تدريب Shadowing: "What is life"-lecture: Denis Noble - تعلم التحدث بالإنجليزية عبر الفيديو

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432 جمل

إذا كانت الجمل قصيرة أو طويلة جدًا، انقر على Edit لتعديلها.

Well, thank you very much, Peter, for that introduction.

حسنًا، شكرًا جزيلًا لك يا بيتر على هذه المقدمة.

And let me say what a huge pleasure it is to come back to the Karolinska Institute.

واسمحوا لي أن أقول إن من دواعي سروري البالغ العودة إلى معهد كارولينسكا.

The last time I was here I think was about three years ago for a meeting on systems, biology and cancer.

أعتقد أن آخر مرة كنت هنا كانت قبل حوالي ثلاث سنوات لحضور اجتماع حول الأنظمة والبيولوجيا والسرطان.

You know, I'm always asked to talk about subjects about which I have no right to claim any knowledge whatsoever.

أنت تعلم، يُطلب مني دائمًا التحدث عن مواضيع ليس لدي أي حق في الادعاء بامتلاك أي معرفة بها على الإطلاق.

Interestingly enough at that meeting I think quite a lot of other people thought exactly the same.

ومن المثير للاهتمام، في ذلك الاجتماع، أعتقد أن عددًا كبيرًا من الأشخاص الآخرين كانوا يفكرون بنفس الطريقة تمامًا.

We had a very interesting meeting.

لقد عقدنا اجتماعًا مثيرًا للاهتمام للغاية.

What I'm going to do today is to address Schrodinger's question,

ما سأقوم به اليوم هو معالجة سؤال شرودنغر،

which of course was the question, what is life?

وهذا بالطبع كان السؤال، ما هي الحياة؟

those

تلك

lectures were given in 1943 at the Dublin Institute of Advanced Studies

أُلقيت المحاضرات في عام 1943 في معهد دبلن للدراسات المتقدمة.

and they were of course the lectures in

وكانت بالطبع المحاضرات في

which Schrodinger first made his famous prediction that the genetic material would be what he called a non-periodic crystal

حيث قدم شرودنغر لأول مرة تنبؤه الشهير بأن المادة الوراثية ستكون ما أسماه بلورة غير دورية.

I still, and I think many others do too, still think that's an extremely good description,

ما زلتُ أعتقد، وأظن أن الكثيرين يشاركونني هذا الرأي، أن هذا الوصف ممتاز للغاية.

of course, of what was eventually found in the DNA.

بالطبع، عما تم العثور عليه في النهاية في الحمض النووي.

He also, though, drew a comparison between, on the one hand, physics, and on the other hand, biology.

ومع ذلك، قام أيضاً برسم مقارنة بين الفيزياء من جهة، وعلم الأحياء من جهة أخرى.

And his idea in that book was that they were really very different.

وكانت فكرته في ذلك الكتاب هي أنهم كانوا مختلفين تمامًا في الحقيقة.

because physics deals with order emerging from disorder.

لأن الفيزياء تتعامل مع النظام الذي ينشأ من الفوضى.

You have the disorder of the random movements of the molecules of a gas, but you also have the order of the gas laws and of thermodynamics.

لديك فوضى الحركات العشوائية لجزيئات الغاز، ولكن لديك أيضًا ترتيب قوانين الغازات والديناميكا الحرارية.

By contrast, he argued, biology is about order from order, because where is the order down at the low level,

في المقابل، كما يجادل، فإن علم الأحياء يدور حول نشوء النظام من النظام، فأين هو النظام على المستوى الأدنى،

it is in that aperiodic crystal.

إنه في ذلك البلور غير الدوري.

And I think his idea gave rise, of course, later on, or helped to give rise,

وأعتقد أن فكرته أفضت بالطبع في وقت لاحق، أو ساهمت في إحداث ذلك.

to the interpretations that were made of the early results in molecular biology of DNA

إلى التفسيرات التي تم التوصل إليها حول النتائج المبكرة في البيولوجيا الجزيئية للحمض النووي الريبي منقوص الأكسجين (DNA)

when the double helix was discovered and when people began to work out what the coding was between DNA and proteins,

عندما تم اكتشاف الحلزون المزدوج، وعندما بدأ الناس في تحديد طبيعة الترميز بين الحمض النووي والبروتينات،

which was to lead to the idea that there was, in a sense, in the DNA, a determinant program.

الأمر الذي أدى إلى ظهور الفكرة القائلة بأن هناك، بمعنى ما، برنامجًا محددًا داخل الحمض النووي.

So unlike physics, you would go from particular events in molecules to particular events in the global property of the organism,

لذا، على عكس الفيزياء، ستنتقل من أحداث معينة في الجزيئات إلى أحداث معينة في الخاصية الكلية للكائن الحي.

that is, the phenotype.

أي النمط الظاهري.

Now, of course, it's a hard thing to say that perhaps Scherzinger was wrong, but I think he was.

الآن، بالطبع، من الصعب القول بأن شيرزينغر ربما كان مخطئًا، لكنني أعتقد أنه كان كذلك.

