genetic mutation

Hugo de Vries: Genetic Mutation Theory’s Role in Modern Motherhood

It is hard not to notice that children often look and act like their parents. For centuries, people have been aware, for example, that a man and woman with blue eyes generally produce offspring with blue eyes. Let that same couple produce an heir with brown eyes and rumors swirl.

Only in the last 150 years or so has science dared, or been able, to ask why. One person to thank for that is Hugo de Vries. He was a botanist and one of the first geneticists. In 1889, he postulated that different characters have different hereditary carriers. He specifically postulated that inheritance of specific traits in organisms comes in certain particles….

Botanist to Geneticist to Gene

Born in the Netherlands in 1848, de Vries studied botany at the University of Leiden in the Hague. While there, he discovered Darwin‘s “Origin of a Species” and became curious about variations in species and the role those variations play in evolution. After graduating with a doctorate in plant physiology in 1870, de Vries continued his studies in Germany. His experimental work shifted to heredity and in 1889 he published “Intracellular Pangenisis”, a work that used Darwin’s term “pangene” and defined it as a particle of heredity that produced the individual traits of an organism. Today, we know the term simply as “gene.”

Genes, Heredity and Genetic Mutation Theory

De Vries, as a pioneer geneticist, was widely-known in his time for the introduction of genetic mutation theory. Noticing that individual plants of the evening primrose, Oenothera lamarckiana, growing in his garden were different enough to be a separate species, de Vries began to cross-pollinate them. The resulting variants of the plant he called “mutants.” In his 1901 work, “The Mutation Theory”, de Vries proposed that his mutational jumps better explained evolution than Darwin’s natural selection theory.

De Vries Got it Wrong

There are no fancy monuments to de Vries and, with little mention in literature and no standard biography, he has largely faded into oblivion. Partly, that is because de Vries got it wrong. He thought that the mutations he saw in the evening primrose represented a large genetic mutation rift and thus could explain evolution differently from Darwinian theory. It turns out that is not true. The evening primrose differences that de Vries noticed are now known polymorphisms, a genetic mutation that occurs in more than one percent of a population. Polymorphisms are responsible for normal individual differences like eye and hair color.

The Foundation of Modern Genetics

Although de Vries’ theory was wrong from an evolutionary standpoint, his work, along with others, laid the foundation for modern genetics. He is partially responsible for the term “gene” and the recognition that such a particle determines the characteristics of an individual. His studies also showed that a genetic mutation can be inherited from a parent and that same genetic mutation can be passed to future generations.

Genetic Mutation Theory Today

Today, genetic mutation is defined slightly differently. According to the National Library of Medicine, Genetics Home Reference, genetic mutation is a

“permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people.”

Thanks to de Vries, much is now known about the human genome and the specific role of genetic mutation in disease and birth defects. Genetic mutations are now known to be either inherited (hereditary mutations) or acquired (somatic mutations). Both can cause disease or genetic disorders and both are off course of concern to motherhood.

Genetic Mutation and Motherhood

Knowledge is power. Potential mothers need to consider the risk of both inherited and acquired genetic mutation. Testing is available for many inherited diseases. Often a quick blood test can determine if the mother carries a certain gene and its risk of passing to future offspring. Once pregnant, other tests can determine if the fetus is healthy allowing the mother to be proactive in healthcare.

But inherited genetic mutation is not the only concern to mothers. Environmental factors play a role in acquired genetic mutation. For that reason, mothers are cautioned about smoking and drinking during pregnancy as both alcohol and tobacco can cause acquired mutations. Nutrition also plays a role in acquired genetic mutation. New mothers are urged to take folic acid, for instance, to avoid known birth defects.

Recent studies have also shown nutrition in motherhood is even more important than previously thought—and not just during pregnancy. The London School of Hygiene & Tropical Medicine published a study in “Nature Communications” that revealed, for the first time, mother’s diet has a permanent effect on her offspring’s genetics. In the words of Dr. Branwen Hening, Senior Investigator Scientist involved in the study,

“Our results represent the first demonstration in humans that a mother’s nutritional well-being at the time of conception can change how her child’s genes will be interpreted, with a life-long impact.”

