Why were Mendel's laws of inheritance not accepted for so many years?
A personal inquiry

- Shigeru Kondo -

Who is the greatest biologist of all times?

If you are a biologist or a biology student, you will most probably have had discussions in the past about who deserves the title of “The greatest Biologist of all Times”. Undoubtedly, many can make a legitimate claim. Should it be Aristotle (384-322 B.C.), the first zoologist or Carl von Linné (1707-1778), the founder of taxonomy? Or rather Edward Jenner (1749-1823), considered the father of immunology? Or perhaps Louis Pasteur (1822-1895), who's experiments dispelled the theory of generatio spontanea, widely accepted in his time? And what about Robert Koch (1843-1910), who identified bacteria as the cause of disease, or Alexander Fleming (1881-1955), discoverer of antibiotics, or maybe…?
Surely, not a few would grant the title of greatest biologist to Charles Darwin (1809-1882), author of “On the Origin of Species”. His theory about evolution has revolutionized biology and has eventually freed the biological sciences from the dogma of religion. It is no exaggeration to state that his ideas have substantially contributed to the intellectual shaping of our modern society and as such his influence can hardly be overestimated. However, I would like to recommend a contemporary of Darwin for this prestigious title: Gregor Mendel (1822-1884). Why? Because his laws of inheritance constitute nothing less than the beginning of modern genetics and have substantially contributed to the rise of the new, powerful science of molecular biology. Without knowledge of Mendel's laws, genetic experiments - and a lot of biological experiments for that matter - would not be interpretable. As a matter of fact, I consider the contribution of Charles Darwin - without defying the importance of the concept of evolution - to modern biology rather modest, in comparison with the magnificent work of Gregor Mendel.

Why were Mendel's discoveries neglected for such a long time?

The laws of inheritance are the most important laws in biology. Nevertheless, after publication in 1865, they were not accepted by biologists and remained in oblivion for more than 30 years, until they were re-discovered by three biologists in 1900. By then Gregor Mendel had died and thus was never to receive during his life the fame, he so righteously deserved for his scientific work. It is widely known that he lived as a friar in a monastery. At first, because of this, I imagined that Mendel had not been trained as a scientist and therefore had presumably not presented his work in an appropriate manner. Now I know that I was wrong. He did present his scientific work the appropriate way and according to the standards of his time. He also lectured on his new theory during several biological meetings and his scientific publication was sent to many well known biologists; the rumor even goes that a copy of the paper was found in Darwin's desk.
During Mendel's time, selective breeding was already widely practiced and offered an important tool for breeders, who desperately longed for better crops, cattle, racing horses, dogs or carrier pigeons. For them, understanding the laws of inheritance would have been nothing less than the Holy Grail that would have made them rich. It is therefore no exaggeration to state that late 19th century society was desperately seeking to understand the rules of breeding and would certainly have welcomed a theoretical framework allowing for an understanding - and thus an improvement - of selective breeding. Nonetheless, Mendel's work was completely neglected. How can this be possible? In contrast, during the same period, Darwin's theory about evolution was widely accepted in many circles of Victorian society and all over Europe, in spite of its fragmenting the religious views on the origin and the very essence of life. Moreover, the immediate impact of Darwin's ideas on crop selection or cattle breeding was close to none.
One could argue that Mendel was certainly far ahead of its time and it was therefore to be expected that his ideas would be received with some disbelief. Possibly so, but I strongly feel that - for the reasons I just came to mention - this cannot entirely explain why his theory remained unknown for more than three decades. This cannot be the whole story. There must be other reasons.
In search for answers, I read the original article “Versuche über Pflanzen-Hybriden”, originally published in “Verhandlungen des naturforschenden Vereins Brünn” (1865). After having read the paper several times, I have to say that it struck me as “strange” and I started to feel sympathy for those biologists at the time, having difficulties grasping the theoretical concepts that were introduced. They can certainly not be blamed if they failed to do so. Indeed, Mendel wrote his paper in a way that was not easily understandable for a biologist in mid-19th century and as a matter of fact, I can imagine that not a few among them have stopped reading after the first pages. If one of my students would present me such writing, I would advise him to reformulate his ideas in such a way that other people might understand them…
Since Mendel can claim to have achieved one of the greatest discoveries in the history of biology, it is probably not entirely wrong to accuse him of supreme intelligence. This might of course explain his “strange” writing as well as the fact that very few biologists could grasp the consequences of his findings. But then - studying the paper very carefully and reading it over and over - I started to develop alternative ideas which finally crystallized into a hypothesis on how Mendel came to develop his theory and why he came to write it the way he did. As so often, I found that also in this case history carefully conceals the hidden meaning behind the facts. It takes time and patience to read the clues.

