"It sounds strange…but her cells done lived longer than her memory." – Henrietta Lacks’ cousin Cootie

Unfortunately, the photos for this post were taken from the web :(

Ok, so the last post about HeLa cells focused on their origin and how they were/are used in research. We’re going to shift gears now and move away from the pure science-y stuff and dive into the controversies surrounding these microscopic yet valuable biological materials! I’ve divided the issues into 3 main categories based on my own thoughts and discussions from the book club:   

Race/poverty

In the 1950s, African Americans still faced rampant segregation. At Johns Hopkins, Henrietta received treatment in the public charity ward set aside for African American and underprivileged patients. Unfortunately, Henrietta classified as both black and poor.

Segregated ward at Hopkins. Source: magazine.nursing.jhu.edu

Doctors often treated public ward patients for free.  Yet, healthcare providers at the time had few scruples about taking advantage of indigent patients for research. We could wonder if doctors at the time would have taken Henrietta’s cells without consent had she been a wealthy Caucasian.  Yet, this point is moot even today. There is still no requirement for consent by anyone in most tissue research. 

Additionally, scientists are often blind as to cells’ more personal origins: naming Henrietta Lacks’ cells HeLa, for example, contributed to a certain type of anonymity. Even Lacks’ family knew little of their ubiquitous use in research until the book’s author, Rebecca Skloot, brought the matter to their attention. Were they not informed about such things due to their race and class status? Should the Lacks family receive monetary compensation for each vial of HeLa cells sold?  I think these are interesting questions to think about.

The Lackses are still poor – Henrietta’s descendants lack healthcare coverage, many of them can’t afford to go to college, and some have been unemployed because they were serving jail time. This is ironic since her cells have tremendously advance biomedical research and providing profit for companies selling these cells. In response to the family’s situation Rebecca Skloot set up The Henrietta Lacks Foundation to donate a portion of the book’s proceeds.  Donations can be made on the website (www.HenriettaLacksFoundation.org). The foundation aims to provide scholarships to educate Lacks’ descendants as well as funds for healthcare coverage for the family.

Bioethics

HeLa cells are now widely used in biomedical research, but there’s been a lot of controversy as to how to take care of these cells, what to use them for, and the fear of creating “monsters” from these cells by manipulating their DNA. There is also the question as to whether the cells actually genetically belong to Henrietta.

The DNA in tumor cells are not inherited – they arise from environmental changes (ex: exposure to mutagens). Therefore, do these cells really belong to Henrietta, and should the family receive compensation for “property” that belongs to them? Biologically, I think the cells still belong to Henrietta – the basic DNA is the same, it’s just been chemically modified with other substances found within her body. With regard to personal property, I think cells should be taken with the permission of the patient, just as people are asked to be organ or blood donors.

Science education/awareness 

The Lackses were unaware for a long time that Henrietta’s cells were being used in research, and after finding that out, it took them a while to understand the science behind the cells. First of all, it had to be explained to them what is DNA, a cell, how cells are cultured, etc. I think as a scientist I take our daily research routine for granted. I used HeLa cells during my first year of graduate school.  At the time, I only knew that they were a human cancer line and that HeLa was an abbreviation of a woman’s name but nothing about the cells’ fascinating historical context. Often, when we work with cells in the lab, we don’t necessarily tie those cells to a specific human being—to an individual with a distinct life story. 

I realized this after reading a particular section in the book when Rebecca Skloot accompanies Henrietta's daughter Deborah and son Zakariyya to Christoph Lengauer’s lab, which contains HeLa cells. Christoph patiently explains how the cells are cultured in the dish, how they are maintained in a special liquid containing nutrients to keep them happy, and how their DNA can change over time due to exposure to environmental cues such as temperature and light. He acknowledges that Zakariyya’s mom’s cells have advanced science tremendously and, for the first time, the Lackses receive a formal appreciation for what Henrietta had provided. The experience of witnessing research with their mother’s precious cells before their eyes offers some closure to the family and alleviates their anger. In the end, more than monetary compensation, the family just wishes for everyone to acknowledge that the cells came from Henrietta Lacks.

Wildtype HeLa cells under a microscope. Image taken by a senior research scientist in a lab that I rotated in my first year of grad school. Goodwin EC et al. PNAS 2000; 97:10978-10983.

The Lackses were not the only ones confused and fearful about HeLa cells' use in research. In 1965, researchers fused HeLa cells with mouse cells to create a cross-species hybrid cell line, intended to help map the human genome.  The public increasingly began to fear the cells, imagining a half human, half mouse (=humice? Actually, there are "humanized mice" whose immune systems have been wiped out so that they can carry functioning human genes, cells, tissues, and/or organs for medical research) hybrid unleashed from the laboratory and taking over the world a la Rise of the Planet of the Apes.  