And I would like to substitute that, the view that I and many others now express about biology,

وأود أن أستبدل ذلك، الرأي الذي أعبر عنه أنا والكثيرون الآخرون الآن حول علم الأحياء،

and it's certainly expressed in the book The Music of Life,

وقد تجلّى ذلك بالتأكيد في كتاب "موسيقى الحياة"،

which is that indeed physics deals with order from disorder,

وهي أن الفيزياء في الحقيقة تتعامل مع نشوء النظام من الفوضى.

but biology also must most of the time do the same

لكن علم الأحياء أيضاً يجب أن يفعل الشيء نفسه في معظم الأحيان.

because what do we find down at the level of the individual gene expressions?

لأننا ماذا نجد عند مستوى التعبيرات الجينية الفردية؟

We find stochasticity.

نجد العشوائية.

If I take the gene expression levels in the ventricular cells of one region of the heart

إذا أخذت مستويات التعبير الجيني في الخلايا البطينية لمنطقة واحدة من القلب

and compare them to the expression levels of those genes in an adjacent region of the heart,

ومقارنتها بمستويات التعبير الجيني لتلك الجينات في منطقة مجاورة من القلب،

I will find that they vary.

سأجد أنهم يختلفون.

Now, of course, they vary to some extent according to the anatomy of the heart, and that is both well known and is also important in the functioning of the heart.

الآن، بالطبع، تختلف هذه الخصائص إلى حد ما بناءً على تشريح القلب، وهذا أمر معروف جيدًا كما أنه مهم أيضًا في أداء وظائف القلب.

but they also vary stochastically, even between neighboring cells.

ولكنها تختلف أيضًا بشكل عشوائي، حتى بين الخلايا المجاورة.

Stochasticity, therefore, has to be a feature of biology as well as order.

لذلك، يجب أن تكون العشوائية سمة من سمات البيولوجيا تمامًا مثل النظام.

Of course, we have a little bit of a dilemma, which I'll refer to a little bit later on,

بالطبع، نواجه معضلة صغيرة، سأشير إليها لاحقًا قليلاً.

which is that we know well that there are certain changes that occur down at the molecular level,

وهو أننا نعلم جيدًا أن هناك تغييرات معينة تحدث على المستوى الجزيئي،

particular mutations which will produce or be the cause of a major change in function at the level of the phenotype.

طفرات معينة من شأنها أن تحدث أو تكون السبب في حدوث تغيير كبير في الوظيفة على مستوى النمط الظاهري.

But what has emerged in the research that's been done over the last decades is that those cases are actually quite rare.

ولكن ما توصلت إليه الأبحاث التي أجريت على مدى العقود الماضية هو أن هذه الحالات نادرة إلى حد كبير في الواقع.

I find that in my work on the heart.

أجد ذلك في عملي المتعلق بالقلب.

There are certain modifications, certain mutations of particular ion channels that can produce a catastrophic situation predisposing towards arrhythmia.

هناك تعديلات معينة، وطفرات معينة في قنوات أيونية محددة، يمكن أن تؤدي إلى حالة خطيرة تؤهب لحدوث اضطراب نظم القلب.

But most of the time, the heart works perfectly well, just as the pancreas does, just as the brain does,

لكن في معظم الأحيان، يعمل القلب بشكل مثالي تمامًا، تمامًا كما يعمل البنكرياس، تمامًا كما يعمل الدماغ.

despite all the variations that occur at the lower levels.

رغم كل الاختلافات التي تحدث في المستويات الدنيا.

So why should a physiologist be concerned about the question, what is life?

إذن، لماذا يجب على عالم الفسيولوجيا أن يهتم بالسؤال: ما هي الحياة؟

First of all, to be concerned with that, you have got to be concerned with the central theory of biology

أولاً وقبل كل شيء، لكي تهتم بذلك، يجب أن تكون مهتماً بالنظرية المركزية في علم الأحياء.

or the central story of biology because I think that what we call evolutionary theory is actually a story,

أو القصة المركزية لعلم الأحياء، لأنني أعتقد أن ما نسميه النظرية التطورية هو في الحقيقة مجرد قصة.

it's a history, which of course is the central idea

إنها تاريخ، وهي بالطبع الفكرة المحورية.

without which any form of discussion of the question of what is life can't make sense.

بدون ذلك، لا يمكن لأي شكل من أشكال النقاش حول مسألة ما هي الحياة أن يكون له معنى.

moreover the dominant theory of evolution over most of the 20th century and into this century was of course the modern synthesis

علاوة على ذلك، كانت النظرية السائدة للتطور خلال معظم القرن العشرين وحتى هذا القرن هي بالطبع التركيب الحديث.

sometimes called neo-Darwinism and

يُسمى أحيانًا الداروينية الجديدة و

that of course was a gene-centered theory of evolution with its determinate idea of there being a program

كانت تلك بالطبع نظرية للتطور تتمركز حول الجينات، مع فكرتها الحتمية القائلة بوجود برنامج محدد.

that leads to the development of the organism

يؤدي ذلك إلى تطور الكائن الحي

but in fact organisms are extremely good at immunizing themselves from

لكن في الحقيقة الكائنات الحية ممتازة للغاية في تحصين نفسها ضد

variations in their genomes we're going to look at a few examples of

التباينات في جينوماتها، وسنلقي نظرة على بعض الأمثلة على ذلك.

that in just a moment and some of the examples are discussed in

سيتم مناقشة ذلك في لحظة، كما سيتم تناول بعض الأمثلة ضمن هذا السياق.

that article in the Royal Society's new journal Interface Focus

تلك المقالة في المجلة الجديدة للجمعية الملكية Interface Focus

let's just give a little bit of background from my own work

لنقدم قليلاً من السياق من عملي الخاص.

as the introducer said I was responsible for working on some

كما قال المقدم، كنت مسؤولاً عن العمل على بعض منها.

of the early discoveries of ion channels in the heart and

من الاكتشافات المبكرة لقنوات الأيونات في القلب و

that led me to put this model of rhythm in the heart together in 1960.

