Brother Gregory: Gene One Read online

  Mendel, therefore, used controls not simply to support his good results, he also used them to discount and deflect any criticism of poor or unexpected results.

  Author's note: I am a fan of Mendel, his work, his life and his discoveries, but nobody is perfect, Mendel included. As I have noted elsewhere, Mendel probably lost his audience in the Realshule and later when he wrote up his results as a paper, by giving huge amounts of gardening detail, something that even the most 'fanatic-for-detail' might consider unnecessary in a scientific paper.

  But there are also a few other questionable aspects to Mendel. He is very honest about the fact that he simply threw away plants he considered gave him poor or unexplainable results. This may be a common practice, even today, but it is hardly admirable, except for its honesty (most modern scientists would never even admit to this practice!).

  Even more questionable is his choice of starting material for his work. His paper reports the results he obtained from crosses involving seven characters. He never explains how or why he came to choose exactly those seven characters and why he abandoned the rest. With his usual honesty he lists fifteen possible characters, and then ignores more than half of them. A charitable explanation would be that he never had time to carry out all the experiments he wanted, but ...

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  Fertilization

  Fertilization takes place in angiosperm plants when the haploid male nucleus of the male gamete fuses with the nucleus of the female haploid gamete. Their journeys to this union can sometimes be very long.

  It starts with reproductive cells produced in the male and female sex organs of the flower. Meiosis divides up the chromosomes, DNA and the genes they carry into separate, haploid packages. This very special type of cell division only occurs in sex cells and only to produce gametes.

  The outcome is two fold; each gamete only has half the genetic material found in the diploid parental cell, and the separation of chromosomes is independent of one another, so the mixtures of chromosomes is random. Male and female gametes, therefore are genetically different not only from the parental cell, but also from each other. In this way the genetic diversity is increased at each meiosis.

  Male gametes are made in large numbers and packaged into well protected traveling cases; pollen. Female gametes go through an elaborate development in which triploid material is formed which will eventually nourish the seed. But eventually several well stocked eggs are produced which line up in the ovary awaiting the arrival of the male gametes to fertilize them.

  Now begins a remarkable journey. Pollen grains are scattered from the anthers onto some carrier. In some plants, this is just the wind, but in many other plants the carrier is an insect, beetle, bird, mouse or moth. Stuck to the back of a bee, pollen moves from one flower to another. As the carrier feeds off the next flower the pollen is shed into the area of the ovary and can be picked up by the sticky stigma.

  Triggered by its arrival, the pollen grain puts out a long tube which dissolves its way along and through the style, eventually entering the ovary and making contact with one of the egg cells. Back in the pollen grain the haploid nucleus, which is all that is left of the male gamete, begins the last stage of its journey. It moves down the tube and into the egg cell. Finally the two haploid nuclei fuse and the next generation has begun.

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  Flowers and Fertilization

  Flowers are the reproductive structures of angiosperm plants. They house the male and female reproductive organs and are the site where fertilization takes place. After fertilization the seeds start to develop inside the flower, which usually withers away. The flower is eventually replaced by the fruit (if the plant has one).

  Inside the protective petals (called the keel in this case) of Mendel's flowers, he found the male and female organs. The female structure consists of an ovary which holds a row of eggs. After fertilization these become the typical peas seeds. A short style, a solid tube, connects to the stigma which collects the pollen.

  The male parts of the flower are long, thin filaments that hold at their tip, anthers where the male pollen grains are produced.

  In many flowering plants, insects and other carriers, arrive at the flowers attracted by the color and the promise of nectar. They push their way into the flower and pick up the pollen on the backs or tongues. They then travel to other flowers and inadvertently place the male pollen onto the stigmas of female parts.

  In this way male sex gametes (in the pollen grains) are brought close to the female sex gametes (in the egg cells). A tube grows out of the pollen grain, down and through the style and into the ovary. At the right moment a haploid male gamete moves down the tube and enters one of the haploid egg cells. Fertilization has taken place. The genetic material carried by the gametes fuses and the seed starts to develop.

  In Mendel's peas both the male and female parts are protected and covered by a special set of petals. This keel hides the anthers and ovaries, so normally these flowers are self-fertilizing. Mendel, in his experiments, would artificially move pollen from the flowers of one plant onto the styles of ovaries of another plant. This is the first step in a genetic cross.

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  'Fluids' and 'Blending'

  In Mendel's time, the prevalent explanation for inheritance was dominated by two ideas; offspring were a "blend" of two "fluids" donated by their parents and that the male parent's donation was more important than the female's donation to the offspring.

  Blending inheritance was an old idea. It was common then, and is still common today, to talk of a person being "half Italian" or being "part Polish", and the metaphors used as a mechanism to explain inheritance drew more on the idea of "blending" two cans of paint than mixing gene combinations. Mix a can of red paint with a can of white paint, and the result is a pink color. Most scientists felt that the offspring was just such a "blend" of controlling "fluids" given by the parents.

