We Pioneered a Technology to Save Millions of Poor Children, But a Worldwide Smear Campaign Has Blocked It
In a few weeks it will be 20 years that we three have been working together. Our project has been independently praised as one of the most influential of all projects of the last 50 years.
Two of us figured out how to make rice produce a source of vitamin A, and the rice becomes a golden color instead of white.
The project's objectives have been admired by some and vilified by others. It has directly involved teams of highly motivated people from a handful of nations, from both the private and public sector. A book, dedicated to the three of us, has been written about our work. Nevertheless, success has, so far, eluded us all. The story of our thwarted efforts is a tragedy that we hope will soon – finally – reach a milestone of potentially profound significance for humanity.
So, what have we been working on, and why haven't we succeeded yet?
Food: everybody needs it, and many are fortunate enough to have enough, even too much of it. Food is a highly emotional subject on every continent and in every culture. For a healthy life our food has to provide energy, as well as, in very small amounts, minerals and vitamins. A varied diet, easily achieved and common in industrialised countries, provides everything.
But poor people in countries where rice is grown often eat little else. White rice only provides energy: no minerals or vitamins. And the lack of one of the vitamins, vitamin A, is responsible for killing around 4,500 poor children every day. Lack of vitamin A is the biggest killer of children, and also the main cause of irreversible childhood blindness.
Our project is about fixing this one dietary deficiency – vitamin A – in this one crop – rice – for this one group of people. It is a huge group though: half of the world's population live by eating a lot of rice every day. Two of us (PB & IP) figured out how to make rice produce a source of vitamin A, and the rice becomes a golden color instead of white. The source is beta-carotene, which the human body converts to vitamin A. Beta-carotene is what makes carrots orange. Our rice is called "Golden Rice."
The technology has been donated to assist those rice eaters who suffer from vitamin A deficiency ('VAD') so that Golden Rice will cost no more than white rice, there will be no restrictions on the small farmers who grow it, and nothing extra to pay for the additional nutrition. Very small amounts of beta-carotene will contribute to alleviation of VAD, and even the earliest version of Golden Rice – which had smaller amounts than today's Golden Rice - would have helped. So far, though, no small farmer has been allowed to grow it. What happened?
To create Golden Rice, it was necessary to precisely add two genes to the 30,000 genes normally present in rice plants. One of the genes is from maize, also known as corn, and the other from a commonly eaten soil bacterium. The only difference from white rice is that Golden Rice contains beta-carotene.
It has been proven to be safe to man and the environment, and consumption of only small quantities of Golden Rice will combat VAD, with no chance of overdosing. All current Golden Rice results from one introduction of these two genes in 2004. But the use of that method – once, 15 years ago - means that Golden Rice is a 'GMO' ('genetically modified organism'). The enzymes used in the manufacture of bread, cheese, beer and wine, and the insulin which diabetics take to keep them alive, are all made from GMOs too.
The first GMO crops were created by agri-business companies. Suspicion of the technology and suspicion of commercial motivations merged, only for crop (but not enzymes or pharmaceutical) applications of GMO technology. Activists motivated by these suspicions were successful in getting the 'precautionary principle' incorporated in an international treaty which has been ratified by 166 countries and the European Union – The Cartagena Protocol.
The equivalent of 13 jumbo jets full of children crashes into the ground every day and kills them all, because of vitamin A deficiency.
This protocol is the basis of national rules governing the introduction of GMO crops in every signatory country. Government regulators in, and for, each country must agree before a GMO crop can be 'registered' to be allowed to be used by the public in that country. Currently regulatory decisions to allow Golden Rice release are being considered in Bangladesh and the Philippines.
The Cartagena Protocol obliges the regulators in each country to consider all possible risks, and to take no account of any possible benefits. Because the anti-gmo-activists' initial concerns were principally about the environment, the responsibility for governments' regulation for GMO crops – even for Golden Rice, a public health project delivered through agriculture – usually rests with the Ministry of the Environment, not the Ministry of Health or the Ministry of Agriculture.
Activists discovered, before Golden Rice was created, that inducing fear of GMO food crops from 'multinational agribusinesses' was very good for generating donations from a public that was largely illiterate about food technology and production. And this source of emotionally charged donations would cease if Golden Rice was proven to save sight and lives, because Golden Rice represented the opposite of all the tropes used in anti-GMO campaigns.
Golden Rice is created to deliver a consumer benefit, it is not for profit – to multinational agribusiness or anyone else; the technology originated in the public sector and is being delivered through the public sector. It is entirely altruistic in its motivations; which activists find impossible to accept. So, the activists believed, suspicion against Golden Rice had to be amplified, Golden Rice had to be stopped: "If we lose the Golden Rice battle, we lose the GMO war."