Mendel's article is surprisingly short

When I first got hold of Mendel's paper, I found it much shorter then I intuitively expected it to be. The article is no longer than 88,000 characters, including all tables (there are no figures). For comparison, the “Author's Guide” of the EMBO Journal stipulates a maximum of 55,000 characters, not including figure legends, references or extended data. For a theory of inheritance overthrowing existing dogmas in biology and, at the time, challenging plain common sense, this paper seems surprisingly short.

Would a contemporary biologist have understood Mendel's paper?

As I already came to mention, the art of Mendel's scientific writing does not seem very inviting, even for readers in those days. In his paper, he starts with commenting on the past experiments that failed to discover the laws of inheritance and explains why: the number of counted individuals was too low to reach unambiguous conclusions, while the selection of species and genetic traits was inappropriate. In the following chapter, he describes how he came to select Pisum sativum (common pea) as the species of his choice, which (seven) genetic traits he studied and how the experiments were set up. This part of the article is build up in a logical manner and is quite comprehensive. Nevertheless, I daresay that it can presumably be understood only by a person who has already knowledge of the laws of inheritance. Scientist unfamiliar with those laws would find it difficult to understand. For example, Mendel wrote that - in order to obtain purebred seeds - he crossed the peas for two generations. However, to know that two generations is enough, one needs an understanding of the law of segregation. For his experiment, he selected those traits whose phenotype in the F1generation is the same as in one of the parents. In order to explain this genetic phenomenon, Mendel coined the terms “dominant” and “recessive”. However, these concepts were incompatible with the widely accepted theory of those days, namely “blending inheritance”, whereby it was postulated that the F1 phenotype (for any given trait) is somehow a mixture of the respective phenotypes of both parents.
Moreover, in the following chapter - and this with hardly any explanation - Mendel makes use of symbols such as Aa or AaBb to characterize the genetic status of the hybrid F1 generation. It goes without saying that the use of such symbols and a thorough understanding of their exact meaning lie at the heart of Mendel's laws of inheritance. Taken together, the writing of the paper was obviously hypothesis (Mendel's law of inheritance) driven, but this was not explicitly stated. As such, probably only those scientists who had already an understanding of the theory - perhaps only Mendel himself - could grasp the meaning of the article.

A whole lot of mathematics…

The Result section of the article is composed of two parts, namely proving the laws of 1) segregation and 2) independent assortment. Mendel did the pollination of the individual flowers by hand. As such this would allow him to unambiguously define the genetic status for a given trait (homo-or heterozygous) of the hybrid F1 generation and would ensure that the genetic traits would be evenly inherited among the offspring. As Mendel's experiments demonstrate, this ratio apparently remains unchanged over generations. As such, it should suffice to write down the crossing schemes for the F1 and F2 generation. Mendel however kept continuing this pollination procedure not only for F3, but for several generations thereafter, including all the data in a rather cumbersome way in his article. At the end of this chapter, he introduces the equation, describing segregation of a given trait for any given Fn generation: 2n-1:2: 2n-1 (Fig.2).
I immediately recognized the mathematical beauty revealed in this universal principle of inheritance, but at the same time was struck by the overwhelming amount of equations. After all, this is a biological paper - and one of the most influential ones written to date - and not an exercise in algebra. I started to vividly imagine biologists having trouble keeping awake during a lecture of Gregor Mendel - who after all, as his work convincingly shows, had the patience of a monk - writing down equation after equation after equation on the blackboard…

A very theoretical paper: why?

