Information

Why are HeLa tumors purple?


I remember hearing that the tumor where HeLa cells originated from was purple and jelly like, and I've seen pictures from studies with rats and HeLa tumors, and their tumors appear to also be purple. So what makes these tumors purple?


HeLa cells themselves are not pigmented, and usually appear translucent/gray under light microscopy. The growth medium may however be colored, and a common color is magenta.

The tumors themselves will appear purple, as most tumors do, due to the broken vascularization. Tumors commonly secrete growth factors leading to angiogenesis, but the resulting vessel networks are convoluted and not well organized, commonly full of anastomoses. The resulting poor vascularization leads to significant hypoxia, which results in a bluish coloring of the blood.


The Science Behind Henrietta Lacks' Immortal Cells

Henrietta Lacks unknowingly gave a great gift to science.

By the time Henrietta Lacks died in 1951 at the age of 31, she had already achieved a sort of immortality.

Without her knowledge, her doctor had harvested cells from a tumor on her cervix, where her cancer proliferated, and was attempting to keep them alive outside her body. Normally, human cells do not survive long once they have been severed from the organism they belong to: they will divide no more than about 50 times, then die through a process called apoptosis. Lacks’s doctor at Johns Hopkins Hospital, George Gey, figured he could cure cancer if only he had a line of cells that could reproduce indefinitely, but all of his cultures failed, until he met Henrietta. Her cells, later labeled HeLa, just kept dividing.

What was special about this woman, who was recently featured in an HBO movie, The Immortal Life of Henrietta Lacks?

The answer has to do with particular mutations in her cells caused by the human papillomavirus that had infected them. HPV inserts its own DNA into that of the host, resulting in a genetic hybrid. Not all HPV infections lead to cancer, and not all cancer has the potential to be an immortal cell line, but Lacks’s specific mutations had at least two characteristics that made her cervical cells special.

For one, HeLa cells are prolific dividers. Gey was surprised at just how quickly his cultures doubled in number. Even among cancers, these cells were reproductive superstars.

Secondly, they have an enzyme called telomerase that is activated during cell division. Normally, it is the gradual depletion of telomeres — a repetitive strand of DNA on the ends of the chromosomes — that stops cells from dividing indefinitely. But active telomerase rebuilds telomeres cut during division, allowing for indefinite proliferation.

HeLa cells are not the only immortal cell line from human cells, but they were the first. Today new immortal cell lines can either be discovered by chance, as Lacks’s were, or produced through genetic engineering.

The cells have been a boon to biomedical science, playing a role in the development of the polio vaccine and thousands of other patented discoveries. HeLa gives researchers a way to conduct repeatable experiments on human cells without testing directly on humans, although the cells are arguably no longer human at all.

Genetically, HeLa cells contain parts of Henrietta Lacks’s own DNA, mutations introduced by the strain or strains of HPV that infected her, as well as uncounted numbers of new mutations introduced organically through cellular division after the original cells were harvested from her body. A normal human cell has 46 chromosomes — a HeLa cells tends to have between 70 and 90.

According to some scientists, the HeLa cell line should properly be considered its own species. It is a sort of single-cellular organism that reproduces asexually through division and evolves through mutations that compound over time. It is a domesticated species, dependent on humans for food and shelter — the cow of microbial life, perhaps.

The story of the woman who non-consensually gifted HeLa to the world was largely unknown for decades after her death, even as the cells themselves contributed to significant advances in medicine. That changed thanks to The Immortal Life of Henrietta Lacks, a book that chronicles the efforts of author Rebecca Skloot to find Lacks’s family and tell her story. The HBO movie, starring Oprah Winfrey, is based on that account.


HeLa cell

Our editors will review what you’ve submitted and determine whether to revise the article.

HeLa cell, a cancerous cell belonging to a strain continuously cultured since its isolation in 1951 from a patient suffering from cervical carcinoma. The designation HeLa is derived from the name of the patient, Henrietta Lacks. HeLa cells were the first human cell line to be established and have been widely used in laboratory studies, especially in research on viruses, cancer, and human genetics.

HeLa cells are a common source of cross-contamination of other cell lines and a suspected cause of numerous instances of cell line misidentification. The HeLa cell genome has also been shown to be highly unstable, housing numerous genomic rearrangements (e.g., abnormal numbers of chromosomes) in a phenomenon known as chromothripsis.

This article was most recently revised and updated by Kara Rogers, Senior Editor.


HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution

293 cell line (widely known as the Human Embryonic Kidney 293 cells) and its derivatives were the most used cells after HeLa in cell biology studies and after CHO in biotechnology as a vehicle for the production of adenoviral vaccines and recombinant proteins, for analysis of the neuronal synapse formation, in electrophysiology and neuropharmacology. Despite the historically long-term productive exploitation, the origin, phenotype, karyotype, and tumorigenicity of 293 cells are still debated. 293 cells were considered the kidney epithelial cells or even fibroblasts. However, 293 cells demonstrate no evident tissue-specific gene expression signature and express the markers of renal progenitor cells, neuronal cells and adrenal gland. This complicates efforts to reveal the authentic cell type/tissue of origin. On the other hand, the potential to propagate the highly neurotropic viruses, inducible synaptogenesis, functionality of the endogenous neuron-specific voltage-gated channels, and response to the diverse agonists implicated in neuronal signaling give credibility to consider 293 cells of neuronal lineage phenotype. The compound phenotype of 293 cells can be due to heterogeneous, unstable karyotype. The mean chromosome number and chromosome aberrations differ between 293 cells and derivatives as well as between 293 cells from the different cell banks/labs. 293 cells are tumorigenic, whereas acute changes of expression of the cancer-associated genes aggravate tumorigenicity by promoting chromosome instability. Importantly, the procedure of a stable empty vector transfection can also impact karyotype and phenotype. The discussed issues caution against misinterpretations and pitfalls during the different experimental manipulations with 293 cells.

