On 2016 Oct 13, Andy Collings commented:

Jeffrey Friedman and colleagues' response to Markus Meister's paper, Physical limits to magnetogenetics, is available here, https://elifesciences.org/content/5/e17210#comment-2948691685, and is reproduced below:

On the Physical Limits of Magnetogenetics

In a recent paper, Markus Meister comments on data published by our groups (and a third employing a different approach) [1] showing that cells can be engineered to respond to an electromagnetic field [2-4]. Based on a set of theoretical calculations, Meister asserts that neither the heat transfer nor mechanical force created by an electromagnetic field interacting with a ferritin particle would be of sufficient magnitude to gate an ion channel and then goes on to question our groups’ findings altogether.

One series of papers (from the Friedman and Dordick laboratories) employed four different experimental approaches in cultured cells, tissue slices and animals in vivo to show that an electromagnetic field can induce ion flow in cells expressing ferritin tethered to the TRPV1 ion channel [2,3]. This experimental approach was validated in vitro by measuring calcium entry, reporter expression and electrophysiological changes in response to a magnetic field. The method was validated in vivo by assaying magnetically induced changes in reporter expression, blood glucose and plasma hormones levels, and alterations in feeding behavior in mice.

These results are wholly consistent with those in an independent publication (from the Guler and Deppmann laboratories) in which the investigators fused ferritin in frame to the TRPV4 ion channel [4]. In this report, magnetic sensitivity was validated in vitro using calcium entry and electrophysiological responses as outputs. Additionally, in vivo validation was demonstrated by analyzing magnetically induced behaviors in zebrafish and mice, and through single unit electrophysiological recordings.

In his paper, Meister incorrectly states our collective view on the operative mechanism [1]. While we are considering several hypotheses, we agree that the precise mechanism is undetermined. Lastly, although mathematical calculations can often be used to model biologic phenomena when enough of the relevant attributes of the system are known, the intrinsic complexity of biologic processes can in other instances limit the applicability of purely theoretical calculations [5]. It is our view that mathematical theory needs to accommodate the available data, not the other way around. We are thus surprised that Meister would stridently question the validity of an extensive data set published by two independent groups (and a third using a different method) without performing any experiments. However, we too are interested in defining the operative mechanism(s) and welcome further discussion and experimentation to bring data and theory into alignment.

Jeffrey Friedman, Sarah Stanley, Leah Kelly, Alex Nectow, Xiaofei Yu, Sarah F Schmidt, Kaamashri Latcha

Department of Molecular Genetics, Rockefeller University

Jonathan S Dordick, Jeremy Sauer

Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute

Ali D Güler, Aarti M Purohit, Ryan M Grippo

Christopher D Deppmann, Michael A Wheeler

Sarah Kucenas, Cody J Smith

Department of Biology, University of Virginia

Manoj K Patel, Matteo Ottolini, Bryan S Barker, Ronald P Gaykema

Department of Anesthesiology, University of Virginia

(Laboratory Heads in Bold Lettering)

References

1) Meister, M, Physical limits to magnetogenetics. eLife, 2016. 5. http://dx.doi.org/10.7554/eLife.17210

2) Stanley, SA, J Sauer, RS Kane, JS Dordick, and JM Friedman, Corrigendum: Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles. Nat Med, 2015. 21(5): p. 537. http://dx.doi.org/10.1038/nm0515-537b

3) Stanley, SA, L Kelly, KN Latcha, SF Schmidt, X Yu, AR Nectow, J Sauer, JP Dyke, JS Dordick, and JM Friedman, Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature, 2016. 531(7596): p. 647-50. http://dx.doi.org/10.1038/nature17183

4) Wheeler, MA, CJ Smith, M Ottolini, BS Barker, AM Purohit, RM Grippo, RP Gaykema, AJ Spano, MP Beenhakker, S Kucenas, MK Patel, CD Deppmann, and AD Guler, Genetically targeted magnetic control of the nervous system. Nat Neurosci, 2016. 19(5): p. 756-61. http://dx.doi.org/10.1038/nn.4265

5) Laughlin, RB and D Pines, The theory of everything. Proc Natl Acad Sci U S A, 2000. 97(1): p. 28-31. http://dx.doi.org/10.1073/pnas.97.1.28