Activism continues to this day. And any Environment Ministry, with no responsibility for public health or agriculture, and of course an interest in avoiding controversy about its regulatory decisions, is vulnerable to such activism.
The anti-GMO crop campaigns, and especially anti-Golden Rice campaigns, have been extraordinarily effective. If so much regulation by governments is required, surely there must be something to be suspicious about: 'There is no smoke without fire'. The suspicion pervades research institutions and universities, the publishers of scientific journals and The World Health Organisation, and UNICEF: even the most scientifically literate are fearful of entanglement in activist-stoked public controversy.
The equivalent of 13 jumbo jets full of children crashes into the ground every day and kills them all, because of VAD. Yet the solution of Golden Rice, developed by national scientists in the counties where VAD is endemic, is ignored because of fear of controversy, and because poor children's deaths can be ignored without controversy.
Perhaps more controversy lies in not taking scientifically based regulatory decisions than in taking them.
The tide is turning, however. 151 Nobel Laureates, a very significant proportion of all Nobel Laureates, have called on the UN, governments of the world, and Greenpeace to cease their unfounded vilification of GMO crops in general and Golden Rice in particular. A recent Golden Rice article commented, "What shocks me is that some activists continue to misrepresent the truth about the rice. The cynic in me expects profit-driven multinationals to behave unethically, but I want to think that those voluntarily campaigning on issues they care about have higher standards."
The recently published book has exposed the frustrating saga in simple detail. And the publicity from all the above is perhaps starting to change the balance of where controversy lies. Perhaps more controversy lies in not taking scientifically based regulatory decisions than in taking them.
But until they are taken, while there continues a chance of frustrating the objectives of the Golden Rice project, the antagonism will continue. And despite a solution so close at hand, VAD-induced death and blindness, and the misery of affected families, will continue also.
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In December 1958, on a vacation with his wife in Kenya, a 28-year-old British tea broker named Robin Cavendish became suddenly ill. Neither he nor his wife Diana knew it at the time, but Robin's illness would change the course of medical history forever.
Robin was rushed to a nearby hospital in Kenya where the medical staff delivered the crushing news: Robin had contracted polio, and the paralysis creeping up his body was almost certainly permanent. The doctors placed Robin on a ventilator through a tracheotomy in his neck, as the paralysis from his polio infection had rendered him unable to breathe on his own – and going off the average life expectancy at the time, they gave him only three months to live. Robin and Diana (who was pregnant at the time with their first child, Jonathan) flew back to England so he could be admitted to a hospital. They mentally prepared to wait out Robin's final days.
But Robin did something unexpected when he returned to the UK – just one of many things that would astonish doctors over the next several years: He survived. Diana gave birth to Jonathan in February 1959 and continued to visit Robin regularly in the hospital with the baby. Despite doctors warning that he would soon succumb to his illness, Robin kept living.
After a year in the hospital, Diana suggested something radical: She wanted Robin to leave the hospital and live at home in South Oxfordshire for as long as he possibly could, with her as his nurse. At the time, this suggestion was unheard of. People like Robin who depended on machinery to keep them breathing had only ever lived inside hospital walls, as the prevailing belief was that the machinery needed to keep them alive was too complicated for laypeople to operate. But Diana and Robin were up for the challenges – and the risks. Because his ventilator ran on electricity, if the house were to unexpectedly lose power, Diana would either need to restore power quickly or hand-pump air into his lungs to keep him alive.
Robin's wheelchair was not only the first of its kind; it became the model for the respiratory wheelchairs that people still use today.
In an interview as an adult, Jonathan Cavendish reflected on his parents' decision to live outside the hospital on a ventilator: "My father's mantra was quality of life," he explained. "He could have stayed in the hospital, but he didn't think that was as good of a life as he could manage. He would rather be two minutes away from death and living a full life."
After a few years of living at home, however, Robin became tired of being confined to his bed. He longed to sit outside, to visit friends, to travel – but had no way of doing so without his ventilator. So together with his friend Teddy Hall, a professor and engineer at Oxford University, the two collaborated in 1962 to create an entirely new invention: a battery-operated wheelchair prototype with a ventilator built in. With this, Robin could now venture outside the house – and soon the Cavendish family became famous for taking vacations. It was something that, by all accounts, had never been done before by someone who was ventilator-dependent. Robin and Hall also designed a van so that the wheelchair could be plugged in and powered during travel. Jonathan Cavendish later recalled a particular family vacation that nearly ended in disaster when the van broke down outside of Barcelona, Spain:
"My poor old uncle [plugged] my father's chair into the wrong socket," Cavendish later recalled, causing the electricity to short. "There was fire and smoke, and both the van and the chair ground to a halt." Johnathan, who was eight or nine at the time, his mother, and his uncle took turns hand-pumping Robin's ventilator by the roadside for the next thirty-six hours, waiting for Professor Hall to arrive in town and repair the van. Rather than being panicked, the Cavendishes managed to turn the vigil into a party. Townspeople came to greet them, bringing food and music, and a local priest even stopped by to give his blessing.
