Thursday, November 24, 2016

Denis Noble's Dance to the Tune of Life launch

Denis with President and past-President of Physiological Soc. 
I promised a blog post on Denis Noble's outstanding new book Dance to the Tune of Life whose launch I attended on Monday.

This is a really important book which brings together much of the work that Denis has done to rethink the conceptual foundations of evolutionary biology. The launch was in the form of a lecture at the Physiological Society, which summarised the essence of the book and also reported to some extent on the major scientific meeting at the Royal Society earlier that month.  This was a joint meeting between the Royal Society and the British Academy which brought together about 300 people. Sadly very few of the hand-line "neo-Darwinists" attended so there wasn't much fundamental debate about the views expressed, which is partly because the scientific evidence is now completely overwhelming.

Denis argues that we need to move from a 20th Century Reductionist Approach to a 21st Century Integrative Approach, which recognises that biology works on many levels and that organisms harness stochasiticty to generate functionality.

He points out that the dogmatic adherence to the tenets of Neo-Darwinism has done significant harm to the advance of science. Barbara McClintock did her initial pioneering work on how whole units of genetic material move around, rather than "random mutations" in the 1930s and 1940s but she was told in 1957 that her work was not believed and she stopped publishing for some years. When she was awarded a Nobel Prize in 1983 she was able to state clearly that "the genome is an organ of the cell."  Conrad Waddington was also sidelined for similar reasons.

One of the key areas where it is perfectly clear that  organisms harness stochasiticty to generate functionality is in somatic hypermutation. There is no doubt at all that much higher rates of mutation are allowed on specific parts of the genome in B-Cells. It's also clear that antibiotic resistance in bacteria is not acquired or transmitted simply by "random mutations" but by mechanisms such as horizontal gene transfer. So in fact the dogmatism of the Neo-Darwinists has actually damaged the development of science and medicine.  It seems that they are still at it: there was apparently a concerted campaign to prevent the RS from holding the scientific meeting earlier this month.

Denis kindly signed a copy of the book for me and another for my son. And I'm honoured and delighted to find my name in the acknowledgements, between Sir Patrick Bateson and Steven Bergman.

Wednesday, November 23, 2016

Joyce In War and Peace - amazing!

Joyce and colleagues taking a bow
Very busy few days. On Monday to the great Denis Noble launching his book Dance to the Tune of Life - which needs a blog post of its own - and then to The Red Barn at the National (a big disappointment - far too melodramatic).

But yesterday we went to hear the great Joyce DiDonato at the Barbican in her In War and Peace recital which was probably the finest singing recital I have ever been privileged to attend. This is really the album tour, since she has recorded these with the outstanding period-instrument orchestra Il Pomo d'Oro.

As you will see from the photo (apologies for low quality, we had seats quite far back and it's only an iPhone) there was a considerable element of staging, and in fact there was a fine dancer (Manuel Palazzo) who also performed during many of the numbers, without in any way detracting from the transcendent music.

Handel was the dominant composer and we opened with "scenes of horror, scenes of woe" from Jephtha. Then two rarities: "Prendi quel ferro, o barbaro!" from Leonardo Leo's Andromaca and the orchestral Sinfonia from Representatione di anime a di corpo by Emilo de'Cavalieri - composed in 1600.  Then "When I am laid to rest" from Dido and Aeneas - transcendently powerful and poignant! Can anything follow that?  Well after an aria from Handel's Agrippina and an orchestral arrangement of Gesualdo's 'Tristis est anima mea' we found out. 'Lascia ch'io pianga' from Handel's Rinaldo. I cannot imagine a finer performance. Heartbreakingly beautiful!

After the interval the mood lightened. 'They tell us that you mighty powers' from Purcell's unfinished The Indian Queen was followed by 'Crystal streams in murmers flowing' from Handel's Susanna. "Da tempeste il legno infranto" from Handel's Giulio Cesare has Cleoparta rejoicing at her deliverance - Joyce at her most triumphant.

Then to the 20th Century for an orchestration of Arvo Part's Da pacem, Domine.the remarkable 'Augelleti, che cantate' from his Rinaldo where one of the 2nd violins (Anna Fusek) took up the sopranino recorder to be birdsong. Apparently during performances in 1711 real sparrows were released into the theatre each night during the aria to enhance the effect! Then Jommelli's 'Par che di giubilo' - a wonderful celebration which the did again, in part, as an encore.

Finally, after a moving speech from Joyce, she gave us a song of hope: Morgen! by Richard Strauss. What an evening!

I had a filthy cold so didn't go backstage but sent a bottle of champagne and our best wishes.

