LESS BRIEF OUTLINE AND HISTORY

2:LESS BRIEF OUTLINE AND HISTORY

April 1953 – The Watson Crick Double helix (W-C), a beautiful right handed spiral stuns the world.

But how do you untwist a molecule that long in the time required to replicate? I mean that’s over 100 revolutions per second.’

‘Yes. This issue was a problem right from the start and as Max Delbruck said in a letter to Watson “…the difficulties of untangling the chains do seem, after all, insuperable to me.” Max Delbruck 12 May 1953. Watson and Crick addressed the issue head on in their follow up paper of 30th May 1953 where they claimed to be reasonably sure the problems would not be ‘..insuperable.”

1960, 62 and 68 work done on base stacking by Langridge and then by others confirms right handed base stacking

But they only bothered to look at the right handed options.’

‘Yes, I know it’s odd isn’t it?’

1976-81 Sasisekharan does the only work before or since which examined the component elements of the molecule in fine detail and concludes it can stack 35o left or right. He produces his side by side model (SBS) which alternates 5 base pairs right, then 5 base pairs left.

So?’

‘Well, you see it isn’t twisted and simply has to pull apart to replicate. And it can do it from multiple start points along the line at the same time – far quicker.’

1976 The author who is at Kingston College of Further Education (Secondary School/High School), sees the report of Sasi’s work and idly muses that there is a difference between dead (in vitro) DNA and living (in vivo) DNA.

1981 The author, now an anthropology under graduate at UCL writes a summary of Sasi’s work. Being young and cheeky and wanting an ‘A’ he adds a critique.

1) Sasi’s evidence points to the stacking being pragmatic to specific base sequences and so the idea of any regular structure, W-C or SBS makes no sense.

2) Sasi’s evidence shows that the energy gradients in the backbone and between left and right base stacks are easily achievable. Since the whole thing is operating at warm temperatures this means that in its raw, naked state it must be moving, thermodynamically active. The author read the results graphs as probability statements showing the time at which certain conformations were held before dynamically transitioning.

But it isn’t raw or naked, it’s got histones and other protein stuff all round it.’

‘Yes, I know but you have to get down to the basics to really understand anything.’

3) With the well known repeat (homogenous) sequences being more thermodynamically stable you can envisage that by raising the temperature of the whole molecule the coding (heterogenous) sequences would open for template formation while the adjacent repeat sequences would stay together, acting as ‘zip ends’.

4) W-C DNA is seen as very stable and inert and in need of assistance from other molecules to perform its basic functions. The ASDT model turns this on its head. It proposes a molecule that arose as a dynamically active entity with sequence specific functionality. This may help explain how and why it originally evolved and became so dominant. This approach sees the current associated proteins as elements that have subsequently evolved to modify and enhance the molecule’s elemental energy.

Ah I see now. And the evolution part.’

‘Anthropology eh? Gets into everything.’

1982 The author sends summary paper to renowned nucleic acids guy at another London college. They meet.

Renowned guy: Well you know more about DNA than most science graduates because you’ve been able to focus on it.

Author: OK

Renowned guy: But Sasi and his team are charlatans. We see them at seminars all the time.

Author: OK?

They chat a bit and author makes to leave.

Renowned guy: Do you have a copy of this paper?

Author:No

Renowned Guy makes a copy of this layman’s summary of the work of charlatans – go figure.

‘Charlatans is very strong language.’

‘I thought so and a couple of weeks later I got the letter from Sasi (www.sidebysidedna.com Sasi papers 11) explaining that his student Pattabiraman was now at Langridge’s lab in San Francisco. So how could they be charlatans?’

1982–1995 The author has life

1995-2004 The author writes novel ‘A Singing Dancing Thing’ in a fairly desperate attempt to get the story out. Like any self respecting fiction about molecular biology it opens with the liberation of Dachau, sweeps through the US Civil Rights struggle, Black Panthers, FBI-Cointelpro, DARPA/Pentagon conspiracy secret science, Los Alamos, the Sabra and Shatila massacres, San Fransisco, the AIDS crisis and the Gallo scandal – what’s not to like?

PS 1st 3 chapters available on this site. Get in touch using the ‘Rest of novel request form’ if you’d like to read more of it.

2004-2011 The author has more life

2011 The author gets animation made by Luk and Idoya at Somersault18:24 https://www.somersault1824.com and incorporates it into 3 minute film 2013: A DNA Story – available on request – it’s complicated.

2013 The author discovers Sasi is still alive and sharp as a tack at 80 (now 89).

2013-2020 More life still

2020 The author is stuck at home with Covid and writes short story ‘Being Misunderstood’ – available on this site. The author finally launches website www.sidebysidedna.com. Most of Sasi’s researcher co-authors get in touch. Author reaches out to the great and good in the DNA research community.

Enthusiastic responses from science world then?’

‘Not so much.’

Distinguished Emeritus: Well, yes Sasi was very well qualified and his work was sound which is why he was published.

