.youtube.com/embed/2jla1ofRIiY" width="560"></iframe>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com1tag:blogger.com,1999:blog-20579732.post-82821426564362728322017-02-12T10:33:00.003-08:002017-02-12T10:41:39.974-08:00I Bought AmgenI bought Amgen just before they won <a href="https://www.zacks.com/stock/news/210811/amgen-wins-pcsk9-lawsuit-sanofi-and-regeneron-to-appeal">their lawsuit</a> against Regeneron/Sanofi. I didn't know about the pending PCSK9 lawsuit though. I was betting on a comeback. They were down 10% from last year and they are winning the CGRP race (migraine headache medicine). That could be a big thing. So far it looks like I got lucky. I got in around 147 and today AMGN is around 167.<br />
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I had three close calls with working for Amgen. I had interviews and phone conversations. I was flown to Thousand Oaks. I interviewed in Seattle for what turned out to be an RNAi group. That was humorous because they didn't tell me that upfront. I went on a rant about how I wouldn't work with RNAi. I could see in their eyes that they were planning on using RNAi to achieve their goals. Long story short, I did not succeed at securing employment at Amgen. Had I done so there would be little chance I would still be there today. It would have been a bad investment of ones career. Amgen has more ex-employees than most biotech.<br />
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The way I see the world of work these days is in terms of <a href="https://en.wikipedia.org/wiki/Value_investing">value investment. </a> I would not want to work at Amgen nor any biotechnology company because they do not provide career value. The main reason is because they are in the biotechnology industry. I can go to my LinkedIn account and search through the ruined careers of many a smart charismatic scientist with fancy degrees, publications and patents. Where are they today? I don't know because when you lose your biotech career it is not wise to put your new job at Starbucks on your LinkedIn account. The value of those degrees, patents, publications, years building new skills, and associations with big players like Amgen, can all add up to a job at Starbucks.<br />
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Back to my stock portfolio.<br />
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My next pick was going to be General Electric. I want a solid dividend payer. In my research however I came across <a href="http://www.refinery29.com/2017/02/139921/ge-women-hiring-initiative-workplace-equality">the fact </a>that they are planning to add more women for the sake of diversity.<br />
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<span style="background-color: white; color: #333333; font-family: "georgia" , "times new roman" , serif; font-size: 17px;">Today, GE announced its goal of having 20,000 women in STEM roles at the company by 2020, resulting in an impressive 50:50 gender balance in technical entry-level positions. Right now, GE has 14,700 women in engineering, manufacturing, IT, and product management positions. </span></blockquote>
The value of a company that depends on science and engineering comes from the scientists and engineers. What makes for a good scientist or engineer? Apparently GE thinks that preference for those with vaginas will aid in their search. If they had a preference for those with penises I would also have a problem. You hire scientists and engineers based on their skill and knowledge. A college degree from a good school is one indication that a person has what it takes. MIT, CalTech... Next I would seek value in candidates based on their work history. I would look for publications. I would speak with them about their work to find out how interested they are in what they do.<br />
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When it comes to a company like GE, the engineers matter. They, unlike biotech, make things that have to work. If my refrigerator conks out it's going back. Biotech on the other hand does not make products that work. They don't have to. See my post on <a href="http://cargocultscience.blogspot.com/2016/09/sereptas-cargo-plane-has-landed.html">Serepta. </a>They only need to convince the FDA and the doctors that their statistics indicate some efficacy. I value Amgen, not for their science and technology prowess, but for how they will make investors feel.<br />
