Yeast cells. Computer illustration of budding yeast cells (Saccharomyces cerevisiae). Known as ... [+]
At first glance a dish of baker’s yeast in 2020 has little to do with starving pregnant women in Holland in the winter of 1944-1945. However, both produced evidence that nineteenth-century naturalist Charles Darwin was wrong when he called the ideas of late eighteenth- and early nineteenth-century naturalist Jean-Baptiste Lamarck “veritable rubbish.”
To be clear, though, Darwin was at least a little right about Lamarck, some of whose ideas were malarkey. For example, Lamarck thought that inanimate objects can spontaneously become animate. He thought that simple organisms aspire to become complex.
Even so, he had a few interesting notions. He believed that transmutation (a term that eventually was replaced by Darwin’s “evolution”) can proceed rapidly. Lamarck thought this possible because he also believed that experience can be biologically transferred through generations.
That idea runs directly counter to Darwin’s idea that evolution happens because of random, constitutional changes in the fundamental physical units of organisms — units that would one day be called “genes.” These changes help those lucky organisms in which the random changes occur adapt to environmental pressures (which Darwin sometimes called “selection pressures”). Darwin never suggested that anything as intangible as experience could be biologically passed from parent to child.
Fifty years after Lamarck introduced his idea of transmutation, Darwin’s landmark book On the Origin of the Species by Natural Selection was published. In that book he introduced the concept of evolution, and in a letter that year to colleague Charles Lyell, he wrote that Lamarck’s work was “extremely poor; I got not a fact or idea from it.”
Since that time, Darwin’s insights into evolution have profoundly and deservedly influenced all of the biological sciences. Lamarck’s, on the other hand, have largely faded from view. That being said, over the last twenty years or so, one of Lamarck’s positions has seemed to sneak back at least a bit into the mainstream. It is the idea that experience can be biologically transferred through generations.
Now, in 2020, a mysterious epidemiological event dating from mass starvation in 1944 and 1945 may begin to make sense. This is at least partly thanks to a Lamarckian and Darwinian experiment with hundreds of generations of yeast in a lab led by Yale University’s Murat Acar.
The Dutch Hunger Winter
During World War II, The Netherlands was occupied by Hitler’s army. In September of 1944, in an attempt to aid the efforts of the Allied forces as they liberated the southern areas of the country, the exiled Dutch government encouraged the national railway to impede the shipment of German troops and armaments by halting train service. In retaliation, the Germans blockaded food shipments to a heavily populated area in the north of the country. About twenty thousand people starved to death over the course of what came to be known as the Dutch Hunger Winter. In general, Dutch people survived on a diet of 400-500 calories a day. Many ate grass and tulip bulbs to stay alive.
Pregnant women, of course, were in dire straits. Not surprisingly, many of the children who were fetuses during the Hunger Winter were small and underweight as newborns. As they grew into adulthood, however, they tended toward obesity. So did those children’s children. Also common among the first generation of babies and their descendants were poor cardiovascular health and early death.
Scientists are still struggling to understand the whys and wherefores of that epidemiology. A behavioral explanation might be that, once food was again plentiful, the mothers who had been pregnant during the Hunger Winter over-valued food. In doing so, they taught their children and ultimately their grandchildren bad dietary habits. This explanation doesn’t quite stand up to scrutiny, however; the younger and older siblings of the children who had been fetuses during the Hunger Winter did not tend toward obesity, poor cardiovascular health, and early death. A pathologically altered family diet did not create family-wide health problems.
Genetic evolution does not work as an explanation, either, for mutations require many generations to accrue and become evident in a population. The Hunger Winter-induced health changes in newborns started abruptly.
Another possibility is that a fundamental physiological change of some sort occurred in pregnant women in response to the starvation. Genes didn’t need to mutate. Instead, in the pregnant women, starvation caused a change in the “expression” of individual genes or gene networks. Once “locked in,” the change in expression got passed from mother to child and then from child to grandchild.
What Is Genetic Expression?
Inside the nucleus of every cell in an organism are chromosomes, and inside every chromosome is a long string of DNA. DNA is comprised of genes. They direct the many complex processes that result in the assembly of protein molecules. Proteins play a role throughout an organism’s development and function.
