This is fascinating but unsurprising given all the things that have come out lately with regard to epigenetics. If your mental model of DNA involves some image of a pristine blueprint that is followed with clockwork-like precision in the exact same way by every cell in your body, your model needed updating quite some time ago.
I feel that many researchers, even geneticists who should know better, still have not internalized the idea that epigenetics is pretty good evidence that somatic DNA is a read/write medium. This leads to sloppy thinking about genetic causes of disease as well as continued persistence of the idea that if we can just collect enough sequences, all genetic causes of disease might be found.
The DNA doesn't sport standard read/write access, what's happening is that the expression or not of some genes can occur on an individual and be inherited by its offspring. The DNA doesn't change (save for the chance of a tiny few random changes, as usual)...
In the situation described by the article, the changes in gene expression are happening in the rat's brains. These changes aren't going to make it into the rat's gametes.
My understanding seems to be at conflict with how I'm reading your description here. Please help me out?
DNA is comprised of four specific nucleic acids which are always the same molecular combination. These acids form into base-pairs which must always be some combination of those four acids.
The DNA itself cannot be 'written to' as if it stores information no less than the following string x = "ACGTACT" can contain additional information beyond those bytes already stored in the string. We could alter the DNA, just as we can alter the string x, but this isn't writing additional data to the binary values, but changing what's stored in those memory locations.
When we're talking about reading/wrting to the DNA, are we actually speaking about modifying the sequence of any given strand, thus "reading/writing to DNA" is a misnomer ? I know there are presently ways to produce DNA synthetically, but what you've said seems to indicate there's room here for any pre-defined sequence I print to end up doing different things in a cloned cell than their synthetic duplicates might.
This is very cool, thank you for sharing. I've been on-and-off involved in some synthetic biology FOSS software, but as a non-biologist so much of this is hard to keep up with and make informed decisions about.
The "epigenetics" they're talking about is the chemical modification of the DNA. So while we usually talk about sequences of A,T,G,C we've actually got an additional symbol e.g. M. Which might be "methylated C".
So, these "base modifications" are actually increasing the alphabet size, you have the normal A,T,G,C bases and then a set of modified bases.
>I know there are presently ways to produce DNA synthetically, but what you've said seems to indicate there's room here for any pre-defined sequence I print to end up doing different things in a cloned cell than their synthetic duplicates might.
yes, or they might get modified so they are similar to the sequences already present.
By this argument, culture can be imprinted into DNA too, no?
This also implies that it would be much tougher to do a Jurassic Park recreation, because the environment is different. You can't just start from scratch with the DNA.
It's a mistake to think there is only one correct path when talking about DNA. Often, there is quite a bit of redundancy involved so Jurasic Park dinosaurs may be slightly different than there historic counterparts but that would not prevent them from being sufficiently viable to pass on there DNA. Because, biology is PASS / FAIL not some pursuit of perfection.
Culture is related to implicit and explicit memories shared by many people.
So (supposing that the results of this study can be generalized), yes, culture ends up imprinted in neuronal DNA, one cell at a time.
Since the imprinting is distributed and varies among the billions of neurons in your head it will not be passed to descendants (which inherit half a cell's worth of DNA).
Methylation can happen in gametes also, making some epigenetic changes heritable. The precise mechanisms of methylation are under intense study, but not well understood; it doesn't appear to be a random process in general.
This points to an almost-paradox in biology, which I call Lamarck's Lemma: There may be evolutionary advantage to being able to pass on acquired traits to one's offspring, and no known physical law that prevents it. Why, therefore, would biology not develop at least some Lamarckian mechanisms, since they could offer fitness in the Darwinian sense?
Answer: there appears to be exactly that. It's an exciting time for genetics.
Relevant to the article, and worth pointing out. It has no direct bearing on my comment, which was about (heritable) methylation of the gametes.
I believe what you mean to say is "We have been able to observe no correlation between methylation of the nerve cells and methylation of the gametes". Unless you can cite detailed studies supporting this null hypothesis. My understanding is that we have no idea.