Keywords: Aneuploidy Chromosome instability Genome theory Heterogeneity Oncogenes Tumor evolution.


Starting Points

Connecting and Relating

  • If you were a family member of Henrietta Lacks, how do you think you would feel knowing her cells were used without her consent? Explain.
  • Would you consider donating your cells to benefit scientific research? Why or why not?
  • If you knew that medical companies would be making a profit from growing and selling your cells, would you want to be financially compensated? To what extent - how much compensation and for how long?

Connecting and Relating

  • If you were a family member of Henrietta Lacks, how do you think you would feel knowing her cells were used without her consent? Explain.
  • Would you consider donating your cells to benefit scientific research? Why or why not?
  • If you knew that medical companies would be making a profit from growing and selling your cells, would you want to be financially compensated? To what extent - how much compensation and for how long?

Relating Science and Technology to Society and the Environment

  • What importance do HeLa cells represent in terms of medical research and treatment of disease?
  • What are some of the other applications HeLa cells have had in advancing medical research and innovation?
  • To what degree should biomedical researchers ensure patients truly understand the implications of research completed using tissue samples they donate? Explain.
  • How has the case of Henrietta Lacks impacted/changed the way medical research is conducted today?

Relating Science and Technology to Society and the Environment

  • What importance do HeLa cells represent in terms of medical research and treatment of disease?
  • What are some of the other applications HeLa cells have had in advancing medical research and innovation?
  • To what degree should biomedical researchers ensure patients truly understand the implications of research completed using tissue samples they donate? Explain.
  • How has the case of Henrietta Lacks impacted/changed the way medical research is conducted today?

Exploring Concepts

  • What is a “cell line”? What was the importance of having a stable cell line for conducting medical research?
  • Why were Henrietta Lacks’ cells unique?
  • How did knowledge of HeLa cells help develop cancer treatments?
  • How is the information from HeLa cells being used in medical research today?

Exploring Concepts

  • What is a “cell line”? What was the importance of having a stable cell line for conducting medical research?
  • Why were Henrietta Lacks’ cells unique?
  • How did knowledge of HeLa cells help develop cancer treatments?
  • How is the information from HeLa cells being used in medical research today?

Nature of Science/Nature of Technology

  • What does the term “informed consent” mean? What are some examples of how informed consent has changed medical practices?
  • Should scientists be held to a higher level of ethical standards than the average citizen? Why/why not?
  • Do you think that the medical advances that have been made using HeLa cells warrant the use of cells without family consent? Explain.
  • Should scientists have the right to perform medical research that may breach a confidentiality clause if it has potential to give better medical care to all citizens? Explain.
  • Would you consider Henrietta Lacks an important figure in medical history? Why or why not?

Nature of Science/Nature of Technology

  • What does the term “informed consent” mean? What are some examples of how informed consent has changed medical practices?
  • Should scientists be held to a higher level of ethical standards than the average citizen? Why/why not?
  • Do you think that the medical advances that have been made using HeLa cells warrant the use of cells without family consent? Explain.
  • Should scientists have the right to perform medical research that may breach a confidentiality clause if it has potential to give better medical care to all citizens? Explain.
  • Would you consider Henrietta Lacks an important figure in medical history? Why or why not?

Media Literacy

  • Did you know about Henrietta Lacks before reading this article? If so, where did you learn about her? If not, why do you think you have not heard of her before? Why do you think this story took so long to surface and be reported in popular media?

Media Literacy

  • Did you know about Henrietta Lacks before reading this article? If so, where did you learn about her? If not, why do you think you have not heard of her before? Why do you think this story took so long to surface and be reported in popular media?

Teaching Suggestions

  • This article and embedded video support understanding of cells and cell lines and their application in biomedical research.
  • Download ready-to-use reproducibles for the Think-Discuss-Decide Learning Strategy for this article in [Google doc] and [PDF] formats.
  • Download ready-to-use reproducibles for the Issues and Stakeholders Learning Strategy for this article in [Google doc] and [PDF] formats.

Teaching Suggestions

  • This article and embedded video support understanding of cells and cell lines and their application in biomedical research.
  • Download ready-to-use reproducibles for the Think-Discuss-Decide Learning Strategy for this article in [Google doc] and [PDF] formats.
  • Download ready-to-use reproducibles for the Issues and Stakeholders Learning Strategy for this article in [Google doc] and [PDF] formats.

