CRISPR is, some believe, as important to science as the invention of the microscope (Credit: natural.society.com)
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, pictured, died from cervical cancer in 1951, aged 31. Cancer cells removed from her body without her knowledge or permission were used to produce the polio vaccine Credit (Henrietta Lacks Foundation).
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.”
A woman with a ‘bionic’ arm. Science fiction is becoming science fact. (Image credit: Telegraph, UK)
Being human means our bodies, tissues and organs, will eventually deteriorate and malfunction. However, advances in medical science mean we can replace aging or diseased hips, knees, even hearts with advanced man-made materials. Many of our bodies, in this way, have become partly artificial or synthetic.
Advances in medical science and engineering mean that a lot more of us, in the developed western world at least, are set to have all manner of misfiring tissues and organs, maybe even our brains, replaced by something synthetic, better, and perhaps an awful lot better. The age of truly bionic man and woman is upon us.
The replacement of body parts with something man-made – what we now call bionics – is something that goes back a long way in human history.
Back as far as 1,500 BC there is a report of an Ancient egyptian mummy having its toe amputated and replaced by a prosthetic made of wood and leather. This was done apparently because the Egyptians felt that amputees would be cursed in life as well as the afterlife.
During the middle ages, crude prosthetic limbs ere available, but only to the very wealthy. These were made of wood, leather and metal, and the replacement leg would resemble a peg leg, with a hook replacing a hand.
Towards the end of the 18th century, in about 1897 the scientist Alessandro Volta – he of electricity fame – found that hearing could be restored by the use of electrical stimulation. This was a big advance in medical bionics.
However, it wasn’t until the mid 1970s that bionics entered the popular consciousness with the arrival of the Six Million Dollar Man and the Bionic Woman on our television screens.
The bionic man, played by Lee Majors, was human, had a bionic left eye, bionic legs, and a bionic right arm, while the Bionic Woman, played by Lindsay Wagner, had similar bionic limbs, but also had a bionic ear.
Science fiction becomes fact
What was science fiction then is now fact. A bionic eye, and ear have already been built, providing people with something even better than the original, while there have been remarkable advances in bionic limbs, including the human hand.
We could today, build a Bionic Man and Woman, with bionic ears, eyes, and limbs (not necessarily with the ability to run at 60 mph, but it could be done if felt necessary), but science is moving beyond what was speculation in the 1970s.
Neuroscientists have begun to decode the language of the brain, so that it is possible to know what word or series of words they are thinking. This is important because it means that people who are disabled, or paralysed can be now trained to move robotic limbs, or a new limb attached to their bodies.
Bionics and neuroscience is, thus, liberating disabled people from their physical dependence on people around them, and they can control their artificial limbs, or wheelchairs by simply thinking. At the same time, materials are becoming more sophisticated, and these can enhance malfunctioning biological tissues.
Bionic eyes, which pick up signals from the environment and transmit electrical impulses straight to the brain will soon help the blind ‘see’ again. A Bionic ear has been developed which restores hearing to the profoundly deaf via an implant which receives and transmits signals in the inner ear.
A bionic hand, with tremendous dexterity has been developed for a Danish man, which has been integrated by neurosurgeons with his existing nervous system. Bionic feet and legs under the thought control of the brain have been developed. A fully artificial heart has been successfully implanted, and there even moves to build an electronic implant to replace malfunctioing parts of the brain, or to construct a fully artificial brain based on the biological brain.
What this all means is that we are seeing a general trend towards humans becoming more artificial, as we live longer, and want to maintain the functioning of our limbs, organs and brain for as long as possible.
What do people want in life? They want to alive at the age of 90, but still active and healthy, physically and mentally. Bionics offers this, and its alluring.
No one knows where this all will end, or how artificial we will eventually become. Some believe that the trend towards having more and more bionic body parts threatens our humanity. How far can we go towards becoming artificial before we stop being human? It is a huge philosophical question we’ll face in future.
