Author: Alex Padron

Digesting The Past

This article is being cross-listed on The Berkeley Science Review. Check out some other really interesting pieces there!

A few weeks ago, I was having coffee with a friend from the Hopkins molecular biology program; he left me somewhat dumbfounded with the story he told me. It involved a walking, talking experiment and an obsessed scientist (which one isn’t?) who revolutionized the concept of what makes humans…well, human; that is, it shifted the idea that the stomach contained the contents of humanity to the brain. This story is also inspired by my recent completion of a neuroscience boot camp at UC Berkeley. So without further adieu, here is the serendipitous and lucky story of Alexis St. Martin: the man with a hole in his stomach and his surgeon, William Beaumont.

On June 6, 1822 in Mackinac Island, Michigan, a French-Canadian fur trader, Alexis St Martin, was shot in the stomach when a shotgun was accidentally discharged (Fig 1). Luckily for Alexis, the fort’s doctor, William Beaumont, was nearby and quickly began to treat him. As if the damaging impact of a shotgun blast wasn’t enough, Beaumont’s treatment was unsterile and anesthetic-free. Mind you, this all happened before Louis Pasteur came up with his famous germ theory of disease. At the time it was generally accepted that God and miasmas caused plague and disease: people would resort to praying and burning tar to ‘cleanse the air’ of disease. I’m therefore sure Alexis relived the pain of his shotgun blast several times during his surgeries with Dr. Beaumont.

Fig 1. An artistic rendering of Alexis St Martin's fistula made by a gunshot wound.

Fig 1. An artistic rendering of Alexis St Martin’s fistula made by a gunshot wound. Source.

Alexis had several wounds from the blast, but the most significant of all was a gaping hole that never fully sealed, which formed a fistula. Nonetheless, he lived, remarkably. And since Alexis was unable to work due to his circumstances, Beaumont hired him as a handyman. This gave Beaumont a fantastic opportunity, one he exploited to a great degree, once he realized what he had in front of him during one of their wound cleaning sessions. That is, a peek (literally) into human digestion: a process people had known little to nothing about prior to Beaumont’s reportings. Before long, Beaumont began performing experiments on Alexis (Fig 2). These involved dipping food into the fistula and measuring the amount of time it took to digest. Vegetables and chunks of meat were tied to a string and inserted into Alexis’ stomach. Beaumont made him fast for hours on end, then removed gastric juice from his stomach and watched it digest foods in vials. Things like corned beef took almost 5 times as long outside the stomach than inside to digest—neat, huh?

I highly recommend checking out “Experiments and Observations on the Gastric Juice, and the Physiology of Digestion.” by William Beaumont, M.D. It’s free and if you skip to page 117 you’ll see Beaumont’s experimental documentation. As an example, I included experiment 68 below:

“Experiment 68.

At 9 o’clock P.M. same day, St Martin having eaten nothing since 2 o’clock, and feeling quite hungry, I put into the stomach, at the aperture, eight ounces of beef and barley soup, introduced gently through a tube with a syringe, lukewarm.”

Fig 2. Mean time of digestion of different foods in the stomach and outside it. Source.

Fig 2. Mean time of digestion of different foods in the stomach and outside it. “H” represents hours and “M” represents minutes for digestion. Source.

The medical profession benefited greatly from Beaumont’s myriad experiments. His findings forged a path for modern physiology based on observation and deductive reasoning. Soon after, other investigators, including Pavlov, began making fistulas—through less explosive means—on animals to better understand digestion and mammalian physiology in general. All in all, Beaumont reshaped the concept of what makes humans…well, human. Initially people thought the stomach contained the essence of humanity, but Beaumont disproved that dogma by decomposing food, chemically, outside the human body. This realization caused people to think more deeply about what it means to be human.

Alex Padron is a first year graduate student in the UC Berkeley Molecular and Cell Biology program. He is interested in science and in empowering the general audience by making science make sense. You can follow him on Twitter @apadr007 and Google+ gplus.to/apadr007

Category: The Student Blog | 1 Comment

Bdelloid Rotifers: Sex,Take 2

This article is being cross-listed on The Berkeley Science Review. Check out some other really interesting pieces there!

Isaac Newton, one of the most famous physicists to have ever existed, lived to be 84 years old and did so under a celibate promise. Imagine a lifetime without sex. Now imagine tens of millions of years without sex: meet the Bdelloid rotifers (Fig 1). These tiny, female-only, metazoans (0.5 mm in length) are well-known for their asexuality and resilience toward desiccation and ionizing radiation. And while other animals like komodo dragons, some sharks, and stick-insects (Timema stick-insects have reproduced asexually for over 1 million generations!) can asexually reproduce, in most cases during the lack of viable males, it’s incredibly rare to see an animal that exclusively reproduces asexually. Bdelloid (pronounced del●loi●d) rotifers are an “evolutionary scandal“ because they do such a thing, completely challenging the sexual reproduction dogma; that is, introducing genetic variation to allow species to adapt to their dynamic environments in addition to mitigating genetic degradation for the benefit of the population. Not having sex isn’t what necessarily makes rotifers scandalous (bacteria don’t have sex and look at how well they’re doing), it’s that they’re complex multicellular organisms who’ve speciated to a degree similar to that of sexually reproducing organisms and who’ve done so asexually.

