From the linked Washington Post story: "The cloned animals were made by injecting one of Willa’s cells into an egg from a domesticated ferret."
Which is kind of interesting, because domesticated ferrets are a different species. (I wonder if this means the clones have mitochondrial DNA from the domesticated ferret egg.)
They do have domestic ferret mitochondria. The plan is to breed them, take only the male offspring, an cross those back into the original population (and thus get rid of the domestic heritage again).
Those would be "captive" ferrets, not "domesticated" ones. (They want to introduce the offspring from the breeding program into the wild, and have in fact done this for about 10,000 offspring.)
This article in Science about the first cloned black-footed ferret (https://www.science.org/content/article/conservation-first-c...) specifically says, "Cloning endangered species faces unique ethical questions, as well. One is whether the clone, which can hold trace DNA from its surrogate mother, is actually the same as the species that researchers are trying to save. For example, black-footed ferret clones are created using eggs from domestic ferrets, meaning they carry that species’ mitochondrial DNA, which is left in the egg after its nucleus is extracted."
(Later in the article: "... apart from her mitochondrial DNA, most of which comes from her domestic mother, genetic analysis shows she is 100% a blackfooted ferret".)
I'm curious how many defects creep into the process. I doubt the scientists have any idea, and I'm pretty sure the process involves a great deal of statistical inference to reconstruct the genome from many, many small chunks of DNA.
How would they even measure their accuracy? By definition, there's not even a baseline to measure against, right?
This process is called genome alignment. It’s actually quite a fascinating computer science problem that has received a ton of study over the years. I think the classical techniques treat it as a dynamic programming problem but I’m not sure how the most modern alignment tools work.
There are a number of ways that we can check for errors. First, there are many different sequencing and alignment tools, each with different characteristics. For example, by cross checking long read sequencing from a nanopore sequencing deveice and more common Illumina paired end sequencing, we can see where they agree or disagree and then further check with another validated method like Sanger sequencing, if we’re really confused about which is correct. Also, we already know a bit about biology, so we can check the sequence for obviously wrong patterns. Like if our sequencing says the ferret has a mutation that would destroy a critical protein’s function (e.g. a frameshift or premature stop codon) but the ferret looks fine, then we can reasonably infer that the sequencing was wrong somehow. Finally, you’re right that there’s not a “baseline”. All processes in biology are inherently lossy. That said genome sequencing uses pieces of the cellular machinery (DNA polymerase) that can copy gene sequences with incredibly high fidelity, so we rely on biology’s incredible achievement to be reasonably sure that we’re getting the “right” answers.
That is a truly fantastic answer. Thank you so much. Our high school son was studying his high school genetics today, so it's also a fantastic tie-in. (He prefers his days off during the week, so he put in some hours today; flexibility FTW.)
Cheers! I hope your son enjoys learning about genetics, sometimes the introductory classes neglect be really weird beautiful fascinating parts in favor of easily tested concepts.
Finding out how accurate this approach is should be trivial, no? Take some other baseline tissue where you know the ground truth, freeze it, then follow the procedure and check what you get. Do this a few times and you'll have a pretty good estimate of the accuracy.
I could not find the answer for you, but I speculate not many: the frozen dna was only stored for 35 years. Cloning also does not need to introduce additional mutations into the dna afaik. So I'd expect very few if any mutations from the material they froze.
And to the reconstruction: I don't think it does in this case. As they talk about working with frozen cells and we are not in the realm of frozen Mammuts who's genomes has degraded and needs to be reconstructed. In that case yes, we would talk about smaller pieces.
My guessis that they already used the same tools with sheeps or rats in a freezer. Combining that info with some other tool to measure how much dqmage the sample gpt [1] may give an estimation.
[1] I guess the exact damage depends on how fast it froze and the changes of tenperature and other difficut to know details.