Robin had become a pioneer, showing the world that a person with severe disabilities could still have mobility, access, and a fuller quality of life than anyone had imagined. His mission, along with Hall's, then became gifting this independence to others like himself. Robin and Hall raised money – first from the Ernest Kleinwort Charitable Trust, and then from the British Department of Health – to fund more ventilator chairs, which were then manufactured by Hall's company, Littlemore Scientific Engineering, and given to fellow patients who wanted to live full lives at home. Robin and Hall used themselves as guinea pigs, testing out different models of the chairs and collaborating with scientists to create other devices for those with disabilities. One invention, called the Possum, allowed paraplegics to control things like the telephone and television set with just a nod of the head. Robin's wheelchair was not only the first of its kind; it became the model for the respiratory wheelchairs that people still use today.
Robin went on to enjoy a long and happy life with his family at their house in South Oxfordshire, surrounded by friends who would later attest to his "down-to-earth" personality, his sense of humor, and his "irresistible" charm. When he died peacefully at his home in 1994 at age 64, he was considered the world's oldest-living person who used a ventilator outside the hospital – breaking yet another barrier for what medical science thought was possible.
Sarah Watts is a health and science writer based in Chicago. Follow her on Twitter at @swattswrites.
In June 2012, Kirstie Ennis was six months into her second deployment to Afghanistan and recently promoted to sergeant. The helicopter gunner and seven others were three hours into a routine mission of combat resupplies and troop transport when their CH-53D helicopter went down hard.
Miraculously, all eight people onboard survived, but Ennis' injuries were many and severe. She had a torn rotator cuff, torn labrum, crushed cervical discs, facial fractures, deep lacerations and traumatic brain injury. Despite a severely fractured ankle, doctors managed to save her foot, for a while at least.
In November 2015, after three years of constant pain and too many surgeries to count, Ennis relented. She elected to undergo a lower leg amputation but only after she completed the 1,000-mile, 72-day Walking with the Wounded journey across the UK.
On Veteran's Day of that year, on the other side of the country, orthopedic surgeon Cato Laurencin announced a moonshot challenge he was setting out to achieve on behalf of wounded warriors like Ennis: the Hartford Engineering A Limb (HEAL) Project.
Laurencin, who is a University of Connecticut professor of chemical, materials and biomedical engineering, teamed up with experts in tissue bioengineering and regenerative medicine from Harvard, Columbia, UC Irvine and SASTRA University in India. Laurencin and his colleagues at the Connecticut Convergence Institute for Translation in Regenerative Engineering made a bold commitment to regenerate an entire limb within 15 years – by the year 2030.
Dr. Cato Laurencin pictured in his office at UConn.
Photo Credit: UConn
Regenerative Engineering -- A Whole New Field
Limb regeneration in humans has been a medical and scientific fascination for decades, with little to show for the effort. However, Laurencin believes that if we are to reach the next level of 21st century medical advances, this puzzle must be solved.
An estimated 185,000 people undergo upper or lower limb amputation every year. Despite the significant advances in electromechanical prosthetics, these individuals still lack the ability to perform complex functions such as sensation for tactile input, normal gait and movement feedback. As far as Laurencin is concerned, the only clinical answer that makes sense is to regenerate a whole functional limb.
Laurencin feels other regeneration efforts were hampered by their siloed research methods with chemists, surgeons, engineers all working separately. Success, he argues, requires a paradigm shift to a trans-disciplinary approach that brings together cutting-edge technologies from disparate fields such as biology, material sciences, physical, chemical and engineering sciences.
As the only surgeon ever inducted into the academies of Science, Medicine and Innovation, Laurencin is uniquely suited for the challenge. He is regarded as the founder of Regenerative Engineering, defined as the convergence of advanced materials sciences, stem cell sciences, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems.
But none of this is achievable without early clinician participation across scientific fields to develop new technologies and a deeper understanding of how to harness the body's innate regenerative capabilities. "When I perform a surgical procedure or something is torn or needs to be repaired, I count on the body being involved in regenerating tissue," he says. "So, understanding how the body works to regenerate itself and harnessing that ability is an important factor for the regeneration process."
