LIFE SCIENCES

-Introduction Biology has become a vast subject which has increasingly merged with traditionally separate disciplines, particularly chemistry and physics. Indeed "life sciences" is now a more appropriate term than "biology." Furthermore the life sciences have provided the basis for most of the advances in medical science which stand up to objective scrutiny. In common with other sciences, the life sciences are an international enterprise and traditional schools of biological study based on personal opinion, ethnic approaches, or religious belief have become mainly obsolete. Indeed attempts to base investigations in the natural sciences on political or ethnic considerations have proved disastrous. Furthermore there is now little prospect that an individual scientist or even a small group of scientists will make an important scientific contribution in isolation. Thus a specifically Jewish interpretation of the life sciences is a matter of continuing historical and ethical interest but of limited relevance to scientific discovery in modern times. In contrast advances in medical science have made ethical issues a matter of central but not exclusive concern to Jews. Nevertheless it is equally mistaken to assume that religious belief has been entirely supplanted by a reductionist approach. Indeed it would be false to conclude that scientists universally explain all aspects of life including human consciousness solely in physico-chemical terms. This remains a live issue for many Jewish and non-Jewish scientists concerned with the life sciences which has scarcely been resolved by the continuing debate of physicists and cosmologists. Advances in genetics have illuminated many genealogical issues of specific Jewish interest such as the history of the kohanim and the nature of many inherited diseases encountered predominantly in Jews. This entry reviews areas of the life sciences to which Jews have made notable contributions since 1800 C.E. It alludes only briefly to related areas of crucial importance to these contributions which are considered in other entries. The following account of the contributions of Jewish scientists in key fields is necessarily brief. Their achievements are described more fully in their separate biographical entries. Their achievements will be better understood by readers who have consulted general sources of scientific information in order to gain some understanding of the areas of scientific endeavor to which Jewish scientists have contributed. -Prelude to the Modern Era Although research in the life sciences is in intellectual terms now entirely non-sectarian, it is nonetheless legitimate to   consider the extent to which discoveries in the modern era were anticipated in traditional Jewish belief. Biological issues are raised in different contexts throughout the Bible. Genesis relates the divinely ordered hierarchy of species and much of Leviticus is concerned with classifying species as the basis for the dietary laws. In the Mishnah and the Talmud the tractates of the order Zera'im deal with agricultural laws and thereby consider many issues relating to animals and plants. These observations are not systematic or analytical in any modern sense. Indeed it is difficult to determine the extent to which they originate from Jewish sources or from the folklore of earlier or contemporary cultures. One of the earliest attempts to collate the then available knowledge of nature systematically was Maimonides' treatise on drug names whose efficacy is no less established than many similar drugs in contemporary complementary medicine. Long in advance of Darwin, there were challenges to the literal interpretation of Genesis that all living species were present at the creation. Indeed some authorities espoused views current in the Hellenistic and Roman world that living organisms can arise from inorganic substances through spontaneous generation. These seemingly fanciful notions have been given scientific respectability by modern debate about the origins of life on Earth and, even more speculatively, elsewhere in the universe. Many Jewish beliefs on biological matters were based on direct observation especially at times when Jews lived predominantly in rural communities and engaged in agricultural pursuits. These observations were undoubtedly embellished by reports of miraculous deeds allegedly witnessed by travelers in an age of greater credulity. However, there is little reason to believe that there was any specific Jewish interpretation of the biological basis for the key events of birth, life, and death in humankind, the life cycle of other species, or of botanical events. The main rabbinical preoccupation was with the religious and ethical dimensions of human life. It is tempting to interpret textual passages in the Bible and other literary sources as evidence for early scientific insight anticipating modern discoveries. For example Jacob's manipulation of Laban's goat herds and sheep flocks is sometimes taken as astonishing insight into Mendelian principles of genetic selection (Gen. 30:32–43). Yet it is entirely possible that his experience had simply endowed him with exceptional powers of observation rather than modern analytical insight. Perhaps most importantly through the ages and often in common with other monotheistic faiths, Judaism's