وذلك دفعني إلى وضع هذا النموذج لإيقاع القلب في عام 1960.

Here's the electrical potential showing rhythm that emerges as a cell property not a molecular property from the interactions

إليكم الجهد الكهربائي الذي يُظهر الإيقاع الناشئ كخاصية خلوية وليس خاصية جزيئية ناتجة عن التفاعلات.

between the various ion channels.

بين القنوات الأيونية المختلفة.

In those days, we actually thought there weren't many more channels than there are in nerve.

في تلك الأيام، كنا نعتقد فعلياً أن عدد القنوات لا يزيد كثيراً عما هو موجود في الخلية العصبية.

A sodium channel, two potassium channels, and a background leak.

قناة صوديوم، وقناتان بوتاسيوم، وتسرب خلفي.

We now know there are many more.

نحن نعلم الآن أن هناك الكثير غيرها.

And in fact, later on, if we go now through to about 25 years later,

وفي الواقع، في وقت لاحق، إذا انتقلنا الآن إلى ما يقرب من 25 عامًا لاحقًا،

in work that I did with Dario Di Francesco, we found there were many, many more potassium channels than we thought initially.

في العمل الذي قمتُ به مع داريو دي فرانشيسكو، توصلنا إلى أن عدد قنوات البوتاسيوم كان أكبر بكثير مما كنا نعتقد في البداية.

And of course, by that time, Harold Reuter had made his great discoveries of calcium channels and of sodium-calcium exchange.

We were also responsible in the work with Dario Di Francesco at discovering a new non-specific cation channel,

which is responsible for this phase of the rhythm, and also for clarifying the role of the sodium-calcium exchange.

Now, that's all technical detail and I don't want to dwell on that.

What I want to do is to use that model to perform a very interesting experiment.

So what we're going to do is to use a version of

that model that was developed for the natural rhythm generator of the heart, which is the sinus node.

and I'm just plotting two of the channel properties,

a background sodium channel and the non-specific cation channel that I referred to earlier.

This one normally contributes about 80% of the depolarizing current.

It is therefore the rhythm generator, if you like.

And as you knock it down, you can notice 20%, 40% all the way to complete knockout.

You might expect a very large change in frequency.

In fact, the change in frequency is very modest, only about 10%.

And what is happening, of course, is the system is allowing this other mechanism to kick in and to keep the rhythm buffered,

as it were, from the change at the lower level.

And you can even use the physiological interpretation of what is going on to work out what is happening

because if you draw a line along those voltage traces,

you can see that the traces at this end are moving into a more negative range of electrical potential.

And it's precisely that that activates the other channel to kick in and to keep the rhythm fairly constant.

And that is a general property of cardiac rhythm.

It's a general property of other rhythm generators too, for example, of circadian rhythm.

There are backup mechanisms.

Many more examples of what you might call knockout that don't actually succeed in producing a very large phenotypic effect.

This is from some work, again fairly technical detail, but I won't dwell on the technical detail other than to say

that a targeted knockout done in experiments first and then by simulation reproducing the experiments of Ken Philipson,

targeted knockout of the sodium calcium exchange produces almost no change in overall electrical function.

Now, is this a specific property of some of Dennis Noble's work on the heart or is it general?

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I was delighted therefore when I saw this systematic study by Hillenmayer and his colleagues in yeast working

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through the 6,000 genes and producing what they called a chemical genomic portrait of yeast.

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What did they find?

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Genetic buffering is general.

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80% of the knockouts are silent under normal physiological conditions.

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That doesn't mean to say that those genes don't have a function far from it.

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They do code for a protein.

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That protein is produced.

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of course what you have to do if you want to reveal that function is to stress the organism

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for example with metabolic stress

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and then you can begin to reveal the function there are many more examples I won't dwell on

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that other than to say that if you want to understand regulators in biological systems

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which is part of an answer to the question what is life life is a regulated process

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then you don't get that most of the time from knockout experiments.

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As I said earlier on, sometimes you do.

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Biology therefore is a mix.

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Occasionally it is order from order

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but often it is also order from disorder in a sense

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just like physics though I think there are some important differences as well.

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For those who want to follow up on that question and this lovely article in bio-essays is worth reading.

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So what is going on?

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And here I want to also digress a little bit on the concept of a gene, because I think two things are going on here.

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First of all, extensive buffering of organisms against genomic change.

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that's now documented I think sufficiently well to say that it's a fairly general phenomenon

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but there's another major concept that I want to introduce

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which is that the concept of a gene has changed

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and changed in a very significant way indeed

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and it's central to understanding what is wrong with current evolutionary biology theory that is the neo-Darwinist theory.

