Fathers of Meat Curing

Fathers of Meat Curing
by Eben van Tonder
1 June 2016

Introduction

A study of curing is a study in the interaction between nitrogen, oxygen and the proteins of meat, myoglobin, with an auxiliary role for blood proteins, haemoglobin.  It is about oxygenation, protonation and reduction.  It has recently been discovered that there exists a close correlation between certain reactions in human physiology and meat curing – the exact same processes are involved.  We trace the contribution of individuals from pre-history to the discovery of this link with human physiology.

Haemoglobin’s role comes in the fact that it was exclusively used in earlier studies of meat curing.  The reason is “mostly a matter of convenience” and “a matter of necessity since myoglobin was not isolated and purified until 1932 (Theorell, 1932).”  “In spite of the differences between haemoglobin and myoglobin, Urbain and Jensen (1940) considered the properties of haemoglobin and its derivatives sufficiently like those of myoglobin to allow the use of haemoglobin in studies of meat pigments.”  (Cole, Morton Sylvan, 1961: 2)

These are then some of the fathers of meat curing and processes that were elucidated by them.  In the case of Da Vinci, he is one of many people who’s work provides a link back to our ancient past and the art of meat curing that is thousands of years old.  Our art is built, in huge part, on the foundations they laid.

7000 BCE to 3000 BCE

Good evidence suggests that meat curing has been practised with sodium or potassium nitrate at various locations around the world where it naturally appears as a salt.  Four locations stand out.  The Atacama Desert in Chile and Peru, the Tarim Basin in Western China, the Dead Sea and Egypt.  It is in the Tarim Basin, where I believe, it was first developed into the art that we recognise today with a level of sophistication in the application of saltpetre by the early Christian Era that has not been fully appreciated until 1987.  (see Salt – 7000 years of meat-curing)

LEONARDO DA VINCI

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Leonardo da Vince (1452–1519) described a method of preserving the cadavers for his own dissection and study. (Brenner, E.; 2014)  The mixture he used consisted of turpentine, camphor (scent masking), oil of lavender (scent masking), vermilion (colouring agent), wine, rosin (a resin used as an adhesive), sodium nitrate, and potassium nitrate.  In his mix, for preservation, he relied on sodium and potassium nitrate and turpentine.  It is clear from these and other examples that the preserving power of nitrates was well known, well before modern day scientific rigour would come to the same conclusions.  The knowledge of the particular taste imparted, the colour formation and the preserving power of curing through nitrate, nitrite and nitric oxide has been harnessed for thousands of years.

GLAUBER, PRIESTLY, CAVENDISH, DAVEY

It is generally believed that nitric oxide, the chemical compound responsible for meat curing, was discovered by Joseph Priestly in 1772.  This is not completely true.  Before the time of Priestly, the production of nitric oxide was known through the reaction of nitric acid (CodeCogsEqn(7)) with any one of a number of commonly available metals.  Nitric acid was, for example, known in the 13th century Europe and was known as aqua fortis.  A known way of making it was was to react sulphuric acid and potassium nitrate as was developed by Johann Glauber (1604 – 1670).  It was observed that a gas was formed when nitric acid was poured over copper, iron, or silver by a number of natural philosophers including Johannes van Helmont (1579 – 1644), Robert Boyle (1627 – 1691) and Georg Stahl (1660 – 1734).  The last two noticed that this gas forms brown fumes when it comes in contact with the atmosphere.

Priestly’s contribution was immense in terms of identifying NO as a distinct chemical entity, separate from other gasses or “airs.” Priestly made important discoveries related to NO and was able to characterise it, but it was the eccentric and brilliant Henry Cavendish (1778 – 1810) who showed that NO is a composition of nitrogen and oxygen.  Humphrey Davey (1778 – 1829) showed the diatomic nature of the compound (Butler, A. R., Nicholson, R.; 2003).            

CARL WILHELM SCHEELE

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In 1777, the prolific Swedish chemist Scheele, working in the laboratory of his pharmacy in the market town of Köping, made the first pure nitrite. (Scheele CW. 1777)   He heated potassium nitrate at red heat for half an hour and obtained what he recognised as a new “salt.”  He realised that there was more than one “acid of niter.”  He distinguished phlogisticated acid of niter or nitrous acid (HNO2), as it became known in the 1800’s, from nitric acid (HNO3) as being a weaker volatile acid produced by the reduction of nitric acid. He also showed that niter, when strongly heated, lost oxygen, and left a salt that readily decomposed into a volatile acid when treated with acid. (http://nitrogen.atomistry.com/)

The two compounds (potassium nitrate and nitrite) were characterised by Péligot and the reaction established as 2KNO3→2KNO2+O2. (Péligot E. 1841: 2: 58–68) (Butler, A. R. and Feelisch, M.)  (Butler, A. R. and Feelisch, M.)