religious authorities have not attempted to interfere with man's attempts to understand the natural world through observation and the exercise of reason. -Life Sciences in the 19th Century In the early 19th century Jews made many contributions which helped to lay the basis for rational investigation. In common with other scholars they were commonly polymaths with the freedom to roam intellectually because of the limited factual knowledge available in general and the constraints on academic activities. Even when antisemitism disrupted academic careers, re-location was relatively simple as individual speculation and observation were all important and laboratory technology was rudimentary. Robert remak was the first (c. 1840) to describe the major constituents of the embryo and also described salient anatomical features of the nervous system. jacob henle made new observations on the structure of the kidney (c. 1830) and theorized that infectious agents existed which are too small to be discernible by conventional microscopes, a prediction fulfilled by the later discovery and characterization of viruses. Between 1850 and 1890 ferdinand cohn improved microscope design and adapted this advance to study the developmental stages of plants, algae, and bacteria. Furthermore he was arguably the first naturalist to discern the association between bacterial infection and disease. In the latter half of the century Nathaneal Pringsheim made fundamental discoveries concerning plant morphology and physiology and founded the German Botanical Society. His contemporary julius von sachs was also one of the first botanists to study and publish systematic studies of plant physiology. At this time eduard strasburger further clarified the life history of plants. His findings have stood the test of time and led to his appointment to a chair in Jena at the age of 24, a remarkable achievement in the Germany of 1869 for a scientist of any religion. Not all the contributions of Jewish scientists of this era were so soundly based. jacques loeb 's work on parthenogenesis from the 1880s on was largely fanciful but still visionary in anticipating the momentous cloning techniques developed more than a century later. -Life Sciences in the Modern Era By the beginning of the 20th century the challenges in the life sciences were at least more clearly defined. These are too numerous to list in full but the major problems were to understand the nature of heredity, the control of cell growth and differentiation, the biochemical processes which maintain the life of cells and organisms, and the processes which enable specialized systems such as the nervous system to operate. Human ability to manipulate these processes for medical or other purposes was so limited that ethical questions were almost entirely philosophical. At the beginning of the 21st century there are few controversies concerning the basic mechanisms operating in areas of former ignorance or the likely directions of future advances. The main challenge to investigators is how to order the vast amount of information generated by the greatly expanded scientific enterprise. Complete mapping of the human genome has opened the still more complex field of proteomics which seeks to categorize and explain the actions and interactions of the huge range of proteins transcribed from the genome. This task would be impossible without the simultaneous advances in computing techniques and the mathematical handling of experimental data. This reality emphasizes the interdependence of all branches of the natural sciences. A related challenge is the daunting range of ethical issues generated by advances in scientific techniques, particularly   when applied to medicine and agriculture. The ethical difficulties are compounded by the social issues. A century ago, scientific progress was understood and debated by a privileged coterie of savants. Even politicians were largely indifferent unless the advance had military applications or was likely to increase national prestige. Today the practical application of most scientific advances is likely to provoke public debate and progress depends on a dialogue between scientists, politicians, and appropriately educated laymen. THE MOLECULAR BASIS OF HEREDITY hermann muller 's early appreciation of the importance of gene mutation in Darwinian selection emphasized that biologists long recognized the need to understand the mechanisms of genetic transmission. The elucidation of the structure of DNA was arguably the greatest achievement of 20th-century science. This discovery started the process of clarifying the molecular basis of genetics. It also established the central dogma that DNA determines the sequence of RNA, which in turn governs protein synthesis, even though exceptions to this rule were found later. rosalind franklin 's crystallographic picture of DNA, the Mona Lisa of scientific illustrations, was the key to Watson's insight that the DNA molecule is a helix. Her experiments were made possible by the application of X-ray crystallography to defining protein structure. Pioneers in this field included john bernal and sir max perutz . Perutz used this technique to Jacobs crossbreeding of Labans flock (Gen. 30). Chart by Jehuda Feliks, Jerusalem.. Chart by Jehuda Feliks, Jerusalem.") Jacob's crossbreeding of Laban's flock (Gen. 30). Chart by Jehuda Feliks, Jerusalem.     