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The ruined careers of chemists, biochemists, biologists, molecular biologists are something that doesn't get media attention. The job losses that have occurred since the big recession of 2007 have not been given proper journalistic attention. Who lost their jobs/careers? Amgen, for example came to Seattle, started a huge campus, started a Masters Degree in Biotechnology at UW, embarked on a decade of research and then the left town. Expedia took over the campus. What did their ho hum hirelings go on to do? Do they have anything of value to share with the rest of us? Has their LinkedIn account stopped marking their progress?<br />
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I want to end this post with an example of finding value in things complicated versus complex. Mark Zuckerberg has done quite well with hiring strong scientists. Here is what he values in employees.<br />
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Then he gets a little full of himself and decides he can do anything. He is now going to <a href="https://www.yahoo.com/tech/mark-zuckerberg-plan-cure-diseases-gets-off-ground-030231579.html">cure all disease.</a> Very noble but disease is not like a computer website. Zuckerberg may have spotted a place where computer science can add value to our lives. He may have found ways of making a ridiculous profit from that work. But now he is venturing into the world of the cargo cults. This stuff is not easy and the scientists are not as smart as the ones he currently employs. I won't be investing in this.Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0tag:blogger.com,1999:blog-20579732.post-52888822974982662632016-12-31T06:06:00.000-08:002016-12-31T06:06:05.053-08:002016 PCRI Dr Eugene Kwon Provenge<iframe allowfullscreen="" frameborder="0" height="344" src="https://www.youtube.com/embed/2MipKsuN3tw" width="459"></iframe>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com2tag:blogger.com,1999:blog-20579732.post-50389932584738854892016-12-03T06:18:00.000-08:002016-12-03T06:18:35.220-08:00History of the Narrative<div class="separator" style="clear: both; text-align: center;">
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<span style="background-color: white; font-family: Arial, Helvetica, sans-serif;">Respect for the truth!</span><br />
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<span style="background-color: white; font-family: Arial, Helvetica, sans-serif;">The narrative, as defined by Wikipedia, is "<span style="color: #252525;">any report of connected events, </span><a class="mw-redirect" href="https://en.wikipedia.org/wiki/Nonfiction" style="background-image: none; color: #0b0080; text-decoration: none;" title="Nonfiction">real</a><span style="color: #252525;"> or </span><a href="https://en.wikipedia.org/wiki/Fiction" style="background-image: none; color: #0b0080; text-decoration: none;" title="Fiction">imaginary</a><span style="color: #252525;">, presented in a sequence of written or spoken words, and/or still or </span><a class="mw-redirect" href="https://en.wikipedia.org/wiki/Motion_picture" style="background-image: none; color: #0b0080; text-decoration: none;" title="Motion picture">moving images</a><span style="color: #252525;">." Bullshit is defined as, "</span><span style="color: #252525;">is mostly a </span><a href="https://en.wikipedia.org/wiki/Slang" style="background-image: none; color: #0b0080; text-decoration: none;" title="Slang">slang</a><span style="color: #252525;"> </span><a href="https://en.wikipedia.org/wiki/Profanity" style="background-image: none; color: #0b0080; text-decoration: none;" title="Profanity">profanity</a><span style="color: #252525;"> term meaning "</span><a href="https://en.wikipedia.org/wiki/Nonsense" style="background-image: none; color: #0b0080; text-decoration: none;" title="Nonsense">nonsense</a><span style="color: #252525;">", especially as a rebuke in response to communication or actions viewed as </span><a href="https://en.wikipedia.org/wiki/Deception" style="background-image: none; color: #0b0080; text-decoration: none;" title="Deception">deceptive</a><span style="color: #252525;">, misleading, disingenuous, unfair or false." Communicating ones scientific research is a narrative. It becomes BS when the communicators are deceptive, misleading and so on. </span></span><br />
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<span style="background-color: white; color: #252525; font-family: Arial, Helvetica, sans-serif;">OK. Serepta offered up a narrative to the FDA. The FDA told the rest of us that Sereptas narrative was not BS and approved the drug. Some disagreed. We covered that in the last post and time will let us know if the Serepta narrative is BS or not. In fact it seems that Janet Woodcocks approach was to approve the drug to find out. It's not the best way forward and here is why.</span><br />
