On 2016 Jan 28, Donald Forsdyke commented:

HYPOTHESIS-DRIVEN RESEARCH

The discoveries of a cytosolic microbial adaptive immune system (CRISPR) and its applications to genome editing are major scientific advances. A review of the history of this magnificent achievement, made mainly by young people close to those with abundant research funds, is welcome. But the implication that this history supports the non-hypothesis-driven approach to research is questionable.

Backed by inexpensive bioinformatic analyses, a hypothesis of cytosolic innate immunity was developed in the 1990s [1-3]. Had this CRISPR-analogous hypothesis been backed by funding, CRISPR and its applications might have been achieved more expeditiously. Thus, there are many roads to Rome. Because the well-equipped army that took route A arrive first, it does not follow that route A is superior to route B. Likewise, this comment could have been written in prose or poetry. Your liking (perhaps) of the present prose rendition, does not disprove the proposition that a poetic version might have been superior.

[1] Forsdyke & Mortimer (2000) Chargaff’s legacy. Gene 261, 127-137.Forsdyke DR, 2000

[2] Cristillo et al. (2001) Double-stranded RNA as a not-self alarm signal: to evade, most viruses purine-load their RNAs, but some (HTLV-1, Epstein-Barr) pyrimidine-load. J Theor Biol 208, 475-491.Cristillo AD, 2001

[3] Forsdyke, Madill & Smith (2002) Immunity as a function of the unicellular state: implications of emerging genomic data. Trends Immunol 23, 575-579.Forsdyke DR, 2002

On 2016 Jan 26, Donald Forsdyke commented:

None

On 2016 Jan 24, Claudiu Bandea commented:

None

On 2016 Jan 19, Emmanuelle Charpentier commented:

I regret that the description of my and collaborators’ contributions is incomplete and inaccurate. The author did not ask me to check statements regarding me or my lab. I did not see any part of this paper prior to its submission by the author. And the journal did not involve me in the review process.

On 2016 Jan 18, JENNIFER DOUDNA commented:

From Cell editor: “…the author engaged in substantial fact checking directly with the relevant individuals.”

However, the description of my lab’s research and our interactions with other investigators is factually incorrect, was not checked by the author and was not agreed to by me prior to publication.

On 2016 Jan 18, JENNIFER DOUDNA commented:

From Cell editor: “…the author engaged in substantial fact checking directly with the relevant individuals.”

However, the description of my lab’s research and our interactions with other investigators is factually incorrect, was not checked by the author and was not agreed to by me prior to publication.

On 2016 Jan 19, Emmanuelle Charpentier commented:

I regret that the description of my and collaborators’ contributions is incomplete and inaccurate. The author did not ask me to check statements regarding me or my lab. I did not see any part of this paper prior to its submission by the author. And the journal did not involve me in the review process.

On 2016 Jan 24, Claudiu Bandea commented:

None

On 2016 Jan 26, Donald Forsdyke commented:

None

On 2016 Jan 28, Donald Forsdyke commented:

HYPOTHESIS-DRIVEN RESEARCH

The discoveries of a cytosolic microbial adaptive immune system (CRISPR) and its applications to genome editing are major scientific advances. A review of the history of this magnificent achievement, made mainly by young people close to those with abundant research funds, is welcome. But the implication that this history supports the non-hypothesis-driven approach to research is questionable.

Backed by inexpensive bioinformatic analyses, a hypothesis of cytosolic innate immunity was developed in the 1990s [1-3]. Had this CRISPR-analogous hypothesis been backed by funding, CRISPR and its applications might have been achieved more expeditiously. Thus, there are many roads to Rome. Because the well-equipped army that took route A arrive first, it does not follow that route A is superior to route B. Likewise, this comment could have been written in prose or poetry. Your liking (perhaps) of the present prose rendition, does not disprove the proposition that a poetic version might have been superior.

[1] Forsdyke & Mortimer (2000) Chargaff’s legacy. Gene 261, 127-137.Forsdyke DR, 2000

[2] Cristillo et al. (2001) Double-stranded RNA as a not-self alarm signal: to evade, most viruses purine-load their RNAs, but some (HTLV-1, Epstein-Barr) pyrimidine-load. J Theor Biol 208, 475-491.Cristillo AD, 2001

[3] Forsdyke, Madill & Smith (2002) Immunity as a function of the unicellular state: implications of emerging genomic data. Trends Immunol 23, 575-579.Forsdyke DR, 2002