Is targeting your target?

Warren Chan’s group published in June a perspective in Nature Reviews Materials entitled “Analysis of nanoparticle delivery to tumours” (Wilhelm et al). A key finding of their analysis of the literature is the absence of increase in the (very small) amount of nanoparticles delivered to tumours in the past 10 years. In a welcome departure from the usually overly diplomatic and confused style that is the trademark of most scientific writing, Wilhelm et al write the following:

 “These advantages [of nanoparticles] have been dampened by the lack of translation to patient care, despite the large investment (more than $1 billion in North America in the past 10 years) and success in imaging and treating tumours in mouse models. As a result, nanomedicine has acquired a reputation of being “hype” that cannot deliver and has not transformed patient care as it promised 15 years ago”

[…]

“We must admit that our current approach is broken, and that is why we have not observed significant clinical translation of cancer nanomedicines. Many academic studies focused on the potential of nanoparticles for in vivo applications and showed that nanoparticles may be delivered to tumours by the EPR effect. However, publishing ‘proof of concept’ studies will only lead to curing mice and will unlikely translate to cancer care, irrespective of the number of nanoparticle design permutations used for cancer targeting studies.”

Recognising the magnitude of the challenge, Wilhelm et al propose a thirty year strategy for nanomedicine.

Not surprisingly the publication sparked a debate; see for example Derek Lowe’s blog “Nanoparticles Mix It Up With Reality” and the comments therein, and the article by Michael Torrice for Chemical and Engineering News “Does nanomedicine have a delivery problem?” which features a number of quotes by various nanomedicine players, some of whom contesting Wilhelm et al’s findings, or their relevance to the development of nanomedicine. The debate has also continued in the scientific literature with a comment by McNeil “Evaluation of nanomedicines: stick to the basics” and a response by Chan.

Another comment by Lammers et al has been published 10 days ago “Cancer Nanomedicine: Is targeting our target?”. The implicit answer of the authors is no, targeting is not our target and therefore the absence of progress noted by Wilhelm et al matters little. Lammers et al’s argument is first that the percentage of the injected dose reaching the tumour is not a good indicator of the potential of a therapy, and second, that nanomedicine has in fact had some successes even without targeting. To illustrate this latter point, their first example is Doxil, a liposomal formulation of the anti-cancer drug Doxurubicin.

It is rather unconvincing that Lammers et al would use Doxil as an indication of the success of nanomedicine given that it was developed in the 80s and 90s, i.e. one or two decades before the “nanomedicine” word had been coined and Clinton had announced the $500M National Nanotechnology Initiative (January 2000). A bibliography search for the word “nanomedicine” suggests that it started to be used in the year 2000, with this MIT Technology Review being one of the very first examples:

Nanomedicine Nears the Clinic

Minuscule “smart bombs” that find cancer cells, kill them with the help of lasers and report the kills. Sound crazy? Guess again. That treatment scenario may be less than a decade away.

by David Voss
January 1, 2000

Since this infamous MIT technology review, we have seen so many similar promises and so little translation that Chan’s review and the debate that it provoked are indeed an incredibly positive and much needed development.

There is another amusing thing about Lammers et al’s review. The title suggesting that targeting is not our target is further echoed in the conclusion as follows:

“Patients do not benefit from targeting as such, and a reported tumour accumulation of 0.7%ID does not mean that nanomedicines do not work. We have to think beyond targeting, and beyond numbers, and focus on carrier-dependent drugs, combination therapies, protocols for patient selection and ways to enable rapid and more efficient clinical translation.”

Yet targeting as such seems very much to have been the target of these authors as the (non-exhaustive) list of articles below illustrate.

