SUPERCOILING AND OTHER ANOMALIES

Human beings evolved as a large bodied primate with fairly limited individual defensive capabilities in predator rich environments. To survive this we were obliged to get both clever technologically and extremely collaborative (of which more later). But our survival as a species fundamentally depended on us being attuned to a 4 dimensional world located roughly mid point in the scale of the physical world between the sub atomic and the cosmic.

This 4 dimensional world was brilliantly codified by Isaac Newton in a theoretical framework that dominated the natural sciences for about 2 centuries. That framework still satisfies 99.99999% or more of us for 99.99999% or more of the time in our daily lives.

But it is that 0.00001% or smaller fraction in which there are anomalies. These are broadly only relevant to a small handful of specialists but by examining them the specialists came to understand and to show that our Newtonian frame of reference is almost an anomaly set against the true scale and astounding nature of the universe.

It is fundamentally important for science to pay attention to anomalies, however inconvenient they may appear to be.

NOLI TANGERE: IN THE GRIP OF STABILITY

There is a 2004 film Something The Lord Made https://www.youtube.com/watch?v=eIgZVmMAkiQ starring Mos Def and the late Alan Rickman about the often stressed relationship between two Southern US heart surgeons, the unqualified but brilliant African American Vivien Thomas (Def) and his also brilliant European American boss Dr Alfred Blalock (Rickman). For years heart surgery had been limited by the practical problems presented by the need to stop the heart to operate on or even near it. Noli tangere (don’t touch) was the dominating principle which the two of them eventually overcame, opening up the field.

One overarching theme in the conceptualisation of the DNA molecule is the need for stability to safeguard the integrity of the sequences and coding. The W-C is seen as delivering this stability and not touching or questioning W-C has become the noli tangere of the field.

This concern partly explains the difficulty people have with even contemplating alternative and apparently less stable structures. We will discuss other reasons for this in more depth later.

Many of the researchers proposing alternative structures have made their views well known and you can find links to the work of Tai Te Wu, You Cheng Xu, Clive Delmonte, Karst Hoogsteen, Mark Curtis and Ken Biegeleisen on Sean’s www.dna.place.com website.

AND IF YOU DO NOTHING ELSE AFTER READING THIS:

WATCH

KEN BIEGELEISEN’S 8 MINUTE VIDEO https://notahelix.net/notahelix_intro.mp4

AND READ

TAI TE WU’S LETTER

‘POLITICS DICTATES SCIENTIFIC TRUTH’ https://drive.google.com/file/d/1EKdG5Ti40_TYVYVhZkYxDCKdqX1G4UJ1/view

Clive Delmonte has produced an excellent book ‘A New Structural Molecular Biology’ (NSMB) which identifies and details most of the W-C anomalies in the literature. You can find Clive’s work on Sean Kettle’s website www.dna.place.com and at https://www.researchgate.net/profile/Clive-Delmonte.

ANOMALIES AND PROBLEMS WITH W-C

There are a number of anomalies or problems in DNA science which must be addressed. They are:

1) Linear supercoiling

2) Unwinding/replication

3) Cross sectional diameters of DNA

4) The reversibility of left handed Z DNA to right handed B DNA

5) The reversibility of left handed synthetic D DNA to right handed A and B DNA

6) Problems with the original x-ray crystallography analysis detailed by Tai Te Wu.

1)SUPERCOILING: Trying very hard indeed

‘So why is supercoiling so important?

‘Well the DNA in each human cell is about 2 metres (6’) long. It has to coil up a lot to fit.

‘Well obviously the one on the left looks crap. It can’t have been done by anyone with a serious reputation. Is that Sasi’s?’

‘No, his is the one on the right.’

‘Is this a trick? Were the Nobel laureates economists or something?’

‘No they were Francis Crick (Nobel 1962)and Aaron Klug (Nobel 1982).’

‘You’re kidding!’

‘It’s worse than that.’

‘How?’

‘This is what they actually published.

‘OMG!!’

In the novel the German American heroine Tina, refers to a string of English sausages and scathingly calls this Crick/Klug model ‘bangers DNA’.

2)UNWINDING/REPLICATION: TOPOISOMERASE AND MULTIPLE REPLICATION POINTS

Sasi’s SBS solves the problem of unwinding by eliminating the winding in the first place. Unfortunately for him a significant development in the mid 1970’s that impacted the perception of his work was the discovery of the topoisomerases. It was found that replication was initiated and speeded up by the inclusion of these enzymes. This was seized on by researchers as a solution to the problem of the unwinding and, as it used to say in the online encyclopedia entry ‘The advent of topoisomerases killed the side by side models’. The current entry under ‘Obsolete models of DNA structure’ is still pretty emphatically dismissive https://en.wikipedia.org/wiki/Obsolete_models_of_DNA_structure .

Except the discovery of topoisomerases doesn’t confirm the W-C at all. All it establishes is that whatever the structure of DNA may be it replicates faster with topoisomerase than without it. The leap to assuming that it confirms the W-C is again problematic from a science procedure/rules point of view.

Explanations for how topoisomerase unwinds the double helix could very easily be reworked to explain how it would work with SBS if people were prepared to take SBS seriously.