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The way I explain this is to say that we have DNA, obviously, we have a phenotype.

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Of course, it's a bit artificial to draw complete distinctions between the two.

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As I will quote with Barbara McClintock later on, the DNA is also, after all, a part of the phenotype.

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But I think we all know what we're saying here.

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Here's the genetic material in the sense that the molecular biologists would use that term today.

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Here's the interaction with the environment.

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Here is, if you like, the complete phenotype.

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And what we know is, of course, that all of these interact in bidirectional ways.

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That's also important with the biological networks, the signaling pathways, the filters, the conditioners, and so on,

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which actually generate the function.

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If we want an answer to the question, therefore, what is life?

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it's inside here.

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If I take the DNA out of a cell, if I could do just that and put it into a Petri dish,

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I could keep it for 10,000 years and it would do nothing.

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It's the rest of the system of course that tells the genome when it wants to make particular proteins.

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It's the rest of the system that gives the dynamism.

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Now I come to the point about the definition of genes When Johansson in 1909 first introduced the word gene,

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of course following in the footsteps of Mendel, who didn't use that word but he had exactly the concept,

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what he actually meant was a discrete inheritable phenotype.

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What we now mean of course by a gene is a particular stretch of DNA.

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Now the important point I want to make is that not only are those two definitions not the same,

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that's obvious from the fact that this only includes this part of the diagram, whereas this includes the whole diagram,

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they are conceptually different too.

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Because Johansson's definition is all-inclusive.

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He actually says that in his article.

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He says, it's a something.

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it doesn't really matter whether it was DNA or not of course they did not know about DNA at that time

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incidentally Richard Dawkins uses exactly the same definition most of the time as Johansson

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he also says it is as it were a general concept it is if you like a catch-all concept

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but of course the problem with catch-all concepts that say and include everything is that they can't be tested

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it is a necessary truth

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a conceptually necessary truth that a gene defined in this way as the cause of a particular phenotype characteristic is just that,

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it is the cause you don't ask the question, is it a cause it is so by definition now, the situation of course with the definition of a gene

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that is done in terms of a DNA sequence is that precisely that question can be asked

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There is an empirical question to be settled, which is, does that particular piece of DNA have a big effect on the phenotype?

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You can perform that experiment with the kinds of knockout experiments that I've already described.

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So the difference is fundamental.

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Now, where is the deep problem in the neo-Darwinist thesis,

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particularly as expressed by people like Richard Dawkins in popularizing it.

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The problem lies here, that if you want to distinguish clearly and unambiguously between the replicator,

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which is of course the DNA, and the vehicle, which of course is the organism that carries the DNA,

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then you must use this definition of the gene.

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If you use this one, the one that Johansson first introduced then it doesn't make sense to draw a distinction between the replicator

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and the vehicle because this definition includes much more than the DNA and I don't think that point has been properly appreciated.

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In relation to knockout experiments of course to represent the fact

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that most knockouts and mutations are buffered

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but knocking out just one gene may not get through to the phenotype

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because it gets absorbed as I showed in those computations

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but also in the experiments on which they're based a bit earlier

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but two of course may be enough to get through

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or you may need to do three who knows that's a matter open to empirical investigation

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so I want to turn now to a few other aspects in which the answer to the question what is life

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taking particularly evolutionary biology as absolutely central to that question and to answering it properly

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poses today some very big problems

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but what we need to do is to first go through a very brief history of evolutionary biology

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And I start by going back just over 200 years to Jean-Baptiste Lamarck, who published the Zoologie Philosophique,

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his great work in 1809, exactly 50 years incidentally before Darwin's Origin of Species.

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Jean-Baptiste Lamarck actually invented the term biology he was one of

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those who first as it were therefore defined our subject as a separate subject from other natural science subjects

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but he also did something else which is very famous he certainly espoused and popularized and used

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the theory that there was inheritance of acquired characteristics.

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And many of you will know that, of course, it is a clear feature of the modern synthesis

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or of neo-Darwinism that that process is excluded for reasons I'll come on to a little bit later.

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Darwin, of course, published his Origin of Species in 1859, proposed, of course, the theory of natural selection.

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of course neither he nor Lamarck or anybody else at

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that time had a theory of genetics and heredity in

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that sense they didn't know of Mendel's work until it was rediscovered later now an important point to make

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Darwin also assumed the presence

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and function of the inheritance of acquired characteristics it's present in the origin of species in 12 different places unambiguous,

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all documented incidentally by Ernst Mayer many years ago in his great book Biological Thought in 1982

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further Charles Darwin in I think it's the fourth edition of

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The Origin of Species specifically praises Lamarck as this great biologist who championed the idea

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that there was transformation of species originating from a common ancestor

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Darwin was not a neo-Darwinist that's a very important message we'll come on to the significance of

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that a bit later on so what gave rise to neo-Darwinism?

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what gave rise to neo-Darwinism was of course the work of Weissman who introduced the idea

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which we now call the Weissman barrier that is the specific exclusion of the inheritance of acquired characteristics.

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And the idea was, of course, that the inherited material, wherever it was, and of course he didn't know where it was at that time,

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is immune from the rest of the system.