  1. Blume, G.; Cevc, G.; Crommelin, M.; Bakkerwoudenberg, I.; Kluft, C.;Storm, G.,Specific targeting with poly(ethylene glycol)-modified liposomes – coupling of homing devices to the ends of the polymeric chains combines effective target binding with long circulation times. Biochimica Et Biophysica Acta 1993, 1149 (1), 180-184.
  2. Vingerhoeds, M. H.; Steerenberg, P. A.; Hendriks, J.; Dekker, L. C.; vanHoesel, Q.;Crommelin, D. J. A.; Storm, G., Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo. British Journal of Cancer 1996, 74 (7), 1023-1029.
    3. Storm, G.; Crommelin, D. J. A., Colloidal systems for tumor targeting. Hybridoma 1997, 16 (1), 119-125.
    4. Mastrobattista, E.; Koning, G. A.; Storm, G., Immunoliposomes for the targeted delivery of antitumor drugs. Advanced Drug Delivery Reviews 1999, 40 (1-2), 103-127.
    5. Mastrobattista, E.; Kapel, R. H. G.; Eggenhuisen, M. H.; Roholl, P. J. M.; Crommelin, D. J. A.; Hennink, W. E.; Storm, G., Lipid-coated polyplexes for targeted gene delivery to ovarian carcinoma cells. Cancer Gene Therapy 2001, 8 (6), 405-413.
    6. Mastrobattista, E.; Crommelin, D. J. A.; Wilschut, J.; Storm, G., Targeted liposomes for delivery of protein-based drugs into the cytoplasm of tumor cells. Journal of Liposome Research 2002, 12 (1-2), 57-65.
    7. Metselaar, J. M.; Bruin, P.; de Boer, L. W. T.; de Vringer, T.; Snel, C.; Oussoren, C.; Wauben, M. H. M.; Crommelin, D. J. A.; Storm, G.; Hennink, W. E., A novel family of L-amino acid-based biodegradable polymer-lipid conjugates for the development of long-circulating liposomes with effective drug-targeting capacity. Bioconjugate Chemistry 2003, 14 (6), 1156-1164.
    8. Metselaar, J. M.; Wauben, M. H. M.; Wagenaar-Hilbers, J. P. A.; Boerman, O. C.; Storm, G., Complete remission of experimental arthritis by joint targeting of glucocorticoids with long-circulating liposomes. Arthritis and Rheumatism 2003, 48 (7), 2059-2066.
    9. Schiffelers, R. M.; Koning, G. A.; ten Hagen, T. L. M.; Fens, M.; Schraa, A. J.; Janssen, A.; Kok, R. J.; Molema, G.; Storm, G., Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin. Journal of Controlled Release 2003, 91 (1-2), 115-122.
    10. Schmidt, J.; Metselaar, J. M.; Wauben, M. H. M.; Toyka, K. V.; Storm, G.; Gold, R., Drug targeting by long-circulating liposomal glucocorticosteroids increases therapeutic efficacy in a model of multiple sclerosis. Brain 2003, 126, 1895-1904.
    11. van Steenis, J. H.; van Maarseveen, E. M.; Verbaan, F. J.; Verrijk, R.; Crommelin, D. J. A.; Storm, G.; Hennink, W. E., Preparation and characterization of folate-targeted pEG-coated pDMAEMA-based polyplexes. Journal of Controlled Release 2003, 87 (1-3), 167-176.
    12. Mulder, W. J. M.; Strijkers, G. J.; Griffioen, A. W.; van Bloois, L.; Molema, G.; Storm, G.; Koning, G. A.; Nicolay, K., A liposomal system for contrast-enhanced magnetic resonance imaging of molecular targets. Bioconjugate Chemistry 2004, 15 (4), 799-806.
    13. Schiffelers, R. M.; Ansari, A.; Xu, J.; Zhou, Q.; Tang, Q. Q.; Storm, G.; Molema, G.; Lu, P. Y.; Scaria, P. V.; Woodle, M. C., Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Research 2004, 32 (19).
