The taintedblood Timeline  -  what really happened...

In a 1981 report of the NBTS Protein Fractionation Technology Working Party, we read of scientific advances in the manipulation of genetic material that led to technological developments introducing the possibility of large-scale production of proteins [of which Factor VIII is one] for therapeutic use from bacteria or from animal cells cultured in vitro [in the test tube or Petri dish].

There have been two major lines of work toward this end: "One has drawn on recombinant DNA techniques to construct bacteria capable of producing "human proteins". The alternative has been to change the characteristics of animal, including human, cells to make them more amenable to large-scale cultivation in vitro.

We are not surprised to see what criteria the NBTS PFT Working Party use to decide whether or not to implement genetic manipulation techniques:

"It is necessary to decide whether the principal plasma proteins could be generally available at a competitive cost and of proven safety in a time-scale which bears upon the development of BPL. If so it is important to decide whether the technology arising from genetic manipulation is one which BPL would logically become engaged in." (page 27, para 3)

"Given prompt action on the redevelopment of conventional fractionation facilities, the return on investment will have been achieved before genetically engineered products can have a major impact. Nevertheless failure to take account of them may lead to a crisis shortly after the new plant has commenced operation." (page 30, final para)

Note: From 1981, it took 13 years for recombinant clotting factors to be licensed for use within the UK (i.e. in 1994). We believe that this could have been done in far less time, like Hyland, who were running human clinical trials of their recombinant in 1987. We would also like to point out that it took Government until 2006 to fully 'roll-out' recombinant factor concentrate to all adult haemophiliacs across the UK.

From 1981, that's a grand total of 25 years of deferment.

In a DHSS internal circular of 30 November 1982, we learn exactly how far on scientists were in developing genetically engineered Factor VIII as early as 1982.

On reading the circular, we discover that highly purified genetically-engineered Factor VIIIc was already being produced by a team at the Royal Free Hospital and that Genentech owned the RF method. We also read that Speywood signed a collaboration agreement with Genentech in relation to genetic engineering of FVIII.

At the end of the circular, under 'STOP PRESS', we read an alarming statement by the DHSS that they thought there could be valuable spin-off from a story in The Times. The DHSS state that they thought it should prompt the CBLA into examining its proposed investment in light of current developments in genetic engineering:

The DHSS in 1982: "I feel that the sooner this exercise is done the better in order to reassure our financial colleagues and the Treasury - otherwise each new reported 'break-through' will have them rushing to cancel the cheques!"

Note: Rather disgracefully, it took another 12 years for recombinant clotting factors (made synthetically) to be licensed for use within the UK in 1994. Compare this with Hyland running human clinical trials of their recombinant Factor VIII as early as 1987, just over 4 years from the date of this DHSS circular.

From the point of being licensed, why did Government take another 12 years (right up to 2006) to make the safe product available to all adult haemophiliacs across the UK?

From 1982, that's a grand total of 24 years of delays.

In a DHSS memorandum regarding a meeting of the Haemophilia Reference Centre Directors on 19th September 1983, we read of further mention of the possibility of genetically-engineered Factor VIII.

Under point 6, it states: "I discussed genetically engineered FVIII - still about 10 years off, is the guess." (Page 2, point 6.)

Note: This estimate of genetically engineered factor VIII being 10 years off was too generous. Somehow, within just 4 years, Hyland (Baxter) had managed to begin human clinical trials of a recombinant Factor VIII concentrate. (See additional source below).

In the minutes of the 14th meeting of the UK Haemophilia Centre Directors on 17th October 1983, the possibility of the production of artificial factor VIII is discussed:

"The question of the production of an artificial source of factor VIII in the near future (that is within the next two to three years) was raised and discussed. Professor Bloom said that he thought that there was still a lot of work to be done on this type of product before any material would be available for use in patients and it was not likely to be available in the near future." (Page 7, final paragraph)

By February 1984, detailed progress had been made with Factor IX and reference is made to the six stages of investigation which need to be passed through for the preparation of genetically engineered blood products. The stages are as follows:

• Obtaining a clone
• Development of the clone
• Fermentation of the clone material
• Purification of protein
• Toxicity trials
• Clinical trials

"It was noted that three groups from the USA had already completed the second stage of developing a clone for Factor IX. [Deleted Name] reported however that no significant progress had been made on Factor VIII, and he outlined the difficulties for its cloning."

"It was noted however that the Genetics Institute, Boston, USA, had reached the stage of obtaining a clone for Factor VIII."

Note: The future role of BPL with regard to genetically engineered products was questioned and the view was expressed that in the long term, the Laboratory would not purely be involved in human products, but rather in the late 1980's or early 1990's it would have the potential for downstream purification of cloned material.

In the minutes of the CBLA in November 1984, there is mention of progress in the cloning of factor VIII:

"The Chairman confirmed that following [Deleted Names] attendance at the Committee's last meeting, he and the Director of BPL had recently visited the USA to discuss possible research and development collaboration for the preparation of Factor VIII through genetic engineering". (Page 1, point 8.1)

"Two firms, namely [Company Names Deleted], had now made significant progress in cloning Factor VIII" (Page 1, point 8.1, line 5.)

In a recovered document entitled "Self Sufficiency in Blood and Blood Products in the UK" the following is stated:

"Ministers will be aware that Factor VIII, the most significant blood product, has been produced in the laboratory by genetic engineering methods." (Point 7. Lines 1 & 2.)

"...it is considered that it will take up to five years at least for this product to be available on a commercial scale." (Point 7, lines 4 & 5)

"This possible development has been borne in mind and the plans for BPL are sufficiently flexible to allow the refining of such products from genetically engineering source material when available in the future." (Point 7. Lines 6-8)

Note: We know that Ministers had knowledge of genetically engineered Factor VIII from as early as November 1982. We should point out, that this knowledge was 3-4 years prior to the completion of the BPL re-development project of 1986.

Background: We know from a DHSS internal circular, around 3 years earlier, that a discussion of genetic engineering or the cloning of Factor VIII took place as early as November 1982. (See Additional Source below).

Hyland begins the first human clinical trials of a recombinant FVIII concentrate.

In 1992, Hyland markets the first genetically engineered FVIII concentrate.