Although they offer FTP access to the genomic data--including population, alignment and sequences (traces, calls, etc.)--the NCBI has hosted the files with a README and guide (aspera_transfer_guide.pdf) about Aspera's "fasp technology" that the NCBI claims to incorporate automated checksum verification for both casual downloaders, via a browser plugin, and bulk downloaders, via a cross-platform command-line application. Aspera is new to me; they claim to have some throughput (bandwidth) advantages as well.
Nevertheless, the sequence data files embed MD5 checksums directly, per NCBI documentation, which I would expect bulk downloaders to take advantage of independent of any third-party "technology."
Just to clarify the headline and summary, and as is pointed out in the quote from Dr. Alan Thornhill in the original article:
Mutations in BRCA1 are linked to breast cancer , not just having the BRCA1 gene itself. BRCA1 is a critical tumor suppressor gene that helps maintain genomic integrity. Again, specific mutations in BRCA1 have been linked to breast cancer, not just "carrying the BRCA1 gene". Most of us carry the BRCA1 gene and it is expressed in a wide variety of tissues throughout our bodies. The BBC article uses the language such as "not carrying the BRCA1 gene", this is not entirely appropriate or even the issue at hand. The child will carry the BRCA1 gene, but without the specific mutations linked to breast cancer. (To be even more specific, the child will carry two alleles of the BRCA1 gene, one from each parent, both of which lack the mutations linked to breast cancer.)
As some folks may know who've endured the procedure, endoscopy usually involves a relatively large tube that has more than the two functions of the tethered "pill" listed here. The tethered "pill" can 1) illuminate and 2) visualize, but it does not allow for 3) irrigation, 4) suction or 5) collection of biopsies (more info here). These are critical functions that most larger-bore endoscopes can currently perform without the requirement of adding a second endoscope that can provide these functions.
As a medical student shadowing a gastroenterologist, I know how critical (3)-(5) are in even "normal" endoscopies, let alone those with possible pathology. However, for screening or exploratory endoscopy on low-risk patients, this seems like an excellent tool.
To review: Natural selection is based on favorable traits that become more common and unfavorable traits that become less common over generations of reproducing. These traits must be heritable, e.g. they must be passed on via genetic code. As king-maniac points out, the favorability of a heritable trait (perhaps what is meant by quality?) can be very relative and hard to determine in the population at any given moment in time.
The "selection" part of natural selection just is not happening any more. ...
Sure, we might have a wider gene pool (by keeping alive people that would not naturally be around) but quality is extremely important.
It is doubtful that natural selection has ceased. Natural selection involves selection at all ages of development, not just adults. And it's not just about "keeping people alive", but about letting their genes pass on to subsequent populations.
First off, natural selection does not just work to weed out unfavorable traits--it passes on those that are favorable. In our population, it is at times hard to qualify favorable traits, but the ability to reproduce is a favorable trait that is still selected for via natural selection (viability selection). Reproductive capability is part and parcel of natural selection. For example, some mutations of the SHH gene allow for complete development of humans, but result in sterile males. This unfavorable trait allows someone to live a generation, but severely limits their ability to reproduce. (Yes, artificial insemination may give them a route to reproduction, but this medicine is hardly accessible to everyone and is by no means a guarantee.)
Secondly, unfavorable traits are still being selected against. There are myriad inborn errors of metabolism and development deficiencies that are not compatible with life. Sure, there are a few that are compatible with life that medical science has helped "cure"--for example, phenylketonuria, where one's diet can be adjusted to deal with their unfavorable trait. But there are many other unfavorable traits--mutations in genes involved in brain development, resulting in still-born babies--that do not allow for sexual selection to occur. (Yes, someday gene therapy may mitigate these diseases at a germ-cell level, but then the unfavorable heritable traits would no longer exist in offspring.)
And another complex example: Think about the couple who can't reproduce; some adopt. Their adopted child does not necessarily carry their inability to reproduce. In fact, their adopted child may have more favorable traits than the individual parents themselves. In this case, if the favorable traits of the adopted child become more common in the future or their unfavorable traits become less common. At the same time, the parents unfavorable traits become less common. Natural selection seems well underway in this--albeit contrived--example.