    14. Verbaan, F. J.; Oussoren, C.; Snel, C. J.; Crommelin, D. J. A.; Hennink, W. E.Storm, G., Steric stabilization of poly(2-(dimethylamino)ethyt methacrytate)-based polyplexes mediates prolonged circulation and tumor targeting in mice. Journal of Gene Medicine 2004, 6 (1), 64-75.
    15. Visser, C. C.; Stevanovic, S.; Voorwinden, L. H.; van Bloois, L.; Gaillard, P. J.; Danhof, M.; Crommelin, D. J. A.; de Boer, A. G., Targeting liposomes with protein drugs to the blood-brain barrier in vitro. European Journal of Pharmaceutical Sciences 2005, 25 (2-3), 299-305.
    16. Zhang, C. F.; Jugold, M.; Woenne, E. C.; Lammers, T.; Morgenstern, B.; Mueller, M. M.; Zentgraf, H.; Bock, M.; Eisenhut, M.; Semmler, W.; Kiessling, F., Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner. Cancer Research 2007, 67 (4), 1555-1562.
    17. Dolman, M. E. M.; Fretz, M. M.; Segers, G. W.; Lacombe, M.; Prakash, J.; Storm, G.; Hennink, W. E.; Kok, R. J., Renal targeting of kinase inhibitors. International Journal of Pharmaceutics 2008, 364 (2), 249-257.
    18. Lammers, T.; Hennink, W. E.; Storm, G., Tumour-targeted nanomedicines: principles and practice. British Journal of Cancer 2008, 99 (3), 392-397.
    19. Lammers, T.; Subr, V.; Peschke, P.; Kuhnlein, P.; Hennink, W. E.; Ulbrich, K.; Kiessling, F.; Heilmann, M.; Debus, J.; Huber, P. E.; Storm, G., Image-guided and passively tumour-targeted polymeric nanomedicines for radiochemotherapy. British Journal of Cancer 2008, 99 (6), 900-910.
    20. Rijcken, C. J. F.; Schiffelers, R. M.; van Nostrum, C. F.; Hennink, W. E., Long circulating biodegradable polymeric micelles: Towards targeted drug delivery. Journal of Controlled Release 2008, 132 (3), E33-E35.
    21. Crommelin, D. J. A., Nanotechnological approaches for targeted drug delivery: hype or hope? New Biotechnology 2009, 25, S34-S34.
    22. Mulder, W. J. M.; Castermans, K.; van Beijnum, J. R.; Egbrink, M.; Chin, P. T. K.; Fayad, Z. A.; Lowik, C.; Kaijzel, E. L.; Que, I.; Storm, G.; Strijkers, G. J.; Griffioen, A. W.; Nicolay, K., Molecular imaging of tumor angiogenesis using alpha v beta 3-integrin targeted multimodal quantum dots. Angiogenesis 2009, 12 (1), 17-24.
    23. Talelli, M.; Rijcken, C. J. F.; Lammers, T.; Seevinck, P. R.; Storm, G.; van Nostrum, C. F.; Hennink, W. E., Superparamagnetic Iron Oxide Nanoparticles Encapsulated in Biodegradable Thermosensitive Polymeric Micelles: Toward a Targeted Nanomedicine Suitable for Image-Guided Drug Delivery. Langmuir 2009, 25 (4), 2060-2067.
    24. Dolman, M. E. M.; Harmsen, S.; Storm, G.; Hennink, W. E.; Kok, R. J., Drug targeting to the kidney: Advances in the active targeting of therapeutics to proximal tubular cells. Advanced Drug Delivery Reviews 2010, 62 (14), 1344-1357.
    25. Lammers, T.; Subr, V.; Ulbrich, K.; Hennink, W. E.; Storm, G.; Kiessling, F., Polymeric nanomedicines for image-guided drug delivery and tumor-targeted combination therapy. Nano Today 2010, 5 (3), 197-212.
    26. Lammers, T.; Subr, V.; Ulbrich, K.; Peschke, P.; Huber, P. E.; Hennink, W. E.; Storm, G.; Kiessling, F., Long-Circulating and Passively Tumor-Targeted Polymer-Drug Conjugates Improve the Efficacy and Reduce the Toxicity of Radiochemotherapy. Advanced Engineering Materials 2010, 12 (9), B413-B421.
