It is unfortunate that drawings of the Tree of Eugenics always omitted the roots which really kept it standing: ‘supremacism’, ‘racism’ and ‘bigotry’. During the 1920s, trial legislation was introduced to prevent undesirables from breeding with desirables. It might seem harsh that a single drop of bad blood on any branch of the family tree could block an otherwise perfect marriage, or that the undesirable was sent to prison for breaking the law – but the process worked well and was widely adopted. More direct action was encouraged by a persuasive paper from the Eugenics Institute on the devastating impact of inherited feeblemindedness. New laws were passed, permitting the surgical sterilisation of men and women to prevent the transmission of undesirable genes; the patient’s consent was not required, and anyway would have been pointless for all those too stupid to understand what was going on. By the outbreak of the Second World War, tens of thousands of people had been castrated or otherwise sterilised.
Nazi Germany is well known for its ruthless eugenic campaign to promote the idealised ‘Aryan’ German, while extinguishing Jews and other ‘undesirables’. However, none of the above took place in Germany.
Eugenics was an English invention, conceived by Darwin’s cousin Francis Galton, who became the first Professor of Eugenics at University College London. The first dedicated eugenics centre was built at Cold Spring Harbor on Long Island, New York, which later hosted the cutting-edge conference series at which Bill Astbury spoke in 1938. It was funded by the philanthropist Andrew Carnegie; huge sums were also pumped into eugenics by John D. Rockefeller and J.H. Kellogg, the Christian fundamentalist begetter of the cornflake and the Race Betterment Foundation of Michigan. The first law against ‘miscegenation’ (mixed-blood interbreeding) was the Racial Integrity Act of Virginia (1924), which barred marriage with individuals who had ‘any trace whatsoever of any blood other than Caucasian’. The Act was endorsed by the Anglo-Saxon Clubs of America and swiftly taken up by twenty-eight of the forty-eight United States. By the end of 1939, 40,000 Americans had undergone involuntary, unconsented sterilisation. But at least nobody had been killed.
Forced eugenic sterilisation was welcomed into Switzerland and Sweden, but found its most natural home in Germany, even before the Nazis took control. Francis Galton’s counterpart was Alfred Ploetz, who made hygiene a dirty word with the concept of Rassenhygiene (‘racial hygiene’) to promote the ideal genetic traits of pure-bred Germans. During the 1920s, Rassenhygiene became an obligatory part of medical training in Germany, interwoven with the classic genetics of Mendel and Morgan – a decade before the swastika first appeared on the cover of German medical journals and professors began their lectures with ‘Heil Hitler!’
The first German laws forbidding the dilution of ‘pure Aryan blood’ with Jewish blood (1936) were actually less draconian than the Virginia Racial Integrity Act, but eugenics rapidly became an integral part of the Nazi machine. Suddenly, genetics was everywhere: Genetic Clinics, Genetic Courts and a whole new breed of Genetic Administrators to run everything smoothly. People judged ‘genetically deficient’ were castrated surgically or sterilised with a blast of X-rays; one devilishly efficient device featured an X-ray tube hidden under a chair on which women sat while filling in deliberately time-consuming paperwork, long enough for their ovaries to catch an adequate dose.
The Nazis soon took negative eugenics to its logical conclusion and went where even Americans had feared to tread. Helped by lawyers, scientists and doctors, a 1920s policy paper was transformed into the Law for the Prevention of Hereditarily Diseased Offspring (1933). Now, a doctor could end the life of the patient sitting across the desk by ticking a couple of boxes and signing the declaration that this life was ‘unworthy of living’. The Aktion T4 programme for killing individuals with defective genes was rolled out across the Nazi diaspora in September 1939. Victims included 789 children with various physical and mental handicaps who lived at the Am Spiegelgrund clinic outside Vienna. They were left in their beds to die of starvation and dehydration, or murdered with injections of sedatives or disinfectants. Some parents were content that the Reich had shed some of its ‘ballast’; those who grieved were told that their child had died of pneumonia.
The eugenic killing programme soon broadened its scope. The list of genetic diseases that demanded eradication was expanded to include manic depression, epilepsy and alcoholism – which were not obviously inherited. And at once that door was opened, it was an easy descent into hell and the industrialised mass murder of Jews, Gypsies, homosexuals and others whose genes were insufficiently Aryan.
