sign in sign up
<<
Home , Alfred Sturtevant, Carl Correns, Curt Stern, Edward Tatum, George Beadle, Gregor Mendel

A Century of

Daniel J. Fairbanks

Abstract—In 1866, published his experiments on In the year 2000, the of genetics celebrated its th in the garden (Pisum sativum). The fundamental 100 anniversary. In the spring and early summer of 1900, principles of inheritance derived from his work apply to nearly all three botanists, , , and Erich von eukaryotic and are now known as Mendelian principles. Tschermack, reported their simultaneous and independent Since 1900, Mendel has been recognized as the founder of genetics. rediscovery of Mendel’s principle of segregation, an event In 1900, three botanists, Carl Correns, Hugo De Vries, and Erich that sparked the rapid establishment of genetics as a new Tschermack von Seysenegg, had independently completed experi- and important science. This paper highlights just a few of ments that were similar to Mendel’s, although much less extensive. the major events that have made genetics one of the most When searching the literature, all three encountered Mendel’s powerful and rapidly progressing . paper and realized that he had described the principles of inherit- Although genetics entered mainstream science rather ance and the experimental data to confirm them 34 years earlier. suddenly in 1900, it traces its origin to the mid-1800s with With their rediscovery, the science of genetics was born in 1900 the experiments of Gregor Mendel. In 1843, Mendel entered along with the 20th century. coined the term the St. Thomas monastery in the city of , now in the “genetics” and was the person most responsible for establishing the , and was soon appointed as a seventh-grade new science in the first decade of the 20th century. Thomas Hunt science teacher. He failed his teacher certification examina- Morgan and his students established the chromosomal basis of tion, an event that prompted the abbot of the monastery to heredity beginning in 1910. During the 1920s and 1930s, classical send him to the . While at the Univer- genetics was established, and became very popular among sity, Mendel was enamored with the teachings of his the more educated and wealthy members of society. Laws mandat- professor, Dr. , who, even though Darwin’s ing sterilization of perceived unfit people were passed and carried Origin of Species had not yet been published, focused his out. By the late 1930s, Nicolai Vavilov had published his theory of teachings on the of species over long periods of centers of origin for cultivated and established a bank geological time. During the time that Mendel was a student, for his collections in Leningrad. During the siege of Leningrad in Unger wrote an article in which he wrote this remarkable 1941–1942, nine of his coworkers chose to die of starvation rather passage that foreshadowed Mendel’s work: “Who can deny than sacrifice the and tubers that Vavilov had collected. In the that new combinations arise out of this permutation of meantime, Vavilov was imprisoned for his opposition to Lysenko- vegetation, always reducible to certain law-combinations, ism. He soon died in prison of maltreatment. In the mid-1940s, which emancipate themselves from the preceding character- and discovered the relationship istics of the species and appear as a new species” (Orel 1996). between and , and and his coworkers Unger’s teachings infuriated the local clergy who attempted discovered that DNA is the genetic material of a bacterial species. to have him dismissed. Among the most vocal was Dr. Sebastian In the early 1950s, and discovered Brunner who wrote of Unger as “a man who openly denied the that DNA is the genetic material of a . Shortly after Creation and the Creator” and as one of the “professors at so- this time, in 1953, and determined the called Catholic Universities [who] deliver lectures on really structure of DNA based on evidence collected in several laborato- beastly theories for years on end” (Olby 1985). Ironically ries. Cracking the became one of the next priorities, a Mendel was a devout member of the clergy, but he appears to task that was completed in the 1960s. During the 1970s, recombi- have sided with Unger. Mendel wrote of his own work as “the nant DNA was made, an event that led to molecular applications in only right way by which we can finally reach the solution of a genetics and . The first genetically engineered question the importance of which cannot be overestimated in pharmaceuticals soon followed. The 1970s and 1980s saw the connection with the history of the evolution of organic forms” development of efficient methods for DNA , which ulti- (Stern and