    27. Oerlemans, C.; Bult, W.; Bos, M.; Storm, G.; Nijsen, J. F. W.; Hennink, W. E., Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release. Pharmaceutical Research 2010, 27 (12), 2569-2589.
    28. Talelli, M.; Iman, M.; Rijcken, C. J. F.; van Nostrum, C. F.; Hennink, W. E., Targeted core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin. Journal of Controlled Release 2010, 148 (1), E121-E122.
    29. van Rooy, I.; Cakir-Tascioglu, S.; Couraud, P. O.; Romero, I. A.; Weksler, B.; Storm, G.; Hennink, W. E.; Schiffelers, R. M.; Mastrobattista, E., Identification of Peptide Ligands for Targeting to the Blood-Brain Barrier. Pharmaceutical Research 2010, 27 (4), 673-682.
    30. Talelli, M.; Hennink, W. E., Thermosensitive polymeric micelles for targeted drug delivery. Nanomedicine 2011, 6 (7), 1245-1255.
    31. Talelli, M.; Rijcken, C. J. F.; Oliveira, S.; van der Meel, R.; Henegouwen, P.; Lammers, T.; van Nostrum, C. F.; Storm, G.; Hennink, W. E., Nanobody – Shell functionalized thermosensitive core-crosslinked polymeric micelles for active drug targeting. Journal of Controlled Release 2011, 151 (2), 183-192.
    32. van Rooy, I.; Mastrobattista, E.; Storm, G.; Hennink, W. E.; Schiffelers, R. M., Comparison of five different targeting ligands to enhance accumulation of liposomes into the brain. Journal of Controlled Release 2011, 150 (1), 30-36.
    33. Crielaard, B. J.; Lammers, T.; Schiffelers, R. M.; Storm, G., Drug targeting systems for inflammatory disease: One for all, all for one. Journal of Controlled Release 2012, 161 (2), 225-234.
    34. Crielaard, B. J.; Rijcken, C. J. F.; Quan, L. D.; van der Wal, S.; Altintas, I.; van der Pot, M.; Kruijtzer, J. A. W.; Liskamp, R. M. J.; Schiffelers, R. M.; van Nostrum, C. F.; Hennink, W. E.; Wang, D.; Lammers, T.; Storm, G., Glucocorticoid-Loaded Core-Cross-Linked Polymeric Micelles with Tailorable Release Kinetics for Targeted Therapy of Rheumatoid Arthritis. Angewandte Chemie-International Edition 2012, 51 (29), 7254-7258.
    35. Dolman, M. E. M.; Harmsen, S.; Pieters, E. H. E.; Sparidans, R. W.; Lacombe, M.; Szokol, B.; Orfi, L.; Keri, G.; Storm, G.; Hennink, W. E.; Kok, R. J., Targeting of a platinum-bound sunitinib analog to renal proximal tubular cells. International Journal of Nanomedicine 2012, 7, 417-433.
    36. Joshi, M. D.; Unger, W. J.; Storm, G.; van Kooyk, Y.; Mastrobattista, E., Targeting tumor antigens to dendritic cells using particulate carriers. Journal of Controlled Release 2012, 161 (1), 25-37.
    37. Kunjachan, S.; Jayapaul, J.; Mertens, M. E.; Storm, G.; Kiessling, F.; Lammers, T., Theranostic Systems and Strategies for Monitoring Nanomedicine-Mediated Drug Targeting. Current Pharmaceutical Biotechnology 2012, 13 (4), 609-622.
    38. Lammers, T.; Kiessling, F.; Hennink, W. E.; Storm, G., Drug targeting to tumors: Principles, pitfalls and (pre-) clinical progress. Journal of Controlled Release 2012, 161 (2), 175-187.
    39. van der Meel, R.; Oliveira, S.; Altintas, I.; Haselberg, R.; van der Veeken, J.; Roovers, R. C.; Henegouwen, P.; Storm, G.; Hennink, W. E.; Schiffelers, R. M.; Kok, R. J., Tumor-targeted Nanobullets: Anti-EGFR nanobody-liposomes loaded with anti-IGF-1R kinase inhibitor for cancer treatment. Journal of Controlled Release 2012, 159 (2), 281-289.
