Dr Tikvah Alper: a short history of her scientific career

Abstract

Purpose

This article can only skim the surface of an extraordinary career of Dr Alper from the early days in South Africa and throughout her life.

Conclusions

She overcame many obstacles to become widely acknowledged as having had an immense effect on the study of radiation biology. Her very considerable personal scientific achievements in no way prevented her from taking time to help and inspire others in the field as well as maintaining a long and happy family life. If an example is needed to show what can be achieved with a combination of total intellectual integrity and determined application, then Tikvah Alper certainly provided this.

Keywords:

• Radiobiology history
• Tikvah Alper
• survival curve shape
• scrapie agent

Dr Tikvah Alper was born in South Africa in 1909, the youngest of four daughters. Tikvah enjoyed an outdoor life with swimming, surfing and sailing but, at the same time, managed even early on to demonstrate her characteristic determination and her impressive academic abilities. She completed her last two years of school education in a single year to win one of the few scholarships, then open to women, enabling her to enter Cape Town University at the age of sixteen. At at that time, the ‘University’, did not consider mathematics a suitable subject for girls. In typical Tikvah fashion she overruled the Faculty Dean and, by age twenty, had qualified with distinctions in physics in both BA and MA degrees. This very impressive start gave her the opportunity to study in Europe and she moved to the Kaiser-Wilhelm Institute in Berlin. There she joined the laboratory headed by Lise Meitner who she would often acknowledge had had a great impact on her. Unfortunately the political situation in Germany at the time meant both Meitner and she left Germany earlier than they might otherwise have done. As a result Meitner effectively lost a share in the Nobel Prize for studies of nuclear fission. The consequence for Tikvah was that she returned to South Africa after completing her work for a PhD, but before being able to arrange her thesis defense. This was a requirement at the Kaiser-Wilhelm for the award of the degree. It is interesting to note that after she published a paper, detailing her thesis studies on the delta-rays produced by alpha particles (Alper 1932) she was awarded the British Association Junior Medal for the work.

On returning to South Africa she held a University teaching post for a short time but, after again meeting her childhood friend Max Sterne, they married. This meant leaving her University position, since academic posts were then not available for married women. With no obvious opportunities of academic work, again in typical manner, she collaborated with her bacteriologist husband and built a laboratory in their garden. It was here that they developed the use of a photoelectric cell to study bacteria in suspension (Alper and Sterne 1933).

In 1936 their first son, Jonathan, was found to have been born profoundly deaf and she traveled to St Louis, USA, to train as a teacher of the deaf so that she would be able to properly educate her son. The result was a long break from scientific research that eventually ended when she came to England in 1946 with Max, who was then on a study leave.

This began her connection with the Hammersmith Hospital, London, where she met L.H. Gray during a visit. He pleasantly surprised her by knowing of her studies on delta-rays. At that time Gray had no positions available at the Hammersmith but he introduced her to Douglas Lea in Cambridge. Lea had just published his book ‘Actions of Radiation on Living Cells’ (Lea 1946). After discussions with Tikvah, about his proposed Target Theory (in which radiation damage was explained as the result of direct energy deposition in specific targets), Lea invited Tikvah to spend time with him in Cambridge on a part time basis. She accepted his offer and took up research again as an unpaid fellow. Cell cultures were prepared by Lea then on the next day she used a return trip from London to carry out experiments on these cultures. Lea’s original radiation experiments’ on phage, had been carried out under dry conditions and had resulted in ‘single hit’ survival curves, implying a ‘one hit’ inactivation. However, when Tikvah used more physiological conditions during irradiation she discovered that cell survival curves had more complex shapes that were also dependent on the timing of cell plating post-radiation. Initially this rather undermined the simpler Lea target theory and suggested indirect action, by the radiolysis of water products in the suspension medium. Her interest in survival curve shapes, the importance of direct and indirect action, and target theory continued from then on throughout her life (e.g. Alper et al. 1960; Rude and Alper 1972).