Sherwood 1966). mately led to whole sequencing. The first bacterial genome In 1852, Mendel began experiments with pea hybrids that was sequenced in 1995, the Brewer’s genome in 1996, and the would last for 8 years. From the scientific literature that he , Arabidopsis, and in 2000. Fittingly, had read extensively he already knew of the concept of the sequencing of the human genome, one of the greatest accom- in for four of the seven traits he studied. His plishments in genetics, came at the 100th birthday of the science of contribution was his development of a mathematical model genetics. to explain heredity. He discovered regular 3:1 ratios in the F2 generations in all seven of his monohybrid experiments, and developed the now familiar mathematical model to explain the 3:1 ratio, which he expressed in the following equation: In: McArthur, E. Durant; Fairbanks, Daniel J., comps. 2001. Shrubland A A a a ecosystem genetics and biodiversity: proceedings; 2000 June 13–15; Provo, +++ UT. Proc. RMRS-P-21. Ogden, UT: U.S. Department of , Forest A a A a Service, Rocky Mountain Research Station. Daniel J. Fairbanks is a Professor in the Department of Botany and Range where the letters in the numerator represent the Science, Brigham Young University, Provo, UT 84602. contributed by the male parent and those in the denominator

42 USDA Forest Service Proceedings RMRS-P-21. 2001 A Century of Genetics Fairbanks as the alleles contributed by the female parent. Because the theory of inheritance espoused by Bateson and the chromo- large A is dominant, three of the four combinations produce somal theory of inheritance promoted by Edmund Wilson, the dominant and one the recessive. He tested also at Columbia. He opted instead for de Vries’ this model by allowing the F2 plants to self fertilize to theory (which differs substantially from our current under- 1 produce F3 offspring. He found that ⁄3 of the F2 plants with standing of mutation). Complaining of the intellectual cli- the dominant phenotype produced offspring with only the mate at Columbia, Morgan wrote in 1905 that it was “an 2 dominant phenotype, and that ⁄3 produced offspring with atmosphere saturated with chromosomic acid” (Allen 1978). both dominant and recessive , precisely as his He completely reversed his views, however, within 5 years model predicted. as he brought Mendelian and chromosomal theories of He then turned his attention to dihybrid and trihybrid inheritance together as a single theory. In 1910 he observed experiments to ascertain whether the inheritance of one a -eyed fruit fly that was to change the direction of his trait influences the inheritance of another. He discovered career and the science of genetics. He discovered that the that all seven traits in various combinations of twos and white-eye phenotype was associated with inheritance of the threes were inherited independently of one another. On X . these two discoveries, the mathematical segregation of dif- At first, he was reluctant to conclude that the genes were fering elements and the independent inheritance of traits, actually a part of the chromosome. However, two discoveries are based the two laws of inheritance attributed to Mendel: by his students, and , made the law of segregation and the law of independent assortment. it clear that their so-called sex-linked genes must be a Mendel presented his paper in 1865 and had it published physical part of the . Sturtevant, as an under- the following year (Mendel 1866). For the next 34 years, no graduate student in 1911, had a flash of genius when he one, including Mendel, recognized that the laws he discov- realized that genes might be located in a linear fashion on ered applied almost universally to plants, animals, and the chromosome. He gathered up the notebooks with the . His paper was not completely forgotten; it was cited data from several of their experiments, and, in his words, “I at least 15 times before 1900. However, it is clear from these went home and spent most of the night (to the neglect of my citations that no one recognized its most important points. undergraduate homework) in producing the first chromo- Mendel sent reprints with cover letters to several botanists, some map” (Sturtevant 1965). He placed five genes on a including Franz Unger, his former professor, but the only linear map and calculated the distances between them one to respond was Karl von Nägeli, who carried on corre- based on the frequencies of crossing over. Bridges discovered spondence with Mendel over a period of 7 years. Mendel had in 1913 that unusual cases of inheritance of sex- initiated studies with the hawkweed, and Nägeli encour- linked alleles were