ANTOINE-LAURENT DE LAVOISIER

Antoine de Lavoisier (1743 – 1794), the father of modern chemistry did landmark work on nitric acid.  In 1790 he coined the terms nitrate and nitrite.  In his work on nitric acid, he noted that different oxidation states of nitrogen have been known for some time.  The term niter was allocated to these compounds by Macquer and Beaumé, but Lavoisier changed this to nitrites and nitrates “as they are formed by nitric or by nitrous acid.”  (Lavoisier, A; 1965: 217)

CARL REMIGIUS FRESENIUS

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A private laboratory was founded in 1848 in Germany by C.  R. Fresenius (his doctoral advisor was none other than Justus von Liebig).  One of the first recorded tests of nitrite as a meat preservative took place at his laboratory. (Morton, I. D. and Lenges. J.,1992: 142) 

JUSTINUS KERNER

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Kerner in Germany makes the link between Saltpetre and food safety particularly in relation to the prevention of botulism.  After studying many outbreaks of botulism, he identifies the omission of saltpetre from the curing brine as the common denominator in the various outbreaks.  (1817, 1820, 1822)  (Peter, F. M. (Editor), 1981.)

HÜNEFELD

Hünefeld in 1840 observed a crystalline substance in the blood of an earthworm thus discovering haemoglobin.  “Reichert, von Kolliker, Leydig, Budge, Kunde, and many others noted that blood from various species yielded a similar crystalline substance. As early as 1852 Funke described the method of laking blood with water and then inducing crystal formation with alcohol and ether. Although he prepared only small quantities of haemoglobin, the principle of this method has been widely used” for many years.  (Ferry, R. M.; 1923)

HUMPHREY DAVY

Humphry Davy

Humphrey Davy (1778 – 1829) in 1812 (cited by Hermann, 1865) and Hoppe-Seyler (1864) was the first to note the action of nitric oxide upon haemoglobin.  (Hoagland, R.; 1914: 213)

HERMANN

Hermann studied the properties of the compound formed in the reaction between haemoglobin and nitric oxide.  He discovered the compound Nitric Oxide-Hemoglobin (NO-Hemoglobin) in 1865 and it was supposed that it existed only in a laboratory. Until the work of Haldane, the compound has not attracted much attention.  (Haldane, J.  1901)

Hermann showed the spectrum of oxyhemoglobin and NO-hemoglobin.  “The blood saturated with nitric oxide was found to be darker in colour than either arterial blood or that saturated with carbon monoxide.”  (Hoagland, R.; 1914: 213)

T. LAUDER BRUNTON

Bronton

In 1867, Brunton identifies nitrite as a treatment for angina, the first nitrovasodilator.  His story is interesting and I quote a section edited by Hurst, J. W. from a 1989 article that appeared in Clinical Cardiology.

“Brunton learned of amyl nitrite from faculty members at Edinburgh who were interested in this substance that had been synthesised in 1844 by the French chemist Antoine Balard.”  (Hurst, J. W.; 1989)  Antoine-Jerome Balard achieved this when he passed nitrogen fumes through amyl-alcohol.  An interesting liquid was formed.  It had a pungent smell and when he inhaled it, it made him blush.  He told a friend that he is a shameless character and nothing makes him blush.  He speculated that the compound dilated the blood vessels and caused a drop in blood pressure.  Bruton thought that anything that dilated the blood vessels of the skin may have the same effect on the heart.  (Dormandy, T..  2006)

“London physician Benjamin Ward Richardson discussed possible medical uses of amyl nitrite at meetings of the British Association for the Advancement of Science between 1863 and 1865.  Arthur Gamgee, a recent Edinburgh graduate, also studied the physiological effects of amyl nitrite and encouraged Brunton to continue these investigations when he discovered that inhalation of the substance reduced arterial tension as measured by the sphygmograph.”  (Hurst, J. W.; 1989)