Excerpt: 'The Immortal Life of Henrietta Lacks'

The Immortal Life of Henrietta LacksBy Rebecca SklootHardcover, 368 pagesCrownList price: $26

The Woman in the Photograph

There's a photo on my wall of a woman I've never met, its left corner torn and patched together with tape. She looks straight into the camera and smiles, hands on hips, dress suit neatly pressed, lips painted deep red. It's the late 1940s and she hasn't yet reached the age of thirty. Her light brown skin is smooth, her eyes still young and playful, oblivious to the tumor growing inside her — a tumor that would leave her five children motherless and change the future of medicine. Beneath the photo, a caption says her name is "Henrietta Lacks, Helen Lane or Helen Larson."

No one knows who took that picture, but it's appeared hundreds of times in magazines and science textbooks, on blogs and laboratory walls. She's usually identified as Helen Lane, but often she has no name at all. She's simply called HeLa, the code name given to the world's first immortal human cells — her cells, cut from her cervix just months before she died.

Her real name is Henrietta Lacks.

I've spent years staring at that photo, wondering what kind of life she led, what happened to her children, and what she'd think about cells from her cervix living on forever --bought, sold, packaged, and shipped by the trillions to laboratories around the world. I've tried to imagine how she'd feel knowing that her cells went up in the first space missions to see what would happen to human cells in zero gravity, or that they helped with some of the most important advances in medicine: the polio vaccine, chemotherapy, cloning, gene mapping, in vitro fertilization. I'm pretty sure that she — like most of us — would be shocked to hear that there are trillions more of her cells growing in laboratories now than there ever were in her body.

There's no way of knowing exactly how many of Henrietta's cells are alive today. One scientist estimates that if you could pile all HeLa cells ever grown onto a scale, they'd weigh more than 50 million metric tons — an inconceivable number, given that an individual cell weighs almost nothing. Another scientist calculated that if you could lay all HeLa cells ever grown end-to-end, they'd wrap around the Earth at least three times, spanning more than 350 million feet. In her prime, Henrietta herself stood only a bit over five feet tall.

I first learned about HeLa cells and the woman behind them in 1988, thirty-seven years after her death, when I was sixteen and sitting in a community college biology class. My instructor, Donald Defler, a gnomish balding man, paced at the front of the lecture hall and flipped on an overhead projector. He pointed to two diagrams that appeared on the wall behind him. They were schematics of the cell reproduction cycle, but to me they just looked like a neon-colored mess of arrows, squares, and circles with words I didn't understand, like "MPF Triggering a Chain Reaction of Protein Activations."

I was a kid who'd failed freshman year at the regular public high school because she never showed up. I'd transferred to an alternative school that offered dream studies instead of biology, so I was taking Defler's class for high-school credit, which meant that I was sitting in a college lecture hall at sixteen with words like mitosis and kinase inhibitors flying around. I was completely lost.

"Do we have to memorize everything on those diagrams?" one student yelled.

Yes, Defler said, we had to memorize the diagrams, and yes, they'd be on the test, but that didn't matter right then. What he wanted us to understand was that cells are amazing things: There are about one hundred trillion of them in our bodies, each so small that several thousand could fit on the period at the end of this sentence. They make up all our tissues — muscle, bone, blood — which in turn make up our organs.

Under the microscope, a cell looks a lot like a fried egg: It has a white (the cytoplasm) that's full of water and proteins to keep it fed, and a yolk (the nucleus) that holds all the genetic information that makes you you. The cytoplasm buzzes like a New York City street. It's crammed full of molecules and vessels endlessly shuttling enzymes and sugars from one part of the cell to another, pumping water, nutrients, and oxygen in and out of the cell. All the while, little cytoplasmic factories work 24/7, cranking out sugars, fats, proteins, and energy to keep the whole thing running and feed the nucleus. The nucleus is the brains of the operation inside every nucleus within each cell in your body, there's an identical copy of your entire genome. That genome tells cells when to grow and divide and makes sure they do their jobs, whether that's controlling your heartbeat or helping your brain understand the words on this page.

Defler paced the front of the classroom telling us how mitosis — the process of cell division — makes it possible for embryos to grow into babies, and for our bodies to create new cells for healing wounds or replenishing blood we've lost. It was beautiful, he said, like a perfectly choreographed dance.

All it takes is one small mistake anywhere in the division process for cells to start growing out of control, he told us. Just one enzyme misfiring, just one wrong protein activation, and you could have cancer. Mitosis goes haywire, which is how it spreads.

"We learned that by studying cancer cells in culture," Defler said. He grinned and spun to face the board, where he wrote two words in enormous print: HENRIETTA LACKS.

Henrietta died in 1951 from a vicious case of cervical cancer, he told us. But before she died, a surgeon took samples of her tumor and put them in a petri dish. Scientists had been trying to keep human cells alive in culture for decades, but they all eventually died. Henrietta's were different: they reproduced an entire generation every twenty-four hours, and they never stopped. They became the first immortal human cells ever grown in a laboratory.

"Henrietta's cells have now been living outside her body far longer than they ever lived inside it," Defler said. If we went to almost any cell culture lab in the world and opened its freezers, he told us, we'd probably find millions — if not billions — of Henrietta's cells in small vials on ice.