Thank you, Hugo de Vries, for starting the marvelous trip into genetic mutation.

genetic mutation
A Mother’s Pearls, Thomas Seir Cummings, 1841
biological clock

The Biological Clock Ticks Faster than Most Think

“Though it seems hard to believe, the biological clock begins ticking before female babies are even born.”  Dr. Marie Savard

In researching this subject, I found that some young women today are still unaware that you cannot have a baby too late in life. But there is an unalterable number of oocytes (eggs) with which a woman is born. Techniques to aid in in conception, such as in-vitro fertilization (IVF) and hormone treatments, cannot change the fact that her eggs are depleted and are of a lower quality later in life. Many factors are involved in fertility as a woman ages.

Facts on the Female Biological Clock

A twenty week old fetus has about seven million eggs, but at birth there are only one to two million left.  By age 30, 90% of eggs have been lost, and the clock begins to tick. At 40 years old, only about 3% remain. Only about 450 of the eggs she was born with will mature.

Common Misconceptions

“I plan to be super fit, super in shape when I’m 40, 50,”

says Lisa Bourne.

“And if I’m physically able to do it, then I will have a child at 55.”

Women delay pregnancy during their highest fertility ages for various reasons, such as career focus, lack of financial stability or they haven’t found Mr. Right. Dr. Pasquale Patrizio, professor in the Department of Obstetrics & Gynecology at Yale School of Medicine and director of the Yale Fertility Center, noticed that women ages 43 or older were coming to his fertility clinic and expecting to easily become pregnant, only to be disappointed. They believed that being healthy and exercising was the big factor in fertility, but it isn’t.

Although IVF procedures for women 41 and older saw a 41% increase during 2003-2009, the pregnancy success rate stayed at the usual 9%. Successful pregnancies still face complications, such as miscarriage and birth defects. By age 37, fertility drops drastically. By age 44, pregnancy with her own eggs is virtually impossible.

Skirting the Biological Clock

There are ways to skirt the ticking of the biological clock, such as oocyte (egg) freezing. The egg contains a large amount of water. Ice crystals will form within the egg, which destroys the DNA. The egg is dehydrated before freezing to prevent this from happening. Cryoprotectants replace the water inside the cell. DNA damage can also occur during thawing. Vitrification is a method that uses a “super-fast cooling” technique, and over 2,000 healthy babies have been born as of 2012. Results are best for women 35 or younger. The cost is pretty high at $10,000 a pop and $500 per year for storage.

Embryo Freezing is another option to outsmart the biological clock. An embryo, a fertilized egg, is frozen for later implantation into the uterus. The younger the parent’s sperm and egg, the more likely it is that they will have a healthy baby later on. Approximately 25% of babies born using IVF procedures are from frozen embryos.  An advantage of freezing embryos instead of eggs is that presently the eggs cannot be tested for defects, while an embryo can.

The ovaries hold the ticking clock, not the uterus. Ovarian tissue cryopreservation is an option. It possible to extract strips of an ovary, or the entire ovary, and freeze it. It can be transplanted into the uterus when the woman is ready. More on this, here on WebMD.

Assessing Reproductive Age

There are hormones that are responsible for egg maturation and conception. These can approximate when the clock will run out. Anti-Mullerian hormone can estimate the remaining egg supply. It peaks at age 24, is half that at mid-30s and practically gone by 40. IVF is less successful when the anti-Mullerian hormone levels fall too low.

Follicle Stimulating Hormone (FSH) is a standard test of how fast the biological clock is ticking, but it is not definitive in its fertility assessment. This is because the eggs may not be quality. FSH is less predictive in younger women. |

New techniques are being developed now that may be able to make primitive cells, called primordial germ cells, which become sperm and egg, from skin cells.

As  shown, the biological clock still tick-tocks, but there are now ways to measure the time left, and sometimes to get around the clock altogether. It seems the message is the earlier the better when it comes to fertility and having a baby. New technology cannot beat the biological clock, but it sure can get around some of the more difficult problems. Nothing is fool proof.

biological clock
Figure of Mother Holding Child, Date 3rd–5th century, Geography Peru, Culture Moche
epigenesis

Epigenesis: Another Reason to Blame Mom?

