Video recording of a talk given by Raphaël Lévy (University of Liverpool, UK) at the European Association for Cancer Research meeting: Nanotechnology in Cancer: Engineering for Oncology Cambridge, UK : 12 – 14 September 2019
At the 2018 American Chemical Society National Meeting in Boston, I asked a question to Chad Mirkin after his talk on Spherical Nucleic Acids. This is what I said:
In science, we need to share the bad news as well as the good news. In your introduction you mentioned four clinical trials. One of them has reported. It showed no efficacy and Purdue Pharma which was supposed to develop the drug decided not to pursue further. You also said that 1600 forms of NanoFlares were commercially available. This is not true anymore as the distributor has pulled the product because it does not work. Finally, I have a question: what is the percentage of nanoparticles that escape the endosome.
I had written my question and I asked exactly this although not in one block as he started answering before I had made all my points. He became very angry. The exchange lasted maybe 5 minutes. Towards the end he said that no one is reading my blog (who cares), that no one agrees with me, he called me a “scientific zealot” and a “scientific terrorist”. The packed room was shell shocked. We then moved swiftly to the next talk.
Two group leaders, one from North America and the other one from Europe, came to me afterwards.
Group leader 1:
Science is ever evolving and evidenced based. The evidence is gathered by first starting to ask questions. I witnessed an interaction between two scientists. One asks his questions gracefully and one responding in a manner unbecoming of a Linus Pauling Medalist. It took courage to stand in front of a packed room of scientists and peers to ask those questions that deserved an answer in a non-aggressive manner. It took even more courage to not become reactive when the respondent is aggressive and belittling. I certainly commended Raphael Levy for how he handled the aggressive response from Chad Mirkin. Even in disagreements, you can respond in a more professional manner. Not only is name calling not appropriate, revealing the outcomes of reviewers opinions from a confidential peer-review process is unprofessional and unethical.*
Lesson learned: Hold your self to a high standard and integrity.
Many conferences suffer from interesting discussions after a talk in such way that there are questions and there are answers. So far so good. Only in rare cases, a critical mind starts a discussion, or ask questions which imply some disagreement with the presented facts. Here I was surprised how a renowned expert like Chad Mirkin got in rage by such questions of Raphael Levy and how unprofessional his reaction was. It was not science any longer, it was a personal aggression, and this raises the question why Chad Mirkin acted like this? I do not think that this strategy helps to get more acceptance by the audience. I tribute to Raphael Levy afterwards, because I think science needs critical minds, and one should not be calm because of the fear to get attacked by a speaker. Science is full of statements how well everything works, and optimism is the fuel to keep research running. There is nothing wrong with this, but definitely one also need critical questions to make progress, and what we don’t need is unprofessional behavior and discreditation.
* Group leader 1 refers here to the outcome of the reviews of this article which you can read on ChemrXiv and which was (predictably) rejected by Nature Biomedical Engineering. During the incident Chad Mirkin used these reviews to attack me.
Update: some reactions on Twitter:
“Do you know Rapha’s blog? Not true that no one is reading it! It is the true gem and a rare truth island!” @zk_nano
“Wow, that’s shockingly uncool.” @sean_t_barry
“What an unprofessional guy.” @SLapointeChem
“Calling a fellow researcher a “scientific terrorist” for raising concerns and asking a question (even if you disagree with them) is shocking. Sorry to hear that there wasn’t any real discussion instead, would’ve been interesting.” @bearore
“Surprised this isn’t getting more pub. One must wonder at what point does one’s ego/reputation become more important than the science, which ABSOLUTELY must include the bad with the good.” @Ben_Jimi440
“Keep fighting the good fight tenaciously, Raphael. Like the detectives in those old film noir shows… ” @drheaddamage
Slide 2: Nanotech is bs Tweet.
Slide 3: Calling Bullshit.
Slide 4: Dinosaur. (from here)
Slide 5: Electron microscopy of Hela cells after the ingestion of colloidal gold; C.G. Harford, A. Hamlin, and E. Parker; 1957
Slide 6: The entry and distribution of herpes virus and colloidal gold in Hela cells after contact in suspension; M. A. Epstein, K. Hummeler, and A. Berkaloff; 1963
- Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation; L. Rosi, D. A. Giljohann, C.S. Thaxton, A.K.R. Lytton-Jean, M.S. Han, C.A. Mirkin; 2006
- Nano-Flares: Probes for Transfection and mRNA Detection in Living Cells;S. Seferos, D.A. Giljohann, H.D. Hill, A.E. Prigodich, and C.A. Mirkin
- Interview of Chad Mirkin: Nanoparticles and the future of medicine; 2013
- Nortwestern press release: New tool for investigating RNA gone awry; 2015
Slide 8: The spherical nucleic acid paradox; D. Mason, G. Carolan, M. Held, J. Comenge, S. Cowman, and R. Lévy; 2015
Slide 9: Excerpt from email (shared with permission).