Her cells were part of research into the genes that cause cancer and those that suppress it they helped develop drugs for treating herpes, leukemia, influenza, hemophilia, and Parkinson's disease and they've been used to study lactose digestion, sexually transmitted diseases, appendicitis, human longevity, mosquito mating, and the negative cellular effects of working in sewers. Their chromosomes and proteins have been studied with such detail and precision that scientists know their every quirk. Like guinea pigs and mice, Henrietta's cells have become the standard laboratory workhorse.

"HeLa cells were one of the most important things that happened to medicine in the last hundred years," Defler said.

Then, matter-of-factly, almost as an afterthought, he said, "She was a black woman." He erased her name in one fast swipe and blew the chalk from his hands. Class was over.

As the other students filed out of the room, I sat thinking, That's it? That's all we get? There has to be more to the story.

I followed Defler to his office.

"Where was she from?" I asked. "Did she know how important her cells were? Did she have any children?"

"I wish I could tell you," he said, "but no one knows anything about her."

After class, I ran home and threw myself onto my bed with my biology textbook. I looked up "cell culture" in the index, and there she was, a small parenthetical:

In culture, cancer cells can go on dividing indefinitely, if they have a continual supply of nutrients, and thus are said to be "immortal." A striking example is a cell line that has been reproducing in culture since 1951. (Cells of this line are called HeLa cells because their original source was a tumor removed from a woman named Henrietta Lacks.)

That was it. I looked up HeLa in my parents' encyclopedia, then my dictionary: No Henrietta.

As I graduated from high school and worked my way through college toward a biology degree, HeLa cells were omnipresent. I heard about them in histology, neurology, pathology I used them in experiments on how neighboring cells communicate. But after Mr. Defler, no one mentioned Henrietta.

When I got my first computer in the mid-nineties and started using the Internet, I searched for information about her, but found only confused snippets: most sites said her name was Helen Lane some said she died in the thirties others said the forties, fifties, or even sixties. Some said ovarian cancer killed her, others said breast or cervical cancer.

Eventually I tracked down a few magazine articles about her from the seventies. Ebony quoted Henrietta's husband saying, "All I remember is that she had this disease, and right after she died they called me in the office wanting to get my permission to take a sample of some kind. I decided not to let them." Jet said the family was angry — angry that Henrietta's cells were being sold for twenty-five dollars a vial, and angry that articles had been published about the cells without their knowledge. It said, "Pounding in the back of their heads was a gnawing feeling that science and the press had taken advantage of them."

The articles all ran photos of Henrietta's family: her oldest son sitting at his dining room table in Baltimore, looking at a genetics textbook. Her middle son in military uniform, smiling and holding a baby. But one picture stood out more than any other: in it, Henrietta's daughter, Deborah Lacks, is surrounded by family, everyone smiling, arms around each other, eyes bright and excited. Except Deborah. She stands in the foreground looking alone, almost as if someone pasted her into the photo after the fact. She's twenty-six years old and beautiful, with short brown hair and catlike eyes. But those eyes glare at the camera, hard and serious. The caption said the family had found out just a few months earlier that Henrietta's cells were still alive, yet at that point she'd been dead for twenty-five years.

All of the stories mentioned that scientists had begun doing research on Henrietta's children, but the Lackses didn't seem to know what that research was for. They said they were being tested to see if they had the cancer that killed Henrietta, but according to the reporters, scientists were studying the Lacks family to learn more about Henrietta's cells. The stories quoted her son Lawrence, who wanted to know if the immortality of his mother's cells meant that he might live forever too. But one member of the family remained voiceless: Henrietta's daughter, Deborah.

As I worked my way through graduate school studying writing, I became fixated on the idea of someday telling Henrietta's story. At one point I even called directory assistance in Baltimore looking for Henrietta's husband, David Lacks, but he wasn't listed. I had the idea that I'd write a book that was a biography of both the cells and the woman they came from — someone's daughter, wife, and mother.

I couldn't have imagined it then, but that phone call would mark the beginning of a decadelong adventure through scientific laboratories, hospitals, and mental institutions, with a cast of characters that would include Nobel laureates, grocery store clerks, convicted felons, and a professional con artist. While trying to make sense of the history of cell culture and the complicated ethical debate surrounding the use of human tissues in research, I'd be accused of conspiracy and slammed into a wall both physically and metaphorically, and I'd eventually find myself on the receiving end of something that looked a lot like an exorcism. I did eventually meet Deborah, who would turn out to be one of the strongest and most resilient women I'd ever known. We'd form a deep personal bond, and slowly, without realizing it, I'd become a character in her story, and she in mine.

Deborah and I came from very different cultures: I grew up white and agnostic in the Pacific Northwest, my roots half New York Jew and half Midwestern Protestant Deborah was a deeply religious black Christian from the South. I tended to leave the room when religion came up in conversation because it made me uncomfortable Deborah's family tended toward preaching, faith healings, and sometimes voodoo. She grew up in a black neighborhood that was one of the poorest and most dangerous in the country I grew up in a safe, quiet middle-class neighborhood in a predominantly white city and went to high school with a total of two black students. I was a science journalist who referred to all things supernatural as "woo-woo stuff" Deborah believed Henrietta's spirit lived on in her cells, controlling the life of anyone who crossed its paths. Including me.