Medical science has yet to allow human beings to pick and choose exactly the genetic code they desire for their offspring. At this point, yes, certain components of natural selection will cease. There may be no sexual selection, but viability selection will still play out I can imagine. Surely, natural selection does not equal viability selection. But human beings picking the most favorable traits for their offspring seems to built on the natural selection that's been going on in the human population all along. How else would we choose the most favorable traits?
With regards to infection, there's a biological precedent for outside-to-inside the skull transmission of fluid--via emissary veins--that connect the scalp and intracranial sinuses that drain CSF. This pathway is called a "danger zone of the scalp." The pathway for infection exists already, but the invasive procedure of installing a heat sink could surely allow for additional means of infection, just based on the required surgery.
Nevertheless, based on the linked diagram from TFA, it appears that the heat sink would rest underneath the scalp's deepest layer, thereby transmitting excess heat outside of the cranial cavity but stopping just superficial to the skull. Therefore it wouldn't project through the skin of the scalp. So it appears IMHO that direct infection through the heat sink would be limited.
... if there's any skin in between the heat sink and the conduit then that skin is going to die
Also, since the heat sink is under the scalp--and skin being the most outer layer of the scalp--there wouldn't be any skin proper between the heat sink and the heat sink's conduit. However, there would be a bunch of connective tissue including arteries, veins and portions of muscle. These could definitely be compromised. Also, if I am correctly interpreting the linked diagram, the heat sink's secondary conduit is the scalp itself! The scalp does an excellent job of dissipating heat from our head as most folks can attest too--particularly those lacking hair. There's also very little fat in our scalp for insulation.
Even after all that, this therapeutic intervention seems incredibly unusual if effective.
Although cancer cells are inherently "self", they do often have significant differences in genotype and phenotype. Even though the may only have one or two significant mutations, these can lead to significant phenotypic differences. For example, almost 40% of glioblastoma multiforme, the most malignant form of brain tumor, have a large deletion in chromosome 10. This deletion affects the expression of PTEN, a tumor suppressor. Lacking PTEN expression, these cancer cells express many different proteins which other cells of the same cell type. Thus, their phenotype--assayed through differential staining and other morphological characteristics e.g. anaplastic, undifferentiated--is not identical, which leaves hope for targeting these differences via therapeutics.
Several cancer cells show heterogenous genotype and phenotype. Glioblastomas are commonly heterogenous, with additional mutations in other genes including MMD2 and EGFR. It has been demonstrated that some prostate cancer cell types can be effectively treated with hormone therapy. However, after treatment any remaining cancer cells which do not respond to hormone therapy proliferate. Thus, hormone therapy is not a cure for prostate cancer and may select cells which are non-responsive to therapy.
But in the end, its the fact that cancer cells are self and very similar to other cells that makes therapy so difficult.
I'm not an "ordained" molecular biologist, but I'll add to your comments. Bright new apple varieties can be introduced into apples via genetic manipulation at the chromosomal (genomic) DNA level. In organisms, from plants to animals, you can inject (or "transfect") a specific gene into a cell relatively easily. This type of injection can be permanent or temporary. A permanent injection could yield a new apple variety. This is direct genetic manipulation.
There is another way. The tried-and-true method for introducing new apple varieties would involve mating (or "crossing") current apple varieties which represent traits of interest. For example, find the two shinest, reddiest apples and cross them to see if you can generate an even shiner, redder apple. This is indirect genetic manipulation, which relies upon specific selection.
Finally, yes, there was a Nobel Prize awarded for the discovery of a mechanism for gene silencing called RNA interference, or RNAi. Scientists tried injecting double stranded RNA (dsRNA) encoding "pink" genes into petunias. This RNA interfered with the normal expression of the pink genes, which yielded white plants. This mechanism, RNAi, is now used to limit (or "knockdown") the expression of specific genes in labs around the world. It is a powerful and useful technique. To clarify, the chromosomal DNA doesn't actually stop expressing the gene--it still makes messanger RNA ("mRNA") for the gene, but does not translate the mRNA into protein. These mRNAs are effectively blocked or degraded before translation via RNAi, as long as the RNAi components are present in the cell. To permanently block the expression of a gene via RNAi, one must use the method of transfection (described above) to insert the RNAi "gene" into chromosomal DNA.
Hope this helps. (I tend to be a bit long-winded.)