Slide 10: Evaluation of SmartFlare probe applicability for verification of RNAs in early equine conceptuses, equine dermal fibroblast cells and trophoblastic vesicles; S. Budik, W. Tschulenk, S. Kummer, I. Walter, and C. Aurich; 2017
Slide 11: SmartFlares fail to reflect their target transcripts levels; M. Czarnek and J. Bereta; 2017
Slide 12: Calcium-Binding Proteins S100A8 and S100A9: Investigation of Their Immune Regulatory Effect in Myeloid Cells; J. Yang, J. Anholts, U. Kolbe, J.A. Stegehuis-Kamp, F.H.J. Claas and M. Eikmans
Slide 13: SmartFlare catalog.
- Abnormal scar identification with spherical nucleic-acid technology; D.C. Yeo, C. Wiraja, A.S. Paller, C.A. Mirkin and Chenjie Xu; 2018
- Re-Evaluating the Spherical-Nucleic-Acid Technology; M. Czarnek, D. Mason, G. Haimovich V.F. Puntes, P. Bergese, J. Bereta and R. Lévy; 2018
This is a guest post by Marie Held reporting from the ELRIG conference held last week.
On 3rd-4th October I attended ELRIG’s flagship event, Drug Discovery 2017, in Liverpool. With around 250 participants, it was the largest of the ELRIG conferences yet. The spacious arrangement of the vendors and posters in the exhibition hall was a refreshing change. There was ample space to mingle, chat and discuss equipment on show.
On day one, I attended the Advances in Imaging stream (one of three parallel streams). The keynote lecture by Tony Ng covered a broad range of the spatial scale, stressing the importance of whole body imaging in cancer in combination with investigating the tumour microenvironment down to super resolution imaging of individual molecules. He outlined their attempts in predicting tumour metastasis enabled via immune system hijacking by the cancer cells. An important conclusion was that with the wealth of imaging methods and tracers being developed, we need standardisation and validation across facilities to bring them closer to the clinic, ultimately improving the lives of patients. The imaging methods discussed in the following six talks ranged from man to molecule, focussing on ever smaller features as the day went on. A transpiring theme was the generation of large amounts of data from different techniques and the associated challenge of deriving meaningful information. Machine learning and artificial intelligence were mentioned time and again as being part of that quest. The last scientific presentation, by Charlotte Dodson, focussed on twinkling enzymes, studying the conformational changes of kinases in disease and after treatment via single molecule spectroscopy. Throughout the imaging stream, twelve men contributed to the presentations, vendor snapshots and poster tasters and three women contributed to the stream. The other streams were a bit more gender balanced but only the workshop on Tuesday achieved a 50/50 split.
On the second day, I attended the Lab of the Future workshop presented by SiLA and ELRIG. The general consensus was that the lab of the future (whether you call it Lab 4.0, Industry 4.0 or something else) is an interconnected space in which smart machines are communicating with each other, running fully automated cycles of fabrication, screening and/or testing. Machinery that can be monitored if not controlled remotely via mobile device apps was mentioned multiple times. Smart products are uniquely identifiable, may be located at any time and “know” their own history, current status and alternative routes to achieving their target state. It left some of the audience wondering where innovation is going to come from. A lot of innovation is not based on a “Eureka” moment but rather lucky accidents or not quite sticking to the protocol and making mistakes. These instances are near on excluded in an automated lab. Another doubt that was raised was: Where is the space, if not need, for the scientist is in this fully automated lab? “He” has more time to think about the science and efficiency gains rather than processing the work. Unfortunately, the scientist was exclusively referred to as a “he” throughout the whole workshop, which irritated myself and another female member of the audience to the extent that it seemed appropriate to clarify that the scientist can be a female scientist. Unconscious discrimination is one of the reasons why there are still so few leading women in science. There was a conspicuous lack of women, both in the audience and in particular in the selection of session leaders, which were all male. It would be nice to see some female panel members in the future. Also, this year only one out of 12 session chairs throughout the whole conference were female.
Near on every panel member in the lab of the future workshop voiced that the interconnectivity should be down scalable to medium and small labs. As a member of the academic research community and a small lab, I felt somewhat left out though. We do not generally use automated machinery, never mind machinery connected to the internet of things. Often enough there is a piece of equipment, that has to be taken off the net entirely because the software is so outdated (and not supplier maintained anymore) that it has to run on an obsolete operating system posing a risk to the University network. That means we are in fact taking a step away from the lab of the future. The audience saw the responsibility with the industrial sector to come up with a solution and I am looking forward to seeing a change in the future. Also, electronic notebooks (find the same presentation here with audio comment) are already a standard in the industrial sector but the academic sector is severely lagging behind. Not all universities have specific guidelines on how to keep a paper lab book, never mind having a system of electronic lab books in place. The responsibility here lies in the academic sector to catch up but it might have to be a bottom up approach to induce a change.