"How else do you explain why your science teacher knew her real name when everyone else called her Helen Lane?" Deborah would say. "She was trying to get your attention." This thinking would apply to everything in my life: when I married while writing this book, it was because Henrietta wanted someone to take care of me while I worked. When I divorced, it was because she'd decided he was getting in the way of the book. When an editor who insisted I take the Lacks family out of the book was injured in a mysterious accident, Deborah said that's what happens when you piss Henrietta off.

The Lackses challenged everything I thought I knew about faith, science, journalism, and race. Ultimately, this book is the result. It's not only the story of HeLa cells and Henrietta Lacks, but of Henrietta's family — particularly Deborah — and their lifelong struggle to make peace with the existence of those cells, and the science that made them possible.

Excerpted from The Immortal Life of Henrietta Lacks by Rebecca Skloot Copyright 2010 by Rebecca Skloot. Excerpted by permission of Crown, a division of Random House Inc. All rights reserved.


Famous "HeLa" Human Cell Line Gets Its DNA Sequenced

The research world&rsquos most famous human cell has had its genome decoded, and it&rsquos a mess. German researchers this week report the genome sequence of the HeLa cell line, which originates from a deadly cervical tumor taken from a patient named Henrietta Lacks.

Established after Lacks died in 1951, HeLa cells were the first human cells to grow well in the laboratory. The cells have contributed to more than 60,000 research papers, the development of a polio vaccine in the 1950s and, most recently, an international effort to characterize the genome, known as ENCODE.

Previous work showed that HeLa cells, like many tumors, have bizarre, error-filled genomes, with one or more extra copies of many chromosomes. To get a closer look at these alterations, a team led by Lars Steinmetz, a geneticist at the European Molecular Biology Laboratory in Heidelberg, Germany, sequenced the popular 'Kyoto' version of the cell line and compared the sequence with that of a reference human genome. The team's results are published in G3.

Steinmetz&rsquos team confirmed that HeLa cells contain one extra version of most chromosomes, with up to five copies of some. Many genes were duplicated even more extensively, with four, five or six copies sometimes present, instead of the usual two. Furthermore, large segments of chromosome 11 and several other chromosomes were reshuffled like a deck of cards, drastically altering the arrangement of the genes.

Without the genome sequence of Lacks&rsquo healthy cells or that of her original tumor, it is difficult to trace the origin of these alterations. Steinmetz points out that other cervical tumors have massive rearrangements on chromosome 11, so the changes in the HeLa cell may have contributed to Lacks&rsquo tumor.

Potential uses
Having been replicating in labs around the world for six decades, HeLa cells have also accrued errors not present in the original tumor DNA. Moreover, not all HeLa cells are identical, and Steinmetz says that it would be interesting to chart the cell&rsquos evolution.

Whatever their origin, the genetic changes raise questions over the widespread use of HeLa cells as models for human cell biology, Steinmetz says. For instance, his team found that around 2000 genes are expressed at levels higher than those of normal human tissues because of the duplications. Alternative cell lines, such as induced pluripotent stem cells generated from patient skin cells, offer a more accurate window on human biology, he says.

Mathew Garnett, a cancer biologist at the Wellcome Trust Sanger Institute near Cambridge, UK, says that HeLa cells could prove useful for studying aspects of the biology of cervical tumors, such as their response to cancer drugs. In recent years, the genomes of many cervical tumors have been sequenced, and so it should be possible to see how these compare with the HeLa genome.

Steinmetz also points out that thousands of research papers based on HeLa cells, along with HeLa resources such as genetically manipulated lines and now a genome, means that labs will continue to stock the cells, even if they are not a perfect model of human biology. &ldquoThese are not going to go out of fashion over the next 10 years,&rdquo he says. "I&rsquom not sure where we&rsquore going to be 20 years from now."

This article is reproduced with permission from the magazine Nature. The article was first published on March 15, 2013.


Chickens, rabbits, warts and mice

More than 10 percent of all cancers in humans are strongly associated with infection by tumor viruses, and roughly 15 percent of all cancer deaths worldwide are caused by viruses. “It’s a very important problem,” DiMaio says. But he also sees tumor virology as a tremendous opportunity. “Once you know that a cancer is caused by a virus, you are far ahead of where you’d be for any other cancer, because you’ve identified the target, you’ve identified the cause and you have well-established ways to prevent or treat the disease that just don’t exist for spontaneously arising tumors.”

To say that certain viruses cause certain cancers can be misleading. You can’t catch cancer from another person, and most people who are infected with HPV, for example, won’t get cervical cancer. However, everyone who gets cervical cancer has the HPV infection. “Other things have to go wrong in order for the cancer to develop,” DiMaio explains, “but the virus contributes in an essential way. If you prevent virus infection by vaccination, you don’t get the cancer, and if you turn off the virus, the cancer can’t grow.”

HPV is the best-understood example of how a virus leads to cancer. Two things have to happen: First, viral gene products cause the cells to become genetically unstable and accumulate mutations that render cells unresponsive to aspects of growth control and the immune response. Second, the viral oncogenes provide a sustained stimulus to cell growth.

The first clue that there was a viral link to certain cancers came in 1911. Using a virus found in chickens, F. Peyton Rous, M.D., a scientist at the Rockefeller Institute for Medical Research, showed that the chicken sarcoma could be induced in other chickens. “There was a lot of doubt about what applicability it had, if any, to human disease,” says Miller. But in 1966 Rous shared the Nobel Prize in physiology or medicine for his research on the link between viruses and cancer, and the chicken virus became known as the Rous sarcoma virus.

