text: An Interview with Professor Manuel Varela: Konrad Emil Bloch- What does he have to do with Cholesterol? | Education News
  Home » Commentaries » An Interview with Professor Manuel Varela: Konrad Emil Bloch- What does he have to do with Cholesterol?
  Jul 4, 2019 by Michael F. Shaughnessy EducationViews Senior Columnist
  1) Professor Varela, Konrad Emil Bloch was born in Germany and studied in Munich- then what happened?
  A 1964 Nobel Laureate in Physiology or Medicine, Dr. Bloch was a famous biomedical scientist who discovered how cholesterol was made naturally in the body. On the 21st day of January, in 1912, Konrad Emil Bloch was born to Jewish parents Fritz (father) and Hedwig Striemer Bloch (mother) in the town of Neisse (presently Nysa), Germany, in the then eastern Prussian province of Silesia, presently Poland.
  In Munich, Germany, Bloch was an undergraduate student majoring in chemistry at the Technische Hochschule (technical university). While a university student young Konrad was inspired by a great professor and scientific investigator, Dr. Hans Fischer, who had just earned a Nobel of his own, in 1930, for his work on hemin, hemoglobin and chlorophyll. It was Prof. Fischer who influenced young Bloch to have an interest in studying the chemistry of naturally occurring molecules, such as fatty acids. As your question alludes, however, there was, at that time, a rather serious problem.
  In 1934, Konrad Bloch had just received his so-called Diplom-Ingenieur degree in chemistry when the dean told him that Prof. Hans Fischer could not accept Bloch into his laboratory as a graduate student. Bloch later learned that the dean had lied to him.
  No doubt because of Nazi Germany's racial laws, signed into legislation in the early 1930s, the real reason for his rejection had been completely different than mere rejection by a prominent scientist. Instead, Bloch's graduate school application at the Technische Hochschule was nefariously denied because he was, of course, of Jewish origin. Thus, Konrad Bloch needed to find a new graduate school, and he needed one quickly as it turned out, because the German Reich movement was spreading rather swiftly.
  Thus, seeking alternatives, Bloch made an inquiry of Prof. A. Butenandt, of the Technische Hochschule at Danzig. Unfortunately, Bloch's plea for graduate school in Danzig was refused there, too.
  Next, Bloch sent an application to Prof. F. Kögl, of Utrecht University, at The Netherlands, and Bloch was rebuffed, as well. While this latter rejection may seem to have been quite unfortunate at the time, because acceptance would have meant being able to leave Germany, it turned out to have two silver linings to it.
  First, Holland became occupied by the German Nazis only a few months after his rejection. Thus, even if Bloch had moved there, he would have been trapped in Europe by the Nazis, and it might have been impossible, therefore, to escape the holocaust. Second, in Prof. Kögl's laboratory, they had claimed to have made two rather fantastic discoveries, one pertaining to new plant hormone, called "heteroauxin" purified from horse urine, and the other discovery pertaining to D-amino acids purified from proteins sampled from tumor tissue. Both of these "fantastic discoveries" turned out to have been faked by a laboratory assistant in Kögl's laboratory. The scandal had become public only after World War II had come to an end.
  Meanwhile, back in the mid-1930s Nazi Germany era, it was clear to Bloch that he was no longer welcome to pursue a graduate education in Germany. Being aware of the anti-Semitic nature of the environment in Germany due principally to Adolf Hitler, his Nazi Party followers, and to the sympathetic general public, Bloch felt that he had no choice but to leave Germany, for good.
  Escape from Nazi-occupied Europe, however, did not happen for Konrad Bloch until 1936. The pathway out for Bloch took place by another route.
  With Prof. Fischer's blessing, Konrad Bloch found a new position as a laboratory assistant at the Swiss Research Institute at Davos, in neutral Switzerland. In Prof. Frederic Roulet's laboratory there, Bloch was put to work in resolving a conflict.
  One idea held that cholesterol could be purified from the lipid material in the human tubercle bacillus, the bacterium called Mycobacterium tuberculosis and the causative agent of tuberculosis. The other idea, supported by the great scientist Dr. Erwin Chargaff, held that such was not the case, that there was no cholesterol in Mycobacterium tuberculosis. That is to say, it was not clear whether the bacteria had cholesterol.
  Bloch's first experimental work had shown that Prof. Chargaff had been correct. Bloch failed to find cholesterol in the tubercle bacilli. The negative result was disappointing, but true. It was never published. Bloch was still trapped in Europe!
