We are living longer with an increase in human lifespan of 2.5 years per decade. Scientists are now focused on achieving healthspans, where we live disease free, which can match our longer lives.
This piece for Drivetime on RTE Radio 1, broadcast on 21st June, features interviews with three leading scientists working on different ways to solve the ageing ‘problem’; Luke O’Neill, TCD, Fergal O’Brien, RCSI, and Emma Teeling UCD.
The immune system works better at certain times of day than others, according to new research, which could help point the way towards the development of new drugs for autoimmune disease such as multiple sclerosis (MS).
“In the year that the Nobel Prize in Medicine was awarded for discoveries on the molecular mechanisms controlling the circadian rhythm, our exciting findings suggest that our immune system is programmed to respond better to infection and insults encountered at different times in the 24-hour clock,” said Prof Mills.
“This has significant implications for the treatment of immune-mediated diseases and suggests there may be important differences in time of day response to drugs used to treat autoimmune diseases such as multiple sclerosis,” Prof Mills said.
Using mice as a model organism, the researchers showed that a master circadian gene, BMAL1, is responsible for sensing and acting on time-of-the-day cues to suppress inflammation. Loss of BMAL1, or induction of autoimmunity at midday instead of midnight, causes more severe experimental autoimmune encephalomyelitis (an analogue of multiple sclerosis) in mice.
Circadian rhythms or 24-hour rhythms are generated by the body clock, allowing us to anticipate and respond to the 24-hour cycle of our planet.
Maintaining a good body clock is generally believed to lead to good health for humans, and disrupting the circadian rhythm (for example, as happens in some people working night shifts) has been associated with immune diseases such as multiple sclerosis; however, the underlying molecular links have been unclear.
“Our study also shows how disruption of our body clocks, which is quite common now given our 24/7 lifestyle and erratic eating and sleeping patterns, may have an impact on autoimmune conditions,” said Dr Curtis.
“We are really beginning to uncover exactly how important our body clocks are for health and wellbeing,” Dr Curtis added.
One thousand volunteers who suffer from obsessions or compulsions due to OCD are being sought by the School of Psychology at UCD to take part in an online survey.
The disorder known as OCD, or Obsessive Compulsive Disorder can drive people to repeating behaviours over and over again, such as washing or checking locks. It can also cause people to struggle to remove disturbing, intrusive and unwanted thoughts.
The disorder can severely impact on a person’s life, with some people actively engaged in thought rumination or performing rituals to reduce anxiety. It is estimated that between 2 and 3 per cent of people in Ireland suffer from OCD – or between 48,000 and 96,000 people.
The online study will be conducted by Patrick McHugh, a psychologist in clinical training at the School of Psychology NUIG, along with Dr Jonathan Egan, Deputy Director of the Clinical Psychology Doctorate Programme.
“Obsessions can feel overwhelming and difficult to control,” said Mr McHugh. “We aim to investigate whether strong emotions like guilt and disgust contribute to such symptoms.”
Dr Egan added: “When people do not reach out to others in order to normalise their thoughts, they may then start to experience distress,”
“Obsessions are often associated with thoughts which feel intrusive and out of your control and if left untended to, can become a worrying pre-occupation and affected a person’s day-to-day life, and may result in the need for a Chartered Clinical Psychologist’s intervention,” said Dr Egan.
The FDA-approved alcohol aversion drug, disulfiram (Antabuse), has been found to be very effective in combating chemotherapy resistance in lung cancer.
Scientists based at TCD and St James’s Hospital, Dublin, have reported the finding for the most common type of lung cancer – non-small cell lung cancer (NSCLC) – in the journal Oncotarget.
“Disulfiram is an already approved drug will well tolerated side effects which can be taken orally,” said Dr Martin Barr, Adjust Assistant Professor and a lead investigator in the Thoracic Oncology Research Group, based at TCD and St James’s.
“Its potential use may give chemotherapeutic drugs such as cisplatin, a new lease of life in the treatment of resistant drug tumours,” Dr Barr added.