A negative result disproves it for the specific kind of memory, e.g. fear of spiders, but you're right that the disproof can't be straightforwardly transferred to claims about other kinds of memories.
The hypothesis is so unlikely given what we know about the brain and reproduction that we'll assume false by default for all memories. Thus the onus is on the experimenter to provide a positive result for some case and also demonstrate that there isn't something else going on.
My views reflect Darwin's. Is he scientific enough for you?
May we not suspect that the vague but very real fears of children, which are quite independent of experience, are the inherited effects of real dangers and abject superstitions during ancient savage times? - Charles Darwin, A Biographical Sketch of an Infant (1877)
The quote you picked doesn't fully support your view - if you read the full quote, Darwin suggests that such inherited effects start to appear at one point in one's life and disappear afterwards. If instincts were truly passed on as memories, then they should be present throughout life and not appear when such evolutionary adaption is needed. This conflicts with evolutionary developmental psychological theory, which suggests that people face different survival adaptive problems at various points of their lifetime. For example, problems of survival as an infant must occur before problems of mating. Mating must predictably occur before parenting, and likewise before grand-parenting. From this, we expect certain "instincts" to appear and disappear as adaptive problems change. This is known to be true in infants: two examples are an infant's ability to swim (which disappears after 6 months) and also the Moro reflex, a potentially lifesaving reflex that occurs while falling. If these were "memories" and not instincts, then they would not appear so rapidly nor so consistently. There's quite a few examples of similar instincts listed on Wikipedia [1].
1. Darwin was pre-DNA. His guesses on the mechanisms of evolution aren't very relevant to the modern understanding.
2. Darwin was not infallible. We pick our scientific heroes because of their ability to advance science, to see farther than others, and be remarkably right given the information they had. Our heroes were still wrong about a lot of things, both outside there areas of expertise and inside their areas of expertise. For instance, Newton was the foremost expert on light of the day, and advanced our understanding of optics greatly, but he thought it was a particle. He was wrong, and we do him no honor by believing it a particle in his name.
I'm fairly certain that there is a lot about DNA that we do not yet fully understand.
Plenty of room for spider fears and bird songs.
Apparently the word "memory" is unsettling to some, but it still seems appropriate to me.
If DNA can grow 10,000 different regions of a brain, why is it unreasonable to think that it could also pre-populate some of those regions with patterns that we can access as memory?
saalweacher has started to cover why, but I'd like to emphasize a request: never ask this question sincerely again.
Darwin is a reasonably valid authority, but it's not because he's "scientific". People are not scientific. Processes are scientific. People who enact scientific processes are scientists. Conclusions drawn from scientific processes are science. "Scientific" should never refer to people.
I think you and Darwin are probably right. That's a long, long, long way from being proven right, though, and it's a huge mistake to assume so from a bit of poetry that Darwin speculated with.
I don't see why it's a paradox. Lots of things would offer fitness - why can't all animals talk? Why can't plants move? Surely these things would offer greater Darwinian fitness.
I did want to address one other total misconception here: Darwinian fitness is a result, not an effect. There is no adaptation, at all, which predictably increases fitness. Evolution is not a direction.
"Surely these things would offer greater Darwinian fitness" is as basic a mistake as "Surely we can figure out whether this program will halt without running it".
EDIT: In fact, as I think about it, there is a deep connection between the thought "Knowing the genes of this organism, we may predict its fitness" and "Knowing the instructions of this program, we may predict its halting". I'd love to see a paper on that.
It's an effect on the side of survival, correct? It's not that some particular change was "selected" in order to increase fitness but instead that all minute changes were selected simultaneously and some were pruned. There needs to be a smooth path from the "current location in design space" to any improvement under which there is never anything damaging enough to prune off that path.
And then, this "smooth path" idea relates neatly with topological notions of computability.
That doesn't seem rit to me. There's lots of adaptations that could probably increase fitness of offspring as a function of the parent's environment. In the same way, you can look at some programs and predict whether they halt, just not all programs, and potentially not even all "interesting" programs, for some definition of interesting.