Saturday, November 19, 2016

Remain - or "I knew a young man"

Although I voted for Remain and campaigned quite hard for the result, the decision is made. I'm very encouraged that we have Theresa May and PM and confident she will make the best job possible. But please forgive this whimsy...


I knew a young man who was thoroughly vex-ed
That people in England had voted for Brexit
He took a position in the USA
The voters for Brexit had driven him away
Perhaps he will stay?

This young man I knew got a terrible hump
When American voters elected the Trump
He said “from this country I’ll get away far”
And he took a position in Austria
He left his home country because he was vex-ed
That people in England had voted for Brexit
The voters for Brexit had driven him away
Perhaps he will stay?

This young man I knew said “I’ve gotta be off – for
The Austrian voters have voted in Hofer
These ignorant voters have led me a dance
I’ll take a position in sensible France"
He’d left the US in a terrible hump
When American voters elected the Trump
He left his home country because he was vex-ed
That people in England had voted for Brexit
The voters for Brexit had driven him away
Perhaps he will stay?

This young man I knew said “They’ve done it again
The French have gone mad and elected Le Pen!
I came here from Austria, whence I was off – for
The Austrian voters had voted in Hofer
I’d left the US in a terrible hump
When American voters elected the Trump
I left my home country because I was vex-ed
That people in England had voted for Brexit
These clodhopping voters just leave me one course…"

He’s back?
Of course!

This is an old Canadian animation with the incomparable Burl Ives singing the original.

PS Fascinatingly, Burl Ives played in Irvin Berlin's This is the Army whose movie version starred Ronald Reagan

Wednesday, November 16, 2016

Kiss Me at the Hampstead Theatre

Claire Lams and Ben Lloyd-Hughes take bows
Last night to Kiss Me at the Hampstead Theatre. This is a remarkable and moving new play by Richard Bean - most famous for the smash-hit One Man Two Governors.

It's a sparse and searing 2-hander where, in the 1920s, "Stephanie" has signed up for a service operated by a radical Doctor (based on Dr Helena Wright though given a different name here) who (in the play) operates a service whereby women who want a baby have a visit from a gentleman caller (Dennis). The scenario is based on a Spectator article which claims that Dr Wright did this with "Derek" who was the son of a rubber planter in Ceylon.

It is a beautifully crafted piece, and excellently played by Claire Lams and Ben Lloyd-Hughes. In fact the play was written by Richard Bean for Claire who had played Pauline Clench in One Man Two Governors. Ben turns out to have been at St Paul's School - his character was at Charterhouse.

It's well worth catching the play if you can. It should certainly transfer at some stage. And look out for Claire and Ben.



Sunday, November 13, 2016

Gerontius + "nobody knows anything"

To Ely Cathedral last night to hear our English Granddaughter sing in The Dream of Gerontius.  I don't think I have been to Ely since I left Cambridge 40 years ago, and the cathedral is certainly extraordinary. The view of the "lantern" of the cathedral in the evening mist was amazing, but didn't photograph at all well.

The Gerontius was part of the Cambridge Music Festival. The soloists were Allan Clayton (Gerontius), Allison Cook (Angel), and Duncan Rock (Priest and Angel of the Agony) who were very fine. The Britten Sinfonia was the orchestra, augmented by a good number of casuals, and the chorus was the combined choirs of Jesus, Clare, Gonville & Caius and Selwyn colleges, Cambridge University Chamber Choir, Ely Cathedral Girls’ Choir and St Catherine’s College Girls’ Choir, conducted by Mark Williams.

It's a wonderful piece I know and love greatly, though I've only sung in it once: when I was at school - I think it was 46 years ago. It must be the greatest piece of large-scale choral music written in the UK for the last 200 years. However I didn't know until I read the fascinating programme notes (I can't see who the author is) that the premiere in 1900 was a complete debacle. This was partly because Elgar was late in producing the proofs for the choir and orchestra the Chorus Master died and his predecessor had to come out of retirement, and the conductor, Hans Richter, hadn't mastered the score. "the critics railed against not only the appalling number of glaring mistakes but also the complete lack of expression."  Indeed it seems to have turned Elgar against God, and towards the end of his life he scandalised a staunchly catholic friend by saying he was "taking all the 'nots' from the Commandments and putting them into the Creed."

This seems to be yet another example of the dictum of the last Robert Altmann that, when it comes to what artistic works will succeed (he was talking about film but I think it applies more widely) "nobody knows anything."