Antabuse has been used to treat alcohol addiction for over 60 years and works by restricting the activity of aldehyde dehydrogenase (ALDH) the main enzyme involved in removing alcohol from the body.
It works by preventing the body from metabolising alcohol, and so the person consuming alcohol will start to feel sick.
Antabuse has now been also found – also by inhibiting ALDH – to decrease tumour cell growth and increase the body’s killing action against lung cancer stem cells. The killing of cancer stem cells is important, because this can prevent the cancer from recurring.
The scientists at TCD and St James’s, working with the Cancer Stem Cell Group at the Coombe Hospital, Dublin, found that lung cancer cells that have high levels of ALDH activity – which is a marker for the presence of cancer stem cells, – become resistant to chemotherapy.
This resistance means that cancer cells can survive chemotherapy and may explain why a large number of lung cancer patients receiving certain types of chemotherapy suffer a relapse in their cancer afterwards.
The development of new drugs is an expensive, time consuming business, and cancer scientists have begun to assess drugs already approved to treat non cancer illness such as Antabuse, for their effectiveness against cancer.
Lung cancer is the leading cause of cancer-related deaths worldwide and accounts for more deaths than breast, colon and prostate cancer combined. In Ireland there are more than 2,300 new cases of lung cancer per year and over 1,800 deaths.
A new gene-editing tool that can precisely ‘cut and paste’ DNA to remove segments that cause disease or insert pieces that promote health benefits is, some scientists believe, as important a scientific invention as the microscope.
Scientists in Ireland are part of the what’s being called the CRISPR revolution and many biological researchers are using this technology has the potential to change the world.
From the ground-shaking discovery of the double-helix of DNA by Watson and Crick in 1953 so much followed in the years, and decades since. We have learned how DNA passing from one generation to the next, how it transmits signals to the cells, and the body, and how, when DNA building blocks get laid down in the wrong way, that it can cause sometimes deadly genetic diseases.
We are now at another historic moment in biological science, because scientists have in their hands a tool, which enables them to precisely manipulate DNA in a way that was never possible before. This tool is CRISPR and some scientists predict it could lead to the end of all genetic diseases, and perhaps even the eradication of all diseases, whether genetic or not.
Luke O’Neill is a professor of biochemistry at Trinity College, and one of the world’s leading immunologists. He is using CRISPR to study specific genes in the immune system, to change them, or modify them and see if they are important.
Breandan Kennedy, is a professor at the School of Biomolecular and Biomedical Science at UCD. He is using CRISPR to try and correct vision loss, blindness due to faulty genes and even non-inherited forms of cancer.
Dr Niall Barron is based at National Institute for Bioprocessing Research and Training, or NIBRT in Dublin. He is using CRISPR to make the manufacture of highly effective, but expensive biologically-based drugs such as Enbrel made by Pfizer in Dublin and Humira, made by Abbvie in Sligo. Both are used to treat rheumatoid arthritis.
Meanwhile, at Our Lady’s Children’s Hospital, Crumlin, Dr Terry Prendiville, a consultant paediatric cardiologist, is using CRISPR, along with colleagues based at NUI Galway, to try and repair inherited cardiac defects in children.
Dr Prendiville points out that it could be some years before CRISPR can be used to help repair the hearts of children with inherited defects.
CRISPR is described by Luke O’Neill as being as important to science as the invention of the microscope, and it has the potential to eradicate many of the debilitating and deadly diseases that are today considered incurable.
The Immortal life of Henrietta Lacks based on the book written by Rebecca Skloot in 2010 will appear on our cinema screens this year, with Oprah Winfrey in the role of Henrietta.
But, who was Henrietta Lacks, what was her story, why is her life described as “immortal” and how has it influenced the lives of millions of people around the world since her death in 1951?
Henrietta Lacks was a poor black woman from the tobacco fields of the state of Virginia, USA, part of the old South.