Humice, not hummus! Ok, actually it's humanized mice. Source: Google Images.

The lack of communication between scientists and the public continues to be a problem.  I think that we really need to work towards removing this barrier, focusing on improving dialogue on the educational, political, literary, and cultural fronts. This book is a great step towards bridging the divide.

“Today it's possible for scientists to immortalize cells by exposing them to certain viruses or chemical, but very few cells have become immortal on their own as Henrietta's did.” – Rebecca Skloot

It’s time for my lab’s annual Secret Santa galore! For a week everyone plays pranks on their designated victim – ahem, I mean – Santee. The flurry of shenanigans culminates at the final lab meeting of the year where everyone receives gifts from their Secret Santa and guesses who had harassed them the weeks leading up to Christmas. Last year my Secret Santa (whom I correctly identified) gifted me the New York Times Bestseller The Immortal Life of Henrietta Lacks, written by Rebecca Skloot, a freelance science writer. 

Although Henrietta Lacks was not a scientist, she unknowingly contributed significantly to the biomedical world. Born into an African American family in Virginia in 1920, Lacks was raised on a tobacco farm and lived in impoverished conditions. 31 years later, she felt a lump inside her cervix and went to Johns Hopkins Hospital to get it checked out. Henrietta thought she was pregnant; however, her doctor dismissed such assumptions after performing a biopsy that confirmed she had stage I cervical cancer. She was treated with radium tube inserts sewn into her cervix (sounds dreadful!), a standard practice at that time. Unfortunately, the cancer had metastasized (spread) throughout her body, and on October 4, 1951, Henrietta Lacks passed away at the age of thirty-one. 

Interestingly, during one of Henrietta’s visits to Johns Hopkins, a hospital resident had taken a separate sample of Henrietta’s tumor to give to George Gey, a researcher at Hopkins. Gey was on a mission. He had been experimenting endlessly to create an immortal human cell line - a group of cells that could divide forever under normal lab conditions. 

To Gey’s amazement, Henrietta’s cells could live indefinitely outside the body and multiply like crazy. The cells adhered to the sides of test tubes, voraciously consumed the medium around them, and in just a few days, layers of cells formed in the petri dishes (plastic cylindrical dishes used to culture cells). After two decades of failed attempts at making an immortalized human cell line that could be used to study the mechanisms of cancer, George had finally struck gold. He decided to give away vials of these cells for free with other researchers (they later became commercialized by companies), and soon many labs around the world had vials of HeLa (Henrietta Lacks) cells stocked in their freezers. Currently, no one knows exactly how many of Henrietta’s cells are circulating – a scientist has estimated that there are a whopping 50 million metric tons of them!

Cells growing in petri dishes filled with media. The cells grow in an incubator kept at 37 degrees.

Ok, let’s pause here. I just want you all understand where and how cells used in research are handled and maintained. For long-term storage, cells are frozen down along with special liquid in cryogenic plastic vials and kept in liquid nitrogen freezers (around -125°C to -196°C). When a researcher wants to use them for experiments, they will thaw the vial for a few minutes in a warm water bath and then grow them on petri dishes containing liquid media (= cell food). Scientists must ensure that these cells remain uncontaminated and healthy. This is achieved by carefully working with the cells inside tissue culture hoods, as shown below, which have a special ventilation system known as laminar flow that blows out dirty air, leaving clean air circulating inside the hood.  

Before and after use, the hood must be wiped down with ethanol, which "denatures" or alters the molecular structure of bacterial proteins, to maintain a sterile environment. Having bacteria float around in your precious cell samples is every scientist’s worst nightmare! Also, every few days one must take some cells out from one dish and transfer them to a new dish with new media. This dilution is necessary so that cells in the older dish don’t overcrowd and start competing with each other for the cell food. This is pretty much what I do every day in my lab! Ok, now back to the HeLa story.

Left: Exterior of 37⁰C incubator where cells are grown in petri dishes. Right: Tissue culture hood, where experiments on cells are performed in order to prevent contamination from the outside environment.

In addition to HeLa cells, other immortalized cell lines do exist. To this day, it is not really known why HeLa cells keep growing. HeLa cells have an overactive telomerase (an enzyme that adds DNA sequence repeats to the ends of telomeres, which protects the end of the chromosome from destabilizing or fusing with neighboring chromosomes during cell division). This hyperactivity prevents the shortening of telomeres that is inherent of aging  and eventual cell death. As such, HeLa cells circumvent the Hayflick Limit, the limited number of cell divisions that most normal cells can undergo before senescence (biological aging). 