  Bloch's next project at Davos, in 1935, was to conduct phospholipid chemistry in order to prepare a compound called phosphatide from the Mycobacterium tuberculosis bacteria. He was supposed to follow the protocol as devised by Prof. Rudolph J. Andersen, from Yale University. When Bloch's preparation showed more phosphorous and much less nitrogen (in fact, no nitrogen) than was expected, he wrote to Dr. Anderson for advice on what to do next. Dr. Anderson's reply was that Bloch's preparation was probably better than his. The reply from Yale provided the needed courage on Bloch's behalf to write again to Dr. Anderson for the daring purpose of asking him for a job. In his 1987 memoirs, published in the prestigious Annual Review of Biochemistry, Bloch writes what happened next.
  In his 1987 review, Bloch reveals that, in 1936, he received two immediate replies from Yale. The first letter was from their dean congratulating him on his acceptance as a laboratory assistant in the Biological Chemistry department at their School of Medicine, and the other letter stating flatly that there were absolutely no funds available for the job offer at Yale.
  Nevertheless, Konrad Bloch arrived as an immigrant to New Haven, Connecticut, in the U.S., in December of 1936, with his life's savings, which were good enough to live on for a month, but nevertheless making good his escape from Nazi-occupied Europe.
  In essence, the immigrant traded his life's savings for his life.
  2) I understand his Ph.D. was from Columbia University in New York City- no mean feat- what did he study there and what was his major focus?
  Obtaining a graduate education at Columbia University is indeed an impressive accomplishment. Konrad Bloch's Ph.D. from the prestigious institution, however, took a rather circuitous route.
  Before having left Europe for good, Bloch had followed the advice of his boss Dr. F. Roulet and attempted to use the work that he (Bloch) had already performed at the Swiss Research Institute in Davos. You'll recall above that Bloch's work at Davos had been carried out in a way that was much improved over the originator of the protocol that was first developed at Yale. The result of Bloch's methodological approach was that he had purified the true product, phosphatidic acid, rather than the expected but elusive (and incorrect) phosphatide from the tubercle bacillus lipid material.
  The work, however, left Bloch forever scarred.
  You see, Bloch had actually injected himself with the phosphatidic acid preparations, one from the human tubercle bacillus into his left arm and the other from cow tubercle bacillus into his left arm. The injection into the left arm produced a reaction and a scar, two-inches in diameter, which stayed with Bloch for the remainder of his life!
  Reminiscing about the incident late in life, the elderly Dr. Bloch realized how greatly naïve the younger version of himself had been, apparently not giving a thought back then, in 1936, to the fact that his tubercle bacillus had stayed alive after multiple exposures to the chemical acetone!
  Despite the scars, or maybe because of them, Bloch's work at Davos, Switzerland, was published in two peer-reviewed scientific journals. Dr. Roulet's idea that these published works, Bloch's first two scientific articles, might suffice for a Ph.D. project, was put to the test. According to the plan, Bloch would enter graduate school at the University of Basel, in Switzerland, and submit his two papers to the graduate committee for acceptance as a Ph.D. thesis. The plan failed to work.
  Bloch's Ph.D. thesis work in 1936 at Basel was rejected by all faculty members of the committee. It had been deemed "insufficient." It was a terrible blow, because he now had to go to another school and start all over again!
  Years later, returning to Basel as a Nobel Prize Laureate and keynote speaker, he presented a seminar at the same institution and couldn't resist relating this earlier incident to his captivated audience. Interestingly, his host's curiosity at Basel was piqued, and after the seminar he decided to look up the old records of the now famous 1936 thesis rejection. In the archives, Bloch's host found that the unanimous rejection in reality took the form of only one faculty member of the graduate committee having actually voted no. The policy was that if one member voted no, then the rejection was considered unanimous. The lone dissenter had been dissatisfied with the thesis because in Bloch's two publications, he had failed to cite the dissenter's own papers!
  Back at Yale, in early 1937, Dr. Anderson, who was instrumental in providing Bloch the opportunity to escape Nazi Germany as an immigrant to the U.S., had given Bloch more advice. The good professor Anderson told Bloch he wouldn't learn much at Yale and that he should, therefore, go to Columbia and study under Prof. Hans Clarke.