Which brings me to Trump.  I don't want to blog too much about this for obvious reasons. President-Elect Trump certainly seems to be taking a much more measured and moderate tone than Candidate Trump. We have to pray that he picks wise advisers and that wise counsels prevail. But one thing really sticks out. The only thing we knew about Clinton vs Trump was that Clinton had vastly greater political experience than Trump, and that her team was full of seasoned and experienced advisers and pollsters who really understood the technical aspects of targeting for a (US) General Election: where to focus your resources to get the most "bang" (Electoral College votes) for your "buck". Yet in the end Trump got 6.47 EC Votes per % popular vote and Clinton only got 4.85, so Trump was 33% more efficient than Clinton. By contrast Obama in 2012 got 6.50 vs Romney's 4.36 (so 49% more efficient).  It seems that, when it came to Clinton's "experts", nobody knew anything either.

Sunday, November 06, 2016

Avi Loeb on diversity of hypotheses, fine tuning and inflation + a step towards testability of maxHELP?

Epicycles - Courtesy Wikipedia
An excellent Comment piece in Nature called Good data are not enough by Prof Avi Loeb at Harvard catches my eye.  He points out that prevailing world views can by highly limiting of scientific progress.
"The astronomy division of the US National Science Foundation, for example, devotes most of its funds to major facilities and large surveys, which are performed by big teams to collect better data within mainstream paradigms. Fields from particle physics to genomics do the same.
The consequences of a closed scientific culture are wasted resources and misguided ‘progress’ — witness the dead end that was Soviet evolutionary biology. To truly move forward, free thought must be encouraged outside the mainstream. Multiple interpretations of existing data and alternative motivations for collecting new data must be supported."
He compares modern cosmology to the theory of Epicycles. He is particularly critical of the deployment of anthropic reasoning with the multiverse theory, deploying 2 objections:
  1. He has a 2016 paper suggesting that "life is 1,000 times more likely to exist 10 trillion years from now around stars that weigh one-tenth the mass of the Sun. This means that terrestrial life might be premature and not the most likely form of life, even in our own Universe." - see also his book chapter here which has several very interesting discussions eg on the implications of slightly fatter "tails" in the assumed gaussian distributions of primadorial fluctuations on the emergence of the earliest forms of life (p2-3)
  2. "The anthropic argument... suppresses much-needed needed efforts to understand dark energy through an alternative theory that unifies quantum mechanics and gravity."
Big problems for Inflation - Table 1 from Ijjas, Steinhardt
and Loeb "Inflationary Schism after Planck2013
He says "The fact that we have not yet converged on such a theory is indicated by paradoxes in other areas of physics. For example, information contained in, say, an encyclopaedia is lost if it is swallowed by a black hole that ultimately evaporates into heat known as Hawking radiation. This contradicts a basic premise of quantum mechanics that information is preserved, and is known as the ‘information paradox’. In addition, currently viable models of cosmic inflation require fine tuning of the conditions of the Universe before and during inflation." (He cites a terrific paper co-authored by Anna Ijjas who seems truly brilliant - I wonder if she knows Corina?)

He rightly advocates that funding agencies should promote the analysis of data for serendipitous purposes beyond major programmes and the main-stream dogma. The need for a change in course is even more timely now. Empirical constraints on expected forms of dark matter (such as weakly interacting massive particles or supersymmetric partners to known particles) are getting tighter, and the hope of identifying testable consequences of string theory is receding. At a minimum, when funding is tight, a research frontier should maintain at least two ways of interpreting data so that new experiments will aim to select the correct one. This should apply to alternatives of inflation when dealing with new cosmological data, and to alternatives of cold dark matter when discrepancies are observed in the properties of dark-matter-dominated galaxies

This is of course one aspect of the herding problem and relates somewhat to my Regulators Dilemma paper. The "optimum" for each individual grant application may be to stay within the mainstream paradigm - not least because there can be considerable academic bitchiness when it comes to refereeing application that have "heretical" ideas - but this is not necessary optimal for advancing knowledge as a whole.

Fig 4A from Loeb et al. Probability distribution for the
emergence of  life within a fixed comoving volume
 of the Universe as a function of  cosmic time. They
show the probability per log time, tdP/dt for
different choices of the minimum stellar mass,
equally spaced in log m between 0.08 MSun and 3 MSun. . 
BTW his fascinating paper cited "Relative Likelihood for Life as a Function of Cosmic Time" has this chart showing that (based on some fairly standard simplifying assumptions) the time with maximal probability per unit time for the emergence of life is roughly now (ie about 2 * 10^10 years from Big Bang) if the minimum stellar mass that can lead to life is about 0.9 MSun, but as this minimum decreases the peak time increases by roughly a decimal order of magnitude for each halving of the mass.

It immediately occurred to me that two reasons why the minimum stellar mass might be constrained to something close to MSun are the need to have a gas giant planet and a significant moon, since without the moon we would have had a many much larger asteroid impacts and life would not have had time to reach substantial levels of intelligence. These points are touched on at the end of their paper (p10) though quite understandably they don't model them because it's extremely complicated to do so.