Slashdot Mirror
Although they offer FTP access to the genomic data--including population, alignment and sequences (traces, calls, etc.)--the NCBI has hosted the files with a README and guide (aspera_transfer_guide.pdf) about Aspera's "fasp technology" that the NCBI claims to incorporate automated checksum verification for both casual downloaders, via a browser plugin, and bulk downloaders, via a cross-platform command-line application. Aspera is new to me; they claim to have some throughput (bandwidth) advantages as well.
Nevertheless, the sequence data files embed MD5 checksums directly, per NCBI documentation, which I would expect bulk downloaders to take advantage of independent of any third-party "technology."
Just to clarify the headline and summary, and as is pointed out in the quote from Dr. Alan Thornhill in the original article:
Mutations in BRCA1 are linked to breast cancer , not just having the BRCA1 gene itself. BRCA1 is a critical tumor suppressor gene that helps maintain genomic integrity. Again, specific mutations in BRCA1 have been linked to breast cancer, not just "carrying the BRCA1 gene". Most of us carry the BRCA1 gene and it is expressed in a wide variety of tissues throughout our bodies. The BBC article uses the language such as "not carrying the BRCA1 gene", this is not entirely appropriate or even the issue at hand. The child will carry the BRCA1 gene, but without the specific mutations linked to breast cancer. (To be even more specific, the child will carry two alleles of the BRCA1 gene, one from each parent, both of which lack the mutations linked to breast cancer.)
As some folks may know who've endured the procedure, endoscopy usually involves a relatively large tube that has more than the two functions of the tethered "pill" listed here. The tethered "pill" can 1) illuminate and 2) visualize, but it does not allow for 3) irrigation, 4) suction or 5) collection of biopsies (more info here). These are critical functions that most larger-bore endoscopes can currently perform without the requirement of adding a second endoscope that can provide these functions.
As a medical student shadowing a gastroenterologist, I know how critical (3)-(5) are in even "normal" endoscopies, let alone those with possible pathology. However, for screening or exploratory endoscopy on low-risk patients, this seems like an excellent tool.
To review: Natural selection is based on favorable traits that become more common and unfavorable traits that become less common over generations of reproducing. These traits must be heritable, e.g. they must be passed on via genetic code. As king-maniac points out, the favorability of a heritable trait (perhaps what is meant by quality?) can be very relative and hard to determine in the population at any given moment in time.
The "selection" part of natural selection just is not happening any more. ... Sure, we might have a wider gene pool (by keeping alive people that would not naturally be around) but quality is extremely important.It is doubtful that natural selection has ceased. Natural selection involves selection at all ages of development, not just adults. And it's not just about "keeping people alive", but about letting their genes pass on to subsequent populations.
First off, natural selection does not just work to weed out unfavorable traits--it passes on those that are favorable. In our population, it is at times hard to qualify favorable traits, but the ability to reproduce is a favorable trait that is still selected for via natural selection (viability selection). Reproductive capability is part and parcel of natural selection. For example, some mutations of the SHH gene allow for complete development of humans, but result in sterile males. This unfavorable trait allows someone to live a generation, but severely limits their ability to reproduce. (Yes, artificial insemination may give them a route to reproduction, but this medicine is hardly accessible to everyone and is by no means a guarantee.)
Secondly, unfavorable traits are still being selected against. There are myriad inborn errors of metabolism and development deficiencies that are not compatible with life. Sure, there are a few that are compatible with life that medical science has helped "cure"--for example, phenylketonuria, where one's diet can be adjusted to deal with their unfavorable trait. But there are many other unfavorable traits--mutations in genes involved in brain development, resulting in still-born babies--that do not allow for sexual selection to occur. (Yes, someday gene therapy may mitigate these diseases at a germ-cell level, but then the unfavorable heritable traits would no longer exist in offspring.)
And another complex example: Think about the couple who can't reproduce; some adopt. Their adopted child does not necessarily carry their inability to reproduce. In fact, their adopted child may have more favorable traits than the individual parents themselves. In this case, if the favorable traits of the adopted child become more common in the future or their unfavorable traits become less common. At the same time, the parents unfavorable traits become less common. Natural selection seems well underway in this--albeit contrived--example.
