Interesting, I've used "Bovine Serum Albumin, Fraction V" a lot in my research. It looks like the "Fraction V" was because it was the 5th fraction in Cohn's procedure.
That's cool! And for the most part, yes! It came out last. Although, last was not always precisely 5th. Some of the fractions came out in multiple parts as time went on and the process was improved/changed. But they kept the early fraction names mostly the same in spite of that.
Really glad you enjoyed it, in particular! I read your original von Neumann post when I was still in college, before I knew much about the history of R&D, and was enthralled. It looms in my head as *the bar* for how enjoyable a blog post in this area can be.
A nicely written article, but something that it fails to mention is that Cohn fractionation is still used today, with few changes, by all the plasma protein companies to extract immunoglobulin G from human plasma. This is a vital medicine for those with primary immunodeficiencies such as CVID and XLA, who cannot produce their own IgG antibodies and are at substantial risk of prolonged, recurrent or serious infections. It is also used in the treatment of those who have certain autoimmune conditions.
Unlike other plasma derived proteins that can now be easily made recombinantly because they only need the one type of protein that is exactly the same, IgG products need the breadth of millions of different IgG antibodies which recognise different targets. Each batch of IgG, which eventually ends up as intravenous or subcutaneous products, results from the pooled plasma donations of 1000+ people so that it has enormous immunological breadth and is hence protective against a wide variety of targets. The actual large scale production process used today is little changed from when it was when it was developed by Cohn and his colleagues, using enormous batch scale processes of steps of cold ethanol extraction, which is very labour-intensive and complex. In the plasma protein industry, it is still state of the art. Modern methods such as ion exchange chromatography have been implemented in parts of the various refined versions of the process used by different companies, but so far nobody has been able to design a method that gives a sufficient purity and yield to be able to replace the Cohn cold ethanol fractionation process.
A continuous flow version of the process would be ideal. Such as process was developed for the Scottish Protein Fractionation Centre (SPFC) in Edinburgh from the mid 1970s. It used in-line monitoring and computer controlled feedback. Overall, it worked exceptionally well, with greatly reduced complexity and effort being required when compared to batch production. Unfortunately, the technology eventually had to be abandoned in the late 1990s due to the vCJD outbreak in the UK. The nature of the continuous flow process meant that it was unable to be guaranteed to be sufficiently decontaminated with agents that could inactivate prions, risking multiple batches being potentially contaminated. At the time there was no way to test plasma donations for prions, and such a method is still not routinely available, so the SPFC had to switch back to a batch process until it eventually closed.
Interesting, I've used "Bovine Serum Albumin, Fraction V" a lot in my research. It looks like the "Fraction V" was because it was the 5th fraction in Cohn's procedure.
That's cool! And for the most part, yes! It came out last. Although, last was not always precisely 5th. Some of the fractions came out in multiple parts as time went on and the process was improved/changed. But they kept the early fraction names mostly the same in spite of that.
Wonderful read!
Really glad you enjoyed it, in particular! I read your original von Neumann post when I was still in college, before I knew much about the history of R&D, and was enthralled. It looms in my head as *the bar* for how enjoyable a blog post in this area can be.
A nicely written article, but something that it fails to mention is that Cohn fractionation is still used today, with few changes, by all the plasma protein companies to extract immunoglobulin G from human plasma. This is a vital medicine for those with primary immunodeficiencies such as CVID and XLA, who cannot produce their own IgG antibodies and are at substantial risk of prolonged, recurrent or serious infections. It is also used in the treatment of those who have certain autoimmune conditions.
Unlike other plasma derived proteins that can now be easily made recombinantly because they only need the one type of protein that is exactly the same, IgG products need the breadth of millions of different IgG antibodies which recognise different targets. Each batch of IgG, which eventually ends up as intravenous or subcutaneous products, results from the pooled plasma donations of 1000+ people so that it has enormous immunological breadth and is hence protective against a wide variety of targets. The actual large scale production process used today is little changed from when it was when it was developed by Cohn and his colleagues, using enormous batch scale processes of steps of cold ethanol extraction, which is very labour-intensive and complex. In the plasma protein industry, it is still state of the art. Modern methods such as ion exchange chromatography have been implemented in parts of the various refined versions of the process used by different companies, but so far nobody has been able to design a method that gives a sufficient purity and yield to be able to replace the Cohn cold ethanol fractionation process.
A continuous flow version of the process would be ideal. Such as process was developed for the Scottish Protein Fractionation Centre (SPFC) in Edinburgh from the mid 1970s. It used in-line monitoring and computer controlled feedback. Overall, it worked exceptionally well, with greatly reduced complexity and effort being required when compared to batch production. Unfortunately, the technology eventually had to be abandoned in the late 1990s due to the vCJD outbreak in the UK. The nature of the continuous flow process meant that it was unable to be guaranteed to be sufficiently decontaminated with agents that could inactivate prions, risking multiple batches being potentially contaminated. At the time there was no way to test plasma donations for prions, and such a method is still not routinely available, so the SPFC had to switch back to a batch process until it eventually closed.
Hey Samuel, thanks for this wonderful comment. This is some really interesting context.