Fig 1. Several scanning electron micrograph images of some species in the genus Rotaria. Adapted from Source.

Fig 1. Scanning electron micrograph images of some species in the genus Rotaria. Adapted from Source.

Normally, sex allows for chromosomal crossover leading to offspring having different combinations of genes from their parents. This gene shuffling mechanism is a major engine for genetic variation in a population by producing gene combinations that can mask deleterious mutations or bring about new positive traits. Despite sex being a successful and prolific mechanism of inheritance, it’s expensive. To name a few of the costs associated with sex we have:

  • Offspring inherit only a portion of your genes
  • Sex can make you susceptible to predators
  • Resources (genetic and behavioral, not just monetary) are often spent trying to seduce mates
  • Parasites, viruses, and bacteria take advantage of sex and spread from host to host during the act of sex

The biggest cost of sex is bullet one. If however, you could manage to make a genetic copy of yourself while introducing genetic variation into the population, you could circumvent most of the costs associated with sex. That’s exactly what rotifers seem to be doing: they’re maintaining genetic diversity in the population while avoiding deleterious mutations, and their doing it without sex.

A recent paper by Flot and colleagues delved into a particular bdelloid rotifer genome (the genome of Adineta vaga). These researchers found an incompatible genome structure with that of meiosis: a precursor to sexual reproduction. The reason? The genome of this particular rotifer (and probably others) doesn’t allow pairing of homologous recombination. Interestingly, the allelic gene pairs from this rotifer appear to be distributed in intrachromatic repeats resulting in vastly different chromosomes and a literal structural incompatibility with sexual reproduction (Fig 2). This also means each allele could potentially code for very different proteins in addition to the existence of a nonconventional mechanism for chromosomal pairing, or lack thereof.

Fig 2. Conventional vs Nonconventional Genome Structures. Each block represents genes and dotted lines represent allelic gene pairs. The normal genome structure of animals (left) who undergo sexual reproduction perform both mitosis and meiosis. The genome structure of a particular bdelloid rotifer (right) undergo mitosis exclusively. Because its alleles are scattered intrachromatically, bdelloid rotifer chromosomes do not have homologous pairs. Source.

Fig 2. Conventional vs Nonconventional Genome Structures. Each block represents genes and dotted lines represent allelic gene pairs. The normal genome structure of animals (left) who undergo sexual reproduction perform both mitosis and meiosis. The genome structure of a particular bdelloid rotifer (right) undergo mitosis exclusively. Because its alleles are scattered intrachromatically, bdelloid rotifer chromosomes do not have homologous pairs. Source.

Is there a method to this madness?

The authors describe two primary reasons why rotifers have been successful following an ameiotic lifestyle: horizontal gene transfer and gene conversion. The predominant reason for horizontal gene transfer appears to be for serendipitous bursts of variation in the population. This makes sense if you consider their environment sculpting their Picasso-painting of a genome. Rotifers can withstand long periods of dehydration at any stage in their life cycle. By long, I mean long. They’re capable of surviving desiccation for 9 years, and once rehydrated, they resume normal function. Not only that, Gladyshev and Meselson showed that bdelloid rotifers are highly resistant to ionizing radiation, capable of withstanding doses resulting in hundreds of DNA double-strand breaks per genome with only a ~20% reduction in fertility; at a dose of 3 times less, there’s 99% sterility in the most resilient invertebrate pupa or adult. And since desiccation and ionizing radiation both cause double strand breaks in DNA, incorporation of foreign DNA through horizontal gene transfer and gene conversion aid as a unifying survival mechanism, in addition to bringing in the much needed genetic diversity. According to Flot and colleagues, at least 8% of this rotifer’s genes have been acquired through horizontal gene transfer from other organisms; while this doesn’t sound like much, it’s more than any other known organism. These super bugs are the Peter Petrelli of the natural world: they can do it all (minus “it”).

In conjunction with horizontal gene transfer, gene conversion replaces one allele with another through DNA repair mechanisms. In doing so, some of the progeny will have a deleterious allele overwritten by a beneficial or neutral one, increasing fitness.

Horizontal gene transfer and gene conversion appears to be a formidable option to sexual reproduction, considering how extensive bdelloid rotifers have speciated. However, we can’t rule out the possibility of males existing and having some type of cryptic sex, compatible with the rotifer genome structure, or at the very least a different type of recombination without males altogether: yes, males have never been found and yes these organisms are meiotically incompatible, but absence of evidence is not evidence of absence.

Alex Padron is a first year graduate student in the UC Berkeley Molecular and Cell Biology program. He is interested in science and in empowering the general audience by making science make sense. You can follow him on Twitter @apadr007 and Google+ gplus.to/apadr007

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