From the above mentioned, I would postulate that the theoretical description and the abundant use of mathematics in the paper are the main reasons why the laws on inheritance were not immediately accepted. That leaves us with the obvious question: ?“Why did Mendel write this article in such an awkward and rather un-biological way?” My guess would be that the answer lies in his education.
Johann Mendel was born in 1822 into an ethnic German family in Heinzendorf bei Odrau, Silesia, in the Austrian Empire. From 1840 to 1843, he studied practical and theoretical philosophy and physics at the University of Olomouc at the faculty of philosophy. After that he became a friar (and during this time received the name Gregor) and worked as a substitute high school teacher for mathematics and greek. In 1851 he was sent to the University of Vienna where he studied physics and mathematics with Christian Doppler (1803-1853), discoverer of the Doppler effect. Judged from his scientific education it is only fair to conclude that Gregor Mendel was more of a physicist than a biologist. As such, theoretical deduction and mathematical oriented thinking were certainly quite natural to him.
It seems obvious to me that Mendel had already worked out some theoretical concepts and designed his experiments accordingly. In other words: his genetic crosses just had to prove what he knew all along. That is why he carefully selected only those genetic traits that fitted in with his hypothesis. Does it have to be stated out loud that there were numerous pitfalls that could have interfered with his proving of ?“Mendel's law?”?
For example, in order to reach straightforward conclusions concerning the law of segregation, a given genetic trait must be controlled by a single gene. Now, we know of course that many genetic traits are controlled by more than one gene. If Mendel would have chosen by accident linked genetic traits, he would have never been able to reach firm conclusions, since the law of independent assortment does not hold in this case. Likewise, lethal genes, parthenogenesis and self-incompatibility could have obscured the outcome of his crosses in a way that would have left Mendel entangled between non-interpretable phenotypes and seemingly meaningless numbers for the outcome of his crosses. But all of this did not happen. Why not? I postulate that Mendel walked undamaged through a scientific minefield because he had a map. If this is indeed the case, how and when did he get it?

How did Mendel develop his theory?

Since Mendel began his crossing experiments with peas shortly after returning from Vienna, it is not unlikely that he developed his ideas on inheritance while studying with Doppler. It is therefore reasonable to assume that he came towards these concepts through theoretical reasoning, rather than by performing biological experiments. His training in physics - a science discipline where highly complex phenomena can often be explained by underlying basic principles that are governed by simple mathematical rules - was certainly most welcome and discussing his ideas with his mentor might have helped him unravel the laws of inheritance. At first sight, it may seem impossible to discover Mendel's laws trough pure theoretical reasoning and deduction. Personally, I don't believe this. I think such a task can be accomplished by a person with an open mind, not obscured by the prejudices of those days.

How to deduce the laws of inheritance?

During the mid 19th century, the widely accepted doctrine in the field of genetics was “blending inheritance”, postulating the irreversible mixing of parental genetic characteristics (as a manifestation of genetic units) in their progeny. However, it was also empirically known that a hidden trait reappeared when hybrids were crossbred, thereby demonstrating that an inherited genetic unit somehow remains unchanged in the progeny, though not always visibly apparent. Therefore, it should have been clear that the concept of blending inheritance is incorrect. Mendel termed the visible genetic units “dominant” and the invisible ones “recessive”. He reasoned, given that a genetic unit in the offspring is derived from both parents, its number in the F1 generation should be more than one. Since the number of genetic units should be identical in every generation, the parents - who are the F1 offspring of their parents - should also have more than one genetic unit for a given trait. At least one of these genetic units is then transferred to the progeny. By making the assumption that a given trait is represented by two genetic units, one can deduce Mendel's law of segregation.
The law of independent assortment determines the relationship between the traits. Theoretically, there are three possibilities: tight linkage, loose linkage or no linkage. This can be tested by carrying out crossing experiments. In case the genetic traits are on the same chromosome, they do not follow the rule of independent segregation. I guess that Mendel was aware of such cases because the number of traits (seven) he deals with in his article, is exactly the same as the haploid number of chromosomes of Pisum sativum. A selected eight trait would demonstrate genetic linkage to one of the other traits.
Of course, all this is retrospective thinking and discovering Mendel's laws must have been a difficult task for a person, unaware that genetic inheritance is controlled by a simple mechanism. But not impossible, and I would argue that such a task is less difficult than deducing the laws of thermodynamics or finding Kepler's laws.

Why were Mendel's theoretical ideas not obscured by reality?

At present - one and a half century after Mendel's discoveries - it is common knowledge that there are numerous exceptions to the three basic laws of inheritance and it turned out that phenotypes controlled by a single gene and alleles showing a segregation into clear dominant-recessive features are rather the exception than the rule. As a matter of fact, if a person were to select arbitrarily a trait and/or a species for his crossing experiments, the chances are very high that he would never manage to discover the laws of inheritance. Mendel must have been aware of this problem. As he describes in his paper, he carefully selected both species and traits for his genetic crosses, being aware of the fact that in most other cases he would never be able to experimentally verify his hypothesis. This clearly demonstrates once again that he had a priori formulated his theory and had a strong belief that he would be capable of proving it. This is his major achievement. But how did he manage to do this, 150 years ago?

A beautiful theory is not necessarily correct. Or is it?

