Thursday 12 September 2013

The first immortal line

Henrietta Lacks
Henrietta Lacks
Henrietta Lacks did not lead a particularly remarkable life. Born in Roanoke, Virginia in 1920 as Loretta Pleasant, at 4 years old she moved to live in a log cabin with her grandfather and cousin, Day Lacks. By the age of 19 she had had two children with her cousin and went on to marry him shortly before her 21st birthday. 
Henrietta Lacks
That year, she moved with her family to Maryland, where her husband Day got a job at the steel mill. Henrietta and Day went on to have another three children in the next nine years. After giving birth to her last child, a boy named Joseph, Henrietta was in significant pain and bleeding profusely. A local doctor tested her for syphilis, and when that came back negative sent her to John Hopkins Hospital – the only hospital in the area that would treat black patients.
At the hospital, Dr Howard Jones examined Henrietta, performed a biopsy on a lump on her cervix and found she was suffering from a malignant epidermoid carcinoma of the cervix (cervical cancer) and treated her with radium tube inserts. During these radiation treatments, further samples of Henrietta’s cervix were taken – both from healthy and cancerous tissues – without her permission.
Eight months after her initial admission to the hospital, Henrietta Lacks died through complications caused by the cancer that had now spread throughout her body. She was buried without a headstone, near to her mother’s grave in Halifax County, Virginia at the age of 31.
The sample taken from the cancerous growth in Henrietta’s cervix was given to George Otto Gey, who was able to grow the cells in vitro. These were the first human cells ever to be successfully propagated in a laboratory and were to have a profound impact on medical research. The cells were named HeLa cells, in an attempt to maintain Henrietta Larks’ anonymity. However within a few years, she was identified in the press. Gey did not attempt to patent the cell line; instead he donated the cells and the processes necessary to grow them to researchers simple for the sake of science and to benefit medical advances.
In the early 1950s, polio epidemics were devastating the USA. In 1952, over 57, 000 cases were reported, leading to 3,145 deaths and 21, 269 cases of disabling paralysis. Dr Jonas Salk was dedicated to finding a way to prevent is horrifically debilitating virus, and required a line of cells, available in large volume, to test his new vaccine before clinical trials. HeLa cells were observed to be susceptible to poliomyelitis and are otherwise stable in culture. The National Foundation for Infantile Paralysis funded the establishment of a cell culture factory at Tuskegee University to supply Salk and other medical researchers with large quantities of the cells.
By 1955, Salk’s vaccine was declared safe and effective and rolled out across the USA, Canada Australia and Western Europe. Within two years, 100 million doses had been given throughout the USA alone, and many countries were reporting virtually no new cases of infection by poliomyslitis. Last year only 291 cases were reported across the whole world, leading to suggestions that soon polio may be eradicated completely.
HeLa cells have been used for research into many different areas of disease, with over 60,000 articles published on research performed on this cell line. From AIDS to hormone signalling to the effects of radiation, cells descended from those taken from Henrietta Lacks in 1951 have had a huge impact on science and are still being used today in research into gene changes and behaviours in cancer.
Henrietta Lacks’ cervical cancer was caused by an infection by the human papillomavirus 18 (for which there is now a vaccine). The virus transferred some of its own genome into that of the cells, causing the original HeLa line cells to have probably 82 chromosomes, rather than the normal 46. This cannot be known for sure, as due to the constant rapid and uneven division that is the nature of cancer cells, the genome of the HeLa cells in incredibly unstable. HeLa cells have also been seen to be capable of “infecting” other cell lines grown in the same laboratory, leading to the suspicion that several other established cell lines may now contain HeLa cells.
Due to the exceptional nature of the HeLa cells, in 1991 evolutionary biologist Leigh Van Valen proposed that they be defined as a new species, Helacyton gartleri. However this definition has not been accepted by the wider scientific community and HeLa cells remain considered as human.
For the Lacks’ family, since discovering in the 1970s that their mother’s cells had become an essential research tool, the continual growth of these cells (current estimates run at 20 tonnes of HeLa cells grown over the last 60 years) and the patenting of discoveries made using them have been a sore point. In the 1980s the family’s medical records were published without their consent and the complete HeLa line genome was sequenced and published on 11th March 2013, however it has since been taken down.
Whist in the 1950s, permission to harvest cells from a patient was not required, the commercialisation of one person’s cells had never occurred before. Whilst in 1990, the Supreme Court in California decreed that discarded cells or tissues are no longer a person’s property, some ethical issues remain with the use of the HeLa cell line. A ruling earlier this year had thankfully prevented the patenting of unmodified genes, stopping any one company or person profiting from all research done with these cells.
As of August this year, it was decided in a meeting with Henrietta Lacks’ surviving family that data on the HeLa cells’ genome would remain available under restricted access. Papers that utilise the HeLa cells will now recognise Henrietta and the contribution that her cells have made to the research. A committee has been formed, which includes members of the Lacks family, who will regulate access to the DNA code of the cells, hopefully allowing the cell lines to remain in medical research use for many years to come.
Henrietta Lacks has become in some way immortal. Her contribution to medicine in the last sixty years has been immense. In 2010, Dr Roland Pattilo donated a tombstone for Lacks, placed near where she is buried, reading:
“Henrietta Lacks, August 01, 1920-October 04, 1951.
In loving memory of a phenomenal woman, wife and mother who touched the lives of many.
Here lies Henrietta Lacks (HeLa). Her immortal cells will continue to help mankind forever.
Eternal Love and Admiration, From Your Family”