“While a house physician at the Edinburgh Royal Infirmary, Brunton became impressed with the lack of effective treatment for angina pectoris. Although the popularity of therapeutic bleeding had declined by the late 1860s, it was still advocated for the treatment of angina by some authors. When Brunton bled patients with angina some of them seemed to improve. He explained, “As I believe the relief produced by the bleeding to be due to the diminution it occasioned in the arterial tension, it occurred to me that a substance which possesses the power of lessening it in such an eminent degree as nitrite of amyl would probably produce the same effect, and might be repeated as often as necessary without detriment to the patient’s health.” Brunton began to study the effects of amyl nitrite on patients in the Edinburgh Royal Infirmary. When it was administered to patients with chest pain thought to represent angina, the discomfort usually disappeared in less than a minute. This was accompanied by facial flushing – an outward sign of the effect of amyl nitrite on the vascular system. Brunton published his observations on the value of amyl nitrite in angina in Lancet in 1867. Amyl nitrite was rapidly accepted by practitioners as an effective agent for angina pectoris.”  (Hurst, J. W.; 1989)

The reason for this inclusion is the fact that amyl nitrite, like alkyl nitrites, as discovered by Brunton, is a very effective vasodilator.  How it achieves this is that alkyl nitrite is a source of nitric oxide, which signals for relaxation of the involuntary muscles. Some of the physical effects are a decrease in blood pressure, headache, flushing of the face, increased heart rate, dizziness, and relaxation of involuntary muscles.

It has been discovered that nitrites and nitric oxide perform this function in the human body as a normal course of physiology.  The reduction step of nitrite to nitric oxide which is the final step in meat curing turns out to be an essential mechanism in the human body that makes life possible.  The full effect of Brunton’s discovery and the link with NO formation would not be realised until 1987 (Salt – 7000 years of meat curing).

There is another interesting reason.  A friend of mine, Gero Lütge, a 3rd generation German Master Butcher grew up in the German town of Braunschweig in Lower Saxony, Germany.

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Apprenticeship book of Otto Lütge, qualified butcher in 1927.

If anyone can tell you anything about meat, it is Gero and as someone who inherited his trade from his father and grandfather, he is a rich source of historical anecdotes, illustrations and information!  He tells a story of his grandfather, Otto Lütge, who used to buy nitrite for meat curing, from the pharmacy.  That would have been somewhere between the years 1950 and 1970 before it actually was regulated by law.

He confirmed that it was indeed nitrite and not nitrate that his grandfather added.  The colour was more intense and stable, but health issues were a big concern, in particular, cancer from which he himself passed away.

Butchers could have bought nitrate also from the pharmacy.  Following Bruton’s application of amyl nitrite for chest pains, William Murrell experimented with glyceryl nitrate to treat angina pectoris and to reduce blood pressure.  After Murrell published on it in 1879, it became widely available as a remedy.  It was officially known as glyceryl trinitrate, but due to a longer curing time, butchers would have preferred nitrate and in all likelihood, if they bought it through pharmacies, it would have been amyl nitrite.  Fascinatingly, this indicates that there is a possibility that amyl nitrite was used in meat curing.

ARTHUR GAMGEE

On 7 May 1868, Dr. Arthur Gamgee, who studied the physiological effects of amyl nitrite along with Brunton at the University of Edinburgh, brother of the famous veterinarian, Professor John Gamgee (who contributed to the attempt to find ways to preserve whole carcasses during a voyage between Australia and Britain), published a groundbreaking article entitled, “On the action of nitrites on the blood.”  He observed the colour change brought about by nitrite.  He wrote, “The addition of … nitrites to blood … causes the red colour to return…”   Over the next 30 years, it would be discovered that it is indeed nitrites responsible for curing and not the nitrates added as saltpetre.

MEUSEL, GAYON AND DUPETIT

The important reduction process of nitrate to nitrite was identified by E. Meusel (1875) who was the first to associate microorganisms with nitrogen losses.  He noted that antiseptic-sensitive agents identified as mixed populations of bacteria in soil and natural waters reduced nitrates to nitrites and even further.  (Meusel, E. 1875)   Gayon and Dupetit coined the term denitrification in 1882. (Gayon, U., and G. Dupetit; 1883)  It was this knowledge that was the basis of Polenske’s speculation about the source of nitrite in curing brine and cured meat.  (See Saltpeter:  A Concise History and the Discovery of Dr Ed Polenske)

POLENSKE

Dr Ed Polenske (1849-1911), working for the Imperial Health Office in Germany, made the first discovery that would lead to a full understanding of the curing action.  He prepared a brine to cure meat and used only salt and saltpetre (nitrates). When he tested it a week later, it tested positive for nitrites.