I, of course, have no proof but I personally feel that what made Mendel so confident about his laws of inheritance was their mathematical beauty. Let's travel back to the middle of the 19th century: biologists were puzzled, inheritance was considered a chaotic and highly individual phenomenon that could not be predicted or described in a simple manner. In short, genetics was not understood. The laws of Mendel changed this view completely. At once, it became clear that inheritance of traits is all but chaotic. On the contrary, it could suddenly be explained by a few universal principles which are the same for every species on the planet. A genetic unit remains unchanged through generations, while different combinations of different units create an infinite variation of genotypes. The theory is astonishingly simple and allows for making predictions about the outcome of any genetic cross. The beauty of Mendel's laws is simply breathtaking and precisely because of this, I can easily imagine that Gregor Mendel was utterly convinced of their truth and would probably have bet on it with his life.
Is this a far-fetched argument? It could be. But have we not all, at one time or another, witnessed similar experiences? For example, the mathematical problem whereby one is asked to calculate the trajectory of a moving point in space. As soon as you find the solution, e.g. a circle passing through an origin, do you not intuitively “feel” that this is the correct answer, precisely because of its simplicity and mathematical beauty?
The fact that a scientific theory is beautiful, does of course not guarantee that it is true. But it surely helps. Nobody less than the world famous physicist Paul Dirac (1902-1984) once said: A theory with mathematical beauty is more likely to be correct than an ugly one that fits some experimental data”. A controversial statement in the field of quantum physics, but I am convinced that Gregor Mendel would have agreed with his whole heart. After all, biological phenomena are fundamentally governed by the laws of physics, no? And here we return to “Versuche über Pflanzen-Hybriden”. One of the most important things Mendel wanted to do in his paper, was to convince the reader of the mathematical beauty of his theory. And that is why he included all his calculations. He wanted to convince his readers and make clear to them: “I believe”.

What we can learn from Mendel?

Before I started to write this article, I told the story to my students. Although most of them admired Mendel's insight and uncanny capacity for theoretical reasoning, some argued that neglecting certain phenotypes - namely those that did not fit in with the hypothesis - is methodologically wrong and not the correct way to perform experimental science. Certainly, this is a legitimate argument. On the other hand, if Mendel would not have excluded certain phenotypes, he would most probably have vanished into oblivion, forever unknown to the scientific community, since the chances of him discovering the laws of inheritance would have been close to zero.
Most biological phenomena emerge as a complex entanglement of related events, which obscure the underlying (often astonishingly simple) principles. Seemingly unrelated, so called “additional effects” make it very difficult to understand the basic rules and mechanisms. I have great admiration for Mendel, precisely because of his capacity to retain those experimental facts that he intuitively knew would help him to discover the universal principles of inheritance and allow him to “steal” the basic laws of genetics from nature. We can only speculate about why other scientists, before Mendel or till the end of the 19th century - unfamiliar with the work of Mendel as they were - failed to find those laws. My guess would be that they did not have enough confidence to perform the big experiment.

Will comprehensive data acquisition lead to a new theory?

With the rise of genome technology, comprehensive data acquisition has become a widely accepted methodology in Life Science research. We expect to find answers to unsolved questions by identifying all genes and characterizing every molecule, thereby generating a gigantic amount of data. And of course, this is a legitimate strategy: it is better to know more than to know less. But we should realize that gathering immense quantities of data alone is not enough and does not necessarily open the door to understanding fundamental principles and gaining insight into the laws of nature. In this context, I would like to bring into remembrance how Isaac Newton (1642-1727) discovered the universal laws of motion. Indeed, exactly through focusing on the orbit of planets and not taking into account the movement of objects on earth, thus neglecting resistance and gravity. Again, this demonstrates the importance of focusing on a specific set of events, while - at least up to some point - not including others. Mendel's story illustrates in the most beautiful way this principle and convincingly shows the importance of insight into experimentally gathered data to reach unambiguous conclusions. I hear you ask: “How can I learn such insight?” I am afraid there is no clear answer to this question. But I am convinced that every scientist has an opportunity to gain such insight and not only those professors who lead a big laboratory, sponsored by immense grants. Maybe on the contrary, such “big bosses” have so much management duties that there quite often remains little time for thinking.
For exploring new scientific horizons, not the size of an institute or the amount of funding money is the most important, but the spirit and fresh ideas of young scientists. This was true in Mendel's time and it is still true today. What counts is that young scientists foster their own ideas and cherish a sense of intellectual beauty, regardless of any trends or so called “common sense”. You say you are not a genius like Mendel? Do not worry: Mendel was probably not a genius either, just a very good scientist with an open mind. Apropos, after he wrote his article - one of the greatest discoveries that would change Biology forever - he failed his exam to become a certified teacher in the monastery…

Translation: Ronny Leemans