Another important development, Miller says, came in the 1930s, when Richard Shope, M.D., one of Rous’ collaborators and the father of the late Yale epidemiologist Robert E. Shope, M.D., HS ’58, was out hunting with a friend. The friend mentioned that he’d seen rabbits with horns—actually giant warts. Shope asked his friend to send him some of the horns, which he then ground up, so he could isolate the virus causing the warts. When he injected the virus into other rabbits, they also grew horns. Interestingly, when New Zealand white rabbits were inoculated with the virus, they grew horns, but Shope couldn’t recover the virus in cottontail rabbits, the virus was retrievable. This discovery raised the question of viral latency, which scientists now know is intrinsic to the behavior and biology of tumor viruses. (Miller is currently researching latency as it relates to the Kaposi sarcoma virus. He’s trying to determine what the suppressor mechanism is and why latent-state viral genomes are suppressed in the tumor cells and then periodically reactivated.)

In the early 1950s Ludwik Gross, M.D., head of cancer research at the Bronx (N.Y.) VA Hospital, opened the field of tumor virology in mammals with his discovery of what became known as the Gross mouse leukemia virus. Gross showed that a virus led to mouse leukemia and could be passed from one generation to the next.

Although these and other studies unequivocally showed that viruses can lead to tumors in animals, making the leap to human tumor viruses wasn’t easy. Researchers encountered several obstacles. For starters, only a small percentage of people who are infected actually develop cancer it takes more than a virus infection for a tumor to form and other factors, such as immunosuppression or exposure to another carcinogen, must be present. Finally, it can take decades for symptoms to appear.

Despite these challenges, in 1965 the first bona fide example of a human tumor virus—EBV—was discovered in cells from Burkitt lymphoma. Since then scientists have identified six viruses that have been shown to play a role in human cancers.

HPVs are a family of small DNA viruses that typically cause benign warts. However, certain high-risk HPV types have been linked to a variety of carcinomas, the most prevalent being cervical cancer. HPV is also thought to play a role in other anogenital cancers, skin cancers and some head and neck tumors.

Hepatitis B virus and hepatitis C virus are genetically unrelated, but both can cause acute and chronic liver disease, which, under certain conditions, can progress to primary hepatocellular carcinoma. EBV is a herpes virus that can cause mononucleosis. However, EBV has also been linked to Burkitt lymphoma and nasopharyngeal carcinoma, and it has been implicated in some forms of Hodgkin disease and gastric carcinoma. Human herpes virus 8 (HHV-8), also known as Kaposi sarcoma herpes virus, is related to EBV. It was first identified in the tumor DNA of a patient with Kaposi sarcoma, a rare tumor until the aids epidemic, when it became one of the most common causes of cancer deaths among aids patients. HHV-8 is also believed to play a role in Castleman disease and body cavity lymphoma. Finally, human T lymphotropic virus type 1 leads to a rare tumor, adult T-cell leukemia/lymphoma, in the Far East and the Caribbean basin, as well as to some nonneoplastic diseases.

“It used to be a job to convince people that viruses were an important part of the cancer story. There had been a lot of research, but people just didn’t believe it. They wondered, for example, why so many people who are infected don’t get cancer,” says Miller. “We had to fill in the details. Now people pretty much accept the idea.”

“When I arrived at Yale in 1983, people didn’t think these viruses were important to cancer,” DiMaio says. “At conferences the human papillomavirus was always the last talk of the meeting. Now it’s taken center stage.” That’s partly because, of all the viruses found to play an etiologic role in human cancers, the HPV types (16 and 18) linked to cervical cancer are probably the best-understood and the ones that hold the greatest promise for vaccines to be used for prevention and treatment.


Henrietta Lacks’ ‘Immortal’ Cells

Medical researchers use laboratory-grown human cells to learn the intricacies of how cells work and test theories about the causes and treatment of diseases. The cell lines they need are “immortal”—they can grow indefinitely, be frozen for decades, divided into different batches and shared among scientists. In 1951, a scientist at Johns Hopkins Hospital in Baltimore, Maryland, created the first immortal human cell line with a tissue sample taken from a young black woman with cervical cancer. Those cells, called HeLa cells, quickly became invaluable to medical research—though their donor remained a mystery for decades. In her new book, The Immortal Life of Henrietta Lacks, journalist Rebecca Skloot tracks down the story of the source of the amazing HeLa cells, Henrietta Lacks, and documents the cell line's impact on both modern medicine and the Lacks family.

Related Content

Who was Henrietta Lacks?
She was a black tobacco farmer from southern Virginia who got cervical cancer when she was 30. A doctor at Johns Hopkins took a piece of her tumor without telling her and sent it down the hall to scientists there who had been trying to grow tissues in culture for decades without success. No one knows why, but her cells never died.

Why are her cells so important?
Henrietta’s cells were the first immortal human cells ever grown in culture. They were essential to developing the polio vaccine. They went up in the first space missions to see what would happen to cells in zero gravity. Many scientific landmarks since then have used her cells, including cloning, gene mapping and in vitro fertilization.