  Along with a letter of recommendation that Dr. Fischer in Germany had provided to Bloch, he also provided some advice, which was basically to seek the advice from the distinguished Prof. Max Bergmann, who had studied under Dr. Fischer and had currently been at the Rockefeller Institute for Medical Research, in New York. The great Profs. Bergmann and Anderson were in complete agreement: Bloch should go to Hans Clarke's laboratory at Columbia.
  The interview with Dr. Clarke ended in an acceptance into graduate school at Columbia University. Bloch attributed his acceptance, perhaps very likely in jest, to the fact that he played the cello, and that Dr. Clarke, who appreciated chamber music, warmly welcomed the new cellist.
  Bloch conveyed the good news of his acceptance to his parents and to Profs. Anderson and Bergmann, at which point Bergmann conveyed more good news. Dr. Bergmann told Bloch that he was aware of a promising funding source for Bloch's graduate education!
  The source of this funding for graduate school was Dr. Leo Wallerstein, in charge of Wallerstein Laboratories, Inc. Dr. Wallerstein had become quite wealthy, having invented a method for clarifying Lager beer using proteolytic enzymes. The lucrative nature of the invention made Dr. Wallerstein a noted philanthropist who was especially interested in helping young scholars and scientists who were refugees trying to escape war torn Europe and Nazi Germany. Bloch was awarded a one-year Wallerstein graduate fellowship for graduate study at Columbia.
  Unlike the case with the unforgiving Basel graduate committee, Dr. Clarke was happy to accept Bloch's first two papers as sufficient for a partial fulfillment of a Ph.D. thesis, but Columbia's policy was that at least some of the graduate work had to be performed at Columbia proper. Thus, Dr. Clarke assigned another small project to Bloch.
  In Clarke's laboratory at Columbia, Konrad Bloch was charged with making several derivatives based on N-alkyl-cysteine, in order to measure how labile the sulfur content was in the products. The project went well, except that at one point, an important product, called N-methyl-cysteine hydrochloride, failed to turn into visible crystals, as had been expected. It was considered a setback.
  However, with sufficient incubation time being allowed the expected crystals managed to surface! Now, it was a cause for celebration!
  Apparently, prominent scientists, one being the famous Prof. Vincent du Vigneaud at Cornell, had also tried to obtain the important N-methyl-cysteine crystals and failed.
  A gleeful Bloch happily provided the du Vigneaud laboratory at Cornell some Columbian crystals to use as a starter material for the Cornell group. A forever grateful Dr. du Vigneaud paid a visit to Columbia University and thanked Bloch in person.
  The N-methyl-cysteine work performed at Columbia, along with the phosphatidic acid work performed at Davos, was deemed sufficient for a graduate thesis, and Konrad was granted a Ph.D. from Columbia University, in 1938.
  3) Life took him to Harvard and eventually to the Nobel Prize- can you re-trace some of his achievements along the way?
  The road to Harvard was also circuitous. After taking his Ph.D. from Columbia University, in 1938, under Prof. Clarke, the newly minted Dr. Bloch worked briefly with Max Bovarnick in the same lab trying to synthesize a so-called "super hormone," that is, one that took a thyroxin derivative and used it to load up with lots of iodine atoms and phenyl rings. It was hoped that the massive end-product would have potent biological activity. Unfortunately, the super hormone product had no activity.
  Next, Dr. Rudolf Schoenheimer, another Columbia University faculty who had been trained earlier with Prof. Anderson at Yale, offered Dr. Bloch a job with him. Prof. Schoenheimer was a young genius who invoked a method for tracing radioactive isotopes through biochemicals in order to elucidate metabolic pathways, an important area of biomedical research. He put Dr. Bloch in charge of making radioactively labeled creatine to trace the nitrogen-15 isotope to creatinine. Next, Dr. Bloch was tasked with attempting to elucidate the biosynthetic pathway for creatine. However, before the second project regarding creatine biosynthesis could be finished, Dr. Bloch received an offer he couldn't refuse.
  Dr. Bloch took a higher-paying job in New York, at the Mount Sinai Hospital Cancer Research center. It paid twice the salary he had been making at Columbia, and he needed the money in order to afford getting married to Lore Teutsch. A year later, however, Dr. Schoenheimer provided a counter offer, matching the New York salary. Dr. Bloch had recalled how happy and productive the work had been in Schoenheimer's laboratory, and he eagerly returned to Columbia, in 1940.