associated with of chro- aged Mendel to continue with these species. Neither Mendel mosomes. The collective data strongly indicated that genes nor Nägeli knew that hawkweed was an apomict, and thus were organized in a linear fashion as part of the chromo- it did not display the patterns of inheritance that Mendel some. Morgan and three of his students, Sturtevant, Muller, had observed in peas, and by now in several other species. and Bridges, published in 1915 a landmark book entitled the Mendel died in 1884, unaware that he would become Mechanism of Mendelian Heredity (Morgan and others 1915) known as the founder of genetics. Sixteen years later, in in which they summarized all of their evidence that Mende- 1900, DeVries working with several species, Correns lian and chromosomal theories of inheritance were one and with peas and , and Tschermak with peas, rediscov- the same. Bateson rejected the idea, but respected their ered Mendel’s principle of segregation and the science of work so much that he aptly wrote “not even the most genetics was born. Two of the three rediscoverers, Correns skeptical of readers can go through the Drosophila work and Tschermak, became strong advocates of Mendelism. De unmoved by a sense of admiration for the zeal and penetra- Vries, on the other hand, dismissed tion with which it has been conducted, and for the great within less than a year of his paper on it. The person most extension of genetic knowledge to which it has led—greater responsible for the establishment of Mendelism was the far than has been made in any one line of work since British naturalist William Bateson. Bateson read Mendel’s Mendel’s own experiments” (Sturtevant 1965). paper while on a train in 1901 and soon thereafter embraced The students who coauthored this work with Morgan, Mendelism with the passion of religious zealot. Bateson was Sturtevant, Bridges, and Muller, were to become three of the so passionately supportive of Mendelism that De Vries most influential in later years. Another laboratory warned him in a 1902 letter, “I prayed you last time, please was also soon to produce a similar group of prominent geneti- don’t stop at Mendel. I am now writing the second part of my cists. At , Rollins Emerson had taken on book which treats crossing, and it becomes more and more George Beadle, Marcus Rhoads, Charles Burnham, and Bar- clear to me that Mendelism is an exception to the general bara McClintock as students to work with him on maize. rule of crossing. In no way is it the rule!” (Olby 1985). The McClintock had hoped to study , but the De- opposition to Mendelism only encouraged Bateson, who, partment of Plant Breeding at Cornell did not admit women together with and Edith Saunders, found at the time, so Emerson invited her to work with him in maize Mendelian inheritance in many different species. It is to genetics. McClintock’s enthusiasm for her knowledge is well Bateson that we owe much of our current genetic terminol- illustrated in the following story, given in her words: ogy (including the word “genetics”) and the establishment of I couldn’t wait to take [the final exam for geology]. I loved Mendelian genetics as a credible science in the first decade th the subject so much that I knew they wouldn’t ask me of the 20 century. anything I couldn’t answer. I just knew the course. So I was an American zoologist at couldn’t wait to get into the final exam. They gave out these who at first rejected both the Mendelian blue books, to write in and on the front page you put down your

USDA Forest Service Proceedings RMRS-P-21. 2001 43 Fairbanks A Century of Genetics

own name. Well, I couldn’t be bothered with putting my name worldwide studies identified the centers of origin and diver- down; I wanted to see those questions. I started writing right sity for the major food crops of the world. Vavilov and his away—I was delighted, I just enjoyed it immensely. Every- associates collected seeds and tubers of those crops and thing was fine, but when I got to write my name down, I created one of the world’s first gene banks in Leningrad. In couldn’t remember it. I couldn’t remember to save me, and I the winter of 1941–1942, Hitler’s army laid siege to Leningrad waited there. I was much too embarrassed to ask anybody and food soon ran out. Tens of thousands of the city’s what my name was, because I knew they would think I was a screwball. I got more and more nervous, until finally (it took residents died of starvation. in the institute about twenty minutes) my name came to me. Vavilov had directed were surrounded by stores of rice, —Keller (1983) wheat, corn, peanuts, potatoes, and peas that contained the