    40. Talelli, M.; Oliveira, S.; Rijcken, C. J. F.; Pieters, E. H. E.; Etrych, T.; Ulbrich, K.; van Nostrum, R. C. F.; Storm, G.; Hennink, W. E.Lammers, T., Intrinsically active nanobody-modified polymeric micelles for tumor-targeted combination therapy. Biomaterials 2013, 34 (4), 1255-1260.
    41. van der Meel, R.; Vehmeijer, L. J. C.; Kok, R. J.; Storm, G.; van Gaal, E. V. B., Ligand-targeted particulate nanomedicines undergoing clinical evaluation: Current status. Advanced Drug Delivery Reviews 2013, 65 (10), 1284-1298.
    42. Heukers, R.; Altintas, I.; Raghoenath, S.; De Zan, E.; Pepermans, R.; Roovers, R. C.; Haselberg, R.; Hennink, W. E.; Schiffelers, R. M.; Kok, R. J.; Henegouwen, P., Targeting hepatocyte growth factor receptor (Met) positive tumor cells using internalizing nanobody-decorated albumin nanoparticles. Biomaterials 2014, 35 (1), 601-610.
    43. Kunjachan, S.; Pola, R.; Gremse, F.; Theek, B.; Ehling, J.; Moeckel, D.; Hermanns-Sachweh, B.; Pechar, M.; Ulbrich, K.; Hennink, W. E.; Storm, G.; Lederle, W.; Kiessling, F.; Lammers, T., Passive versus Active Tumor Targeting Using RGD- and NGR-Modified Polymeric Nanomedicines. Nano Letters 2014, 14 (2), 972-981.
    44. Novo, L.; Mastrobattista, E.; van Nostrum, C. F.; Hennink, W. E., Targeted Decationized Polyplexes for Cell Specific Gene Delivery. Bioconjugate Chemistry 2014, 25 (4), 802-812.
    45. Theek, B.; Gremse, F.; Kunjachan, S.; Fokong, S.; Pola, R.; Pechar, M.; Deckers, R.; Storm, G.; Ehling, J.; Kiessling, F.; Lammers, T., Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging. Journal of Controlled Release 2014, 182, 83-89.
    46. Liu, J.; Jiang, X. L.; Hennink, W. E.; Zhuo, R. X., A modular approach toward multifunctional supramolecular nanopolyplexes for targeting gene delivery. Journal of Controlled Release 2015, 213, E123-E124.
    47. Novo, L.; Takeda, K. M.; Petteta, T.; Dakwar, G. R.; van den Dikkenberg, J. B.; Remaut, K.; Braeckmans, K.; van Nostrum, C. F.; Mastrobattista, E.; Hennink, W. E., Targeted Decationized Polyplexes for siRNA Delivery. Molecular Pharmaceutics 2015, 12 (1), 150-161.
    48. Shi, Y.; Lammers, T.; van Nostrum, C.; Hennink, W. E., Long circulating and stable polymeric micelles for targeted delivery of paclitaxel. Journal of Controlled Release 2015, 213, E127-E128.
    49. Shi, Y.; van der Meel, R.; Theek, B.; Blenke, E. O.; Pieters, E. H. E.; Fens, M.; Ehling, J.; Schiffelers, R. M.; Storm, G.; van Nostrum, C. F.; Lammers, T.; Hennink, W. E., Complete Regression of Xenograft Tumors upon Targeted Delivery of Paclitaxel via Pi-Pi Stacking Stabilized Polymeric Micelles. Acs Nano 2015, 9 (4), 3740-3752.
    50. Ashton, S.; Song, Y. H.; Nolan, J.; Cadogan, E.; Murray, J.; Odedra, R.; Foster, J.; Hall, P. A.; Low, S.; Taylor, P.; Ellston, R.; Polanska, U. M.; Wilson, J.; Howes, C.; Smith, A.; Goodwin, R. J. A.; Swales, J. G.; Strittmatter, N.; Takats, Z.; Nilsson, A.; Andren, P.; Trueman, D.; Walker, M.; Reimer, C. L.; Troiano, G.; Parsons, D.; De Witt, D.; Ashford, M.; Hrkach, J.; Zale, S.; Jewsbury, P. J.; Barry, S. T., Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. Science Translational Medicine 2016, 8 (325).