Women have long been held accountable, sometimes to an alarming and inaccurate extent, for the health and well-being of their offspring. Media coverage of scientific research, especially when condensed to a sound byte, often seems to support this accountability.

‘Mother’s diet during pregnancy alters baby’s DNA'(BBC),

‘Pregnant 9/11 survivors transmitted trauma to their children’ (The Guardian).

The latest pop science fad, epigenetics, also appears to blame the mother for much of a child’s health and development. However, is this fair? Is this even accurate?

What Is Epigenetics?

Epigenetics is the study of traits that result from changes to a chromosome without altering the DNA sequence (Berger, S.L., Kouzarides, T., Shiekhattar, R., & Shilatifard, A. (2009). “An operational definition of epigenetics”. Genes & Development, 23: 781-783. Retrieved ). Research has found that genes can be switched on or off by a variety of mechanisms, such as methylation. Many of these switches are flipped on or off during the earliest periods in development: pregnancy.

As more and more traits are attributed to epigenesis and inheritance, from diabetes to cancer risk to personality to homosexuality, mothers are increasingly being scrutinized for the way even their smallest decisions affect their offspring. Indulge pregnancy cravings? Your baby might get cancer! Catch a flu? Your child could be bipolar! Is epigenetics really a blame game? Or is the media, once again, looking for ways to stoke the flames of the mommy wars?

The Roots of Maternal Blame

This age of epigenetics is not the first time that mothers have been blamed for factors that are more or less out of their control.

Mothers in the early through mid twentieth century were blamed for being too cold and causing a range of mental illnesses from autism to schizophrenia, which are now known to have a biochemical origin (Kanner L (1943). “Autistic disturbances of affective contact“. Nerv Child 2: 217–50. Reprinted in Kanner, L (1968). Acta Paedopsychiatr 35 (4): 100–36.).
Similarly, mothers were later discovered to be the cause of the syndrome now known as Fetal Alcohol Syndrome.
Historically, the mother is assumed to be the source of both a child’s nature and nurture until proven otherwise. While maternal health and mothering are both important to child development, they are not the only factors in a child’s development.

Misrepresentations of Research in Epigenesis

Much of the problems with mother-blaming in epigenetics are a result of reporting mere sound bytes from complicated studies. For example, a 2012 study found that the second generation offspring, or grandchildren, of rodents eating a high fat diet had an 80% risk of developing cancer (Richardson et al, 2014). Headlines were dire:

“Why should worry about grandma’s eating habits,”

and similar scare tactics.

However, when the full study is examined, a more nuanced perspective appears. The rats were bred to have a higher rate of developing cancer, and positive health effects were shown in the third generation of offspring from the fat-craving pregnant rat. In short, there is little cause to blame mothers and grandmothers for cancer, as the popular media seemed to suggest.

What About the Dad?

While epigenesis in the womb is being studied and reported intensively, there is little media interest in a father’s role. Recent research has found the diet and health of a father at the time his body creates sperm can influence offspring’s chance of diverse factors such as heart disease and mental illness. Why aren’t these findings as aggressively reported as similar ones pertaining to the mother? People seem less interested overall in blaming a father when the historical target is female.

How to Avoid Blaming the Mother in Epigenesis Reporting

There are a few ways that the media can fairly report the epigenesis of health and disease. Best not to oversimplify. The international weekly of science on Nature.com had a great article on this same topic. Most studies are more complex than headlines suggest and involve non-human subjects with a variety of mitigating factors. And, discuss the roles of both mothers and father in epigenesis. Third, examine confounding factors such as culture and economics. This is not revolutionary, but rather good science reporting

Epigenesis is a complex and interesting topic that is becoming increasingly studied. The media can and should choose to report study findings in a way that doesn’t unfairly blame women and mothers.
epigenesis
Enrique Simonet – La autopsia – 1890 by Enrique Simonet. Under Public Domain via Wikimedia Commons