You contradict your own point though: yes, we can predict - but we can't know that a program - an arbitrary program - will halt.
Evolution is much the same, but most people are worse at it because they make the mistake of prioritizing human-values as evolutionary advantages for all species.
For example, cows get slaughtered by the billion by humans. But they're an evolutionary success story from a Darwinian perspective: by being easy to domesticate by early tribes and delicious, they've proliferated far beyond anything which would've happened un-aided by humans.
For any very simple arbitrary program, perhaps. But certainly not in general. That's sort of the point of the Halting Problem: you can't know because it is undecidable.
Of course, there are simple and trivial programs that can be specifically analyzed, but we're definitely not to that level on any of the stuff under discussion here. The analogy really is pretty apt.
The halting problem is undecidable much like logic is incomplete. There will always be true statements we can't prove, and there will always be programs that might or might not halt. That doesn't mean that we can't prove lots of interesting things, it just means we can't promise to prove it when handed a program. We can try, and sometimes we'll succeed.
The thing is a very simple program can be argued to be have been executed by the person's reading it. You know it halts because you look at the code, step through it mentally and - hey, it halts.
But that's the nature of the problem: you know it halts because just executed it till it halts.
Yes, running them until they halt is one way of determining that a program halts on a given input. However, we can prove things do or don't halt without that. Consider running, on an idealized machine (so no overflows),
while(i>0) { i * 2; }
I think you would agree that this clearly never halts for any i > 0, and I think it also clear that we did not determine that by running it until it did not halt (because there is no such point).
Turing proved that for some programs there is nothing we can do but run them and see. That doesn't mean that's all we can ever do.
It's not a paradox, it's an almost paradox, which is kind of like being almost pregnant from a logic perspective.
Lamarckian and Darwinian evolution were debated and Darwin won. Lamarck's Lemma, which is a term I made up, points out that, were a random walk to create a mechanism for Lamarckian evolution, Darwinian evolution might well keep it around, as it could offer fitness.
That's why I phrase it as a lemma on Darwin's theory: even if it proves true, as epigenetics suggests, it doesn't make Lamarckian thinking correct. If anything, the opposite: it shows that Lamarckian effects can be explained through natural selection.
Plants can of course move, the classic example being the sensitive plant. Whether or not non-human animals can "talk" depends, basically, on whether one means "signalling" or "language proper". The bee dance can give arbitrarily complex instructions in one particular domain: there is no 'one' bee dance, each performance is roughly as unique as a sentence or so of text.
> Whether or not non-human animals can "talk" depends,
there is at least one animal that we know is able to talk, at least in our definition of "talk" - this animal is humans, so the Evolution did produce a talking animal.
Darwinian natural selection doesn't select for absolute/universal fitness, because there is no such thing. It selects for fitness into a specific, local niche. Humans may be more fit than chimpanzees in some areas, for example, but less fit in others.
It is a fallacy to assume that evolution is linear, and that it progresses toward some sort of universal optimum. There is no universal optimum. There are only specific, local optima.
A good example is the megalodon. From all we know, the megalodon was basically a massive, faster, more badass, more ferocious version of the great white shark. Why did the megalodon die out, and the lines that led to the great white survive? Surely big-badassedness is a desirable quality in an apex predator like a shark, right? Well, not really, because circumstances changed. Ocean temperatures changed, prey got scarcer and smaller, and eventually, size became a detriment. Megalodon was too big not to fail. What fit one day no longer fit the next.
The same thing may happen to humans someday, and some other animal may step up to take our places. It seems unlikely, but nature is the one doing the "selecting" in natural selection -- not us. Environments and circumstances change, and as they change, so do the criteria that "fit" the new context. In the Darwinian sense, "fit" refers to suitability to a habitat; it does not refer to "fitness" in the modern sense of the word. Think "product/market fit," not "physically fit."
> Why can't plants move? Surely these things would offer greater Darwinian fitness.
Not necessarily for plants. They do in fact move. They just do it differently. They have no problem spreading their DNA throughout the world via seeds and pollen. They use a lot less energy too, compared with sprouting legs and getting up to walk around. If they did this, they would likely require much greater quantities of food, including protein, which would put plants at a disadvantage.
