• GhostfaceKrilla

An Open Letter To a SAVA Western Blot Critic

Hello,

Let me start with an introduction and a little background on what I see as a VERY concerning ethical situation. First to introduce myself - I am a scientist (PhD in Chemistry) currently working in the biotech industry and have been investing in Cassava Sciences (SAVA) for several years. Over the past few months, I have been introduced to the work of Dr. Cat (name changed to discourage any Twitter/online trolls from harassing her) due to her criticism of the work of Dr. Burns and Dr. Wang, scientists who discovered a very exciting and promising drug candidate for the treatment of Alzheimer's Disease called Simufilam. Approximately 3 months ago, a Citizen's Petition was filed seeking to halt the on-going Phase 3 trial of Simufilam based upon allegations of image manipulation and outright fraud - resulting in the stock price of SAVA crashing from 120 to 40 and individual SAVA investors, (many who like myself are scientists or doctors that have been personally affected by this terrible disease), losing 6-7 figures in the matter of a few days. This Citizen's Petition was funded by a group of short-sellers who reportedly made more than 50 million dollars that week, closed out their short positions, and walked away with that money in their pockets.

Having ran 100-200+ gels in graduate school, but admittedly not being an expert in Westerns Blots, at first I believed that the Citizen's Petition claims of image manipulation were, in fact, mostly true. This did not lead to me selling my shares, as I strongly believed (and still do) that any issues with gel images from Dr. Wang's lab are immaterial to the efficacy of Simufilam - which is IMO the most promising treatment for Alzheimer's Disease in clinical trials OR pre-clinical development without a doubt.

Recently, however, I read an article by an actual expert in Western Blots (a PI whose lab runs multiple hundreds of these gels per year) who believes many of the issues raised by the Citizen's Petition and Dr. Cat can be explained by artifacts caused by loading, exposure settings, and other technical factors: https://ad-science.org/2021/10/21/of-shorts-and-blots/ I believe the assumption of Dr. Wang's guilt is common to scientists not intimately familiar with Western Blots, especially when biased by self-proclaimed image manipulation experts whole-heartedly corroborating the short sellers accusations.

Since the filing of the Citizen's Petition, Dr. Cat and a cadre of anonymous PubPeer contributors, (who all seemingly go by phylogenic pseudonyms, making me question if they are not all actually alt accounts ran by Dr. Cat), have raised concerns on over 20 of Dr. Wang's papers. Dr. Cat has continued to raise concerns on Twitter and typically includes the stock symbol $SAVA so that everyone that follows the company is notified of her criticisms. Some of the concerns on PubPeer and Twitter seem legitimate, but lately I have noticed they have begun to seem frivolous and far-fetched. Regardless. this has successfully galvanized the academic community and her numerous Twitter followers against SAVA and figuratively dragged the names of Dr. Wang and Dr. Burns through a dirt pile the size of small country. I was, frankly, shocked at Dr. Cat's refusal to accept the companies' completely reasonable explanation of an honest mistake in making an Excel graph and the removal of a single, clearly statistically identifiable outlier from the 100 mg pTau data, (the biomarker most closely correlated with cognitive decline). See an analysis of the data here which found no evidence of misconduct: (https://ad-science.org/2021/09/08/savadx-poster-and-plasma-ptau-181-data/. Also note that the 50 mg cohort has NO outliers removed and still achieves statistical (p < 0.05) significance. How could the 50 mg dose have an impact and not the 100 mg dose? Logically and mathematically the removal of the single outlier in the 100 mg cohort is completely justified!

I have also been disappointed by what I see as Dr. Cat's attention seeking behavior and playing of the victim card whenever possible. As someone solely funded by Patreon donations and guest lecturer spots afforded to her by the quasi-fame she has garnered through her blogging and Twittering, I see great financial and professional incentive for her to both find fraud (whether any exists or not) and also seek sympathy from her audience (whether deserving or not). Although I strongly condemn the instances of online harassment I have witnessed, it seems to me that if one openly and constantly criticizes / accuses a public company of fraud on Twitter, (which directly results in additional losses for loyal SAVA investors), one would expect at least a handful of internet trolls would post memes of you or call you bad names - which from what I've seen is the extent of the constant harassment that Dr. Cat claims.