On 2016 Oct 13, Andy Collings commented:

Jeffrey Friedman and colleagues' response to Markus Meister's paper, Physical limits to magnetogenetics, is available here, https://elifesciences.org/content/5/e17210#comment-2948691685, and is reproduced below:

On the Physical Limits of Magnetogenetics

In a recent paper, Markus Meister comments on data published by our groups (and a third employing a different approach) [1] showing that cells can be engineered to respond to an electromagnetic field [2-4]. Based on a set of theoretical calculations, Meister asserts that neither the heat transfer nor mechanical force created by an electromagnetic field interacting with a ferritin particle would be of sufficient magnitude to gate an ion channel and then goes on to question our groups’ findings altogether.

One series of papers (from the Friedman and Dordick laboratories) employed four different experimental approaches in cultured cells, tissue slices and animals in vivo to show that an electromagnetic field can induce ion flow in cells expressing ferritin tethered to the TRPV1 ion channel [2,3]. This experimental approach was validated in vitro by measuring calcium entry, reporter expression and electrophysiological changes in response to a magnetic field. The method was validated in vivo by assaying magnetically induced changes in reporter expression, blood glucose and plasma hormones levels, and alterations in feeding behavior in mice.

These results are wholly consistent with those in an independent publication (from the Guler and Deppmann laboratories) in which the investigators fused ferritin in frame to the TRPV4 ion channel [4]. In this report, magnetic sensitivity was validated in vitro using calcium entry and electrophysiological responses as outputs. Additionally, in vivo validation was demonstrated by analyzing magnetically induced behaviors in zebrafish and mice, and through single unit electrophysiological recordings.

In his paper, Meister incorrectly states our collective view on the operative mechanism [1]. While we are considering several hypotheses, we agree that the precise mechanism is undetermined. Lastly, although mathematical calculations can often be used to model biologic phenomena when enough of the relevant attributes of the system are known, the intrinsic complexity of biologic processes can in other instances limit the applicability of purely theoretical calculations [5]. It is our view that mathematical theory needs to accommodate the available data, not the other way around. We are thus surprised that Meister would stridently question the validity of an extensive data set published by two independent groups (and a third using a different method) without performing any experiments. However, we too are interested in defining the operative mechanism(s) and welcome further discussion and experimentation to bring data and theory into alignment.

Jeffrey Friedman, Sarah Stanley, Leah Kelly, Alex Nectow, Xiaofei Yu, Sarah F Schmidt, Kaamashri Latcha

Department of Molecular Genetics, Rockefeller University

Jonathan S Dordick, Jeremy Sauer

Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute

Ali D Güler, Aarti M Purohit, Ryan M Grippo

Christopher D Deppmann, Michael A Wheeler

Sarah Kucenas, Cody J Smith

Department of Biology, University of Virginia

Manoj K Patel, Matteo Ottolini, Bryan S Barker, Ronald P Gaykema

Department of Anesthesiology, University of Virginia

(Laboratory Heads in Bold Lettering)

References

1) Meister, M, Physical limits to magnetogenetics. eLife, 2016. 5. http://dx.doi.org/10.7554/eLife.17210

2) Stanley, SA, J Sauer, RS Kane, JS Dordick, and JM Friedman, Corrigendum: Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles. Nat Med, 2015. 21(5): p. 537. http://dx.doi.org/10.1038/nm0515-537b

3) Stanley, SA, L Kelly, KN Latcha, SF Schmidt, X Yu, AR Nectow, J Sauer, JP Dyke, JS Dordick, and JM Friedman, Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature, 2016. 531(7596): p. 647-50. http://dx.doi.org/10.1038/nature17183

4) Wheeler, MA, CJ Smith, M Ottolini, BS Barker, AM Purohit, RM Grippo, RP Gaykema, AJ Spano, MP Beenhakker, S Kucenas, MK Patel, CD Deppmann, and AD Guler, Genetically targeted magnetic control of the nervous system. Nat Neurosci, 2016. 19(5): p. 756-61. http://dx.doi.org/10.1038/nn.4265

5) Laughlin, RB and D Pines, The theory of everything. Proc Natl Acad Sci U S A, 2000. 97(1): p. 28-31. http://dx.doi.org/10.1073/pnas.97.1.28