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The rest of the system, however it develops in the lifetime of an individual, cannot influence the genome, as we would now call it.

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And of course that later became encapsulated in Francis Crick's idea of the central dogma of molecular biology.

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let me just also make a brief explanation at this point in the paper in

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which he defines the central dogma in 1970

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Crick was actually very careful he referred to the fact

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that of course DNA sequences code for protein amino acid sequences

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but amino acid sequences do not code for DNA sequences In that sense, there is a unidirectional flow of information.

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But he did not make the mistake, which was made later by Dawkins and many others,

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of assuming that that meant that no information passes in the other direction.

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And of course, if you ask the question, what makes your heart cell different from your pancreatic cell, different from your liver cell,

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It is precisely the passage of information from the system onto the genome

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to tell the genome to make a completely different pattern of gene expression in a heart cell, a pancreatic cell, a liver cell, a bone cell, and so on.

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So we know already, even just from that observation alone, that there must be information passing the other way.

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We'll come on to the significance of that also a little bit later.

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all of this was put together by Julian Huxley, Fisher, Haldane, Sewell Wright and others

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to form what was called the modern synthesis and it's the modern synthesis

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that is often also called neo-Dawinism now let's look at the popularisation of it in the selfish gene

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I should say that I've interacted with Richard Dawkins on these issues now, ever since he published The Selfish Gene.

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In fact, I've interacted with Richard Dawkins even before he published The Selfish Gene.

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What is it?

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It is, of course, a gene-centered view of natural selection.

228

That is what the modern synthesis is.

229

Accumulation of random mutations.

230

By random here is meant not related to function.

231

Random compared to function then followed by selection.

232

That means, incidentally, that physiological science has nothing to say about the variation in genetic material.

233

Very important, because we'll see that that view is actually wrong.

234

Then the impossibility of the inheritance of acquired characteristics, a view, of course, inherited initially from Weissman and the Weissman barrier,

235

and then later on buttressed and supported by the more popular interpretations of the central dogma of molecular biology.

236

Now, I say that's miscalled Lamarckism because actually,

237

if you look at the history of the idea of the acquisition of characteristics that can be inherited,

238

that idea was not Lamarck's invention.

239

Many others before Lamarck had said the same thing.

240

Lamarck, like Darwin himself, just simply assumed it.

241

They didn't invent it.

242

Neither of them did.

243

The other point that I've emphasized earlier on is the distinction between the replicator genes and the vehicle, the phenotype.

244

And notice what I said earlier on, I'll just repeat it now.

245

The only way in which that distinction can be clear is if the gene is defined as DNA, as what we would now today call the replicator.

246

So the vehicle is separate from the replicator.

247

If, as Richard also does,

248

you see, you define gene to be the original definition by Johansson and implied, of course, by Mendel, though he didn't use that word,

249

then you cannot make that distinction.

250

There's no way of having it both ways.

251

You either define genes in terms of the DNA replicator, and then you have a clear distinction between replicator and vehicle,

252

or you define genes in the way that Johansson originally did in terms of phenotype

253

and then you can't have such a clear distinction.

254

And as I said earlier, these ideas were buttressed by what I would call misinterpretations because I don't think they were intended by Francis Crick,

255

misinterpretations, the central dogma of molecular biology.

256

Now, the main point of my talk today on the question, what is life, is that to answer that question we have to realize

257

that all of these rules have now been broken in ways that I'll just go through.

258

First of all, are mutations random?

259

The answer is no, and by a very long way.

260

In his book recently published, the book by Jim Shapiro in Chicago, Evolution of You from the 21st Century,

261

writes it's difficult if not impossible to find a genome change operator that is truly random

262

in its action within the DNA of the cell where it works.

263

But I want to go a bit further than Jim does.

264

Jim documents with very, very many examples from the empirical literature,

265

scientific literature, the non-random nature in the sense that there are hot spots in the genome,

266

there are great big reorganizations of the genome whole domains as we'll see in a moment

267

that have shifted around in the course of evolution

268

but I think he fails to make an important distinction

269

which has to be added to this which is the big question

270

the big question that should worry the neo-darwinists is some of

271

that non-randomness functional in other words can the functional state of the organism influence the DNA

272

and we'll see in a moment that it can

273

he also makes the point which I want to emphasize that

274

if you look at what emerged from the first sequencing of

275

the human genome you find a very interesting fact for two major classes of proteins transcription factors

276

and chromatin binding proteins the evidence is

277

that they could not have evolved one mutation at a time in a gradual way as the

278

is in accord with the spirit at least of the modern synthesis or neo-Darwinism.

279

This diagram is a little bit technical so I'll just go through it very, very quickly.

280

All you need to know is

281

that these are representations of particular proteins in different organisms all

282

the way from yeast through worm through to the human and the stars that I'm going to put up now

283

are whole domains, that is long stretches of DNA that have clearly moved around in the course of evolution as whole domains,

284

not gradual accumulation of mutations, point mutations or small mutations.

285

And as you can see, there are many of them.

286

And the same is true for the other class of proteins that they studied.

287

So proteins, not all of them anyway, did not evolve just via gradual mutation.

288

Something is enabling the system to reorganize the genome.