Author: So why wasn’t his work repeated and verified/refuted?

Distinguished Emeritus: There was no point. We’re all happy with the W-C model. There are so many examples in the Protein Data Bank which are bound to W-C DNA’s and so much work is done successfully on the premise that it’s W-C that there is no need to question it.

Author: OK? But what if someone did repeat it and confirmed it?

Distinguished Emeritus: It wouldn’t make any difference because there’s no experiential evidence that SBS structures exist.

Author:The issue of evolutionary parsimony seems problematic and the fundamental nature of the relationship between DNA and associated molecules like histones is inverted if you use the SBS and would seem to ease that problem considerably. Can you recommend researchers in molecular bio evolution I might approach?

Distinguished Emeritus: I do not understand your point.

Author: Anomalies like the D DNA circular dichroism still need to be explained. Are there any other similar areas of doubt/confusion that you can highlight?

Distinguished Emeritus: There are none that I know of.

But that’s not very scientific is it?’

‘Well the bit about no anomalies is extremely strange. Certainly unscientific but very anthropological. As to the rest – well yes and no.’

‘How do you mean?’

‘Well, with evolutionary parsimony we were slightly at cross purposes. I’ll go into it later.’

‘Aow!? I want to hear now.’

‘This is the fun, grab their attention part. Stop whining.’

2020 The author, still cheeky writes to all Sasi’s team to say,

‘Look the website is a great resource and if this thing is going to go forward you guys need to do some work. You have to examine the W-C anomalies and show how SBS can solve them. And you have to make the point about the bio evolution of the molecule.’

So that got them going?’

‘No – they all have lives apparently – except one.’

2020 In reply to author’s second letter Samir Brahmachari https://www.linkedin.com/in/samir-k-brahmachari-9782b1105/?originalSubdomain=in, the most eminent of Sasi’s former students gets in touch having seen the website probably and the animation certainly for the first time.

Samir: Interesting. You look at this more as an artist than as a scientist. I like your model.

Author: Thanks. Obviously it’s just a natural extrapolation of Sasi’s work which I’m sure he sees.

Samir: No he doesn’t – and he won’t. He’s stuck.

Author: OK?

Samir: Look I’m about to retire back to Bangalore. When I get there I’m going to recruit a researcher and design a research project to look into your model with another of Sasi’s former students, Mansur Bansal.

Author: OK?

Holy shit. That’s amazing.’

‘You’re telling me. I was stunned.’

2021 Sean Kettle contacts the author out of the blue. He has set up another DNA website www.dna.place also in 2020 based on/inspired by the work of Mark Curtis. It is tremendous and links to lots of other sites and papers about anomalies and alternative structures. It’s an extremely encouraging connection. Looking at the work on Sean’s website the author realises that from the ASDT model you can get to any of the other proposed structures – you can even twist it round itself into a double helix if you would really want to.

2022

Author: Hi Samir I know we had discussed keeping it all quiet because alternative structures are such a big taboo and you wanted to set up the research programme and recruit the researchers with minimum fuss. And I know everything has been put on hold by Covid but I’m not getting any younger. I have recently shown the animation and website to a couple of young scientists and they really liked it. I want this to get on and be discussed. I don’t want to be the guy who gets discovered after his death. I mean I’m in good health you understand but I’m being realistic.

Samir: OK.

Author: So I’m planning to revamp and refocus the website*. Everything that’s there will stay but the commentary will change and it’s going to be focussed on my model. Then I’m going to post the animation and the website link on social media to create attention.

Samir: Ok good.

*The author learned a huge amount from Sean’s website and decided that the departure was too great for tweaking and so have launched this totally new website instead.

So that’s it?’

‘Blimey you don’t want much, do you?’

‘So what about a name for the model?’

‘Well, I guess I’m allowed?’

‘Certainly.’

‘The Johnson model isn’t going to fly.’

‘Certainly not. How about the title of the novel? I like that.’

‘The “Singing Dancing Thing” model. The ‘SDT’model.’

‘Sounds like an embarrassing disease!’

‘Oh yeah, no good. Ok, how about the ‘ASDT’ model?’

‘Yes I think that’ll work.’

2022

In the process of creating this website having absorbed the other material the author reaches back to his original 1981 thoughts and generates a hypothesis which sees the ASDT with it’s inherent sequence specific functionality as the ancestral model of DNA that first emerged from the proceeding ribonucleoprotein world. This theory sees the development of circular plasmid DNA and linear DNA with associated proteins, histones etc as subsequent developments that enhanced and improved the molecule’s function.

The range of ways that the DNA molecule is able to interact with those associated molecules explains how and why different structures have been reported. There is a family of DNA structures within each organism and across organisms.

This is or should be extremely exciting.

There is a massive institutional and mindset block against any alternative models and this is as unscientific as it is unnecessarily destructive.

According to this new theory the DNA molecule is absolutely amazing and deserves so much better from the people presuming to be studying it.