Recently SAVA announced the Journal of Neuroscience had reviewed the images in question from a 2012 paper of Dr. Wang and found NO evidence of image manipulation - much to the chagrin of Dr. Cat who immediately posted on PubPeer requesting access to the raw images so she could critique them further. At this point I would like to point out that Dr. Cat is neither an employee of the NIH, the FDA, or an academic journal - and to my knowledge has never held an editorial position at a journal or even a supervisory role in academia or industry. I question her claimed expertise derived from purposefully examining images for fraud, which has turned from a hobby to her sole means of financial support. I'm sorry but you do not become a great guitarist by sitting on internet forums writing diatribes on how Slash just really isn't *that* groundbreaking of a soloist. Similarly if a research associate that worked for me quit because they did not like the job or failed to get a promotion, I don't believe that qualifies them as an expert - in fact the opposite.

What SAVA absolutely does have is a duty to look out for the interests of their shareholders and the patients they are trying to treat - and there is a group of short sellers with literally billions of dollars trying to stop them from advancing Simufilam through clinical trials to help patients and test the basic scientific hypothesis that this drug works. They have zero obligation to provide raw data to private citizens and, in fact, have a responsibility to not endanger the interests of their shareholders and investors by disseminating confidential information unnecessarily. I strongly believe the official investigations being performed by CUNY, the FDA, the NIH, and the professional journals in question are where the evidence should be viewed and judged by true experts - not in Dr. Cat's social media court where she is the self-appointed judge and jury, all artifacts or honest mistakes are evidence of fraud, and CLEARLY the law of the land is guilty until proven innocent.

Which brings me to why I felt compelled to write this post. Recently, Dr. Cat posted the following to Twitter:




I realize Dr. Cat has suffered both personal and legal repercussions due to her crusade against academic misconduct, fraud, and dishonesty. I would also like to re-state that I am STRONGLY against the examples of abhorrent and abusive behavior that I have seen directed at her. However - I do not believe she received "hundreds of unkind messages" in a day. I believe 5-10, perhaps even dozens, but I DO NOT BELIEVE SHE HAS RECEIVED "HUNDREDS" IN A SINGLE DAY. This may seem like a minor, inconsequential point - but as a self-proclaimed crusader for accuracy, honesty, transparency, and sharing of knowledge and raw information - this seems like a BLATANT DISPLAY OF HYPOCRISY. I realize she has had a rough week, perhaps realizing that she made a serious error in judgement in constantly accusing Dr. Wang and Dr. Burns (who according to personal references I've talked to, is an honest human being and true scientist) of fraud for the last three months - but I cannot stand hypocrisy on this level.

My point is this - as someone who believes any image manipulation or dishonesty completely invalidates the connected research - how can Dr. Cat straight-up LIE about the nature and extent of criticism she receives in order to benefit FINANCIALLY. IMO by mentioning her Patreon account this is an obvious attempt at playing the victim card and profiting from it. I care about scientific integrity but I also believe that constantly accusing INNOCENT scientists trying to cure devastating diseases and advance our knowledge of fraud is both morally / ethically wrong and diametrically opposed to the collaborative / cooperative spirit of science which is integral to the discovery of real breakthroughs.

Just as PubPeer is a site where anonymous individuals request additional information to quell concerns of academic dishonesty - I request that Dr. Cat provides evidence of her claim that she received "hundreds of unkind messages" in a single day. Unlike PubPeer, however, where there is no incentive for people to respond to these requests, I pledge to donate $500 per month to Dr. Cat's Patreon account for the next 6 months if she provides compelling evidence of this level of harassment.

If you donate to Dr. Cat's Patreon account, I ask you to strongly consider whether financially supporting someone who accuses scientists of dishonesty for a living, and then twists the truth / outright lies for financial gain is benefitting the scientific community, or hindering it.

Sincerely,

GFK, Scientist and SAVAge

PS - I also question the practice of manipulating low-res, compressed images in order to demonstrate that they were manipulated to begin with. There are obvious logical issues with this approach and I think this leads to many false accusations of misconduct against innocent scientists - which is not worth the occasional paper-mill / serial manipulator that gets caught. The tainted papers are usually very low impact and I have heard that a primary cause of this is the Chinese Government mandate that requires doctors publish a paper if they want to be hired as staff physicians. One of the first things I learned in graduate school is to never trust papers from low impact journals with surprising claims - that is one of the first chambers on the journey to a PhD IMHO.

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