achieve the first biophysical description of a major molecule of biological importance, namely hemoglobin. marshall nirenberg was one of the scientists who worked out the process by which the genetic information in DNA is transcribed by messenger RNA as the first step in protein synthesis. Once it was realized that the sequence of DNA bases is the genetic language it became necessary to devise methods for reading these sequences. One method was devised by walter gilbert , who also showed that not all base sequences are utilized by the cell in protein synthesis even though these seemingly inactive "introns" later proved to have functional significance. Another important advance was arthur kornberg 's discovery of the first of the enzymes named DNA polymerases which regulate the copying of the DNA strand and hence the transmission of the cell's genetic information in newly synthesized DNA. matthew meselson dissected the mechanisms by which DNA from different sequences recombine in the process of transferring genetic information. He also elucidated some of the ways in which DNA repairs mistakes liable to give rise to harmful mutations, a vital defense against the potentially disastrous effects of UV irradiation and other mutagenic agents. Another key development was the characterization of the enzymes which act on RNA transcribed from DNA to which sidney altman made vital contributions. Indeed his work suggested the possibility that the earliest life forms on Earth may have been solely RNA dependent. THE ORIGINS OF MOLECULAR BIOLOGY Advances in genetics were accompanied by experiments in genetic manipulation using viruses called bacteriophages (phage) which infect bacteria. The interactions between phage and bacteria proved a vitally important model for understanding gene function and also the mechanisms which control gene activation and expression. Exploitation of this system marked the origins of what is now termed molecular biology. The findings in this model have proved broadly applicable to all other living species. gunter stent , salvador luria , francois jacob , and andre lwoff were members of the small and now legendary group of phage workers who transformed biology in a manner analogous to the revolution in physics initiated by quantum theory. They analyzed the interactions between phage and bacterial genes to formulate the general principles which determine the activation of some genes to initiate cellular events and other "repressor" genes which control activated genes. The manner in which repressor genes function was largely elucidated by mark ptashne in an analogous experimental system. These insights into the manner in which genes operate were strengthened by joshua lederberg 's finding that bacteria exchange genes in a process termed recombination thereby altering the characteristics of the recipient bacteria. This work was extended by stanley cohen 's successful isolation and transfer of bacterial and mammalian genes, the technique of gene cloning now in universal use. The isolation and study of defined DNA sequences was advanced by the discovery of enzymes by Daniel Nathans termed "restriction enzymes" which reproducibly cut DNA into manageable segments for analysis. Another vital step in the development of genetic manipulation was Sol Spiegelman's discovery that RNA sequences stick specifically to the DNA sequences from which the RNA was transcribed, a process termed hybridization. The ability to dissect and reconstruct genes was also greatly advanced by paul berg 's experiments with phage and also with mammalian cells infected by the virus SV40. He was also one of the first scientists to appreciate that a powerful method of discovering the function of a gene is to induce a deliberate mutation which will thereby cause the damaged DNA sequence to malfunction. Gene activation and repression is also an essential process in normal embryonic development. chaim cedar discovered that chemical modification of DNA, a process known as methylation, is a key step in gene activation. These advances in genetics were used by sydney brenner to map the genetic control of the developing nervous system in the small worm C. elegans. These studies helped to establish the principle that the origin of human diseases can be investigated by detecting mutant genes and the abnormal proteins these genes encode. robert horwitz 's studies on the same species also highlighted the importance of genetically programmed cell death in normal development and function. VIROLOGY Elucidating the mechanisms of molecular genetics led to a greatly improved understanding of viral replication in cells and known viral infections. The new techniques also disclosed a viral cause for many diseases of previously unknown origin. Furthermore the longstanding suspicion that viruses may play a role in cancer and many chronic diseases is now open to rational investigation. Aaron Shatkin and seymour s. cohen unraveled the sequential stages in viral infection of cells and sir aaron klug 's work clarified the process assembly of new virus particles in infected cells. david baltimore and howard temin found important exceptions to the previous dogma that all genetic information flows from DNA to RNA by showing that some RNA viruses transcribe DNA