289

So the question I'm going to ask now is what happens in this view to selfish genes.

290

And again, I come now to a deep conceptual error.

291

the problem with the selfish gene is very simple

292

the book is written beautifully

293

anybody who's read Richard Dawkins books must admire the skill

294

that he has in expressing the view that he expresses and the way in which he uses language

295

they're brilliant books but when he was asked the question is selfish,

296

in the title of the selfish gene, metaphor by the philosopher Mary Mitchley.

297

He wrote back, that was no metaphor.

298

I believe it is the literal truth.

299

But then he went on to write this very significant qualification.

300

Provided certain key words are defined in the particular ways favoured by biologists

301

and if you've been thinking about the question what is a metaphor?

302

A metaphor is precisely taking a word from one context and changing it and making it perform a new function.

303

It is a way, if you like, of redefining a word.

304

Clearly, in writing this, he didn't understand the question that Mary Midgley was putting to him, was it a metaphor?

305

It clearly is.

306

He didn't think it was.

307

I wrote about this more recently in an article published in the Journal of Physiology just three years ago, and a quote from it is

308

that a metaphor does not cease to be a metaphor simply

309

because one defines a word to mean something other than its normal meaning.

310

It indeed is the function of metaphor to do precisely this.

311

and so at the heart of the neo-Darwinist synthesis at the heart of its popularization

312

there are a number of major conceptual mistakes

313

first of all a mistake about what is the real definition of a gene

314

and it slips between the two according to what the question is

315

and you can't do that you can't do that and be logical

316

and second because as I show in that article

317

but I don't have the time to go through all of

318

that in the lecture it's actually impossible to demonstrate any biological experiment that would distinguish the selfish gene theory from any alternative

319

and incidentally, curiously enough, Richard Dawkins agrees with that in Extended Phenotype,

320

he writes specifically I doubt whether there is any experiment to prove my case.

321

So that aspect, at least, of the neo-Darwinist approach to the question, what is life, is simply not falsifiable.

322

Now we come to the big question, and the difficult one, can acquired characteristics be inherited?

323

I discussed this a number of years ago with John Maynard Smith.

324

We were both at the Novartis Foundation Symposium.

325

He published a lovely book called Evolutionary Genetics in 1998, and he made a very interesting statement.

326

he said John Maynard Smith although he was working totally within

327

the neo-Darwinist view he was I think a great thinker and he said in that book specifically

328

you know Lamarckism is not so obviously false as it's sometimes made out let's have a look, he was absolutely right although he didn't know

329

that at the time there are many examples now those who

330

want to go to my Music of Life website will find a page devoted to what are called answers,

331

answers to very common questions on this central issue, the theory of evolution and the question, what is life?

332

And although I'm just going to give a few examples in this slide, there are many more on that page.

333

Weaver's work looking at the way in which you can mark the genome by behavior in each generation.

334

and that can work even if nothing goes down through the germline.

335

Anway and his colleagues looking at endocrine disruptors where the process does go down through the germline

336

and we think probably through inherited RNAs.

337

This paper also showing male transgenerational responses in the human.

338

Beautiful paper by Yunhua Sun and his colleagues at the Fish Institute in Wuhan in China.

339

doing cross-species cloning.

340

I'll show that in a moment in another slide.

341

And an extraordinary study by Harry Harvey and his colleagues in Cell, published around three years ago,

342

showing not only transgenerational inheritance of an acquired RNA-based response,

343

but also that it persists for a hundred generations.

344

They followed it in C elegans for a whole year.

345

the usual reply of neo-Darwinists to these examples is to say the effects die out

346

well they don't always die out

347

and then they will say well it's rare indeed it is as far as we know at the moment

348

but remember also that speciation is rare

349

it doesn't have to happen very often it hasn't happened in our lifetimes it hasn't happened in the lifetime of humans

350

in fact we've tried very hard with artificial selection of dogs, cats, fish and so on we've produced new varieties but never new species

351

so environmentally induced changes can be inherited I think the evidence for

352

that as I said is now growing very rapidly go to the answers page on the Music of Life website

353

if you want more details I said I'd say what happens in cross species clones

354

and then we come towards the end of the lecture

355

what Jung Ha Sun and his colleagues did in Wuhan was to take a carp which is this one,

356

a goldfish and proceeded to take the nucleus from a carp

357

and insert it into the fertilized

358

but then enucleated egg cell as the goldfish you should get unambiguously a carp

359

if the neo-Darwinist view is correct what you get is intermediate

360

this is the result it's one of the few examples where a cross species works in the sense

361

that you produce an adult and what it produces is an adult whose anatomy is intermediate between the two

362

you can even quantify that if you look at the total number of vertebrae in the goldfish it's about 26

363

there is up or down 1 or 2 and the carp is about 33

364

in the cross species clone you get a figure in between but it's closer marginally to that of the goldfish.

365

There are other respects also in which what they call the inheritance of cytoplasmic information is clearly occurring.

366

And I want to come now to one of the greatest thinkers about genetics and their relation to the phenotype.

367

I have a lovely picture in my office in Oxford of

368

Barbara McClintock at the age of about 81 I think receiving

369

the Nobel Prize here in precisely this lecture theatre standing exactly where I'm standing at the moment

370

and she was giving of course her Nobel Prize lecture which she received in 1983

371

She was of course the person who discovered what we sometimes call jumping genes or mobile genetic elements but she went much,

372

much further than that until she was, I'm sorry to say, prevented from publishing.