War effort
The Nazification of science had major consequences in and beyond Germany. The University Hospital of Tübingen, which once supplied a young Swiss doctor with pus-soiled bandages, reinvented itself as a eugenic centre of excellence whose surgeons performed hundreds of forced sterilisations. At the Robert Koch Institute in Berlin, the brilliant but insufficiently pro-Nazi Fred Neufeld was sacked as director and re-engaged as a low-paid honorary assistant. Neufeld continued his own work without having to oversee the Institute’s new research programmes, such as the typhus vaccines which killed hundreds when tested in the Buchenwald concentration camp.
Gerhard Domagk, head of pharmacology at the chemical giant IG Farbenindustrie, discovered that it was now dangerous for German scientists to have contact with foreigners. Domagk had ushered in the Age of Antibiotics by showing that the aniline dye Prontosil Red killed bacteria and could treat severe infections such as blood poisoning and gonorrhoea. At midnight on 26 October 1939, Domagk was awakened by the arrival of a telegram from Stockholm telling him that he had just been awarded the Nobel Prize for Physiology or Medicine. While Domagk and his wife were digesting this news, the phone rang. It was the Reich’s Press Office in Berlin, reminding him that if he had been offered a Nobel Prize, he had to turn it down.
Foolishly, Domagk wrote a thank-you letter to the Nobel Prize Committee, in which he mentioned that he might not be able to attend the award ceremony. His premonition was entirely accurate. A few days later, by Hitler’s personal command, the Gestapo came for him. Domagk had defied an edict from Hitler, prohibiting all German nationals from accepting Nobel Prizes; this followed the award of the Nobel Peace Prize to Carl von Ossietsky, an anti-Reich journalist whose exposé of Nazi brutality had spoiled the Berlin Olympics. Mercifully, Domagk was released unharmed after a week in prison. While inside, he was appointed an honorary member of the German Society for the Fight against Sexual Diseases – thanks to the efficacy of prontosil in gonorrhoea, then rampant in the German Army. He also left his guard convinced that he was mad, by insisting that he was in prison because he had won a Nobel Prize.†
Domagk’s brush with the Führer galvanised another Nobel laureate into taking dramatic action. Soon after Hitler seized power in 1932, Max von Laue had become Director of the Kaiser Wilhelm Institute for Physics when the current incumbent – Albert Einstein – decided not to return to Germany from a trip to Belgium. Von Laue knew he was under suspicion for having criticised the Nazi-branded Deutsche Physik and supporting the ‘Jewish physics’ of Einstein. Now scared of the unannounced knock on the door, he sent his gold Nobel medal for safekeeping to his friend, the physicist Niels Bohr in Copenhagen. This was risky, because stripping the Reich’s assets by sending valuables out of the country was punishable by death.
Von Laue’s medal enjoyed only a few months of asylum in Copenhagen. On 9 April 1940, German troops invaded Denmark and were outside Bohr’s lab by lunchtime. As the medal was engraved with von Laue’s name, it could have become his death warrant. One of Bohr’s colleagues, the Hungarian chemist George Hevesy, used an old alchemists’ trick to conceal the evidence. He dissolved it in the fiendishly corrosive ‘aqua regia’, made of concentrated nitric and hydrochloric acids. The reaction was agonisingly slow, but the 200-gramme medal eventually melted away into a nondescript orange solution. It was kept in a bottle on a laboratory shelf, waiting in chemical limbo for the end of
the war, when Hevesy reprecipitated the gold and sent it back it to the Swedish Academy. The medal was recast and presented to von Laue again in 1952.
Regime change
In September 1939, life had also become difficult for Oswald Avery. His life was not in danger, but with just four years to run until he reached retirement age, the future was looking uncertain.
The Rockefeller Institute and Hospital were both under new management and had changed course. Simon Flexner, the softly spoken dictator with the piercing blue eyes, had retired in 1936 after thirty-five years as director. His successor, Theodore Gasser, was just as brilliant and just as determined to make his mark – but by defeating cancer, heart disease and tuberculosis. Lobar pneumonia had dropped off the Rockefeller’s hit list. This was tough but fair, because The Captain of the Men of Death seemed to be in retreat, claiming only 25,000 lives in 1936 – half the number of deaths in 1908. And Avery could not claim the credit; he had done great science but had not found a magic bullet to stop the pneumococcus in its tracks.