copies as the initial step in the production of new virus particles through the action of an enzyme called reverse transcriptase. Without this discovery the nature of AIDS and other retroviral infections could not have been rationally investigated. Although others had reported the induction of leukemia in mice with transmissible viruses many years before Charlotte Friend described similar findings in 1957, the interactions with cellular genes responsible for the disease were not elucidated before the work of Harry Rubin in the 1960s and harold varmus in the 1970s. Another achievement in virology was baruch blumberg 's discovery of hepatitis B virus which has proved not only of enormous clinical and epidemiological importance but has also given great insight into the genetic factors which determine the outcome of viral infections in different individuals. The history of research on "viral" infections continues to be unpredictable and a field where yesterday's heresy becomes a new orthodoxy. stanley prusiner 's work has   established that infectious proteins called "prions" are devoid of nucleic acids yet are self-replicating and cause certain degenerative diseases of the nervous system. CELL BIOLOGY Cells have proved to be mini-organisms of great complexity and one can only discuss those fields of research on cell biology to which Jewish biologists have made especially significant contributions. Most tissues consist of self-renewing cells; their life cycles and the factors which regulate these cycles are of great basic interest and medical relevance. Marc Kirschner's work has helped to understand the signal pathways which induce cell division. The cell interior contains a complex network of channels and associated structures for the transport, processing, and degradation of proteins and other complex molecules imported into the cell or exported as the products of specialized cells. The findings of James Rothman and Randy Schekman have helped to clarify the structure and function of the most important of these cellular components. Another area of current basic and potential clinical interest is the identification and propagation of stem cells with full or limited potential to mature into specialized cells. Irving Weissman and leo sachs were amongst the earliest workers to achieve success in this technically demanding field. It has also become apparent that cell division and maturation depend on the actions of growth factors produced by many cell types in a complex, interdependent manner. Nerve growth factor was the first such factor to be identified, by ritalevi-montalcini , and Stanley Cohen. Cohen later discovered epidermal growth factor. These factors are now collectively termed "cytokines." RECEPTORS, SIGNALS, AND PHARMACOLOGY Cell membranes, their receptors, and the signals these receive largely govern the behavior of cells and organs. martin rodbell and alfred gillman greatly expanded our understanding of the receptor molecules which respond to external stimuli such as hormones and toxins and the signals these transmit to the cell in order to induce an appropriate response. Robert Lefkowitz and ephraim katzir 's scientific achievements center on the biophysical properties of membrane receptors. Especially noteworthy events in the development of pharmacology were robert furchgott and Salvador Moncada's contributions to identifying nitrous oxide as a key molecule governing blood vessel flow and the similar role of prostacyclin discovered by Sir John Vane. BIOCHEMICAL PATHWAYS There is a consistent record of major contributions by Jewish scientists to characterizing the biochemical pathways which provide energy and govern other metabolic processes. This progress was greatly assisted by the introduction of isotopic methods for studying biochemical pathways by scientists who included mildred cohn , david rittenberg , and Sidney Udenfriend. The crucial roles of oxidation and energy generation were appreciated early in the history of biochemistry and largely worked out by otto warburg , extended by Fritz Lehmann's analysis of acetylation and further clarified by David Keilin. The related problem of energy creation in muscles was clarified by otto meyerhof . The pathways for carbohydrate and urea metabolism and related intermediate pathways were characterized largely through the research of philip pacy cohen , gerty cori , Hans Krebs, and Sarah Ratner. The steps in cholesterol synthesis were elucidated by konrad bloch . The vital role of cholesterol receptors in controlling blood levels was established by michael brown and joseph goldstein . Modern biochemistry has revealed a myriad biochemical processes other than the classical metabolic pathways. edmond fischer and sir philip cohen have made key contributions to understanding protein phosphorylation, a complex process of fundamental importance for regulating a wide range of cell functions. The regulatory importance of the ubiquitin system has been shown by aaron ciechanover and avram hershko especially with respect to protein degradation. Carbon utilization is central to photosynthesis in plants and carbohydrate metabolism in mammals and was first methodically investigated by melvin calvin . The precise structure of enzymes and other proteins as well as their amino acid sequence is crucial to their function, a problem