Hayflick Limit defines the number of times cells in human body can successfully divide and grow. Circa 1961, a Philly scientist called Leonard Hayflick found this to be ~50 times. It was a shock & heresy when it was announced since conventional wisdom at that time among biological community is that cells could grow continuously forever. Though attempts made for decades to grow biological cells in vitro was never successful as they kept dying after sometime, everyone thought it was due to issues in the culture or processes used. But Hayflick limit showed that cells usually come in with a biological timer set inside their nucleus. In the initial stage, they actively replicate via mitosis and grow. After a while they stop dividing and get into a senescence stage where they just live and in the end they simply commit suicide (apoptosis). During this termination process, the cell nucleus explodes, releasing chemicals that attract other chemicals called phospholipids that practically dissolve the chromosomes helping the body flush it all out as waste. In the 60's it was found that if you replace the nucleus of an old cell with the nucleus of a new cell, it gets a new leash on life and starts mitosis again and goes through the aging process one more time. Subsequently ~1978, the presence of telomeres in cell DNA was found to be possibly the most important mechanism governing this process. Telomeres are small DNA strings found at the end of chromosome pairs. One neat analogy I found in the literature is comparing telomeres to the plastic ends of shoelaces that prevent them from fraying. As cells divide and chromosomes replicate, the telomeres get shortened more and more, eventually leading to a state where there is not much left, stopping further cell divisions and triggering eventual apoptosis.
Only in the 90's a protein called Telomerase was found to manage telomeres. While Telomerase is found in all cells, normally it is dormant and doesn't do anything. But if it is turned on, it seems to provide an RNA template to produce new telomeres at the end of chromosomes in aging cells to keep them in good shape allowing them to keep reproducing endlessly via mitosis..! This in turn explains how cancerous cells grow so well as cancer effectively activates telomerase in malignant cells allowing them to grow quickly without apoptosis. Now a days presence of that protein in urine is used as an indication that the patient should be tested fully for cancer.
Read The Immortal Life of Henrietta Lacks by Rebecca Skloot. Henrietta Lacks is a poor African American woman from the first half of 20th century. She was from a family of tobacco farmers living in Baltimore, Maryland. In 1951 she went to Johns Hopkins seeking treatment for abdominal pain. She in fact, had a severe form of cervical cancer that had effectively shut off the Hayflick Limit in her cancer cells once and for all. A mother of five children, she died soon at the age of 31. While scientists have been trying sample after sample to keep growing tissue cells in-vitro, every sample died after a while. But the tissue samples doctors took from her tumor without her explicit consent continues to grow voraciously to this day. In August 2013 new findings from University of Washington have been published describing in even more detail how her cells continue to grow so well. Thus, it effectively became the first cell line that was successfully grown in the lab for years, a biological holy-grail, bringing into life a multi-billion dollar industry that has produced more than 50 million metric tons of her cells! Think about that number for a second since individual cells practically weigh next to nothing.
Now a days every cell biologist, pharmaceutical company, research lab around the world doing any kind of biological research use this particular cell line named HeLa. Its been involved in polio vaccine development, AIDS research, cloning, gene mapping, radiation research, traveled to space and so on and so forth. While these details are fascinating, the first two paragraphs of this write up is mentioned perfunctorily only in passing in this book. Bulk of the book is written more like a novel detailing the lifestyles, trials and tribulations of all the Lacks family members. They were all quite uneducated and many were in trouble with law, some were in prison, and all of them were extremely poor. While the HeLa cell line is a multibilliondollar industry, none of the Lacks family members got any kind of monetary benefit out of all this and they all feel that their mother/grandmother that contributed so much to the biological sciences is not even properly recognized or honored. This is extremely unfortunate since the author points out others who were able to take control of their cell lines and even make money and direct how the cell line is used. Though this book has been a best seller, is going to be made into a movie soon, spawned a foundation, etc. I found it to be a bit too fluffy focusing way too much on how uneducated and uninformed the Lacks family members were and too little on the science. It seems very intentional to make it popular/easy to read.
While I didn't find details like what was written in a greeting card one family member gave to another or what bible verse or song a family member uttered repeatedly that interesting, I did find a short 13 page "Afterword" written by the author at the end of the book quite interesting. In that last section, the author had discussed the current status of the law and the intertwined ethical dilemma very well. Even now there is no law or standard that requires patients to understand and give explicit consent to the hospital or research institution for using their cells/tissue taken out during a surgery/testing. Comparisons have been made to crude oil found in your back yard where the commercial entity interested in monetizing the find need to compensate the land owner for access rights. This argument has been countered saying unlike in crude extraction, cell lines do not require the research institutions to continuously have access to the owner's property and what they do with the samples taken shouldn't affect the patient anymore and so should be allowed as it will benefit the society. In some cases courts have opined that giving complete control to patients will unnecessarily stifle research. But since the current societal norms completely allow individuals to decide whom to leave their money/property after they die, why shouldn't that be applied to tissues also is a valid question. Complicating the situation, some hospitals routinely save and analyze placenta sample gathered without consent during a delivery to protect themselves against future lawsuits related to birth defects..! In addition, companies like Myriad Genetics patenting human genes (BRCA1 and BRCA2 responsible for most cases of hereditary breast and ovarian cancer) and then charging $3000 for a test offered to women to see if they are predisposed, while preventing any other company from offering cheaper alternate tests pointing out their patents have soured the societal mood in general, indicating that the tissues and samples collected are not being put to egalitarian use but is in fact preventing further research with commercial entities establishing patent and other such barriers. Last summer US Supreme Court ruled that companies cannot patent human genes as they did not invent anything requiring intellectual property protection. The book has generated needed discussion in the realm of ethics related both to patient consent and profit distribution which is certainly timely.
In the end, long after the book's publication this Reuters report states that the Lacks family received some control over the HeLa cell line through an agreement NIH has reached with the descendants of Henrietta Lacks. Better late than never.
As many of my friends working in biological sciences would have lot more thoughts/insight w.r.t HeLa cell line and the associated debate, I look forward to hearing some good feedback.
-sundar.