373

From 1953 onwards she no longer published on this issue until, as far as I can recall,

374

she was awarded the Nobel Prize in 1983.

375

She wrote in that lecture, in the future attention will undoubtedly be centered on the genome

376

and with greater appreciation of its significance as a highly sensitive organ of the cell.

377

The result of her work on maize was to show her just how labile the material is,

378

the genetic material is in response to environmental events.

379

And she wrote, responding to those often by restructuring the genome.

380

Here we come back to what Jim Shapiro was drawing attention to, that clearly during evolution there have been major restructurings of genomes,

381

movements of whole domains corresponding to various proteins.

382

So cytoplasmic changes can be inherited,

383

and I'll deal, I think I'll jump straight to the next slide just to give one example of how strong

384

that inheritance can be.

385

This is the article I would recommend reading if you want what I would regard now as the best example of that,

386

published by Joe Nadeau's lab at that time in Seattle in PNAS at the end of 2012.

387

They write, I won't go through the full details,

388

the heritable epigenetic changes persisted for multiple generations and were fully reversed after consecutive crosses through the alternative germline image.

389

So my main conclusion, environmentally induced changes can be inherited to the question, are they fairly rare?

390

I would give the response I gave earlier on, so is speciation. so

391

when we ask the question do we know what the precise

392

mechanisms of speciation were I think the honest answer is that we don't know

393

not yet anyway

394

now I come to my final conclusion

395

if functional changes in the adult can be inherited and therefore a target for natural selection

396

then the analysis of function is highly relevant to evolution and of course highly relevant to defining the question

397

or an answer to the question, what is life?

398

Because as I said earlier on, this area of biology is central to understanding the answer to that question.

399

I think what I want to do is to leave time for discussion.

400

I'll just jump the remaining slides.

401

They just simply summarize what I've already just said.

402

And the synthesis that I would propose is shown here that we have to recognize that selection is multi-level,

403

that acquired characteristics can be inherited to quote Barbara McClintock the

404

genome is an organ of the cell not its dictator and that genomes are not isolated from the organism and environment

405

those who want to listen to another version of this lecture it's on the Music of Life website and on YouTube

406

and the article there published just last year

407

in experimental physiology also gives chapter and verse on almost everything that I've presented today.

408

And I finish with this lovely picture that I used right at the beginning.

409

Some of you will recognise the left-hand picture as Conrad Waddington's beautiful picture from the strategy of the genes

410

in which he tried to explain the way in which there is plasticity at the developmental level in the phenotype,

411

which is representing by a landscape here,

412

as a consequence of various gene products interacting in networks that,

413

as it were, are situated between the genome level and the phenotype level.

414

I know that's a bit artificial.

415

We can argue about the exact definition of a phenotype and so on.

416

But he's got the message.

417

He's got exactly the system's approach to it.

418

What happened to Conrad Waddington, he was largely ignored, pushed to one side,

419

just as Barbara McClintock was until she received the Nobel Prize.

420

So my final question is, who pulls strings?

421

In any multi-level set of interactions in any biological organism,

422

the answer is, everything can.

423

if you take a three dimensional network just put together some knitting

424

and make a three dimensional knitting structure you pull any bit of it the whole network changes all networks do that

425

so it doesn't make sense to isolate one part and say

426

that is the cause if you have networks as part of the definition

427

and processes in those networks as part of the definition of an organism

428

then the answer to the question what is life is it lies in those processes in the networks.

429

There is no privileged level of causation.

430

And with that, thank you very much.

431

The end of the lecture.

432

Thank you.

تنزيل التطبيق

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تقييم النطق بالذكاء الاصطناعيتقييم كل جملة

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فيديو موصى به

158 جمل

المفردات وملاحظات التحدث لهذا الدرس

هذا الدرس في المحادثة بمستوى C2 مبني على الفيديو “"What is life"-lecture: Denis Noble”. يحتوي هذا الفيديو على 432 جملة و5866 كلمة للتدرب على الترديد. مدة الكلام 43:56. يتكلم المتحدث بسرعة ثابتة، نحو 134 كلمة في الدقيقة، وهي سرعة مريحة للترديد. 80% فقط من الكلمات ضمن أكثر 3,000 كلمة شيوعًا في الإنجليزية، فالمفردات صعبة نسبيًا.