The question is where did the nitrites come from if he did not add it to the brine to begin with.  He correctly speculated that this was due to nitrate being converted by microbial action into nitrite.   He published in 1891.  For a full discussion on this landmark article, see Saltpeter:  A Concise History and the Discovery of Dr Ed Polenske

NOTHWANG

Following Dr Polenski’s observation, the German scientist, Nothwang confirmed the presence of nitrite in curing brines in 1892  but attributed the reduction from nitrate to nitrite to the meat tissue itself.  The link between nitrite and cured meat colour was finally established in 1899 by another German scientist, K. B. Lehmann in a simple but important experiment.

LEHMANN

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Karl Bernhard Lehmann (1858 – 1940) was a German hygienist and bacteriologist born in Zurich.

In an experiment, he boiled fresh meat with nitrite and a little bit of acid.  A red colour resulted, similar to the red of cured meat.  He repeated the experiment with nitrates and no such reddening occurred, thus establishing the link between nitrite and the formation of a stable red meat colour in meat.

K. B. Lehmann made another important observation that must be noted when he found the colour to be soluble in alcohol and ether and to give a spectrum showing an absorption band just at the right of the D line, and a second band, often poorly defined, at the left of the E line. On standing, the colour of the solution changed to brown and gave the spectrum of alkaline hematin, the colouring group.

KIßKALT

In the same year, another German hygienists, one of Lehmann’s assistants at the Institute of Hygiene in Würzburg,  Karl Kißkalt (1875 – 1962), confirmed Lehmann’s observations and showed that the same red colour resulted if the meat was left in saltpeter (potassium nitrate) for several days before it was cooked.

HALDANE

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The brilliant British physiologist and philosopher, John Scott Haldane weighed in on the topic.  He was born in 1860 in Edinburgh, Scotland. He was part of a lineage of important and influential scientists.

J. S. Haldane contributed immensely to the application of science across many fields of life.  This formidable scientist was for example responsible for developing decompression tables for deep sea diving used to this day.

“Haldane was an observer and an experimentalist, who always pointed out that careful observation and experiments had to be the basis of any theoretical analysis. “Why think when you can experiment” and “Exhaust experiments and then think.” (Lang, M. A. and Brubakk, A. O. 2009.  The Haldane Effect)

S. J. Haldane applied the same rigour to cured meat and became the first person to demonstrate that the addition of nitrite to haemoglobin produce a nitric oxide (NO)-heme bond, called iron-nitrosyl-hemoglobin (HbFeIINO).

Haldane showed that nitrite is further reduced to nitric oxide (NO) in the presence of muscle myoglobin and forms iron-nitrosyl-myoglobin. It is nitrosylated myoglobin that gives cured meat, including bacon and hot dogs, their distinctive red colour and protects the meat from oxidation and spoiling.

This is how he discovered it. Remember the observation made by K. B. Lehmann that the colour of fresh meat cooked in water with nitrites and free acid to give a spectrum showing an absorption band just at the right of the D line, and a second band, often poorly defined, at the left of the E line.

Haldane found the same colour to be present in cured meat.  That it is soluble in water and giving a spectrum characteristic of NO-hemoglobin. The formation of the red colour in uncooked salted meats is explained by the action of nitrites in the presence of a reducing agent and in the absence of oxygen upon haemoglobin, the normal colouring matter of fresh meats.  He showed that the redox reaction occurs in meat during curing (1901).

Haldane finally showed the formation of nitrosylhemochromogen from nitrosylhemoglobin (nitrite added to haemoglobin) when thermal processing has been applied and identified this as the pigment responsible for the cooked cured meat colour.  He attributed this formation to NO-hemoglobin denaturing into two parts namely hemin (the colouring group) and the denatured protein (1901).