Later published on Nouse Online

Friday 6 September 2013

The future is in your genes

Phenylketonuria (PKU) is a genetic disorder that causes the build-up of the amino acid phenylalanine in the blood. Although babies born with this disorder initially appear normal and healthy, after a few months the children develop permanent intellectual disability, with delayed development and seizures frequently occurring. PKU is, however, symptomless if infants are given the correct treatment and the child will grow to a normal, healthy adult.
Many serious genetic diseases are initially symptomless but benefit greatly from early intervention. This is why all newborn babies in the UK are given a blood spot screening test; this checks for diseases such as PKU, cystic fibrosis and sick cell disease. These screening programs allow families either some piece of mind or time to prepare for the future of their child who may require specialised care.
The costs of sequencing DNA have, in recent years, dropped remarkably. The newborn blood spot test costs in the region of £65 and to sequence an entire human genome in now a little under £3500. A lot of the human genome however does not code for proteins (faulty proteins being the most likely cause of genetic disorders) – a vast amount of the human, around 99%, regulates the activity of the coding 1%, plays a structural role or has a currently unknown function; it is unlikely to be all completely unnecessary “junk”. The 1% of the genome that does actually encode proteins, the exome, can be sequenced for around £650, with remarkable accuracy.

Would you like to know if you were going to get Alzheimers? ©Tom Varco; Image credit: WikimediaCommons
Whilst this focus on prices may seem cold and calculating, the cost of research plays a major role in diagnoses. A child suffering from a mysterious illness twenty years ago, say a case of inflammatory bowel disease that was causing the gut to leak into the abdomen, may well have undergone years of intensive surgery with no successful outcomes. But now, as in the case of Nicholas Volker, a full sequencing of his genome allowed the cause to be identified as a mutation in theXIAP gene, leading to a leukaemia-like disorder. One bone marrow transplant later and Nicholas is able to lead a healthy life.
Exome sequencing is allowing patients with rare disorders to finally get the diagnosis that they need, both to receive treatment and plan their lives correctly – for example the tragic case of an infant girl with late stage liver disease, that was found to be caused by a series of mutations that would soon lead to fatal neurodegeneration and heart failure, this spared the infant the further trauma of a liver transplant and meant that her family was able to simply keep her comfortable for her last days. Although these diseases are rare, each one affecting maybe a handful of people across the whole world, rare diseases add up. Taken all together, rare hereditary diseases affect 25 million people in the United States alone.
Rare hereditary diseases affect 25 million people in the United States
Sequencing, for these patients, means a diagnosis rather than just treatment of symptoms. Here is it used for an explanation, not as a forecast; but this is what it could be. With sequencing costs reducing every year, it may not be long until all newborns have their entire exomes sequenced at birth, or until you may go to your doctors and ask what your future health may hold for you.
Children of patients suffering from Huntington’s diseaseare already offered a test to see if they carry it themselves; if they are, they may wish to avoid passing it on should they also have children. In the case of Huntington’s, carrying a faulting a faulty HTT guarantees that you will suffer from the neurodegenerative disorder. However few other diseases are quite so clear cut.
When Angelina Jolie found out she had a mutation in her BRCA1 gene, increasing her risk of breast cancer to 65-87% (calculations are dependent on the details of the mutation) she decided to undergo a double mastectomy, reducing her risk to getting breast cancer to <5 able="" again="" an="" and="" being="" do="" future="" genetic="" have="" health.="" here="" impact="" incredibly="" invoke="" knowing="" may="" mutations="" on="" one="" positive="" reduce="" risk="" s="" something="" the="" they="" to="">

But would you like to know if you had a copy of a variant APOE4 gene, doubling the risk of Alzheimer’s disease? Alzheimer’s is currently incurable, and can leads to years of suffering, both to the patients and their families. Many people may feel uncomfortable knowing that such a fate is likely to await them, yet others would argue that this would allow those at high risk to prepare better for their future.
Pre-emptive treatments, from statins given to those with moderately high cholesterol to a half aspirin a day for those at risk to blood clots, have been with us a long time. Perhaps it is time that these measures become tailored to each individual, dependant in their genetic profiles. In countries with private health care however, this is a sticking point. Insurance premiums for those deemed high risk for various diseases would do through the roof, likely preventing health care access to those who actually need it most.
The NHS too, may be unable to support such a system. Lifetime treatments become incredibly expensive, especially for a disease that may or may not have come to pass. Could a “life time risk” cut-off be put in place? How high would your disease risk have to be to quality for the treatment? 40%? 80%?
Currently, however, exome sequencing is only an option for those suffering from rare diseases. The human genome contains so many variants from person to person that evaluating risk for many complicated combinations of mutations will require vast amounts of in-depth knowledge of our genetic code, as the signal-to-noise ratio of mutations is still far too high to be clear. Drugs companies too will need to change their stance. Instead of making universal treatments worth billions of dollars, every drug will have to be targeted for individuals.
Ethical issues come in to play here too. Would you counsel those carrying many risky mutations to avoid having children, and those with particularly health codes to donate sperm and eggs? These are extreme fears, and cries that exome profiling will lead to eugenics have already been made, but likewise could a doctor morally allow two people to have a child if it meant that child would suffer from a debilitating disease.
These barriers, both ethical and financial stand still stand in the way of genetic health profiling for all, and many years of debates are yet to come as we try to navigate out way through the rapidly changing landscaper of modern medicine.

Published on The Yorker Online