collected by Vavilov and his associates. Although McClintock is best known for her later discovery Recognizing the need to preserve that diversity, they made of transposable elements in maize, among her most signifi- a pact among themselves that none of them would eat the cant publications was her demonstration that seeds and tubers. Nine of the scientists died of starvation were the physical carriers of genes. The work of Morgan and while at their posts in the Institute rather than sacrifice the his students had shown the association of genes and chromo- genetic diversity that was stored there. somes, which led them to conclude that genes were on A few years earlier, Vavilov was the most prominent chromosomes. However, McClintock and her coworker in Russia. However, in the 1930s, Trofim Lysenko had observed cytological evidence of cross- began to promote his Lamarckian ideas that the environ- ing over that was clearly associated with the recombination ment could direct specific changes in hereditary elements, of linked genes in maize. Morgan gave a lecture at Cornell in and referred in distaste to Vavilov and his colleagues as “the 1931, and then took a tour of the labs. Creighton and dogmatic followers of Mendel and Morgan” (Medvedev 1969). McClintock showed Morgan their data, which they felt were Vavilov publicly resisted Lysenko, but in the end, Stalin rather meager. They had intended to grow their maize declared Lysenko’s views as state policy. In 1939, at one of plants another year to collect more data before publishing his last attempts to challenge Lysenko, Vavilov stated his the results. Morgan knew of similar work in Drosophila resolve, “We shall go to the pyre, we shall burn, but we shall being conducted by , but did not tell them of it. He not retreat from our convictions” (Medvedev 1969). Shortly insisted that Creighton and McClintock publish their re- thereafter, in 1940, Vavilov and several other Soviet geneti- sults immediately. He asked for a pen and paper and in their cists were arrested and imprisoned for their refusal to follow presence wrote a letter to the editor of the Proceedings of the Lysenko. As Hitler’s army advanced during 1941, Vavilov as National Academy of Sciences telling him that he would a prisoner was evacuated from St. Petersburg to Saratov receive within 2 weeks a significant article from Creighton prison and placed in a windowless underground called a and McClintock that should be immediately published. The death cell. There he died in January 1943, a year after the article beat Stern’s by several months. Explaining his ac- deaths of his colleagues in the institute. Numerous Soviet tions, Morgan simply said, “I thought it was about time that geneticists were imprisoned and killed because of their corn got a chance to beat Drosophila” (Keller 1983). refusal to accept . Lysenko reigned over Soviet Like most other sciences, genetics was not immune to genetics for nearly 3 decades until 1964 when Khrushchev, political influences. The eugenic movement gained momen- who had firmly supported Lysenko, was forced to resign. tum in the period from turn of the century to the 1930s. We now return to the . In the early 1940s, Based on incorrect assumptions about the inheritance of George Beadle, one of Emerson’s former students, and Ed- such traits as feeblemindedness, imbecility, and criminal- ward Tatum discovered that genes were related to enzymes. ity, antimiscegenation and mandatory sterilization laws In a sense, they had simply clarified the same concept that were passed in many states and in several European coun- Archibald Garrod and William Bateson had proposed in tries. Before such laws were rescinded, over 60,000 people 1902, but with much more evidence and in much more detail. suffered involuntary sterilization in the United States. Al- The association between genes and was evident, though many geneticists favored eugenics to some degree, but their real relationship was yet to be revealed. some of them pointed out the theoretical flaws implicit in Although DNA was discovered by Friedrich Miescher these laws. Morgan in particular renounced his membership shortly after Mendel did his work, the connection between in a society that promoted eugenics, and later in his Nobel DNA and heredity began to surface about the same time that acceptance speech, given in 1935, he stated, “The claims of Beadle and Tatum demonstrated the association of genes a few enthusiasts that the human race can be entirely and proteins. In 1944, Oswald Avery, Colin McLeod, and purified or renovated at this later date, by proper breeding, Maclyn McCarty found that the hereditary substance of the have I think