largely resolved by the contributions of christian anfinsen and william stein . Two examples serve to illustrate specialized fields in the life sciences in which Jewish scientists have been especially prominent. THE NERVOUS SYSTEM Working out how each of the one hundred billion nerve cells in the brain communicates with one thousand other nerve cells is an enduring, largely unsolved challenge. The once controversial role of chemical neurotransmitters in communication between brain cells was firmly established by julius axelrod 's work on noradrenaline and paul greengard 's analysis of dopamine mediated signaling. The details of how peripheral nerves activate muscle fibers by releasing acetylcholine have been clarified by sir bernard katz . The part played by chemical neurotransmitters in transmission in the sympathetic and parasympathetic nervous system was also controversial until otto loewi unequivocally demonstrated the role of acetylcholine and adrenaline. The basis of peripheral nerve function conduction was equally difficult to resolve before joseph erlanger 's detailed analysis of the electrical impulses involved in this process. The mechanisms of drug action on the brain are of practical importance, an area greatly illuminated by Hans Kosterlitz's studies in the field of natural opiate substances produced by the brain and the receptors on which these act. A still more formidable problem is to understand one of the brain's most distinctive functions, namely memory; eric kandel 's work showed that protein synthesis generated by nerve connections is involved in this process. The special senses pose different questions. selig hecht and george wald have analyzed the molecular basis of the events in the retina which induce visual images after light exposure. richard axel was one of the   two scientists who showed that the recognition of the wide range of smells depends on receptors in the brain and not in the nose as one might have assumed. Another crucial issue is the role of genetic factors on brain function and susceptibility to neurological disease, an area of study largely founded by seymour benzer . THE IMMUNE SYSTEM Simply stated, the central problem in immunology is to understand how the body rapidly generates molecules which combine specifically with the distinctive, mainly protein antigens expressed by infectious agents while avoiding autoimmune reactions with its own tissues. An early clear statement of the issues formed the basis of Ilya Mechnikov's 1908 Nobel lecture. michael heidelberger and Felix Haurowitz were amongst the first scientists to analyze the antibody response in detail. This process culminated in the development by cesar milstein and his colleagues of homogeneous monoclonal antibodies reactive with a single antigen. This advance has had momentous implications for the diagnosis and treatment of immunological and other diseases, for laboratory diagnosis and for biotechnology. The immune response to infections and indeed all foreign antigens is genetically controlled, a discovery largely based on the work of baruj benacerraf , michael sela , and Phil Leder. This control is largely determined by surface structures termed histocompatibility antigens in general and the HLA system in man which are expressed primarily by cells engaged in immune responses. jack strominger contributed to the chemical and structural characterization of these antigens. The first recognition that certain human diseases result from autoimmunity came from the work of Noel Rose, Deborah Doniach, and Ivan Roitt. Among the greatest achievements of applied immunology is the virtual elimination of poliomyelitis with vaccines developed by jonas salk and albert sabin . ORIGINS OF LIFE Modern times have witnessed a loss of any inhibitions by Jewish scientists about discussing the origins of life on Earth. This has expanded into exobiology, the possibility that life exists elsewhere in the universe. Sol Spiegel and Leslie Orgel have proposed that self-replicating RNA was the primordial molecule in all life forms. Sidney Fox argued that amino acids, the building blocks of proteins, became self organized into replicating microspheres, an idea for which Stanley Miller has provided experimental support. A more general theory advanced by Stuart Kauffman is that randomly associating molecules in the correct chemical medium of the primitive Earth became autocatalytic and matured into living forms on a random basis. The subject has matured into a respectable topic for debate in scientific and religious circles. -Conclusions The success of Jewish scientists in the life sciences as in other branches of science reflects a logical extension of traditional Jewish reverence for learning. However, this success has not been achieved by ignoring other aspects of Jewish learning and enterprise. An analysis of their careers shows that many have continued to support Jewish communal activities and even more have identified with Israel in general or have forged links with Israeli academic institutions. Indeed traditional scholarship and scientific discovery have been mutually supportive. "A scientific paper is a grave act to be undertaken with the utmost seriousness. To me it's holy writ and it should be an achievement that cannot be altered" (Joshua Lederberg, 1996). (Michael Denman (2nd ed.)