My limited (and likely wrong) understanding of Syrian hamsters is they're all descended from a few specimens someone collected a long time ago. Is there something special in hamsters that prevents genetic issues? Do they not have a lot of recessive characteristics?
I’m ignorant about cloning progress made since Dolly. Have they made advances on the problem where the clones have accelerated aging because they are made from cells that are aged?
>On 14 February 2003, Dolly was euthanised because she had a progressive lung disease and severe arthritis.[6] A Finn Dorset such as Dolly has a life expectancy of around 11 to 12 years, but Dolly lived 6.5 years.
Or was it even a problem at all? It seems clones made later haven’t had that issue? It shows the power of a meme in installing that idea in the consciousness of society.
Google is telling me this in its AI answer.
>Research suggests that telomeres are rejuvenated during nuclear reprogramming by somatic cell nuclear transfer (SCNT).
Telomere length is dynamically regulated. It sounds like SCNT does well at triggering the correct reprogramming to reset epigenetic features that might have led to Dolly's troubles (although it seems these were greatly overstated: https://blog.cirm.ca.gov/2016/07/27/cloning-breakthrough-dol...)
I'm curious what rabbithole you went down where you think this whole thought makes sense, but mostly the concept of people thinking of their clones as children is wild.
> the concept of people thinking of their clones as children is wild
I dont think so. The clones would be children in every sense that matters to society. They grow up to be adults, like any other human and with the disclaimer that early experiments will have genetic problems. Cloning is a go-to strategy for situations where traditional/assisted procreation is failing catastrophically or unavailable (eg spacefaring colonies that are sterilized mid-transit).
Treating specific genetic sequences as a legally special class, is a different discussion that arises in treating clones as something other than children, as they are literally descendants.
From the linked Washington Post story: "The cloned animals were made by injecting one of Willa’s cells into an egg from a domesticated ferret."
Which is kind of interesting, because domesticated ferrets are a different species. (I wonder if this means the clones have mitochondrial DNA from the domesticated ferret egg.)
They do have domestic ferret mitochondria. The plan is to breed them, take only the male offspring, an cross those back into the original population (and thus get rid of the domestic heritage again).
I think "domesticated" in this context refers to the 24 Black-Footed ferrets they initially captured.
"officials captured 24 ferrets and started a breeding program."
Those would be "captive" ferrets, not "domesticated" ones. (They want to introduce the offspring from the breeding program into the wild, and have in fact done this for about 10,000 offspring.)
This article in Science about the first cloned black-footed ferret (https://www.science.org/content/article/conservation-first-c...) specifically says, "Cloning endangered species faces unique ethical questions, as well. One is whether the clone, which can hold trace DNA from its surrogate mother, is actually the same as the species that researchers are trying to save. For example, black-footed ferret clones are created using eggs from domestic ferrets, meaning they carry that species’ mitochondrial DNA, which is left in the egg after its nucleus is extracted."
(Later in the article: "... apart from her mitochondrial DNA, most of which comes from her domestic mother, genetic analysis shows she is 100% a blackfooted ferret".)
"Domestic ferret" refers to the domesticated European polecat (e.g., https://www.inaturalist.org/taxa/399272-Mustela-furo).
I'm curious how many defects creep into the process. I doubt the scientists have any idea, and I'm pretty sure the process involves a great deal of statistical inference to reconstruct the genome from many, many small chunks of DNA.
How would they even measure their accuracy? By definition, there's not even a baseline to measure against, right?
This process is called genome alignment. It’s actually quite a fascinating computer science problem that has received a ton of study over the years. I think the classical techniques treat it as a dynamic programming problem but I’m not sure how the most modern alignment tools work.