Medical science has yet to allow human beings to pick and choose exactly the genetic code they desire for their offspring. At this point, yes, certain components of natural selection will cease. There may be no sexual selection, but viability selection will still play out I can imagine. Surely, natural selection does not equal viability selection. But human beings picking the most favorable traits for their offspring seems to built on the natural selection that's been going on in the human population all along. How else would we choose the most favorable traits?
... and you do not want a brain infectionWith regards to infection, there's a biological precedent for outside-to-inside the skull transmission of fluid--via emissary veins--that connect the scalp and intracranial sinuses that drain CSF. This pathway is called a "danger zone of the scalp." The pathway for infection exists already, but the invasive procedure of installing a heat sink could surely allow for additional means of infection, just based on the required surgery.
Nevertheless, based on the linked diagram from TFA, it appears that the heat sink would rest underneath the scalp's deepest layer, thereby transmitting excess heat outside of the cranial cavity but stopping just superficial to the skull. Therefore it wouldn't project through the skin of the scalp. So it appears IMHO that direct infection through the heat sink would be limited.
... if there's any skin in between the heat sink and the conduit then that skin is going to dieAlso, since the heat sink is under the scalp--and skin being the most outer layer of the scalp--there wouldn't be any skin proper between the heat sink and the heat sink's conduit. However, there would be a bunch of connective tissue including arteries, veins and portions of muscle. These could definitely be compromised. Also, if I am correctly interpreting the linked diagram, the heat sink's secondary conduit is the scalp itself! The scalp does an excellent job of dissipating heat from our head as most folks can attest too--particularly those lacking hair. There's also very little fat in our scalp for insulation.
Even after all that, this therapeutic intervention seems incredibly unusual if effective.Although cancer cells are inherently "self", they do often have significant differences in genotype and phenotype. Even though the may only have one or two significant mutations, these can lead to significant phenotypic differences. For example, almost 40% of glioblastoma multiforme, the most malignant form of brain tumor, have a large deletion in chromosome 10. This deletion affects the expression of PTEN, a tumor suppressor. Lacking PTEN expression, these cancer cells express many different proteins which other cells of the same cell type. Thus, their phenotype--assayed through differential staining and other morphological characteristics e.g. anaplastic, undifferentiated--is not identical, which leaves hope for targeting these differences via therapeutics.
Several cancer cells show heterogenous genotype and phenotype. Glioblastomas are commonly heterogenous, with additional mutations in other genes including MMD2 and EGFR. It has been demonstrated that some prostate cancer cell types can be effectively treated with hormone therapy. However, after treatment any remaining cancer cells which do not respond to hormone therapy proliferate. Thus, hormone therapy is not a cure for prostate cancer and may select cells which are non-responsive to therapy.
But in the end, its the fact that cancer cells are self and very similar to other cells that makes therapy so difficult.
I'm not an "ordained" molecular biologist, but I'll add to your comments. Bright new apple varieties can be introduced into apples via genetic manipulation at the chromosomal (genomic) DNA level. In organisms, from plants to animals, you can inject (or "transfect") a specific gene into a cell relatively easily. This type of injection can be permanent or temporary. A permanent injection could yield a new apple variety. This is direct genetic manipulation.
There is another way. The tried-and-true method for introducing new apple varieties would involve mating (or "crossing") current apple varieties which represent traits of interest. For example, find the two shinest, reddiest apples and cross them to see if you can generate an even shiner, redder apple. This is indirect genetic manipulation, which relies upon specific selection.
Finally, yes, there was a Nobel Prize awarded for the discovery of a mechanism for gene silencing called RNA interference, or RNAi. Scientists tried injecting double stranded RNA (dsRNA) encoding "pink" genes into petunias. This RNA interfered with the normal expression of the pink genes, which yielded white plants. This mechanism, RNAi, is now used to limit (or "knockdown") the expression of specific genes in labs around the world. It is a powerful and useful technique. To clarify, the chromosomal DNA doesn't actually stop expressing the gene--it still makes messanger RNA ("mRNA") for the gene, but does not translate the mRNA into protein. These mRNAs are effectively blocked or degraded before translation via RNAi, as long as the RNAi components are present in the cell. To permanently block the expression of a gene via RNAi, one must use the method of transfection (described above) to insert the RNAi "gene" into chromosomal DNA.
Hope this helps. (I tend to be a bit long-winded.)