Concept image of a structure of the genetic code.
Because all of the DNA in an organism is identical, all of the genes are, as well. That being said, the behavior of individual genes and the results of their work are not all the same. The type and number of proteins that a gene or a network of genes help create are controlled by chemical compounds attached to the genes. Those compounds function both as on/off switches and as volume controls, “expressing” the genes or quieting them in response to real-time environmental pressure.
Over the last few decades, experiments have shown that changes to the on/off and volume control switches of genes can be permanent. Some scientists have speculated that changes in gene expression can be inherited. For example, in the case of the Dutch Hunger Winter, starvation (an environmental pressure) may have turned on some switches, turned off others, and turned the volume up or down on still others, creating an acquired characteristic such as insatiable hunger or a slow metabolism that kept the pregnant Dutch women alive despite their increased nutritional need. That acquired characteristic may have been passed on to unborn children that the starving women were carrying. If so, that would be a perfect example of a quintessentially Lamarckian idea.
Epigenetics
“Epigenetics” is a term often associated with Lamarck. It refers to heritable changes in gene expression. (The Greek prefix “epi” means “in addition to.”)
While epigenetics could explain the effect of the Dutch Hunger Winter through three generations, it might also help explain some observations as well as the results of a host of scientific experiments. For example:
· Epigenetics could account for the fact that certain environmental chemicals that were found to promote disease in an initial generation of pregnant rats affected their descendants generations later.
· Epigenetics may have been responsible for multi-generational changes to growth and flowering in a first generation of plants exposed to drought and cold.
· Epigenetics may even play a role in the heritability of psychological trauma — though a strong argument can also be made that being raised by traumatized parents is itself traumatizing.
Ever since 1942 when British developmental biologist, paleontologist, geneticist, and embryologist Conrad Waddington first coined the term, epigenetics has been used to explain many non-genetic intergenerationally-consistent changes.
And now it may help explain what happened to Murat Acar’s baker’s yeast.
Murat Acar’s Baker’s Yeast
Acar originally trained as a physicist. He is now a systems biologist at Yale, where he is on faculty in both the Physics and Molecular Cellular & Developmental Biology programs.
Baker's yeast.
Curious about epigenetics, Acar designed a lab experiment that could give him a clear picture of evolution at work in real time.
Acar’s experiment focused not on a single gene but on a single type of gene network. It was the GAL gene network. Easily found inside yeast cultures, it helps yeast cells metabolize the sugar galactose. Acar chose to examine GAL networks because they are fairly well-known among biologists. As he explained in a phone conversation, “Almost everything about the GAL network is known, though its real-time evolution is an exception.”
Yeast offered Acar another experimental advantage. Yeast populations reproduce asexually and rapidly, replicating at a pace of about one generation every one hundred minutes. Also, yeast are simple organisms. As Acar explained, “Because of the obvious challenges associated with the interpretation of the evolution of multicellular systems, we chose a single-cell organism as our experimental model.”
The cells in the initial population of the yeast that Acar used were genetically identical. (That’s usually the case for yeast grown from a single isolated colony.) Even so, random differences in cellular processes including the expression of genes and gene networks generally cause some diversity in the physical characteristics of individual yeast cells.
During the course of their experiment, Acar and his team observed differences in the genetic expression of the GAL network. The differences were made evident (or, as Acar explained, “reported”) by fluorescent proteins, which are commonly added to yeast populations in labs. On a daily basis for seven days, Acar and his team sorted yeast cells based on the expression level of florescent proteins showing the activity of GAL networks. A high expression level would indicate a high capacity to metabolize galactose. A low level would indicate a low capacity.
Only cells with reported expression levels within one of three ranges (either the lowest five percent, the middle five percent, or the highest five percent) were removed from the main yeast population and placed in separate dishes, where they were allowed to grow further using the same growth medium.
The First Hundred Generations
Calculating the rate of cell replication at one generation per one hundred minutes, the yeast populations probably grew by about fourteen and a half generations every day. This means that, over seven days of repeated sorting and growing, the researchers probably monitored GAL network activity across about one hundred generations.