She has made a huge contribution to mankind, because of the cells she unwittingly gave to the world, so called ‘HeLa cells’ which were taken from the cancer that killed her in 1951 and grown in labs around the world to combat disease, and help scientists develop techniques like cloning and I.V.F.
The cells have been used to produce a vaccine for polio, leading to its eradication in the USA and most parts of the world, but they have also been used to produce commercial revenue. Henrietta didn’t provide ‘consent’ for her cells to be used in this way, but in 1951, consent was not a requirement for doctors to remove cells or tissues from patients for research purposes.
Henrietta was born with the name Loretta Pleasant on the 1st August 1920 in Roanoke, the biggest town, but still a small-ish city, in southwestern Virginia. At some stage, for reasons not clear, she became Henrietta, a name that was shortened to ‘Hennie’ after the death of her mother.
Henrietta’s mother died when Henrietta was 4 and ‘Hennie’ and her nine siblings were sent to live with various aunts and uncles and cousins in the little farming town of Clover, Virginia.
Hennie ended up with her grandfather, who was also trying to raise one of Hennie’s first cousins – David. They lived in a two-story cabin built of hand-carved logs, and held together by pegs that was once the slave quarters of their ancestors.
In 1924 rural Virginia, black people were no longer slaves, but their social, economic and living circumstances, even the actual buildings that that lived in, hadn’t changed much since the Emancipation Proclamation was issued by President Abraham Lincoln on 1st January 1863. This executive order changed the federal legal status of some 3 million black slaves trapped in the Confederate south from ‘slave’ to ‘free’.
The former slave quarters that Hennie found herself living in with her grandfather and cousin David looked over the family cemetery where Hennie’s ancestors, who were black, but some of whom were also white, including one of her great grandfathers, were buried.
All around the slave house, or ‘home house’ as its residents called it were hundreds of acres of tobacco fields. The area was, and is known as Lacks Town, as many of the people living in and around the tobacco fields were ‘kin’ to Henrietta.
Hennie had honey coloured skin, a round face, and an attractive, welcoming smile. After a time, according to cousins accounts, Hennie and David, who was called ‘Day’ became an item, even though they had been raised like a brother and sister.
Children followed. Lawrence was born in 1935, and Elsie, who was “deaf and dumb”, and ended up later in a home for the Negro Insane, was born in 1939.
In 1941, Hennie and Day got married, and made plans to get out of Clover, forget the tough life of tobacco farming, and join the many black people that were heading for Baltimore and Washington DC to get jobs in the booming wartime shipyards and steel mills.
Hennie, according to accounts, settled into her new life as housewife in a brick city apartment, but she missed the country and would often grab her kids, and pile them onto a bus for a trip back to Clover.
It seems Hennie loved being a mother, and more children came with Sonny born in 1947, and Deborah in 1949. Their fifth child, Joe, was born in 1950.
A few months after Joe was born Hennie shared a secret with her cousin Sadie, Sadie later recalled. She started bleeding, even though it was not her time of the month, and one morning when she was taking a bath she felt a lump.
Hennie decided to attend the outpatient centre at Johns Hopkins Hospital in Baltimore – a renowned centre for medical excellence in February 1951 and the gynaecologist on duty when Henrietta came in was Dr Howard Jones. Dr Jones examined Henrietta and found something remarkable: a glistening, smooth growth that resembled what he called “purple Jell-O” (jelly).
The growth was about the size of a US quarter, and positioned at the lower right of Henrietta’s cervix. The growth bled easily when it was touched.
Dr Jones thought it might be an infection and tested for syphilis, but the results came back negative. He ordered a biopsy and got the diagnosis: sadly for Hennie, it was cancer.
Henrietta came back for treatment 8 days later, and another doctor took another slice off her tumour. Henrietta wasn’t told about this, but, at the time, that was normal medical practice.
Capsules of radium were placed around her cervix to try and kill the cancer cells and she was released from hospital and went home. Henrietta didn’t tell anyone about her illness, and continued with home life as normal.
She came back regularly for treatment, but the cancer cells were growing faster than radium could kill them and it was difficult for her now to hide her pain.