A National Physics Laboratory had been established in South Africa (circa 1947) and Tikvah returned briefly as Head of Biophysics. Luckily, for the many of us who later benefited from exposure to Tikky, she very clearly let her views be known in a petition against the government erosion of colored Voter’s rights, the start of apartheid in South Africa. The response that this produced meant that she and the family came to settle in England where she again started work as an unpaid fellow at the MRC Experimental Radiopathology Unit (ERU) at Hammersmith Hospital, London. On this occasion, she was given a small MRC grant to continue studies on the irradiation of bacteriophage. At this time (Alper 1952), the Unit had a functioning Van de Graaff generator that could accelerate positive ions as well as well as electrons. It was this machine that enabled the earliest experiments into oxygen effects for damage from fast neutrons (Alper and Howard-Flanders 1956). Over the next few years the facilities in the Unit were further developed with the installation of an 8 MeV Linear Accelerator and, in the MRC Cyclotron Unit, a Cyclotron. The close collaboration between the MRC Units meant that although the cyclotron was used for radiotherapy during the day, it was also made available for experimental studies during the evenings. It was in this environment that Dr Alper’s scientific career finally took off, despite now being well into her thirties and lacking a Ph.D., something that she often used to joke about in later life.

She became a staff member of the ERU in 1953 where she both continued her interests into survival curve shapes but also studied the infectious agent causing scrapie. In the paper in Nature with Neil Gillies and Mort Elkind (Alper et al. 1960) she proposed the use of an ‘extrapolation number’ instead of ‘hit number’, since variations in mammalian survival curves would rule out a simple target model. She later proposed that there were two potential targets (one being the DNA) for radiation damage and developed the idea of an O and N type model based on differences in the sensitivity of these targets to the presence or absence of oxygen (Alper 1963). The idea of the O and N type model was later extended by some of her colleagues at the Hammersmith Hospital (Cramp et al. 1972).

She was appointed the Director of the Experimental Radiopathology Unit, Hammersmith Hospital in 1962, a time in radiobiological research when it was reasonably assumed that the DNA in cells was the prime target for radiation damage. The range of facilities at the Hammersmith meant that it was possible to examine in detail the effects of different radiation qualities in respect of LET (linear energy transfer) on RBE (relative biological efficiency). Clearly this was of importance in radiotherapy, a point emphasized by the ongoing neutron therapy trials under Mary Catterall that were taking place in the same MRC building (Alper, 1963; Catterall et al. 1971). Also at this time it became obvious that the effects of oxygen on cell survival required further serious investigation since, in tumors, some tumor cells were likely to be protected by anoxia (Howard-Flanders and Alper 1957; Hodgkins and Alper 1963). All these areas of research were followed under Dr Alper in a variety of cell and tissue systems (Fowler et al. 1963).

At this time, as with her earlier studies with Lea in Cambridge, she demonstrated her liking for ‘inconvenient facts’. These meant that simple models often had to be modified to properly accommodate these facts. This approach was not always popular with the authors of the simple theories! Those of us who attended BIR radiobiology meetings will remember Tikvah and Shirley Hornsey sitting together in the front row whispering to each other during a talk. This was a sign that some serious but always justified points would be brought to the attention of the author of the talk, something experienced by the current authors when they were students. During her period as Director of the MRC Unit she regularly attended the lunchtime coffee meetings in the Unit library. These were in many ways a continuation of the tradition introduced by Gray of afternoon tea, providing opportunities to meet informally with other scientists and throw around ideas. On most days collections of visiting scientists, members of other departments plus both junior and senior staff members would gather after their varied lunch breaks to indulge in the seriously strong coffee brew available. In this relaxed context, Tikvah became Tikky but this did not hinder serious discussions of culture, politics and science. Nothing was too sacred to be safe from challenge. In warm summer days she also acquired another name as she frequently crossed the rail lines running past the Hammersmith Hospital to use the open air swimming pool in Bloemfontein Road. Here, in early season before the pool had warmed up, she could be found swimming vigorously while others stood on the side, put off by the low water temperature. Moby Tik was not easily put off: she knew she could warm up with strong coffee and a good argument in the Library.

Her dedication to science, abhorrence of sloppy thinking and determination that theories should fully take account of all the data, in no way prevented her from being a gracious and generous host. This was evident in the regular and often extended Sunday brunch parties she held with husband Max at their apartment in nearby Philbeach Gardens, sometimes after a swim in Fulham Baths. These are happy memories of her, for many of us. After retirement she no way slowed down but spent time at the Gray Laboratories in Northwood writing ‘Cellular Radiobiology’. This was published by Cambridge University Press (Alper 1979). Subsequently she and Max moved to a site near Southampton where they designed and built a house (naturally with a large outdoor swimming pool) and with a nearby anchorage for their yacht.

