Monthly Archives: April 2008

Sonic hedgehogs and two-faced babies

two faced babyEarlier this week, it was reported that a baby with two faces was born to a young couple in rural northern India. Lali, born last month in a normal delivery, has a condition known as craniofacial duplication. Diprosopus is well-documented in the literature, but the number of cases in which the diprosopic infant is complication-free is very low. Complications of this condition include anencephaly (the absence of a brain/skull cap), upper gastrointestinal organ malformations as well as cardiac abnormalities.

wieschausnussleinvolhardHow does something like this happen?, you might wonder. Recall that there is a series of genes in our genome known as homeobox (Hox) genes, responsible for the basic body plan. These genes are present in animals, fungi as well as plants and have been highly conserved in each of these kingdoms over time, with only slight modifications. The set of Hox genes (located on chromosome 7) in humans responsible for determining placement and size of facial features is known as the Sonic Hedgehog homolog (SHH).

The SHH genes were first discovered by Christiane Nusslein-Volhard and Eric Wieschaus, two researchers who studied embryonic development in Drosophila and whose work was rewarded in 1995 with a Nobel Prize. Along with Edward Lewis, a developmental geneticist, Nusslein-Volhard and Wieschaus discovered the set of genes responsible for segmentation of fruit fly bodies. These same genes are the ones responsible for proper placement and development of digits on human limbs, facial features, patterning of blood vessels, lung development and even brain development. How SHH regulates organogenesis is through production of a protein known as a ligand which binds to a certain protein on the cell’s extracellular matrix. The concentration of the SHH protein that is produced determines the effects the protein has on the cells it affects. This is known as the French Flag model.

SHH genesIn Drosophila, if mutated, the SHH genes cause small spikes to form all over the body of the fly, hence the “hedgehog”-like appearance. The mutation of the SHH genes causes a loss of function so that the protein does not function as it should if it were normal, as many gene mutations do. In humans, if mutated, SHH genes cause multiple malformations of the head, brain and other organs whose organogenesis is controlled by the production of the SHH protein.

lali familyIt is unknown whether or not Lali, the original subject of this post, has any other developmental abnormalities. Her parents have been quoted in the press as saying that she is behaving normally and that she does not need medical attention. However, doctors are concerned that Lali may have other developmental abnormalities that cannot be seen with the naked eye that require imaging technology to view, such as potential duplication of internal organs. Currently, Lali is able to see with all 4 of her eyes, hear with both of her ears and eat with both of her mouths. It is unknown (and may remain so) if she has two esophagi and two tracheas, as her parents refuse to allow Lali to be examined by doctors for other abnormalities.

Currently, Lali is visited by hundreds of people from her village as well as surrounding villages, as she is thought to be an incarnation of a Hindu goddess who also possesses two faces.

Isn’t it interesting that something so small as the interaction of proteins on the cell’s membrane can have such drastic consequences? How does Lali’s condition illustrate to you the importance and relationship of genes to protein production and their role in development? What do you think about her parents’ decision to disallow Lali to be further examined by medical professionals?

Autism: Genes or Environment?

This week, CNN.com is running a series about autism. If you are not familiar with autism, here’s a little primer about this condition.

Autism is a disorder of brain development that usually appears before the age of 3 that results in developmental delays causing problems with communication, social development and interaction. Many children with autism are of average to high intelligence, but some children are more profoundly affected than others, which results in their being unable to function independently. Autism has no cure, and persists throughout the person’s life.

Some autism advocates contend that autism is caused by vaccinations, but many experts have dismissed that claim as fallacious and that vaccinations are not the cause of autism. However, a recent legal ruling siding with a Georgia family who claims their daughter developed autism only after receiving the MMR vaccine (a widely administered vaccine to children of school age, and required by Texas state law for students in public school) has given autism advocates fuel for this argument.

However, this story at CNN.com seems to point to a genetic link to autism. The women in the story were all single women who wanted to have children, so they turned to a sperm bank to obtain donor sperm for artificial insemination. Women who were inseminated with “Donor X”‘s sperm bore children who later went on to develop autism.

Researchers have identified regions of the genome that perhaps contribute to the development of autism but that have not actually been identified as actual causative agents of the condition.

How does the discovery of genomic regions help to provide evidence supporting an organic cause for autism rather than an environmental cause? More importantly, how does the Georgia case illustrate the effect of environmental factors on gene expression? Genes are not autonomous entities that control their own expression on their own terms.

Other questions that can and should be raised by this issue are: should sperm donors be screened for potentially deadly/disabling genes in their genomes? Is something like this practical? What other problems arise from a reproductive medical system that allows almost any man to donate sperm for artificial insemination, regardless of genomic content?

And you’d thought you’d heard it all…

Remember this post? Remember the rhetorically speculative nature of the possibility of men becoming pregnant that was addressed?

Well, it seems that a pregnant man actually exists.

Last week, Good Morning America ran a segment on a transgendered man, Thomas Beatie, who lives in Oregon with his wife, Nancy. Beatie was born female, but opted for sexual reassignment surgery later in his life so that he could be a man. Like many transgendered people, Beatie also decided to leave his reproductive organs (internal as well as external genitals) intact. In order to appear physically male, Beatie had breast reduction surgery and took testosterone injections so that he would develop male secondary sex characteristics such as facial and body hair as well as a deeper voice.

Legally, Beatie is male; biologically, he is female, still possessing the two X chromosomes that are the genetic mark of all human females.

Beatie and his wife decided to begin a family, and it was decided that he would carry the couple’s child since Nancy had undergone a complete hysterectomy in her early 20′s due to illness and was physically unable to do so. When it was decided that Beatie would carry the couple’s child, the testosterone treatments were stopped and Beatie’s menstrual cycle resumed 4 months later. Beatie underwent in vitro fertilization, but lost the triplets that were the result of the first IVF attempt as well as a Fallopian tube. His second attempt at in vitro was successful, and resulted in the baby he now carries, due in July.

It is not physically impossible for a transgendered man who still possesses female internal reproductive organs (ovaries and uterus) to bear a child. Biologically, as long as the person does not take testosterone–which, in high enough doses, would suppress the action of female hormones– pregnancy is certainly possible. Transgendered men still secrete hormones such as oxytocin and prolactin, so nourishing a baby would also be possible.

But what will the ramifications of such a pregnancy be? Moral issues aside, what side effects could the fetus face? Remember that a mother’s eggs are as old as she is, and that whatever chemicals, drugs or hormones she is exposed to will affect the viability of the egg and the genetic material within. There are some experts that speculate that Beatie’s fetus may face increased risk of certain types of cancer due to his taking testosterone injections for so long (10 years). Many doctors are unsure, as there has only been one other documented transgendered pregnancy before Beatie’s. There simply isn’t enough research out there to substantiate any claim that the fetus may be more likely to develop certain types of cancer.

There are other considerations as well. Certainly a case such as this raises questions about gender roles and identity in society. Beatie’s case will be something that bioethicists, psychologists and biologists will chat about for quite a long while. He and his wife are slated to appear on Oprah tomorrow to talk about their experience.

There is not much available press about Beatie and his wife, however, a first-person piece written by Beatie about his decision to become pregnant appears in this week’s issue of the Advocate, a national magazine about gay and lesbian issues.

What do you think? I have definite opinions about this particular topic but I will reserve my commentary so that I can see what you all think.