Monday, August 26, 2013

Henrietta Lacks' Immortal Cells

This month brought some progress to the family of Henrietta Lacks, whose cells were collected more than fifty years ago while Lacks suffered from cervical cancer. The resulting HeLa cell line has been critical for the development of cell culture, the generation of the Polio vaccine and many other important scientific discoveries. Recently, the genome sequence of HeLa cells was published online, a development that concerned Lacks' family members. As of this writing, the NIH has agreed to include two members of the Lacks family in the decision making process for the future use of the cells (check here and here for coverage of varying depth). The agreement does not result in any remuneration for the family. While this agreement is a clear step forward, this is still an isolated case and has not set a standard for consent about the use and sharing of genomic data.

I wanted to write something about this event because it brings the excellent book by Rebecca Skloot back into my mind. The Immortal Life of Henrietta Lacks is definitely on my top five list for best science books; this list includes books by Stephen Jay Gould and Carl Sagan. Skloot has received many accolades, and with good reason. The book does an amazing job of laying out the history of a complex story in an easy, digestible way and she makes the story compelling. The book was written in such a way that you feel the thrill of the investigation, as well as an emotional connection to the Lacks family. Skloot was careful not to place blame on the scientists involved. Rather, she presents the issues surrounding the case with the professionalism and rigor of a journalist, rather than someone trying to sensationalize the case, which is certainly easy to do in a situation like this, where the patient was a poor, African-American woman whose cells were taken without permission (at the time, there was no standard for informed consent).

Henrietta Lacks was infected with both human papillomavirus (HPV) and syphilis (probably by her husband), which were likely the cause of and a contributing factor to the aggressiveness of her cervical cancer. Now, several groups of researchers are sequencing the genome from HeLa cells to pinpoint what made HeLa cells grow so robustly. In a paper published in the August 8 edition of Nature, Adey and colleagues report that the HeLa genome is hypertriploid (meaning that the cells had just over three sets of chromosomes, whereas healthy cells would have two copies; aneuploidy or abnormal chromosome numbers is a hallmark of cancer cells), has a surprisingly low rate of point mutations during the course of normal cell culture, and has had a fairly stable chromosome count since the initial isolation of the cells. Most interestingly, the study describes the insertion of the HPV genome at a fragile site on one copy of chromosome 8. Only two thirds of the HPV genome was observed at chromosome 8; importantly, copies of the E6 and E7 oncogenes of the HPV genome were integrated. These oncogenes have been linked to cervical cancer progression, malignancy, and cell immortalization. Notably, the sequence for E2, the inhibitor of E6 and E7, was absent. Finally, the site of HPV integration was 500 kilobases from MYC, a canonical proto-oncogene; MYC showed very high expression, but only from the copy of chromosome 8 that included the HPV genome. Essentially, the oncogenes from HPV were hyper-activated, as was the MYC oncogene from the HeLa genome and this was directly caused by the insertion of HPV near the MYC oncogene. Thus, the research suggests that the interaction between the HPV DNA and the HeLa DNA may underlie the robust growth characteristics of the HeLa cell line. These results are exciting and suggest that we still have a lot to learn about HeLa cells. 






Sunday, August 11, 2013

Amy Stewart's Wicked Bugs, Lyme disease, and me (or my lousy summer has really ticked me off)

I had Lyme disease this summer. I was very lucky to catch it early, so the treatment was effective and the issues resolved quickly. The symptoms that I had were different each day and included the standard flu-like presentation as well as some very violent thoughts that nearly provoked me to punch someone on the subway. In my defense, the person probably was talking too loudly on the phone or taking up several seats. (It is a testament to how sick I was that I was riding the subway to work rather than biking.) Needless to say, it was a strange trip. Once the antibiotics started to work and the misery started to fade, I became more interested in the bug, as well as the bacteria, that caused all the trouble in the first place. 


Thus, I picked up Wicked Bugs by Amy Stewart. Two aesthetic things that I really liked about the book: the design of the cover and the illustrations. This is Stewart's second book in the Wicked series and both books have the same pocket size and general cover design. The unusual size of the book makes me wonder the intention (if any) of the book design. The illustrations, such as the one of a deer tick on the right, are so detailed and lovely; it makes you forget some of the more ick-inducing details about the bugs in question.

The book covered a large variety of interesting bugs. My only complaint was that there was not more narrative. Instead, the book read like a compendium of interesting factoids about bugs. Surprisingly, this made it very easy to read in small bites. The louse mentioned in the subtitle of the book (The Louse That Conquered Napoleon's Army) was actually one of the less interesting stories in the book. It seems that Napoleon's army was decimated by typhus caused by body lice; in addition, Napoleon also had scabies for a good portion of his life.

According to Stewart, termites were an important factor is the destruction of New Orleans in the wake of hurricane Katrina (more information can be found here). Both the foundations of buildings in the city and the levees themselves were affected by the bugs, which compromise structural stability with their webs of tunnels through wood. The seams of the flood walls were sealed with bagasse, which is the pulp of the sugarcane leftover after the extraction of sugar. As you can imagine, bugs love that. Thus, termites may have played a role in the failure of the levees. In the aftermath of the storm, the mass exodus of residents meant that fewer people were keeping up with pest control, which led to increases in the populations of termites and further damage to the buildings, which were already ravaged by the storm. To my surprise, she doesn't mention the most interesting thing about termites: termites rely on a symbiotic bacteria in their gut to digest the cellulose. Those bacteria, in turn, rely on another symbiont to produce some of the digestive enzymes required for this process.

Like many of the insects covered in this book, deer ticks have a strange life cycle, which can involve three hosts. The larvae feed on rats, mice, or birds; as nymphs, they feed on small rodents or humans; and as adults that feed on deer. Sometimes, at the larval stage, ticks are infected by the bacteria that causes Lyme disease, a spirochete called Borrelia burgdorferi. Interestingly, Lyme disease was noted in medical writings dating as far back as 1550 BC, when it was called the "tick fever". In the northeast United States, cases have shown continual increases over the past decade. Climate change and loss of predators are thought to be the cause of these increases.

A chapter entitled "Zombies" focused on some other curious life cycles in insects. This section is certainly not for the squeamish. In fact, some of these stories make my skin crawl. Generally, these insects all seem to have a similar M.O.: they sting another insect and take control of it, typically to lays their eggs inside the poor victim. In the case of the emerald cockroach wasp, the wasps deliver a sting directly into its victim's (a cockroach) brain. At this point, the wasp can have total control of the cockroach. The cockroach will serve as a nest, a source of food, and eventually a cocoon for the wasp's offspring. The adult wasp will emerge from the cockroach, leaving only a shell of the former insect behind. These stories are all so unusual. How would something this devious evolve? What is inside that sting that can be such a powerful paralytic? These are some follow up questions I will have to research. One thing is certain, these stories make me hope that reincarnation is not real.

While Wicked Bugs wasn't the best book I read this year, I will be adding Wicked Plants to my reading list.

Enjoy this video from the author, Amy Stewart.