HOAGLAND

Ralph Hoagland

Ralph Hoagland was the Senior Biochemist, Biochemie Division, Bureau of Animal Industry, United States Department of Agriculture in Chicago.  Prior to this appointment, Hoagland was the department head of the Minnesota College of Agriculture (part of the University of Minnesota), appointed in 1909.  Presently, the College of Agriculture is the College of Biological Sciences. (http://cbs.umn.edu/ and The Bismarck Tribune; 1912)

In 1908 he published results obtained upon studying the action of saltpeter upon the color of meat and “found that the value of this agent in the curing of meats depends upon its reduction to nitrites and nitric oxide, with the consequent production of NO-hemoglobin, to which compound the red color of salted meats is due.”  He found that “saltpetre, as such, [had] no value as a flesh-color preservative.”  (Hoagland, R.  1914.)

The results of his 1914 publication are summarised by himself as follows:

a.  The colour of uncooked salted meats cured with potassium nitrate, or saltpetre, is generally due, in large part at least, to the presence of NO-hemoglobin, although the colour of certain kinds of such meats may be due in part or in whole to NO-hemochromogen.  (Hoagland, R.  1914.)

b.  The NO-hemoglobin is produced by the action of the nitric oxide resulting from the reduction of the saltpetre used in salting upon the haemoglobin of the meat.  (Hoagland, R.  1914.)

c.  The colour of cooked salted meats cured with saltpetre is due to the presence of NO-hemochromogen resulting from the reduction of the colour of the raw salted meat on cooking.  (Hoagland, R.  1914.)

BARCROFT AND MULLER

They did not discover the link between nitrite and methaemoglobin, but they were the first to venture an opinion in 1911 on the quantitative relationship that exists between nitrite added and the formation of methaemoglobin.  (reported by Greenberg, L. A. et al.; 1943)  This is a form of haemoglobin where the iron in the heme group is in the ferrous (CodeCogsEqn (1)) state and not in the ferric (CodeCogsEqn (2) ) state.  In this state, it can not bind oxygen and in the body, an enzymic action is required to convert it back to haemoglobin.

The reason why haemoglobin turns brown is that nitrite is a very strong heme oxidant.  It is the same reason why meat (in particular comminuted meat) that has been injected or tumbled with nitrite also turns brown.  This capacity of nitrite increases as the pH decreases.  Nitrite itself may be partially oxidised to nitrate during the process of curing and during storage.  (Pegg and Shahodi, 2000)

LADISLAV NACHMÜLLNER

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In 1915, at age 19, Ladislav Nachmüllner invents Praganda, the first legal commercial curing brine containing sodium nitrite in the city of Prague.  He says that he discovered the power of sodium nitrite through  “modern-day professional and scientific investigation.”  He probably actively sought an application of the work of Haldane. He quotes the exact discovery that Haldane was credited for in 1901 that nitrite interacts with the meat’s “haemoglobin, which is changing to red nitro-oxy-haemoglobin.”  (The Naming of Prague Salt)

MITCHELL AND COLLABORATORS

In February 1916, H. H. Mitchell, H. A. Shonle and H. H. Grindley from the Department of Animal Husbandry at the University of Illinois, Urbana, published “The Origin of the Nitrates in the Urine,” showing that mammals produce nitrate.

LEWIS AND MORAN

In 1928, these researchers suggested that nitrite had antimicrobial efficacy.  This was later confirmed by others.  (example Evans and Tanner, 1934; Tarr, 1941, 1942, 1944).  This becomes one of the great examples of the discovery and continued re-discovery of the same fact by successive civilisations.  Beginning with Lewis and Morgan, the antimicrobial efficacy of nitrite was now being subjected to a modern scientific scrutiny despite thousands of years of evidence to the facts.  (Peter, F. M. (Editor), 1981)

BROOKS

The reaction of nitrite through the formation of nitrous acid and “its reaction with deoxyhemoglobin to form nitric oxide (NO) and methemoglobin was more fully described by Brooks in 1937.  (Gladwin, M. T., et al.; 2008)

DOYLE

The mechanism and unusual behaviour of the reaction of nitrite with deoxyhemoglobin and nitric oxide formation are further described by Doyle and colleagues in 1981.”  (Gladwin, M. T., et al.; 2008)

STEINKE AND FOSTER

In 1951 they became the first to demonstrate conclusively the antimicrobial efficacy of nitrite in meat products when added at the levels in use today by commercial curing operations.  (Peter, F. M. (Editor), 1981)

H. C. HORNSEY

In 1956 he demonstrated that the characteristic red pigment of cooked cured meat could be extracted completely by an 80% acetone-water mixture.  This made the collection of data on the electronic adsorbance and reflectance of the cooked cured meat pigment possible and provided an invaluable tool for future researchers.  (Hornsey, 1956)