been greatly exaggerated. Rather must we look bacterium was DNA. In 1952, to medical research to discover remedial measures to insure Alfred Hershey and Martha Chase demonstrated that the better health and more happiness for mankind” (Morgan hereditary material of the bacteriophage T2 was also DNA. 1935). Eugenics reached its most tragic point with the However, even in light of these results, most scientists still genocide of millions by the Nazi regime before and during refused to accept DNA as the hereditary substance. Accord- World War II. Unfortunately, eugenic measures are still ing to James Watson, “Al Hershey had sent me a long with us. Reports of genocide and ethnic cleansing are still an letter...summarizing the recently completed experiments by atrocious part of our modern world. which he and Martha Chase established that a key feature Some of the most tragic effects of politics and war on of the infection of a bacterium by a phage was injection of genetics were in Russia in the 1930s and 1940s. Nicolai DNA.…Their experiment was…a powerful new proof that Vavilov was a brilliant Russian plant geneticist who recog- DNA is the primary genetic material.…Nonetheless, almost nized the need to preserve genetic diversity in plants. His

44 USDA Forest Service Proceedings RMRS-P-21. 2001 A Century of Genetics Fairbanks no one in the audience of over four hundred microbiologists bacterial genome was sequenced, the , seemed interested as I read long sections of Hershey’s letter” one of the most ambitious undertakings in the history of (Watson 1969). science, was begun. To sequence the 3 billion of The disinterest didn’t last long. In 1953, Watson and the human genome, scientists required substantial improve- Francis Crick, using data gathered entirely from the experi- ments in laboratory automation and vast cooperation among ments of others, deduced the structure of DNA. One of the many different laboratories. The projected cost of the project chief requirements of the hereditary material was the ability was enormous and it drew significant criticism because to self-replicate. At the conclusion of their classic paper, they many perceived it as drawing research funding away from penned this now-classic line, “It has not escaped our notice other projects. However, the benefits that came from it, that the specific pairing we have postulated immediately automated DNA sequencing in particular, have benefited suggests a possible copying mechanism for the genetic ma- genetic research in many areas, including much of the terial” (Watson and Crick 1953). research presented in these proceedings. About this same time, it was clear that DNA somehow In 1995, and his colleagues at the Institute encoded the composition of proteins, and that RNA was an for Genomic Research published the first genomic sequence intermediate between DNA and . The relationship of a cellular organism, that of the bacterium Haemophilus between sequence and amino acid sequence was influenzae with 1,830,137 nucleotide pairs in its genome yet to be established. Through brilliant mathematical analy- (Fleischmann and others 1995). Goffeau and others (1996) sis by Syndey Brenner, and through analysis of the effect of published the first sequence of a eukaryotic genome, that of on amino acid sequence, geneticists realized that , Brewers yeast, whose genome the genetic code must be nonoverlapping and that three contains about 13 million nucleotide pairs and 6,000 genes. nucleotides must encode each amino acid. These realiza- The sequences of numerous bacterial species and that of the tions led Marshall Nirenberg, Heinrich Matthaei, Severo nematode worm were also com- Ochoa, , Francis Crick, and others to decipher pleted. In March 2000, the genomic sequence of Drosophila the genetic code. By 1965, they had identified the amino melanogaster was published, with 120 million nucleotide acids for 50 of the 64 codons. Then in 1966, the final gaps pairs in the euchromatic regions and about 13,600 genes were bridged, and the genetic code was revealed. (Adams and others 2000). was the first The genetic code turned out to be nearly universal, an plant species to be sequenced (The Arabidopsis Genome observation that had profound implications. Because of a Initiative 2000). Fittingly, at the conclusion of one century of universal code, a gene transferred from one species to another genetics, the first draft of the human genome was an- should encode the same protein in the recipient species as in nounced, 5 years ahead of schedule. the original species. This opened up great possibilities of We have come a long way from Mendel’s garden to the genetic engineering, especially