There are a number of ways that we can check for errors. First, there are many different sequencing and alignment tools, each with different characteristics. For example, by cross checking long read sequencing from a nanopore sequencing deveice and more common Illumina paired end sequencing, we can see where they agree or disagree and then further check with another validated method like Sanger sequencing, if we’re really confused about which is correct. Also, we already know a bit about biology, so we can check the sequence for obviously wrong patterns. Like if our sequencing says the ferret has a mutation that would destroy a critical protein’s function (e.g. a frameshift or premature stop codon) but the ferret looks fine, then we can reasonably infer that the sequencing was wrong somehow. Finally, you’re right that there’s not a “baseline”. All processes in biology are inherently lossy. That said genome sequencing uses pieces of the cellular machinery (DNA polymerase) that can copy gene sequences with incredibly high fidelity, so we rely on biology’s incredible achievement to be reasonably sure that we’re getting the “right” answers.
That is a truly fantastic answer. Thank you so much. Our high school son was studying his high school genetics today, so it's also a fantastic tie-in. (He prefers his days off during the week, so he put in some hours today; flexibility FTW.)
This is the best of what the intenet can be.
Cheers! I hope your son enjoys learning about genetics, sometimes the introductory classes neglect be really weird beautiful fascinating parts in favor of easily tested concepts.
Finding out how accurate this approach is should be trivial, no? Take some other baseline tissue where you know the ground truth, freeze it, then follow the procedure and check what you get. Do this a few times and you'll have a pretty good estimate of the accuracy.
I could not find the answer for you, but I speculate not many: the frozen dna was only stored for 35 years. Cloning also does not need to introduce additional mutations into the dna afaik. So I'd expect very few if any mutations from the material they froze.
And to the reconstruction: I don't think it does in this case. As they talk about working with frozen cells and we are not in the realm of frozen Mammuts who's genomes has degraded and needs to be reconstructed. In that case yes, we would talk about smaller pieces.
Thanks, that's another fantastic answer.
It's an interesting question but prompts the rebuttal, isn't that just how things work in nature?
No process is 100% clean in biology, that's how we get random mutation and evolution of species
> How would they even measure their accuracy?
My guessis that they already used the same tools with sheeps or rats in a freezer. Combining that info with some other tool to measure how much dqmage the sample gpt [1] may give an estimation.
[1] I guess the exact damage depends on how fast it froze and the changes of tenperature and other difficut to know details.
How much genetic diversity do you really need?
My limited (and likely wrong) understanding of Syrian hamsters is they're all descended from a few specimens someone collected a long time ago. Is there something special in hamsters that prevents genetic issues? Do they not have a lot of recessive characteristics?
I’m ignorant about cloning progress made since Dolly. Have they made advances on the problem where the clones have accelerated aging because they are made from cells that are aged?
>On 14 February 2003, Dolly was euthanised because she had a progressive lung disease and severe arthritis.[6] A Finn Dorset such as Dolly has a life expectancy of around 11 to 12 years, but Dolly lived 6.5 years.
https://en.wikipedia.org/wiki/Dolly_(sheep)
Or was it even a problem at all? It seems clones made later haven’t had that issue? It shows the power of a meme in installing that idea in the consciousness of society.
Google is telling me this in its AI answer.
>Research suggests that telomeres are rejuvenated during nuclear reprogramming by somatic cell nuclear transfer (SCNT).
Telomere length is dynamically regulated. It sounds like SCNT does well at triggering the correct reprogramming to reset epigenetic features that might have led to Dolly's troubles (although it seems these were greatly overstated: https://blog.cirm.ca.gov/2016/07/27/cloning-breakthrough-dol...)
[flagged]
I'm curious what rabbithole you went down where you think this whole thought makes sense, but mostly the concept of people thinking of their clones as children is wild.
> the concept of people thinking of their clones as children is wild
I dont think so. The clones would be children in every sense that matters to society. They grow up to be adults, like any other human and with the disclaimer that early experiments will have genetic problems. Cloning is a go-to strategy for situations where traditional/assisted procreation is failing catastrophically or unavailable (eg spacefaring colonies that are sterilized mid-transit).
Treating specific genetic sequences as a legally special class, is a different discussion that arises in treating clones as something other than children, as they are literally descendants.