  Mendel made an important contribution to genetics when he confronted this issue head on and stressed that in his experiments there was a complete dominance of one form (at least most of the time). A theory that included the idea of "blending" could not explain his findings.

  Although not unique, Mendel's work also started the debunking of another theory of inheritance; that the male parent's contribution was most important. Mendel insisted from the beginning that the contribution from the "pollen parent" was no more (or no less) important in influencing the form of the hybrid than the contribution by the female parent. This idea of "equal contribution" not common either in contemporary studies of inheritance.

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  Inspiration

  It is always difficult to know where a good idea comes from. In Mendel's case it is particularly difficult as, like Darwin, he presents it in almost complete form, a concept that is totally new and totally revolutionary. Where did this idea begin?

  In his scientific paper Mendel writes that part of the motivation for his work may have come from the observation that hybridization in plants was remarkably predictable. The names he mentions in his talk; Joseph Gottlieb Kolreuter (1733-1806), Carl Friedrich von Gartner (1772-1850), Max Ernst Wichura (1817-1866), and others, were botanists who investigated plant hybrids. He seems very familiar with their work.

  He also seems very familiar with the limitations of this work. He notes, that no one yet has been able to predict the form that hybrids will take, even if you know the forms of the parents. No one should be surprised by this, he says, since the relevant experiments are difficult. They require a great amount of time to carry out, and the experiments must be carefully worked out in order to be successful.

  Mendel's written work makes it clear that he was motivated to find a law that governed the production of hybrid forms. But this is not enough. What gave him the idea of two "elemen
tes" (what we would call genes today)? Maybe we will never know, but there are tantalizing hints in some of the research data he presented. (See later)

  The introduction to his paper, however, makes it clear that the law he wanted to find had to be quantitative as well as qualitative; numbers, as the fictional Grunewald would say, are critical. Mendel wanted to be able to predict not just the kinds of hybrids that would appear in a genetic cross but also their "statistical relations".

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  It Works!

  In science as in life, success is important. In his talk, Mendel was reporting to the Society his successful experiments in plant hybridization and what he thought he had discovered. What he did not report, however is almost as interesting as what he did say.

  For example, he told his audience the exact number of varieties he procured from the seedsman, and the exact details of how to perform an artificial fertilization. What he does not tell, however, is the reason why he chose only 22 of the varieties he had been given. Any modern scientist could provide the answer to this question; the seeds that he reported on gave results that "worked".

  Over and over again in the scientific literature, the only experiments that are reported are those that produced results. It is very rare (almost never) that non-productive experiments are presented. In some ways this is understandable. Most experiments do not produce reliable results for a variety of reasons; not all the variables were controlled, the wrong conditions were chosen, or simply the hypothesis was wrong. If all non-productive results were reported the literature would be swamped.

  But the creative side of the scientific mind is as interesting as the conclusions that eventually make it into the literature and history. It would be fascinating to learn where Mendel got the idea for his experiments. Many historians of science consider that Mendel already had an idea of the answer, before he started asking the question, or doing the hybridizations. There is nothing wrong with this, but it does explain his choice of starting material; it gave the results he wanted to see.

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  Bismarck

  Otto von Bismarck, who, during his life, was also known as Otto Eduard Leopold, Prince von Bismarck, Count von Bismarck-Schšnhausen, Duke von Lauenburg, was one of those critical, larger than life, historic persons who have changed the course of history. He was also a Prussian statesman.

  It was largely by his efforts that a diverse group of middle European states became united in 1871. Bismarck founded the first (and last) German Empire and served as its first chancellor for 19 years.

  His greatest work established, he cleverly and skillfully wove his way through the labyrinth of 19th century policies in foreign affairs, mostly to the advantage of Germany. It is to his credit that, after making war on almost every small and weak state in Europe he also succeeding in preserving the peace for about two decades.

  In the time of Mendel, Bismarck was very active in foreign policy. He hoped, like many leaders before and since, that success abroad would weaken his domestic enemies at home. He found the perfect opportunity bullying a small country.

  Since 1848, trouble had been brewing between the Germans living in the duchies of Schleswig and Holstein and their nominal master, the Danes. At this time, both duchies were in union with Denmark, but the majority of the Schleswig population were of German stock, and Holstein was a member of the German Confederation.

  Bismarck got his chance to make trouble when the Danish king acted rashly, and he struck swiftly. He saw to it that Prussia and Austria spoke out for the interests of the German citizens of these duchies, and launched a quick, successful, war against the unfortunate and ill prepared country of Denmark.