  It is back at Columbia where Dr. Schoenheimer had asked Dr. Bloch to now study cholesterol synthesis. The question put to them was where did the oxygen in cholesterol come from? That is, did the oxygen come from water or molecular oxygen (i.e., O2)? As brilliant as these two hypotheses were (water versus O2), the project went nowhere. Unfortunately, the mass spectroscopy methodology that was badly needed in order to measure the incorporated oxygen atoms into cholesterol hadn't been invented at the time.
  Then, to make matters worse, a terrible disaster happened.
  Although Dr. Schoenheimer was a genius, he was also a manic depressive, and on September 11, 1941, he committed suicide. In his wake he left behind mayhem and uncertainty in the laboratory.
  Following the advice of Dr. Hans Clarke, the group that had been left behind thus chose to finish the remaining projects and then study whatever they might so desire afterwards. The problem was, however, that no one had actually been charge of the individual projects in Dr. Schoenheimer's laboratory. It was not certain who would take over each of the various projects. After much discussion, Dr. Bloch got the so-called lipid project; and Dr. D. Rittenberg had gotten the protein synthesis project, while Dr. D. Shemin got the amino acid project.
  However, Dr. Bloch had soon thereafter lost all interest in pursuing the oxygen origin question for cholesterol. Another laboratory group from Germany had found that the hydrogen and oxygen atoms in acetate were readily converted into sterols. Dr. Bloch focused, instead, on examining cholesterol as a source of bile acids and steroid hormones. He continued with this area of study at the University of Chicago, where he took on an academic post as an assistant professor in their Biochemistry department. During this time, he also began a systematic evaluation of the reactions that made cholesterol, using acetate, of course, as a starting point. The cholesterol synthesis work, though labor intensive and time consuming, nevertheless, proved to be fruitful.
  In 1954, Dr. Bloch, an established investigator in his own right, moved to Harvard. In his 1987 memoir, Dr. Bloch wrote that he had no reason to leave Chicago, except that the Bloch family had long lived to go to the big city. Probably another reason to leave Chicago was that Dr. Bloch's salary would be endowed, and he would thus become the new Higgins Professor of Biochemistry, a prestigious position at a prestigious institution.
  Back in Chicago, before the untimely death of Prof. Schoenheimer and with the knowledge firmly in hand that the starting point for making cholesterol was the 2-carbon molecule called acetate, Dr. Bloch had invoked the labelling approach to study cholesterol synthesis. It proved to be a daunting task because cholesterol had 27 carbon molecules! Using radiolabeled acetate as a starting point they found that at least half of the carbons in cholesterol came from acetate.
  Besides acetate, another clue to making cholesterol was shark fat.
  The 1926 work of Prof. Harold John Channon at University College, London, showed that when laboratory test animals were fed a preparation of shark oil called squalene, cholesterol levels increased, indicating that squalene was an intermediate, probably between acetate and the cholesterol end product. Furthermore, in 1934, Prof. Robert Robinson at Oxford had hypothesized that the shark squalene could form a circle upon itself, a process known as cyclization, to form the ring-based cholesterol structure. It was an intriguing idea.
  Meanwhile, the cholesterol synthesis experiments of Prof. Bloch continued in the Chemistry department at Harvard, after his move to Cambridge, Massachusetts, in 1954.
  Prof. Robinson had proposed a rather specific mechanism for circularizing the squalene to form cholesterol in one step. But when Prof. Bloch and his colleague Dr. Robert Woodward considered the cyclization phenomenon, they felt that another intermediate called lanosterol would be formed, instead, of cholesterol. Using radiolabeled acetate, they found that the appropriate radioactive carbon of the acetate ended up in lanosterol, as predicted, demonstrating that the so-called Bloch-Woodward mechanism that squalene circularized to form lanosterol was correct. Furthermore, it showed that the Robinson proposal that squalene circularized to make cholesterol was inaccurate.
  In 1965, Prof. Konrad Bloch shared the Nobel with Prof. Feodor Lynen, in the category of Physiology or Medicine.
  The path from Munich to Harvard and the Nobel had been circuitous indeed.
  4) Bloch apparently shared the Nobel Prize in Physiology or Medicine back in 1964- interestingly enough when the Beatles were arriving on American shores with Feodor Lynen. Who was Lynen and how did they come to collaborate?