They conclude "The probability distribution dP(t)/dlnt is of particular importance for studies attempting to gauge the level of fine-tuning required for the cosmological or fundamental physics parameters that would allow life to emerge in our Universe." with which of course I agree. It seems to me that this is a step towards being able to address at least some of the partial derivatives in the MaxHELP hypothesis, although clearly a lot more work needs to be done.

Tuesday, November 01, 2016

On the probable authorship of Hebrews - by Priscilla

Icon of Aquilla and Priscilla
I'm pleased to see that the second most visited post of all time in this blog is currently "Hebrews was almost certainly written by a woman, probably Priscilla" (Feb 2014) though I would be even happier if it were No 1. I added an update in 2015 but perhaps it's helpful to bring everything together here, and to respond to some points that I've read.

I don’t of course claim that the attribution to Priscilla is certain - Origen is clearly right to say “But as to who wrote the epistle, only God knows the truth”. The full quote is quite interesting: "But as for myself, if I were to state my own opinion, I should say that the thoughts are the apostle's but that the style and composition belong to one who called to mind the apostle's teachings and, as it were, made short notes of what his master said. If any church, therefore, holds this epistle as Paul's, let it be commended for this also. For not without reason have the men of old time handed it down as Paul's. But who wrote the epistle, in truth, God knows."  Eusebius, Ecc Hist, Bk 6, Ch 25.13-14 quoting Origen

But what I think we can say is that Hebrews was written by:
  1. A very wise and learned early Christian teacher
  2. Who was very close to Paul but not Paul himself
  3. Who had strong connections with the Jewish community in Rome
  4. Who was confident to reason from the scriptures but never appeals to personal authority
  5. Who for some reason the Church found it wise not to attribute authorship to widely - despite the fact that it must have been known to the first recipients.
It's fair to point out that Clement of Alexandria clearly thinks it is by Paul (See Stomata Bk 4 Ch 21, "Description of a Perfect Woman") and Eusebius quotes Clement as saying "the Epistle to the Hebrews is the work of Paul, and that it was written to the Hebrews in the Hebrew language; but that Luke translated it carefully and published it for the Greeks, and hence the same style of expression is found in this epistle and in the Acts" (Ecc Hist Bk 5 14.1-7). But it's not really in the same style as Acts.  Severian of Gabala (4th C) says "Paul was hated by the Jews on the grounds that he was teaching apostasy from the law...[...]. Therefore, writing something useful to the Hebrews, he does not append his name, so that they might not lose any advantage they could have derived from the letter because of their hatred against him. And he writes to them in the tongue of the Hebrews, which was also translated by one of his disciples"  Fragments on the Epistle to the Hebrews (prologue) but he also thought the Earth was Flat and was an enemy of St John Crysostom.

Of the people we know about only Priscilla and Aqullia fit (1-4) Luther suggested Apollos but he was from Alexandria not Rome. Tertullian suggested Barnabas but he was from Cyprus. Others have suggested Timothy but he was from Lystra. Only Priscilla fits (5). It has been suggested that Apollos, Barnabas or Timothy might have had their names suppressed because they were not apostles, but nor were Mark and Luke. Furthermore there is a very early extra-canonical Epistle of Barnabas so there was certainly no reluctance to attribute works to such figures.

We get some idea of how highly Priscilla was regarded by Luke from the fact that whenever he mentions "Priscilla and Aquilla" it in that order, as does Paul when he is sending greetings to them - interestingly when he is sending greetings from them he uses the conventional order of Aquilla and Priscilla (c/f “Andronicus and Junia” in Romans 16) and several scribes "corrected" the order on the occasions when Luke refers to them. Of course when Luke refers to Paul meeting them he says Paul first met Aquilla and then Priscilla but that is chronological.

There is also the very interesting detail that Luke refers to Priscilla and Aquilla taking Apollos aside and expounding the ways of God more accurately he uses the word ἐξέθεντο (exethento) which comes from ἐκτίθημι (extithEmi) which means expose of explain/expound. This occurs only 4 times in the NT and always in Acts:

  • (7:21) when it refers to Moses being exposed
  • (11:4) when Peter is explaining
  • (18:26) when Priscilla and Aquilla are instructing Apollos
  • (28:23) when Paul is expounding the scriptures to the Jews in Rome.
It's also at least somewhat suggestive that that author uses language about newborn babes and milk. This was a trope of Paul's as well of course, but makes it marginally more likely to be a woman.

Finally I observe that (s)he concludes "I want you to know that our brother Timothy has been released. If he arrives soon, I will come with him to see you." It would be pretty well impossible for woman to travel to Rome by herself, but in company of her brother it would be feasible.

None of this is certain, but cumulatively highly suggestive.