Other evidence is cited: ‘However, the structure of DNA was subsequently confirmed in solution via gel electrophoretic methods [26] and later via solution NMR[27] and AFM[28] indicating that the crystallography process did not distort it. The structure of DNA in complex with nucleosomes, helicases and numerous other DNA binding proteins also supported its biological relevance in vivo.[29]’

It is simply not scientifically valid to assert that DNA fragments/elements in the lab are not artifacts and then go on to claim that they support in vivo conclusions without making very careful and considered qualifications. This manages to be both fallacious and arrogant – as unappealing as it is unscientific.

In addition the evidence showing multiple replication points in a single DNA molecule driven along by the work of topoisomerases is offered as confirming the W-C, with the multiple points radically reducing or eliminating the need for any unwinding.

You should try this with a twisted double rope and as many fingers as you can to separate it. You’ll find that it doesn’t solve the problem at all – it’s a complete fudge.

Again you have this issue of people doing everything they can to prop up the W-C with undue haste and forcefulness to say the very diplomatic least.

This is bafflingly unscientific but regrettably understandable from the perspective of the stability obsession and also from an anthropological, psychological, hierarchical, power-structure point of view. Ken Biegeleisen and Tai Te Wu are very strong on these points. We will look at this later.

3)CROSS SECTIONAL DIAMETERS OF DNA

Along with detailed discussion of the literature relating to most of the DNA anomalies Clive Delmonte’s NSMB details the work done on establishing the diameter of the DNA molecule (NSMB pp24-26 et al). Delmonte shows the problems with establishing this apparently simple measurement. He goes through the unexpected range of measurements from 7 angstroms (Å) to 22 Å. He discusses the problems of false assumptions made by various researchers and their often unwarranted convictions regarding the soundness of their techniques and the accuracy of their results. He also addresses the issue of hierarchy and power in science which as we have discussed is supposed to be held in check by good science practice.

Of all the work surveyed he concludes that some of the best work in this area was done by James and Mazia published amazingly in March 1953 – that remarkable Spring (Surface Films of Desoxyribonucleic Acid; T.W. James & D. Mazia; Biochim. Biophys. Acta 10 (1953) pp367 – 370). Their elegant work concluded that the molecule wasn’t circular but elliptical with heights in the two planes of 11.7 Å and 21.6 Å. This is consistent with Sasi’s SBS.

4) THE REVERSIBILITY OF LEFT HANDED Z DNA TO RIGHT HANDED B DNA

5) THE REVERSIBILITY OF LEFT HANDED SYNTHETIC D DNA TO RIGHT HANDED A AND B DNA

Sasi’s demonstration that both of these apparently major changes were fairly easily reversible is extraordinary evidence that the molecule is extremely flexible. It also indicates that it can take up a transitional structure like SBS for instance. Why haven’t people pursued this?

6) PROBLEMS WITH THE ORIGINAL X-RAY CRYSTALLOGRAPHY ANALYSIS BY TAI TE WU

Tai Te Wu’s work is very important and he is remarkably well qualified to be examining the issue (but his work is not addressed by Delmonte in NSMB). This work is Wu, TT ‘Secondary structures of DNA’ PNAS 63(2):400-405 1969 and Wu R and T.T.Wu (1996) ‘A novel intact circular dsDNA supercoil’ Bull.Math.Biol, 58(6): 1171-1185. Wu sets out a convincing critique of the interpretation of the original crystallographic work done by Wilkins and Franklin. He details exchanges with Wilkins. Wu is seeking access to a properly sized copy of the original x-ray crystallography photograph to verify measurements. Wilkins claims to have ‘lost’ the original which is peculiar.

Wu goes on to present an alternative structure based on his own analysis and in the process strongly critiques the W-C bandwagon.

Ken Biegeleisen website (http://notahelix.net) addresses a lot of the same general ground and critiques of DNA science as this site and Sean Kettle’s site. Biegeleisen then goes into Wu’s work in detail and uses it for his own original work on protamine/DNA complexes in sperm nuclei. This work is compelling and has been published ‘The probable structure of the protamine-DNA complex’ J of Theoretical Biology Vol 241 (2006) pp533-540.

Most importantly Ken has produced a series of powerpoint/videos which are extremely helpful in understanding the structures and the science.

ANOMALIES: viable alternatives

Sasi, Delmonte, Xu, Wu, Biegeleisen and Hoogsteen’s work all point out the problems with the W-C. Xu takes the trouble to outline proposed research programmes to elucidate these key issues. As you will see on Sean Kettle’s site they have all critiqued W-C and proposed important alternatives. Then there is the artist Mark Curtis and whose work inspired Sean to develop the site.

The big point is that despite the clear evidence of many anomalies and problems with W-C from many highly qualified researchers the DNA research establishment is remaining effectively willfully obtuse, obstinate and unreceptive to the point of, as Biegeleisen describes it ‘…deliberate deception.’ in the case of Stettler, Kohler, Weber and Weissman (1979).

Author: But what about the anomalies?

Distinguished Emeritus: There are none that I know of.

This is extremely unscientific and damaging to the field.

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