 

A welcome Nature Editorial

I reproduce below a comment I have left on this Nature editorial entitled “Go forth and replicate!“.

Nature Publishing Group encouragement of replications and discussions of their own published studies is a very welcome move. Seven years ago, I wrote a letter (accompanying a submission) to the Editor of Nature Materials. The last paragraph of that letter read: “The possibility of refuting existing data and theories is an important condition of progress of scientific knowledge. The high-impact publication of wrong results can have a real impact on research activities and funding priorities. There is no doubt that the series of papers revisited in this Report contribute to shape the current scientific landscape in this area of science and that their refutation will have a large impact.” [1]

The submission was “Stripy Nanoparticles Revisited” and it took three more years to publish it… in another journal; meanwhile Nature Materials continued to publish findings based on the original flawed paper [2]. The ensuing, finally public (after three years in the secret of peer review), discussions on blogs, news commentary and follow up articles were certainly very informative on the absolute necessity of changing the ways we do science to ensure a more rapid discussion of research results [3].

One of the lessons I draw from this adventure is that the traditional publishing system is, at best ill suited (e.g. Small: three years delay), or at worst (e.g. Nature Materials) completely reluctant at considering replications or challenges to their published findings. Therefore, I am now using PrePrints (e.g. to publish a letter PNAS won’t share with their readers [4]), PubPeer and journals such as ScienceOpen where publication happens immediately and peer review follows [5].

So whilst I warmly welcome this editorial, it will need a little more to convince me that it is not a complete waste of time to use the traditional channels to open discussions of published results.

[1] The rest of letter can be found at https://raphazlab.wordpress.com/2012/12/17/letter-to-naturematerials/
[2] The article was eventually published in Small (DOI:10.1002/smll.201001465

2 comments on PubPeer

); timeline: https://raphazlab.wordpress.com/2012/12/20/stripy-timeline/
[3] https://raphazlab.wordpress.com/stripy-outside/
[4] https://raphazlab.wordpress.com/2015/11/16/pnas-your-letter-does-not-contribute-significantly-to-the-discussion-of-this-paper/
[5] https://raphazlab.wordpress.com/2015/11/17/the-spherical-nucleic-acids-mrna-detection-paradox/

Nanoparticles for imaging and sensing in biology

This is the title of a 3x1H45 course which I will give early September at the European School On Nanosciences and Nanotechnologies (ESONN) in Grenoble. The focus is on inorganic nanoparticles, e.g. gold, silver, iron oxide, quantum dots for biological applications. It will be the third year I give this course. It is a small class format with 21 students coming from all over the world, from New Zealand to South Africa, Denmark, Italy, India and France.

I have opted for a mostly discussion-based format centered around selected publications. I am asking readers of this blog (optional but very much welcome!) as well as students registered for the track B of ESONN15 (mandatory) to suggest at least one article for discussion. To suggest a paper, simply add a comment to this post with a reference (link to the paper would be even better).

Papers can be selected because they are historic landmarks in the field; or because they are recent ground breaking discoveries; or because they raise important questions that we need to discuss to move forward. Please provide one or two lines of justification for why you think we should discuss this paper.

Over to you!

How many people are using the #SmartFlares? Freedom of Information request provide insights

Quick summary of previous episodes for those who have not been following the saga: Chad Mirkin’s group developed a few years ago a technology to detect mRNAs in live cells, the nano-flares. That technology is currently commercialised by Merck under the name smartflares. For a number of reasons (detailed here), I was unconvinced by the publications. We bought the smartflares, studied their uptake in cells as well as their fluorescent signal and concluded that they do not (and in fact cannot) report on mRNAs levels. We published our results as well as all of the raw data

This question – how many people are using the SmartFlares? – is interesting because surely, if a multinational company such as Merck develops, advertises and sells products, to scientists worldwide, these products have to work. As Chad Mirkin himself said today at the ACS National Meeting in Philadelphia “Ultimate measure of impact is how many people are using your technologies“.

So, we must be wrong. SmartFlares must work.

But our data say otherwise, so what is going on?

One hint is the very low number of publications using the smartflares and the fact that some of those are not independent investigations. This, however does not tell us how many groups in the world are using the smartflares.

Here is an hypothesis: maybe lots of groups worldwide are spending public money on probes that don’t work… and then don’t report the results since the probes don’t work. That hypothesis is not as far fetched as it may seem: it is called negative bias in science publishing and it is one of the causes of the reproducibility crisis.

To test this hypothesis, we would need to know how many research groups worldwide have bought the smartflares, an information that I suspected Merck was not going to volunteer. So, instead, I made Freedom of Information requests to (nearly) all UK research intensive universities (the Russell group) asking whether they had evidence of smartflare purchase orders.

Some Universities (6) declined because it would have been too much work to retrieve the information but most (14) obliged. The detailed results are available here. They show that a minimum of 76 different purchases were made between the launch of the product and June 2016. The money spent is £38k representing 0.0013% of these UK universities research income. As far as I can see, none has resulted in a publication so far.

All I can say is that these data do not falsify our hypothesis.

And if after reading this, you are still unconvinced of the need to publish negative data, check the upturnedmicroscope cartoon (warning: scene of violence).