JOHN KENDREW AND MAX PERUTZ

“In 1958 and 1960 molecular biologist John Kendrew published  “A Three-Dimensional Model of the Myoglobin Molecule Obtained by X-ray Analysis” (with G. Bodo, H. M. Dintzis, R. G. Parrish, H. Wyckoff,) Nature 181 (1958) 662-666, and “Structure of Myoglobin: A Three-Dimensional Fourier synthesis at 2 Å Resolution” (with R. E. Dickerson, B. E. Strandberg, R. G. Hart, D. R. Davies, D. C. Phillips, V. C. Shore). Nature 185 (1960) 422-27). These papers reported the first solution of the three-dimensional molecular structure of a protein, for which Kendrew received the 1962 Nobel Prize in chemistry, together with his friend and colleague Max Perutz, who solved the structure of the related and more complex protein, haemoglobin, two years after Kendrew’s achievement.”  (www.historyofinformation.com)  This becomes a crucial tool to progress our understanding of the interaction of nitrite and nitric oxide with the meat protein.

SALVADOR MONCADA AND LOUIS IGNARRO

A phenomenal discovery was made when nitric oxide was identified as a key signalling molecule in human physiology, showing that meat curing is a “natural process”.  “Lining almost all blood vessels on the inside is a layer of cells known as the endothelium.  A very important function of the endothelium was first reported in 1890 by Furchgott and Zawadzki.  The presence of acetylcholine (a small biologically active molecule) in the blood stream effects vasodilation and it was generally assumed that acetylcholine acted directly upon vascular muscle.  However, this was found not to be the case.  Furchgott and Zawadzki showed convincingly that that acetylcholine acted, not upon the muscle of the artery, but upon the endothelium and the endothelium produces a “second messenger” which then acts upon the muscles to effect relaxation.  This second messenger was christened “the endothelium-derived relaxing factor” (EDRF).”  (Cullen, C, Lo, V.;  2005)

During the 1980’s, an intense effort was effected to identify the EDRF.  It was initially assumed that it would turn out to be a complex molecule like a hormone.  This speculation enhanced the surprise when the chemical nature of the molecule was finally determined.  It turned out to be a small diatomic molecule called Nitric Oxide (NO).  “That it had a physiological role, in a process as important as vasodilation, came as a complete surprise.” (Cullen, C, Lo, V.;  2005)

“The discovery was made simultaneously by a group at the Wellcome Research Laboratories in Beckenham led by Professor Salvador Moncada and by a group in the USA led by Professor Louis Ignarro.  The 1998 Nobel Prize in Physiology and Medicine was awarded for this discovery.  Once nitric oxide had been detected in one physiological process it was found to have roles in many others, from inflammation to crying.”  (Cullen, C, Lo, V.;  2005)

The debate on the safety of nitrites and nitrates in meat curing are not settled by these developments. What it does is to bring to bear much greater interest upon nitrite and nitric oxide and their role in human physiology, including the health risks associated with their intake. It is nevertheless an astounding fact that meat curing has, through the ages, kept so close to natural physiological processes.

CONCLUSION

These formidable scientists laid the scientific foundation for the full understanding of the mechanism behind curing.  All questions have still not been answered yet, but we continue to build on the work of these men.  Together, their work shapes our understanding of the action of nitric oxide on blood and muscle protein.  Meat curing is, in the end, a natural process that has been practised for thousand of years.

(c) Eben van Tonder

 

References:

Extracts from:

Concerning the direct addition of nitrite to curing brine

The Naming of Prague Salt

Additional information references:

The Bismarck Tribune (Bismarck, North Dakota); 10 July 1912; page 2.

Brenner, E..  2014.  Human body preservation – old and new techniques Erich Brenner.  J. Anat.(2014) 224, pp316–344 doi: 10.1111/joa.12160

Butler, A. R., Nicholson, R..  2003.  Life, Death and Nitric Oxide. Royal Society of Chemistry.

Butler, A. R. and Feelisch, M.  New Drugs and Technologies.  Therapeutic Uses of Inorganic Nitrite and Nitrate From the Past to the Future.  From:  http://circ.ahajournals.org/content/117/16/2151.full

Cole, Morton Sylvan, “Relation of sulfhydryl groups to the fading of cured meat ” (1961). Retrospective Theses and Dissertations. Paper 2402

Cullen, C, Lo, V..  2005.  Medieval Chinese Medicine: The Dunhuang Medical Manuscripts.  Routledge Curzon.