  Professor Feodor Lynen shared the Nobel Prize with Prof. Bloch in 1964. Dr. Lynen was housed at the prestigious Max-Planck Institute for Cell Chemistry. It's not entirely clear that these two biomedical investigators collaborated together. Each investigator had somewhat distinctive interests. Prof. Bloch's interest was primarily concerned with the metabolism of cholesterol while that of Prof. Lynen was in the area of lipid and amino acid metabolism.
  The main scientific connection between Profs. Bloch and Lynen was acetyl coenzyme A (acetyl CoA), an important molecule described by the famous Nobel Laureate Fritz Lipmann. At Harvard Prof. Lipmann delineated the biochemical conversion of pyruvate, the glycolytic oxidative breakdown product of glucose, to acetyl CoA, which is a central metabolite.
  In Prof. Bloch's case, acetate was converted to acetyl CoA and it could combine with acetoacyl CoA to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) and about 30 more biochemical steps later, cholesterol was made in the end. Acetyl CoA was the starting point, and Prof. Bloch's interest was, thus, a biosynthetic process.
  In Prof. Lynen's case, acetyl CoA was formed after the breakdown of lipids. The enzyme lipase participates in fat breakdown and releases free fatty acids, which are long hydrocarbon chains. The fatty acid breakdown releases acetyl CoA molecules. The acetyl CoA was the endpoint of fatty acid breakdown, and Prof. Lynen's interest was, thus, a degradative process.
  During the process of fatty acid breakdown metabolism, two carbons are cleaved off of the long chain fatty acids, in a step-by-step series of biochemical reactions. Such fatty acid molecules can be quite lengthy, anywhere on average of about 16 carbons, sometimes shorter or longer, depending on the lipid composition. For example, a fatty acid that consists of 16 carbons along the chain will, therefore, yield 8 molecules of acetyl CoA. Each acetyl CoA molecule contains two carbons. The fatty acid breakdown pathway is called beta-oxidation and is often denoted as β-oxidation.
  If the fatty acid chain consists of an odd number of carbons in the chain, acetyl CoA molecules are still produced but eventually a three-carbon version will also be made, called propionyl CoA which has to be handled somewhat differently, biochemically speaking. Propionyl CoA can be converted to a succinyl CoA, which can then be further metabolized.
  The end commodities of fatty acid breakdown, acetyl CoA and propionyl CoA, are oxidized by the famous Krebs cycle, also known as the citric acid cycle or the tricarboxylic acid cycle, a pathway for which Sir Dr. Hans Krebs shared the Nobel Prize, in 1953, with Prof. Lipmann.
  5) Cholesterol and fatty acid metabolism seem to be the main thrust of their work. Why is this stuff so important and did it serve as any kind of foundational work?
  Cholesterol is important for several reasons. First, it is known to be acutely involved in cardiovascular disorders such as atherosclerosis and coronary artery disease. These conditions can in turn lead to increased risks of stroke and heart attacks. Associated with this, certain genetic diseases are known in which cholesterol concentrations in the blood are hyper-elevated, leading to serious medical conditions. These issues are enormously important in biomedical science.
  While the reduction and maintenance of cholesterol in the blood to healthy levels is a major objective in human cardiovascular medicine, cholesterol may also serve useful purposes. Thus, another reason cholesterol is important is the role it plays as a starting point, a precursor if you will, for the synthesis of signaling molecules, such as steroid hormones. Among these biomolecules include cortisol, estradiol, progesterone, and testosterone.
  A fourth reason cholesterol is important is that when it is incorporated into the insides of biological membranes, which surround living cells, cholesterol serves to regulate the fluidity of the membranes. Another justification for the relevance of cholesterol is that in the skin, it serves as a precursor to the synthesis of vitamin D using ultraviolet light from the sun in order to do so. The vitamin D in turn plays a role in controlling the levels and biochemistry of calcium and phosphorous. Cholesterol is also an important precursor in the formation of bile salts, which in turn are useful for emulsifying dietary fats and in inhibiting the growth of potentially dangerous microbes, especially certain Gram-positive bacteria.
  Fatty acids are important for several reasons. First, the fatty acids can be used as a sort of energy storage system in living beings. The storage form of lipids consists of molecules called triacylglycerols. These triacylglycerols consist of a glycerol backbone connected to three long chain fatty acids. Another reason fatty acids are important is that they can be used as a biological fuel, i.e., energy for conducting living purposes. When an individual needs biological energy, it can be obtained from the stored lipids.