She was admitted to hospital for the last time in August 1951, for what would be the last time. A few months later, on 4th October 1951 Henrietta died, aged 31, with an autopsy showing that she had cancerous lumps in her chest cavity, lungs, liver, kidney and right through her bladder. The cancer had been relentless, and grew and spread at a pace that proved uncontrollable.
Henrietta was buried in an unmarked grave her the ‘home house’ in Clover. Her children remember it as a day when the rain poured from the sky as though heaven were weeping for ‘Hennie’.
The death of Hennie was devastating to Henrietta’s family, her husband Day and their five children. This is apparent, as even all these years later they get upset talking about her death, it seems.
Her death was something of a taboo subject, and no-one was comfortable talking about it, as it affected them so deeply.
Day tried to keep the show on the road by working shifts at the shipyard, while minding his three youngest children. Elsie was now in a home for the Negro Insane and family visits were not as frequent was when Henrietta was alive, as she visited Elsie regularly. Lawrence, the eldest left to join the Army.
Two relatives moved in to live with Day and the three children, one of which was described as ‘evil’ and life became brutal and horrible, with the children being beaten for no reason and having little food to eat.
As the children grew older, they – understandably – wanted to get away as much as possible from the nightmare house in Baltimore and they regularly returned to Clover to work on tobacco, as their mum had done, keeping their abuse a secret.
Elsie died in 1955, aged just 16, and it appears that sadly she had been abused, and she may even have had holes drilled in her head for some kind of human experimentation.
When Henrietta’s children had their own children, it seems that – perhaps sensing something from their parents – they too avoided the subject of their grandmother, how she lived and how she died.
Henrietta’s family knew nothing until the early 1970s when family members received phone calls from researchers asked for them to donate blood samples. The researchers said that they wanted to find out more about their mother’s genetic make-up.
Naturally, the family members wanted to know why they were interested in this, now, many years after Henrietta’s death. They were then told – and this must have been utterly shocking to them – that part of their mother, some of her cells, were still alive and growing now, more than 20 years after her death.
The Lacks family finally learned that tissue from their mother’s second biopsy in 1951 had been given to Johns Hopkins researcher Dr George Gey, who was searching for a cure to cancer, and had, towards this end, but trying – unsuccessfully – to grow human cells outside the body, so that they could be closed studied in the lab.
Dr Gey’s lab technicians got Henrietta’s cells, but – by now programmed for failure – expected them to do what many previous cell samples had done – live for a short time, a few days tops, then die. Yet, what happened astonished them. Henrietta’s cells multiplied in petri dishes, uncontrollably spreading and piling up on one another.
On the very same day that Henrietta died, 4th October 1951, Gey was appearing on a TV show called ‘Cancer Can be Conquered.” On the show he held a bottle close to the camera, and in it he said was the first human cell line ever grown. This was Henrietta’s legacy.
The cells were called “HeLa cells” by Gey, to acknowledge the first two letters of Henrietta Lacks’ first and last names. He then gave samples out to other researchers around the USA. The idea was that HeLa cells would work enough like normal cells so that doctors could test, probe and unlock their secrets and weaknesses in the lab. This new knowledge, it was hoped, would lead to a cure for cancer.
The biggest impact, without doubt, that HeLa cells have, so far at least, made on the world is by helping Jonas Salk create a vaccine which has almost eradicated – worldwide – what was a crippling disease affecting children.
Salk infected HeLa cells with the poliovirus – something that could easily be achieved – and studied how they reacted. After a number of years of work, in 1955, he had created a working vaccine.
This received huge attention because polio mainly affects children under 5 years of age, so young children had been dying and the name polio was a terrifying one until Salk came along.
Polio is highly infectious. It kills when some infected children become paralysed and their breathing muscles immobilised. It is still a threat in certain parts of the world, according to the WHO, but the number of cases, worldwide have decreased from 350,000 cases in 1988 to just 74 reported cases in 2015.