Rufus Cole had retired as director of the hospital in 1938. Cole had been Avery’s collaborator and close friend. The new director, Tom Rivers, was neither of those things. Rivers was also clever, workaholic, ruthless and a bully. Known as ‘the father of American virology’ he was bored with bacteria. Pneumonia was only interesting if caused by viruses, which meant that no bacteriologist was going to succeed Avery as chief of the pneumonia research lab.
Avery’s latest young hopeful was Colin MacLeod, who had been with him for five years. MacLeod was a fellow Nova Scotian whose childhood had also been disrupted by religion. Despite criss-crossing Canada with his father, a Presbyterian minister, Colin had been ready to start medicine at McGill at the age of fifteen; they were not ready for him so he trod water for a year, filling in for a single-handed primary school teacher.
After qualifying as doctor in 1932, MacLeod had won a scholarship to work in Avery’s lab. He arrived during the summer of 1934, while Avery was on holiday in Maine. He knew exactly what he wanted to do, and without waiting to be Red Sealed, began to teach himself how to transform pneumococci. In the process, he created an R variant of a nasty Type III pneumococcus which had killed one of Cole’s pneumonia patients in 1916. It was wonderfully user-friendly: absolutely harmless and as stable as a rock, yet easily transformed into lethal S by extracts of dead S. MacLeod named it ‘R36’ to commemorate the number of times he had to run it through subcultures to tame it.
When Avery returned from his summer break, he found Colin MacLeod to be only slightly taller than himself, quiet and quick-witted. The old master joined his new apprentice at the bench and for the first time dabbled personally in the dark art of transformation. They made a good team, and Avery boldly declared his intention to ‘ascertain the nature and properties of the transforming principle’, which he believed could cast new light on ‘induced variations of living cells, not only pneumococci, but also those of other biological systems’.
Unfortunately, they discovered nothing interesting, and Avery’s new enthusiasm soon ran out. They tried to write a paper but it stalled at the first draft, written in pencil by MacLeod and heavily annotated by his chief. Avery drifted back to other projects, leaving MacLeod alone to chase the phenomenon on which he had pinned his career hopes. One, two and then three years of barren experiments went by, and the transforming principle was beginning to look like the kiss of death. After three years at the Rockefeller, where researchers were expected to ‘publish or perish’, MacLeod could only claim a couple of dull papers, neither of them about transformation.
In 1938, MacLeod’s fourth year in Avery’s lab, his luck changed dramatically. His salvation was something that could have wiped out everything that had made Avery famous – the antibiotic sulfapyridine, which killed all pneumococci, of every type, and appeared to be safe in humans. At a stroke, the whole business of typing and serum therapy, in which the Rockefeller had led the world, was redundant. Treating lobar pneumonia no longer needed clever people like Avery; it could be done better by any doctor who could spell ‘sulfapyridine’.
Tom Rivers, the cynical and all-powerful virologist, noted that sulfapyridine could ‘knock everything into a cocked hat’, but Avery and his group were quick to turn threat into opportunity. They moved straight in on the new wonder drug, working out its mechanism of action, benefits and risks. They were remarkably successful, and one of the best at riding the wave of novel research was Colin MacLeod. Now that he had abandoned the transforming principle, which had hung around his neck like an albatross, he was churning out papers and his career was back on course.
The conflict in faraway Europe had little impact on the Rockefeller until early summer 1940, when pessimists began predicting war between America and Japan. Tom Rivers encouraged his staff to join the Naval Reserve, and clandestine research projects on blood transfusion, war wound infections and mustard gas poisoning quietly got under way.
In September 1940, the Rockefeller was set back by the extinction of one of its brightest and most errant stars. Phoebus Levene died at the age of seventy-one, having worked beyond retirement and right up to his last day. He was remembered with affectionate respect for his immense energy and productivity, his polymathic knowledge and his artistic nature. There was no real need for an epitaph, because Levene had already summed up everything that mattered most to him: ‘So long as Life continues, the human mind will create mysteries and biochemistry will play a part in their solution.’ With the arrogance of hindsight, we might see a delicious irony in those words.