The majority of the work in Ireland in this area is on the repair of body parts, through what is called regenerative medicine, rather than bionics, which involves the complete replacement of a tissue or organ, with something new and artificial.
Bionics, and regenerative medicine are moving ahead together and in parallel. It is perhaps a bit like the car industry.
There will always be a market for a brand new cars. Some people will buy a new car because they can afford it, and they want the latest technology and performance capabilities.
Others might want a new car because they have crashed their old one, and is beyond repair. However, there are also people who do not feel the need for a new car, and are quite happy to have their old car service, fixed, and on the road for as long as possible.
Ireland, in this sense, is more in the service and repair market, than the new car sales market, but both are equally important areas.
In terms of bionics, researchers in the University of Limerick, led by Dr Leonard O’Sullivan, along with an industrial partner, MTD Precision Engineering (Cork) are aiming to develop a full body Bionic Suit to help the elderly.
The Axo Suit project aims to help the aging live independently and stay mobile. The suit needs to be light enough to allow them to do daily tasks, such as going for a walk, or putting clothes on the line, but strong enough to give support.
The goal is to produce an ‘exoskeleton’ or bionic suit, which will sell for between 5k and 10k. This could keep many people out of nursing homes.
It could also lead to printing of organs or tissues made up of a combination of natural and artificial components, or even totally artificial components. There has already been a successful transplant of an artificial heart, and with natural organs hard to come by, this trend is set to increase.
Also at TCD, Dr Mark Ahearne’s group are developing bioengineered corneas which can be used for cornea transplants to restore sight or relieve pain. The artificial cornea has been made by using artificial fibres that mimic the ability of natural collagen fibres in the cornea to allow light to penetrate through. The researchers believe this will help people suffering from corneal blindness.
Meanwhile, At the Regenerative Medicine Institute at NUI Galway, or REMEDI there is a clinical trial underway where stem cells are being used to tackle osteoarthritis. The idea here is to insert stem cells into, for example knee joints damaged by arthritis to facilitate the growth of new, healthy bone tissue.
The potential for knee repair is incredible. For example, Professor Fergal O’Brien, based at the Royal College of Surgeons in Ireland and AMBER, developed a new material which repaired the severely damaged knee joints of a competitive show jumping horse called Beyonce. The horse was facing euthanasia, but after the material was used, it began competitive show jumping again.
REMEDI researchers are also working with colleagues our Lady’s Hospital for Sick Children, to use stem cells to overcome congenital heart defects in children. In terms of organ repair, or fixing the sky is now the limit.
Is humanity threatened?
Bionics and regenerative medicine are set to help millions of people around the world who are suffering the effects of diseased or damaged tissues or organs. We are living longer, and this technology will help us live better, no doubt.
But, there are some issues, or concerns. For example, some well known scientists in the field, such as Hugh Herr at MIT, believe that synthetic materials such as titanium and silicon will one day replace flesh and blood.
Do we want that? Will this spell the end of humanity, at our own hand?
Herr got caught in a snow blizzard while climbing a mountain at the age of 17, and lost both legs to severe frostbite. Now in his 50s, he is the co-director of MIT’s Center for Extreme Bionics, where he is designing artificial legs (including his own) feet, ankles, knees and hips.
Herr’s view is that we will become more artificial, and eventually totally artificial, but that we will retain our humanity. We already have ‘augmented’ abilities, such as the ability to fly, and devices that improve our memory and ability to communicate.
Herr believes that our humanity, our ideas, our personalities, and our creativity, will become ‘embedded’ into artificial ‘designable’ bodies. We will come to see this as normal in the way, he says, and that artificial legs, or body parts will be considered part of us in the same way as biological legs are now. This is all part of the natural progression, or evolution, or humanity, Herr says.
Others disagree, and argue that as we shed our biology, we will shed our humanity, and that this technology represents an existential threat to mankind.