It is estimated that the polio vaccine, and, thus, HeLa cells that helped created it, have saved the lives of one million people, many of them young children, around the world since 1955, who would otherwise have died of polio.
In 1952, just three years beforehand, there was a polio outbreak in the USA which killed 3,145 people, including 1,873 children. At that rate, some 192,000 Americans would have died if the polio vaccine had not been available there from 1955.
The HeLA cells were ideal for developing a polio vaccine because they could be easily infected by poliomyelitis, which caused infected cells to die. However, a large volume of HeLa cells were needed to test Salk’s vaccine, and this led to the mass production of HeLa cells from 1953 in a cell culture ‘factory’ at Tuskegee University.
Controversially, however, companies also used HeLa cells to test cosmetics, and to measure the effects of radiation on human cells. They were used to test how human cells responded to other viruses, and were used in a number of cancer trials.
HeLa were the first ‘cell lines’, they stored well, were robust and could be sent out to laboratories all over the world. They replicate very fast, which is useful, but can also cause problems for scientists in terms of contamination of the lab.
HeLa cells have been used to study all kinds of viruses, and helped in the creation of a vaccine to HPV, the human papillomavirus, as well as to act as a testbed for new medications for cancer and Parkinson’s disease. They have also been used to test how certain products, such as cosmetics, affect human cells.
Because some HeLa cells behave differently to others, it has been possible for scientists to isolate a specific cell type, multiple it, and start a new cell line. This method of isolating a cell and keeping it alive is the basic technique behind I.V.F. which is so much part of our world today.
One discovery from HeLa cells has big potential in the fight against cancer. It was found that HeLa cells used an enzyme to repair their DNA and keep functioning when other cells would have died. Anti cancer trials against this enzyme are currently ongoing.
There are some who would say that the importance of HeLa cells in saving lives has been overstated. For example, saving one million lives with the polio vaccine, is small potatoes compared to, say the Measles vaccination, which has saved about 17 million lives since 2000.
Henrietta’s family were angry when they finally heard the full story of the HeLa cells. They felt that Johns Hopkins Hospital had removed Henrietta’s cells without permission. The hospital had done that, they didn’t deny it, and neither did they deny that they hadn’t asked permission. Permission to do this wasn’t required back in 1951.
The Lacks family were also confused by all the scientific jargon that started to come their way. I think they their initial reaction was that their mother, and themselves had been exploited by researchers. For instance, they said that they gave blood to the researchers when asked, but the researchers did not bother to follow up with them when results came out or to explain results.
None of the children have developed their mother’s aggressive cancer, so Henrietta left no deadly legacy to her children.
There was a financial issue also, as far as the Lacks family were concerned because biomedical companies in the decades since their mother’s death had been mass producing HeLa cells, like a license to print money, and sending them out all over the world.
Fortunes were being made on the back of their mother’s cells, while they themselves, could even afford health insurance.
They were also apparently hurt that so many people, researchers, scientists and doctors, appeared to know so much about their mother, and that they, her children, knew very little.
Their father Day died in 2002 (41 years after his wife Henrietta) but the family only managed recently to pool together money for a headstone for his grave.
Johns Hopkins have honoured the contribution of Henrietta, and others like her, to their research, but they remain sensitive to criticism of their role in the Lacks’ story. They made the point that the hospital as it was in 1951 can’t be judged by today’s standards, and that patient consent, now a basic standard, wasn’t even considered in 1951.
The HeLa cells, Johns Hopkins state, were given away by their researcher Dr Gey, acting on his own and the hospital never patented the HeLa cells or sold them to make money. Dr Gey, they add was acting with good intent as he passed the cells on in the hope researchers could develop a module from which scientists could learn more about human cell function (and by corally, cancer cell function).
HeLa cells have today multiplied to the point where they weigh some 20 tonnes, all together, while, according to the US Patent and Trademark Office there are close to 11,000 patents that involve HeLa cells. The cells are so widely available that they can be ordered for delivery on the Internet.
The words on Henrietta’s gravestone, composed by her grandchildren reads:
“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.”