The Birth of the Vision
Laurencin's passion for regeneration began when he was a sports medicine fellow at Cornell University Medical Center in the early 1990s. There he saw a significant number of injuries to the anterior cruciate ligament (ACL), the major ligament that stabilizes the knee. He believed he could develop a better way to address those injuries using biomaterials to regenerate the ligament. He sketched out a preliminary drawing on a napkin one night over dinner. He has spent the next 30 years regenerating tissues, including the patented L-C ligament.
As chair of Orthopaedic Surgery at the University of Virginia during the peak of the wars in Iraq and Afghanistan, Laurencin treated military personnel who survived because of improved helmets, body armor and battlefield medicine but were left with more devastating injuries, including traumatic brain injuries and limb loss.
"I was so honored to care for them and I so admired their steadfast courage that I became determined to do something big for them," says Laurencin.
When he tells people about his plans to regrow a limb, he gets a lot of eye rolls, which he finds amusing but not discouraging. Growing bone cells was relatively new when he was first focused on regenerating bone in 1987 at MIT; in 2007 he was well on his way to regenerating ligaments at UVA when many still doubted that ligaments could even be reconstructed. He and his team have already regenerated torn rotator cuff tendons and ACL ligaments using a nano-textured fabric seeded with stem cells.
Even as a finalist for the $4 million NIH Pioneer Award for high-risk/high-reward research, he faced a skeptical scientific audience in 2014. "They said, 'Well what do you plan to do?' I said 'I plan to regenerate a whole limb in people.' There was a lot of incredulousness. They stared at me and asked a lot of questions. About three days later, I received probably the best score I've ever gotten on an NIH grant."
In the Thick of the Science
Humans are born with regenerative abilities--two-year-olds have regrown fingertips--but lose that ability with age. Salamanders are the only vertebrates that can regenerate lost body parts as adults; axolotl, the rare Mexican salamander, can grow extra limbs.
The axolotl is important as a model organism because it is a four-footed vertebrate with a similar body plan to humans. Mapping the axolotl genome in 2018 enhanced scientists' genetic understanding of their evolution, development, and regeneration. Being easy to breed in captivity allowed the HEAL team to closely study these amphibians and discover a new cell type they believe may shed light on how to mimic the process in humans.
"Whenever limb regeneration takes place in the salamander, there is a huge amount of something called heparan sulfate around that area," explains Laurencin. "We thought, 'What if this heparan sulfate is the key ingredient to allowing regeneration to take place?' We found these groups of cells that were interspersed in tissues during the time of regeneration that seemed to have connections to each other that expressed this heparan sulfate."
Called GRID (Groups that are Regenerative, Interspersed and Dendritic), these cells were also recently discovered in mice. While GRID cells don't regenerate as well in mice as in salamanders, finding them in mammals was significant.
"If they're found in mice. we might be able to find these in humans in some form," Laurencin says. "We think maybe it will help us figure out regeneration or we can create cells that mimic what grid cells do and create an artificial grid cell."
What Comes Next?
Laurencin and his team have individually engineered and made every single tissue in the lower limb, including bone, cartilage, ligament, skin, nerve, blood vessels. Regenerating joints and joint tissue is the next big mile marker, which Laurencin sees as essential to regenerating a limb that functions and performs in the way he envisions.
"Using stem cells and amnion tissue, we can regenerate joints that are damaged, and have severe arthritis," he says. "We're making progress on all fronts, and making discoveries we believe are going to be helping people along the way."
That focus and advancement is vital to Ennis. After laboring over the decision to have her leg amputated below the knee, she contracted MRSA two weeks post-surgery. In less than a month, she went from a below-the-knee-amputee to a through-the-knee amputee to an above-the-knee amputee.
"A below-the-knee amputation is night-and-day from above-the-knee," she said. "You have to relearn everything. You're basically a toddler."
Kirstie Ennis pictured in July 2020.
Photo Credit: Ennis' Instagram
The clock is ticking on the timeline Laurencin set for himself. Nine years might seem like forever if you're doing time but it might appear fleeting when you're trying to create something that's never been done before. But Laurencin isn't worried. He's convinced time is on his side.
"Every week, I receive an email or a call from someone, maybe a mother whose child has lost a finger or I'm in communication with a disabled American veteran who wants to know how the progress is going. That energizes me to continue to work hard to try to create these sorts of solutions because we're talking about people and their lives."
He devotes about 60 hours a week to the project and the roughly 100 students, faculty and staff who make up the HEAL team at the Convergence Institute seem acutely aware of what's at stake and appear equally dedicated.
"We're in the thick of the science in terms of making this happen," says Laurencin. "We've moved from making the impossible possible to making the possible a reality. That's what science is all about."