أهم المفردات في هذا الفيديو

أصعب 15 كلمة في الفيديو، مع النطق والمعنى:

الكلمة	النطق	المعنى
genome اسم	/ˈd͡ʒiː.noʊm/	مَجِين, جِينُوم
phenotype اسم	/ˈfiː.nəˌtaɪp/	نَمَط ظَاهِرِيّ
organism اسم	/ˈɔɹ.ɡəˌnɪz.əm/	كَائِن حَيّ
inherit فعل	/ɪnˈhɛɹɪt/	وَرَثَ
mutation اسم	/mjuˈteɪʃən/	طَفْرَة
rhythm اسم	/ˈɹɪð.əm/	إِيقَاع
metaphor اسم	/ˈmɛt.ə.fɚ/	اِسْتِعَارَة
synthesis اسم	/ˈsɪnθəsɪs/	تَرْكِيب
inheritance اسم	/ɪnˈhɛɹɪtəns/	مِيرَاث, إرْثْ
characteristic اسم	/ˌkæɹ(ə)ktəˈɹɪstɪk/	صِفَة
incidentally ظرف	/ˌɪnsəˈdɛn(t)l̩i/	عَلَى فِكْرَة
sodium اسم	/ˈsəʊ.di.əm/	صُودِيُوم
colleague اسم	/ˈkɒliːɡ/	شَرِيك, شَرِيكَة
carp اسم	/ˈkɑɹp/	شَبُّوط
dogma اسم	/ˈdɔɡ.mə/	عَقِيدَة

الأفعال المركبة التي ستسمعها

الكلمة	المعنى
die out فعل	اِنْقَرَضَ
go down فعل	نَزَلَ

جمل تستحق التكرار

جمل قصيرة وكاملة من الفيديو يمكنك استخدامها في الحديث اليومي:

If we want an answer to the question, therefore, what is life?
I'll show that in a moment in another slide.
I'll just jump the remaining slides.
They just simply summarize what I've already just said.
I know that's a bit artificial.

القواعد في هذا الفيديو

أكثر التراكيب التي يستخدمها المتحدث، مع العبارات نفسها من الفيديو:

التركيب	في الفيديو
الجمل الشرطية if + جملة، will/would + فعل — شرط ونتيجته	if you want what I would regard
المضارع التام have/has + اسم المفعول — حدث ماضٍ ما زال له أثر الآن	has emerged · has changed · I've already described
المبني للمجهول be + اسم المفعول — التركيز على ما يحدث لا على من يفعله	were given · were made · was discovered
جمل الوصل who / which + جملة — معلومة إضافية عن شخص أو شيء	mutations which will · heart, which is · those who want

نطق يحتاج إلى انتباه

يستخدم المتحدث 71 من الصيغ المختصرة، مثل don't, I'll, didn't. انطقها بصيغتها القصيرة كما تسمعها.

أصوات “th”: rhythm /ˈɹɪð.əm/, synthesis /ˈsɪnθəsɪs/
أصوات “sh” و“zh”: mutation /mjuˈteɪʃən/, evolutionary /ˌiː.vəˈluː.ʃən.ɛɹ.i/, goldfish /ˈɡoʊldfɪʃ/, speciation /ˌspi.siˈeɪ.ʃən/, accumulation /əˌkjuːm.jəˈleɪ.ʃən/
الكلمات الطويلة — انتبه لموضع النبر: organism /ˈɔɹ.ɡəˌnɪz.əm/, replicator /ˈɹɛplɪkeɪtɚ/, inheritance /ɪnˈhɛɹɪtəns/, characteristic /ˌkæɹ(ə)ktəˈɹɪstɪk/, incidentally /ˌɪnsəˈdɛn(t)l̩i/

أصوات يجدها متحدثو العربية صعبة:

/p/ — ليس /b/: انطقه مع نفخة هواء: phenotype /ˈfiː.nəˌtaɪp/, replicator /ˈɹɛplɪkeɪtɚ/, carp /ˈkɑɹp/, speciation /ˌspi.siˈeɪ.ʃən/, empirical /ɪmˈpɪɹɪkəl/
/v/ — ليس /f/: مع اهتزاز الأوتار الصوتية: evolutionary /ˌiː.vəˈluː.ʃən.ɛɹ.i/, variation /ˌvɛəɹiˈeɪʃn̩/, devote /dɪˈvəʊt/, invent /ɪnˈvɛnt/
تتابع الصوامت — لا تضف حركة بينها: mutation /mjuˈteɪʃən/, inheritance /ɪnˈhɛɹɪtəns/, incidentally /ˌɪnsəˈdɛn(t)l̩i/, carp /ˈkɑɹp/, goldfish /ˈɡoʊldfɪʃ/

كيف تتدرب بهذا الفيديو

استمع إلى الفيديو كاملًا مرة واحدة دون أن تتكلم، ودوّن الكلمات التي لا تعرفها.
ردّد جملة جملة بالسرعة العادية، وكرّر كل جملة حتى يتطابق إيقاعك مع المتحدث.
سجّل صوتك وقارنه بالأصل، مع الانتباه إلى كلمات مثل genome, phenotype, organism.

ما هي تقنية التظليل الصوتي؟

التظليل الصوتي (Shadowing) تقنية تعلم لغة مدعومة علمياً، طُورت أصلاً لتدريب المترجمين الفوريين المحترفين. الطريقة بسيطة لكنها قوية: تستمع لصوت إنجليزي أصلي وتكرره فوراً بصوت عالٍ — كظل يتبع المتحدث بتأخير 1-2 ثانية. تُظهر الأبحاث تحسناً كبيراً في دقة النطق والتنغيم والإيقاع وربط الأصوات والاستماع والطلاقة.

تقنية الشادوينغ: اقرأ الدليل الكامل خطوة بخطوة →

تدريب Shadowing: "What is life"-lecture: Denis Noble - تعلم التحدث بالإنجليزية عبر الفيديو

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