Additionally, scientists know that Henrietta’s cervical cancer was caused by Human Papilloma Virus (HPV), so some think that the multiple copies of HPV DNA combined with a region in Henrietta’s DNA to cause the cells to grow out of control (HeLa cells have a whopping 82 chromosomes! Humans normally have 46). Also, Henrietta had syphilis, which can suppress the immune system and cause cancer cells to grow even more rapidly. But many people have had HPV and syphilis and their cells weren’t able to grow at a crazy rate like the HeLa cells. Henrietta continues to perplex us!

Research using HeLa cells was crucial to the development of the polio vaccine, as well as drugs for treating herpes, leukemia, influenza, hemophilia, and Parkinson's disease. It has also helped understand the mechanisms of cancer and the effects of the atom bomb, and led to important advances like cloning, in vitro fertilization, and gene mapping. Additionally, in the past ten years, research involving HeLa cells has garnered five Nobel Prizes. Check out the timeline of HeLa research below (Click the link in the caption for a magnified view).

Image from Wired magazine. http://www.wired.com/magazine/wp-content/images/18-02/st_henrietta_f.jpg

A few weeks ago, the Graduate Student Book Club discussed The Immortal Life of Henrietta Lacks. It had been a while since I had read the book, so I skimmed it to prepare myself for talking about literature and history from a scientist’s viewpoint over some tea and cookies.

A number of issues were discussed at the Book Club, which were more ethical than scientific. I could go on and on about everything that deals with these topics, and that’s why I’ll stop here to spare you guys from reading a super long post. Stay tuned for part II of the HeLa saga!

"How beautifully leaves grow old. How full of light and color are their last days." -John Burroughs

I went hiking with some lab peeps a few weekends ago at Chatfield Hollow State Park. I was pretty stoked about frolicking in the New England foliage, but the bleak scenery we witnessed during the 30 minute drive didn’t seem too promising. When we arrived at the park, we were pretty bummed to see the leaves sporting a dull brown coat and surprised that many had already decided to retire, revealing bald spots to many trees’ chagrin. One friend would excitedly point out any glimpse of red that caught his eye, and we lauded these vibrant and persevering leaves with a chorus of oo’s and aa’s accompanied by a jig around the chosen tree.

Yuck, brown leaves.

Oo, a glimpse of orange!

Let’s take a moment here to explain how leaves change colors. As the tree grows throughout the spring and summer months, chlorophyll, which gives the leaves their green color, is constantly replaced in the leaves. During the summer, new stems grow from overwintering buds (those that passed through the winter season). Then, in the late summer/early fall, as the days get shorter and the nights longer, the cells near the juncture between the leaf and the stem divide rapidly but do not expand. This results in blocking the transport of carbohydrates (which include sugars, starches, and cellulose) from the leaf to the branch as well as the minerals from the roots into the leaves. The blockage at the juncture is known as the abscission layer. As a result, the production of chlorophyll slows down to almost a halt, allowing yellow (xanthophylls), orange (carotenoids), and red/purple (anthocyanins – produced from sugars trapped in the leaf) pigments to have their turn in the spot(sun) light and replace the verdant hues. 

You can thank anthocyanins for the red pigments...

...and xanthophylls for the yellow ones.

Why has the foliage been so gosh-darn disappointing this year? I’m just going to hop onto the “global warming is messing up our world” train to irk the Tea Partiers out there (they’re also messing up the world, but that’s another story). Basically, temperature, sunlight, and soil moisture majorly impact the quality of foliage. The growing season occurs during the summer, and ideal conditions for a dazzling foliage display involve ample rainfall in the spring, followed by a warm and fairly dry summer, and concluding with dry, warm sunny days and cool (but not freezing) nights in early autumn. The most important factor is the slow and steady onset of cool weather. 

Foliage from two years ago, end of October.

Foliage from this year, end of October.

However, this year’s conditions in New England were less than ideal – there was ample rain in the spring, but hot and humid drought-like summer combined with heavy precipitation in the fall, which most likely disrupted the photosynthesis cycle and thus delayed the growth of the leaves. A drought during the growing season can cause the abscission layer to form early and cause the leaves to drop before they change color. In late August, Hurricane Irene trampled the Northeast, and the heavy winds and rain that accompanied her caused the leaves to fall before they fully developed color. Heavy rainfall near the end of the growing season does not help, as many of the junctures are blocked, so the water cannot circulate throughout the plant or get absorb properly from the soil via the roots. So, yes, blame the abnormal weather for the sepia-toned foliage this fall. And Sarah Palin. Ok, blame the political undertones on my recent science policy trip to D.C!

Aftermath of Irene. Many leaves were already blown off the trees by September.

It snowed in late October - no hope for beautiful foliage.

By the way, the reason for why leaves change colors in the fall is still not completely understood. Read Carl Zimmer’s post about speculations as to why trees even bother doing this. 

Also, if you are interested in science policy and reforming science education, be sure to check out the Yale Science Diplomat's blog! And while you're there, read my post on our trip to D.C. to explore science career opportunities.