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<span style="color: #252525; font-family: Arial, Helvetica, sans-serif;"><a href="http://www.biospace.com/News/latest-deaths-in-juno-trial-puts-unwanted/440147" style="background-color: white;">Juno!</a></span><br />
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<span style="background-color: white; color: #252525; font-family: Arial, Helvetica, sans-serif;">I've talked the fateful airplane trip that introduced Lawrence Corey of the Fred Hutchinson Cancer Research Center with David Fallace of the <a href="https://en.wikipedia.org/wiki/Alaska_Permanent_Fund">Alaska Permanent Fund. </a>These two got Juno off the ground leaving the details to be filled in by the cargo cult scientists of Seattle. The unemployed tribesmen were gathered and put back into the watch towers with their coconut and stick antenna headsets. Once again they fired up the ceremonies of another biotech pharmaceutical company. The <a href="http://www.biospace.com/News/latest-deaths-in-juno-trial-puts-unwanted/440147">end result i</a>s death and destruction. </span><br />
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<span style="background-color: white; font-family: Arial, Helvetica, sans-serif;"><span style="color: #252525;">It is a very interesting scientific development. Unlike the DNA manipulation that is <a href="http://cargocultscience.blogspot.com/2016/09/sereptas-cargo-plane-has-landed.html">the narrative of Sereptas </a></span><span style="color: #333333;">Exondys 5, something very powerful is happening with Junos JCAR015. In July of this year the clinical trial known as ROCKET was put on hold after two patients died from a cerebral </span><span style="color: #333333;">edema. The deaths were attributed to a protocol change (cargo cult alert!) that added <a href="https://en.wikipedia.org/wiki/Fludarabine">fludarabine </a>(chemotherapy) to the treatment. Juno convinced the FDA that fludarabine caused the deaths and the FDA let them continue on. The cold hard reality cut into that narrative. Since restarting the ROCKET trial 12 patients have been tested. two more patients have died of the same issue, cerebral edema. Take away the emotion of judging the FDA and Juno. What is happening? What would the mechanism of action be with CAR-T therapy directed at CD19 in patients with B Cell Acute Lymphoblastic Leukemia (B-ALL)?</span></span><br />
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<span style="background-color: white;"><span style="font-family: Arial, Helvetica, sans-serif;"><span style="color: #333333;">In a Utopian world we would set a team of scientist on the case. What is happening. In the cargo cults we tend to focus on getting the endpoints (the cargo) we want. When we don't get them we try other avenues without understanding the basic science. We pursue the narrative even when BS has presented itself. Brian Orelli of Motley Fool pointed out, "</span>Fortunately, Juno has other CAR-T cancer treatments, JCAR014 and JCAR017, in particular, which appear to be safer, and JCAR015 might still be useful in patients with other blood cancers, such as non-Hodgkin lymphoma. </span><span style="font-family: Arial, Helvetica, sans-serif;">While this issue may be specific to JCAR015 and late-stage ALL, investors in Bellicum Pharmaceuticals, Kite Pharma, and Bluebird should keep in mind that CAR-T is largely uncharted territory that could result in other unanticipated issues with their treatments."</span></span><br />
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<span style="background-color: white; font-family: Arial, Helvetica, sans-serif;">So we keep on keeping on and wait to see who else dies. The patients are in bad condition coming into the trials. This is a part of the bigger problem of treating end of life conditions as diseases we can cure. This is a narrative and it is BS. People being turned into patients for biopharma greed is what we are witnessing. If Juno, Bellicum, Kite and Bluebird can statistically demonstrate longer life (quality of life is not an issue) they can make money. So far Juno has demonstrated the opposite. </span><br />
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<br />Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com1tag:blogger.com,1999:blog-20579732.post-76802546974882840462016-11-04T05:57:00.002-07:002016-11-04T05:59:22.588-07:00All Trials TEDTalk<a href="https://youtu.be/-RXrGLolgEc">https://youtu.be/-RXrGLolgEc</a>Ginsberghttp://www.blogger.com/profile/04147844947196103191noreply@blogger.com0