End game
Neither Avery nor MacLeod ever explained why, in late 1940, they went back to the frustrations of transformation. Perhaps MacLeod now felt secure with all his papers on sulfapyridine, or Avery saw the clock ticking – now just under two years to retirement – and seized one last chance to crack the most irritating mystery of his career.
This time, they threw everything at the transforming principle. They were assisted by a brute of a machine, billed ‘The Best in the World’, which churned out virulent S pneumococci by the kilo, rather than the gramme. This was an industrial cream separator, made by the Sharples Company. Milk was centrifuged inside a hollow cylinder, mounted vertically and spun at high speed by compressed air, producing a layer of cream that was siphoned off continuously. Some modifications were needed to concentrate live bacteria rather than cream; high-pressure steam was used to spin the cylinder even faster and it was encased in a splash-proof housing to stop Avery’s lab from being turned into a germ warfare testing-chamber. The ‘Sharples’ could charge through hundreds of litres of liquid culture medium in a morning, producing a thick crust of live S pneumococci which had to be scraped out of the cylinder by hand. (This was the procedure that Avery could not bring himself to watch.) The S pneumococci were then killed and the transforming principle extracted and purified using Henry Dawson’s recipe.
Avery and MacLeod picked up where they had left off three years earlier. Experiment No. 1 took place on either 13 October 1940 (according to MacLeod’s lab notebook) or 20 October (Avery’s record), and this time fortune smiled on them. MacLeod’s R36 performed impeccably, the purified transforming principle worked like a dream and, at last, they began to make real progress. The transforming principle was tantalising and infuriating. They knew exactly what it looked like and could even touch it, but had no idea what it was. When they added alcohol, as Lionel Alloway had done, attractive white fibres fell out of the solution; these could be collected, dried, weighed and redissolved – all without damaging its ability to turn R36 into a killer. It had other striking properties: a concentrated solution was so viscous that it barely flowed and it did peculiar things to light; when viewed from a critical angle, the clear liquid glowed with a beautiful silky sheen, like a moonstone.
But what was it?
Avery and MacLeod began by eliminating the likely suspects. SSS was already off the list, because purified SSS from virulent S pneumococci could n
ot transform R36. MacLeod finally killed off the notion with a decisive experiment which showed that R36 could still be transformed by dead Type III S pneumococci from which the peat-bog bacterial enzyme had stripped all the SSS. Could it be a protein? This was a stronger contender; proteins did everything else, so why not transformation? However, active solutions of transforming principle contained very little protein, especially when MacLeod added in a good shake with chloroform as a final purification step. Moreover, extracts of transforming principle still worked after being treated with heavy-duty protein-digesting enzymes, such as pepsin and the newly discovered trypsin. Maddeningly, though, the last tiny traces of protein could not be annihilated.
Some hints emerged about the composition of the transforming principle; biochemists like the late Phoebus Levene could have given Avery and MacLeod a valuable steer, but the findings meant nothing to them at the time. Extracts of transforming principle stopped working altogether when incubated with ‘phosphatase’, an enzyme from bone which destroyed phosphate groups. Could phosphate be an essential building-block of the transforming principle? Another clue came when MacLeod experimented with reagents that turn a tell-tale colour in the presence of a specific compound. History might have been rewritten if he had tried the colorimetric tests for purine or pyrimidine bases, but he had no reason to do that. Instead, he found that a solution of transforming principle became bright red on adding bial – a reaction that identifies an unusual sugar called D-ribose.
On reading about it, MacLeod learned that D-ribose was the hallmark of yeast nucleic acid, also known as ribose nucleic acid. Could this be the transforming principle? There was plenty of ribose nucleic acid in the extracts, but it turned out to be an innocent bystander. Avery’s colleague René Dubos‡ had recently isolated a peculiar enzyme, which he called ‘ribonuclease’ (‘RNase’) because its sole purpose was to break down ribose nucleic acid. MacLeod found that the transforming principle still worked after being treated with RNase, and so eliminated ribose nucleic acid as well. Soon after, according to MacLeod’s lab records, he tried out another colorimetric reagent. The result could have assured his place in history, but by then his mind was on other things because he had just made the greatest blunder of his career.
Unravelling the Double Helix Page 20