The high point of the second day and probably the conference as a whole was the plenary keynote by Dr Nessa Carey asking whether we can fix big pharma. Her keynote was eloquent, inspiring and also entertaining. We can all do our bit to help fix big pharma. It is not the evil it is often made out to be. Millions of lives have been saved by pharmacological advances and still are being saved, however it does suffer from the worst PR there is.
Overall, I enjoyed the ELRIG Drug Discovery 2017 and am looking forward to the next instalments in London in 2018 and back in Liverpool in 2019.
This is a guest post by Sumaira Ashraf.
Last month, I got the opportunity to attend and present my work at the 254th ACS conference held in Washington DC. The session was organized by Raphaël Lévy, Niveen Khashab, and Zhihong Nie. I presented preliminary data regarding my work on multimodal imaging probes for stem cell tracking. I enjoyed the conference but was disappointed by some of the talks. Many speakers exaggerate their results to impress their audience and hype the worth of their work. I did wonder if it is productive to point out mistakes as no one seems interested in correcting them, but, instead, they might become your lifelong rivals. Here is an example. I know from practical experience that liposomes loaded with small molecule dyes cannot be used as long-term imaging modality because within 24 hrs of loading ~99% signal intensity is lost due to leakage from the liposomal cavity. But speakers presented quantitative imaging data based on these approaches. I wanted to point this problem out but I did not want to get involved in never ending discussion where no one will be ready to admit their errors. Eventually, I did not say anything.
Of course, my own work with polylelectrolyte capsules has some limitations as well: while they are good candidates for protecting imaging probes from intracellular degradation and intracellular species from potentially toxic probes, the limit of detection depends on the amount of contrast agent delivered which still remain low. In my current experiments, I need to overcome this limitation by modifying or choosing an alternate approach.
— (((Raphael Levy))) (@raphavisses) August 22, 2017
The Kavli lectures were really very informative… but I could not attend the full talk of the 2nd speaker because the air conditioning was set at a temperature so low that I could not tolerate it: I was forced to leave this interesting lecture. The industry exhibition downstairs the convention centre was massive and fun. I particularly liked the Bruker stall which had good explanation of NMR, mass spectrometers, etc., (covering theoretical and experimental data evaluation). There were other advantages to the visit of the exhibition: chocolates, bags, T- shirts, ice cream (prepared in liquid nitrogen within 3 minutes), lunch, free L’Oréal products, and lucky draw (especially when you win; I won a Swag Bag of merchandise from the ACS Store worth USD$75.00). I was lucky to see the solar eclipse through the cover glasses provided by the conference.
— Wilmad-LabGlass (@WilmadLabGlass) August 23, 2017
I missed the opportunity to visit the reflecting pool near Lincoln memorial and some interesting museums due to time limitation. I am looking forward to some forthcoming opportunity to see them.
I came back with some thoughts to work with new nanocomposites (recent work presented in one of the talk by Amit Joshi; based on doping materials rather than combining them inside big capsules or attaching via linkers) for multimodal imaging which might have potential to overcome the flaws associated with above mentioned materials. But I need to try… without trying one cannot be sure of anything.
Congratulations to the organisers of the World Biomaterials Congress for having a high profile debate on the following proposition:
Nanotechnology is more hype than hope
I wish I could have attended as it is a topic I have given some thought… Thankfully, one of the attendees, Professor Laura Poole-Warren has done some live tweeting from the floor. So here is a storify.
Update (19/08/2015): Dave Mason has posted a detailed critique of this paper at PubPeer
Update (19/10/2015): We have submitted a response to this paper as a Letter to the Editor of PNAS. It is currently available as a preprint.
Update (16/11/2015): Inder Verma, Editor of PNAS, has decided that our letter “does not contribute significantly to the discussion of the StickyFlare paper.”
A quick post before I take off to Boston tomorrow for the American Chemical Society national meeting. I informed Chad Mirkin of my Monday talk where I will discuss the SmartFlares (talk on Monday, abstract). In his reply, he pointed me to a contributed PNAS paper they published in July on StickyFlares (Links: article, Northwestern press release). The questions that this technology raises are the same as the ones raised by the SmartFlares, as discussed in a previous post. Eight years after the initial NanoFlare paper, they are still not answered in this new article.