with . In the late sequence of the human genome. I’ll resist the temptation to 1970s, Goeddel and others (1979) successfully introduced a speculate about what the future holds. One of the delights of cDNA from the human gene into Escherichia studying the is to see how wrong many coli, and with a little genetic engineering of the promoter and authors were when they wrote decades ago about genetics in initiation codon regions, achieved expression of pure human our day. This much I feel confident in predicting, however, growth hormone in bacteria. This initiated the age of genetic that the future of genetics is very bright. pharmacology, which now produces such important human proteins as , interferon, and clotting factors in bacteria for medicinal use. So valuable is this industry that the References ______University of California and Eli Lilly & Co. spent over 30 Adams, M. D.; Celniker, S. E.; Holt, R. A.; Evans, C. A.; Gocayne, million dollars in legal fees fighting each other over the patent J. D.; Amanatides, P. G.; Scherer, S. E.; Li, P. W.; Hoskins, R. A.; for genetically engineered insulin. Lilly won the dispute. Galle, R. F.; and others. 2000. The genome sequence of Drosophila For the most part, the molecular revolution and tradi- melanogaster. Science. 287: 2185–2195. tional genetics and breeding remained almost separate Allen, G. E. 1978. Thomas Hunt Morgan: The man and his science. Princeton, NJ: Princeton University Press. 447 p. fields. Then in the 1980s came the convergence of the two Fleischmann, R. D.; Adams, M. D.; White, O.; Clayton, R. A.; with the use of DNA markers to address questions of inher- Kirkness, E. F.; Kerlavage, A. R.; Bult, C. J.; Tomb, J.F.; Dougherty, itance and to improve the efficiency of both medical and B. A.; Merrick, J. M.; and others 1995. Whole genome random se- agricultural genetics. The 1980s marked the beginning of quencing and assembly of . Rd. Science. . Genetic maps, which before had taken years to 269: 496–512. Goeddel, D. V.; Heyneker, H. L.; Hozumi, T.; Arentzen, R.; Itakura, develop, now could be completed sometimes in a period of K.; Yansura, D. G.; Ross, M. J.; Miozzari, G.; Crea, R.; Seeburg, weeks. DNA markers overcame the obstacles that had pre- P. H. 1979. Direct expression in of a DNA se- vented efficient in humans, and the first quence coding for human growth hormone. 281: 544–548. saturated human genetic map was completed in 1994. Goffeau, A.; Barrell, B. G.; Bussey, H.; Davis, R. W.; Dujon, B.; Feldmann, H.; Galibert, F.; Hoheisel, J. D.; Jacq, C.; Johnston, The ultimate genetic map, however, was the entire nucle- M.; Louis, E. J.; Mewes, H. W.; Murakami, Y.; Philippsen, P.; otide sequence of a genome. , who devel- Tettelin, H.; Oliver, S. G. with 6000 genes. 1996. Science. 274: oped the basic process that is now used in automated 546, 563–567. sequencers, reported with colleagues in 1977 the first entire Keller, E. F. 1983. A feeling for the organism. San Francisco: nucleotide sequence of a genome, that of the phage phi X-174 W.H. Freeman and Co. 235 p. Medvedev, Z. A. 1969. The rise and fall of T.D. Lysenko. Trans. which consists of 5,386 nucleotide pairs (Sanger and others I. M. Lerner. New York, NY: Columbia University Press. 284 p. 1977). It was a huge step from those days to the sequence of Mendel, G. 1866. Versuche über Pflanzen-Hybriden. Verhandl the genome from a cellular organism. Long before the first naturf Verein Brünn 4:3–47.

USDA Forest Service Proceedings RMRS-P-21. 2001 45 Fairbanks A Century of Genetics

Morgan, T. H. 1935. The relation of genetics to and Stern, C.; Sherwood, E. R., eds. 1966. The origin of genetics: A medicine. Scientific Monthly. 40: 5–18. Mendel source book. San Francisco, CA: W. H. Freeman. 179 p. Morgan, T. H.; Sturtevant, A. H.; Muller, H. J.; Bridges, C. B. 1915. Sturtevant, A. H. 1965. A history of genetics. New York, NY: Harper The mechanism of Mendelian heredity. New York, NY: Henry and Row. 165 p. Holt & Co. 262 p. The Arabidopsis Genome Initiative. 2000. Analysis of the genome Olby, R. 1985. Origins of Mendelism, Second Edition. Chicago, IL: sequence of the Arabidopsis thaliana. Nature. Press. 310 p. 408: 796–815. Orel, V. 1996. Gregor Mendel: The first geneticist. Oxford, UK: Watson, J. D. 1969. The double helix. New York: Mentor. 143 p. . 353 p. Watson, J. D.; Crick, F. C. 1953. A structure for deoxyribonucleic Sanger, F.; Air, G. M.; Barrell, B. G.; Brown, N. L.; Coulson, A. R.; acid. Nature. 171: 737–738. Fiddes, C. A.; Hutchison, C. A.; Slocombe, P. M.; Smith, M. 1977. Nucleotide sequence of bacteriophage phi X174 DNA. Nature. 265: 687–695.

46 USDA Forest Service Proceedings RMRS-P-21. 2001