There has been a lot of confusion over the years about the source of HeLa cells. Why?
When the cells were taken, they were given the code name HeLa, for the first two letters in Henrietta and Lacks. Today, anonymizing samples is a very important part of doing research on cells. But that wasn’t something doctors worried about much in the 1950s, so they weren’t terribly careful about her identity. When some members of the press got close to finding Henrietta’s family, the researcher who’d grown the cells made up a pseudonym—Helen Lane—to throw the media off track. Other pseudonyms, like Helen Larsen, eventually showed up, too. Her real name didn’t really leak out into the world until the 1970s.

How did you first get interested in this story?
I first learned about Henrietta in 1988. I was 16 and a student in a community college biology class. Everybody learns about these cells in basic biology, but what was unique about my situation was that my teacher actually knew Henrietta’s real name and that she was black. But that’s all he knew. The moment I heard about her, I became obsessed: Did she have any kids? What do they think about part of their mother being alive all these years after she died? Years later, when I started being interested in writing, one of the first stories I imagined myself writing was hers. But it wasn’t until I went to grad school that I thought about trying to track down her family.

A HeLa cancer cell dividing. (© Dr. Thomas Deerinck / Visuals Unlimited / Corbis) The metaphase stage of a human HeLa cell division. (© Dr. Richard Kessel / Dr. Gene Shih / Visuals Unlimited / Corbis) Subspecies of HeLa cells have evolved in labs and some feel that the cell line is no longer human, but a new microbial life form. These cells are shown in green the cytoplasm is red and structures within the cytoplasm are blue. (© Nancy Kedersha / Science Faction / Corbis) The prophase stage of mitosis in the division of these human HeLa cells. (© Dr. Richard Kessel / Dr. Gene Shih / Visuals Unlimited / Corbis) This fluorescence micrograph of a HeLa cell shows the cytoskeletal microfilaments in red and nuclei stain with Hoechst in blue. (© Visuals Unlimited / Corbis)

How did you win the trust of Henrietta’s family?
Part of it was that I just wouldn’t go away and was determined to tell the story. It took almost a year even to convince Henrietta’s daughter, Deborah, to talk to me. I knew she was desperate to learn about her mother. So when I started doing my own research, I’d tell her everything I found. I went down to Clover, Virginia, where Henrietta was raised, and tracked down her cousins, then called Deborah and left these stories about Henrietta on her voice mail. Because part of what I was trying to convey to her was I wasn’t hiding anything, that we could learn about her mother together. After a year, finally she said, fine, let’s do this thing.

When did her family find out about Henrietta’s cells?
Twenty-five years after Henrietta died, a scientist discovered that many cell cultures thought to be from other tissue types, including breast and prostate cells, were in fact HeLa cells. It turned out that HeLa cells could float on dust particles in the air and travel on unwashed hands and contaminate other cultures. It became an enormous controversy. In the midst of that, one group of scientists tracked down Henrietta’s relatives to take some samples with hopes that they could use the family’s DNA to make a map of Henrietta’s genes so they could tell which cell cultures were HeLa and which weren’t, to begin straightening out the contamination problem.

So a postdoc called Henrietta’s husband one day. But he had a third-grade education and didn’t even know what a cell was. The way he understood the phone call was: “We’ve got your wife. She’s alive in a laboratory. We’ve been doing research on her for the last 25 years. And now we have to test your kids to see if they have cancer.” Which wasn’t what the researcher said at all. The scientists didn’t know that the family didn’t understand. From that point on, though, the family got sucked into this world of research they didn’t understand, and the cells, in a sense, took over their lives.

How did they do that?
This was most true for Henrietta’s daughter. Deborah never knew her mother she was an infant when Henrietta died. She had always wanted to know who her mother was but no one ever talked about Henrietta. So when Deborah found out that this part of her mother was still alive she became desperate to understand what that meant: Did it hurt her mother when scientists injected her cells with viruses and toxins? Had scientists cloned her mother? And could those cells help scientists tell her about her mother, like what her favorite color was and if she liked to dance.

Deborah’s brothers, though, didn’t think much about the cells until they found out there was money involved. HeLa cells were the first human biological materials ever bought and sold, which helped launch a multi-billion-dollar industry. When Deborah’s brothers found out that people were selling vials of their mother’s cells, and that the family didn’t get any of the resulting money, they got very angry. Henrietta’s family has lived in poverty most of their lives, and many of them can’t afford health insurance. One of her sons was homeless and living on the streets of Baltimore. So the family launched a campaign to get some of what they felt they were owed financially. It consumed their lives in that way.

These HeLa cells were stained with special dyes that highlight specific parts of each cell. The DNA in the nucleus is yellow, the actin filaments are light blue and the mitochondria—the cell's power generators—are pink. (© Omar Quintero) Henrietta Lacks' cells were essential in developing the polio vaccine and were used in scientific landmarks such as cloning, gene mapping and in vitro fertilization. (Courtesy of the Lacks family) Margaret Gey and Minnie, a lab technician, in the Gey lab at Johns Hopkins, circa 1951. (Courtesy of Mary Kubicek) In The Immortal Life of Henrietta Lacks, journalist Rebecca Skloot tracks down the story of the source of the amazing HeLa cells. (Courtesy of Random House, Inc.) Skloot first learned about Henrietta in 1988 from a community college biology teacher. (Courtesy of Random House, Inc.)