For the cells with expression levels upon the first sorting that lay in the middle five percent and highest five percent groups, the researchers observed no significant expression-level changes over the course of those seven days. The team wasn’t surprised that the cells whose GAL network expression level was in the middle five percent didn’t, after sorting, drift towards average expression levels. Those cells were already expressing at an average level. Neither were the researchers surprised that the cells sorted for the highest expression level did not, after sorting, express at an even higher level; the team attributed the lack of expression change to the likelihood that the GAL network activity would not be physiologically capable of reaching a higher level. Acar and his team were impressed, however, that yeast cells that were sorted for the lowest GAL network activity continued to display expression reduction, and they did so even after the sorting had stopped. (Acar considered the sorting itself to be the Darwinian selection pressure.)
“The yeast cells with reduced expression levels seemed to have ‘memorized’ or have been ‘locked into’ the low-expression state,”Acar explained by phone.
Two Hundred Thirty More Generations, Followed by Even More, and Then a Discovery
After the seven-day period, nine populations of yeast with low GAL network activity were grown selection-free for another two hundred thirty generations. Eight out of the nine populations retained the expression level reduction.
The researchers then repeated the sorting experiment, this time with two differences. They used an additional fluorescent reporter and they tracked the activity of a different gene network. Again, cells sorted for low GAL network activity showed consistent expression level reduction. However, the activity of the other network did not.
“From this we concluded that the dependably reduced expression levels we observed were due to factors in the GAL network rather than global factors controlling the many other genes and networks in the yeast,” Acar wrote in an email.
Finally, for each yeast strain that the team used, they employed a variety of techniques to measure and compare both phenotypic (observable) and genetic changes.
“The GAL network activity pattern that we repeatedly witnessed during our evolution experiments could not be explained only by genetic changes or by the classic Darwinian interpretation of evolution,” Acar explained. “There was a clear Lamarckian epigenetic mechanism contributing to gene network evolution.”
Acar and his team described their paper this October in the journal Cell Reports.
Were Both Darwin and Lamarck Right?
Answers to questions about whether catastrophic traumas like war, famine, imprisonment, or family violence can change the very biology of people in multiple generations will never point only to epigenetics. This is because, whether or not biology is changed in a heritable way, behavioral adaptations that affect the family environment can become indelible stressors in and of themselves. They can be passed from parent to child and on and on.
circa 1875: British naturalist and writer of 'The Theory of Evolution' Charles Robert Darwin (1809 ... [+]
Even so, the evidence is growing that permanent, heritable biological change can quickly be forced by physiological selection pressure.
In physics there is a concept known as the Grand Unified Theory. It explains all of the forces of the universe as well as the apparent contradictions among them. It is still only a twinkle in physicists’ eyes, of course; no one has yet successfully devised such a scheme.
Color engraving shows French naturalist Jean Baptiste Lamarck (1744 - 1829), late 18th or early 19th ... [+]
Acar, who works as a systems biologist but trained as a physicist, suggested in a a phone call that it’s possible that someday another sort of Grand Unified Theory might explain all of evolution. He also indicated, however, that a less grand theory might help scientists sort things out, as long as it incorporates both Darwin’s brilliance and that of Lamarck.
While neither Lamarck nor Darwin knew a thing about genetics, Darwin understood evolutionary mutation to depend to some degree on fundamental units of heredity. He thought change to those units happened both randomly and incrementally, and at a glacial pace. On the other hand, Lamarck reasoned that an organism’s immediate biological adaptations to an environmental stressor can result in trans-generational changes.
Darwin’s theory of evolution has ruled the biological sciences for over one hundred fifty years; yet it cannot easily accommodate an idea like intergenerational psychological trauma. Neither can it explain what happened to the children and grandchildren of the women who were pregnant during the Dutch Hunger Winter.
Lamarck’s ideas, though, might make some sense of them both.
In which case, it seems that neither Darwin’s nor Lamarck’s ideas were “veritable rubbish.” Perhaps both men were right, and both men were wrong.