Dormandy, T..  2006.  The Worst of Evils: The Fight Against Pain. Yale University Press.

Ferry, R. M..  1923.  STUDIES IN THE CHEMISTRY OF HEMOGLOBIN.
Department of Physical Chemistry, in the Laboratory of Physiology; Harvard Medical School, Boston

Gladwin, M. T., Grubina, R., Doyle, M. P..  2008.  The New Chemical Biology of Nitrite Reactions with Hemoglobin: R-State Catalysis, Oxidative Denitrosylation, and Nitrite Reductase/Anhydrase.  Acc. Chem. Res., 2009, 42 (1), pp 157–167, DOI: 10.1021/ar800089j, Publication Date (Web): September 11, 2008, American Chemical Society

Greenberg, L. A. Lester, D., Haggard, H. W., 1943.  THE REACTION OF HEMOGLOBIN WITH NITRITE, From the Laboratory of Applied Physiology, Yale University, New Haven, Received for publication, September 10, 1943.

Gayon, U., and G. Dupetit. 1883. La fermentation des nitrates. Mem. Sot. Sci. Phys. Nat. Bordeaux Ser. 2. 5:35-36.

Haldane, J.  1901.  The Red Colour of Salted Meat.

Hoagland, R.  1914.  Cloring matter of raw and cooked salted meats.  Laboratory Inspector, Biochemie Division, Bureau of Animal Industry.  Journal of Agricultural Research, Vol. Ill, No. 3 Dept. of Agriculture, Washington, D. C. Dec. 15, 1914.

Hornsey, H. C. “The Colour of Cooked Cured Pork. I. Estimation of the Nitric oxide-Haem Pigments”. J. Sci. Food Agric. 1956, 7, 534-540.

Hurst, J. W., 1989.  M. D., T. Lauder Brunton, 1844- 19 16, w. B. FYE, M.D Cardiology Department, Marshfield Clinic, Marshfield, Wisconsin, USA. Clin. Cardiol. 12, 675-676 (1989)

Lavoisier, A.  1965.  Elements of Chemistry.  Dover Publications, Inc.  A republication of a 1790 publication

Mitchell, H. H.., Shonle, H. A., Grindley, H. S..  1916.  THE ORIGIN OF THE NITRATES IN THE URINE, From the Department of Animal Husbandry, University of Illinois, Urbana

Morton, I. D. and Lenges. J.  1992.  Education and Training in Food Science: A Changing Scene.  Ellis Hornwood Limited.

Meusel, E. 1875. De la putrefaction produite par les batteries, en presence des nitrates alcalins. C. R. Hebd. Seances Acad. Sci. 81:533-534.

Peter, F. M. (Editor), 1981.  The Health Effects of Nitrate, Nitrite, and N- Nitroso Compounds.   Part 1.  National Acadamy Press

Pegg, R. B. and Shahidi, F.. 2000.  Nitrite curing of meat.  Food & Nutrition Press, Inc.

Péligot E. 1841.  Sur l’acide hypoazotique et sur l’acide azoteux. Ann Chim Phys.; 2: 58–68.

Scheele CW. 1777. Chemische Abhandlung von der Luft und dem Feuer. Upsala, Sweden: M. Swederus.

http://cbs.umn.edu/academics/departments/bmbb/about/history/timeline

http://www.historyofinformation.com/expanded.php?id=3015

Photo Credits:

L Da Vinci:  https://www.codeavengers.com/c/gabrielj/leonardodavinci.html

Carl Scheele:  http://www.explicatorium.com/biografias/carl-sheele.html

Justinus Kerner:  https://en.wikipedia.org/wiki/Justinus_Kerner

C.  R. Fresenius:  https://de.wikipedia.org/wiki/Carl_Remigius_Fresenius

Humphrey Davy:  https://global.britannica.com/biography/Sir-Humphry-Davy-Baronet

Lehmann:  http://www.kumc.edu/

J S Haldane:  https://en.wikipedia.org

T. LAUDER BRUNTON:  Hurst, J. W., 1989.  M. D., T. Lauder Brunton, 1844- 19 16, w. B. FYE, M.D Cardiology Department, Marshfield Clinic, Marshfield, Wisconsin, USA. Clin. Cardiol. 12, 675-676 (1989)

Hoagland.  Popular Science. 1912.

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