What are the lessons from this book?
For scientists, one of the lessons is that there are human beings behind every biological sample used in the laboratory. So much of science today revolves around using human biological tissue of some kind. For scientists, cells are often just like tubes or fruit flies—they’re just inanimate tools that are always there in the lab. The people behind those samples often have their own thoughts and feelings about what should happen to their tissues, but they’re usually left out of the equation.

And for the rest of us?
The story of HeLa cells and what happened with Henrietta has often been held up as an example of a racist white scientist doing something malicious to a black woman. But that’s not accurate. The real story is much more subtle and complicated. What is very true about science is that there are human beings behind it and sometimes even with the best of intentions things go wrong.

One of the things I don’t want people to take from the story is the idea that tissue culture is bad. So much of medicine today depends on tissue culture. HIV tests, many basic drugs, all of our vaccines—we would have none of that if it wasn’t for scientists collecting cells from people and growing them. And the need for these cells is going to get greater, not less. Instead of saying we don’t want that to happen, we just need to look at how it can happen in a way that everyone is OK with.


Measuring Biological Responses with Automated Microscopy

Rhonda Gates Williams , . Paul A. Johnston , in Methods in Enzymology , 2006

Assay Development on the ArrayScan 3.1 Imaging Platform

Treatment of MK2‐EGFP HeLa cells with 100 ng/ml anisomycin produces a significantly larger MK2‐EGF translocation response than treatment with 50 ng/ml TNF‐α when quantified on the ArrayScan 3.1 ( Fig. 6A and B ). However, the time course of MK2‐EGFP export from the nucleus appears similar for both stimuli ( Fig. 6A ). The amount of MK2‐EGFP that translocates from the nucleus to the cytoplasm appears to increase in a roughly linear fashion for 20 to 25 min post stimulation and then remains stable for as long as 90 min ( Fig. 6A ). A 25‐min period of stimulation with anisomycin (100 ng/ml) was selected as the standard treatment to induce maximal MK2‐EGFP translocation. The observed time course for MK2‐EGFP translocation is consistent with published data ( Engel et al., 1998 .). Seeding densities between 0.5 and 16 × 10 3 A4 cells per well produce fairly comparable MK2‐EGFP translocation responses ( Fig. 6B ) for both stimuli. A seeding density of 5 × 10 3 cells per well was selected for the remaining assay development effort. Because compound‐screening libraries are typically solubilized in dimethyl sulfoxide (DMSO), we evaluated the DMSO tolerance of the MK2‐EGFP translocation response in A4 cells that were treated for 25 min with media, 100 ng/ml anisomycin, or 50 ng/ml TNF‐α at the indicated DMSO concentrations ( Fig. 6C ). The MK2‐EGFP translocation response appears unaffected at DMSO concentrations ≤ 0.65%. However, at DMSO concentrations ≥1.25%, irrespective of the stimulus, the Cytonuc difference was increased. At DMSO concentrations ≥1.25%, the majority of the A4 cell population assumes a rounded morphology rather than the well‐attached, flat morphology more typical of this clone ( Figs. 2 and 3 ). The rounded A4 cells have a much smaller cytoplasmic area than normal, and the Cytonuc difference algorithm therefore has difficulty segmenting the cytoplasm and nuclear areas to make the difference calculation.

Fig. 6 . MK2‐EGFP translocation assay development. (A) Stimulation time course. HeLa‐MK2‐EGFP cells (5 × 10 3 ) from the HeLa‐MK2‐EGFP‐A4 clone were seeded into each of the 96 wells of Packard View plates in EMEM + 10% FBS and incubated overnight at 37° and 5% CO2. Cells were treated ± 100 ng/ml anisomycin or ± 50 ng/ml TNFα for the indicated times and fixed in 3.7% formaldehyde + 2 μg/ml Hoechst dye, and fluorescent images were collected on the ArrayScan 3.1. (B) Cell‐seeding density. The indicated numbers of cells from the HeLa‐MK2‐EGFP‐A4 clone were seeded into each of the 96 wells of Packard View plates in EMEM + 10% FBS and incubated overnight at 37° and 5% CO2. Cells were treated ± 100 ng/ml anisomycin or ± 50 ng/ml TNFα for 25 min and fixed in 3.7% formaldehyde + 2 μg/ml Hoechst dye, and fluorescent images were collected on the ArrayScan 3.1. (C) DMSO tolerance. HeLa‐MK2‐EGFP cells (5 × 10 3 ) from the HeLa‐MK2‐EGFP‐A4 clone were seeded into each of the 96 wells of Packard View plates in EMEM + 10% FBS and incubated overnight at 37° and 5% CO2. Cells were treated ± 100 ng/ml anisomycin or ± 50 ng/mL TNFα containing the indicated concentrations of DMSO for 25 min and fixed in 3.7% formaldehyde + 2 μg/ml Hoechst dye, and fluorescent images were collected on the ArrayScan 3.1. The nuclear translocation algorithm was used to analyze the images captured on the ArrayScan 3.1 and quantify the anisomycin and TNFα‐induced translocation response.