  Another important aspect to fatty acids is that they are the staring points for the biosynthesis of phospholipids, which in turn can be used to make biological membranes that surround living cells. Without biological membranes, there would be no life, and fatty acids play an important role in maintaining this life process.
  Fatty acids can also be used biochemically to modify proteins. Fatty acids can be attached to certain proteins in order to alter their structure and, thus, their functions. This is an important way to regulate the activities of proteins.
  In cancer, fatty acid metabolism is altered in such a way that fatty acid synthesis is enhanced. This is because when tumor tissue is produced, the cancer cells being made need membranes to surround them, and fatty acids are needed to make the membranes.
  Pathologically, cholesterol and fatty acids can work together. A diet rich in both cholesterol and fatty acids can result in greatly enhanced formation of atherosclerotic plaques, which can block coronary arteries, reducing oxygen-rich blood flow to the heart and increasing the risk of strokes and myocardial infarctions, i.e., heart attacks.
  6) What have I neglected to ask about this famous scientist?
  While Prof. Bloch's prime interest of study was focused on cholesterol biochemistry, as mentioned above, there were several other areas that held his investigative curiosity, as well. For instance, while Prof. Lynen's focus was on fatty acid hydrolysis, Dr. Bloch's focus, in contrast, was in the biosynthesis of fatty acids. Regarding this latter focus, Dr. Bloch took advantage of microbes, such as bacteria and yeasts, to study fatty acid production.
  He found out from several of his colleagues that these kinds of microbes could easily be made into mutant versions that exhibited important properties which could be exploited for the study of lipid metabolism. For instance, Prof. Bloch used microbial mutants to examine the oxygen requirements for the synthesis of the fatty acid called oleic acid from stearoyl CoA and oleoyl CoA precursors.
  Dr. Bloch was a key investigator in the discovery of an important protein, called acyl carrier protein, ACP. The ACP molecules were demonstrated to be important in making fatty acids. Many of the precursor intermediates formed during fatty acid biosynthesis had ACP molecules attached to them. During their studies, it was found out that another research group headed by Dr. Roy Vagelos was working along the same lines, studying the ACP processes, as well. After agreeing to meet at a scientific conference over cocktails, the two groups decided that instead of partaking in a race to the finish, each group would instead focus on separate projects so as to not duplicate their efforts. Thus, Dr. Bloch's group studied the production of unsaturated fatty acids under oxygen-free conditions while Dr. Vagelos's research laboratory focused on studying the process of fatty acid chain elongation.
  Using mutant microbes, Prof. Bloch also managed to learn about the biochemistry of unsaturated fatty acids, such as olefinic acid, in lactic acid bacteria like Lactobacillus. There were conflicting ideas regarding the production of olefin, an unsaturated form of fatty acid. One idea was that it formed because of an oxidative dehydrogenation mechanism versus the notion that olefin production involved a dehydration step of so-called β-hydroxy acids. To support their contention, bacterial Escherichia coli mutants were used to purify the necessary enzyme responsible, called β-hydroxydecanoyl thioester dehydrase, which they colloquially, perhaps affectionately, referred to simply as their "dehydrase."
  In Dr. Bloch's continued study of the β-hydroxydecanoyl thioester dehydrase enzyme it turned out to produce a rather startling discovery!
  To better examine the so-called dehydrase enzyme, Dr. Bloch's laboratory needed its substrate in order to do so. However, the required substrate, 3- hydroxydecanoyl thioester, was not available commercially for purchase. So they set about to make necessary substrate in their laboratory, which turned out to be an arduous painstaking, but fortuitous, effort!
  First, they found a mixture of contaminating molecules in their substrate preparation. The mixture included not only the necessary substrate but also a confounding inhibitor molecule! The Bloch laboratory managed to purify each of the compounds in the mixture, including the pure substrate, but also another substance, called 3-decynoyl thioester, which when purified to homogeneity, inhibited the dehydrase enzyme! Shockingly, the dehydrase enzyme MADE this confounding inhibitor! That is to say, by making its own specialized inhibitor, the enzyme committed suicide!
  Dr. Bloch called this phenomenon "enzyme suicide!"
  On the 15th day of October, in the year 2000, died from congestive heart failure, at the age of 88 years. His beloved wife Lore passed away 10 years later, at the age of 98 years. The Bloch couple had had two children, Peter and Susan, plus 2 grandchildren.