Many would consider her a feminist - she never wore a ring or took kindly to being called Mrs Sterne but this did not affect a very happy marriage to Max. They were clearly well suited, both physically active with ocean sailing into their eighties and both serious scientists (Max developing a key vaccine against anthrax and also an important fermenter technology for clostridial organisms). An amusing result of Tikky’s ‘feminist’ attitudes occurred when a message of congratulation from the Queen was mooted at the time of their diamond wedding anniversary, addressed to Dr and Mrs Sterne. She made clear this was not acceptable and after some discussion the congratulatory message arrived from the Palace satisfactorily amended and addressed to Dr Sterne and Dr Alper. In some ways this series about women’s contribution to radiobiology could have fallen foul of her approach as she always considered it was irrelevant who did the work, its scientific merit was entirely dependent on how well it was done.

If Tikvah felt something needed doing she would get on and do it, but this did not prevent scientific collaborations in which others could contribute. When living in their house near the Hamble River, Tikvah gained local fame when she opened the door to discover a would-be robber carrying a gun and wearing a balaclava. He quickly found out his mistake as she grabbed his gun and forced him to run, losing his disguise. So even at nearly eighty she was not to be messed with, nor did she even wait for help from Max who had been the South African Universities welterweight boxing champion! She still maintained her scientific interests and was actively contributing up until a few weeks before her death. Tikvah was always proud in private of her collaboration with her husband in determining the size of the scrapie agent detail of which was first published in 1966 (Alper et al. 1966). This interest in scrapie continued after her formal retirement in 1988. The suggestion from her husband Max that they use radiation and target theory, was alluded to in a Special Lecture Tikvah presented at the Radiation Research Society, Dallas 1993, entitled ‘The Scrapie Enigma: Insights from Radiation Studies’ (Figure 1). Based on these studies they were able to show that the size was so small that, almost uniquely among living organisms, that it was unlikely to contain nucleic acids (Alper 1993). They were able to confirm this, using UV exposures, by showing that infectivity was not affected by the UV. She retained an interest in this area well after her retirement as the 1970s BSE epidemic awakened further investigation into these unusual organisms. Her further contributions to the scrapie story (e.g. 1997a and 1997b) are good examples of the extent to which some of her early radiobiological studies remained of critical importance decades later.

Figure 1. Dr Tikvah Alper in the foreground with members of the Radiation Research Society (from left to right: K Held, P Olive, J Denekamp, S Wallace, K Mason, M Oleinick and H Evans) after her special lecture to the Radiation Research Society, Dallas, 1993. Photograph by Bill Osborne, from the Archives of the Radiation Research Society.

There is no question that Tikvah had a very forceful personality and was never inhibited in saying if she ever felt something was incorrect or wrong. This could sometimes cause problems for those who did not know these were the automatic consequences of her intellectual brilliance and integrity. For those of us lucky enough to have known her there are also happy memories of a person of great warmth, kindness and generosity. Her contributions both to science and to the scientists who worked with her were immense.

Only a few of her publications are mentioned above in their contexts. They are merely examples of her well over 100 scientific papers published in a variety of Journals including Nature, Radiation Research, International Journal of Radiation Biology and the British Journal of Radiology.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Notes on contributors

Peter G. Coultas

Dr Peter G Coultas completed his Ph.D. in 1971, based on work carried out earlier in the Physics Department, Royal Marsden Hospital, University of London. He then joined the staff of the MRC Experimental Pathology Unit/MRC Cyclotron Unit (1972–1988), when his scientific development was very much influenced by Dr Tikvah Alper. Prior to retirement he spent periods undertaking radiobiological research at The Health Sciences University, Portland, Oregon, USA and the Peter McCallum Hospital, Melbourne, Australia.

John W. Hopewell

Professor John W. Hopewell was the Director of Radiobiological Research, University of Oxford, between 1980 and 2001. His primary research interest has been the study of different aspects of normal tissue toxicity related to radiotherapy: pathogenesis, fractionation and dose-rate, volume effects and retreatment.