 

 

 

PhD student at the Frontiers in BioImaging conference

Blog and Log

65787098 Jennifer presents her poster at the conference

Guest post by Jennifer Francis, PhD student in the Institute of Integrative Biology.

I recently attended the Frontiers in BioImaging conference in London (14th-15th July 2016), organised by the Royal Microscopical Society (RMS). Since this highly specialised conference was relatively small, I got the opportunity to speak one-to-one with experts within the field of super-resolution microscopy about their cutting-edge imaging techniques. A number of microscopy companies, including Carl Zeiss and Leica, also showcased their latest products. The highlight of this trip, was presenting my poster entitled “Exploiting Fluctuations to Enhance Imaging Resolution of Biological Structures“, which generated lots of encouraging interest. Whilst in London, I also got the chance to explore the famous landmarks, whose architecture never fails to impress.

76544879As well as, attending the talks, I also sat in on the Annual General Meeting (AGM), where the…

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Chad Mirkin on Nano Hype

Chad Mirkin did a Reddit AMA yesterday (h/t Neil Withers).

Capture

 

(highlight mine)

Of these 1800 commercial products, 1700+ are in fact a single product, the famous Spherical Nucleic Acids/SmartFlares.

More on this blog and our paper (The spherical nucleic acids mRNA detection paradox) here.

With the risk of being accused of having cynical views…

The Internet of NanoThings

Nanosensors and the Internet of Nanothings” ranks 1st in a list of ten “technological innovations of 2016” established by no less than the World Economic Forum Meta-Council on Emerging Technologies [sic].

The World Economic Forum, best known for its meetings in Davos, is establishing this list because:

New technology is arriving faster than ever and holds the promise of solving many of the world’s most pressing challenges, such as food and water security, energy sustainability and personalized medicine. In the past year alone, 3D printing has been used for medical purposes; lighter, cheaper and flexible electronics made from organic materials have found practical applications; and drugs that use nanotechnology and can be delivered at the molecular level have been developed in medical labs.

However, uninformed public opinion, outdated government and intergovernmental regulations, and inadequate existing funding models for research and development are the greatest challenges in effectively moving new technologies from the research lab to people’s lives. At the same time, it has been observed that most of the global challenges of the 21st century are a direct consequence of the most important technological innovations of the 20st century.

Understanding the implications of new technologies are crucial both for the timely use of new and powerful tools and for their safe integration in our everyday lives. The objective of the Meta-council on Emerging Technologies is to create a structure that will be key in advising decision-makers, regulators, business leaders and the public globally on what to look forward to (and out for) when it comes to breakthrough developments in robotics, artificial intelligence, smart devices, neuroscience, nanotechnology and biotechnology.

Given the global reach and influence of the WEF, it is indeed perfectly believable that decision-makers, regulators, business leaders and the public could be influenced by this list.

Believable and therefore rather worrying for – at least the first item – is, to stay polite, complete utter nonsense backed by zero evidence. The argument is so weak, disjointed and illogical that it is hard to challenge. Here are some of the claims made to support the idea that “Nanosensors and the Internet of Nanothings” is a transformative  technological innovations of 2016.

Scientists have started shrinking sensors from millimeters or microns in size to the nanometer scale, small enough to circulate within living bodies and to mix directly into construction materials. This is a crucial first step toward an Internet of Nano Things (IoNT) that could take medicine, energy efficiency, and many other sectors to a whole new dimension.

Except that there is no nanoscale sensor that can circulate through the body and communicate with internet (anyone knows why sensors would have to be nanoscale to be mixed into construction materials?).

The next paragraph seize on synthetic biology:

Some of the most advanced nanosensors to date have been crafted by using the tools of synthetic biology to modify single-celled organisms, such as bacteria. The goal here is to fashion simple biocomputers [Scientific American paywall] that use DNA and proteins to recognize specific chemical targets, store a few bits of information, and then report their status by changing color or emitting some other easily detectable signal. Synlogic, a start-up in Cambridge, Mass., is working to commercialize computationally enabled strains of probiotic bacteria to treat rare metabolic disorders.

What is the link between engineered bacteria and the internet? None. Zero. I am sorry to inform the experts of the WEF that bacteria, even genetically engineered ones, do not have iPhones: they won’t tweet how they do from inside your gut.

I could go on but will stop. Why is such nonsense presented as expert opinion?