In any case, plants have also evolved on a completely different fitness track than that of animals. Plants have evolved incredible manipulation of chemistry, far beyond what humans can produce today, let alone even understand.
I recently finished reading Botany of Desire (Michael Pollan) where he describes how plants have co-evolved with humans, appealing to our selection of flowers, fruits, and vegetables to further distribute their DNA. Who's actually farming who? Interesting stuff.
I was being a bit tongue-in-cheek. You're absolutely right that supposed "benefits" might have unforeseen tradeoffs. In this case, having some sort of pseudo-Lamarckian inheritance could possibly be a detriment due to energy requirements or something like that. Or indeed it could have a neutral effect on fitness, in which case it's unlikely to take hold in the population, barring genetic drift or other non-selection evolutionary mechanisms.
>I don't see why it's a paradox. Lots of things would offer fitness - why can't all animals talk? Why can't plants move? Surely these things would offer greater Darwinian fitness.
this is why we have live organisms that able to move - it is called animals, and we have animals that can talk, and we'll possibly have [some milleniums later] animals that are able to efficiently transfer memory through DNA (possibly after these animals become able to calculate and select what memories they'd like to encode into their own DNAs and what of these memories they want to transfer to the offsprings)... Evolution isn't finished as of today, it is possibly only starting :)
Even without Methylation, we have another mechanism for passing on traits to offspring, raising them. Admittedly, there are many species where this is not relevant, but for species where the young live with their parents, or other members of the older generation, it seems reasonable that information and traits could be passed by cross generation interactions.
The most obvious example of this is humans, who have minimal (if any) genetic advantage over cave-men. I suspect we can find simmilar instances in other species.
I'd need to read the paper, but the write up seems to ignore the possibility that methylation is required to express the genes necessary to form memories, and not that the methylation itself is, in any meaningful sense, the memory itself (as in "memories [...] get written onto DNA).
This was my first reaction as well. Blocking methylation is a drastically global operation for a cell as methylation is involved in so much of the epigenetic regulation. Turning it off probably disabled much of the normal functioning of those cells and could have had all kinds of downstream effects.
It doesn't seem fair to jump to the conclusion that the memory is actually encoded in the methylation pattern somehow. Based on a skim of the paper, the researchers don't seem to claim this either.
Ah, I only skimmed the article describing it, and originally jumped to the conclusion they had actually claimed that "memory state" (IE factual encoding) was being stored in methylation.
Modification of gene expression of genes associated with memory (in the form of changes to neuronal toplogy and excitation thresholds) seems like a more mundane and reasonable explanation.
the title in the write up is unnecessarily sensational, your impression is exactly the model proposed in the paper. You could not read out the methylation pattern in a cell and retrieve the memory, the memory is the methylation + the cells.
I'm hoping this turns out to be incorrect - a false lead. It would really suck if in order to download mindstates, we needed to get inside the chemistry of neuronal cells.
We can conceivably find an imaging technique that would let us 3D snapshot a brain and all it's connections. But its a big step from that big step down to getting nanoscopic views of the chemistry in every cell.
If you want to download a mindstate, you will almost have to deal with details at a molecular level. I am not familiar with the details of how the brain works, but consider that their is likely a huge evolutionary advantage to storing data more densely.
Interesting that they could also block memory formation in addiction centers. I wonder if there is a preventative treatment possible in that direction, by blocking addiction before it happens? It's a nice dream, anyway.
Err, err, centralized government bureaucracy imposing own will-of-committee between world and consciousness to inflict totalitarian conformance to pre-approved homogeneity ... not good, even if: drugs/childporn/terrorism/etc.
I feel that many researchers, even geneticists who should know better, still have not internalized the idea that epigenetics is pretty good evidence that somatic DNA is a read/write medium. This leads to sloppy thinking about genetic causes of disease as well as continued persistence of the idea that if we can just collect enough sequences, all genetic causes of disease might be found.