  The fate of Schleswig and Holstein was now in the hands of Bismarck and the Austrians, who promptly fell to haggling over the spoils. At the time of our story, Mendel would have know about the growing stress between the "Iron Chancellor" and his own leaders of the Austrian Empire. In the very year that he gave his talk on Plant Hybridization, the Convention of Gastein (signed on Aug. 20, 1865) provided for Schleswig to be administered by Prussia and Holstein by Austria.

  But back in Germany Liberals in the government were still unhappy at Bismarck and by Prussian military prowess and once again handed Bismark and the Emperor a serious defeat when the army bill came up for a vote in January 1865.

  Tensions between Germany and Austria continued to rise. Bismarck repeatedly told the Austrians that they would be wise not to get him angry and to yield dominance in everything to Germany. His warning and his words fell on deaf ears. So, after making sure that Russia would not stab him in the back, and after making temporary friends with Italy, he started stirring up conflict with the Austrians.

  Using Hungarian nationalism against Austria as an excuse, on June 9, 1866, Prussian troops invaded Holstein, and a few days later Austria. Within six weeks Prussia had inflicted a major defeat on the Austrians at Koniggratz (Sadowa), and Mendel had a new master.

  Bismarck craftily counseled moderation so Austria would not be humiliated, and he urged a quick cessation of hostilities. In this way he prevented other powers from intervening. The rest of Europe was stunned. Overnight the man of Iron and his Prussian military machine had transformed the essential distribution of power in central

  Europe. Austria, once a major power, was now a secondary player.

  Mendel was forgotten.

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  Transmission mechanism: the Gene

  A gene is a length of DNA that codes for a single polypeptide chain.

  This simple definition of the Mendelian "transmission element" was not known or understood until the 1950's and 1960's. Although chromosomes had been discovered much earlier, and it was strongly suspected that they carried the units of heredity, the exact chemical nature of the gene remained a mystery for over 60 years.

  Oswald Avery made a critical breakthrough in the search for the chemical nature of the gene in 1944. In a series of carefully controlled experiments, Avery and his co-workers at the Rockefeller Institute, were able to show that a molecule of DNA was able to "transform" a harmless Pneumococcus. bacterium into one which was lethal to mice. DNA-digesting enzymes destroyed the "transforming principle", whereas enzymes that only digested protein had no effect. DNA carried the "transmission element".

  Ironically, the substance called DNA had been discovered by a German chemist, Friedrich Miescher, in 1869, only four years after Mendel gave his seminars, but few scientists considered it an interesting molecule. It was boringly simple with only three different components; phosphate groups, five carbon sugars and nitrogen containing bases (purines and pyrimidines). This was discovered by P.A. Levine in the 1920's.

  With Avery's work, and even more exciting work on bacterial viruses by Hershey and Chase in 1952, DNA suddenly became important, and the race was on to determine its structure. This race was won in 1953 when two young scientists, working at Cambridge University, published a likely structure of the DNA molecule. These were James Watson, then a postdoctoral student and an English scientist Francis Crick.

  Using models, and other people's data, they hit on the breakthrough idea that DNA consisted of two chains of nucleotides held together by phosphate groups and twisted around each other in a double spiral they termed a double helix. The nitrogenous bases pointed into the center of this double spiral and paired up with each other in a fixed manner; adenine with thymine and guanine with cytosine.

  Although Watson and Crick's model of DNA immediately suggested a mechanism for its own replication (and hence how DNA could act as the molecule of heredity), it took a lot longer to workout the details of how the DNA carries the information that produced the traits seen in Mendel's peas.

  But the gene was now firmly located on the DNA molecule, which in turn was the central core of the chromosome. Mendel would have understood.

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  Pisum sativum

  Mendel's green pea (Pisum sativum), is also called the garden pea or English pea. It was a good choice for experiments in genetics for several reasons. Peas can be planted early in the spring, often while the ground it still cold from the winter. They grow and fruit quickly and are among the earliest vegetables to be picked each year. The monks in Mendel's monastery would have really appreciated his crops as peas are best if eaten almost immediately. Like corn, peas lose their sweet flavor very rapidly.

  One of the distinct characteristics about peas, that Mendel used, is that peas can be classified as either smooth or wrinkled. This depends on the way their seeds look when dried. Every gardener knows that wrinkled varieties of peas are sweeter than smooth ones, and only wrinkled varieties were eaten in Mendel's monastery.

  As early as possible each spring Mendel would rush into his experimental garden and plant the seeds he had collected the previous year. The length of time he would have to wait before getting his results would vary for each variety. From the time his seeds were sown in the Monastery soil, until the plants were ready to be harvested depended on the kind on plant. Tall-growing types (one of his characteristics) are the 4- to 5-foot high and take 74 days; whereat the shorter types and two 2 1/2-foot and only take 67 days. Dwarf types (another characteristic) are about 15-inches at maturity and only take 64 days. The difference in maturation times must have given him a certain amount of trouble.