Oliver Smithies:

To Book U, November 22nd, 1966, going through March 26 or thereabouts, of 1967.  It’s a very thick book, with loads of images of completely un‑useful (laughs) information, as far as I’m concerned, at this point.  Tom’s medium test, is the beginning, Sunday the 27th.  And, “This medium appears no better than [F‑10?] and insulin.  As such, appears to have no effect.”  So anyway, that was that.  It might have been Tom Wegmann, who joined the lab as a — I think, as a postdoc.  Mm-hmm.  We’ll just look [00:01:00] that up.  (break in audio) Yes, that must have been Tom Wegmann.

So beginning many pages of images of thymus and hemoglobin tests, to see whether that could help things.  For example, on Tuesday, November 29th, hemoglobin tests, with conclusion, “Hemoglobin may have an effect at low concentration.  But these cultures are all quite good, especially with regard to medullary cell.”  So I could keep my thymus reasonably alive, if I didn’t make it too thick.  Images again, pages and pages of images of the thym‑‑

[00:02:00] Cattle hemoglobin tests, Thursday — Saturday, December 3rd.  (long pause)

These sort of comments, page 17, “It is clear that the reticular microphage migrate out o‑‑ migrate out of the medulla into the dying cortex.”  [00:03:00] (pause) So on Monday…  Let’s see what it says on Monday, December 5th.  “A general review of thymus-alone experiments to date.”  There is the summary of what was going on.  (pause) [00:04:00] Effect of adrenalectomy — radiated adrenalectomize.  So maybe I had understood that it was the cortisone.  In fact, I know I understood it.  But I adrenalectomized — and irradiated.  Adrenalectomize minus one.  And the thymuses are looking good.  And then, on the following page, there are irradiated and sham adrenalectomize — irradiated, controlled.  And they do look very similar, at that point.  And rather nice images there, on page [00:05:00] 30 and 31, of irradiated, sham adrenalectomized.  Where the control is — I don’t see the control at the same magnification — though here, on the following page, is irradiated and adrenalectomized.  This is sham.  And — but no interpretation of the results.  However, I was trying with and without adrenalectomy.  And there are many more — it looks to me, at least o‑‑ there are more dead cells in the sham adrenalectomized than the irradiated adrenalectomized.  [00:06:00] More experiments of similar type, going on pages and pages — of images of the thymus.

Submerged culture tests, De‑‑ Saturday, December 10.  “Clear answer that either cell migration and/or submersion leads to residual cells dying,” etc., etc.  Trying to culture the thymus.  Pages and pages of images.  An oxygen incubator test, on Tuesday, December 20th.  “Clear improvement.  [00:07:00] But we need to know whether the integrity of the thymus and” side “affe‑‑ and size affect survival, as not all cultures are good.  Consider a” hypo‑‑ “hyperbaric death.”  More images, more images, pages of pictures of the thymu‑‑

Various culture attempts, Friday, December 22nd, on popliteal lymph nodes, femurs, to get the bone marrow, and thymus, etc., kidney, spleen.  And LNT, which is (laughs) “very successful.”  “LNT very successful.”  But what is LNT?  Popliteal lymph nodes?  [00:08:00] Lymph node test, LNT, presumably.  Lymph node.  (pause) So — continuing.  And the following page, is a comment that “Ten-day cultures from the cloning experiment Monday, January 2nd.  The kidney really works!”  [00:09:00] (long pause) Looks I did — there.  (pause) LNT must [00:10:00] be lymph node.  But it — I’m not sure why there is a T after it.  Probably LNT is lymph node time series — probably.  But not very clear, at this stage.

Anyway, experiments were going on of this general type.  For example, on Saturday, December 24, page 79, decreasing sizes of thymus and decreasing sizes of spleen, and a whole of a lymph node, etc.  And even whole embryos.  [00:11:00] Cultures, cultures, cultures.  Ru‑‑ page 85, December 28th, Wednesday, rough lymph node time series.  That will be LNT — plus or minus antigen.  And sections with time.  (inaudible) into images of that.

Trying hyperbaric tests, where the — I had a pressure indicator and set up the culture [00:12:00] under increased pressure.  But probably the pressure went to zero, probably before morning — maybe all the time, as a tube came off.  So chemical problems with the hyperbaric test — which were repeated on the following day, December 31st, Saturday.  And cultures are shown — images of the culture, at one atmosphere and at two atmosphere, to see what the difference is.  And three atmospheres and four atmospheres.  So I was quite capable of quite high-pressure cultures.  [00:13:00] But no comments on the results.

Tuesday, January 3rd, active lymph node tests.  Left and right popliteal lymph node, etc., etc.  Culturing these lymph nodes.

An attempt, on Friday, January 13th, to disperse the thymus cells and then get them repacked.  (pause) Thymus mush death, on January the 14th — [00:14:00] with some mitoses being visible and labeled — and identified in the sections.  Saturday, January 14th, with the thymus mush.  Tested bits of trimmed filter cells, not more than a few layers thick, and found mitoses.  So that’s — I was pleased to see them, having dispersed the thymus into a mush.  [00:15:00] Next page, “24‑hour cells show cells several layers thick in places.  Found one mitosis.  [Minced?], not much better.  One mitosis.”  Continuing with the thymus mush tests, a repeat.  (long pause)

[00:16:00] Here’s an ambitious plan, on March 7th, recovery test, referring back to Book S, page 53 — which was the design of a recovery experiment.  Friday, February 25th, recovery experiment — s‑‑ to — referring back to that recovery test.  “The aim is to set up a primary response in a series of animal and inactivate” the “cell re‑‑ inactive cell replication by x‑rays, etc., and attempt to reutilize the replicated primary information in cells from a suitable donor.”  [00:17:00] Sounds very complicated.  But it’s all related to this business of transferring information from one cell to another.

And here’s the test.  And at the bottom it says, “Result:  All were consistently zero at four days.”  (laughs) And on the following page, 125, “Results suggest that either the idea is quite wrong or the route of cells is quite wrong,” etc.  But I still decided to go on.

Some attempts at improving cultures, as usual.  [00:18:00] For example, on Thursday, March 22nd, solid RBC cultures.  “Three layers of red blood cells, cow, agar-made.”  With some difficulties. Etc.  Cultures, trying to use these red cells, in some obscure way.  And this book is rapidly drawing to an end.  Some blank pages, in the 130 — 140 area.  And Thu‑‑ Wednesday, March 29, “0.75% agar with 20% cells.”  [00:19:00] On the opposite page, “All pretty well dead.”  And so ends this book, Book U.